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CHEMICAL ENGINEERING METHODS AND TECHNOLOGY

TRANSITION METALS


CHARACTERISTICS, PROPERTIES AND USES


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CHEMICAL ENGINEERING METHODS AND TECHNOLOGY








TRANSITION METALS


CHARACTERISTICS, PROPERTIES AND USES







AJAY KUMAR MISHRA
EDITOR















Nova Science Publishers, Inc.
New York
Copyright 2012 by Nova Science Publishers, Inc.

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Library of Congress Cataloging-in-Publication Data

Transition metals : characteristics, properties and uses / editor, Ajay Kumar Mishra.
p. cm.
Includes index.
1. Transition metal alloys. I. Mishra, Ajay Kumar, 1965-
TN693.T7T73 2011
661'.06--dc23





Published by Nova Science Publishers, Inc. New York
ISBN: 978-1-62417-380-6 (eBook)









CONTENTS


Preface vii
Chapter 1 Role of Reactivity of Transition Elements in Life 1
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam
and Afaf Ezzat
Chapter 2 Nonlinear Optical Properties of Transition Metal Nanoparticles
Synthesized by Ion Implantation 63
Andrey L. Stepanov
Chapter 3 Self-Organization of the Nanocrystalline Structure
and Radiation Resistance of Structural Materials 119
V. P. Kolotushkin and A. A. Parfenov
Chapter 4 Transition Metal Complexes of Schiff Base Ligands
of 3-Formylsalicylic Acid: Synthetic Pathways
and Useful Properties 165
Saikat Sarkar and Kamalendu Dey
Chapter 5 Structural and Magnetic Characterization of Cu-Picolinate
and Cu-Quinaldinate Molecular Systems 221
Bogumia urowska
Chapter 6 Review: Transition Metals in Medicine 263
Hanan F. Abdel-Halim
Chapter 7 Application of Transition Metals as Active Compounds
in Separation Techniques 299
Iwona Rykowska and Wiesaw Wasiak
Chapter 8 Chromium Pigment 327
Mohammad Fikry Ragai Fouda , Hanan. F.Abdel-Halim
and Samia Abdul Raouf Mostafa
Chapter 9 Transition Metals: Bioinorganic and Redox Reactions
in Biological Systems 349
Marisa G. Repetto and Alberto Boveris
Contents vi
Chapter 10 Hydrodesulfurization of Dibenzothiophene over Various
CoMoP/Al
2
O
3
Sulfide Catalysts Prepared from Co and Mo
Phosphoric Acids 371
Masatoshi Nagai, Yuki Nakamura and Shoji Kurata
Chapter 11 Mixed Transition Metal Acetylides with Different Metals
Connected by Carbon-Rich Bridging Units: On the Way
to Hetero-Multimetallic Organometallics 383
Heinrich Lang and Alexander Jakob
Chapter 12 Reactivity of Unstable Chemicals in the Presence
of Transition Metals 453
Mieko Kumasaki
Index 483













PREFACE

In this book, the authors present topical research in the study of the characteristics,
properties and uses of transition metals. Topics discussed include the nonlinear optical
properties of transition metal nanoparticles synthesized by ion implantation; the structural and
magnetic characterization of Cu-Picolinate and Cu-Quinaldinate molecular systems;
application of transition metals as active compounds in separation techniques; the reactivity
of unstable chemicals in the presence of transition metals and the bioinorganic and redox
reactions in biological systems of transition metals. (Imprint: Nova)
Transition metals are commonly known as d-block elements that forms the bridge
between the main group elements of the periodic table. These elements are lustrous / shiny
solids or liquids and possess metallic properties which include hardness, toughness and strong
metallic atom-atom bonding. Some of the characteristic properties of these metals include its
ability to form colour compounds, exhibiting many oxidations states and their magnetic
behaviour. Besides these properties, these metals are good conductors of heat and electricity
and have many free electrons per atom to carry thermal and electrical energy. These metals
can be easily hammered and bent into different shapes. Due to the strong metallic bonding,
the transition elements show high melting point, boiling point and high density. Transition
metals are used as alloy and useful as structural materials due to their strength and hardness
properties. They are also used as pigments for artwork and give bright colours to stained glass
and ceramic glazes.
Due to metallic properties, the transition metals have been exploited for many industrial,
commercial, strategic, environmental, ornamental, medial, biomedical applications. Among
these, the common use at technological scale is their use as catalysts in industrial chemical
processes and also in the anti-pollution catalytic converters in car exhausts. Due to the
catalysis behaviour of the transition metals, a variety of new synthetic methodologies has
been developed and applied to industrial processes. It is very difficult to find a multi-step
synthesis of complex organic molecules where transition metal catalyzed processes are not
employed. Significant progress in homogeneous catalysis and the depth understanding of the
mechanisms and also from developments based on the new information derived in studying
the behaviour of organotransition metal complexes. The organotransition metal chemistry and
homogeneous catalysis area has been extensively studied with the ferrocene, Ziegler catalyst,
and the Hoechst-Wacker process. This prompted the organotransition metal chemistry in a
significant increase in the number and novel chemical features that are applicable to catalysis.
The advantage of homogeneous catalysis over conventional heterogeneous catalysis allows
Ajay Kumar Mishra viii
the clarification of the reaction mechanisms at the molecular level by catalytic cycles
consisting of elementary processes.
Transition metals have a key role in the development of medicine, coordination
chemistry, plant biology, materials science, polymer science and also by biochemists and
biologists as well. The transition metals ions and complexes play a central role in controlling
the reactivity and mechanism of the chemical reaction of interest. This can be due to the
actual reaction occurring at the metal centre and/or the catalytic activity of the metal complex
in an overall chemical process. The unique ability of transition metal ions and complexes to
control the chemistry of environmental, industrial, and biological processes has increased the
importance of clarifying their mechanistic behaviour in simple and complex chemical
processes. The role of the central metal atom or ion has received considerable attention not
only in fundamental inorganic and organometallic chemistry but also in more applied areas
such as in environmental, bioinorganic, and bioorganic chemistry.
Transition metal catalyzed polymerization, synthesis of compounds of interest for
material research, the use of non-conventional solvents such as water, supercritical fluids, and
ionic liquids, and reactions employing polymer supported reactants have gained enormous
attentions. The polymer synthesis has also been widely studied by the olefin polymerization
and copolymerization by late transition metal catalysts. Polymer synthesis has been
influenced by the development of single-site polymerization of olefins by complexes of the
transition metals where the coordination and insertion modes of monomers are controlled by
the ligand. Ring opening metathesis polymerization developed the studies of metal carbene
type transition metal complexes. This methodology can be involved through studies on the
elementary processes which can be applied to prepare new materials of unique properties for
various applications.
This book covers the a wider domain of research and development where the use of
transition metals have been investigated for various applications such as drug delivery,
organometallics, bio-organometallic chemistry, chemotherapy, clinical and pharmaceutical
aspects. This will enlighten the beginners by providing an excellent source of high quality
information for experts in the field. This book will also allow the bioinorganic chemists, the
pharmaceutical industry, chemists and biochemists to innovate their ideas using
multidisciplinary approach and applications of transition metals.
The book covers broad literatures in the area of transition metals in organic synthesis
including novel reactions, new catalysts, ligands, and reaction conditions and applications in
synthesis of complex organic molecules. The book is especially beneficial to the scholars who
are planning or are working towards their graduate and postgraduate degrees in this field of
bioinorganic chemistry. The advance aspects of the bioinorganic chemistry is a platform for
all levels of academics and research as it provides background for the recent research
literature, abbreviation summaries of the inorganic chemistry, biochemistry and spectroscopy.
The book is thus an interesting read for those who wish to obtain a general overview of the
most important transition metals, fundamentals concept and also will provide a useful
steppingstone for further exploration of the literature. The book also covers a wide research
area that integrates biology, chemistry, materials science, engineering and nanotechnology to
present an interdisciplinary approach for solving multitude problems. The unique approach to
cover the fundamental knowledge along with the recent advancements for the research and
development in the field of transition metals is sure to make a niche for extensive knowledge
dissipation to all ages.
In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0
Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc.






Chapter 1



ROLE OF REACTIVITY OF TRANSITION
ELEMENTS IN LIFE


Mohamed Fikry Ragai Fouda
1
, Omar Mohamed Abdel-Salam
2

and Afaf Ezzat
3

1
Professor of Inorganic Chemistry, Department of Inorganic Chemistry,
National Research Centre, Cairo, Egypt
2
Professor of Pharmacology, Department of Toxicology and Narcotics,
National Research Centre, Cairo, Egypt
3
Professor of Biochemistry, Department of Nutrition and Food Sciences,
National Research Centre, Cairo, Egypt


INTRODUCTION

In the last two decades, the field of biological inorganic chemistry has shown a rapid
explosion with a tremendous increase in our understanding of the roles of transition metals in
both higher plants and human life. The 25 elements that have been shown to be essential to
life in microorganisms are belonging to "s", 'b' and 'd' block elements. The "s" block
elements are namely H, Na, B, K, Mg and Ca, whereas the "b" block elements are; C, N, O, F,
Si, P, S, Cl, Se, I and As. The "d" block elements namely are V, Cr, Mn, Fe, Co, Ni, Cu and
Mo, whereas the "d" closed shell elements are Zn and Cd. Amongst all the following four 'b"
block elements, H, C, N and O are the most abundant elements in living organisms, where
they make up 99.3% of all the atoms in the body, but the remaining 21 elements only account
for 0.7 %.
Apart form the last four elements, which constitute the outermost percentage of elements
essential for life, the remaining twenty one elements can be divided into two groups: (i) the
macronutrients: these consist of seven elements; calcium, phosphorous, potassium, sulphur,
chlorine, sodium and magnesium, which are found in greater concentrations in the body than
are the remainder of the 21 elements; (ii) the trace elements: these consist of fourteen
elements; iron, manganese, copper, zinc, molybdenum, cobalt, vanadium, chromium, nickel,
fluorine, silicon, selenium, arsenic and iodine. All the 21 elements of the macronutrients and
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 2
the trace elements are found in living systems, either as ions, or covalently bonded to organic
residues.
This monograph is confined to throw the light on the importance of V, Cr, Mn, Fe, Co,
Ni, Cu, which are belonging to first transition series, as well as closed shell zinc element, in
addition to molybdenum which is a member in the second transition series. This monograph
is also oriented to clarify the importance of the elements mentioned before as micronutrients
for higher plants and their participation in various enzyme systems in the plant. In that context
the sources of these inorganic micronutrients in the soil is taken into consideration. In
addition, it is aimed to explain the important role of these elements in body life, where they
are able to create oxidative stress inside the body on one hand and the ability of them to act as
antioxidants in case of attachment to some proteins, on the other hand.
Some of these metals are contained in several enzymes such as iron (transferrin),
molybdenum (xanthine oxidase), vanadium (hemovanadin), zinc (carbonic anhydrase), and
copper (hepatocuprein). There is also an evidence linking some diseases and the deficiency of
a number of transition elements. At the same time, an increase in some of transition elements
has been suggested to lead to neurodegenerative disorders e.g., iron in case of Parkinson's
disease and copper in Alzheimer's disease. In addition, the so called metallo- therapeutics
have been used in the last few decades in the treatment of some human aliments. The
application of metallo-therapy includes the use of some organometallics or metal-organic
complexes, such as using some gold and platinum complexes as antiarthritis and antitumour
drugs, respectively. The metal-based photodynamically active compounds are in use
nowadays in treatment of some types of human malignancies. Deficiency in the first raw
transition elements as well as Zn and Mo leads to deficiency in enzymes containing them in
the body. The excess amounts of these soft and borderline metals prefer to react with the soft
bases e.g., glutathione and sulfur proteins which are considered antioxidants. The different
phenomena showed by the aforementioned elements will be discussed in the light of affinity
of their cations towards several anions.


TRANSITION METALS AND PLANTS

The higher plants which are usually contain chlorophyll as a photosensitizer synthesize
their nutrients and tissues from simple substances from air and different constituents in the
soil (e.g.CO
2
,O
2
, H
2
O, NO
-
3
, SO
-2
4
, Cl
-
, Ca
2+
, Mg
2+
, Fe
+2
, Mn
2+
, CO
2-
3
, etc.). These elements
can be classified to three categories based on demands of them by plant. These categories are
macro-micro- and benefitial nutrients [1, 2].
The macronutrients are those elements which are required for plant with a quantities
ranged between few- and many hundreds of kilograms / hectare. These elements namely are,
hydrogen, oxygen, nitrogen, carbon, phosphorous, calcium, magnesium and sulphur. Based
on the electronic configuration of these elements one can be classified as "s" and "b" block
elements [3].
On the other hand both micro- and beneficial elements (Mn, Fe, Co, Ni, Cu, Zn, Mo, B)
are belonging to "d" block elements except B which belongs to "s" block elements.
The last two categories of elements are required for healthy plants, with a quantity ranged
between few and several hundreds of grams/hectare. These elements have important roles in
Role of Reactivity of Transition Elements in Life 3
plants and microbial vital processes [4]. The most common ones of these roles especially their
participation in the enzyme systems [see table (1)][2].

Table 1. Functions of several micronutrients in higher plants

Micronutrients Functions in higher plants
Manganese Activates decarboxylase, dehydrogenase, and oxidase enzymes;
important in photosynthesis, nitrogen metabolism, and nitrogen
assimilation.
Iron Present in several peroxidase, catalase, and cytochrome oxidase
enzymes; found in ferredoxine which participates in oxidation
reduction reactions (e.g. NO
-
3
and SO
4
2-
reduction, nitrogen
fixation; important in chlorophyll.
Cobalt Essential for nitrogen fixation; found in vitamin B
12
.
Nickel Required as a component of the urease enzyme.
Zinc Present in several dehydrogenase, proteinase and peptidase
enzymes; promostes growth hormones and starch formation;
promotes seed maturation and production.
Molybdenum Present in nitrogenase (nitrogen fixation) and nitrate reductase
enzymes; essential for nitrogen fixation and high oxidizing.
Boron Activates certain dehydrogenase enymes; facilitates sugar
translocation and synthesis of nucleic acids and plant hormones;
essential for cell division and development.
Copper Present in laccase and several other oxidase enzymes; important in
photosynthesis, protein and carbohydrate metabolism, and probably
nitrogen fixation.

Based on these foregoing findings one can notices that macronutrient elements all among
the highly abundant elements in nature, where as micro- and beneficial elements are
considered as ones from less common elements [3], except iron.
The requirements of higher plants for hard acidic ions such as Ca
2+
, K
+
, [PO
2
]
1
can be
gained from constituents of soil as well as from artificial fertilizers such as Ca(NO
3
)
2
,
(NH
4
)
2
SO
4
, Ca (H
2
PO
4
)
2
, K
2
SO
4
, KNO
3
etc. These fertilizers do not suffer from
inconsistency in case if they applied in an alkaline soil.
The microand beneficial nutrients are considered as soft and borderline elements except
Fe
3+
and B
3+
.
The positive ions of these elements are being soft or borderline ones except Fe
3+
and B
3+

which are hard acidic species. Based on the foregoing discussions one can say that their
bearing compounds are found as of insoluble compounds. The last ones are found in nature
[3] according to the following:
Mn (Mn-oxides, silicates and carbonates); Fe (Fe-oxides, sulphides and silicates); Co(Co-
sulphides and silicates); Ni (Ni-sulphides and silicates); Cu (Cu- sulphides, hydroxy
carbonates and oxides); Zn (Zn-sulphides, carbonates, and silicates). The molybdenum may
be found as sulphides, oxides and molybdates [3].
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 4
The previous forms are mostly insoluble so that they are converted to soluble salts (e.g.
sulphates, nitrates) before application as fertilizers). In case of application of these salts as
fertilizers in an alkaline soil, their ions suffer from inconsistancy and transformed to
insoluble hydroxides. In such case these nutrients given to the plant in the form of metal-
organic complexes stable at alkaline medium [4]. Here in the following one can find the
nomenclature as well as chemical formulae and abbreviations of the most chelating agents
used in preparation of the corresponding micro and beneficial metal organic complexes
which derived from ethylencdiaminetelra acetic acid and its derivates as well as citric and
oxalic acids: Ethylendiaminetetroacetic acid, (C
10
H
16
O
8
N
2
, EDTA); Diethylemetriamepenta
acetic acid (C
14
H
22
O
12
N
3
); cyclohexanediaminetetroacetic (C
14
H
22
O
8
N
2
, CDTA);
Nitriloacetic acid (C
6
H
9
O
6
N, HEDTA); Hydroxyethylemediaminetetroacetic acid (C
10
H
18
O
7
N
2
); Ethylenediaminedichydroxyphenyl-acetic acid (C
18
H
20
O
6
, EDDHA); Citric acid (C
6

H
8
O
7
, CIT); Oxalic acid (C
2
H
2
O
4
,OX) [5].


CHEMICAL ELEMENTS IN LIFE

Chemical elements essential to life forms can be divided into: (1) bulk elements (H, C, N,
O, P, S) which are present in large quantities; (2) macrominerals and ions; are those needed
by the body in relatively large amounts; being composed of the "s" block elements Na, K, Ca,
Mg and "p" block elements Cl and PO3- 4); (3) micro/trace minerals; are those needed in
small amounts and consist of the d-block elements vanadium, chromium, molybdenum,
manganese, iron, cobalt, nickel, copper and zinc, and are also known as the trace metals as
well as fluorine, silicon, selenium, arsenic and iodine. The bulk metals form 12% of the
human body-weight whereas the trace elements represent less than 0.01% [6]. Within cells,
distribution of metal ions is more complex in that the cells must themselves control any
competition between the metal ions in the same internal compartment; moreover, the metal
ions must also have a functional value. Those elements that are found prominently in most
cells, together with their free concentrations in the central cell compartment [6-8]. The
concentration of these elements varied from an element to another.

Table 2. The concentration of selected elements in the human body [6,7]

Element Concentration in body
(Wt)
Concentration in
cytoplasm (mol/L)
Na
+
0.1 10
-3

K
+
0.1 10
-1

Mg
2+
0.04 10
-3

Ca
2+
10
-7

Mn
2+
2 x 10
-5
10
-7

Fe
2+
0.005 10
-7

Co
2+
9 x 10
-6
< 10
-9

Ni
2+
2 x 10
-5
< 10
-9

Cu
2+
(Cu
+
) 2 x 10
-4
< 10
-14

Zn
2+
0.003 10
-11

MoO
4
-2
10
-8

Role of Reactivity of Transition Elements in Life 5
NUTRITIONALLY ESSENTIAL AND NON-ESSENTIAL METALS

Metals can also be classified as being nutritionally essential for humans such as cobalt,
chromium (III), copper, iron (II) and iron (III), manganese and molybdenum, in addition to
non-metal namely selenium and "d" closed zinc element. On the other hand metals one such
as arsenic, cadmium, lead, and mercury, and their inorganic compounds can even be toxic to
human health [9]. One can satte that these elements are considered as soft ones and can
perform stable compounds with soft sulfur compounds such as glutathione reductase and
thioproteins, preventing the last ones from preventing oxidative stress. Still there are some
metals which are not essential to human health but may have some beneficial effects at low
levels of exposure e.g., silicon, nickel, boron, and vanadium. These elements have the
capability of forming oxygen compounds. Meanwhile, boron, nickel, silicon, and vanadium
have been shown to have biological functions in plants and some animals but essentiality for
humans has not been demonstrated [9].
Soft elements are characterized by high polarizability, low electronegativity, small
negative charge, large size, covanent type of bond usually associated with the base (electron
donor), available empty orbitals on donor atom are low lying and associative. Hard elements
are characterized by low polarizability, high electronegativity, large negative charge, small
size, ionic electrostatic type of bond usually associated with the base, high energy and
associative available empty orbitals on donor atom.

Table 3. Nutritionally essential and non-essential elements

Nutritionally essential
elements (soft and
borderline elements)
Elements with possible
beneficial effects (hard and
borderline elements)
Elements with no known
beneficial effects (soft and
hard elements)
Cobalt : d block element
Chromium III : d block
element
Copper : d block element
Iron: d block element
Manganese : d block element
Molybdenum : d block
element
Zinc : d block element
Selenium : b block element
Boron : s block element
Vanadium : d block element
Nickel : d block element
Silicon : p block element

Aluminum s: block element
Barium s : block element
Beryllium s : block element
Strontium s: block element
Thallium s: block element
Silver : d block element
Antimony : p block element
Arsenic : p block element
Cadmium : p block element
Lead : p block element
Mercury (p)


THE BIOLOGICAL VALUES OF IRON, COPPER, MANGANESE,
NIKEL, CHROMIUM, ZINC, MOLYBDENUM, COBALT AND
VANADIUM IN HUMAN

Trace elements are those elements occurring in the human body but constituting 0.01% of
body weight [10]. The trace elements include iron, manganese, copper, zinc, molybdenum,
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 6
cobalt, vanadium, chromium, nickel, fluorine, silicon, selenium, arsenic and iodine. Their
concentrations, however, vary in different tissues. In particular iron, copper, selenium,
manganese, chromium, molybdenum and iodine are essential to human health that
metalloproteins represent about one third of all structurally characterized proteins with a
biological activity and over 40% of all enzymes contain metals [6, 11]. These metals are also
required to maintain the brain's biochemistry. Their interchangeable prevalent ionic forms and
affinity for functional groups occurring in proteins are unique properties of transition metals
that make them useful in biochemical redox reactions [12, 13]. Metals determine the
geometry of enzymatic active sites, act as centers for enzyme reactivity, and act as biological
oxidationreduction facilitators [8]. Transition metals that exist in multiple oxidation states
serve as electron carriers e.g., iron ions in cytochromes; as facilitators of oxygen transport
e.g., iron ions in hemoglobin and as sites at which enzyme catalysis occurs e.g., copper ions
in superoxide dismutase. Transition metal ions that exist in single oxidation states, such as
zinc(II), function as structural elements in superoxide dismutase and zinc-finger motifs [8].
Proteins with which transition metals and zinc are most commonly associated catalyze the
intramolecular or intermolecular rearrangement of electrons. Although the redox properties of
the metals are important in many of the reactions, in others the metal appears to contribute to
the structure of the active state, e.g., zinc in the Cu-Zn dismutases and some of the iron in the
photosynthetic reaction center. Sometimes equivalent reactions are catalyzed by proteins with
different metal centers; the metal binding sites and proteins have evolved separately for each
type of metal center [7].Copper- and zinc-containing superoxide dismutase, manganese-
containing superoxide dismutase, catalase, and glutathione peroxidase form the primary
enzymic defense against toxic oxygen reduction metabolites. But, metal-induced uncontrolled
redox reactions or displacement of endogenous metal cofactors from their cellular binding
sites can also lead to cellular perturbations [12, 13]. Moreover, any of the trace elements has
the potential to be toxic if given in sufficiently large quantities, but that for most trace
elements normal physiological or dietary conditions are extremely unlikely to achieve such
levels [14]. Whilst Fe, Cu, Cr, V and Co undergo redox-cycling reactions, for a second group
of metals, Hg, Cd and Ni, the primary route for their toxicity is depletion of glutathione and
bonding to sulfhydryl groups of proteins. Arsenic (As) is thought to bind directly to critical
thiols, however, other mechanisms, involving formation of hydrogen peroxide under
physiological conditions, have been proposed [15]. [As
5+
+ H
2
O
2

OH + As
3+
]. Iron and
copper are redox-active metals (i.e. can switch between oxidized and reduced forms:
Cu
2+
/Cu
1+
and Fe
3+
/ Fe
2+
) and often participate in electron transfer [16] (see below). Iron and
copper are also involved in dioxygen (O
2
) storage and carriage via metalloproteins [e.g.
hemoglobin, myoglobin and hemocyanin] [6]. Copper is found in essential proteins such as
cytochrome c oxidase, catechol oxidase, and ascorbate oxidase, a Cu/Zn superoxide
dismutase, and many other oxidoreductases, and monooxygenases. It is responsible for
oxidation-reduction processes that involve electron transfer, dioxygen chemistry, and
reduction of nitrogen oxides. Its position in the middle of the elements of the first transition
series (so designated because their ions have incompletely filled d orbitals) implies that iron
has the possibility of various oxidation states (from II to +VI), the principal ones being II
(d6) and III (d5), although a number of iron-dependent monooxygenases generate high valent
Fe(IV) or Fe(V) reactive intermediates during their catalytic cycle [17](Crichton, 2001).
Copper exists mainly in two oxidation states, Cu(I) and Cu(II), and often changes between
these two states while catalyzing reactions. Transition metals such as iron and copper are
Role of Reactivity of Transition Elements in Life 7
involved in both metal-catalyzed (auto) oxidations and reactions leading to hydroxy1
radical production from superoxide, a species frequently proposed to initiate lipid
peroxidation. Similar mechanisms involving the Fenton-like production of superoxide anion
and hydroxyl radical appear to be involved for iron, copper, chromium, and vanadium.
However, with some metal ions, such as mercury, nickel, lead, and cadmium, depletion of
glutathione and protein-bound sulfhydryls may play a primary role in the overall toxic
manifestations [12].

2O
2
-
+2H
+
H
2
O
2
+O
2

Fe
2+
+H
2
O
2
Fe
3+
+

OH+OH
-

Traces of Fe
3+
can react further with H
2
O
2
:

Fe
3+
+H
2
O
2
Fe
2+
+O
2
-
+H
+

Possible more reactions:

OH+H
2
O
2
H
2
O+H
+
+O
2
-

O
2
-
+Fe
3+
Fe
2+
+O
2

OH+Fe
2+
Fe
3+
+OH
-

2H
2
O
2
+ Fe salt catalyst2H
2
O+O
2

Cu
+
+ H
2
O
2
Cu
2+
+

OH +OH
-
CH
3
OH+

OH H
2
O+

CH
2
OH
Cl+

OHCl

+OH
-

H
2
O
2
+O
2
-
O
2
+OH
-
+

OH
Fe
3+
+O
2
-
Fe
2+
+ O
2

(O2- reducing the iron salt)

Fe
2+
+ H
2
O
2
Fe
3+
+

OH +OH
-

(Fenton reaction)

Net : O
2
-+H
2
O
2
+ Fe salt catalyst O
2
+

OH+OH
-


The levels of essential metals are strictly regulated by specific metal transporters at
gastrointestinal tract and blood-brain barrier. When dietary levels of essential metals are low,
levels of the corresponding transporters increase in the intestine, after which there is a greater
potential for increased transport of toxic metals. The divalent metal transporter 1 (DMT1),
actively transport Fe, Zn, Mn, Co, Cd, Cu, Ni, and Pb, via a proton-coupled mechanism [18].
Involvement of intracellular transporters for copper and zinc has been shown in animal
models of Alzheimer's disease, raising the possibility that higher levels of iron, zinc and
copper might be due to a disruption in the activity of transporters. Accordingly, exposure to
toxicants that affect the activity of transporters potentially could contribute to the
aetiology/progression of neurodegenerative diseases [19] as we will see later. Two non-
enzymatic proteins, ferritin and ceruloplasmin, also appear to play important roles in
transition-metal storage and antioxidant defense in vivo. Ferritin, which binds iron in the
cytoplasm of mammalian cells, and ceruloplasmin, which binds copper in plasma, are thought
by many to contribute a significant antioxidant capacity to bodily fluids. Other proteins that
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 8
bind metals include transferrin, haptoglobin, albumin and metallothioneins are in the same
sense protective. The latter belong to a family of low molecular weight, cysteine rich
intracellular proteins that bind transition metals, including zinc and cadmium [20].


Iron

Iron is the most abundant transition metal and the second most prevalent metal of the
earths crust [17]. Iron is essential for microbial, plant, animal, and human life [21]. The
amount of total body iron is around 3 to 4 grams which is contained mainly in the
haemoglobin of the erythrocytes. The major site of iron storage in the body is the liver. Red
cell turnover constitutes the major pool of iron turnover in the body [22, 23]. Most iron is in
the form of heme iron that is found in hemoglobin, myoglobin, and iron-containing enzymes
(such as catalase and the cytochromes). More than two thirds of the bodys iron content is
incorporated into hemoglobin in developing erythroid precursors and mature red cells. The
rest of the total body iron exists as a nonheme iron, which consists of plasma iron, iron bound
to transferrin, and stored iron in ferritin and hemosiderin [22, 24]. Iron is a key player in some
of the most central processes of biological systems, including oxygen transport and
utilization, electron transfer, metabolism of nucleic acids and many other key biological
molecules, degradation of biological pollutants, and many other reactions [25]. The
duodenum and proximal jejunum are the main sites of absorption of dietary iron. Haem iron is
absorbed more efficiently than non-haem iron, apparently by endocytosis of the intact iron
protoporphyrin complex at the enterocyte brush border. Iron is then liberated from the haem
moiety by the action of haem oxygenase and enters the intracellular iron pool from which it
can be transferred across the basolateral membrane, bind to transferrin and enter the
circulation. Meanwhile, absorption of non-haem iron requires reduction of ferric iron at the
brush border membrane, followed by internalization by a proton coupled transporter [2]. In
normal human plasma, serum iron (~ 20 M) exists primarily in the Fe
3+
form and is
complexed with the high affinity iron binding protein transferrin, an 80-kd glycoprotein that
is synthesized in the liver (Tf; ~ 40 M) in a 2:1 ratio. At blood pH (7.4), each molecule of
transferrin can bind two atoms of ferric iron [27]. Only one third of the transferrin is saturated
with iron which implies that all the iron in the circulation is bound to transferring. In
circumstances in which the binding capacity of transferring becomes saturated, as for
example in iron loading disorders, iron forms low-molecular-weight complexes, the most
abundant of which is iron citrate [26]. Most cellular uptake of ferric iron (Fe
3+
) occurs via
receptor-mediated endocytosis of transferrin (vesicular import pathway IN2) which binds to
specific membrane-bound transferrin receptor (TfR). Inside the cell, members of the Steap
family of ferric reductases localize to the endosome and reduce Fe
3+
(ferric) to its Fe
2+

(ferrous) form before Fe
2+
is released into the cytosol by the divalent metal transporter-1
(DMT1) in an H
+
-dependent manner [28]. DMT1 is not specific to iron; it can transport a
wide variety of divalent metal ions, including manganese, cobalt, copper, zinc, cadmium, and
lead [22]. Free Fe
2+
in the cytosol constitutes a labile iron pool (~ 2-3 M) for cellular
utilization, supplying Fe
2+
molecules as co-factors for many Fe
2+
-dependent enzymes in the
cytosol, mitochondria, and nucleus. If cytosolic iron is not immediately used, it can also be
rapidly sequestered by cytosolic Ft into a non-reactive Fe
3+
- Ft complexes. Iron can be
Role of Reactivity of Transition Elements in Life 9
released from cells by the iron exporter ferroportin [29]. Fe
3+
can be bound in the
extracellular space by Tf, citrate, ascorbate, or ATP. Cytosolic or intralysosomal iron
overload may catalyze the production of free radical oxides via the Fenton reaction. Radical
oxides may cause cellular damage by oxidizing macromoleucles such as lipids, DNA, and
proteins. Iron transport across the blood brain barrier is the result of receptor-mediated
endocytosis of iron-containing transferrin by capillary endothelial cells, followed by recycling
of transferrin to the blood and transport of non-transferrin-bound iron into the brain. The
principle sources of extracellular transferrin in the brain are hepatocytes, oligodendrocytes,
and the choroid plexus [30].


Copper

Copper is the third most abundant metallic element in the human body, following iron
and zinc, and it is important in all other life forms. The daily intake of Cu ranges from 0.6 to
1.6 mg / day with the main sources of Cu being seeds, grains, nuts, beans, shellfish, and liver.
It is estimated that the adult human body contains between 50-150 mg [31, 32]. Free Cu2+
content of human plasma is approximately 2x10-16 M [33-36] and total copper
concentrations in most tissues are approximately 5x10-5 M total copper [37]. Clinically
apparent copper deficiency is extremely rare and difficult to achieve by dietary means, but
loss-of-function mutations in the ATP7A gene encoding a copper-transporting P1B-type
Atpase, involved in the delivery of copper to the secreted copper enzymes and required for
copper absorption and homeostasis is associated with Menkes disease, resulting severe tissue
copper deficiency, seizures, neurodegeneration, psychomotor deterioration, failure to thrive,
and death in early infancy [38, 39]. On the other hand, the toxicity associated with excess
copper manifest in Wilson disease, a rare, autosomal recessive disorder of copper metabolism
where tissue copper accumulation results in hepatic, neurologic, or psychiatric
disturbances. Mutations in the ATP7B gene which is located on the long arm (q) of
chromosome 13 (13q14.3) cause failure of copper excretion into the bile and a defective
incorporation of copper into ceruloplasmin [40]. Copper homeostasis is maintained by
adjusting intestinal copper absorption and copper excretion in bile. Copper is absorbed in the
proximal intestinal tract, facilitated by the simultaneous absorption of amino acids and
decreased by zinc and vitamin C. Excretion which occurs primarily through the bile is
increased by molybdenum, as well as by diets high in calcium and phosphorus. The excretion
of

copper into the gastrointestinal tract increases when dietary copper is high and more is
absorbed, thereby, protecting against excess accumulation of

copper in the body. Vice versa,
low copper intake is associated with little endogenous copper is

excreted, protecting against
copper depletion [41]. This is controlled by specific transporters that take up metals at the
apical surface and export them at the basolateral surface of intestinal cells, and are involved in
their intracellular distribution. The level of these transporters increases or decreases in the
intestine according to the dietary levels of essential metals [19]. The uptake of Cu into the
cells is mediated by two transporter proteins; Cu transporter 1 (Ctr1) and divalent metal
transporter 1 (DMT1) that transports Cu across the plasma membrane (located on the plasma
membrane). ATP7A and ATP7B are membrane-bound copper-transporting P-type ATPases
that catalyze an ATP-dependent transfer of Cu to intracellular compartments or participate in
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 10
Cu efflux from the cell [42]. Cellular copper excretion also involves COMMD1 [copper
metabolism (Murr1) domain containing 1] [43]. Most of Cu ions absorbed from the small
intestine are distributed to liver and kidneys; they are transported in blood mostly (65-90%)
by tightly binding to protein "ceruloplasmin", synthesized in the liver where it binds Cu and
the rest of Cu loosely binds with albumin, transcuprein and amino acids (e.g., histidine) [33].
Only reduced Cu can be transported [43]. Cu is transported into the brain through the blood
brain barrier as a free Cu ion [44]. Redox cycling between Cu
2+
and Cu
1+
can catalyse the
production of highly toxic hydroxyl radicals, with subsequent damage to lipids, proteins,
DNA and other biomolecules. Free intracellular copper is detoxified primarily by
metallothionein (MT) proteins. Metallothioneins are ubiquitous low molecular weight
proteins rich in cysteine residues that have high metal-binding capacities. They bind heavy
metal ions (mainly Cd, Zn and Cu) via metal-thiolate clusters, thus they are essential in metal
homeostasis and protect against metal toxicity [45, 46]. The incorporation of intracellular
copper into the structure of different cuproenzymes is carried out by copper chaperones;
Atox1 (delivers copper to copper transporting ATPases in the late Golgi), CCS (copper
chaperone for SOD, required for copper incorporation into Cu/Zn superoxide dismutase), and
Cox17, Sco1 and Sco2 (delivers copper to subunits of mitochondrial cytochrome c oxidase)
[43, 47]. Copper chaperones through transporting copper in the cytoplasm to the site of
utilization by copper-dependent proteins, ensure that copper can reach its specific target
protein and also prevent inappropriate copper interactions with other cellular, protecting the
cell from the deleterious effects of free copper e.g., protection against oxidative stress [48].
An increase in the endogenous level of Atox1 expression have been demonstrated protect
neurons against oxidative stress. Furthermore, overexpression of an Atox1 metal binding
mutant is detrimental to cell viability. Furthermore, mutations in the copper binding motif of
Atox1 result in a dominant negative phenotype where the cell viability is diminished [49].
The copper chaperone for the superoxide dismutase gene is necessary for expression of an
active, copper-bound form of

superoxide dismutase in vivo in spite of the high affinity

of
superoxide dismutase for copper. This metallochaperone protein

activates the target enzyme
through direct insertion of the copper

cofactor and apparently functions to protect the metal
ion from

binding to intracellular copper scavengers. Thus intracellular [Cu]
free
is limited to
less than one free copper

ion per cell and a pool of free copper ions is not

used in
physiological activation of metalloenzymes [50]. The highest concentration of CCS is found
in the kidney and liver. There is also a significant amount of this copper chaperone protein in
the CNS being found throughout the neuropil, with expression largely confined to neurons
and some astrocytes [51]. Cu is required as a catalytic cofactor in various cuproenzymes,
including the mitochondrial cytochrome c oxidase, a component of the electron transport
chain, caeruloplasmin, monoamine oxidase, dopamine B-hydroxylase, tyrosinase, involved in
the production of melanin histaminase, lysyl oxidase, involved in the cross-linking of elastin
and collagen, and Cu/Zn-superoxide dismutase. The enzyme superoxide dismutase (SOD)
occurs in three forms in mammalian systems: (1) CuZnSOD (SOD1) found in the cytosol, (2)
MnSOD (SOD2) found in mitochondria, and (3) CuZnSOD found in extracellular space
(SOD3). The active site in Cn/Zn superoxide dismutase consists of one Cu atom and one Zn
atom, coordinated to a common histidine ligand; His63 in human SOD1 and His61 in human
SOD2. The copper atom is coordinated by three other histidine residues and zinc is
coordinated by two other histidine residues and one asparagines [52]. Additionally, many
Role of Reactivity of Transition Elements in Life 11
bacterial SOD enzymes contain iron. Copper is also an essential component of chromatin and
is involved in chromatin scaffold proteins. Food copper (organic

copper) is processed by the
liver and is transported and sequestered

in a safe manner. Inorganic copper, such as that in
drinking

water and copper supplements, largely bypasses the liver and

enters the free copper
pool of the blood directly. This copper

is potentially toxic because it may penetrate the
blood/brain

barrier [53]. Cu toxicity comes about from its ability to produce reactive oxygen
species, displace other metal ions, peroxidize lipids, and directly cleave DNA and RNA.
Copper exists physiologically in two redox states, as cuprous Cu1+ (reduced) or cupric Cu
2+

(oxidized) and can interchange between these forms by accepting or donating an electron.
This allows the cation to participate in biochemical reactions as a reducing or oxidizing agent
[54]. This same properties which make copper being essential for various enzymatic
reactions, is also responsible for copper toxicity via its ability to generate free radicals, in
particular, the highly reactive hydroxyl radical through Fenton chemistry, which subsequently
can damage lipids, proteins, DNA and other biomolecules [55]. Most extracellular copper is
Cu(II) and most, if not all, intracellular copper is Cu(I). Typical intracellular copper-binding
proteins, such as the Cu-transporting P-type ATPases ATP7B and ATP7A bind copper as
Cu(I)[54]. It has been suggested that, the toxic and carcinogenic potential of mineral dusts
inhaled into the lungs is related, in part, to biochemical reaction mechanisms involving iron
and reactive oxygen species that occur at the mineral surface [56, 57]. Many cancer tissues
contain highly elevated levels of Cu [58, 59]. The reasons for this elevation are unclear but
one possible result is increased angiogenesis [60, 61]. The copper-chelating agent, trientine,
suppressed tumor development and angiogenesis in the murine hepatocellular carcinoma cells
[62]. A copper transporter, Ctr1p, was discovered to mediate cisplatin uptake in yeast and
mammals. Increased cisplatin resistance caused by deletion of the Ctr1 gene suggests its
important role in cellular resistance. This finding presents a potential target for modulating
cisplatin antitumor efficacy [63].The combined treatment with a copper chelator and cisplatin
increased cisplatin-DNA adduct levels in cancerous but not in normal tissues, impaired
angiogenesis, and improved therapeutic efficacy. Others reported increased accumulation of
iron, nickel, chromium, zinc, cadmium, mercury, and lead in breast cancer samples [64].
Cancerous cells have more transferrin receptors than normal cells [65] because of their need
for oxygen. In our opinion, the high levels of singlet oxygen attacks the species of sulphur
(glutathione) which acts as an antioxidant. The complexation of metals with SH bearing
compounds leads to a decrease in antioxidant capacity.


Manganese

Manganese (Mn) is the 12th most abundant element in the earths crust comprising about
0.1% of the earths crust [66, 67]. Manganese is an essential mineral for humans, animals, and
plants. It is present in virtually all diets at low concentrations. Mn is present in most tissues of
all living organisms and is present naturally in rocks, soil, water, and food. Humans maintain
stable tissue levels of Mn via tight homeostatic control of both absorption and excretion of
ingested Mn and limit tissue uptake at low to moderate levels of inhalation exposure [68-70].
The most significant source of manganese exposure for the general population is food. The
highest manganese concentrations are found in nuts (up to 47 g/g) and grains (up to 41
g/g). Lower levels are found in milk products (0.020.49 g/g), meat, poultry, fish, and eggs
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 12
(0.103.99 g/g), and fruits (0.2010.38g/g). Tea and leafy green vegetables have also been
found to be dietary sources of manganese [71]. Mn is absorbed from the gastrointestinal tract,
within the plasma, Mn is largely bound to gamma-globulin and albumin, and a small fraction
of trivalent (3+)Mn is bound to the iron-carrying protein, transferring [70]. The Mn adequate
intake for adult men and women is 2.3 and 1.8 mg/day, respectively [71]. Serum
concentration of Mn in healthy subjects is about 0.050.12 g/dl [72].
The total amount of manganese in the adult human (70 kg) has been determined to be
about 10-20 mg, most of which is found in skeleton, liver, kidney, pancreas and the heart. The
rest is distributed widely throughout all the tissues and fluids. A daily requirement for
manganese has not been established; however, it appears that a minimum intake of 2.5 to 7
milligrams per day meets human needs. In humans, manganese is an essential nutrient that
plays a role in bone mineralization, protein and energy metabolism, metabolic regulation,
cellular protection from damaging free radical species, and the formation of
glycosaminoglycans. An adequate amount of this trace mineral would be absolutely vital
during gestation for normal foetal growth and development [73,74]. Mn dependent enzyme
families include oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases.
Manganese metalloenzymes include arginase (liver urea), glutamine synthetase (brain
ammonia metabolism), phosphoenolpyruvate decarboxylase (gluconeogenesis). Mn is also the
key component of superoxide dismutase (Mn-SOD) found in mitochondria of the cells. The
manganese-containing superoxide dismutase (MnSOD) is a major component of the cellular
defence mechanisms against the toxic effects of the superoxide radical [75].
While Mn deficiency is extremely rare in humans, toxicity due to overexposure of Mn is
more prevalent. Mn toxicity has been reported in individuals exposed to high environmental
levels of Mn e.g. miners, welders and those living near ferroalloy processing plants. Toxicity
can also result from dietary overexposure and is evidenced primarily in the central nervous
system, although lung, cardiac, liver, reproductive and fetal toxicity have been noted [72].
The brain appears to be especially vulnerable to Mn accumulation resulting in is an
established clinical entity, referred to as manganism which is a progressive disorder of the
extrapyramidal system similar to Parkinson's disease in its clinical features, both in laboratory
animals and humans [69, 70]. Neurotoxicity due to excessive brain manganese (Mn)
accumulation can occur via occupational exposure to aerosols or dusts that contain extremely
high levels (>1-5 mg Mn/m(3)) of Mn, consumption of contaminated well water, or parenteral
nutrition therapy in patients with liver disease or immature hepatic functioning such as the
neonate(decreased biliary excretion). Although Mn exposure via parenteral nutrition is
uncommon in adults, in premature infants, it is more prevalent [76].
Transport of manganese across the blood-brain barrier occurs by means of a series of
transporters. Movement can take place by facilitated diffusion, active transport [77] via
divalent metal transport and transferring (Tf)-dependent transport. Biliary excretion
represents the main mechanism by which manganese is eliminated from the body [78]. Mn
disposition in vivo is influenced by dietary iron intake and stores within the body since the
two metals compete for the same binding protein in serum (transferrin) and subsequent
transport systems (divalent metal transporter, DMT1). There appear to be two distinct carrier-
mediated transport systems for Mn and ferrous ion: a transferrin-dependent and a transferrin-
independent pathway, both of which utilize DMT1 as the transport protein [79]. In primary
astrocyte cultures derived from neonatal rats.. Both iron deprivation (ID) and iron overload
(+Fe) caused significant increases (p<0.05) in (54)Mn uptake in astrocytes. The decreased
Role of Reactivity of Transition Elements in Life 13
TfR associated with +Fe treatment and the increased DMT-1 levels suggest that DMT-1 is a
likely putative transporter of Mn in astrocytes [80]. Fe deficiency can enhance brain Mn
accumulation even in the absence of excess Mn in the environment or the diet, suggesting that
there is homeostatic relationship among several essential metals in the brain and not simply
between Fe and Mn [81]. Mn transport appears to be temperature, energy, and pH dependent,
but not Fe or Na(+) dependent. These data suggest that Mn transport across the BBB is an
active process [82]. After intravenous contrast injection, normal (enteral) regulation
mechanisms for manganese homeostasis are bypassed, and there is a danger of individual
overdosing. Excess manganese, for example in patients with chronic liver disease or with
chronic parenteral nutrition, has already been detected by magnetic resonance imaging in the
basal ganglia and was found to coincide with neurologic symptoms [83].


Zinc

Zn is the trace element which is essential for cell growth and maintenance of cellular
integrity. It is an integral structural component of nearly 300 enzymes and other proteins
involved in the expression of genetic information and cellular signal transduction. Zinc is
present in all body tissues and fluids. The total body zinc content has been estimated to be
30mmol (2g). Skeletal muscle accounts for approximately 60% of the total body content and
bone mass, with a zinc concentration of 1.53mol/g (100200g/g), for approximately 30%.
Lean red meat, whole-grain cereals, pulses, and legumes provide the highest concentrations of
zinc: concentrations in such foods are generally in the range of 2550mg/kg (380
760mol/kg) raw weight. Fish, roots and tubers, green leafy vegetables, and fruits are only
modest sources of zinc, having concentrations <10mg/kg (<150mol/kg) [84].
Zinc deficiency can result from low-zinc-containing diets (e.g., vegetarians), prolonged
intravenous alimentation, gastrointestinal disease associated with diarrhea [85]. In humans,
inherited zinc deficiency is rare and associated with defects in membrane-bound putative
zinc transporters leading to impairment of zinc absorption in the gut and the syndrome of
acrodermatitis enteropathica, characertized by skin lesions, alopecia, diarrhoea,
neuropsychological disturbances and reduce immune function and led to death of the patient
in the absence of treatment. A zinc deficiency disorder also occurs in premature breast fed
infants [86].
Zinc is relatively abundant in biological materials being an essential component of
hundreds of proteins and metalloenzymes including alkaline phosphatase, lactate
dehyrogenase, carbonic anhydrase, angiotensin-converting enzyme, collagenase, -
aminolevulinic acid anhydrase, protein kinase C, phospholipase C, aspartate
transcarbamylase, nucleotide phosphorylase (5-nucleotidase) carboxypeptides, and DNA and
RNA polymerases found in most body tissues [85, 87]. The major location of zinc in the body
is metallothionein, which also binds copper, chromium, mercury, and other metals. Among
the well-characterized zinc proteins are the Cu-Zn superoxide dismutases (other forms have
Fe or Mn), carbonic anhydrase (an abundant protein in red blood cells responsible for
maintaining the pH of the blood), alcohol dehydrogenase, and a variety of hydrolases
involved in the metabolism of sugars, proteins, and nucleic acids. Zinc is a common element
in nucleic-acid polymerases and transcription factors, where its role is considered to be
structural rather than catalytic [88].
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 14
Zinc plays specific and important catalytic, co-catalytic and structural roles in enzyme
molecules and in many other proteins and biomembranes. A well-known example of the
structural role of zinc in cellular and subcellular metabolism is the zinc finger motif,
ubiquitous in transcription proteins. The configuration of zinc fingers, critical to DNA
binding, is determined by the single zinc atom at their base. The linking of zinc fingers to
corresponding sites on the DNA initiates the transcription process and gene expression.
Motifs similar to zinc fingers have been identified in nuclear hormonal receptors including
those for vitamin D, estrogen and testosterone. Zinc plays an important role as ionic signaling
in large number of cells and tissues. Zinc-binding proteins account for nearly half of the
transcription regulatory proteins in the human genome, and during the past two decades, well
over 2000 zinc-dependent transcription factors involved in gene expressions of various
proteins have been reported [87, 88].
Among the transition metals playing key roles in biological systems, zinc is second only
to iron in biological prevalence. Unlike iron and copper, zinc has only one oxidation state
accessible under physiological conditions, and therefore does not participate in catalysis of
redox chemistry or electron transfer reactions. Unlike other first-row transition metals (e.g.,
Sc
2+
, Ti
2+
, V
2+
, Cr
2+
, Mn
2+
, Fe2+, Co
2+
, Ni
2+
and Cu
2+
), the zinc ion (Zn
2+
) contains a filled d
orbital (d10) and therefore does not participate in redox reactions but rather functions as a
Lewis acid to accept a pair of electrons [89]. The types of enzymatic reactions in which zinc
is found to play a role include peptidases and amidases, phosphatases, phospholipase,
phosphotriesterase, deaminases and alcohol dehydrogenase, among others. One mechanism
by which zinc is believed to facilitate some of these reactions is through binding and thereby
lowering the pKa of water, generating a localized high concentration of metal-bound
hydroxide in the active site, which can act as a nucleophile in the hydrolytic reactions [25].
Zinc is very different from magnesium, manganese and calcium. It binds nitrogen and
sulfur much more readily and also shows lower coordination numbers in spite of its size
(which is intermediate between that of magnesium and divalent manganese. It was found that
the predominant ligand to zinc depends on the coordination number of the metal ion, whereas
the other metal ions just listed each prefer oxygen at all coordination numbers. Zinc tends to
form 4-, 5-, and 6- coordinate complexes with about equal ease. When the coordination
number is four, sulfur is as likely a ligand as oxygen, when it is 5 nitrogen is the most
common ligand, and for coordination numbers 6 and 7 oxygen predominates as a ligand.
Thus, zinc can possibly replace magnesium or divalent manganese (since they both bind
oxygen when their coordination number is 6), but it has other options for coordination, in
keeping with its reactivity in the active sites of enzymes (often involving a change in
coordination number). [90].


Molybdenum

Molybdenum is a very rare element with a crustal abundance of about 1.2 mg/kg [91].
Molybdenum is the only second-row transition metal that is required by most living
organisms [92]. The tolerable upper intake level for the United States and Canada was set at 2
mg/d in 2002 [93], and the European Commission suggested an upper limit of 0.6 mg/d
[94].The availability of molybdenum to biological systems is due to the high water solubility
of oxidized forms of the metal. In man, absorption of molybdenum after oral intake is in the
Role of Reactivity of Transition Elements in Life 15
range of 28-77% and urinary excretion is 17-80% of the total dose [95]. Stable-isotope studies
of molybdenum metabolism have been conducted in which molybdenum was added to the
diet and was assumed to be absorbed and utilized similarly to the molybdenum in foods.
These studies showed that molybdenum is well absorbed over a range of intakes, that it is
rapidly excreted via the urine, and that total body molybdenum retention is regulated
primarily via urinary excretion. With high molybdenum intake, molybdenum absorption
increases and excretion is more rapid [96]. In healthy young men, absorption of molybdenum
from the intestine increased at higher molybdenum intakes.Urinary output appears to be the
key pathway for regulating the body's exposure to molybdenum. Higher molybdenum intake
resulted in higher rates of urinary excretion [97]. Because molybdenum toxicity is associated
with copper intake or depleted copper stores in the body, humans who have an inadequate
intake of dietary copper or some dysfunction in their copper metabolism that makes them
copper-deficient could be at greater risk of molybdenum toxicity [95].
Deficiency is rare in humans and is limited primarily to genetic defects leading to serious
abnormalities. Molybdenum cofactor deficiency in humans results in the loss of the activity of
molybdoenzymes sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. The
resultant severe phenotype, which includes progressive neurological damage leading in most
cases to early childhood death, results primarily from the deficiency of sulfite oxidase.
Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency are autosomal
recessive inborn errors of metabolism with severe neurological symptoms resulting from a
lack of sulfite oxidase activity [98, 99].
The metal itself is biologically inactive unless it is complexed by a special cofactor. With
the exception of bacterial nitrogenase, where Mo is a constituent of the FeMo-cofactor, Mo is
bound to a pterin, thus forming the molybdenum cofactor (Moco) which is the active
compound at the catalytic site of all other Mo-enzymes. Several enzymes in humans contain
molybdenum catalysing diverse redox reactions. In man, these enzymes, sulfite oxidase,
xanthine oxidase, and aldehyde oxidase, contain the same molybdenum complex,
molybdopterine. The molybdenum enzymes xanthine oxidase, sulfite oxidase and aldehyde
oxidase are involved in the human diseases of gout, combined oxidase deficiency and radical
damage following cardiac failure. Sulfite oxidase catalyzes the final step in the degradation of
sulfur-containing amino acids and is involved in detoxifying excess sulfite. Xanthine oxidase
is the final enzyme in the conversion of hypoxanthine to xanthine, and subsequently, to uric
acid. Aldehyde oxidase catalyzes the oxidation of aldehydes, pynmidines, purines, pteridines,
and related compounds [100, 101].



Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 16


The metal is found in three different oxidation states (IV, V and VI) and has the desirable
ability to couple biological compounds that are obligatory two-electron carriers (e.g. NADH)
with obligatory one-electron carriers (e.g. iron-sulphur centres and cytochromes) [102].


Cobalt

Cobalt is the least abundant 3dr transition metal (in sea water and earth crust). Cobalt is
found in vitamin B12 , its only apparent biological site. Vitamin B12 occurs in the body
mainly as methylcobalamin, adenosylcobalamin and hydroxycobalamine(a precursor to
methyl and adenosylcobalamine). Hydroxycobalamine is most stable form of all cobalamine
and is water soluble. B 12 is found in animal protein and not in vegetables. Cobalt is an
essential metal for humans and has to be ingested in the form of cobalamines (vitamin B12).
Only microorganisms can biosynthesize cobalamine. Cobalt in cobalamines can be reduced
and oxidized (2-one electron steps), thus cobalamine containing enzymes participate in redox
reactions. Vitamin-B 12 deficiency causes the severe disease of pernicious anemia in humans,
which indicates the critical role of cobalt [103, 104].
The vitamin B
12
cofactors coenzyme B
12
or 5-deoxy-5-adenosylcobalamin (AdoCbl),
and methylcobalamin (MeCbl) consist of cobalt(III) bound to a substituted corrin ring and an
alkyl group (either adenosyl or methyl). Adenosylcobalamin (AdoCbl) or coenzyme B12 is an
organometallic cofactor that functions as a radical reservoir and is used by enzymes to
catalyze rearrangement reactions in which a hydrogen atom and a variable group on adjacent
carbons are interchanged (mutases and eliminases). Methylcobalamin (MeCbl) is the cofactor
of several methyltransferases, such as methionine synthase (MetH), which catalyzes
methionine biosynthesis both in mammals and bacteria [104, 105].


Chromium

Chromium is an essential nutrient required for sugar and fat metabolism. The estimated
safe and adequate daily dietary intake for Cr is 50 to 200 microg. However, most diets contain
less than 60% of the minimum suggested intake of 50 microg, suggesting that the normal
Role of Reactivity of Transition Elements in Life 17
dietary intake of Cr for humans is suboptimal. Trivalent Cr has a very large safety range and
there have been no documented signs of Cr toxicity in any of the nutritional studies at levels
up to 1 mg per day [106]. Trivalent chromium is an essential nutrient required for sugar and
fat metabolism. Most recent evidence strongly supports the conclusion that there is little fear
of toxic reactions from chromium consumption. In addition to type 2 diabetes mellitus,
chromium supplementation may be useful to direct overall weight decrements specifically
towards fat loss with the retention of lean body mass and to ameliorate many manifestations
of aging [107]. There is growing evidence that chromium may facilitate insulin signaling and
chromium supplementation therefore may improve systemic insulin sensitivity. However,
supplementation with chromium picolinate, a stable and highly bioavailable form of
chromium, has been shown to reduce insulin resistance and to help reduce the risk of
cardiovascular disease and type 2 diabetes [108]. However, controversy exists as to whether
dietary supplementation with chromium should be routinely recommended in subjects
without documented deficiencies [109]. Whether chromium is an essential element has been
examined for the first time in carefully controlled metal-free conditions using a series of
purified diets containing various chromium contents. Animal studies reveal that a diet with as
little chromium as reasonably possible had no effect on body composition, glucose
metabolism, or insulin sensitivity compared with a chromium-"sufficient" diet [110].


Vanadium

Vanadium, a dietary micronutrient, is yet to be established as an essential part of the
human diet. Vanadium is abundant in rocks and soil [110]. Constituting 0.015% of earth's
crust, vanadium is about as abundant as zinc [111]. In water the presence of vanadium derives
almost exclusively from the solubilization of the metal present in soil and in rocks [110].
Exposure to the vanadium in water is enough to affects its presence in the daily diet and
determines greater values of the element in the principal biological liquids in people [112].
The metal is present in comparatively high concentration of vanadium in sea water, being
second most abundant transition metal (30 nM Na
+
2VO
-
4
), only surpassed by molybdenum
(100 nM molybdate), and clearly more abundant than iron (0.021 nM). Vent-derived iron
oxides have been shown to scavenge vanadium from sea water and thus to contribute in
controlling the concentration and cycling of vanadium in the oceans [111]. Concentrations in
soil vary in the range 3-310 g/g and may reach high values (up to 400 g/g) in areas polluted
by fly ash. The concentration of vanadium in water is largely dependent on geographical
location and ranges from 0.2 to more than 100 g/litre in freshwater, and from 0.2 to 29
g/litre in seawater [113]. Vanadium is introduced into man through the intake of food,
especially whole meal cereals, but also beef, chicken, milk, spinach, mushrooms, parsley
[114]. The mean vanadium concentration in the diet was reported to be 32 g/kg (range 19-50
g) and the mean daily intake was estimated to be 20 g/day [113]. Absorbed vanadium is
transported mainly in the plasma, bound to transferrin. Pentavalent vanadium is reduced in
erythrocytes to the tetravalent form. This reduction is a glutathione-dependent process [113].
It appears that values, around 1 nmol/l for blood and serum and around 10 nmol/l or slightly
lower for urine may be considered tentative normal values [115].
This transition element is known to influence a battery of enzymatic systems, namely
phosphatases, ATPases, peroxidases, ribonucleases, protein kinases and oxidoreductases.
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 18
In biological conditions, vanadium fulfils two conditions for a potential biometal: (i)
redox activity in an electrochemical potential (and free energy) frame relevant for
biochemical processes, and (ii) susceptibility for nucleophilic substrates.Vanadium easily
switches between the oxidation states V and IV (which, along with III, are the oxidation states
of naturally occurring vanadium compounds). The redox potential at pH 7 for the couple
H
2
VO
4
-
+4H
+
+e
-
VO
2+
+ 3H
2
O amounts to -0.341 V and thus is in the range where
vanadyl (VO
2+
) is oxidised to vanadate under aerobic conditions, and vanadate reduced to
vanadyl by cellular components such as cysteine containing peptides (glutathione) and
proteins, ascorbate, NADH, and phenolic compounds. The main species present under
physiological aerobic conditions is the acid-base pair H
2
VO
4
-
HVO
4
2-
+ H
+
(pk
a
= 8.1)
[111].


Nickel

Nickel is widely distributed in the environment. Natural sources of atmospheric nickel
include dusts from volcanic emissions and the weathering of rocks and soils. Thus, humans
are constantly exposed to this ubiquitous element although in variable amounts. The daily
dietary intake of nickel is 2535 g, and it is more than triple the daily requirement [116].
Generally, greater than 250 g nickel of Ni/g of diet are required to produce signs of Ni
toxicity such as depressed growth and anaemia in animals [117]. Ni-dependent enzymes are
urease, [NiFe] hydrogenase, [Ni] superoxide dismutase, CO dehydrogenase, and S-methyl-
CoM reductase, which catalyzes the terminal step in methane production by methanogenic
bacteria. All the Ni-proteins known to date are from plants or bacteria [116].


TRANSITION METALS AND HUMAN DISEASE

Role of Transition Elements in Cancer

Cancer is undoubtly one of the most grave human disease known so far. Several
transition metals, including chromium(vi), nickel, and cadmium have been suggested as
human carcinogens [118]. All these elements are soft and borderline elements i.e., they are
able to associate with thiols or compounds containing SH group. Metals are widely
distributed elements, usually occurring at low levels in the earths crust, although some
geographic areas have naturally high levels in soil. Metals are released into the environment
during mining operations, industrial and manufacturing processes, and as by-products of
combustion. Metals are generally present at low concentrations in ambient air, although much
higher concentrations have been measured near metal processing facilities. Metals typically
do not require bioactivation, at least not in the sense that an organic molecule undergoes
enzymatic modification that produces a reactive chemical species [119]. Cadmium, lead, and
nickel compounds have been shown to be mutagenic and carcinogenic in rodent studies [120]
because of their ability to inhibit the repair of damaged DNA. In addition, they can enhance
the mutagenicity and carcinogenecity of directly-acting genotoxic agents [121].
Role of Reactivity of Transition Elements in Life 19
A case-control study of breast cancer and metal exposure found an increased risk for
women exposed to a group of metals (chromium, arsenic, beryllium, and nickel), as well as
exposure to lead and cadmium individually [122]. A highly significant accumulation of iron,
nickel, chromium, zinc, cadmium, mercury, and lead was found in the cancer samples when
compared to the control group [63]. Increased Cu concentrations were also found in human
lung cancer biopsies [123] and in other tumors [124]. Excessive lipid peroxidation induced
malondialdehyde-DNA adducts was detected in the breast tissue of women with breast cancer
leading to endogenous DNA modifications [125].
The most common airborne exposures to nickel compounds are to insoluble nickel
compounds such as elemental nickel, nickel sulfide, and the nickel oxides from dusts and
fumes. Contributions to nickel in the ambient air are made by combustion of fossil fuels,
nickel plating, and other metallurgical processes. The most common oxidation state of nickel
is the divalent (Ni
2+
) form [126]. Nickel is also used in electroplating baths, batteries, textile
dyes, and catalysts. Ni (II) in the presence of H2O2 produced greater base damage to the
DNA in chromatin than to isolated DNA, unlike Co (II) [127]. Nickel compounds are
carcinogenic to humans and metallic nickel is possibly carcinogenic to humans. A 2-year
inhalation study of nickel oxide in rats and mice conducted by the National Toxicology
Program [128] indicated a carcinogenic effect of nickel oxide in the lungs. Occupational
exposure to nickel producing anelevated risk of nasal cancer and a 30% excess of lung cancer
in the workforce nasal cancer and a 30% excess of lung cancer [129]. It has been shown that
histone demethylase JMJD1A and DNA repair enzyme ABH2 family of dioxygenases is
highly sensitive to inhibition by nickel ions through by replacing the ferrous iron in the
catalytic centers. Inhibition of these dioxygenases by nickel is likely to have widespread
impacts on cells (e.g. impaired epigenetic programs and DNA repair) and may eventually
lead to cancer development [130].
The U.S. National Toxicology Program (NTP, 2002)[131] carcinogenicity study of
inhaled V(2)O(5) in rats and mice, concluded that clear evidence of lung tumors was seen in
mice of both genders and that there was some evidence of carcinogenicity in male rats. In
response to this study, vanadium pentoxide (V(2)O(5)) and other inorganic vanadium
compounds have recently been evaluated by several occupational exposure limit setting
committees and expert groups. It has been argued that, because of inherent weaknesses in
design and procedure, the U.S. National Toxicology Program study of the carcinogenicity of
inhaled vanadium pentoxide does not provide adequate evidence to support the classification
by regulatory authorities of vanadium pentoxide as a Group 2B (possible) human carcinogen
[132, 133]. The lungs are a significant site of entry of vanadium in the case of community
exposure [113]. Vanadate enters cells where it is reduced by glutathione and other agents to
vanadyl species (VO
2+
) and stabilized as such by various ligands. Vanadyl binds readily to
proteins, amino acids, nucleic acids, phosphates, phospholipids, glutathione, citrate, oxalate,
lactate, ascorbate, edetate, etc. [134]. Welding fumes contain many different metals including
vanadium typically present as particulates containing vanadium pentoxide (V2O5). Recently,
inhalative exposure to vanadium pentoxide in workers from a V(2)O(5) factory has been
reported to cause oxidation of DNA bases, affect DNA repair, and induce formation of
nucleoplasmic bridges and nuclear buds in leukocytes, suggesting that the workers are at
increased risk for cancer and other diseases that are related to DNA instability [135]. In vitro,
human peripheral lymphocyte cultures were exposed to 1, 2, 4, or 8 microg/mL of
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 20
vanadium(III) trioxide, vanadium(IV) tetraoxide, or vanadium(V) pentoxide (V(2)O(3),
V(2)O(4), or V(2)O(5), respectively. These cultures were then screened for structural
chromosomal aberrations, and mitotic index (MI) measurements were made. Cytogenetic
evaluations showed that only V(2)O(4) increased the percentage of aberrant cells (without
gaps) and chromosome damage (including and excluding gaps), while all compounds led to a
decrease in the MI. These results demonstrate that vanadium(III), vanadium(IV), and
vanadium(V) are all capable of inducing cytotoxicity, but only oxidation state IV induces
clastogenic effects [136]. Furthermore, vanadium pentoxide induced pulmonary inflammation
and tumor promotion in some strains of mice [137]. Vanadate generates the hydroxyl radical
via a Fenton-like reaction rather than a Haber-Weiss reaction [138].

V(V)+O
2
-
V(V)+ O
2


V(V)+ H
2
O
2
V(V) +

OH+OH
-


Some essential metals e.g., chromium VI and iron can also be carcinogenic. Chromium is
naturally occurring in rocks, animals, plants, soil and in volcanic dust and gases. Trivalent
chromium (III) is an essential nutrient for the body. Hexavalent chromium (VI), is generally
produced by industrial processes. Non-occupational exposure to Cr(VI)compounds occurs
from cigarette smoke, automobile emissions, areas of landfills and hazardous waste disposal
sites [139, 140]. Cr(VI) compounds have been classified as group I human carcinogens by the
International Agency of Research in Cancer in 1990 [141]. When inhaled, chromate particles
dissolve to form soluble Cr(VI) oxyanions that enter cells through non-specific anionic
transporters and are metabolically reduced within the cell by ascorbic acid and low molecular
weight thiols glutathione and cysteine to their lower oxidation states such as Cr(V), Cr(IV)
and Cr(III) ), the most stable form of Cr in cells. During the one-electron reduction of Cr(VI),
superoxide anion (O
2

) and hydroxyl radicals are produced causing DNA damage [142,-146].


Reactive oxygen species were produced by the decomposition of Cr(V)(O2)4 -3 ion, resulting
in DNA damage. The generation of hydroxyl radical was detected by ESR [147]. Cr(III)
forms coordinate covalent and ionic interactions with DNA bases and the phosphodiester
backbone, respectively [148, 149].

Cr()+O
2
-
Cr()+ O
2


Cr()+ H
2
O
2
Cr() +

OH+OH
-


Cr(V)+O
2
-
Cr(V)+ O
2

Cr(V)+ H
2
O
2
Cr(V) +

OH+OH
-


Hypervalent Cr species (Cr(V), Cr(IV)), and carbon based and oxygen radicals may also
react with DNA following Cr(VI) reduction [147, 150]. During Cr(VI) reduction, a diverse
range of genetic lesions are generated including Cr-DNA binary (mono) adducts, Cr-DNA
ternary adducts, DNA-strand breaks, DNA-protein crosslinks, oxidized bases, abasic sites,
and DNA inter- and intrastrand crosslinks. The damage induced by Cr(VI) can lead to
Role of Reactivity of Transition Elements in Life 21
dysfunctional DNA replication and transcription, aberrant cell cycle checkpoints,
dysregulated DNA repair mechanisms, microsatelite instability, inflammatory responses, and
the disruption of key regulatory gene networks responsible for the balance of cell survival and
cell death, which may all play an important role in Cr(VI) carcinogenesis [151, 152]. Electron
spin resonance (ESR) and fluorescence analysis revealed that Cr(VI) increased intracellular
levels of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide anion
radical in dose-dependent manner [153]. Mitochondrial ROS, specifically superoxide anion
(O
2

), mediates Cr(VI)-induced apoptosis of human lung epithelial H460 cells [154]. Cr(VI)
induced a mitochondrial-mediated and caspase-dependent apoptosis in skin epidermal cells
through reactive oxygen species-mediated activation of p53 [153]. Evidence indicates that
trivalent chromium compounds do not cause cancer, although high concentrations in some in
vitro systems have shown genetic toxicity. Hexavalent chromium compounds cause cancer in
humans, in experimental animals and exert genetic toxicity in bacteria and in mammalian
cells in vitro. Epidemiological evidence and animal studies indicate that the slightly soluble
hexavalent salts are the most potent carcinogens [155]. In their study, Gibb et al.[156]
demonstrated a strong dose-response relationship of cumulative hexavalent chromium
exposure and the risk for lung cancer in exposed human workers; cumulative trivalent
chromium exposure was not. The excess risk of lung cancer associated with cumulative
hexavalent chromium exposure was not confounded by smoking status.
Several epidemiological studies have reported a possible correlation between measures of
iron status and cancer among people in the general population and it is possible that iron
accumulation in the liver is a risk factor for hepatocellular carcinoma in patients with
haemochromatosis who also had increased incidence of extrahepatic cancer as well [157-
159]. In this disease status in which Fe
++
accumulates in tissues as a result of an autosomal
recessive genetic disease leading to enhanced gastrointestinal absorption of iron that leads to
a progressive increase of iron stores, the concentration of this redoxactive transition metal
capable of catalyzing and/or generating free radicals like superoxide, hydrogen peroxide, and
hydroxyl radical is markedly increased inducing cellular lipid peroxidation and DNA-attack
[160, 161]. Studies have shown a greater ability than normal cells for tumor cells to grow and
survive in the presence of high concentrations of iron [162]. In contrast, tumor growth in iron-
deficient mice [163]. Iron may also act as a promoter of already initiated hepatocytes in the
development of liver cancer in the rat [164]. A study of a national cohort of United States
adults suggested an increased risk of dying from cancer with higher levels of serum iron,
transferrin, and serum copper at baseline in males and females. The association of cancer with
serum iron and transferrin tended to be stronger among women, whereas the association with
serum copper tended to be stronger among men [165]. One study found higher serum iron
concentrations in individuals with colorectal cancer than control subjects [9]. However, the
evidence for a relationship between dietary iron intake and cancer, particularly colorectal
cancer in the general population, is inconclusive, with reports linking high dietary Fe and Cu
to colorectal cancer [166, 167] and a more recent study founding a non-significant inverse
association for dietary iron and colorectal cancer risk, and a significant inverse association for
serum ferritin and colorectal cancer risk. In this study, serum ferritin, serum iron and
transferrin saturation were all inversely associated with colon cancer risk specifically, but not
rectal cancer risk, whereas serum serum unsaturated iron binding capacity was associated
with a greater risk for colon cancer [168].
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 22
There is a clear evidence linking over production of free radical species and the risk of
cancer development. Oxidative damage to DNA can cause single point mutations which,
when undetected and unrepaired by enzyme repair systems, can lead to transversion
mutations, and errors in the DNA sequence. Indeed the chemical properties of some transition
metals suggests a role for them in carcinogenesis. Fe or Cu can generate the reactive
oxygen species including hydroxyl radicals via Fenton- and Haber-Weiss-reactions,
ascorbate autoxidation, lipid peroxidation processes, and formation of DNA
strand breaks [169, 170]. Several mechanisms have been proposed to explain the
carcinogenic potential of iron. First, ferric ions are reduced by superoxide and the ferric
product is reoxydized by peroxide to yield hydroxyl radicals which can attack DNA causing
point mutations, DNA cross linking and DNA strand breaks. Second, iron can bolster the
growth of cancer cells by suppressing host defenses. Finally, being an essential micronutrient,
iron is important tumour cell multiplication [161].
It has been suggested that three predominant mechanisms generally account for
carcinogenicity: (1) interference with cellular redox regulation and induction of oxidative
stress, which may cause oxidative DNA damage or trigger signaling cascades leading to
stimulation of cell growth; (2) inhibition of major DNA repair systems resulting in genomic
instability and accumulation of critical mutations; (3) deregulation of cell proliferation by
induction of signaling pathways or inactivation of growth controls such as tumor suppressor
genes. In addition, specific metal compounds exhibit unique mechanisms such as interruption
of cell-cell adhesion by cadmium, direct DNA binding of trivalent chromium, and interaction
of vanadate with phosphate binding sites of protein phosphatase [171].
In our opinion it is thus possible to categorize transition metals that has been suspected
in the process of carcinogenesis into two categories depending on their reactivity. The first of
them are the oxidizing ones i.e., metals that have high oxidation number which can liberate
free radicals via the Fenton reaction eg., [VO
3
]
1-
, [CrO
4
]
2-
,[FeO
2
]
1-
,[CuO
2
]
2-
or V
5+
, Cr
6+
,
Fe
3+
and Cu
2+
. The second group of them includes the soft and borderline (between soft and
hard) metals that can react with the antioxidant compounds containing SH or OH reactive
groups such as glutathione and picolines. These metals are namely Cu
2+
, Fe
2+
, Co
2+
, Ni
2+

and Zn
2+
. Thus Fe
3+
complexes can react with H
2
O
2
to produce free radicals while Fe
2+
an
react with the antioxidant glutathione thus impairing antioxidant defense mechanisms
increasing the vunerability of the cell to carcinogenic stimuli. It should also be noted that
As
5+
reacts with H
2
O
2
leading to the formation of As
3+
+ H
2
O + O
-
2
. (the latter species is a
highly reactive one which can lead to DNA alterations).


Role of Transition Elements in Some Neurodegenerative Diseases

The brain contains a relatively high concentration of a number of metals such as Fe, Zn,
and Cu (in the order of 0.10.5 M) [172]. Metal ions, particularly redox-active metal ions
like copper and iron are the transition metals of marked significance in human disease and
have been reported to accumulate in particular brain regions with aging [173]. An increase in
their tissue concentration has been associated with the development of two important human
diseases; haemochromatosis and Wilson's disease. The former is characterized by a genetic
predisposition to an increased absorption of enteral iron with a consequent increased iron
Role of Reactivity of Transition Elements in Life 23
level in the blood and tissues [174]. Wilson's disease, is a disorder of copper metabolism in
which copper accumulation in tissues causes liver inflammation, fibrosis and neurologic
complications including movement and psychiatric disorders [175]. Under these pathological
conditions, transition metals and their transport proteins may accumulate in different target
organs inducing cellular lipid peroxidation and DNA-attack. Redox active metals such as Cu,
Fe and Mn can result in metal-catalyzed protein oxidation, while metal-protein associations
can result in protein aggregation [176]. Recently, there has been much interest in the
contribution to transition metals and in particular iron and copper to neurodegenerative
diseases which will be highlighted in the following sections. We will focus on two well
known and indeed the most common brain diseases namely Alzheimer's disease and
Parkinson's disease.

Fe()+O
2
-
Fe()+ O
2

Fe()+ H
2
O
2
Fe() +

OH +OH
-

Cu()+O
2
-
Cu()+ O
2

Cu()+ H
2
O
2
Cu() +

OH+OH
-

2O
2
-
+2H
+
H
2
O
2
+O
2

Cu
2+
+ H
2
O
2


OH + Cu
1+


TRANSITION METALS AND ALZHEIMER'S DISEASE

This progressive neurodegenerative disorder is characterized by a profound memory
impairment and cognitive decline [177, 178] which is associated with loss of central
cholinergic neurons in the neocortex. The disease is estimated to affect 15 million people
worldwide. The most common risk factor is age with an incidence of 0.5% per year at the age
of 65 years to nearly 8% per year after the age of 85 years [179]. Most cases (95%) are
sporadic, with only 5% of genetic origin. Neuropathologically, there is gliosis and tissue
atrophy, most pronounced in the frontal and temporal cortices [180]. The disease is also
characterized by the presence of amyloid beta (A) senile plaques and neurofibrillary tangles
as well as dystrophic neuritis and degenerating neurons [181]. Senile or neuritic plaques
consist principally of extracellular deposites of an ~ 4.3 kDa polypeptide, amyloid (A)
peptide, derived from the proteolytic cleavage of the amyloid precursor protein (APP), a
membrane bound normal protein molecule with 771 amino acids produced by neuronal and
non-neuronal cells [182-184]. (forms when an alternative (beta-secretase and then gamma-
secretase) enzymatic pathway is utilized for processing.). The A peptide can be between 39
and 43 residues in length. Neuritic plaques are composed of an extracellular core of filaments
that measure 5-10 nm in diameter and are surrounded by dystrophic neurites and other debris,
as well as microglial cytoplasmic processes and astrocytic processes containing glial
filaments. Dense bodies, autophagic vacuoles and other membranous debris are common
[185]. Neurofibrillary tangles are intracellular aggregates of a hyperphosphorylated form of
the microtubule associated protein "tau", whose function is to regulate microtubule assembly
and helps stabilize stabilize the neuronal microtubule skeleton [186].
Strong evidence implicates transition metals such copper, iron, and zinc in the
pathophysiology of Alzheimers disease. In this respect, copper appears to have an important
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 24
role, though zinc as well as iron have also been implicated. Increased iron was found within
the glial cells surrounding the neuritic plaques [187](Cu
2+
is soft acid whereas Zn
2+
and Fe
2+

are borderline ones). High concentrations of copper (0.4 mM), zinc (1 mM) and iron (1mM)
have been found within amyloid plaques [188]. In red blood cells patients affected by
Alzheimer's disease, levels of Cu, Zn SOD activity increased early in the disease [189].
Studies suggested increased Zn in hippocampus, amygdala, and multiple neocortical areas of
patients with Alzheimers disease [190-192]. More recent studies suggest a significant
decrease of serum Zn in men with mild cognitive impairment (which accompany normal
aging) (MCI) compared to women with MCI and with normal men [193]. There were
significant elevations of the Zn transporter proteins ZnT-1 and ZnT-6, responsible for export
of Zn to the extracellular space in brain of Alzheimer's disease patients [194,195]. Copper
serum was increased in patients with Alzheimers disease patients when compared with
healthy controls [196] while a high concentration of copper was found within senile plaques
and neurofibrillary tangles of Alzheimers disease brains [188, 197, 198]. Free serum copper
(not bound to ceruloplasmin) was significantly elevated in patients with Alzheimers
compared to controls [53]. Free copper in serum predicted the annual change in Mini-Mental
State Examination. Hyperlipidemic patients with higher levels of free copper seemed more
prone to worse cognitive impairment [199]. In those with normal mental state, there was a
significant inverse correlation of the serum levels of free copper (though not ceruloplasmin-
bound copper) with both Mini-Mental State Examination and attention-related
neuropsychological tests scores [200]. Studies suggested that an increase of 1 micro mol/L in
serum copper account for 80% of the risk of having Alzheimers disease and correlate with
poor neuropsychological performance and medial temporal lobe atrophy. The latter correlated
also with decreased antioxidant capacity [196]. Oral Cu supplementation itself [Cu-(II)-
orotate-dihydrate; 8 mg Cu daily] in patients with mild Alzheimers disease for 12 months,
however, had neither a detrimental nor a promoting effect on the progression of the disease
[201]. Ceruloplasmin fragmentation occurs in the serum of Alzheimers disease patients,
possibly related to free copper deregulation in this disease [202]. The loss of the copper
chaperone for superoxide dismutase (CCS) which binds to the -site APP cleaving enzyme,
increases A production [203, 204]. Strozyk et al. [204] suggested that excessive interaction
with copper and zinc may induce neocortical A precipitation in Alzheimers disease, but
soluble A degradation is normally promoted by physiological copper and zinc
concentrations. The authors observed a significant inverse correlation of cerebrospinal fluid
A42 with copper, zinc, iron, manganese and chromium, but there was no association with
selenium or aluminum. In vitro data suggested that low concentrations (2 M) of exogenous
Zn and Cu promoted the degradation of synthetic A added to CSF samples.
Our opinion is that soft acid ion such as Cu
2+
and borderline (laid between soft and hard
ions) ions such as Fe
2+
, Mn
2+
, Cr
3+
could have a role in Alzheimers disease. On the
contrary, Alzheimers disease is not associated with hard acid ions e.g., Al
3+
. Based on the
results of numerous investigations, we can conclude that the first step in the pathogenesis of
Alzheimers disease (and possibly other neurodegenerative diseases)is the interaction
between reactive oxygen species e.g., O
2

,
1
O
2
with the cell membrane which in turn suffers
from alteration of its chemical structure; the highly polymerized membrane being changed to
a less polymerized one with the above mentioned species forming tetrahydral coordination
Role of Reactivity of Transition Elements in Life 25
compounds. Change in membrane structure may lead to changes in its electricity, which
enhances the transportation of different metals such as Zn, Cu and Fe.


Amyloid Beta Protein (A) Deposition in the Brain is a Hallmark of
Alzheimer's Disease

The analysis of the assembly pathway of A in vitro and biochemical characterization of
A deposits isolated from Alzheimers disease brains indicate that A oligomerization occurs
via distinct intermediates, including oligomers of 350 A monomers, annular oligomers,
protofibrils, fibrils and plaques. Of these, the most toxic species appear to be small A
oligomers. Aggregation is believed to be transition metal-dependent [205].

Monomeric A + metal ions Dimers OligomersProtofibrillsAmyloid

Peptides containing the 40- or 42-residue forms of A, and shorter derivatives, form
amyloid-like fibrils in vitro, which are morphologically, tinctorially, immunologically,
spectroscopically and ultrastructurally similar to fibrillar aggregates extracted from
Alzheimers disease amyloid plaques. Structural model of amyloid-like fibrils have been
proposed that is composed of several protofilaments, which consist of hydrogen-bonding -
sheet structures with the -strands running perpendicular to the long fibre axis, a structure
known as a cross-conformation [206]. There exist two conformational states for A
aggregates: (i) the non-sheet, an amorphous, non-fibrillar, state and (ii) the -sheet, a highly
ordered, fibrillar, state which is neurotoxic [26]. It is largely thought that A peptide
aggregation into insoluble fibrils is an important early event in a cascade of events leading to
neuronal cell death in the brains of Alzheimers disease patients [184, 207]. There is however
more convincing evidence that soluble oligomers may in fact be the most toxic species [208].
Oligomeric Abeta can disturb the structure and function of cell membranes and alter
membrane mechanical properties, such as membrane fluidity and molecular order. Much of
these effects are attributed to their capability to trigger oxidative stress and inflammation
[209].These oligomeric assemblies of A, which surround plaques, induce calcium mediated
secondary cascades that lead to dystrophic neurites, dendritic simplification, and dendritic
spine loss in both neurons in culture and in the adult mouse brain [210]. The observation of
the co-deposition of metals and amyloid-
42
(A
42
) in brain tissue in Alzheimers disease
indicated the need to understand the role of metals in A aggregation. The aggregation of
Abeta can be induced by Zn(2+) or Cu(2+) [211]. Huang et al. (1999) [212] suggested an
obligatory role for metal ions in initiating Abeta amyloidosis and oligomerization. In vitro
precipitation and amyloidosis of Abeta1-40 initiated by Abeta1-42 were abolished by
chelation of trace metal contaminants. Iron(III) ion produced both the oligomerization of the
peptide and iron-rich high molecular mass complexes [213]. In our opinion, the oxidation of
thiol compounds to sulphoxides decreases the ability of soft and borderline ions such as Cu
2+
,
Hg
2+
, Co
2+
, Ni
2+
and Zn
2+
so that these ions preferentially form coordination complexes with
monomer and oligomer A peptide species.
Human A can bind metal ions [214, 215] due to the presence of a low and high affinity
binding site for both Cu and Zn via three N-terminal histidine imidazole rings with the
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 26
stoichiometry for Cu:A being 1:1 and for Zn:A ranging from 1:1 to 3:1[216, 217]. It has
been suggested that interaction of both Zn2+ and Cu2+ ions with Abeta peptides may occur in
brain areas affected by Alzheimer's disease and Zn2+-induced transition in the peptide
structure might contribute to amyloid plaque formation [218]. Elucidation of the chemistry
through which transition-metal ions participate in the assembly and toxicity of Abeta
oligomers is important to drug design efforts if inhibition of Abeta containing bound metal
ions becomes a treatment for Alzheimer's disease.


Figure 1. Illustration of CU
2+
coordination by A, where the metal is believed to be coordinated by His-
6, His-13 and His-14 and Tyr-10. The imidazole side chain of a His residue bridges between two CU
2+

atoms to form dimeric A.
The N-terminal region of A can access different metal-ion-coordination environments
and different complexes can lead to profound changes in A self-assembly kinetics,
morphology, and toxicity [219]. Metals can bind A-peptides in an intra- as well as in an
inter-peptide coordination mode [220, 221]. Raman microscopy showed that Zn
2+
ions are
bound to A via the histidine imidazole rings within senile plaque cores [222]. One form of
metal coordination that can drive peptide aggregation is the formation of histidine bridges,
where the imidazole side chain of a His residue in a Cu-bound A can also coordinate to the
copper of a second A peptide [223]. The novel distorted six-coordinated (3N3O) geometry
around copper in the A-Cu
2+
complexes include three histidines: glutamic, or/and aspartic
acid, and axial water [217]. A1-40 bound easily one copper ion to form the [M+Cu+ 4H]6+
complex [213]. Stellato et al [221]suggested differences in the structural conformation of the
complex that depend on the nature of the coordinated metal. In (Cu-A)1 complex, the metal
is tightly bound to three histidines in a fairly closed structure, which protects the metal
against any further interaction. This contrasts with the open structure of the (Zn-A)1
complex, making available the metal for further interaction [221]. Zn
2+
coordination is
dominated by inter-molecular coordination and the formation of polymeric species. His6,
His13 and His14 residues are implicated in Zn-Ah binding [224]. Miller et al. [225] observed
that Zn
2+
coordination promotes A
42
aggregation leading to less uniform structures. In
oligomeric Zn
2+
-A
42
, Zn
2+
can simultaneously coordinate intra- and intermolecularly,
bridging two peptides. Zinc coordination significantly decreases the solvation energy for large
Zn
2+
-A
42
oligomers and thus enhances their aggregation tendency. Increasing Zn
2+

concentration could slow down the aggregation rate, even though the aggregation rates are
still much higher than in Zn
2+
-free solution.
Investigation of the temperature dependence of the EPR signal for Cu
2+
bound to
soluble A or Cu
2+
in fibrillar Abeta showed that the Cu
2+
center displays normal Curie
Role of Reactivity of Transition Elements in Life 27
behavior, indicating that the site is a mononuclear Cu
2+
site. Fibrils assembled in the presence
of Cu
2+
contained one Cu
2+
ion per peptide. Thus the ligand donor atom set to Cu
2+
does not
change during organization of Abeta monomers into fibrils and neither soluble nor fibrillar
forms of Abeta(1-40) with Cu
2+
contain antiferromagnetically exchange-coupled binuclear
Cu
2+
sites in which two Cu
2+
ions are bridged by an intervening ligand [214]. Jun et al. [226]
proposed that A (1-40) has a second copper-binding site in a proton-rich environment and
that the second binding Cu(II) ion interferes with a conformational transition into amyloid
fibrils, inducing the formation of granular amorphous aggregates. Sarell et al. [227] suggested
that A fibers are able to bind a full stoichiometric complement of Cu
2+
ions with little
change in their secondary structure and have coordination geometry identical to that of
monomeric A. A Cu
2+
affinity for A of 10
11
M
1
supports a modified amyloid cascade
hypothesis in which Cu
2+
is central to A neurotoxicity.
Zn
2+
causes rapid aggregation of A [228]. It has also been reported that Zn
2+
may play a
neuroprotective role since A may capture redox inactive Zn
2+
ion thereby preventing A
from participating in redox cycling with other metals, in particular, Cu2+ ions [229]. Zn(II)
induces the Abeta aggregation at acidic-to-neutral pH, while Cu(II) is an effective inducer
only at mildly acidic pH. Zn(II) binds to the N(tau) atom of the histidine imidazole ring and
the peptide aggregates through intermolecular His(N(tau))-Zn(II)-His(N(tau)) bridges. The
N(tau)-metal ligation also occurs in Cu(II)-induced Abeta aggregation at mildly acidic pH. At
neutral pH, however, Cu(II) binds to N(pi), the other nitrogen of the histidine imidazole ring,
and to deprotonated amide nitrogens of the peptide main chain. The chelation of Cu(II) by
histidine and main-chain amide groups results in soluble Cu(II)-Abeta complexes. Under
normal physiological conditions, Cu(II) is thus expected to protect Abeta against Zn(II)-
induced aggregation by competing with Zn(II) for histidine residues of Abeta [220]. pH-
dependent metal binding to A1-40 may induce conformational changes, which affect the
affinity toward other metals. A significant copper and zinc binding to A1-40 peptide at pH
5.5 (and a 1:1 Cu:A molar ratio ) was found, whereas nickel ions commonly bind to each
molecule of -amyloid peptide. On increasing pH, up to 12 ions of zinc may bind to a single
A molecule. A1-40 peptide displayed a high affinity toward nickel ions even at low pH and
nickel ions proved to enhance A oligomerization [213].
In that respect we can say that Zn
2+
ions are not involved in the creation of oxidation
stress like Cu
2+
, Cr
3+
, Cr
IV-V
, Fe
3+
and [MoO
2
]
2+
, but only involved in formation of
tetrahedral complexes with monomeric and oligomeric A species.
Suzuki et al. [230]found that Cu(II) effectively inhibits the Abeta aggregation by
competing with Zn(II) for histidine residues. The cross-linking of Abeta through binding of
Zn(II) to the N(tau) atom of histidine is prevented by chelation of Cu(II) by the N(pi) atom of
histidine and nearby amide nitrogens. The inhibitory effect is strongest at a Cu/Abeta molar
ratio of around 4. Above this ratio, Cu(II) itself promotes the Abeta aggregation by binding to
the phenolate oxygen of Tyr10. The authors emphasized the importance of regulation of
Cu(II) levels to inhibit Abeta aggregation. Other researchers provided data suggesting that
both Zn(II) and Cu(II) may in fact prevent A from participating in fibrillogenesis by forming
metal-induced aggregates, whose structural characteristics are distinct from fibrous self -
aggregates. Moreover, this inhibitory effect of metals on A-aggregation via conformational
enforcement was directly correlated with their protective effects against cell toxicity. Soluble
A also promoted cytotoxicity in the presence of Cu(II), indicating that Cu(II) is capable of
promoting potentially toxic, pro-oxidative reactions [231].
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 28
Karr et al. [232]suggested that peptides that contain the proposed binding site for
Cu(2+)-three histidines (H6, H13, and H14) and a tyrosine (Y10)-but lack one to three N-
terminal amino acids, do not bind Cu(2+) in the same coordination environment as the native
peptide. Cu(2+) binds to Abeta fibrils in a manner that permits exchange of Cu(2+) into and
out of the fibrillar architecture.
More recently, Smith et al. (2006) [223] have reported the formation of a toxic A-Cu
2+

complex formed via a histidine-bridged dimer, as observed at Cu
2+
/peptide ratios of >0.6:1 by
EPR spectroscopy. The toxicity of the A-Cu
2+
complex to cultured primary cortical neurons
was attenuated when either the -or -nitrogen of the imidazole side chains of His were
methylated, thereby inhibiting formation of the His bridge. A and A-Cu
2+
complexes
interacted at the surface of a lipid membrane.
The binding of metals to A was found to be dependent on the Abeta conformation. The
latter was found to depend on pH and trifluoroethanol (TFE). The aggregation induced by
Abeta itself or its associated metals is completely diminished for Abeta in 40% TFE. Only in
5% and 25% TFE can A undergo an alpha-helix to beta-sheet aggregation, which involve a
three-state mechanism for the metal-free state, and a two-state transition for the metal-bound
state, respectively. The aggregation-inducing activity of metals is in the order, Cu
2+
> Fe
3+
>
or = Al
3+
> Zn
2+
.[233].
Copper facilitated the A aggregation and precipitation of both wild-type and a mutant
A in which a histidine residue was replaced by arginine [234]. Ha et al. [235]found that Cu
2+

and Zn
2+
ions accelerated both Abeta40 and Abeta42 deposition but resulted only in the
formation of "amorphous" aggregates. In contrast, Fe3+ induced the deposition of "fibrillar"
amyloid plaques at neutral pH. Under mildly acidic environments, the formation of fibrillar
amyloid plaques was not induced by the metal ions. Studies with mixed metal ions suggested
that Zn
2+
was required at much lower concentrations than Cu
2+
to yield nonfibrillar
amorphous Abeta deposits. Sequential addition of Zn
2+
or Cu
2+
on fibrillar aggregates formed
by Fe3+ demonstrated that Zn
2+
and Cu
2+
could possibly change the conformation of the
aggregates induced by Fe
3+
[236].
Yang et al. [237]found that Cu(II) could disrupt the already formed beta-sheet structure,
convert beta-sheeted aggregates into non-beta-sheeted aggregates and promote oligomeric A
to precipitate in a non-beta-sheeted aggregation way. Other researchers have shown that
copper abolished the -sheet secondary structure of pre-formed, aged amyloid fibrils of A
42
.
Copper may thus protect against the presence of -sheets of A
42
in vivo, and its binding by
fibrillar A
42
could have implications for Alzheimers disease therapy [238].
In our opinion, one can say that reactive oxygen species (ROS) have two drawbacks. The
first arises from the formation of oxidized cellular molecules resulting from the interaction
with different chemical compounds (e.g., DNA , RNA ). The second arises from the oxidation
of thiols and mercaptans and the corresponding sulphoxides which leads to variation in their
function. The increase in ROS may lead to abstraction of borderline elements such as Zinc
which is found for example in the insulin molecule. The soft acidic ions such as Cu2+ and
Fe2+ play a role in the formation of reactive oxygen species in case of their interaction with
sulphur A species as we can see later.


Role of Reactivity of Transition Elements in Life 29
TRANSITION METALS, A AND OXIDATIVE STRESS

Oxidative stress is increased in Alzheimers disease. Medial temporal lobe atrophy
appears to correlate with decreased antioxidant capacity [196] (Squitti et al., 2002b). Abeta
(1-42) causes oxidative stress and neurotoxicity to neurons in mechanisms that are inhibited
by Vitamin E and involve the single methionine residue of this peptide [239-241]. The ability
of A to bind metals and the presence of redox-active iron in plaque cores could explain the
development of oxidative stress in the brain of Alzheimers disease patients. Oxidative stress,
probably mediated by the hydroxyl radical and generated by the Fenton reaction, is essential
for A
142
toxicity in vivo. Rival et al. [242] have shown that the expression of the 42-amino-
acid isoform of A (A
142
) changes the expression of genes involved in oxidative stress in a
Drosophila model of Alzheimers disease. the iron-binding protein ferritin and the H
2
O
2

scavenger catalase were the most potent suppressors of the toxicity of wild-type and Arctic
(E22G) A
142
. Copper may participate in oxidative stress through redox-cycling between its
+2 and +1 oxidation states to generate reactive oxygen species (ROS).A peptide can reduce
Cu(II) and Fe(III) ions leading to Fenton and Haber-Weiss chemistry, the formation of
hydroxyl radicals, and oxidative damage in brain tissue. Solutions of A(beta) 1-40, A(beta) 1-
42, A(beta) 25-35 all liberate hydroxyl radicals upon incubation in vitro followed by the
addition of small amounts of Fe(II). These hydroxyl radicals were readily detected by means
of electron spin resonance spectroscopy, employing 5,5-dimethyl-1-pyrroline N-oxide
(DMPO) as a spin trapping agent. Hydroxyl radical formation was inhibited by the inclusion
of catalase or metal-chelators during A(beta) incubation. The direct production of hydrogen
peroxide during formation of the abnormal protein aggregates might thus be one fundamental
molecular mechanism underlying the pathogenesis of cell death in Alzheimers disease [243].
Ascorbate radical and hydroxyl radical (either via fluorescent detection or spin-trapped
adducts) have been detected upon redox-cycling of the ACu system [244].
Metal-binding to A is thought to induce its aggregation and redox chemistry that is toxic
to neurons through the generation of reactive oxygen species which induces membrane lipid
peroxidation and oxidative modification of various membrane and associated proteins (e.g.,
receptors, ion transporters and channels, and signal transduction and cytoskeletal proteins)
[245]. Neuronal cell death induced by GSH depletion was dependent on trace levels of
extracellular copper in the culture medium (1.6 microM). Neurons were protected against
GSH depletion-mediated toxicity when cultured in Chelex 100-treated medium containing
tenfold less copper (0.16 microM) than normal medium. The addition of copper, but not iron
or zinc, to Chelex 100-treated medium restored the neurotoxicity induced by GSH depletion.
The neurotoxic effects of copper in GSH-depleted neurons involved generation of copper(I)
and subsequent free radical-mediated oxidative stress [246]. The abnormal combination of A
with Cu or Fe induces the production of hydrogen peroxide, which may mediate the oxidative
damage to the brain in Alzheimers disease [247]. An inevitable, age-dependent rise in brain
Cu and Fe might hypermetallate the A peptide, causing the catalysis of H(2)O(2) production
that mediates the toxicity and auto-oxidation of Abeta [172] (Bush, 2003). In cellular
environments, the reduction potential of the Abeta-Cu(II) complex is sufficiently high to react
with antioxidants (e.g., ascorbic acid) and cellular redox buffers (e.g., glutathione), and the
Abeta-Cu(I) complex produced could subsequently reduce oxygen to form hydrogen peroxide
via a catalytic cycle. Hydrogen peroxide produced, in addition to its role in damaging DNA,
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 30
protein, and lipid molecules, can also be involved in the further consumption of antioxidants,
causing their depletion in neurons and eventually damaging the neuronal defense system.
Another possibility is that Abeta-Cu(II) could react with species involved in the cascade of
electron transfer events of mitochondria and might potentially sidetrack the electron transfer
processes in the respiratory chain, leading to mitochondrial dysfunction [248]. In human
cerebrospinal fluid, copper but not iron supplementation provoked a significant increase in
hydroxyl free radical generation in cerebrospinal fluid (CSF) treated with H
2
O
2
. However, in
a binary copper/iron containing Fenton system, iron catalytically activated copper. EDTA
completely prevented copper's redox activity in CSF, while iron chelation led to a significant
increase in hydroxyl radical generation, indicating that copper and iron do not only have
diverse catalytic properties in the CSF but also that their redox activities are differently
modulated by ligands [249]. Jiang et al. [250]found that in the presence of ascorbic acid,
Abeta-Cu(II) complexes facilitate the reduction of oxygen by producing H
2
O
2
as a major
product. Cu(II) bound to oligomeric and fibrous Abeta aggregates was less effective than free
Cu(II) and the monomeric Abeta-Cu(II) complex in producing ROS. Other studies suggested
that monomeric and fibrillar forms of Abeta does not generate any more reactive oxygen
species (ROS) than controls of Cu(2+) and ascorbate. Rather hydroxyl radicals produced as a
result of Fenton-Haber Weiss reactions of ascorbate and Cu(2+) rapidly react with Abeta;
thus the potentially harmful radicals are quenched. Specific oxidation sites within the peptide
were identified at the histidine and methionine residues [251]. EPR spectroscopy of ascorbate
reduction of ACu
II
under inert atmosphere and subsequent air oxidation of ACu
I
to
regenerate ACu
II
suggested that O
2
oxidation of the ACu
I
complex is kinetically sluggish,
and A damage is occurring following reoxidation of ACu
I
by O
2
. it was hypothesized that
Cu
I
is ligated by His13 and His14 in a linear coordination environment in A, that A may be
playing a neuroprotective role, and that metal-mediated oxidative damage of A occurs over
multiple redox-cycles [252]. Tabner et al., 2005 [253] have shown that A(140), A(142)
and A(2535) generate hydrogen peroxide which can be converted into hydroxyl radicals,
via the Fenton reaction, upon addition of Fe(II). Hydrogen peroxide was not generated
continuously throughout the aggregation process, but was formed as a short burst
comparatively early on during the peptide incubation period i.e., during the very early stages
of protein aggregation, when protofibrils or soluble oligomers were present as revealed by
atomic force microscopy. Mature A fibrils lacked the ability to generate hydrogen peroxide.
A1-42 is a potent inhibitor of the terminal complex cytochrome c oxidase in a dose-
dependent manner that was dependent on the presence of Cu
2+
and specific "aging" of the
A1-42 solution. Thus, Cu
2+
-dependent A-mediated inhibition of cytochrome c oxidase may
be an important contributor to the neurodegeneration process in Alzheimer's disease [254].
It appears that when the sensitive metal balance in the brain is sufficiently disrupted, it
can lead to the self-perpetuating pathogenesis of Alzheimers disease. Maynard et al.,
2005)[215]. A is derived from intracellular proteolytic cleavage of amyloid precursor
protein (APP). APP undergoes intramolecular cleavage by -, - and -secretases A is a 39-
43-residue heterogeneous peptide derived from proteolytic processing of the -amyloid
precursor protein (APP) by -secretase, the protease that cleaves at the amino-terminus, and
-secretase, the protease that cleaves at the carboxy-terminus. A1-40 is the major species
found in cerebrospinal fuid [182-184]. Amyloid precursor protein (APP) is a major regulator
of neuronal copper homeostasis via its copper binding domain, being acting as a neuronal
Role of Reactivity of Transition Elements in Life 31
metallotransporter [256]. APP is able to bind Cu
2+
and reduce it to Cu
+
through its copper-
binding domain. APP knockout mice have elevated cellular copper levels [257], whereas
transgenic mice overexpressing the Swedish mutant of APP have reduced brain copper [258].
The interaction between Cu
2+
and APP leads to a decrease in A production. On the other
hand, lowering Cu concentrations can down regulate the transcription of APP, showing that
APP and A form part of the Cu homeostatic machinery in the brain [215]. APP possesses
ferroxidase activity mediated by a conserved H-ferritin-like active site, which is inhibited
specifically by Zn
2+
. Like ceruloplasmin, APP catalytically oxidizes Fe
2+
, loads Fe
3+
into
transferring. Duce et al. [259] proposed that endogenous Zn
2+
originating from Zn
2+
-laden
amyloid aggregates and correlating with A burden can inhibit APP ferroxidase activity,
inducing marked brain iron accumulation in Alzheimers disease. Metallothioneins (MTs) are
the major endogenous zinc- and copper- binding protein within the brain. MT-1/2 can bind 7
divalent (Zn
2+
) and up to 12 monovalent (Cu
+
) metal ions in vivo through two distinct metal-
thiolate clusters, termed the - and - domains [45, 260]. Metallothionein-3 (MT-3) binds
with a high affinity essential monovalent and divalent d
10
metal ions Cu(I) and Zn(II). In cell
cultures Zn
7
MT-3, protects neurons from the toxicity of A. Zn
7
MT-3 scavenges free Cu
2+

ions through their reduction to Cu
+
and binding to the protein. In this reaction thiolate ligands
are oxidized to disulfides concomitant with Zn
2+
release. Zn
7
MT-3 in the presence of
ascorbate completely quenches the copper-catalyzed hydroxyl radical (OH
)
production
[261]. MT-2A prevented the in vitro copper-mediated aggregation of A
140
and A
142
. This
action of MT-2A appears to involve a metal-swap between Zn
7
MT-2A and Cu(II)-A.
Zn
7
MT-2A blocked Cu(II)-A induced changes in ionic homeostasis and subsequent
neurotoxicity of cultured cortical neurons [262].
Metals can also induce neurodegeneration via pathways independent of A aggregation.
Neurotrophins are an important family of neurotrophic factors e.g., nerve growth factor, brain
derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5. They exert their effects by
binding to and activating specific cell surface receptors of the Trk gene family. Activated
receptors initiate a cascade of intracellular events, which ultimately induce gene expression
and modify neuronal morphology and function [263]. The amyloid protein precursor of
Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth
[264]. The transition metal cations Zn
2+
and Cu
2+
bind to histidine residues of nerve growth
factor (NGF) and other neurotrophins (a family of proteins important for neuronal survival)
leading to their inactivation. Cu
2+
has greater binding affnity to NGF than Zn
2+
at acidic
conditions, consistent with the higher affnity of Cu
2+
for histidine residues [265].


METAL BRAIN LOWERING IN ALZHEIMER'S DISEASE

Metal ligands such as clioquinol , DP-109 or pyrrolidine dithiocarbamate (PDTC) have
shown promising results in animal models of AD and could have therapeutic benefits for
Alzheimers disease. The 8HQ (8-hydroxyquinoline) derivative 5-chloro-7-iodo-8-
hydroxyquinoline or clioquinol was shown to dissolve plaques in vitro by removal of metals
[266].

Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 32

Figure 2. Clioquinol.
A recent placebo-controlled trial in 36 patients with Alzheimers disease showed that
clioquinol (250-750 mg daily) reduced plasma concentrations of A
142
, raised plasma
concentrations of zinc, and-in a subset with moderate dementia-slowed cognitive decline over
24 weeks [267]. In culture, cells over expressing APP when incubated with the metal ligand
clioquinol and Cu
2+
or Zn
2+
~ 85-90% reduction of secreted Abeta-(1-40) and Abeta-(1-42)
was observed compared with untreated controls. The secreted Abeta were rapidly degraded
through up-regulation of matrix metalloprotease (MMP)-2 and MMP-3 after addition of
clioquinol and Cu
2+
. Metal ligands that inhibited A induced metal-dependent activation of
PI3K and JNK, resulted in JNK-mediated up-regulation of metalloprotease activity and
subsequent loss of secreted A [268]. Dithiocarbamates are metal chelating compounds.
Pyrrolidine dithiocarbamate (PDTC) is a metal chelator and an inhibitor of nuclear factor-B
which increases the intracellular level of copper [269]. Oral therapy with PDTC prevented the
decline in cognition in Alzheimers disease mice without altering -amyloid burden or gliosis,
increased the copper concentration in the brain, rescued cultured hippocampal neurons from
the toxicity of oligomeric A and reduced tau phosphorylation in the hippocampus of
Alzheimers disease mice [270]. In Drosophila model of Alzheimers disease, treatment with
clioquinol increased the lifespan of flies expressing Arctic A
142
.[242]. Moreover, nicotine
treatment of APP
V717I
(London mutant form of APP) transgenic mice led to significant
reduction in the metal contents of copper and zinc in senile plaques and neuropil; effect that
appears to be independent of the activation of nicotinic acetylcholine-receptor [271].
Lowering of copper concentrations in brain of patients with Alzheimers disease is thus an
interesting therapeutic strategy. D-penicillamine, a copper chelating agent reduced extent of
oxidative stress (though not the rate of cognitive decline) in these patients [272]. There are
also data suggesting that copper deficiency markedly alters APP metabolism and can elevate
A secretion [273] making the situation more complex. In their study, Crouch et al.
[274]found that in the brains of APP/PS1 transgenic AD model mice, the use of copper-
bis(thiosemicarbazonoto) complexes to increase intracellular copper bioavailability, can
restore cognitive function by inhibiting the accumulation of neurotoxic A trimers and
phosphorylated tau. Hung et al. [275]found that total cellular copper is associated inversely
with lipid raft copper levels, so that under intracellular copper deficiency conditions,
Acopper complexes are more likely to form. This explains the paradoxical hypermetallation
of A with copper under tissue copper deficiency conditions in AD.

Role of Reactivity of Transition Elements in Life 33
TRANSITION METALS AND PARKINSONS'S DISEASE

Parkinson's disease is the second most common neurodegenerative disorder after
Alzheimers disease and is also a disease of the aging population in which the prevalence
increases exponentially with age between 65 and 90 years. The mean age of onset is about 65
years and the overall age-adjusted prevalence is 1% worldwide. The clinical features of
Parkinson's disease result from a progressive degeneration of dopamine-producing neurons in
the substantia pars compacta (SNc) of the midbrain that project to the striatum. The SNC is
one of five distinct subcortical interconnected nuclei whose primary function is the control of
motor function. In Parkinson's disease there is slowness and difficulty with movement
initiation "bradykinesia", muscular rigidity as well as tremor of the hands. Parkinsonian
symptoms start to appear when 5060% of SNc dopaminergic neuons and 7080% of striatal
nerve terminals are lost [276]. Apart from an idiopathic form, the disorder can be the result of
vascular factors, brain trauma, manganese poisoning or drugs. Only ~5% of all cases are of
genetic origin. The exact cause that leads to the the selective destruction of the nigrostriatal
dopaminergic pathway has remained unknown but accumulating evidence suggests that it
might represent the final outcome of interactions among multiple factors, including a signifi-
cant genetic component for susceptibility to idiopathic Parkinson's disease, exposure to
environmental toxin (s) and the occurrence of inflammation in the brain [277].
Several factors underlie the unduly high susceptibility of the brain tissue to oxidative
stress. Owing to its high metabolic activity the brain has high oxygen consumption rate being
~ 20% of total oxygen consumption in adult human despite that it accounts for only a few
percent of body weight. Hence it processes a lot of O
2
per unit tissue mass. The brain is also
rich in highly oxidizable polyunsaturated fatty acids. Other factors causing increased
oxidative burden are the metabolism of monoamine neurotramsmitters noradrenaline,
serotonin and dopamine, yielding free radicals and brain iron content [176].


Dopamine

Dopamine [2-(3,4-dihydroxyphenyl)-ethylamine] is a neurotransmitter that plays an
important role in PD. When a solution of dopamine is exposed to air, after a while it turns
pink due to oxidation to dopaminochrome even in the absence of metal ions. Finally the pink
colour disappears to be replaced by a precipitate of the polymeric material melanine. The rate
determining step is assumed to be hydrogen atom abstraction from the monodeprotonated
species by O
2
.Addition of a small amount of acid inhibits this oxidation, unless metal ions
such as Fe
3+
, Cu
2+
or VO
2+
are present. Although in acid solution added metal ions initially
start an oxidation process, this soon comes to an end as the metal ions are efficiently removed
from the solution by the melanine. The in vitro chemistry of dopamine reactions under the
presence of Fe (III) and dioxygen showed that the reaction pathway essentially involved an
FeL intermediate, which decomposes releasing Fe(II) and dopaminochrome which reacts
further under involvement of both Fe (III) and dioxygen [279].

Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 34

Figure 3. Dopamine and Dopaminochrome.
The metabolism of dopamine can be a source of free radicals production via multiple
pathways. Dopamine can auto-oxidize to produce free radicals particularly in the presence of
iron and other heavy metals [280]. Dopamine forms quinones and semiquinones,which are
themselves toxic and may lead to generation of reactive oxygen species [281]. In addition, the
reduction of Cu
2+
to Cu
1+
and the formation of a peroxide lead to the oxidation of dopamine
with formation of DNA adducts and oxidative base damage [282]E:\Documents and
Settings\Lisa\Local Settings\Temporary Internet Files\Content.Outlook\9DAVGS4D\New
Folder33\science.htm - en976560fn1. It has been suggested that increased turnover of
dopamine in the early stages of PD should be associated with an oxidative stress derived
from increased production of hydrogen peroxide with the subsequent formation of hydroxyl
radical leading to dopaminergic cell death. The peroxide is formed during the oxidative
deamination of dopamine by monoamine oxidase [283]. It has been shown that increased
presynaptic metabolism of neurotransmitter alters the redox state of dopamine nerve terminals
in the striatum. The H202 that is generated by MAO is scavenged by glutathione (GSH)
peroxidase, leading to the formation of glutathione disulfide (GSSG).

(1)

(2)

(3)

Normally, GSSG is efficiently reduced by glutathione reductase. The ratio of oxidized to
reduced glutathione reflects, in part, the redox state of the tissue [283].
We can conclude that the formation of singlet oxygen and the derives ractive oxygen
species lead to the oxidation of thiol compounds to dimeric (GSSG). The alkaline medium
prohibits the formation of GSH as can be seen from equation [3] which clarified that the
transformation step usually takes place in an acidic medium. The liberation of ammonia
inside the cells raises the pH value intracellularly to the alkaline region. This situation may
lead to the precipitation of iron, copper and zinc which may alter the homeostasis of these
transition elements in the brain. In addition, the high pH value enhances the reaction between
hydrogen peroxide and sodium hypochlorite leading to formation of singlet oxygen which
possesses a very stron damaging effect on different molecules forming the different cellular
components (e.g., cell membrane, DNA) according to the following equation:
he
lin
ac
T
un
M
pa
Fi
ox
Fi
su
ot
m
NaOCl + H

The above
epatic precom
nked to increa
In addition
ctivity increas
he increased
nchanged extr
MAO-B is sig
athogenesis of

igure 4. Format
xidation. In the

igure 5. Metabo
uperoxide anion
Brain meta
ther enzymes
mitochondrial m

Role o
H
2
O
2

1
O
2
+
is likely to ha
ma where chan
ased brain amm
n, brain MAO
ses with age, t
MAO-B activ
rasynaptosom
gnificantly inc
f PD.
tion of free radi
presence of tra
olism of DA lea
ns (O2), dopam
abolism genera
e.g., monoam
membranes of
of Reactivity o
NaCl + H
2
O
ave an importa
nges in conscio
monia level.
O-B (involved
thereby, expos
vity in aging
mal MAO-B..
creased by A
cals from dopam
ansition metals,
ads to the forma
minequinone s
ates excess H
2
mine oxidases A
f neurons and
of Transition E
ant implication
ousness and n
in the catabo
sing cells to o
is due to an
There are al
Al
3+
[285], thu
mine (DA) by m
H2O2 is conve
ation of several
species (SQ) an
2
O
2
, not only v
A and B, flav
glia. They cat
Elements in Li
ns also in som
neurobehaviou
olism of dopam
oxidative stres
increased con
so data show
us implicating
monoamine oxi
erted to hydroxy
cytotoxic mole
nd hydroxyl rad
via superoxide
voprotein enzy
alyze the reac
ife
me pathological
ural alterations
mine) (but no
ss-mediated in
ncentration of
wing that the
g this metal

dase (MAO) or
yl radical [286,2
ecules, including
dicals (OH)[28
e dismutases,
ymes located i
ction
35
l states like
s are highly
ot MAO-A)
njury [284].
f otherwise
activity of
ion in the
r auto-
287].
g
6,287].
but also by
in the outer
radical
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 36


and generate substantial H
2
O
2
in the brain [288].
DA quinone readily participates in nucleophilic addition reactions with sulfhydryl groups
on free cysteine, glutathione, or and sulfhydryl groups in proteins [289-292]. The reaction
between DA quinone and cysteine results in the formation of 5-cysteinyl-DA (Figure 1).
Because cysteinyl residues are often found at the active site of proteins, the covalent addition
of the catechol moiety to cysteine may inhibit protein function and possibly lead to cellular
damage and/or cell death. In addition, DA quinone is able to react with the sulfhydryl group
of cysteine in glutathione, which may decrease levels of this important antioxidant. The
reactive quinones and free radicals produced by the oxidation of DA may contribute to the
oxidative stress associated with PD.


Figure 6. The oxidation of DA to DA quinine and the resultant conjugation with cysteine (5-Cys-DA).
Oxidation of dopamine to an o-quinone and its subsequent product, aminochrome (2,3-
dihydroindole-5,6-dione) may also result in redox cycling. Key reactions promoting the
formation of reactive oxygen species, with a consequent prooxidant effect, include one-
electron reduction of quinines catalysed by favoproteins, such as NADPH:cytochrome P-450
reductase, and the subsequent reaction between the formed semiquinone radical and
dioxygen. One-electron reduction accompanied by autoxidation and redox cycling in the
presence of dioxygen contributes greatly to the toxicity characterizing many quinines [293].
The human glutathione transferases (GSTs), in particular GST M2-2 (also in the substantia
nigra of human brain), catalyse the formation of glutathione conjugates of o-quinones derived
from physiologically important catecholamines. Glutathione conjugation of these quinones is
a detoxication reaction that prevents redox cycling, thus indicating that GSTs have a
cytoprotective role involving elimination of reactive chemical species originating from the
oxidative metabolism of catecholamines [294].
Oxidized catecholamines can also induce modification of Cu,Zn-SOD that migkht induce
the perturbation of cellular antioxidant systems and led to a deleterious cell condition. When
Cu,Zn-SOD was incubated with the oxidized 3,4-dihydroxyphenylalanine (DOPA) or
dopamine, the protein was induced to be aggregated. The deoxyribose assay showed that
Role of Reactivity of Transition Elements in Life 37
hydroxyl radicals were generated during the oxidation of catecholamines in the presence of
copper ion [295].


Neuromelanin

Neuromelanin (NM) is a dark pigment polymer belonging to the family of melanins.
which occupies a large proportion of the cytosol within certain catecholaminergic neurons in
the human brain [296]. Melanised neurons are most abundant in the human SN and The dark
appearance of the SN results from the presence of NM and for which it was named (lat.
substantia nigra, black body) [297, 298]. Less neuromelanin is found in Parkinson's disease
and depletion of this pigment results in pallor of the SN which is one of the most striking
pathological features. Neuromelanin is synthesized from quinones and semiquinones
produced by enzymatic or non-enzymatic oxidation of dopamine and noradrenaline in the SN
and LC, respectively. In substantia nigra, dopamine is the major source. In the locus
coeruleus, noradrenalin, and in the diffuse brain stem raphe system, serotonin is the chief
precursor. The complex polymers contain also other oxidation metabolites of dopamine and
L-DOPA, cysteinyl-DOPA [299], 5-S-cysteinyl-dopamine [300], proteinacious components
and lipids [301,302. Neuromelanin also accumulates -synuclein [303] as well as transition
metals e.g., iron, copper and zinc [304].
The role of neuromelanin is a matter of debate. Neuromelanin has been proposed to play
a protective role via trapping free radicals [302] as well as its ability to chelate transition
metals, such as Fe Zn, Cu, Mn, Cr, Co, Hg, Pb, and Cd [301, 305, 306]. But the presence of
neuromelanin in dopaminergic neurons of the SNc was also be taken as an indication that NM
might in fact account for their vulnerability in Parkinsons disease [307, 308]. Other
researchers reported that neuromelanin, in contrast to synthetic dopamine melanin without
iron, increased the oxidative stress and induces onset of oxidative stress in mitochondria.
Superoxide dismutase and deferoxamine completely suppressed the increase, indicating that
superoxide produced by an iron-mediated reaction plays a central role [309].Neuromelanin
binds iron in the ferric form. Neuromelanin contains both high- and low-affinity iron binding
sites and additional iron is added to existing iron clusters in NM, analogous to the formation
and growth of the ferritin iron core [310]. neuromelanin is thought to be only partially
saturated with iron in vivo, thus maintaining a residual chelating capacity to protect the
substantia nigra against iron toxicity [311]. It was suggested that the increased brain iron
content encountered in the SN of Parkinson's disease patients might saturate iron-chelating
sites on NM, and a looser association between iron and neuromelanin may result in an
increased, rather than decreased, production of free radical species (metal-ion binding
capacity will be exceeded). This redox-active iron could be released and involved in a
Fenton-like reaction leading to an increased production of oxidative radicals. The resultant
radical-mediated cytotoxicity may contribute to cellular damage observed in PD [312]. It is
likely that at low iron concentrations native neuromelanin does not induce cell damage but
rather protects cells in culture from oxidative stress. This protective function appears to be
lost at high iron concentrations where neuromelanin saturated with iron functions as a source
of oxidative load, rather than an iron chelator. Changes to the structure of neuromelanin and
tissue iron load in Parkinsons disease may decrease the ability of the pigment to chelate iron,
thus increasing the potential for cell damage [313].
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 38
In our opinion, the protective role of neuromelanin may arise from its ability to form
metal-organic complexes with iron, Cu
2+
, which will prevent or reduce their involvement in
formation of free radicals via the Fenton reaction. In addition, neuromelanin might form a
stable free radicals which interact with potently oxidizing species (O
2

,
1
O
2
) thereby
minimizing their effects on cellular molecules.this hypothesis is supported by the presence of
neuromelanin in healthy persons and its decrease or even absence in individuals with
Parkinson's disease.


THE ROLE OF IRON

Parkinson's disease is another neurodegenerative disorder in which transition metals and
in particular Fe appear to have an important role. Owing to irons ability to donate electrons
to oxygen, increased iron levels can lead to the formation of hydroxyl radicals and hydroxyl
anions via the Fenton Reaction (Fe
2+
+ H
2
O
2
Fe
3+
+ OH + OH

). Iron is found throughout


the brain and important iron-containing proteins include cytochromes, ferritin, aconitases,
non-heme iron proteins in the mitochondrial electron transport chain, cytochromes P450, and
tyrosine and tryptophan hydroxylases [176]. The combination of high concentration of iron
and the neurotransmitter, dopamine, may contribute to the selective vulnerability of the SNPc.
Fe concentrations in SN values around 100200 g/g in normal subjects [301]. Increased Fe
content in the SNc of patients with Parkinson's disease has been reported. There was a
significant increase in total iron and iron (III) in substantia nigra of severely affected patients
and a shift in the iron (II)/iron (III) ratio in favor of iron (III) with a significant increase in the
iron (III)-binding protein, ferritin as well as a significantly lower glutathione content [314].
The increased iron content is mainly due to increased loading of ferritin [315]. High field
strength MRI demonstrated SNC abnormalities consistent with increased iron content early in
the disease [316]. It has been shown that the properties of the main iron-binding structure in
human brain, the ferritin differ from those of ferritin in liver or spleen with the iron-cores of
brain ferritin being significantly smaller than the iron-cores of liver ferritin. Also the ratio
between the heavy and light subunits of the protein shell of ferritin (H/L) is different in liver
and in brain structures, being the highest for hippocampus. Such differences in properties of
brain ferritin may speak in favor of more rapid iron turn-over in brain compared to liver
which might increase the possibility of oxidative stress [317].
Total iron intake was not associated with an increased risk of Parkinson's disease, but
dietary nonheme iron intake from food was associated with a 30% increased risk of
Parkinson's disease. This increase in risk was present in those who had low vitamin C intake
[318]. Epidemiological studies suggest that exposure to pesticides, such as rotenone, paraquat
or maneb, may contribute to the higher incidence of sporadic Parkinsonism among the
population of rural areas [319, 320]. The combined

environmental exposure to paraquat and
Fe was shown to result in accelerated

age-related degeneration of nigrostriatal dopaminergic
neurons [321]. The divalent metal transporter 1 (a widely expressed mammalian ferrous ion
(Fe
2+
) transporter [18] appears to be a key regulator of brain iron accumulation in PD. A
subtype containing iron response element (IRE) (DMT1+IRE) which is under control by iron
regulatory proteins is increased in 6-hydroxydopamine-induced PD model along with
elevation in iron uptake and oxidative stress [250, 322].
Role of Reactivity of Transition Elements in Life 39
Fe accumulation in the SNc of patients with Parkinson's disease is particularly important
because iron is a redox-active metal, that can interact with molecular oxygen to generate
superoxide anion (O
2

), which in turn, generates hydroxyl radical (_OH), a highly reactive


oxygen specie (ROS). As a consequence of Fe
2+
reaction with O
2
, Fe
3+
is generated, that can
trigger lipid oxidation through its reaction with lipid hydroperoxides normally present in
biological systems. Finally, many neurotransmitters are auto-oxidizable molecules [323].


ROLE OF OTHER TRANSITION METALS

Parkinson's disease is also characterized by the presence of proteinaceous deposits in the
residual dopaminergic neurons of the SNc (Lewy bodies and Lewy neuritis). These consist
mainly of aggregated forms of -synuclein [324] which is a normally placed presynaptic
protein involved in synaptic function and plasticity [325] (Clayton and George, 1998). The
mechanisms underlying the gradual transition of soluble -synuclein into virtually insoluble
Lewy bodies or Lewy neurites are still unknown [326, 327]. Studies suggest that some metals
can directly induce -synuclein fibril formation. Uversky et al. [328] noted that several di-
and trivalent metal ions caused significant accelerations in the rate of -synuclein fibril
formation. Aluminum was the most effective, along with copper(II), iron(III), cobalt(III), and
manganese(II). The effectiveness correlated with increasing ion charge density. A correlation
was noted between efficiency in stimulating fibrillation and inducing a conformational
change, ascribed to formation of a partially folded intermediate. The potential for ligand
bridging by polyvalent metal ions is proposed to be an important factor in the metal-induced
conformational changes of -synuclein.
It seems that Al
3+
and Fe
3+
which are considered as hard acids posses a large probability
to react with -synuclein which can be considered in this case as hard or borderline base.
Copper(II) also interacts with -synuclein ands binds tightly near the N-terminus at pH 7
[329]. Cu(II) ions are effective in accelerating -synuclein aggregation at physiologically
relevant concentrations without altering the resultant fibrillar structures. By using numerous
spectroscopic techniques (absorption, CD, EPR, and NMR), the primary binding for Cu(II)
was delineated to a specific site in the N terminus, involving His-50 as the anchoring residue
and other nitrogen/oxygen donor atoms in a square planar or distorted tetragonal geometry.
The carboxylate-rich C terminus, originally thought to drive copper binding, is able to
coordinate a second Cu(II) equivalent, albeit with a 300-fold reduced affinity. The NMR
analysis of ASCu(II) complexes reveals the existence of conformational restrictions in the
native state of the protein [330].
Cu
2+
binding of recombinant human -synuclein was examined using Electron
Paramagnetic Resonance (EPR) spectroscopy [331]. Wild type -synuclein was shown to
bind stoichiometric Cu
2+
via two N-terminal binding modes at pH 7.4. Electron spinecho
envelope modulation (ESEEM) studies of wild type -synuclein confirmed the second
binding mode at pH 7.4 involved coordination of His50 and its g and A
parameters correlated with either {NH
2
, N

, -COO

, N
Im
} or {N
Im
, 2N

} coordination
observed in -synuclein fragments. At pH 5.0, His50-anchored Cu
2+
binding was greatly
Mohamed Fikry Ragai Fouda, Omar Mohamed Abdel-Salam

et al. 40
diminished, while {NH
2
, N

, -COO

, H
2
O} binding persisted in conjunction with another
two binding modes.
Mn is another transition metal which has been linked to the development of a clinical
entity simulating Parkinson's disease in humans. Mn2 may be oxidized to Mn3 , which is
rather reactive and more toxic than Mn3 rapidly associates with Tf to form a stable complex.
In tissues, Mn may exist primarily in the form of Mn2 . Mn-induced neurotoxicity from excess
respiratory or dietary exposures has been well described. Oxidative stress is one of many
factors implicated in Mn induced neurotoxicity [68]. The divalent manganese ions can
interact with glutathione formaing a metal-organic complex which reduces the concentration
of free GSH in the cell.


Figure 7. Oxidative DNA damage induced by dopamine oxidation [332].
Dopamine oxidation by Mn is a potential mechanism for Mn-induced oxidative stress,
especially since Mn preferentially accumulates in dopamine-rich brain regions (e.g., basal
ganglia) [333]. Manganese toxicity has been suggested to relate to the formation of the
trivalent cation, which contains four unpaired d-orbital electrons which are
thermodynamically unstable compared to the three more favourably paired electrons present
in the divalent cationic state. Production of ROS can result from impairment of mitochondrial
function but may also be generated from the oxidation of dopamine in the presence of copper
(Cu (II))[78].

Role of Reactivity of Transition Elements in Life 41

Figure 8. Manganese induced dopamine oxidation [334].
Vanadium compounds in high oxidation states can induce oxidative transformations. A
recent study found that vanadium can exert neurotoxic effects in dopaminergic neuronal cells
via caspase-3-dependent PKCdelta cleavage, suggesting that metal exposure may promote
nigral dopaminergic degeneration [335]. Studies on rat liver mitochondria revealed that
(VO(2+), VO(3)(-), VO(acac)(2) and VOcit (1-100microM) could induce mitochondrial
swelling in a concentration dependent manner and disrupt mitochondrial membrane potential
in a time dependent manner. Vanadium compounds thus induced oxidative stress on
mitochondrial [336]. The oxidation stress of [VO]
1+
and [VO]
2+
may be ascribed to the
ability of these cations to produce

OH radicals due to interaction with H2O2 in faintly or


acidic medium.


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In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0
Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc.






Chapter 2



NONLINEAR OPTICAL PROPERTIES OF TRANSITION
METAL NANOPARTICLES SYNTHESIZED BY
ION IMPLANTATION


Andrey L. Stepanov
*

Laser Zentrum Hannover, Hannover, Germany
Kazan Federal University, Kazan, Russian Federation
Kazan Physical-Technical Institute, Russian Academy of Sciences,
Kazan, Russian Federation


ABSTRACT

Composite materials containing metal nanoparticles (MNPs) are now considered as a
basis for designing new photonic media for optoelectronics and nonlinear optics.
Simultaneously with the search for and development of modern technologies intended for
nanoparticle synthesis, substantial practical attention has been devoted to designing
techniques for controlling the MNP size. One of the promising methods for fabrication of
MNPs is ion implantation. Review of recent results on ion-synthesis and nonlinear optical
properties of cupper, silver and gold nanoparticles in surface area of various dielectrics as
glasses and crystals are presented. Composites prepared by the low energy ion
implantation are characterized with the growth of MNPs in thin layer of irradiated
substrate surface. Fabricated structures lead to specific optical nonlinear properties for
picosecond laser pulses in wide spectral area from UV to IR such as nonlinear refraction,
saturable and two-photon absorption, optical limiting. The practical recommendations for
fabrication of composites with implanted MNPs for optical components are presented.


1. INTRODUCTION

The search for new nanostructured materials is one of the defining characteristics of
modern science and technology [1-6]. Novel mechanical, electrical, magnetic, chemical,

*E-mail: aanstep@gmail.com
Andrey L. Stepanov 64
biological, and optical devices are often the result of the fabrication of new nanostructured
materials. The specific interest of this review is recent advantages in optical science and
technology, such as development of nonlinear optical random metal-dielectric and metal-
semiconductor composites based on metal nanoparticles (MNP) synthesized by ion
implantation. Simultaneously with the search for and development of novel technologies
intended for nanoparticle synthesis, substantial practical attention has been devoted to
designing techniques for controlling the MNP size. This is caused by the fact that the optical
properties of MNPs, which are required for various applications, take place up to a certain
MNP dimension. In this content, ion implantation nanotechnology allows one to fabricate
materials with almost any MNP structures, types of metals and their alloys [7-9]; this opens
new avenues in engineering nanomaterials with desired properties. Such composites possess
fascinating electromagnetic properties, which differ greatly from those of ordinary bulk
materials, and they are likely to become ever more important with a miniaturization of
electronic and optoelectronic components.
Nonlinear optics plays a key role in the implementation and development of many
photonics techniques for the optical signal processing of information at enhanced speed. The
fabrication of novel useful nonlinear optical materials with ultrafast time response, high
resistance to bulk and surface laser damage, low two-photon absorption and, of course, large
optical nonlinearities is a critical for implementation of those applications. In additional,
nonlinear materials for optical switching should be manufactured by processes compatible
with microelectronics technology. Nonlinear materials with such characteristics are
interesting for waveguide applications. The earliest studies of optical analogs to
electronicintegrated circuits or integrated optics were based on the recognition that
waveguide geometries allowed the most efficient interaction of light with materials.
Optoelectronic devices could be converted to all-optical configurations, with a number of
technological advantages, by developing waveguide media with intensity-dependent
refractive indices. Nonlinear optical switches must provide conversion of laser signal for
pulse duration as short as from nano- to femtoseconds. The nonlinear properties of MNP-
containing materials stem from the dependence of their refractive index and nonlinear
absorption on incident light intensity. Giant enhancement of nonlinear optical response in a
random media with MNPs is often associated with optical excitation of surface plasmon
resonances (SPR) that are collective electromagnetic modes and they are strongly dependent
on the geometry structure of the composite medium [4]. Therefore, MNP-containing
transparent dielectric and semiconductor materials can be effectively applied in novel
integrated optoelectronic devices.
Although both classic and quantum-mechanical effects in the linear optical response of
MNP composites have been studied for decades [4], the first experimental results on the
nonlinear optical effects of MNPs in ruby-glass was obtained quite recently in 1985 by
Ricard et al. [10]. Driven by the interest in creating nonlinear optical elements with MNPs for
applications in all-optical switching and computing devices, variety of experimental and
theoretical efforts have been directed at the preparation of composite materials. In practice, to
reach the strong linear absorption of a composite in the SPR spectra region, attempts are made
to increase the concentration (filling factor) of MNPs. Systems with a higher filling factor
offer a higher nonlinear susceptibility, when all other parameters of composites being the
same.
Nonlinear Optical Properties of Transition Metal Nanoparticles 65
MNPs hold great technological promise because of the possibility of engineering their
electronic and optical properties through material design. The transition metals of choice are
usually gold, silver, or copper, as these metals show SPR modes in the visible or near-infrared
spectral range [4]. The advantages of devices based on MNP materials can be understood
from the spectacular successes of quantum well materials [11, 12]. The capability of band gap
engineering in these structures permits wavelength tuning, while their small size alters the
electronic structure of these particles. This provides greater pumping efficiency for
applications in optical limiting and switching. The potential advantages of MNP composites
as photonic materials are substantial improvement in the signal switching speed. Up to 100
GHz repetition frequencies are expected in communication and computingsystems of the 21th
century [11]. Figure 1 compares in graphical form the switching speed and switching energies
of various electronic, optical materials and devices (adapted from [11, 13]). Within the broad
range of parameters covered by conventional semiconductor microelectronics, current
metal-oxide-semiconductor field-effect transistor devices made in silicon have low switching
energies, but switching time in the nanosecond range. Photonic devices based on multiple
quantum well (MQW) structures SEED and GaAs MQW devices and Fabry-Perot (FP)
cavities based on ferroelectric such as lithium niobate have extremely low switching speed
in comparison to MNPs [11, 12].

Figure 1. Plot of various photonic materials showing their switching energies and switching speed.
Adapted from [11, 13].
Davenas et al.pioneered synthesis of MNPs in dielectrics by ion implantation in 1973
[14, 15], when nanoparticles of various metals (sodium, calcium, etc.) in ionic crystals of LiF
and MgO were created. Late in 1975, noble metal nanoparticles such as Au and Ag were
fabricated in silicate glasses by Arnold and Borders [16, 17]. As shown in reviews [7-9, 18-
23], now developments expanded from the metal implants to the use of compounds, including
Andrey L. Stepanov 66
metal alloys and totally different composition precipitate inclusions. Implanted MNP were
fabricated in various materials, as polymers, glass, artificial crystals, and minerals.
Number of publications on nonlinear optical properties of MNPs fabricated in transparent
dielectric and semiconductor matrix is increasing every year. There arereview articles
observed partly this progress [11, 18, 19, 24, 25]. Unfortunately, some of this reviews are
already quite old and do not reflect a modern knowledge of the field or restricted to numbers
of selected publications only. However, as followed from a comprehensive list of publications
presented in Table 1 by 2011 [26-118], the geography of interest to nonlinear properties of
ion-synthesized MNPs covers all world continents. The data in Table 1 includes information
on all known types of metal ions and transparent matrices, ion implantation conditions for
fabrication of MNPs and for measurements of their optical properties. Nonlinear optical
characteristics of composites such as nonlinear refraction (n
2
) and absorption () coefficients,
real (Re[
(3)
]) and imaging (Im[
(3)
])parts of third order nonlinear susceptibilities (
(3)
) and
saturation intensities (I
sat
) are presented as well. As shown in Table 1, near one hundred
articles were already published. It should be mention, that ion implantation technique was
first used for ion-synthesis of MNPs in dielectrics to create nonlinear optical materials in
1991 to form copper and gold nanoparticles in silica glass [42, 100]. The present review
focuses on advantages in nonlinear optical properties of MNPs fabricated generally by low-
energy ion implantation and measured in wide spectral area from ultraviolet to infrared.


2. OPTICS OF METAL NANOPARTICLE COMPOSITES

The nonlinear optical response of medium with MNPs can be described by expanding the
i-th component of the polarization P induced by an applied optical field to third order in a
power series in this electric field E = E
0
e
lex
[11, 12]

P
i
=
y
(1)
E
j
+
j


yk
(2)
E
j
E
k
+
jk


yki
(3)
E
j
E
k
E
i
+
jki


, (1)

where the summation indices refer to Cartesian conditions in the material-dependent
(q)
and
to the polarization of the applied optical field.
The first-order susceptibility
(1)
is related to the linear refractive index n
0
and the linear
(Lambert-Beers law) absorption coefficient
0
through the following equation [13]

n
0
= Re 1+
(1)

and
0
=

n
0
c
Im
(1)

, (2)

where c speed of the light, - the optical frequency. The value
(3)
of a centrosymmetric
composite has an analogous relationship to the nonlinear coefficients n
2
and [45]

n
2
=
12
n
0
Re 1+
(1)

and =
96
2

n
0
2
c
2
Im
(1)

. (3)

Table 1. Types optically transparent dielectric and semiconductor matrixes with metal nanoparticles synthesized by ion implantation.
Abbreviations: soda-lime silicate glass (SLSG), indium-tin oxide (ITO), degenerate four wave mixing (DFWM), pump-probe transient
nonlinear spectroscopy (PPTNS), Z-scan and RZ-scan by reflection and vectorial self-diffraction (VSD)


Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm
2
,
Current density (J),
A/cm
2

Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I
0
), W/cm
2

Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n
2
), cm
2
/W
Absorption coef. (),
cm/W
Satur. intensity (I
sat
),
W/cm
2

Re[
(3)
], Im[
(3)
], |
(3)
|, esu
Authors

Co

SiO
2

E = 50
D = 410
16

J = 2

Z-scan
= 770
= 0.13
= 7610
9

I
0
= 11.410
9

n
2
= 1.810
-9
Cattaruzza et al. 1998
[26]

Ni

SiO
2

E = 100
D = 610
16



Z-scan
= 770
= 0.13
= 7610
9

I
0
= 9.810
9

n
2
= 1.710
-10
Falconieri et al. 1998
[27]
Cattaruzza et al. 2002
[28]

Cu

Al
2
O
3
E = 40
D = (0.5 1.0)10
17

J = 2.5 12.5

RZ-scan
= 1064
= 55
= 2
I
0
= 7.710
9




n
2
= -(1.3 1.7)10
-11

Re[
(3)
] = -(1.0 1.4)10
-9

Ganeev et al. 2005 [29]
2006 [30]
Ryasnyanskiy et al. 2005
[31]



Table 1. (Continued)


Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Cu

Al
2
O
3
E = 60


Z-scan
= 500 - 700
= 0.2
= 10
3

I
0
= 1.110
7

500-580
< 0

580-700
> 0


Plaksin et al. 2008
[32]


Cu

ITO

E = 40
D = (0.5 7.5)10
16

J = 4

Z-scan
= 532
= 7.010
3

= 10
I
0
= (6.2 - 15.5)10
9

n
2
= (5.2 8.3)10
-8

Re[
(3)
] = (5.4 7.4)10
-6

= -(3.5 3.6)10
-3

Im[
(3)
] = -(1.2 1.3)10
-6

|
(3)
| = (5.5 7.5)10
-6

Ryasnyanskiy et al.
2006 [33]


Cu

LiNbO
3
E = 60
D = (0.3 2.0)10
17

J = 10

PPTNS
= 574
= 0.2
= 10
3

P = 16
Bleaching absorption in 590 -
620 nm

Takeda et al. 2002
[34-36]
Kishimoto et al.
2003 [37]
Plaksin et al. 2005
[38]
2006 [39]

Cu

MgAl
2
O
4
E = 60
D = 3.010
16

J = 10

DFWM
= 532 |
(3)
| = (1.0 3.0)10
-8
Kishimoto et al.
2000 [40]




Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Cu

MgO
2
Al
2
O
4
E = 60
D = 3.010
16

J = 1-100

PPTNS
= 574
= 0.2
= 10
3

P = 16
Bleaching absorption in 590 -
620 nm

Takeda et al. 2002
[34-36]
2001 [41]


Cu

SiO
2
E = 160
D = 6.010
16

J = 2 7.5

Z-scan
= 532
= 100
= 7610
9

I
0
= 5.010
6



n
2
= 2.010
-15


Becker et al. 1991
[42]
Haglund et al. 1992
[43]


Cu

SiO
2
E = 160
D = 1.210
17

J = 2.5

Z-scan
= 570 - 600
= 6
I
0
= 5.010
8

n
2
= (2.0 4.2)10
-10

Re[
(3)
] = 2.410
-8

= -(0.1 1.0)10
-6





Haglund et al. 1993
[44]
1994 [45]
1998 [46]
Magruder et al. 1994
[47]
Yang et al. 1994 [48]






Table 1. (Continued)


Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Cu

SiO
2
E = 160
D = 1.210
17

J = 0.7 7.5

DFWM
= 532
= 10 and 35

n
2
= 2.010
-7

|
(3)
| = (2.4 7.3)10
-8

Haglund et al. 1994
[45]
1998 [46]
1995 [42]
Yang et al. 1994 [48]
1996 [49]
[
Cu

SiO
2
E = 160
D = 1.210
17

J = 2.5

Z-scan
= 532
= 100
= 7610
9

I
0
= 1.010
7

n
2
= (2.0 4.2)10
-14

Re[
(3)
] = 2.410
-8

= -(3.0 - 8.0)10
-3


Magruder et al.
1994 [47]


Cu

SiO
2

E = 90
D = 610
16



Z-scan
= 770
= 0.13
= 7610
9

I
0
= 9.810
9

n
2
= 5.010
-11
Falconieri et al.
1998 [27]
Cattaruzza et al.
2002 [28]

Cu

SiO
2
E = 2.010
3

D = (1.0 4.0)10
17

J = 2.0
T = 1000, 1 h

Z-scan
= 532 and 555 - 600
= 4.5
= 7610
9

I
0
= 8.810
9

n
2
= (4.0 6.8)10
-19

|
(3)
| = (0.3 4.7)10
-7

Ila et al. 1998 [50]
Sarkisov et al.
1998 [51]





Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Cu

SiO
2
E = 60
D = 3.010
16

J = 1-100

DFWM
= 532 and 561
= 7.010
3

I
0
= (0.1 1.0)10
6

|
(3)
| = (0.2 2.2)10
-8
Takeda et al. 1999
[52]
2000 [53]


Cu

SiO
2
E = 50
D = 8.010
16

J = 10

DFWM
= 585
= 13
= 400
I
0
= 1.010
8



|
(3)
| = 1.010
-7
Olivares et al. 2001
[54]



Cu

SiO
2
E = 60
D = 3.010
16

J = 1-30
T = 800, 1 h

PPTNS
= 574
= 0.2
= 10
3

I
0
= 8.010
11

Bleaching absorption in 590 -
620 nm

Takeda et al. 2002
[34-36, 55]
2001 [41]
2004 [56, 57]


Cu

SiO
2
E = 50
D = 8.010
16

J = 10

Z-scan
= 354.7
= 55
= 2
I
0
= 4.110
9

n
2
= -0.610
-7

Re[
(3)
] = -1.310
-8

= -6.710
-6

Im[
(3)
] = -2.910
-9

|
(3)
| = 1.410
-8
Ganeev et al. 2003
[58]
2004 [59]





Table 1. (Continued)


Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Cu

SiO
2
E = 50
D = 8.010
16

J = 10

Z-scan
= 532
= 55
= 2
I
0
= 5.410
9
= -6.010
-6

I
sat
= 4.310
8

Ganeev et al. 2003
[60]
2004 [61]



Cu

SiO
2
E = 50
D = 8.010
16

J = 10

Z-scan
= 1064
= 35
= 2
I
0
= 1.010
10

n
2
= -1.410
-7

Re[
(3)
] = -3.210
-8

= -9.010
-6

Im[
(3)
] = 6.510
-9

|
(3)
| = 3.310
-8



Ganeev et al. 2003
[62, 63]
2004 [64]
Stepanov et al.
2003 [65]



Cu

SiO
2
E = 60
D = 1.010
17

J = 10
T = 800, 1 h

Z-scan
= 540 - 610
= 0.2
= 1
I
0
= 8.010
11
Re[
(3)
] = -3.110
-9

Im[
(3)
] = 1.710
-9

|
(3)
| = -(-1.6 - 3.1)10
-8

Takeda et al. 2005
[66]
Plaksin et al. 2008
[32]






Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Cu

SiO
2
E = 180
D = (0.5 - 2.0)10
17

J = 1.5
T = 500 - 900, 1 h

Z-scan
= 790 - 800
= 0.15
= 7610
9

I
0
= (8.0 14.5)10
9

n
2
= -1.610
-10

Re[
(3)
] = (0.9 1.4)10
-7

= -(1.6 - 9.0)10
-6

Im[
(3)
] = (0.8 1.7)10
-7

|
(3)
| = (1.2 - 2.3)10
-7

Ren et al. 2006
[67]
Wang et al. 2006
[68, 69]



Cu

SiO
2
E = 100 -200
D = 3.010
16

T = 300 - 400, 1 h

Z-scan
= 533
= 710
3

= 0.1
I
0
= 0.910
9

n
2
= -3.710
-15

Re[
(3)
] = 3.710
-12

= (2.8 - 6.4)10
-9

Im[
(3)
] = 3.710
-14

|
(3)
| = 3.710
-12

I
sat
= (2.9 5.0)10
7

Ghosh et al. 2007
[70]
2009 [71]



Cu

SiO
2
E = 2.010
3

D = 4.010
16

T = 900, 1 h

VSD
= 533
= 26
P = 16
n
2
= -1.110
-12

= -2.010
-11

|
(3)
| = 8.410
-11

Torres-Torres et al.
2008 [72]



Cu

SiO
2
E = 2.010
3

D = 4.010
16

T = 900, 1 h

VSD
= 533
= 710
3

P = 16
n
2
= -1.210
-11

= -2.010
-12

|
(3)
| = 8.810
-10

Torres-Torres et al.
2008 [72]





Table 1. (Continued)


Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Cu

SiO
2
E = 180
D = (0.5 1.0)10
17

J = 1.5


Z-scan
= 532
= 38
= 10
I
0
= 0.910
9

n
2
= -(1.3 0.6)10
-10

= -(458- 151)10
-9

|
(3)
| = (2.1 - 0.8)10
-7

Wang et al. 2009
[73]
Wang et al. 2010
[74]



Cu

SiO
2
E = 180
D = (0.5 1.0)10
17

J = 1.5


Z-scan
= 1064
= 38
= 10
I
0
= 0.3810
9

n
2
= -(1.1 0.6)10
-10

|
(3)
| = (1.2 - 0.8)10
-7

Wang et al. 2009
[73]
Wang et al. 2010
[74, 75]



Cu

SLSG

E = 50
D = 8.010
16

J = 10

Z-scan
= 1064
= 35
= 2
I
0
= 3.010
10

n
2
= 3.610
-8

Re[
(3)
] = 0.810
-8

= -3.410
-6

Im[
(3)
] = 2.510
-9

|
(3)
| = 0.910
-8

Ganeev et al. 2003
[62, 63]
2004 [64]
Stepanov et al.
2003 [65]






Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Cu

SrTiO
3
E = 60
D = 3.010
16

J = 10

PPTNS
= 574
= 0.2
= 10
3

Bleaching absorption in 605 -
690 nm and positive
absorption in 516 - 506 nm
Takeda et al. 2002
[35, 55]
2004 [76]


Cu

SrTiO
3
E = 60
D = 3.010
16

J = 10
T = 300, 1 h

Z-scan
= 540 - 610
= 0.2
= 1
I
0
= 6.010
11

Re[
(3)
] = -(0.1 2.0)10
-9

Im[
(3)
] = -(0.2 1.2)10
-9

|
(3)
| = (1.0 - 2.0)10
-9

Takeda et al. 2006
[77]


Cu

SrTiO
3
D = (0.1 - 1.0)10
17



DFWM
Z-scan
= 775
= 0.25
= 1
n
2
= (1.8 6.2)10
-12

|
(3)
| = (1.6 - 5.33)10
-10

Cetin et al. 2010
[77]


Cu

TiO
2
E = 60
D = 3.010
16

J = 10

PPTNS
= 574
= 0.2
= 10
3

Bleaching absorption in 585 -
760 nm
Takeda et al. 2002
[35]


Cu

ZnO

E = 160
D = (0.1 - 1.0)10
17

J = 20

Z-scan
= 532
= 55
= 2
I
0
= 5.010
8
= -(0.4 2.1)10
-3


Stepanov et al.
2004 [79]
Ryasnyansky et al.
2005 [80]






Table 1. (Continued)


Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Cu

ZnO

E = 160
D = (0.1 - 1.0)10
17

J = 20

Z-scan
= 532
= 7.510
3

= 10
I
0
= 3.210
7

= -(0.7 5.5)10
-3


Ryasnyansky et al.
2005 [80]


Ag

Al
2
O
3
E = 30
D = 3.810
17

J = 3 10

RZ-scan
= 1064
= 55
= 2
I
0
= 4.310
9

n
2
= (1.1 1.8)10
-11

Re[
(3)
] = (0.9 1.5)10
-9

Ganeev et al. 2005
[29]
2006 [30]
Ryasnyanskiy et al.
2005 [81]


Ag

LiNbO
3
E = 1.510
3

D = 2.010
16

T = 500, 1 h

Z-scan
= 555 - 600
= 4.5
= 7610
6

I
0
= 8.810
7

n
2
= (0.8 1.3)10
-8


Sarkisov et al.
1998 [51]


Ag

LiNbO
3
E = 1.510
3

D = 2.010
16

T = 500, 1 h

Z-scan
= 532
= 40 - 70
= 10
I
0
= 1.010
10

n
2
= 5.010
-10


Williams et al.
1999 [82]
Sarkisov et al.
2000 [83]





Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Ag

SiO
2
E = 1.510
3

D = 4.010
16

J = 2
T = 500, 1 h

Z-scan
= 532
= 4.5
= 7610
6


|
(3)
| = 5.010
-7
Ila et al. 1998 [50]


Ag

SiO
2
E = 60
D = 4.010
16

J = 10

Z-scan
= 354.7
= 55
= 2
I
0
= 1.310
9


n
2
= -2.710
-7

Re[
(3)
] = -6.010
-8

= -1.410
-5

Im[
(3)
] = -6.110
-9

|
(3)
| = 6.110
-8

Ganeev et al. 2003
[58]
2004 [63]

Ag

SiO
2
E = 60
D = 4.010
16

J = 10

Z-scan
= 532
= 55
= 2
I
0
= (2.5 14)10
9

n
2
= -(6.2 - -0.7)10
-10

Re[
(3)
] = -(3.5 - -0.4)10
-8

= -(3.6 - -0.5)10
-5

Im[
(3)
] = -(1.3 - -0.2)10
-8

Ganeev et al. 2004
[84]
Stepanov et al.
2010 [85]

Ag

SiO
2
E = 60
D = 4.010
16

J = 10

Z-scan
= 1064
= 35
= 2
I
0
= 1.010
10

n
2
= 1.510
-8

Re[
(3)
] = 2.510
-9


Ganeev et al. 2003
[62]
2004 [63]

Ag

SiO
2
E = (1.7 2.4)10
3

D = (4.0 7.0)10
16

J = 0.3
T = 500, 1 h

Z-scan
= 532
= 7.010
3

P = 0.14

Three-photon absorption

Joseph et al. 2007
[86]


Table 1. (Continued)


Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Ag

SiO
2
E = 2.010
3

D = 7.010
16

T = 600, 1 h

Z-scan
= 527
= 0.233
= 10
3

= -(2.6 - 1.8)10
-6

Im[
(3)
] = 4.710
-10
I
sat
= (1.2 3.5)10
7

Rangel-Rojo et al.
2009 [87]
2010 [88]

Ag

SiO
2
E = 200
D = 2.010
17

J = 2.5

Z-scan
= 532
= 38
= 10

n
2
= -3.010
-11

Re[
(3)
] = 3.010
-8

= -7.010
-8

Im[
(3)
] = 2.610
-8

|
(3)
| = 4.010
-8

Wang et al. 2009
[89]


Ag

SiO
2
E = 200
D = 2.010
17

J = 2.5

Z-scan
= 1064
= 38
= 10
n
2
= -1.710
-10

Re[
(3)
] = 1.810
-7

|
(3)
| = 1.810
-7

Wang et al. 2009
[89]


Ag

SLSG

E = 60
D = 4.010
16

J = 10

Z-scan
= 532
= 55
= 2
I
0
= (2.5 14)10
9
n
2
= -(4.1 - -1.7)10
-10

Re[
(3)
] = -(2.4 - -1.4)10
-8

= -(6.7 - -1.7)10
-5

Im[
(3)
] = -(0.6 - 2.4)10
-8

Ganeev et al. 2004
[84]


Ag

SiO
2
E = 60
D = 4.010
16

J = 10

Z-scan
= 1064
= 35
= 2
I
0
= 3.010
10

n
2
= 3.510
-8

Re[
(3)
] = 5.710
-9


Ganeev et al. 2003
[63]
2004 [64]


Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (), Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Sn

SiO
2
E = 400
D = 2.010
17

J = 1

DFWM
= 460-540
= 510
3

I
0
= 3.010
10

|
(3)
| = 3.010
-6
Takeda et al. 1993
[90]
1994 [91]

Sn

SiO
2
E = 350
D = 8.010
17

J = 2
T = 200, 0.5 - 1 h

Z-scan
= 460-540
= 4.5
= 7610
6


|
(3)
| = 1.510
-6
Ila et al. 1998 [50]


Ta

SiO
2
E = 60
D = 3.010
16

J = 0.3
T = 900, 1 h

PPTNS
= 574
= 0.2
= 10
3

Bleaching absorption in 502 -
605 nm
Takeda et al. 2003
[92]


Au

Al
2
O
3
E = (2.75 3.0)10
3

D = 2.210
16

T = 1100, 1 h

DFWM
= 532
= 35 40
= 10
I
0
= 1.010
9

|
(3)
| = 7.010
-9
White et al. 1993
[93]


Au

Al
2
O
3
E = 160
D = (0.6 1.0)10
17

J = 10
T = 800 - 1100, 1 h

RZ-scan
= 1064
= 55
= 2
I
0
= (1.8 - 2.3)10
9

n
2
= -(0.1 1.5)10
-10

Re[
(3)
] = -(0.8 1.2)10
-8

Ganeev et al. 2005
[29]
2006 [30]
Stepanov et al.
2005 [94]
2006 [95]


Table 1. (Continued)


Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Au

Al
2
O
3
E = 60
D = 2.010
17

J = 10

PPTNS
= 568
= 0.2
= 10
3
Nonlinear dielectric
functions
Takeda et al. 2006
[96]
2007 [97]


Au

SiO
2
E = 2.7510
3

D = (0.3 1.5)10
17

T = 600 - 1100, 2.2 h

DFWM
Z-scan
= 532
= 6 and 35
= 3.8 and 10
I
0
= 4.510
8

n
2
= (1.0 - 8.9)10
-10

= (3.7 - 4.8)10
-5

|
(3)
| = (1.0 1.7)10
-10

Haglund et al.
1994 [45]
Yang et al. 1996
[49]
Magruder et al.
1993 [98]
White et al. 1994
[99]

Au

SiO
2
E = 1.510
3

D = 5.610
16
J = 0.7
T = 700 - 1200

DFWM

= 532
= 510
3

I
0
= 1.010
9

|
(3)
| = (0.12 5.0)10
-8
Fukumi et al. 1991
[100]
1994 [101]


Au

SiO
2
E = 3.010
3

D = 1.210
17
J = 2.0
T = 1200, 0.5-1 h

Z-scan
= 532
= 4.5
= 7610
6


|
(3)
| = 6.510
-7
Ila et al. 1998 [50]





Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Au

SiO
2
E = 2.7510
3

D = 1.510
17
T = 400

DFWM

= 532
= 410
3

I
0
= 1.910
6

|
(3)
| = (0.3 1.3)10
-7
Lepeshkin et al.
1999 [102]
Safonov et al. 1999
[103]


Au

SiO
2
E = 60
D = (1.0 2.0)10
17
J = 10 -17


PPTNS
= 554 and 568
= 0.2
= 10
3
I
0
= (0.7 0.9)10
9

Nonlinear dielectric
functions, positive absorption
in 500 650 nm

Takeda et al. 2006
[96]
2007 [104]

Au

SiO
2
E = 2.010
3

D = 2.810
16
T = 1100, 1 h

VSD
= 532
= 710
3

P = 0.14

n
2
= -2.010
-8

Re[
(3)
] = 1.910
-9

= -5.010
-6

Im[
(3)
] = -1.610
-9

|
(3)
| = 2.210
-9

Torrres-Torres et
al. 2007 [105]


Au

SiO
2
E = 1.510
3

D = (0.3 - 1.0)10
17
T = 400, 1 h

Z-scan
= 532
= 710
3

= 0.1
I
0
= 1.210
10

n
2
= -1.510
-11

Re[
(3)
] = 1.510
-8

= -(2.6 - 8.0)10
-8

Im[
(3)
] = -1.510
-10

|
(3)
| = 1.510
-8
I
sat
= (1.9 2.6)10
7
Ghosh et al. 2008
[71]
2009 [106]



Table 1. (Continued)


Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Au

SiO
2
E = 250 - 300
D = 1.010
17
J = 2.5


Z-scan
= 532
= 38
= 10
I
0
= 0.910
9

n
2
= -(1.2 1.4)10
-10

Re[
(3)
] = -1.210
-7

= -(9.7 - 21.0)10
-10

Im[
(3)
] = -3.610
-8

|
(3)
| = (1.3 1.6)10
-7
Wang et al. 2008
[107, 108]


Au

SiO
2
E = 250 - 300
D = 1.010
17
J = 2.5


Z-scan
= 1064
= 38
= 10
I
0
= 3.810
8
n
2
= -0.410
-10

Re[
(3)
] = -(4.3 - -1.2)10
-8

|
(3)
| = (0.1 4.3)10
-8
Wang et al. 2008
[107, 108]


Cu-Ni

SiO
2

E = 90 and 100
D = 610
16
and 610
16



Z-scan
= 770
= 0.13
= 7610
9

I
0
= 9.810
9

|
(3)
| = 6.810
-10
Falconieri et al.
1998 [27]
Cattaruzza et al.
2002 [28]

Cu-Ni

SiO
2

E = 90 and 100
D = 610
16
and 610
16



Z-scan
= 532
= 6
= 0.5 - 1
I
0
= 2.010
9

n
2
= 1.510
-10

|
(3)
| = 5.010
-12

Cattaruzza et al.
2002 [28]
Battaglin et al.
2000 [109]





Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Cu-Ag

SiO
2

E = 160 and 305
D = 1.210
16

J = 1.3 - 3


Z-scan
= 570
= 6
= 3.810
6

I
0
= 4.010
8

n
2
= (0.1 - 1.6)10
-9

= -(1.4 - -3.8)10
-5


Magruder et al.
1994 [110]


Cu-Ag

SiO
2

E = 30 and 43
D = (1.0 2.0)10
17




Z-scan
= 790
= 0.15
= 7610
9

I
0
= 8.810
9

n
2
= -(3.8 - 4.3)10
-12

= (1.0 - 2.2)10
-6

|
(3)
| = (0.8 1.5)10
-8

Wang et al. 2007
[111]


Cu-Ag

SiO
2

E = 180 and 200
D = (1.0 2.0)10
17

J = 1.5 2.5

Z-scan
= 1064
= 38
= 10
n
2
= (0.6 - 3.0)10
-10

|
(3)
| = (0.6 2.1)10
-7

Wang et al. 2008
[112]
2010 [113, 114]

Ag-Au

SiO
2

E = 130 and 190
D = 9.010
16

J = 2
T = 800, 1 h

Z-scan
= 572
= 5
= 1
I
0
= (1.6 -5.0)10
9
n
2
= -1.610
-10

= 1.310
-5

|
(3)
| = (0.9 1.7)10
-8

Cattaruzza et al.
2003 [115]
2005 [116]








Table 1. (Continued)


Metal
(Ion)

Matrix
Synthesis conditions:
Energy (E), keV
Dose (D), ion/cm2,
Current density (J),
A/cm2
Annealing temper.
(T), C and time
Study
nonlinear
optical
method
Laser parameters:
Wavelength (), nm
Pulse duration (), ps
Repetition rate (),
Hz
Intensity (I0), W/cm2
Pulse energy (P), mJ
Nonlinear parameters:
Refract. coef. (n2), cm2/W
Absorption coef. (), cm/W
Satur. intensity (Isat),
W/cm2
Re[(3)], Im[(3)], |(3)|,
esu
Authors

Ag-Au

SiO
2

E = 130 and 190
D = 3.010
16

T = 800, 1 h

Z-scan
= 525
= 6
= 1
I
0
= 0.810
9
= -(3.42 - -1.7)10
-4

I
sat
= (0.1 3.2)10
8

Cesca et al. 2010
[117]


Ti-Au

SiO
2

E = 320 and 1.110
3

D = (0.6 - 2.0)10
16

T = 900, 2 h

Z-scan
= 532
= 6
= 3.810
6

I
0
= 4.010
8
n
2
= (0.6 - 1.2)10
-9

= 5.310
-6


Magruder et al.
1995 [118]

For comparison some data for ion synthesized nontraditional MNPs are also presented.
Nonlinear Optical Properties of Transition Metal Nanoparticles 85
The susceptibility
(3)
is a fourth-rank tensor with eighty-one components; however,
material symmetries often reduce the number of non-vanishing components substantially.
For a MNP with a dielectric constant () =
1
()+i
2
() occupying a relative volume
fraction (filling factor) p << 1in a host of dielectric constant
h
, the absorption can be
presented as [45, 119]

0
=

n
0
c
Im
(1)
()

= 9p

h
3/2
c

2

1
+2
h
( )
2
+
2
2
= p

n
0
c
f
1
()
2

2
, (4)

where the f
1
() is the local-field enhancement factor. The absorption coefficient
0
has a
maximum at the SPR frequency [4] where
1
()+2
h
() = 0.
The effective third-order nonlinear optical susceptibility of the dielectric medium with
MNPs
eff
(3)
can be derived by applying Maxwells equations to the first order in the
electromagnetic field to yield [3, 120]

eff
(3)
= p
3
h

1
+2
h
2
3
h

1
+2
h

met
(3)
= p f
1
2
f
1
2

met
(3)
, (5)
where f
1
is the same local-field enhancement factor of the polarization describing the
(1)
.
This equation shows that the nonlinearity of composites with MNPs comprises two factors:
the nonlinearity due to the MNPs itself, and the enhancement contributed by the host matrix.
Note that whereas the
0
varies as f
1

2
, the
eff
(3)
varies as f
1

2
f
1
2
. Hence, it is expected a
significantly greater enhancement due dielectric nonlinearity in the
eff
(3)
.


3. NONLINEAR OPTICAL PROPERTIES OF ION-SYNTHESIZED
NANOPARTICLES NEAR IR-AREA (1064 NM)

3.1. Nonlinear Absorption of MNPs Studied by Z-Scan

In numerous studies, the nonlinear optical characteristics of the composite materials with
MNPs fabricated by various methods were generally studied using lasers operating at
frequencies that correspond to the spectral range of the SPR in particles [120] and Table 1.
One other hand, one should take into account that, when used in practice as optical switches,
optical limiters, and so on, these nonlinear materials have to operate at the wavelengths of the
most frequently used industry available lasers, such as Nd:YAG ( = 1064 nm), Ti:Al
2
O
3

( = 800 nm), and so on. Hence, in order to create new materials promising for practical use
in laser systems and integral optics and to optimize their characteristics, one should study the
nonlinear optical properties of these materials not only in the SPR spectral region, but also at
the frequencies specific for industrial lasers. Materials characterized with nonlinear properties
in near IR are now searching for applications in the field of telecommunication.
Here, recent results on nonlinear optical properties of copper and silver nanoparticles [62-
65], synthesized by ion implantation in glass host matrices studied by the classical Z-method
Andrey L. Stepanov 86
[121, 122] at the wavelength of a picosecond mode-locked Nd:YAG laser ( = 1064 nm) are
presented. The used Z-scan setup is shown in Figure 2. Laser pulse duration was 35 ps, pulse
energy 1 mJ and 2-Hz pulse repetition rate. The radiation had a spatial distribution close to
Gaussian and was focused by a 25-cm focal length lens (1) onto the samples (2). The beam-
waist diameter of the focused radiation was measured to be 90 m using a CCD camera. The
samples were transferred in steps of 2 mm along Z-axis when scanning focal region. The
maximum laser intensity at the focal point was 310
10
W/cm
2
, whereas the intensities of
optical breakdown were 610
10
W/cm
2
and 810
10
W/cm
2
for the glasses with copper and
silver nanoparticles, respectively. The fluctuations of the laser energy from pulse to pulse did
not exceed 10 %. The energy of single laser pulses was measured by a calibrated photodiode
(3). The samples were moved by a translation stage (7) along the Z-axis. A 1-mm aperture (9)
with 1 % transmittance was fixed at the distance of 100 cm from the focusing plane (closed-
aperture scheme). A photodiode (5) was kept behind the aperture. The radiation energy
registered by photodiode (5) was normalized relative to the radiation energy registered by
photodiode (3) in order to avoid the influence of non-stability of laser parameters. The
experimental data accepted as normalized transmittance T(z). The closed-aperture scheme
allowed the determination a value of n
2
and the open-aperture scheme was used for the
measurements a value of .


Figure 2. Z-scan setup. (1) focal length lens; (2) sample; (3) and (5) photodiodes; (4) and (6) digital
voltmeters; (7) translation stage; (8) computer; (9) aperture.
The samples with copper were prepared by Cu-ion implantation into amorphous SiO
2
and
soda lime silicate glasses (SLSG) as described in details [65]. The energies of 50 keV and
dose 810
16
ion/cm
2
and at a beam current density of 10 A/cm
2
were used. The penetration
depth of the MNPs in the glasses for given energy of implantation was not exceed 80 nm.
Optical transmittance spectra of implanted samples Cu:SiO
2
and Cu:SLSG are presented in
Figure 3. MNPs such as Cu in dielectric medium show optical absorption determined by SPR
[4]. The spectra are maximized near 565 nm Cu:SiO
2
and 580 nm for Cu:SLSG that gives
evidence for formation of the Cu nanoparticles in the glasses. Depending on the ion
implantation conditions, the incorporation of accelerated ions into silicate glasses leads to the
generation of radiation-induced defects, which can initiate reversible and irreversible
tr
di
am
fr
in
ra
U
ob
Fi
ex
U
M
in
ex
Fi
en
co
th
co
in
sp
ap
av
N
ransformations
ifferent types,
morphization,
rom implanted
ncrease in its v
adiation-induc
UV fundament
bserved in th
igure 3. It sho
xposure of the
UV spectral ran
MNPs and gla
nterband transi
xperimental re

igure 3. Transm
nergy of 50 keV

Figure 4 sh
ontaining copp
he measureme
oefficient . S
ntensities. It c
pecific feature
pproached an
veraging over
Nonlinear Opti
s in the glas
such as the g
the formation
d ions, etc. In
volume and th
ced defects are
al absorption
he short-wave
ould be noted t
e samples to la
nge of the lin
asses. For thi
itions and rad
esults.
mittance spectra
V and dose of 8
hows the exp
per nanopartic
ents carried o
Silicate glasse
can be seen f
es inherent in
d reaches a m
r the values m
ical Properties
s structure [6
generation of e
n of a new pha
n particular, th
he generation
e responsible f
edge in the sp
length range
that, presented
aser radiation
near absorption
is reason, in
iation-induced
a of (1) SiO
2
a
10
16
ion/cm
2
(2
erimental dep
cles in the Z-s
out in this sch
es did not dem
from Figure 4
n nonlinear ab
minimum at Z
measured for
s of Transition
6]. This can
extended and p
ase either from
he formation o
of internal st
for an increas
pectrum of the
of the optica
d here nonline
at a waveleng
n attributed to
what follow
d defects will
and (3) SLSG b
2) Cu:SiO
2
and
pendences of
scan scheme w
heme make it
monstrate the
4 that the ex
bsorption: the
Z = 0. Each p
40 pulses. So
n Metal Nanop
result in stru
point defects,
m atoms involv
of MNPs in th
resses within
e in the absor
e glass. In our
al transmittan
ear optical stud
gth of 1064 nm
o the SPR and
ws, the contrib
be eliminated
before and after
(4) Cu:SLSG [6
the T(z) me
with an open a
t possible to
nonlinear abs
xperimental de
e T(z) decreas
point in the g
ome distributi
particles
uctural imperf
local crystall
ved the glass s
he glass bring
an implanted
rption in the ra
r case, this ef
nce spectra di
dy were perfo
m, which lies f
d interband tra
butions assoc
d from the ana
r Cu-ion implan
65].
asured for bo
aperture [65].
determine the
sorption at ap
ependences T
ses as the foc
graphs was o
ion of the ex
87
fections of
ization and
structure or
gs about an
layer. The
ange of the
ffect can be
isplayed in
ormed upon
far from the
ansitions in
ciated with
lysis of the

ntation with
oth glasses
Recall that
e nonlinear
pplied laser
T(z) exhibit
cal point is
btained by
xperimental
88
po
pa
Fi
co
w
35
re
[1
op
lig
q(
re
w
is
8
oints in the gr
art, by the tim

igure 4. Norm
omposites in th
with energy of 4
5 ps [65].
The nonli
elationship for
122, 123]

T(z) = q(z)
-

Here, q(z)
ptical path wit
ght passed thr
(z) describes
elationship hol

1/q(z) = 1/G

where G(z) = z[
s the diffracti
raphs is cause
me instabilities
malized transmi
he z-scan schem
40 keV and dose
near coeffici
r the T(z), whi
-1
ln(1+q(z)).
= I(z)L
eff
is
th MNPs in th
rough the sam
the propagat
lds
G(z)-2/w
[1+z
0
2
/z
2
]is th
ion length of
Andre
ed, to some e
of laser radiat
ittance as a f
me with an ope
e of 810
16
ion/
ient of com
ich, in the case
the laser beam
he sample, Lis
mple as a funct
tion of the la
w
2
-i/w
2
,
e radius of the
f the beam, k
ey L. Stepano
extent, by the
tion.
function of the
en aperture. Sa
/cm
2
.Laser inten
mposite mater
e of the schem
m parameter,
the sample th
tion of its pos
aser beam in
e wave front c
k= 2/is the
v
energy instab
e Z-position o
amples fabricate
nsity is 810
9
W
rials can be
me with an ope
L
eff
= (1e

hickness, and I
sition along th
the material,
curvature in th
wave vector
bilities and, fo
of Cu:SiO
2
and
ed by Cu-ion i
W/cm
2
and pulse
e determined
en aperture, is

0
L
) /
0
is th
I(z) is the inten
he Z-axis. The
, because the
he Z-direction,
r, =
0
/(
or the most

d Cu:SLSG
implantation
e duration is
from the
s written as
(6)
he effective
nsity of the
e parameter
e following
(7)
, z
0
= kw
2
/2
(1+ z
0
2
/z
2
),
Nonlinear Optical Properties of Transition Metal Nanoparticles 89

0
= (2/)n
2
I
0
L
eff
- phase shift of frequency gained by the radiation passed through the
sample, w(z) = w
0
(1 + z
0
2
/z
2
)
2
is the beam radius at the point Z, and w
0
is the beam radius at
the focal point (at a level of 1/e
2
).

At Z = 0 (focal plane), the parameter q(0) = q
0
is defined by the expression

q
0
= I
0
L
eff
, (8)

where I
0
= I(0) intensity at the focal point.
Using formulas (6) and (8), it is possible to write

T
0
= q
0
-1
ln(1+q
0
), (9)

where T
0
is the minimum of T(z) in the focal plane in the scheme with an open aperture.
Expression (9) permits to determine the nonlinear absorption coefficient . The values of
calculated in this way from the experimental data for the Cu:SiO
2
and Cu:SLSG composites
are equal to 9.010
6
and 3.4210
6
cm/W, respectively (Table 2).

Table 2. Nonlinear optical parameters of silicate glasses with ion-synthesized copper and
silver nanoparticles measured at the wavelength of 1064 nm

Sample n
2
,
10
-8
esu
,
10
-6
cm/W
Re
(3)
,
10
-9
esu
Im
(3)
,
10
-9
esu

(3)
,
10
-8
esu
Cu:SiO
2
-13.7 9 -32.0 6.5 3.28
Cu:SLSG 3.6 3.42 8.3 2.5 0.87
Ag:SiO
2
1.5 2.5
Ag:SLSG 3.5 5.7
SLSG 8.110
-6
1.410
-6
1.410
-6


As can be seen, the nonlinear coefficients for these composites differ by a factor of
2.63. However, to compare correctly the coefficients for the Cu:SiO
2
and Cu:SLSG, it is
necessary to take into account the individual linear coefficients
0
for layers with copper
nanoparticles in different glasses (
0
SiO
2
= 9340 and
0
SLSG
= 5800 cm
1
). By assuming
that the thicknesses of the layers with MNPs in the implanted glasses are virtually identical
(~80 nm) [124], the nonlinear coefficient to the linear coefficient
0
for the relevant
composite (U = /
0
) can be normalized. As a result, the normalized values of U
SiO
2
=
9.6410
10
and U
SLSG
== 6.7310
-10
cm
2
/W, which differ by a factor of 1.432, were obtained.
To account for this discrepancy between the parameters U for different samples, proper
allowance must be made not only for the difference in the linear absorption coefficients but
also for the specific features in the location of the SPR peaks attributed to copper
nanoparticles. As can be seen from Figure 3, the SPR peaks assigned to MNPs is observed at
565 nm (
p
= 17699.1 cm
1
) for the Cu:SiO
2
composite and at 580 nm (
p
= 17241.4 cm
1
)
for the Cu:SLSG composite. In such MNP systems a two-photon resonance related to the SPR
Andrey L. Stepanov 90
can be assumed [3, 11]. On the other hand, it is known that, in the range of excitations and
their associated transitions in nonlinear medium, the optical nonlinearities become more
pronounced with a decrease in the detuning of the frequency from the resonance (in a case,
two-photon) excitation [125]. In present experiment, the frequency detuning should be treated
as the difference between the SPR frequency and the frequency of two photons of the laser
radiation used
20
= 18797 cm
1
(532 nm). The difference in the location of the SPR peaks
for copper nanoparticles in the SiO
2
and SLSG composites can be estimated from the
following ratio:

M =
20

p
Cu:SiO
2
( )
1
/
20

p
Cu:SLSG
( )
1
=1.42
. (10)

This value is in qualitative agreement with a ratio of 1.432 between the nonlinear
coefficients normalized to the linear coefficients
0
for different glasses.
The most interesting feature in the nonlinear optical properties of glasses with copper
nanoparticles irradiated at a wavelength of 1064 nm is the fact that the doubled frequency of
the laser radiation is close to the SPR peak frequency of copper particles. This is illustrated by
the diagram in Figure 5, which shows the spectral positions of the SPR peaks of the MNPs in
the samples studied and the spectral positions of the fundamental and doubled frequencies of
the laser radiation [63, 64]. Thus, from the above date, it can draw the following conclusions:
(1) In the near-IR range, the large nonlinear absorption coefficients determined
experimentally for glasses containing copper nanoparticles are explained by the SPR in
MNPs; (2) The efficient nonlinear absorption in the composites with copper nanoparticles
considered is associated with both the linear absorption of the material and the effect of two-
photon resonance at the SPR frequency for copper nanoparticles, which leads to the two-
photon transition at the wavelength 1064 nm.
The theoretical realization of two-photon absorption associated with the SPR of colloidal
metal (silver) particles in a solution was previously discussed in [126, 127], but in these
experiments the authors were difficult to analyze this possibility due to the experimental
problems related to the efficient aggregation of colloidal silver under laser irradiation, which
changed the nonlinear optical properties of the samples in time.
When analyzing the results presented here, it is expedient to dwell on the possible fields
of practical application of the studied composites. As is known, media with nonlinear (in
particular, two-photon) absorption are very promising as materials for optical limiters, which
can serve, for example, for the protection of eyes and highly sensitive detectors against
intense optical radiation [128]. Early, the majority of studies in this field have been performed
using nanosecond laser pulses. In this case, the main mechanisms responsible for nonlinear
effects are associated with the reverse saturable nonlinear absorption (fullerenes and organic
and metalloorganic compounds) and nonlinear scattering (solutions of colloidal metal
aggregates). Picosecond and subpicosecond laser pulses have been used only to examine the
optical limiting in media belonging primarily to semiconductor materials (two-photon
absorption and strong nonlinear refraction).
Since two-photon absorption at a wavelength of 1064 nm is observed in the Cu:SiO
2
and
Cu:SLSG samples, it is of interest to investigate the optical limiting effect in these composites
in the scheme with an open aperture. Here, it was assumed that the sample is located in the
re
T
10
co
in
co
co
se
pr
Fi
na
3
Fi
ap
fe
su
im
re
ch
de
co
w
M
be
N
egion correspo
he nonlinear
0
11
W/cm
2
[6
oefficients, the
n Figure 6. It
omposite is ch
omposite exhi
erve as nonlin
referable from

igure 5. Diagram
anoparticles [63

.2. Nonlinea

Consider th
igure 7 shows
perture. Each
eature of the
ubstrate glass
mplantation co
egion (the no
haracterized b
emonstrate a s
To recogni
opper nanopa
wavelength of
MNPs synthesi
e considered w
Nonlinear Opti
onding to a m
absorption w
2, 63]. With
e dependences
can be seen
haracterized b
ibits an approx
ear materials f
m the practical
m of the SPR fr
3, 64].
ar Refractio
he nonlinear o
s the T(z) dep
point on the
samples with
s demonstrat
onditions. From
onlinearity si
by self-defocu
self-focusing e
ize the reason
articles, the
the laser rad
ized by the im
within the fra
ical Properties
minimum trans
was studied ex
the use of t
s of the norma
n from Figure
by an approxim
ximately three
for optical lim
standpoint.
requencies for t
on of MNPs
optical refract
pendences of
plot correspon
h copper nan
te opposite
m the position
ign), it can
using of the
effect (n
2
> 0)
for the differ
observed sel
diation used in
mplantation [6
amework of th
s of Transition
mittance, i.e.,
xperimentally
the linear and
alized T(z) on
e 6 that, at th
mately fifteen
e-fold limiting
miting. It is cle
the glasses with
Studied by
tion of Cu:SiO
the samples
nds to a value
noparticles is
signs of no
n of the T(z) p
be can conc
laser beam (
.
rent signs of n
f-action effec
n this study
6, 9], the optic
he effective m
n Metal Nanop
, in the focal p
at an operati
d nonlinear (
the laser radi
he maximum
n-fold limiting
g. Consequent
ear that the Cu
h implanted copp
y Z-Scan
O
2
and Cu:SL
in the Z-scan
e averaged ov
that the plot
nlinear refra
peak in the pos
clude that th
(n
2
< 0), while
nonlinear refra
cts has to b
considerably
cal properties
medium theory
particles
plane of a bea
ing intensity
(two-photon)
iation intensity
m intensity, th
g, whereas the
tly, these comp
u:SiO
2
compos
per and silver
SG composite
n scheme wit
ver 40 pulses.
s for differen
ction under
sitive or negat
he Cu:SiO
2
s
e the Cu:SLS
action in the g
by analyzed.
exceeds the s
of the nanopa
y [4]. Such an
91
am (Z = 0).
from10
7
to
absorption
y presented
he Cu:SiO
2
e Cu:SLSG
posites can
site is more

es [63, 65].
th a closed
A specific
nt types of
the same
tive Z-scan
sample are
SG sample
glasses with
Since the
size of the
articles can
n approach
92
al
pr
Fu
C
re
el
re
de
co
re
no
el
fr
ne
ab
tr
co
2
llows to cons
resence of MN
ug. 6. Calculate
u:SLSG compo
In general,
efractive inde
lectronic resp
esonance trans
epending on
ontributions to
esonance inte
onlinear index
lectromagnetic
requency of th
egative only f
bove the two-p
For a hom
ransitions, on
orresponding e

sider the com
NPs in them.
ed curves T(z) a
osites [62].
, among nonli
x, it should
ponse of atom
sitions in the
the type o
o the n
2
of su
eractions invo
x n
2
is determ
c laser wave
he material (
for frequencie
photon resona
mogeneous con
ne can consid
equation for th
Andre
mposites as o
as a function of
inear optical p
be taken into
ms and molec
medium [129
of interaction
uch medium a
olving one-ph
mined from th

10
(or a mu

p
in the case
es that are slig
ances [130].
ndensed medi
der the stand
he nonlinear in
ey L. Stepano
ptically homo
the incident rad
processes con
o account the
cules [125] a
9]. The nonlin
n (resonance
as glasses are
hoton or two
he difference b
ultiple freque
of MNPs). In
ghtly below t
ium character
dard two-lev
ndex n
2
will h
v
ogeneous mat
diation intensity
ntributing to t
e optical Ker
and associated
near index n
2
e or nonreso
usually positi
o-photon proc
between the f
ency
i0
) and
n particular, t
the one-photo
rized by the o
vel energy m
have the form
terials, disreg
y for (1) Cu:SiO
the nonlinear
rr effect, caus
d with the p
2
may vary co
onance). Non
ive [130]. In t
cesses, the si
frequency of a
the intrinsic
the nonlinear
n resonances
occurrence of
model [125].
garding the

O
2
and (2)
part of the
sed by the
presence of
onsiderably
nresonance
the case of
ign of the
an incident
resonance
index n
2
is
or slightly
f resonance
Then, the
w
re
ac
na
n
2

de
an
w
co
ph

Fi
sc
do
m
fo
sa
Si
ph
N
n
2
= 2

where
p
and
espectively; th
ctive excitatio
anoparticles in
As follows
2
(the sign of t

i0
. Keeping in
etermining the

sgn Re


nd analyze it o
which lies in th
onsidered the
hotons and the
igure 7. Depend
cheme with a cl
ose of 810
16
ion
As was me
maxima for MN
or the Cu:SLS
amples lies ne
iO
2
and SLSG
hoton excitati
Nonlinear Opti
N

i 0
n
0
(
io

i0
correspond
he subscript i d
on centers c
n the sample);
from equation
the nonlinearit
n mind that
e sign of the n

(3)

(
only for the fre
he vicinity of t
effect that th
e SPR frequen
dence of the cur
ose aperture. Sa
n/cm
2
. Laser int
entioned (Figu
NPs in glass h
SG samples is
ear 565 nm. Su
G (Figure 5) a
ion of the la
ical Properties
0
4

p
)
3
,
d to the frequ
denotes one- a
considered to
and
i0
is the
n (11), N and
ty), which is d

(3)
depends li
nonlinearity as

20

p
)

equency
20
, i
the SPR of the
he frequency d
ncy exerts on n
rves T(z) for (a)
amples fabricat
tensity is 810
9
ure 7) the sam
host matrices o
s in the vicini
ubstituting the
and the freque
ser radiation
s of Transition
uencies of the
and two-photo
be dipoles
transition dip

i0
have no ef
determined on
inearly on n
2

3
= sgn
i.e., for the do
e samples with
detuning betw
nonlinear optic
) Cu:SiO
2
and (b
ted by Cu-ion im
W/cm
2
and pul
mples show di
of different ty
ity of 580 nm
e frequencies
ency
20
~ 18
used) into eq
n Metal Nanop
SPR of MNP
on processes; N
(virtually eq
pole moment a
ffect on the sig
nly by the detu
[125], it can

i 0
,
oubled frequen
h copper partic
ween the sum
cal processes.
b) Cu:SLSG co
mplantation wit
se duration is 3
ifferent spectr
ypes. For exam
m, while the SP
of the SPR of
8797 cm
1
(th
quation (12),
particles
P and the laser
N is the conce
qual to the n
at the frequenc
gn of the nonli
uning from the
be written th
ncy of the lase
cles. In other w
frequencies o
omposites in the
th energy of 40
5 ps [65].
ral positions o
mple, the SPR
PR peak of th
f copper nanop
he frequency o
a negative s
93
(11)
r radiation,
entration of
number of
cies
i0
.
inear index
e resonance
he relation
(12)
er radiation,
words, it is
f two laser

e Z-scan
keV and
of the SPR
R maximum
he Cu:SiO
2
particles in
of the two-
sign of the
Andrey L. Stepanov 94
detuning is obtained, which points to a negative contribution to the nonlinear susceptibility
for the matrices of both types. These conditions correspond to the self-defocusing of laser
radiation, which was experimentally observed for the Cu:SiO
2
sample (Figure 7a). Thus, the
two-level model used in this paper gives the proper sign of nonlinearity in the Cu:SiO
2
system
excited by laser radiation at a frequency lying outside the SPR region of its particles, namely,
at a frequency about two times lower than the SPR frequency.
A noticeable contribution to the n
2
can also be made by the thermal effect, i.e., by the
heat transfer from MNPs and defects of a dielectric host matrix heated by laser radiation
[131]. The rise time
rise
of n
2
variations is determined by
rise
= R
beam
/V
s
, where R
beam
is the
beam-waist radius and V
s
is the sound velocity in the lattice.In present case (R
beam
= 75 m,
V
s
5500 m/s) the time necessary for both the distribution of the density of a material and its
n
2
to reach their stationary values t
relax
~ 1315 ns is three orders of magnitude longer
than the pulse duration (35 ps). This allows one to exclude from consideration the influence
of the thermal effect on the nonlinear optical properties of the composites at present
experimental conditions and regard the electronic optical Kerr effect in MNPs as the main
factor.
On the other hand, for the Cu:SLSG sample, the self-focusing of the laser radiation
(Figure 7b) was observed [63], which contradicts the conclusions derived from equation (12).
To reveal the reasons for the different self-action effects in the glasses, it is necessary to
consider the influence of the substrate on the nonlinear optical properties of the composites.
For this purpose, the dependences of the T(z) for both types of glasses without MNPs was
measured. The SiO
2
substrate shows no noticeable changes in the character of the T(z) under
irradiation with the intensities used in this study; i.e., this glass does not demonstrate
nonlinear refraction and the nonlinearities observed in the Cu:SiO
2
samples are evidently
caused by the copper nanoparticles.
At the same time, the SLSG matrix exhibits a self-focusing effect (Figure 8). To estimate
the contribution of the glass substrate to the optical refraction of the Cu:SLSG sample, it was
determined and compared the values of
(3)
for the SLSG and Cu:SLSG samples.
In the general case, when a material simultaneously exhibits both nonlinear refraction and
nonlinearabsorption, the nonlinear susceptibility is a complex quantity

(3)
= Re
(3)

+iIm
(3)

(13)

where the real part is related to the nonlinear index n
2
and the imaginary part is related to the
nonlinear coefficient . As was mentioned the used glasses, contrarily to the samples with
nanoparticles, have no nonlinear absorption and, hence,
(3)
for the SLSG substrates is directly
real-valued and can be expressed in terms of n
2
as

Re
(3)

=
n
0
3
n
2 . (14)

This parameter can be experimentally estimated using the known Z-scan relations [122]

w
m
ph
Fi
su
pa
ob
w
pa
su
to
el
N
T
mv
=

where T
m-v
i
measured T(z),
hotodiode.

igure 8. Depend
Applying r
ubstrate, a val
arameter was
btained that, f
while Re[
(3)
] f
Taking into
arameter, who

Im
(1)


Using equa
usceptibility is
Since the R
o such nonlin
liminate the in
Nonlinear Opti
0.404(1 S
s the differen
, Sis the perc
dence of the cur
relations (15)
lue of n
2
= 8.
detected to be
for SLSG, wh
for Cu:SLSG i
o account tha
ose imaginary

=
n
h

h
c
2


ation (13) and
s |
(3)
| = 8.710
Re[
(3)
] is respo
near parameter
nfluence of bo
ical Properties
S)
0.25

0
nce between
ent of radiati
rves T(z) for SL
) to the expe
110
14
esu w
e of n
2
= 3.61
hich shows no
is equal to 8.3
at the nonline
part is expres

.
d the value of
0
9
esu (Table
onsible for the
rs (Table 2) f
oth the linear
s of Transition
the maximum
ion passing th
LSG in the z-sca
erimental data
was estimated,
10
8
esu. Usin
nonlinear abs
10
9
esu (Tab
ar susceptibil
sed via the no
f Im[
(3)
] for t
2) [63].
e nonlinear ref
for the SLSG
absorption an
n Metal Nanop
m and the m
hrough the ap
an scheme with
a (Figure 8)
, while for th
ng relation (14
sorption, |
(3)
|i
ble 2).
lity in Cu:SLS
onlinear coeffi
the given med
fraction in a m
G and Cu:SLS
nd the differen
particles
minimum (vall
perture and re
a close apertur
obtained for
he Cu:SLSG s
4) for the Re[
is equal to 1.4
SG is a comp
cient as
dium, then the
material, it was
SG samples. I
nce in the thic
95
(15)
ley) of the
eaching the

re [63].
the SLSG
sample this

(3)
], it was
410
14
esu,
plex-valued
(16)
e nonlinear
s compared
In order to
cknesses of
Andrey L. Stepanov 96
the samples, in practice, one does not compare directly the values of Re[
(3)
], but rather their
normalized values Re[
(3)
]L
eff
(in this case, L
eff
includes a correction for the linear absorption).
Using L
eff
of the wavelength 1064 nm for the samples of both types, it is possible to
getRe[
(3)
] L
eff
= 4.9210
14
esucm for Cu:SLSG,Re[
(3)
] L
eff
= 3.4510
15
esucm for SLSG.
Therefore, the nonlinear parameters of pure SLSG are lower by an order of magnitude than
the same parameters for the glasses containing nanoparticles.
Discussing the reasons for the self-focusing observed in the experiment (Figure 7), i.e.,
the reasons for the positive contribution to the nonlinear susceptibility of Cu:SLSG, it should
be take into account the considerable (~30%) linear absorption of SLSG in the spectral region
ofthe laser radiation (Figure 3). If a material exhibits the effect of saturation at the laser
wavelength, the total absorption will decrease upon the laser irradiation. However, if a
material is characterized by nonlinear absorption, the total absorption will increase, as is
observed for the glasses with nanoparticles. The nonlinear absorption of Cu:SLSG causes an
additional decrease in the intensity of the transmitted light in the focal plane by approximately
1012%, while for Cu:SiO
2
, whose linear absorption is ~15%, this value is equal to 18%.
Irrespective of the conditions of the laser radiation which was choose here, the increase in the
total absorption of Cu:SLSG can be caused by the nonlinear thermal effect predicted early
[132], and observed in [133] for silicate glasses containing radio-frequency sputtered copper
nanoparticles with size of 2.20.6 nm irradiation at the wavelength 1064 nm, when positive
nonlinear susceptibility was recorded using trains of picosecond pulses (100 pulses in a train).
Consider nonlinear refraction of glass containing silver nanoparticles. The composites
with silver were prepared by Ag-ion implantation into amorphous SiO
2
and soda lime silicate
glasses (SLSG) as described [23]. The energies of 60 keV and dose 410
16
ion/cm
2
and at a
beam current density of 10 A/cm
2
were used. The penetration depth of the MNPs in the
glasses for given energy of implantation did not exceed 80 nm [124]. Optical transmittance
spectra of implanted samples Ag:SiO
2
and Ag:SLSG are presented in Figure 9. MNPs such as
Ag in dielectric medium show optical absorption determined by SPR with maximum near
415 - 440 nm [4]. Figure 10 shows the experimental dependences of the T(z) of the samples
Ag:SiO
2
and Ag:SLSG during Z-scanning in the scheme with a closed aperture. As follows
from Figure 10, both types of glasses with silver nanoparticles demonstrate self-focusing of
laser radiation. The values n
2
and Re[
(3)
] are presented in Table 2. The nonlinear absorption
was not detected for these samples.
Estimate the nonlinear optical contributing to both the magnitude and the sign of the
nonlinear susceptibility
(3)
. Similarly to the case of sample with copper nanoparticles, the
spectral positions of the SPR bands in the glasses with silver nanoparticles depend on the type
of substrate (Figure 9). The SPR maximum lies at about 415 nm (
p
= 24096.4 cm
1
) for the
Ag:SiO
2
and at 440 nm (
p
= 22727.3 cm
1
) for the Ag:SLSG samples. As can be seen from
the diagram in Figure 5, the frequency of the sum of two photons of the laser radiation is
lower than the SPR frequency for nanoparticles in either matrix, which corresponds to a
positive sign of the detuning and, as a consequence, leads to a positive contribution to the
nonlinear susceptibility. Hence, no two-photon absorption occurs in the samples with silver
nanoparticles.

Fi
en
Fi
sc
do
3
m
[1
N
igure 9. Transm
nergy of 60 keV

igure 10. Depen
cheme with a cl
ose of 410
16
ion

.3. RZ-Scan

There are
materials, for e
137], Z-scan [
Nonlinear Opti
mittance spectra
V and dose of 4
ndence of the cu
ose aperture. Sa
n/cm
2
. Laser int
n Technique
different appr
example, dege
121, 122]). As
ical Properties
of (1) SiO
2
and
10
16
ion/cm
2
(3
urves T(z) for (a
amples fabricat
tensity is 810
9
e
roaches for th
enerate four-w
s was mention
s of Transition
d (2) SLSG befo
3) Ag:SiO
2
and
a) Ag:SiO
2
and
ted by Ag-ion im
W/cm
2
and pul
he study of no
wave mixing [
ned the latter t
n Metal Nanop
ore and after Ag
(4) Ag:SLSG [2
(b) Ag:SLSG c
mplantation wit
se duration is 3
onlinear optic
136], nonlinea
technique allo
particles
g-ion implantat
23].
composites in th
th energy of 60
5 ps [63].
cal properties
ar optical inte
ows determinin
97

ion with

he Z-scan
keV and
of various
erferometry
ng both the
Andrey L. Stepanov 98
value and the sign of nonlinear optical indexes n
2
and . There are several modifications of
the Z-scan technique, such as transmission Z-scan (TZ-scan) [121, 122], eclipsing Z-scan
[138], two-beams [139], reflection Z-scan (RZ-scan) [140-142], time-resolved Z-scan [143],
etc. The RZ-scan has an advantage with comparing to the others that allows studying the
optical nonlinearities of materials with a limited optical transparency. This technique is based
on the analyze of the surface properties of materials, whereas the others are used for
theinvestigation of bulk characteristics of media. The application of RZ-scan was firstly
presented in [14], where the nonlinear refraction of gallium arsenide was studied in at a
wavelength of 532 nm at which this semiconductor is fully opaque. On the other hand, this
technique can also be applied for transparent materials and can be used for the comparison
with conventional TZ-scan.
Ricently, the RZ-scan technique was applied for measurement of nonlinear characteristics
of low-transparency dielectric layers with MNPs beyond the region of the SPR absorption of
particles [29, 94]. Consider some examples with composites based on dielectric with copper,
silver and gold nanoparticles synthesized by ion implantation. As a substrate for such model
composites an artificial sapphire (Al
2
O
3
) was used. Whose surface of the sapphire opposite to
the implanted surface was frosted, because of which the sample was almost nontransparent in
visible and IR-spectral area. Ion implantation was performed with Ag
+
, Cu
+
and Au
+
[95, 144]. Experimental conditions of ion implantation used for fabrication of MNPs in Al
2
O
3

are shown in Table 3 [30].

Table 3. Ion implantation conditions and nonlinear optical parameters of Al
2
O
3
with
ion-synthesized silver, copper and gold nanoparticles measured at the wavelength of
1064 nm. * - thermal annealing [30]

Sample No. Energy,
keV
Current
density,
A/cm
2

Ion dose,
10
17

ion/cm
2

I
0
,
10
9

W/cm
2

n
2
,
10
-11

cm
2
/W
Re[
(3)
],
10
-9

esu
Ag:Al
2
O
3
1 30 3 3.75 4.3 3.40 0.94
Ag:Al
2
O
3
2 30 6 3.75 4.3 3.89 1.07
Ag:Al
2
O
3
3 30 10 3.75 4.3 5.36 1.48
Cu:Al
2
O
3
4 40 2.5 0.54 7.7 -3.75 -1.04
Cu:Al
2
O
3
5 40 12.5 1.0 7.7 -4.96 -1.38
Au:Al
2
O
3
6 160 10 0.6 2.3 -28.15 -7.77
Au:Al
2
O
3
7* 160 10 0.6 2.8 -32.68 -10.0
Au:Al
2
O
3
8 160 10 1.0 2.3 -38.76 -10.7
Au:Al
2
O
3
9* 160 10 1.0 2.8 -44.30 -12.2

The RZ-scan setup for measurement of nonlinear refraction is presented in Figure 11. The
Nd:YAG laser ( = 1064 nm, = 55 ps) operated at a 2 Hz pulse repetition rate was applied.
Laser radiation was focused by a 25-cm focal length lens (1). The maximum intensity and the
beam waist radius in the focal plane were measured to be I
0
= 710
9
W/cm
2
and 72 m,
respectively. The sample (2) was fixed on the translation table (7) and moved along the Z-
axis. The angle of incidence of laser radiation on the surface of sample was 30. A part of
radiation was reflected from the beam splitter (9) and measured by photo-diode (3) to control
th
th
ra
ra
Fi
vo
ex
no
re
ap
(t
th
ex
be
no
R
fo
po
gr
a
fe
ab
w
N
he energy of la
he mirror (10)
adiation by ph
atio R(z) betwe

igure 11. RZ-sc
oltmeters; (7) tr
In the case
xample, see [
onlinearities a
esponsible for
perture before
that are the su
he influence of
The princip
xperiment thro
eam change
onlinear effec
(z) of the ref
ocal plane, the
ositive nonlin
rowth of R(z).
decrease of R
eature will be
bout the sign o
The expres
written in the fo

I
R
z ( )=

Nonlinear Opti
aser pulses. T
) and than col
hoto-diode (5).
een the reflect
can setup. (1) fo
ranslation stage
e of RZ-scan
[145]). In TZ
and the apert
r the amplitud
e the detector
ubject of prese
f phase change
ples of RZ-sc
ough the foca
due to the in
cts appear whe
flected and inc
e laser intensit
ear refraction
After crossin
R(z) down to p
observed with
of n
2
from the
ssion for the in
orm [140-142]
I
0
R
0
V
0
1
(
(
ical Properties
he radiation r
llected by the
. To decrease t
ted signal and
ocal lens; (2) sam
; (8) computer;
the refractive
Z-scan scheme
ture is neede
de changes of
r. The measur
ent studies) we
es caused by n
can can be de
al plane of fo
nfluence of n
en the sample
cident laser ra
ty becomes hi
(n
2
> 0), the m
ng the focal pla
previous value
h the valley ap
R(z) depende
ntensity of rad
]
z ( )+ R
1
( )
s of Transition
eflected from
lens (11) tha
the influence
the incident o
mple; (3) and (5
(9) beam splitt
e nonlinearitie
e, the phase
ed in this ca
f reflected rad
rements of the
ere carried ou
nonlinear abso
escribed as fo
cusing lens. T
nonlinear refra
is positioned
adiation is co
igher and the
movement of
ane the nonlin
e. In the case o
ppearing in th
nce.
diation reflecte
) n
2
ik
2
( )
I
n Metal Nanop
the surface o
at allowed reg
of the instabil
one was accep
5) photodiodes;
ter; (10) mirror;
es are measure
changes are
ase. The refra
diation so the
e refractive n
ut without an a
orption.
ollows. The sa
The amplitude
action and no
d far from the
onstant. When
nonlinear effe
sample close
near refraction
of self-defocus
he R(z) depend
ed from the su
I z ( )V
1
1
z ( )
particles
f sample was
gistering all th
lity of laser rad
ted.
; (4) and (6) dig
(12) lens.
ed without ap
produced by
active nonline
ere is no need
nonlinearities
aperture, thus
ample moves
e and phase o
onlinear abso
focal plane, s
n the sample a
ects occur. In
to the focus l
n diminishes th
sing (n
2
< 0) th
dence. One ca
urface of a sam
) 1 ix' ( )
)
2
99
directed to
he reflected
diation, the

gital
perture (for
absorptive
earities are
d to use an
of samples
neglecting
during the
of reflected
orption. No
so the ratio
approaches
the case of
leads to the
hat leads to
he opposite
an conclude
mple can be
2
. (17)
Andrey L. Stepanov 100
Here, k
2
is the coefficients of nonlinear extinction; R
0
is the linear reflection coefficient,
V
m
(z) = g(z) id/d
m
, g(z) = d/d
0
x, d is the distance from the sample to the far-field aperture;
d
m
= k
2
m0
/2,
2
m0
=
2
(z)/(2m+1),
2
(z) =
2
(1+x
2
), x = z/z
0
, z
0
= k
2
0
/2 is the diffraction
length of the beam;
0
is the beam waist radius; z characterizes the sample position:

R
1

( )
=
2n
0
3
cos() 4n
0
cos()Sin
2
()
n
0
4
cos
2
() n
0
2
+ sin
2
()
n
0
2
sin
2
()
[ ]
1 2
, (18)

and is the angle of incidence of the beam [145]. Substituting into equation (17) the
parameters given above, it will be obtained the following expression for the normalized
reflection:

R z, ( )= 1
4R
1
( )/ R
0
( )I
0
k
2
x'
x'
2
+ 9
( )
x'
2
+1
( )
+
2R
1
( )/ R
0
( )I
0
n
2
(x'
2
+ 3)
x'
2
+ 9
( )
x'
2
+1
( )
+
R
1
( )/ R
0
( )
2
I
0
2
(n
2
2
+ k
2
2
)
x'
2
+ 9
( )
x'
2
+1
( )
.
(19)


Here, the first expression on the right-hand side is responsible for the nonlinear
absorption, the second expression describes the nonlinear refraction, and the third expression
characterizes their joint effect. It should be noted that equation (18) was derived without
taking into account the effect of thermal processes, which are characteristic of nanosecond
pulses [131] or of radiation with a high pulse repetition rate [131]. To determine the real part
of the third-order nonlinear susceptibility, the expression (14) was used.
For practical purpose the R(z) power could be presented as follows [144] :

P(z) =1+2Re R(n
2
+ik
2
)
[ ]
E(, z)
4
d
0

E(, z)
2
d
0

, (20)

where the radial coordinates, and E(,z) is the incident beam amplitude.
This equation describes the general case, when both nonlinear refraction and
nonlinearabsorption appear simultaneously during the reflection from the sample. However,
the application of open-aperture RZ-scan allowed neglecting the influence of nonlinear
absorption for the measurements of nonlinear refraction [146].

3.3.1. RZ-Scan Study of Ag:Al
2
O
3

The spectra of linear optical reflection for both virgon Al
2
O
3
and Ag:Al
2
O
3
composites
obtained by ion implantation under different conditions presented in Figure 12. Samples 1 - 3
Ag:Al
2
O
3
were implanted at fixed doses and energies but at different ion current densities,
which increases with the sample number (Table 3). The thickness of a substrate layer
containing silver nanoparticles was about 50 nm [124].

Fi
do
ar
ba
ob
na
sh
fr
A
im
(M
ir
io
re
SP
sh
Si
po
im
di
at
N
igure 12. Reflec
ose of 3.7510
17
As is seen
re characterize
and with a m
btained at hig
anoparticles in
harp increase
romapproxima
Al
2
O
3
matrix an
As was sh
mplantation of
MNPs) in the
rradiated by hi
ons and thus t
esult in an inc
PR absorption
hould be relat
ince the spec
ossible to conc
mplantation in
imensions, wh
The experi
t the waveleng
Nonlinear Opti
ctance spectra o
7
ion/cm
2
and di
from Figure 1
ed by the pres
maximum nea
gher ion curre
n the implante
e in the refle
ately 380 nm (
nd by interban
hown recentl
f silver ions i
sample. This
igh ion curren
their more ef
crease both in
n of MNPs. T
ed to a larger
ctral positions
clude that an i
nto Al
2
O
3
res
hich would im
imental R(z) d
gth 1064 nm a
ical Properties
of Al
2
O
3
before
ifferent current
12, in contrast
sence in the vi
ar 460 nm, w
ents. This refle
ed Al
2
O
3
and
ection intensi
(beyond the SP
nd transitions i
ly [147], an
into SiO
2
lead
is explained
nts and, hence
fficient incorp
the number o
Therefore, the
portion of m
s of the SPR
increase in the
sults in a hig
mmediately cau
dependences f
at the laser rad
s of Transition
and after Ag-io
densities (1) 3;
t to nonimplan
isible spectral
whose intensity
ection band a
corresponds t
ity in the sh
PR band) is ca
in metal NPs.
increase in
ds to an incre
by an increas
, by a higher
poration into M
of MNPs and
rising in the
etallic silver i
band maxim
e ion current d
gher concentr
use a spectral s
for the Ag:Al
2
diation intensi
n Metal Nanop
on implantation
(2) 6 and (3) 1
nted Al
2
O
3
, al
l region of a b
y is slightly
appears due to
to the SPR abs
horter wavele
aused by the a
the ion curr
ase in the por
se in the temp
diffusion mob
MNPs. In the
in their sizes,
SPR reflectio
in Al
2
O
3
impl
ma almost do
density under t
ration of MN
shift of the SP
2
O
3
samples m
ty I
0
= 4.310
9
particles
n with energy of
0 A/cm
2
[30].
ll the implante
broad selective
higher for th
o the formatio
sorption in M
ength region
absorption of l
rent density
rtion of the m
perature of the
bility of impla
e general case
which leads
on intensity in
anted at highe
not change, h
these condition
NPs rather tha
PR reflection m
measured by RZ
9
W/cm
2
are p
101

f 30 keV,
.
ed samples
e reflection
he samples
on of silver
NPs [4]. A
beginning
light by the
during the
metal phase
e dielectric
anted silver
e, this may
to a higher
n Figure 12
er currents.
hence it is
ns of silver
an in their
maximum.
Z-scanning
presented in
10
Fi
up
to
cu
in
ar
op
ou
va
of
hi
Fi
do
is
3.
pr
M
na
an
la
im
02
igure 13. Dep
pward, symme
ops of the be
urrents, i.e., fo
Virgin Al
2
ntensity up to
re caused by
ptical nonline
utside the SPR
Using mod
alues of n
2
and
f the results sh
igher values o

igure 13. Depen
ose of 3.7510
17
4.310
9
W/cm
2

.3.2. RZ-Scan
The second
revious series
MNPs was var
anoparticles (s
nd a low ion
arger dose (1
mplantation w
endences R(z)
etrical with re
ell-shaped dep
or the samples
2
O
3
shows no
the optical br
the presence
earities of silv
R absorption o
deled R(z) dep
d Re[
(3)
] in ea
hows that the
of n
2
and Re[
(
ndence of the cu
7
ion/cm
2
and di
2
and pulse dura
n Study of Cu
d type of sam
s of Ag:Al
2
O
ried by using
sample 4) was
current (2.5
10
17
ions/cm
2
)
as equal to 40
Andre
) for all the sa
espect to Z = 0
pendences are
s with a higher
o such optical
reakdown. Thu
of silver nan
ver particles
of the MNPs.
pendences (Fig
ach sample we
samples with
(3)
].
urves R(z) for A
ifferent current
ation is 55 ps. S
u: Al
2
O
3

mples is the A
3
samples (1
different ion
s obtained by
A/cm
2
), whil
) and a hig
0 keV for both
ey L. Stepano
amples have th
0, and by the p
e higher for t
r content of m
l nonlinearity
us, the nonline
noparticles in
are observed
gure 13) and f
ere estimated a
a higher conc
Ag:Al
2
O
3
compo
densities (1) 3;
olid line is a fit
Al
2
O
3
with cop
3) presented
current densi
implantation w
le the other sa
gher current
samples (Tab
v
he shape of a b
positive n
2
. It
the samples i
etallic silver.
y in experime
ear optical eff
Al
2
O
3
. It is
at laser irrad
fitting by them
and presented
centration of s
osites implanted
(2) 6 and (3) 1
tting [30].
pper nanopart
in Table 3, i
ities, one of t
with a small d
ample (sampl
(12.5 A/cm
2
ble 3).
bell with the to
should be not
implanted at
ents with lase
fects shown in
also interestin
diation at a w
m the experim
in Table 3. T
silver nanopar
d with energy o
0 A/cm
2
. Lase
ticles. In cont
in which the
the samples w
dose (0.5410
1
e 5) was imp
2
). The energ
op directed
ted that the
higher ion
er radiation
n Figure 13
ng that the
wavelength
mental data,
he analysis
rticles have

of 30 keV,
er intensity
trast to the
content of
with copper
7
ions/cm
2
)
planted at a
gy of ion
al
in
lin
w
co
~
sa
of
fo
Fi
an
an
in
(i
it
op
ob
se
in
w
na
op
al
N
The choice
llowed to obta
n particular, w
near reflection
whose maxima
opper nanopa
650 nm) than
ample 5 [21, 1
f MNPs also
orsample 5 is n

igure 14. Reflec
nd different par
nd 12.5 A/cm
2
The experi
n Figure 15. S
n particular, in
was chosen
ptical propert
btained are als
elf-focusing in
n contrast to t
which clearly t
anoparticles,
ptical properti
lso observed
Nonlinear Opti
e of ion impl
ained samples
with different s
n spectra of C
take clearly d
articles, exhib
n sample 4 (~
148]. A pronou
manifests its
noticeably hig
ctance spectra o
ameters: dose o
2
(3) [147].
imental and ca
Since the effic
n films, wires
a somewhat h
ties I
0
= 7.710
so bell-shaped
n the Cu:Al
2
O
the case with
testifies to the
i.e., to a neg
ies of Ag:Al
2
in transmissi
ical Properties
lantation regim
with a notice
sizes of MNP
Cu:Al
2
O
3
with
different positi
bits the band
~ 610 nm), w
unced differen
self in the int
gher than that f
of Al
2
O
3
before
of 0.5410
17
ions
alculated depe
ciency of the
, etc.) is know
higher intensi
0
9
W/cm
2
(Ta
d and symmetr
O
3
samples due
h Ag:Al
2
O
3
, w
e self-defocus
gative n
2
(Tab
2
O
3
and Cu:A
on Z-scan m
s of Transition
mes (Table 3)
eably different
s. This is illu
h the SPR ab
ions. Sample 5
at a longer
which points
nce in the port
tensity of the
for sample 4.
(1) and after C
s/cm
2
and 2.5
endences R(z)
electronic SPR
wn to be notice
ity of laser ra
able 3) than f
rical with resp
e to the presen
when the tops
sing of the las
ble 3). Such a
Al
2
O
3
samples
easurements
n Metal Nanop
) in the case
t filling factor
strated in Figu
bsorption band
5, which has a
wavelength
to the presen
tion of the me
SPR bands.
u-ion implantat
A/cm
2
(2) and
) for the Cu:A
R excitation i
eably lower th
adiation for m
for Ag:Al
2
O
3
.
pect to the poi
nce of copper
of the bells
ser beam in t
a different be
(a difference
at the same w
particles
of copper na
r of the metal
ure 14, which
ds of copper N
a higher conce
(with the ma
nce of larger
etal phase and
The reflectio
tion with energy
dose of 1.010
17
Al
2
O
3
samples
in copper nan
han in silver pa
measuring their
. The R(z) de
nt Z = 0, whic
nanoparticles
are directed d
the samples w
ehavior of the
in the signs
wavelength o
103
anoparticles
phase and,
h shows the
NPs [148],
entration of
aximum at
r MNPs in
d in the size
on intensity

y of 40 keV
7
ion/cm
2

are shown
nostructures
articles [4],
r nonlinear
ependences
ch points to
. However,
downward,
with copper
e nonlinear
of n
2
) was
of 1064 nm
10
in
C
pr
(s
Fi
(1
cu
is
3.
na
re
0.
[9
su
nu
so
(T
Fi
of
Fi
im
04
nSiO
2
with silv
Cu:Al
2
O
3
by sim
resented in T
sample 5) has

igure 15. Depen
1) dose of 0.54
urrent density o
a fitting [30].

.3.3. RZ-Scan
Samples (6
anoparticles, w
egion. As in
.110
17
ions/cm
94, 95]. Since
ubsurface laye
ucleation of M
ome of sampl
Table 3) [94, 9
The spectra
igure 16. The
f SPR reflectio
igure 16), obt
mplantation do
ver and coppe
mulating the R
able 3. It is f
higher |n
2
| and
ndence of the c
410
17
ions/cm
2

of 12.5 A/cm
2
.
n Study of Au
69) described
which are also
the case with
m
2
, but high
e, at such hig
er of the irradi
MNPs accumu
les 7 and 9 w
95].
a of linear op
formation of
on bands peak
ained directly
ose (sample 8
Andre
er nanoparticle
R(z) dependen
found that the
d |Re[
(3)
]|.
curves R(z) for
and current de
. Laser intensity
u:Al
2
O
3

d in Table 3
o characterized
h copper ion
er irradiation
gh energies,
ated dielectric
ulates over a l
were annealed
ptical reflectio
gold nanopart
ked at about 6
y by ion impla
8) results in a
ey L. Stepano
es (Table 2). E
nces and comp
e sample with
Cu:Al
2
O
3
com
ensity 2.5 A/c
y is 7.710
9
W/c
are the Al
2
d by efficient
ns, two differe
n energies, 1
the implanted
c [124], the im
longer time. In
d in a furnac
n from the Au
ticles by ion im
10 nm. Compa
antation, it is p
slight shift of
v
Estimated val
paring them wi
h a higher con
mposites implan
cm
2
and (2) dos
cm
2
and pulse d
2
O
3
containin
SPR absorptio
ent implantat
60 keV (sam
d impurity ac
mpurity concen
n order to inc
e for 1 h at a
u:Al
2
O
3
samp
mplantation is
aring samples
possible to se
f the maximu
ues of n
2
and
ith experimen
ntent of the m
ted with energy
se of 1.010
17
i
duration is 55 p
ng ion-synthe
on in the visib
tion doses, 0.
mples 6 and 8
ccumulates in
ntration necess
crease the size
a temperature
ples 69 are p
s proved by th
6 and 8 (curv
ee that an incr
um of the SPR
d Re[
(3)
] in
ntal data are
metal phase

y of 40 keV
ion/cm
2
and
ps. Solid line
sized gold
ble spectral
.610
17
and
8, Table 3)
n a thicker
sary for the
e of MNPs,
e of 800C
resented in
he presence
ves 1 and 3,
rease in the
R reflection
(t
in
hi
of
le
re
7,
re
m
ob
Fi
cu
Sa
na
fo
fo
pr
th
re
ch
pr
N
to ~ 620 nm),
nthe previous
igher filling fa
f these sample
eads to a shar
eflection shou
, curve 2 in F
edistribution o
material and, he
bserved in exp

igure 16. Reflec
urrent density o
amples anneale
At present,
anoparticles in
or Au:Al
2
O3 w
or samples 6
resents the de
hermal treatme
espect to the
haracterized b
resented in Ta
Nonlinear Opti
which is acco
case with the
actor of the m
es almost doe
rp increase in
lder (sample 9
Figure 16) ap
of the metal p
ence, with the
periments with
ctance spectra o
f 10 A/cm
2
wi
d after ion impl
, there are no
n a solid matri
were given in
and 7, which
ependences for
ent. As is seen
point Z = 0,
by self-defocus
able 3.
ical Properties
ompanied by
e implantation
metal phase in s
es not change
n the reflectio
9, curve 4 in F
ppearing near
hase in the di
e formation of
h fractal aggre
of Al
2
O
3
before
ith different dos
lantation during
data in the li
ix in the near-
[94, 95] and p
h were obtain
r samples 8 a
n, the R(z) de
, with the to
sing, which co
s of Transition
a noticeable i
n with copper
sample 8 (Au:
the positions
on in the long
Figure 16) or
the SPR refl
ielectric volum
f aggregates of
egates of silver
and after Au-io
ses of 0.610
17
i
g 1 h at tempera
iterature on th
-IR region (10
presented in F
ned directly by
and 9, obtained
pendences ha
ops directed
orresponds to
n Metal Nanop
increase in the
r ions (sample
:Al
2
O
3
). Subse
of the maxim
g-wavelength
even an addit
lection bands
me due to the
f MNPs. Simil
r particles but
on implantation
ions/cm
2
(3, 4) a
ature of 800C (
he nonlinear o
064 nm). The f
igure 17. Figu
y ion implant
d by ion impl
ve a bell-like
downward. T
a negative n
2
a
particles
e intensity. Th
es 4 and 5), p
equent therma
ma of the SPR
spectral range
tional maximu
can be assoc
high tempera
lar spectral be
t in solutions [

n with energy of
and 1.010
17
ion
(2, 4) [94, 95].
optical propert
first experime
ure 17a shows
tation, while
lantation and
shape symme
Thus, sample
and Re[
(3)
] wh
105
his fact, as
points to a
al treatment
R bands but
e. A broad
um (sample
ciated with
ature of the
ehavior was
149].
f 160 keV,
n/cm
2
(1, 2).
ties of gold
ental results
s the curves
Figure 17b
subsequent
etrical with
s (6-9) are
hich values
10
Fi
w
di
im
1
lin
06
igure 17. Depen
with doses 0.610
ifferent doses o
mplantation (1, 3
h at temperatur
ne is a fiting [94
ndence of the cu
0
17
ions/cm
2
(1,
f 0.610
17
ions/c
3) and samples
re of 800C (2, 4
4, 95].
Andre
urves R(z) for A
2) and 1.010
17
cm
2
(3, 4) and 1
created by ion
4). Laser intens
ey L. Stepano
Au:Al
2
O
3
compo
7
ion/cm
2
(3, 4)
1.010
17
ion/cm
2
n implantation w
sity is 2.310
9
W
v
osites implanted
at current dens
2
(1, 2). Sample
with subsequent
W/cm
2
and pulse
d with energy o
ity of 10 A/cm
es created by ion
t thermal anneal
duration is 55 p


of 160 keV
m
2
with
n
ling during
ps. Solid
Nonlinear Optical Properties of Transition Metal Nanoparticles 107
3.3.4. Nonlinear Refraction of MNPs Studied by RZ-Scan
For the composites based on Al
2
O
3
, the frequencies
p
are equal to 22222 cm
1

(~ 450 nm, Figure 12) for silver nanoparticles, 16393 15384 cm
1
(~ 610 650 nm,
Figure 14) for cupper nanoparticles, and 16129 cm
1
(~ 620 nm, Figure 16) for gold
nanoparticles. Consider relation (12) for the case of a one-photon process (i = 1), i.e., for the
frequency
10
= 9398 cm
1
( = 1064 nm), which is the fundamental frequency of the laser
radiation used. Substituting the values of
10
and
p
into relation (12), positive values of
Re[
(3)
] and a negative detuning
10
for all the samples can be obtained. The positive Re[
(3)
]
and n
2
correspond to the self-focusing of the laser radiation in the sample, which was
observed experimentally for the Ag:Al
2
O
3
samples (samples 13, Table 3).
On the other hand, the positive values of the signs of Re[
(3)
] and n
2
contradict the self-
defocusing experimentally detected in the samples with cupper and gold nanoparticles
(Figures 15 and 17). Hence, the description of nonlinear processes in the approximation of
one-photon excitation for the Cu:Al
2
O
3
and Au:Al
2
O
3
systems is incorrect. Therefore,
consider the case of two-photon excitation for all the composite systems studied using again
expression (12) but with the doubled frequency of the laser radiation,
20
= 18797 cm
1

( = 532 nm). This frequency lies in the vicinity of the SPR frequencies of MNPs in Cu:Al
2
O
3
and Au:Al
2
O
3
. Determine the signs of
20
for composites and see how they correlate with the
nonlinear optical processes observed experimentally. In this case, the signs of Re[
(3)
] for the
Cu:Al
2
O
3
and Au:Al
2
O
3
systems are negative, which agrees with the self-defocusing detected
in experiments and suggests the occurrence of two-photon absorption in these samples. For
the Ag:Al
2
O
3
samples, this sign turns out to be positive again, as in the case of one-photon
excitation, and correlates with the self-focusing observed in experiments. However, for silver
nanoparticles in Al
2
O
3
, it is difficult to choose between the one-photon and two-photon
excitation mechanisms. Probably, the two mechanisms are simultaneously realized in this
type of MNPs and their manifestation depends on the dominant frequency of laser excitation.
Thus, the two-level model correctly predicts the sign of the nonlinearity in the Cu:Al
2
O
3
and
Au:Al
2
O
3
systems in the case of excitation by laser radiation at a frequency divisible by the
doubled SPR frequency.
As was mention a change in n
2
of a composite material can be caused by the thermal
effect due to heat transfer from MNPs or defects of the dielectric host matrix heated by laser
radiation [131]. Despite the duration of laser pulses used was rather short ( = 55 ns), the
influence of the thermal effect on the nonlinear refraction can be analyzed. Estimate how
large a change in the refractive indexof crystalline sapphire n
Al
2
O
3
caused by heating can
be.
The change in the refractive index due to the thermal effect can be represented in the
form [131]

n(r, z, t) =
1
C
h
p
h
dn
dT
(r, z, t)
, (21)

where C
h
and
h
are, respectively, the heat capacity and the density of the host matrix with
MNPs (in the case of sapphire, C
h
= 0.419 J/gK and
h
= 3.97 g/cm
3
); dn/dT is the thermo-
optic coefficient, equal to 13.710
6
1/K; and E(r, z, t) is the energy of the radiation absorbed
Andrey L. Stepanov 108
in a unit volume of the material over a time t. The thermo-optic coefficient for sapphire is
positive, and, hence, the thermal effect should lead to the self-focusing of laser radiation in all
the samples.
Since the self-focusing of laser radiation was experimentally observed only for the
samples with silver nanoparticles the thermal effect for such samples were analyzed using
present experimental conditions of nonlinear measurements [94, 95]. Thus, in the case of
Ag:Al
2
O
3
, the energy of the absorbed radiation is 3.8710
6
J. For the layer with silver
nanoparticles of 50 nm thickness and the beam waist radius 72 m, the analyzing volume is
4.8810
10
cm
3
. In this case, the energy E(r, z, t) is 7.9210
3
J/cm
3
. Substituting these values
into equation (21), the value of n(r, z, t) 6.5310
2
will be obtained. In same time, the
experimental values are from 4.3310
2
to 6.8310
2
. Hence, the thermal effect may manifest
itself in the case of samples with silver nanoparticles. However, as it was mentioned the time

rize
necessary for a change in the medium density and a corresponding change in the refractive
index is determined by the ratio of the beam waist radius to the speed of sound. Taking into
account our experimental conditions (
0
= 72 m at the wavelength 1064 nm and V
s
~ 5000
5500 m/s),
rize
1315 ns will be again estimated. This time is three orders of magnitude
longer than the pulse duration used (55 ps), and, hence, the thermal effect caused by the
propagation of an acoustic wave can be excluded from consideration in our case.
In conclusion, RZ-scan method is suited for study of nonlinear refraction of samples
based on dielectrics with MNPs. Although the sensitivity of the RZ-scan method is slightly
lower than that of the classical transmission Z-scan, the RZ-scan method allows one to extend
the spectral range of study to the region of low transparency of composite materials. The sign
of the Re[
(3)
] is analyzed on the basis of the two-level model, and it is shown that Re[
(3)
] of
the samples with copper and gold nanoparticles are determined by the two-photon process. It
is difficult to make similar conclusion for samples with silver nanoparticles.


4. NONLINEAR OPTICAL ABSORPTION OF ION-SYNTHESIZED SILVER
NANOPARTICLES IN VISIBLE RANGE

The silver nanoparticles doped in different dielectrics demonstrate variable nonlinear
optical properties in visible range [120]. The interest on such structures is based on the
prospects of the elaboration of optical switchers with ultrafast response, optical limiters, and
intracavity elements for mode locking. Silver nanoparticles have an advantage over another
metal nanoparticles (i.e., gold and copper) from the point of view that the surface plasmon
resonance energy of silver is far from the interband transition energy. So, in the silver
nanoparticle system it is possible to investigate the nonlinear optical processes caused solely
by SPR contribution. It should be noted that previous studies of nonlinear optical parameters
of silver nanoparticles-doped glasses were mostly focused on determination of third-order
nonlinear susceptibility
(3)
.

The saturated absorption in silicate glasses doped with ion-synthesized Ag nanoparticles
at wavelength of 532 nm and their dependence on laser radiation intensity are considered at
present review. As was shown the ion-synthesized silver nanoparticles in Ag:SLSG and
Ag:SiO
2
demonstrate the SPR band with minimum transmission in the range of 410440 nm
(Figure 9). Early, it was predicted that glasses with silver-doped nanoparticles could possess a
Nonlinear Optical Properties of Transition Metal Nanoparticles 109
nonlinear saturated absorption [150]. The spectral dispersion of the imaginary part of
susceptibility Im[
(3)
] of such glass was detected as negative value in the spectral SPR range
of 385 436 nm. The nonlinear coefficient is also negative in the case of saturated
absorption.
The T(z) dependences of Ag:SLSG and Ag:SiO
2
samples measured using open aperture
Z-scan scheme at laser radiation intensity of I
0
= 2.510
9
W/cm
2
and pulse duration of 55 ps is
presented in Figure 18 [84]. The transmission of samples was increased due to nonlinear
saturated absorption as they approached close to the focal plane. Experimentally estimated
nonlinear parameters of the are -6.710
-5
cm/W in Ag:SLSG and -3.610
-5
cm/W in Ag:SiO
2
.
Note that the coefficient can be presented as = /I
s
whereI
s
is saturated intensity. Then
the values of I
s
are 1.110
9
and 1.410
9
W/cm
-2
and the Im
(3)
are -2.410
-8
and -1.310
-8
esu in
Ag:SLSG and Ag:SiO
2
, respectively.


Figure 18. Normalized transmittance Ag:SLSG (1) and Ag:SiO
2
(2) samples at laser radiation intensity
of I
0
= 2.510
9
W/cm
2
. Solis lines show is a fittings [84].
In Figures 19 and 20 values of in dependence of laser intensity varied from 10
9
to
210
10
W/cm
2
are presented. As seen from the figures there are a decrease of for higher
intensities. In particularly, a 21- and 12-fold decrease of was measured at
I
0
= 1.1510
10
W/cm
2
for Ag:SLSG and Ag:SiO
2
, respectively, compared to detected at
I
0
= 110
9
W/cm
2
.
The variations of nonlinear transmission in MNP structures in dielectrics were early
attributed in some cases to the fragmentation, or fusion of nanoparticles following the their
photothermal melting [151, 152]. It was reported about the alteration of the sign of nonlinear
refractive index of small Ag clusters embedded in SLSG [153]. They noted that thermal
Andrey L. Stepanov 110
effects could change the properties of nanoclusters. The transparency in these samples was
associated with oxidation of Ag nanoparticles. However, no irreversible changes of
transmittance were observed in present experiments.


Figure 19. Coefficient of Ag:SLSG in dependence of laser intensity.

Figure 20. Coefficient of Ag:SiO
2
in dependence of laser intensity.
Nonlinear Optical Properties of Transition Metal Nanoparticles 111
The reverse saturated absorption can be responsible for the decrease of negative nonlinear
absorption of Ag nanoparticles and it could be assume that in the case of picosecond pulses
the reverse saturated absorption starting to play an important role in the overall dynamics of
nonlinear optical transmittance of MNPs contained compounds, taking into account the
saturation of intermediate transitions responsible for saturated absorption.Thus, saturated
absorption in Ag:SLSG and Ag:SiO
2
was dominated at small intensities and decreased with
the growth of intensity due to influence of competing effects, whereas the selfdefocusing at
low intensities was changed to self-focusing at high intensities. The possible mechanism of
the decrease of Im[
(3)
] is the influence of nonlinear optical processes with opposite
dependences on laser intensity, also such as two-photon absorption [122]. The wavelength
range corresponded to the interband transitions in Ag is located below 320 nm, so the two-
photon absorption connected with interband transitions can be involved in the case of 532 nm
radiation. The possibility of two-photon absorption due to interband transition of
photoexcited electrons was previously demonstrated for Ag particles [154]. The three-photon
absorption connected with interband transition for Ag nanoparticles was analysed in (Kyoung
et al., 1999). Thus, saturated absorption in Ag:SLSG and Ag:SiO
2
was dominated at small
intensities and decreased with the growth of intensity due to influence of competing effects,
whereas the self-defocusing at low intensities was changed to self-focusing at high intensities.


ACKNOWLEDGMENTS

I wish to thank my partners and co-authors from different countries D. Hole,
P.D. Townsend, I.B. Khaibullin, V.I. Nuzhdin, V.F. Valeev, Yu.N. Osin, R.A. Ganeev,
A.I. Ryasnyanskiy, T. Usmanov, M.K. Kodirov, V.N. Popok, and U. Kreibig, Also, I grateful
to the Alexander von Humboldt Foundation and the DAAD in Germany, Austrian Scientific
Foundation in the frame of Lisa Meitner Fellowship and the Royal Society in UK for
financial support. This work was partly supported by the Ministry of Education and Science
of the Russian Federation (FTP Scientific and scientific-pedagogical personnel of the
innovative Russia No. 02.740.11.0779).


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In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0
Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc.






Chapter 3



SELF-ORGANIZATION OF THE NANOCRYSTALLINE
STRUCTURE AND RADIATION RESISTANCE OF
STRUCTURAL MATERIALS


V. P. Kolotushkin
*
and A. A. Parfenov
JSC VNIINM A.A. Bochvar,
Moscow, Russia


ABSTRACT

Radiation resistance of structural materials depends on the ability of their structure to
reduce the rate of accumulation of secondary radiation defects. The introduction of
interstitial or substitutional atoms into the matrix, increasing the density of dislocations
and other external factors, can accelerate the recombination of primary point defects.
We have studied the use of internal structural factors in recombination accelerating
of vacancies and interstitials. The principal difference between the two approaches lies in
the next. In the proposed metastable alloys the traps of point defects forms the matrix
itself but not embedded in a matrix artificial species. The crystal lattice distortions arising
in synergistic effect of neutron irradiation and short-range ordering become the traps of
vacancies and interstitials. Distortions capture vacancies and interstitials, thus occurs a
self-organization of the crystal structure of material.


1. INTRODUCTION

Structural materials of reactor cores are simultaneously impacted the neutron radiation,
high temperatures, and the temperature gradient across the thickness of products, mechanical
stress and chemical interaction with the environment. Under these conditions the materials
must provide the strength of the reactor equipment units, the stability of their geometric
shapes and sizes throughout the campaign [1]. The most important damaging factor is the
neutron irradiation. When impacted into the metal atom a neutron with energy of 1 MeV can

*
Email: kolotush@bochvar.ru
V. P. Kolotushkin and A. A. Parfenov 120
transfer energy to 50 keV sufficient to displace the atom from the lattice site (20-50 eV). The
destruction of the crystal lattice and the mixing of atoms in the displacement cascade alter the
qualitative structure of the metal. The size of a cascade is 10 nm. In this region is released
an energy of primary knock-on atom. Although most of this energy is released as heat in the
process of Frenkel pairs recombination, much of them remain creating a microstructure
changes that lead to changes in the phase diagram [2].
Typical values of activation energy of migration of vacancies and interstitials are
respectively E
mV
= 1 eV and E
mi
= 0.4 eV. At temperatures around 800 K both types of
defects are mobile. Due to the supersaturating of lattice vacancies and interstitials there are
the clusters of these defects. Accumulation of vacancies leads to the formation of vacancy
pores as well as clusters of interstitial atoms form an additional extra planes bounded by edge
dislocations. These secondary radiation defects (clusters) determine the change in material
properties.
Behavior of point defects imposed into the metal during irradiation depends mainly on
the temperature and material structure. In this case unlike the case of thermal diffusion
vacancies and interstitials are introduced into the material in equal amounts during irradiation.
It is clear that depending on the temperature the effect of irradiation will be different. The low
temperature irradiation can freeze almost all input defects which in subsequent annealing start
migrating and interact with each other and with the available material sinks.
Analysis of experiments shows that due much higher mobility the interstitial atoms are
quickly assembled into clusters and form dislocation loops which rather rapidly grow to
noticeable size in process of irradiation. The formation of vacancy clusters and loops runs
more slowly. This process is temperature dependent; usually the formation of vacancy-type
defects with other things being equal occurs at higher temperatures and these defects are
smaller than the defects of interstitial type.
In order to maintain a stable structure and high mechanical characteristics of materials it
is necessary to create the structure conditions for reducing the rate of accumulation of
secondary radiation defects (dislocation loops, vacancy pores, excess phases, etc.).
Accumulation of secondary radiation defects is determined by the rate of appearance and
recombination of vacancies and interstitials [3]. The morphology of the multiphase structure
under irradiation, ultimately, determined counteraction of dissolution in the displacements
cascades and the phase formation due to freely migrating radiation point defects [4].
Investigations show that the interstitial or substitution atoms doping of austenitic steels
and alloys accelerates the recombination of radiation point defects [5]. On the other hand it
has been found that in the number of transition metal alloys for the increasing of the radiation
resistance it is need not stabilize the structure by means of certain doping, but on the contrary,
to create an unstable, metastable structure, prone to the formation of short-range order [6].
Such alloys showed the functional properties exceeding the analogues properties [7]. In these
alloys at the stage of short-range order nucleation occur crystal lattice distortions, which are
the traps for the vacancies and interstitials and accelerate their recombination [8]. It was also
found that formation of the cluster sub lattice of short-range order with the period 5 nm in
the solid solution during neutron irradiation is the most effective mechanism for the enhance
of radiation resistance of alloys at temperatures of 573-623 K [9].
Thus on improving the structure and mechanical properties of materials under neutron
irradiation as follows from [3, 10] affects the no equilibrium metastable character of alloys
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 121
original structure. Studies of the metastable alloys of nickel - chromium basis showed
extremely high radiation resistance of Ni-42Cr-1Mo alloys. Such alloys are not susceptible to
radiation swelling; changes of their mechanical properties are minimal [11]. These features
are caused by the fact that during the formation of short-range order in their structure arise
domains of tension and compression [8], which are lattice distortions and act as centers of
attraction for the vacancies or interstitials, depending on the sign of distortion.
The analysis shows that the reactor structural materials, having transitional from the
ordering to the bundle structure, with near-zero enthalpy of mixing, can be developed on the
basis of transition metal alloys for a number of systems: Fe-Cr, Ni-Cr, Ni-V, Ni-Cr-V, V-Ti,
and V-Ti-Cr etc. Working temperature of alloys of Ni-Cr can be temperature 623 K, for
alloys of the Fe-Cr 823 K, for alloys V-Ti-Cr 1023 K, respectively.
Despite the huge number of works devoted to the physics of radiation damage and the
explaining of the behavior of structural materials under neutron irradiation, a complete
understanding of the nature of radiation damage, as well as the mechanisms and the ways of
its reducing does not exist. This makes it impossible to effectively decide the tasks of reactor
material science. However, lately there have been data that allow us to hope that this situation
can be corrected with the appropriate formulation of tasks. Such a problem is the
establishment of the stability and metastability of materials interrelation. Changes in the
structure of metastable alloys during irradiation is directed toward stability, but this change
stops without a phase transition at the stage of formation of short range order nanodomains in
size 2.5 nm [9].
It is known that the nanodomains (clusters) represent the intermediate link between
elementary particles (atoms and molecules) and bulk solids. Due to the discrete structure of
energy levels and a large value of the surface ratio to a volume the properties of clusters differ
from the properties of individual atoms and the properties of bulk substance. Clusters with the
number of particles N 102 represent the nanoparticles [12]. During irradiation of
nanoobjects as well as coarse-grained materials are formed cascades of atomic displacements,
i.e. are formed as the single vacancies and interstitials as their complexes in the form of loops
and vacancy nanopores. If the size of nanoobjects is comparable with the diffusion way of
defects to sinks we can expect a higher radiation resistance of nanomaterials in comparison
with their coarse counterparts that actually observed in most studies [13].
The exceptional interest that represents the formation of short-range order nanodomains,
stems from the fact that the difference in volume and the electronic subsystems of the
component atoms creates during irradiation the ordered static distortions and dimensional
effect whose value is determined by the degree of short-range ordering and can change not
only the mobility of vacancies and interstitials but also the mechanism of their annihilation.
The development of approaches to the creation of radiation-resistant nanocrystalline
materials is a promising problem of metal science. It will allow creating a new class of
materials. Such materials will have a neutron irradiation stable structure and properties and
elevated service life. This paper is devoted to the development and detailing of the
phenomenological model of self-organization of the nanocrystalline structure ensuring the
stability of properties of structural materials of nuclear power plants.


V. P. Kolotushkin and A. A. Parfenov 122
2. EXPERIMENTAL PROCEDURE

In this paper we study the structure, composition and properties of steels and alloys based
on iron and nickel-based alloys with chromium and molybdenum in the states before and after
neutron irradiation (electrons).
To study the dependence of radiation damage of austenitic steel on the parameters of
niobium carbonitrides the samples have been prepared in the form of rings 10 mm high for
structural studies and 2.5 mm for mechanical testing. The samples were annealed in vacuum
horizontal furnace at 1300C, 1 h. Extent of deformation of the samples was about 67 %. The
deformed specimens were subjected to recrystallization annealing at temperatures of 800-
1250C for 1 h and additional annealing at 680C for 2 h. After the annealing the containers
with the samples was cooled in water. Then the samples were irradiated in a reactor MIR
with neutrons up to ~ 1.5 dpa at 330C.
In order to calculate the concentration of the niobium carbonitrides the particles were
divided by size into 6 groups (from the < 50 nm to ~ 300 nm). In each size group was
determined the number of particles K
i
. Concentration of particles (the parameters of the
dislocation loops are calculated the same way) related to a given size group was determined
by the formula
i=[
i

2
]/[S(t + d
i
)], where M - the picture increase, equal to the product of instrumental
increase the photographic, S - area of the image, on which were count the particles, t -
thickness of the foil, d
i
- size of particles in size group. The total concentration of particles
was determined as the sum of the particle concentrations in all size groups =
i
.
The average particle size was calculated using the expression: (d = (d
i

i
)/. The volume
fractions of excess phase particles of each size group were as follows: (V/V)
i
= 4/3r
i
3

i
100
% = ~ 0,52 d
3

i
100 %. The total volume fraction of particles of excess phase equals the sum
of volume fractions of particles of all size groups V/V=(V/V)
i
. From here was calculated
amount of the niobium, carbon and nitrogen as part of the niobium carbonitrides: = (4
V)/V

A, = (2 V)/V

A. Here and - volume fractions respectively of the niobium and


carbon (nitrogen), V - volume of particles Nb (CN) in 1 m
3
, V - unit cell volume of Nb
(CN), equal to 0.087366 nm
3
, A - number of atoms in 1 m
3
of austenite, which equals
8,6510
28

-3
.
The study of structural phase changes in Ni-Cr alloys was carried out on experimental
nonstoichiometric nickel alloys with chromium 32-47 wt% containing additional ~ 1.3 wt%
molybdenum. Experimental samples were manufactured from metal open-induction melting.
Ingots weighing 10 kg were reformed into billets of thickness 40 mm followed by hot rolling
to a thickness of 5 mm at 1100 - 1250C. Hot-rolled plates were subjected to cold rolling to a
thickness of 2 mm. From these sheets were produced the specimens for testing and research.
The starting processing of the samples of alloys Ni-Cr-Mo was annealing in an argon
atmosphere at temperatures from 1050 to 1220C for 30 min to obtain a homogeneous solid
solution. Annealed specimens were quenched in water.
Samples of steel of type Fe-18Cr-20Ni and some of the samples of the alloy Fe-20Cr-
40Ni-5Mo-Nb were irradiated with neutrons in the reactor 27-BM.
Other steels and alloys based on iron were irradiated in the reactor BOR-60 with neutron
dose of 10 dpa.
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 123
In BOR-60 were also irradiated specimens of the alloy Ni-42Cr-1Mo with a diameter of
working part 3 mm and 15 mm long and the ring specimens of the alloy Ni-47Cr-1Mo. At the
bottom of the ampoules the temperature was equal to the temperature of sodium at the reactor
inlet. With the rise of the sodium temperature increased, reaching 350 C in the middle of the
ampoule in height. Alloys were exposed to ~ 32 dpa.
As the objects for electron microscopic studies were used the disks diameter of 3 mm,
obtained of foil, rings, and of tensile samples.
Major investigations of the material microstructure were carried out under an electron
microscope EM-301. Thinning of the samples was carried out in installation of jet electro
polishing "Struers" in solution of 4-10 % vol. perchloric acid and 90-96 % vol. icy acetic acid
at ~ -10C and a voltage of 65 V.
The diffractograms were recorded on a DRON-4, on the copper Cu K radiation using a
pyrographite crystal - monochromator. The shooting mode is "on points", the time is 10 s to a
point, step 0.05 of 2. The samples of the size 15x8x2 mm were subjected to electrochemical
polishing in a solution of 60 % phosphoric acid and 40 % glycerol to remove the surface layer
of 10-20 microns.
Profile analysis of reflections was performed to estimate the physical broadening of the
reflections of structural imperfections in the phases. In order to determine the hardware
profile of the diffractometer the standard sample of powder monocrystal Ge were used for the
measurements.
The measurements of the density alloys were performed by hydrostatic weighing in water
with preliminary evacuation of air, thermostatic, and after adjusting for buoyancy force of the
suspension and the temperature correction of the water density. The total error in determining
of the density is 0.01 g/cm
3
.


3. EXPERIMENTAL RESULTS

3.1. Influence of Carbide-Forming Elements on the Formation of Secondary
Radiation Defects in the Steels and Alloys under Neutron Irradiation up to
~10 dpa

In order that a structural reactor material maintained its performance it is necessary that
the amount accumulated in the structure of radiation defects did not exceed the critical value
at which the change in the shape of the material becomes more than acceptable, or there is
destruction. It means that it is necessary in the initial material to create non-equilibrium
structure in which the accumulated during neutron irradiation the vacancies and interstitial
atoms are forced to recombine. There are a number of different mechanisms that provide such
an opportunity. First we estimate the dependence of the formation of point radiation defects
complexes from the state of the metal solid solution, which is due to the dissolution of the
niobium carbonitrides enriched in the process of initial thermomechanical treatments with the
interstitial atom.

V. P. Kolotushkin and A. A. Parfenov 124
3.1.1. Features of Radiation Damage of Austenitic Steel, Depending from the
Thermomechanical Treatment at a Dose of Radiation Damage ~1.5 dpa
The standard treatment of steels and alloys as the structural reactor materials involves the
processes of cold deformation and heat treatments. The purpose of the final annealing is to
create a material structure with a certain grain size and excess phases. The atoms, which
create an excess phase in the present case niobium carbonitrides, may be dissolved into
matrix or incorporated into large or small particles. Depending on the position of interstitial
atoms, their influence on the irradiated with neutrons material will vary. Investigation of the
structure of Fe-16Cr-15Ni-3Mo-Nb-0.021C steel (Table 1) was performed before and after
irradiation in the reactor MIR with neutron dose 1.5 dpa at 330.

Table 1. Chemical composition of the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C in wt%

C Si Mn Cr Ni Mo Nb N Fe Al
0.021 0.080 0.79 16.35 15.30 2.67 0.39 0.010 . 0.03

The content of carbon and nitrogen in the solid solution was changed as follows: particles
of Nb (CN) were dissolved in the matrix by homogenizing annealing at 1300C for 1 h. The
samples were then deformed at room temperature for 67 % (Fig. 1). Cold deformation
increased the dislocation density to 1x10
16
m
-2
, formed multiple slip planes and micro
twins. After deformation, specimens were subjected to recrystallization annealing at
temperatures 800 - 1250.


Figure 1. Structure of the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C after cold deformation (the deformation
ratio is 67 %).
With increasing the temperature of recrystallization annealing the number of remaining in
solid solution C and N atoms was increased, and after annealing at 1250C almost all the
atoms of Nb, C and N were in the solid solution. The lattice period of solid solution as the
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 125
result of raising the temperature of recrystallization annealing and the amount of carbon and
nitrogen in the matrix increased from 0.35943 to 0.35949 nm.
The study showed that during the recrystallization annealing at temperatures 800-900C
the largest number of the niobium carbonitrides was formed. A maximal concentration of
particles Nb (CN) has been found after annealing at 800C (Fig. 2). In structure of these
samples along with

recrystallized grains are preserved and deformed grains with a high
concentration of particles Nb (CN). In the recrystallized grains behind the front
recrystallization the particle size and concentration are, respectively, ~ 7 nm and ~ 210
21
m
-3
.
In the deformed grains are allocated the fine particles Nb (CN) of a higher concentration
(average particle size of ~ 3 nm, the concentration ~410
21
m
-3
). The volume fractions of
particles of Nb (CN) are, respectively, 0.05 and 0.005 % in the recrystallized and deformed
regions.
It follows that the passage of the front recrystallization leads to a more intensive release
of particles Nb (CN) from the solid solution and the greater its purification by carbon,
nitrogen and niobium.


Figure 2. Particles Nb (CN) in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C after recrystallization annealing
at 800C.
Dispersed particles of the niobium carbonitrides after recrystallization annealing at 800C
are located mainly on the footsteps of the slip planes of the deformed grains (Fig. 2). Chains
of the niobium carbonitrides often pass through the boundary of adjacent grains. Similar
processes occurred at temperatures of 850 and 900C. Rising of recrystallization annealing
temperature to 1000C and above led to a decrease in the number of particles of Nb (CN) and
the enlargement (Fig. 3). It should be noted that the distribution of precipitated particles of
Nb (CN) sufficiently no uniform, for example, after recrystallization annealing at 1000 C
particles are arranged with an interval from 30 to 300 nm.
Depletion of the solid solution of steel Fe-16Cr-15Ni-3Mo-Nb-0.021C of the interstitial
atoms during annealing at 800 and 1000C occurs in different ways. At 800 C the solubility
of the atoms Nb, C and N into the recrystallization front boundary is higher than in the
V. P. Kolotushkin and A. A. Parfenov 126
matrix, so most of the dissolved in the matrix atoms Nb, C and N swept out the
recrystallization front. On the boundary of the front there is an accumulation of atoms. High
diffusion mobility in the bulk of the moving front recrystallization boundary promotes the
nucleation and growth of Nb (CN). Growing particles inhibit the movement of the front of
recrystallization, but upon reaching a certain critical particle size of Nb (CN) curved
boundary of recrystallization front separates from them (Fig. 2). Behind the boundary
remains depleted on the Nb, C and N matrix, which are interspersed with small and large
particles of Nb (CN).


Figure 3. Particles Nb (CN) in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C after recrystallization annealing
at 1000C.
When the annealing temperature increases, the solubility of Nb, C and N in solid solution
also increases. Therefore, at 1000C much of the interstitial atoms are not enjoys the front of
the recrystallization, but remains in solid solution. Therefore, an additional annealing at
680C, 2 h following the recrystallization annealing at 1000C, even more clean matrix,
binding the atoms of Nb, C and N in the smallest particles of Nb (CN).
Due to differences in the volume fraction of particles of Nb (CN) in the original samples
and the corresponding difference in the enrichment of solid solution of C and N atoms under
neutron irradiation the accumulation of radiation defects in the samples of steel Fe-16Cr-
15Ni-3Mo-Nb-0.021C differed. Irradiation at 330C led to the formation in the solid
solution mainly of prismatic dislocation loops (Fig. 4) and, in the some states, vacancy pores.
The distribution of dislocation loops in the matrix is fragmented, apparently in accordance
with inhomogeneity of chemical composition and distribution in the matrix of C and N atoms
and particles Nb (CN). In the various sample grains concentration of loops sometimes
differed by 2-3 times. The size of the loops varies from 1 to 50 nm. The main part of
dislocation loops has a size of less than 10 nm.

Self-Organization of the Nanocrystalline Structure and Radiation Resistance 127

Figure 4. Dislocation loops in irradiated alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C.
On the histogram of the dislocation loops distribution in size in irradiated samples of Fe-
16Cr-15Ni-3Mo-Nb-0.021C steel is clearly seen that the temperature increasing of
recrystallization annealing entails an increase in the number of loops (Fig. 5). It is caused by
the increasing an enrichment of solid solution with carbon and nitrogen atoms, which poison
the dislocation loops slowing their growth. Preferential absorption of interstitials by
dislocation loops decreases, respectively, decreasing the growth rate of loops.


Figure 5. Dislocation loop size distribution in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C irradiated
at 330C.
The sharp difference in the concentration of dislocation loops in the samples after
recrystallization annealing and the samples after additional annealing at 680C is formed
mainly due to the dislocation loops with the size of 10 nm. The concentration of such loops
in the samples with additional annealing is much lower. The difference in the concentration of
larger loops is less significant. In the Fig. s is clearly seen that in the samples not annealed at
V. P. Kolotushkin and A. A. Parfenov 128
680C (Fig. 6a), dislocation loops are smaller, and their concentration is accordingly higher
than in samples with an additional annealing (Fig. 6b). Thus, additional purification of the
matrix from carbon and nitrogen reduces the possibility of poisoning of dislocation loops and
promotes their growth in the process of neutron irradiation at 330C.


Figure 6. Dislocation loops in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C: a) irradiation following the
recrystallization annealing 1000C, b) irradiation following the recrystallization annealing 1000C plus
an additional annealing 680C.
With the release from the solid solution of steel Fe-16Cr-15Ni-3Mo-Nb-0.021C the
niobium carbonitrides particles is linked another mechanism of reduction the radiation
damage. Particles Nb (CN) create in the lattice during separating from the solid solution the
zones of structural distortions due to lattice period mismatch of the phase and of the matrix.
In relation to point defects such distortions in the initial period of Nb (CN) particle formation
may be the regions of compression or tension, which can serve as traps for vacancies or
interstitials. Fixing of point defects in the neighborhood of distortion zones accelerates their
recombination. As a consequence, the growth of dislocation loops and the formation of
vacancy pores slow. Effectiveness of the latter mechanism is clearly visible when comparing
the concentration of dislocation loops in samples of 1000C and 1000C +680C (Fig. s 5 and
6).
In the structure of steel Fe-16Cr-15Ni-3Mo-Nb-0.021C samples recrystallized at 800 -
950C and additionally annealed at 680C, after irradiation were found the vacancy pores
(Fig. 7). The pores are distributed in the matrix unevenly like the dislocation loops. The pore
size does not exceed 10 nm; the total relative swelling was less than 0.02 %.

Self-Organization of the Nanocrystalline Structure and Radiation Resistance 129

Figure 7. Vacancy pores in the alloy Fe-16Cr-15Ni-3Mo-Nb-0.021C: a) irradiation following the
recrystallization annealing 850C plus an additional annealing 680C, b) irradiation following the
recrystallization annealing 800C plus an additional annealing 680C.
The analysis shows that the formation of vacancy pores in the steel Fe-16Cr-15Ni-3Mo-
Nb-0.021C samples correlated with depletion of the original solid solution the atoms Nb, C
and N. For example, in the structure of the sample after recrystallization annealing at 800C
plus an additional annealing at 680C vacancy pores were found only in areas with the
recrystallized structure, depleted the atoms Nb, C and N. In the deformed grain the pores are
not revealed. Thus, the experiments show that depletion of the matrix with carbon nitrogen
and niobium during the passage of the front recrystallization results in the growth of
dislocation loops and reducing their concentration as well as the appearance of vacancy pores.
Taking into account that the degree of solid solution depletion with carbon, nitrogen and
niobium after recrystallization annealing at 800 and 1000C is different, and the neutron
irradiation was conducted under the same conditions it may be concluded: decrease in the
amount of carbon and nitrogen in solid solution increases the preferential absorption of
interstitials by dislocation loops. The confirmation of this was found in specimens after
recrystallization annealing at 1000C, plus an additional annealing 680C. But there is
appears to be a certain critical concentration of carbon and nitrogen in solid solution. It is
created by recrystallization annealing at 800-850C plus an additional annealing 680C. At
the lower concentration than critical the dislocation loops absorb a higher proportion of
interstitials. As a result, the matrix sate by vacancies, the rate of recombination of point
defects is reduced, and vacancy swelling begins.
These experimental results underscore the importance of considering the content of
interstitial impurities in the solid solution of austenitic steels, and ensuring uniformity of their
structure-phase state.

3.1.2. Effect of Interstitial Atoms on the Accumulation of Radiation Defects in Steels
and Alloys Under Neutron Irradiation to 10 dpa
Described in section 3.1.1 results have shown a qualitative dependence of structure
changes of Fe-16Cr-15Ni-3Mo-Nb-0.021C steel after neutron irradiation at ~ 330C from the
V. P. Kolotushkin and A. A. Parfenov 130
initial processing and content in solid solution of atoms niobium, carbon and nitrogen. In the
present section the quantitative evaluation of the influence of carbide-forming elements in
solid solution of iron-based steels and alloys (Table 2) on radiation damage of materials under
neutron irradiation of higher damage dose is conducted.

Table 2. Chemical composition of materials studied in wt%

Materials C Si Mn Cr Ni Mo Nb N
Fe-16Cr-15Ni-3Mo-Nb-
0.020C
0.020 0.08 0.94 16.99 15.45 2.73 0.37 0.010
Fe-16Cr-15Ni-3Mo-Nb-
0.026C
0.026 0.31 0.51 16.00 14.97 2.68 0.39 0.040
Fe-20Cr-25Ni-Nb 0.013 0.05 1.48 20.1 24.60 - 0.72 0.008
Fe-20Cr-25Ni-Nb-Si 0.012 0.92 1.80 20.1 24.80 - 0.79 0.008
Fe-20Cr-40Ni-5Mo-Nb 0.014 0.09 1.68 19.80 40.80 4.73 0.57 0.020

Initial state of material structure changed during recrystallization annealing (Table 3).
The volume fraction of particles of excess phase varied in accordance with the final heat
treatment. With increasing annealing temperature, as seen from the table, the number of
atoms of carbide-forming elements in solid solution grows, and the volume fraction of
niobium carbonitrides is reduced. A higher content of carbon and nitrogen in the matrix
corresponds to annealing at higher temperature.

Table 3. Distribution of Nb, C and N in the structure of alloys in the initial state

Materials

Operation of
recrystallizat
ion annealing
Parameters of the niobium
carbonitrides
The content of
elements in the matrix
in wt%
Number
density (m
-3
)
Size
(nm)
Volume
fraction,
%
Nb C + N
Fe-16Cr-15Ni-
3Mo-Nb-
0.020C
800, 1 310
20
20 0.15 0.17 0.012
900, 30 110
21
10 0.1 0.29 0.018
1200,1 - - <0.01 0.37 0.030
Fe-16Cr-15Ni-
3Mo-Nb-
0.026C
950, 30 110
21
180 0.43 0.09 0.010
Fe-20Cr-25Ni-
Nb
1000, 30 210
18
150 0.45 0.34 <0.010
Fe-20Cr-25Ni-
Nb-Si
1000, 30 110
19
40 0.05 0.70 0.015
Fe-20Cr-40Ni-
5Mo-Nb
800, 1 210
19
60 0.20 0.34 0.010
1000, 1 110
18
30 0.01 0.54 0.032

Self-Organization of the Nanocrystalline Structure and Radiation Resistance 131
The samples of steels and alloys were irradiated in the BOR-60 reactor with neutrons up
to ~ 10 dpa at 350C. In the process of irradiation the phase composition of steels and
alloys has not changed. The results of determining the parameters of secondary radiation
defects are shown in Table 4. These results show a significant effect of changing the quantity
of carbide-forming elements in the solid solution: of niobium, carbon and nitrogen on the
recombination of point radiation defects. In the structure of materials under neutron
irradiation were formed, as a rule, the dislocation loops. In some specimens in addition to
dislocation loops have appeared and the vacancy voids. Dislocation loops were mostly perfect
prismatic loops of embedded type. In specimens of steels and alloys with higher content in
solid solution of atoms Nb, C and N the concentration of dislocation loops was greater and
the average size of loops is less.

Table 4. Parameters of secondary radiation defects in the alloys after irradiation in
BOR-60 reactor with neutrons up to ~ 10 dpa at 350C

Materials

Annealing
temperature, C
/ Contents (C+N)
in the matrix in
wt%
Parameters of the vacancy
pores
Parameters of
the dislocation
loops
(10
21

m
-3
)
d

(nm)
Swelling,
%


(10
21

-3
)
d
(nm)
Fe-16Cr-15Ni-
3Mo-Nb-
0.020C
800 / 0.012 - - - 12 20
900 / 0.018 - - - 15 15
1200 / 0.030 - - - 20 10
Fe-16Cr-15Ni-
3Mo-Nb-
0.026C
950 / 0.010 3 10 0.20 4 40
Fe-20Cr-25Ni-
Nb
1000 / <0.010 0,3 13 0.04 4 30
Fe-20Cr-25Ni-
Nb-Si
1000 / 0.015 - - - 10 20
Fe-20Cr-40Ni-
5Mo-Nb
800 / 0.010 3 9 0.10 9 30
1000 / 0.032 - - - 30 8

In the samples of Fe-16Cr-15Ni-3Mo-Nb-0.020C steel the temperature raise of
recrystallization annealing increases the amount of niobium, carbon and nitrogen in the
matrix (Table 3). After neutron irradiation, as seen from Table 4, in accordance with the
enrichment of solid solution with atoms of Nb, C and N the concentration of dislocation loops
increases, and their average size decreases.
On the structure and phase composition of steel Fe-16Cr-15Ni-3Mo-Nb-0.026C of
electroslag remelting in the initial state appears to be influenced the peculiarities of its
creation that is the composition (Table 2), the smelting and the processing. Samples were
subjected to recrystallization annealing at a lower temperature of 950C, compared with the
standard annealing temperature of 1050C. As a result of this annealing, niobium, carbon and
nitrogen were significantly linked in the particles of niobium carbonitrides (Fig. 8a). In this
case, the total content of carbon and nitrogen in solid solution was decreased to the level of
V. P. Kolotushkin and A. A. Parfenov 132
0.01 wt%. Apparently due to the fact that during exposure in the depleted by interstitial
impurities matrix the interstitials mainly went to major ( 40 nm) dislocation loops, in the
solid solution formed an excess of vacancies, which formed the vacancy pores (Fig. 8b).


Figure 8. Structure of the alloy Fe-16Cr-15Ni-3Mo-Nb-0.026C: a) initial state, b) irradiation to 10 dpa
at 350C.
In the samples of steel Fe-20Cr-25Ni-Nb with a silicon content of 0.05 wt% in the
process of recrystallization annealing of the initial samples the carbide-forming elements of
niobium, carbon and nitrogen were mostly linked in the particles of niobium carbonitrides Nb
(CN) (Fig. 9a). Solid solution of these samples was depleted on carbon and nitrogen to
<0.010 wt%. Therefore under neutron irradiation to 10 dpa in clean from introduction
impurities solid solution a separate vacancy pores were formed (Fig. 9c).
In samples of steel Fe-20Cr-25Ni-Nb (Fig. 9b) which had increased silicon content
(Table 2), the solid solution after the recrystallization annealing was enriched in carbon and
nitrogen resulting from the substitution these elements with silicon at the grain boundaries
and in solid solution. Enrichment of solid solution on carbon and nitrogen (0.015 wt%)
probably contributed to the increasing the recombination rate of vacancies and interstitials
and the nucleation of vacancy pores has not been detected (Fig. 9d).
Recrystallization annealing of the alloy Fe-20Cr-40Ni-5Mo-Nb at 800 C for 1 h (Fig.
10a) caused extensive appearance of carbonitrides of niobium and led to the depletion of the
solid solution on carbon and nitrogen. Subsequent neutron irradiation created in the pure on
introduction impurities the solid solution vacancy pores and large dislocation loops (Fig. 10).
Their emergence and rapid growth are due to a decrease in the rate of recombination of point
defects in the equilibrium matrix.
The temperature rise of recrystallization annealing of the alloy Fe-20Cr-40Ni-5Mo-Nb up
to 1000C (Fig. 10b) led to a more than threefold (0.032 wt%) enrichment of the matrix on
carbon and nitrogen. As a result the neutron irradiation increased the concentration of smaller
dislocation loops. At the same time the rate of recombination of point defects on the
equilibrium distortions of the solid solution increased, and the vacancy voids during
irradiation were not revealed (Fig. 10d).
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 133


Figure 9. Structure of the alloy Fe-20Cr-25Ni-Nb: a, b) initial state: melting with 0,05 and 0,92 % Si,
respectively; c, d) irradiation of 10 dpa at ~ 350 C: melting with 0,05 and 0,92 % Si, respectively.
Moreover all the chromium-nickel steels and alloys behave practically identically. In all
materials there is an accumulation of Frenkel pairs to the level of > 10
25
m
-3
that is 1 - 20 %
of the quantity of Frenkel pairs in the cascade of displacements which equal 10
27

-3
.
Summarizing the experimental results obtained on effect of interstitial atoms carbon and
nitrogen on the process of recombination of vacancies and interstitials in neutron irradiation
of steels and alloys based on iron it is possible to come to such conclusion: if the solid
solution of steels and alloys is depleted by carbon and nitrogen in the initial heat treatment to
a level 0,01 wt% ( 500 ppm at) there is a stabilization of the structural state of alloy, the
disequilibrium decreases. The location of the structural distortions of the solid solution with
an average linear spacing of more than 12 interatomic distances does not create enough of
traps or sinks for point defects. Therefore the rate of recombination is reduced and neutron
irradiation to 10 dpa at a temperature of 350C causes the formation of the vacancy pores
and the large dislocation loops in the solid solution.

V. P. Kolotushkin and A. A. Parfenov 134


Figure 10. Structure of the alloy Fe-20Cr-40Ni-5Mo-Nb: a, b) in its original condition after
recrystallization annealing at: a) 800C, b) 1000C, c, d) after neutron irradiation to ~10 dpa at 350C:
c) 800C, d) 1000C.

3.1.3. The Influence of Oversized Substitutional Atoms on the Acceleration of the
Recombination of Radiation Defects
Examined in the previous section, the mechanism of influence of carbide-forming
elements on the radiation damage of steels and alloys outlined the important role of carbon
and nitrogen atoms in a change in the rate of the point defects recombination. If the carbon
and nitrogen atoms there are in the solid solution, they accelerate the recombination of
vacancies and interstitials. Upon binding of carbon and nitrogen in niobium carbonitrides
particles their effect on recombination is reduced. When considering the mechanism of the
effect of carbide-forming elements on the radiation-damage susceptibility was not separately
accounted for the influence of so-called "oversized" atoms of niobium and molybdenum.
The radius of the niobium atoms (the Goldschmidt) by 15%, and molybdenum atoms by
10% larger than that of iron atoms. When replacing the main on the oversized atoms in the
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 135
crystal lattice there are distortions that can serve as traps for vacancies and to accelerate the
recombination of point defects. The influence of oversized substitution atoms on the
recombination of point defects was evaluated in the study [5] of the samples of high purity
steel Fe-18Cr-20Ni (Fig. 11a) and complex doped alloy Fe-20Cr-40Ni-5Mo-Nb (Fig. 12a).


Figure 11. Structure of the alloy Fe-18Cr-20Ni: a) initial state, b) irradiation with neutrons with a
fluence of 4.6x10
24
n/m
2
, E > 0.8 MeV.
The steel Fe-18Cr-20Ni in the initial state after recrystallization annealing has a
homogeneous structure of the solid solution. In the structure there is no excess phase and
oversized atoms. The total concentration of carbon and nitrogen in solid solution is about
0.015 wt%. Alloy Fe-20Cr-40Ni-5Mo-Nb, unlike steel Fe-18Cr-20Ni, has an additional 5
wt% oversized atoms of molybdenum and niobium, so the structure of the alloy Fe-20Cr-
40Ni-5Mo-Nb (Fig. 12a) contains also particles of niobium carbonitrides Nb (CN),
concentration and average size equal to ~ 2x10
18
m
-3
and 0.2 microns.
The samples of steel Fe-18Cr-20Ni and the alloy Fe-20Cr-40Ni-5Mo-Nb were irradiated
with neutrons in a reactor 27VM at 320-340C for 7400 h up to 1 dpa.
After neutron irradiation up to 1 dpa change in phase composition of materials was not
observed (Fig. s 11b, 12b). In the structure of steel and alloy formed prismatic dislocation
loops, the average size and the concentration, as well as the numbers of displaced atoms in the
loops are shown in Table 2.9. From the results of exposure can be seen that the concentration
of dislocation loops in steel Fe-18Cr-20Ni with an increase in the neutron fluence rapidly
reaches saturation. Already after the fluence 4x10
24
n/m
2
concentration of loops remains
practically unchanged as the number of displaced atoms in the loops.

V. P. Kolotushkin and A. A. Parfenov 136

Figure 12. Structure of the alloy Fe-20Cr-40Ni-5Mo-Nb: a) initial state, b) neutron irradiation with a
fluence of 6.2 x10
24
n/m
2
, E > 0.8 MeV.

Table 5. Parameters of dislocation loops in neutron-irradiated samples of the alloys Fe-
18Cr-20Ni and Fe-20Cr-40Ni-5Mo-Nb

Alloys

(10
24
n/m
2
,
>0,8 MeV)
Parameters of dislocation loops
Mean size
(nm)
Number density
(10
22
m
-3
)
Number of atoms in
the loops (10
24
m
-3
)
Fe-18Cr-20Ni
4.0
4.6
6.3
4.0
6.0
5.0
3.2
3.0
3.2
9.0
16.0
14.0
Fe-20Cr-40Ni-
5Mo-Nb
1.4
4.9
6.2
6.0
6.0
6.5
0.1
0.7
2.0
0.5
3.2
11.0

In the complex doped alloy Fe-20Cr-40Ni-5Mo-Nb the development and accumulation of
dislocation loops in the initial stages of irradiation is much slower than in steel Fe-18Cr-20Ni.
However, upon reaching the neutron fluence of ~ 5x10
24
n/m
2
and the hereinafter
concentration of dislocation loops and the number of displaced atoms in the loops in the alloy
increases rapidly and almost reach the level of damage to the steel Fe-18Cr-20Ni in the
studied range of irradiation. The average size of dislocation loops in the alloy Fe-20Cr-40Ni-
5Mo-Nb in the course of irradiation changes little.
The resulting dependence of the accumulation rate of secondary radiation defects on the
amount of impurities in the solid solution shows that the increase in the number of interstitial
atoms in solid solution, especially after the neutron irradiation of small fluences, accelerates
the formation of dislocation loops. A longer incubation period of accumulation of dislocation
loops in the alloy Fe-20Cr-40Ni-5Mo-Nb can, apparently due to the fact that oversized
substitutional atoms Mo and the Nb in solid solution create a traps for the displaced atoms
and the vacancies, accelerating their recombination. However, the difference in the
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 137
concentration of dislocation loops and the number of displaced atoms in the loops is almost
eliminated with increasing the neutron fluence up to ~ 6.2x10
24
n/m
2
, i.e. at a dose of damage
1 dpa.
Furthermore the presence in the solid solution of steel Fe-18Cr-20Ni a comparatively
large amount of carbon and nitrogen promotes more intensive poisoning of dislocation loops.
In the alloy Fe-20Cr-40Ni-5Mo-Nb significant part of the carbon and nitrogen was bound
with niobium, so poisoning of the loop was smaller. As a consequence the dislocation loops
in the alloy Fe-20Cr-40Ni-5Mo-Nb are larger and have a smaller concentration. It should be
noted that the width of the histogram loop size is much larger in the alloy than in the steel.
For example, in neutron-irradiated to a fluence of 6.3x10
24
n/m
2
(E> 0.5 MeV) samples of
steel Fe-18Cr-20Ni were observed the loop of maximum size 10 nm, and in irradiated at
similar conditions the samples of the alloy Fe-20Cr-40Ni-5Mo -Nb correspondingly 15 nm.
Analysis presented in the last sections of the results displays comparatively higher
efficiency of the influence of carbon and nitrogen atoms on the acceleration of recombination
vacancies and interstitials in steels and alloys. Heat treatments of chromium-nickel steels and
alloys, creating a depletion of the solid solution on the carbon and nitrogen to the level of
0.01 wt% contribute to the development of during neutron irradiation of vacancy porosity.
When the total content of carbon and nitrogen is > 0.01 wt% vacancy pores are not formed at
the dose of 10 dpa.
Thus, the combined impact of carbide forming and oversized atoms and interstitial atoms
(carbon and nitrogen) increases the duration of the incubation period of radiation damage by
more than one order of magnitude compared with the effect only oversized substitution
atoms.
The traps created by oversized atoms, the interstitial atom in the excess phases or in the
form of interstitial impurities can affect the change in flows of point defects in the incubation
period, but are not the unsaturated traps, i.e. do not possess sufficient effectiveness to provide
a continuous recombination of vacancies and interstitials. The most important shortcoming in
the conduct of such traps in steels and alloys is the change in their morphology and
composition during neutron irradiation. The phase particles, formed during the initial
thermomechanical treatments are destroyed in the displacement cascade and as a result of
radiation-induced segregation become radiation-stable phase. Turning into the stable
formations, they lose the ability to be the traps of point defects. Thus, it can be assumed that
the methods of accelerating the recombination of point radiation defects with the help of a
homogeneous and uniform decay of particles of excess phases, and thereby increasing their
radiation resistance, apparently, are not effective.


3.2. Effect of Short-Range Order on Recombination Accelerating of
Radiation Point Defects

Accumulated to date data on the impact of various factors on the radiation damage of
chromium-nickel steels and alloys have highlighted the crucial role of recombination
accelerating of point radiation defects. To understand the changes in the behavior of steels
and alloys under neutron irradiation it is necessary to understand the influence of non-
equilibrium structure on the kinetics of these changes.
V. P. Kolotushkin and A. A. Parfenov 138
Structural disequilibrium in metals occurs if the rate of cooling after recrystallization
annealing is so high that the diffusion processes in the solid solution did not have time to go,
and quenching structure is fixed. In the basis of their origin virtually all types of non-
equilibrium structures have changing the solubility of the components with temperature
changes. The disequilibrium of structure depends mainly on the doping, quenching rate, the
presence of impurities, etc. The structure with no uniform chemical composition acquire
during the rapid cooling all the construction materials used in nuclear energy sector. In this
connection it is interesting to consider the communication nature of the damage, which
develops in metals during irradiation with the disequilibrium of the structure.
In studying the mechanical properties of the alloy Ni-42Cr-1Mo, irradiated in BOR-60
reactor with neutrons up to 32 dpa, it was surprisingly found that with the accumulation the
dose the mechanical properties and especially the relative total and uniform elongation of the
alloy at temperatures of irradiation and test up to 350C virtually unchanged. At the same
time in austenitic stainless steels the total elongation becomes < 3 % for neutron irradiation of
lower dose (Fig. 13). This means that the alloy Ni-42Cr-1Mo significantly less susceptible to
radiation damage as compared to austenitic stainless steels [11].


Figure 13. Effect of irradiation on the mechanical properties of the austenitic alloys of type 316, 304
and alloy Ni-42Cr-1Mo.
Studies of the structure of materials whose properties are shown in Fig. 13 using electron
microscopy showed that the size of dislocation loops in the alloy Ni-42Cr-1Mo irradiated
with neutrons up to 32 dpa, was 2-3 times more, and concentration of loops - one order of
magnitude lower than in austenitic steel Fe-16Cr-15Ni-3Mo-Nb-0.026C (Fig. 14a). The
concentration of dislocation loops in the alloy is ~ 3x10
21
m
-3
(Fig. 14b), and in the steel ~
3x10
22
m
-3
. It should be noted at the same time that the steel Fe-16Cr-15Ni-3Mo-Nb-0.026C
was irradiated by neutrons in the order of lower dose compared with the alloy.

Self-Organization of the Nanocrystalline Structure and Radiation Resistance 139

Figure 14. Structure of alloys after neutron irradiation at 350C: a) Fe-16Cr-15Ni-3Mo-Nb-0.026C,
2.5 dpa, b) Ni-42Cr-1Mo, 32 dpa.
Larger dislocation loops with a low concentration in the alloy Ni-42Cr-1Mo impede
dislocation motion weaker; therefore the effect of radiation hardening in the alloy respect of
the steels is weak. In the turn, lowering the concentration of secondary radiation defects in the
alloys of Ni-Cr type of Ni-42Cr-1Mo can be, apparently, associated with acceleration of
recombination of vacancies and interstitials in the process of neutron irradiation.
Radiation damage of structural materials under the action of neutron flux begins with the
appearance in the structure of vacancies, interstitials and the formation of their clusters.
Gathering of point defects in complexes: dislocation loops, vacancy pores, the participation of
point defects in segregation processes that alter the phase composition of materials and
mechanical properties, means a change in the stability of the structure and deterioration of the
radiation resistance. Thereby, one of the ways of improving the stability of the structure
material is the recombination accelerating of vacancies and interstitials and lowering the rate
of accumulation of radiation defect.
Therefore the principal goal of this paper was to investigate the possibilities of creating in
the construction-traditional materials such original structure, which accelerates the
recombination of vacancies and interstitials.

3.2.1. Features of Radiation Damage of of Ni-Cr Alloys
Alloys of the system Ni-Cr, which showed significant benefits in neutron irradiation have
been investigated in the connection with the need creation of the material, the complex match
to the requirements of high radiation and corrosion resistance, high mechanical properties and
structural stability at temperatures of 300-350C.
In studying of alloys of the system nickel-chromium were obtained the first experimental
data on the significant influence of metastable structure on the recombination of point defects.
In the particular, it was found that the concentration of dislocation loops in the alloy Ni-42Cr-
1Mo after irradiation by neutrons up to 32 dpa at 350C was almost one order of magnitude
smaller than in the alloy Ni-47Cr-1Mo [3].
V. P. Kolotushkin and A. A. Parfenov 140
The alloys Ni-42Cr-1Mo and Ni-47Cr-1Mo (Table 6) after quenching have FCC lattice
based on nickel. Volume fraction of particles of excess - phase in the alloy Ni-42Cr-1Mo
(Fig. 15) did not exceed 0.05 %. In the solid solution of tension samples of the alloy Ni-
47Cr-1Mo were remained not dissolved in holding for quenching globular particles of -
phase based on chromium BCC and inhomogeneously distributed titanium carbide particles
of size ~ 100 nm and the concentration of ~ 8 x 10
18
m
-3
. Volume fraction of particles -
phase in the alloy was 0.1 %, the dislocation density ~ 1x10
13
m
-2
.

Table 6. Chemical composition of alloys Ni-Cr-Mo in wt%

Alloys C Si Mn S P Cr Mo Al Fe Ti
Ni-42Cr-1Mo 0.003 0.05 0.05 0.001 0.003 41.65 1.01 0.21 0.23 0.21
Ni-47Cr-1Mo 0.013 0.15 <0.05 0.007 0.007 46.69 1.36 0.23 0.24 0.25


Figure 15. Structure of the Ni-42Cr-1Mo alloy after quenching from a temperature of 1100C.
Under irradiation in BOR-60 at ~ 350C by neutrons dose of 10 dpa in the tensile
samples of the alloy Ni-47Cr-1Mo were formed dislocation loops, vacancy pores and the
linear dislocations (Fig. 16). In addition to the globular precipitates of - phase in the
structure were observed the titanium carbide particles (Fig. 16a) with the lattice constant
0.435 nm, the size of 100 nm and the concentration 8x10
18
m
-3
. Concentration of dislocation
loops reached ~ 2x10
21
m
-3
, the average size of ~ 16 nm. Vacancy pores (Fig. 16b) had a size
of ~ 9.5 nm and a concentration of ~ 3x10
21
m
-3
and the swelling was ~ 0.14 %. There were
near the grain boundaries depleted zones in the pores of a width of 100 nm.

Self-Organization of the Nanocrystalline Structure and Radiation Resistance 141

Figure 16. Structure of the alloy Ni-47Cr-1Mo samples after neutron irradiation to ~ 10 dpa at ~350:
a) - phase and titanium carbides, b) dislocation loops, voids and linear dislocations.
In the ring samples of the alloy Ni-47Cr-1Mo after irradiation in BOR-60 reactor at a
temperature of 350C by neutrons dose of ~ 32 dpa vacancy pores were not detected.
Concentration of dislocation loops was ~ 3x10
22
m
-3
(Fig. 17a), the average size of loops -
7.5 nm. In the structure were observed the linear dislocations, carbides of titanium and
randomly distributed particles - phase (Fig. 17b).


Figure 17. Structure of the alloy Ni-47Cr-1Mo samples after neutron irradiation to ~ 32 dpa at ~350:
a) dislocation loops and line dislocations, b) - phase and titanium carbides.
Analysis of the structural features of the irradiated samples of the alloy Ni-47Cr-1Mo
shows that his damage is analogous to by neutrons damage of austenitic steels and alloys
(Section 3.1.2). In the samples in tension of this alloy during the initial hot repartition the
solid solution was depleted of interstitial impurities. Therefore under neutron irradiation dose
of 10 dpa interstitial atoms are arranged in the large size of dislocation loops and dislocation
V. P. Kolotushkin and A. A. Parfenov 142
network, as well vacancy - in the pores. In the ring samples irradiated up to ~ 32 dpa,
interstitials are located in the higher concentration dislocation loops (~ 3x10
22
m
-3
) and the
smaller size, as well vacancies are located in the vacancy loops d < 10 nm, ~2x10
22
m
-3
.
In such a way, the radiation damage of the alloy Ni-47Cr-1Mo affects the content of
interstitial impurities in solid solution. Reducing the number of carbon atoms in solid solution
reduces the decorating of the dislocation loops, which increase in size by absorbing the
interstitials. As a result, the recombination rate of Frenkel pairs slows down. The
concentration of radiation-induced vacancies in the matrix increases and causes the
appearance of porosity in the samples in tension of the alloy Ni-47Cr-1Mo. Under the carbon
content in the ring samples of the alloy Ni-47Cr-1Mo at the level of the original concentration
the dislocation loops are screened by carbon, the growth of loops slows down. The increased
amount of interstitial atoms in the matrix accelerates the recombination of point defects. Not
exchanged radiation vacancies can be united into vacancy dislocation loops.
In the samples for tensile of the alloy Ni-42Cr-1Mo, irradiated in the BOR-60 at 350C
by neutrons dose of ~ 32 dpa, dislocation loops were formed and the linear dislocations (Fig.
18). The volume fraction of particles of excess phase (Fig. 18a) does not exceed 0.05 %.
Diffraction contrast of the matrix has a tweed structure (Fig. 18b) showing the homogeneous
formation of the short-range ordering. Homogeneous short-range ordering in the alloy matrix
manifested brighter after heating of the irradiated samples for mechanical testing: in the
electron diffraction patterns - in the form of diffuse streaks around the main reflections (Fig.
19a) as well in the microphotographs in the form of clusters of dark spots, whose
concentration was 10
24
m
-3
. An increase the sizes of short-range ordering regions is not
large ( 2 nm, Fig. 19b) due to the short duration of heating of samples for tensile testing.


Figure 18. Structure of the alloy Ni-42Cr-1Mo after neutron irradiation to ~ 32 dpa: a) the grain
boundary, and b) the dislocation structure.
A tendency to developing of short-range order means that in conditions of neutron
irradiation the atoms of a disordered after quenching solid solution are rebuilt to form clusters
of the ordered structure. Occurring during the nucleation of clusters the lattice distortions
increase the probability of recombination of vacancies and interstitials. Accelerating of the
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 143
recombination of vacancies and interstitials reduces the amount of secondary radiation defects
including dislocation loops and vacancy pores. After irradiation under identical conditions,
the concentration of dislocation loops in the disposed to the short-range ordering alloy Ni-
42Cr-1Mo was several times lower than in the alloy Ni-47Cr-1Mo. Accordingly, uniform and
total elongation of the alloy Ni-42Cr-1Mo after neutron irradiation dose of 32 dpa was 2 - 3
time higher.


Figure 19. Short-range ordering in the alloy Ni-42Cr-1Mo, irradiated at ~ 350 to ~ 32 dpa after
mechanical tests: a) electron diffraction pattern, b) structure after tensile testing at 500.
Now we shall return to the problem of different radiation damage of austenitic stainless
steel Fe-16Cr-15Ni-3Mo-Nb-0.026C and alloy Ni-42Cr-1Mo, which had been irradiated by
neutrons in a factor of 10 the higher fluence and at the same time had a factor by 10 smaller
concentration of dislocation loops than steel. In this connection there appeared one more
unexpected experimental fact. Alloy Ni-47Cr-1Mo alloy was different from the Ni-42Cr-1Mo
only the fact that had the content of chromium in 5 % more (Table 6). However under
neutron irradiation a dose of 32 dpa this alloy has accumulated secondary radiation defects,
not as a nickel alloy with 42 % chromium, but as austenitic steel Fe-16Cr-15Ni-3Mo-Nb-
0.026C. Despite the slight differences in chemical composition, the concentration of
dislocation loops in the nickel alloy with 42 % chromium was an order of magnitude smaller
and the number of not recombine defects - 3 times less.
The recombination rate, the concentration of dislocation loops, longer incubation period
of damage show that the structure of the alloy Ni-42Cr-1Mo under neutron irradiation is
changed according to some different mechanism than in austenitic stainless steels and alloys
and nickel alloy with 47 % chromium.
Study of the mechanisms and laws of point defects recombination accelerating in alloys
of the system Ni-Cr is discussed in the next section.

3.2.2. The Short-Range Ordering Nanodomains of the Ni-Cr System
To elucidate the mechanism of accelerating of point defects recombination in the alloy
Ni-42Cr-1Mo under neutron irradiation were carried out comprehensive studies of the
V. P. Kolotushkin and A. A. Parfenov 144
structure, resistivity, lattice parameters, density and other features of the experimental alloys
of the Ni-Cr system (supplemented with. 1 at% Mo, table 7 ) in the initial state and after
thermal and radiation exposure.

Table 7. Chemical composition of experimental alloys Ni-Cr-Mo in wt%

Alloys C Ni Cr Cr* Mo S
Ni-32Cr-1Mo 0.027 . 32.11 34.94 1.28 0.006
Ni-38Cr-1Mo 0.027 . 37.85 40.90 1.30 0.005
Ni-39Cr-1Mo 0.022 . 38.90 42.00 1.30 0.005
Ni-41Cr-1Mo 0.028 . 41.35 44.49 1.30 0.005
Ni-43Cr-1Mo 0.025 . 43.06 46.24 1.30 0.005
Ni-44Cr-1Mo 0.026 . 44.48 47.69 1.30 0.005
* at%.

The starting state for the alloys investigated [7] is the state after quenching from the
single-phase - region of state diagram. Alloys for the investigations were quenched from the
single-phase - region of state diagram, and then annealed at temperatures of 300-450C
(points on the graph show the position of alloy before quenching and with aging, Fig. 20).
The typical structure of alloys in the initial state is shown in Fig. 21. The structure is a
homogeneous solid solution of nickel. Significant differences in the structural-phase state of
alloys after the quenching occur with increasing chromium content of more than 38 wt%. In
the body of grains of alloys with such a chromium content remain did not dissolved by
annealing for quenching particles of - phase of chromium with the volume fraction 0,1 %
(Fig. 21a. At the grain boundaries are observed seldom selections of chromium carbides
M
23
C
6
(Fig. 21b).


Figure 20. The alloys investigated in the phase diagram of the system Ni-Cr.
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 145

Figure 21. Structure of the alloy Ni-41Cr-1Mo after quenching: body (a) and grain boundary (b).
In the microstructure of quenched alloys is observed diffraction tweed contrast (Fig. 22a.
Tweed contrast becomes sharper detected after the annealing at 450C for 9 000 h (Fig. 22b).
Oscillation period of the fragments of contrast is 5 nm.
Study of the kinetics of structural features in the annealing process at 300 - 450C for up
to about 40 000 hours spent on the experimental samples of nickel alloys with chromium, has
shown that annealing in the temperature range 300 - 400C did not cause significant structural
and phase changes which are practically not detected by electron microscopy [14].
At 450C in the alloys there are structural-phase changes in accordance with the
chromium content in the matrix. The increase in chromium content stimulates grain boundary
precipitation of - phase, especially if the chromium content > 41 wt% (Fig. 23).
In the alloys with 32 and 38 wt%. of chromium on the high-angle grain boundaries were
formed chromium carbides type M
23
C
6
[6]. In the alloy Ni-38Cr-1Mo having a larger amount
of chromium the grain-boundary processes were developed more intensively. Further increase
in amount of chromium (alloy Ni-39Cr-1Mo) is even more intensified phase transformation at
grain boundaries. There were formed the plates of M
23
C
6
carbides and the plates of - phase
that is the beginning of discontinuous disintegration. Apparently due to the chemical no
uniformity the phase decomposition at the grain boundaries occurs uneven. On some sections
of the grain boundaries were formed carbides M
23
C
6
; on the others - there was the beginning
of discontinuous disintegration.

V. P. Kolotushkin and A. A. Parfenov 146

Figure 22. Tweed contrast in the alloy Ni-42Cr-1Mo: a) after quenching, b) after quenching and
annealing at 450, 9 000 h.

Figure 23. Structure of grain boundaries in alloys of Ni-Cr-Mo after annealing at 450, 40 000 h.
In the alloy Ni-41Cr-1Mo at the grain boundaries is observed occasional precipitation of
carbides M
23
C
6
and plates - phase. Increasing the chromium content to 43 wt% leads at
450C to intensive phase decomposition of frontier regions of the alloy Ni-43Cr-1Mo
emitting chromium-rich particles. There is the development of discontinuous disintegration
and precipitation of carbides M
23
C
6
. In the alloys with more than 43 wt% chromium the
discontinuous disintegration covers most of the grain body.
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 147
Fine structure of alloys at long (40 000 h) annealing varies in accordance with the
equilibrium phase diagram. Fig. 24 shows that in the alloy near the stoichiometric
composition at 450C for 40 000 h were formed Ni
2
Cr domains of superstructure with a
concentration > 7x10
21
m
-3
and the size of 4 - 10 nm. In the electron diffraction pattern in
addition to the matrix reflections are present reflections from the superstructure, in the light of
which was shown dark-field image of long-range ordering domains. Long-range order
develops in the whole volume of the matrix.
In the alloy Ni-38Cr-1Mo concentration and size of the domains of the superstructure
constitute respectively 1.2x10
23
m
-3
and 1-2 nm. Closer to the grain boundaries, on which is
allocated the phase based on chromium, the amount of long-range ordering domains more,
and their concentration is lower ( d 2 nm, = 5x10
22
m
-3
. The smaller size of the long-range
order domains, which according to their size have been called "nanodomains", in the alloy Ni-
38Cr-1Mo, apparently due to lower nickel content.


Figure 24. Structure of the alloys Ni-Cr-Mo (32, 38 and 39 wt% Cr) after annealing at 450, 40 000 h.
With increasing chromium content up to ~ 39 wt% intensity of superstructure
precipitation is reduced (Fig. 24). In the matrix of the alloy Ni-39Cr-1Mo, as in the matrix of
alloy Ni-38Cr-1Mo homogeneous nucleation of superstructure nanodomains Ni
2
Cr occurs.
Their concentration and size constitute are 1.4x10
23
m
-3
and 1-2 nm, respectively.
The parameters of phases after the aging at 450C show that increase in the chromium
content with increasing distance from the stoichiometric gradually lowers the amount of long-
range ordering superstructure. The intensity of the reflections from the superstructure Ni
2
Cr
V. P. Kolotushkin and A. A. Parfenov 148
nanodomains in the electron diffraction patterns decreases. And finally, in the alloy with
content of chromium 41 wt% during aging at 450C appears to be formed only the short-
range order. Reflections from the superstructure Ni
2
Cr nanodomains in the electron
diffraction patterns of the alloy Ni-41Cr-1Mo did not detected (Fig. 25). In such a way, in the
fine structure of the alloy with 41 wt% of chromium after the prolonged aging at 450C
occurs only the short-range order, phase transitions are not observed.
In the kinetics of transformation of the solid solution of the alloy Ni-44Cr-1Mo at 450C
was clearly demonstrated the effect of chromium. At the grain boundaries were formed the
fields of discontinuous decomposition (Fig. 25) size up to 5 microns. The precipitation of
chromium carbides M
23
C
6
was observed at grain boundaries. In the alloys with 43 and
especially 44 wt% chromium the discontinuous disintegration with the formation of - phase
of chromium in the form of plates occurs very rapidly, at the same time due to of enrichment
in nickel the matrix adjacent to the - phase domains forms large domains of the
superstructure Ni
2
Cr. The domains of superstructure have a size of 2 nm far away from grain
boundaries to 70 nm closer to precipitates, which are enriched with chromium.


Figure 25. Structure of the alloys Ni-Cr-Mo (41, 43 and 44 wt% Cr) after annealing at 450, 40 000 h.
An important feature of the restructuring of the atoms of nickel and chromium at the long
range ordering of FCC solid solution by type Ni
2
Cr lies in the fact that after formation of a
superstructure Ni
2
Cr the slip planes {111} become structurally not equivalent. The
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 149
arrangement of atoms in the two systems {111} planes corresponds to planes of type I (Fig.
26), in two other systems - planes of type II.


Figure 26. Location of atoms in different planes {111} of superstructure Ni
2
Cr [8].
Another important aspect in the formation of domains and the nucleation of the
superstructure nanodomains is a distortion of values of the matrix lattice parameters. In the
crystal lattice of the matrix (Fig. 27) the lattice parameters in the directions [110] [111]
increase while in the directions [311] and [331] decrease as compared with the original cubic
lattice parameters. At the same time in the crystal lattice of the matrix appear tetragonal
distortions.


Figure 27. The unit cell of superstructure Ni
2
Cr in the fcc lattice based on nickel [15].
The crystal lattice spacings of experienced alloys of the system Ni-Cr calculated from the
reflections [111] and [331] are shown in Fig. 28. It is seen that the lattice spacings of all the
alloys determined from the reflection of [111] is greater, as well from reflection of [331] -
smaller than the spacing of the original cubic lattice
cube
(Table 8).

V. P. Kolotushkin and A. A. Parfenov 150

Figure 28. The lattice spacings of Ni-Cr alloys after aging at 450C, 40 000 h, calculated from the main
reflections (111) and (331).
The values of changes of the matrix lattice parameters for different basic reflections
compared with the parameters of the original cubic lattice, also shown in Table 8.

Table 8. Changes in the lattice parameters of Ni-Cr alloys as a result of short-and long-
range ordering during annealing 450C, 40 000 h

Alloys
Changes of lattice parameters upon annealing
(d
450
- d
cube
)/ d
450
, %
The lattice period
of initial alloys

cube
(nm) d
220
d
111
d
311
d
331

Ni-32Cr-1Mo +0.07 % +0.07 % -0.19 % -0.27 % 0.35726
Ni-38Cr-1Mo +0.11 % +0.11 % -0.14 % -0.11 % 0.35860
Ni-39Cr-1Mo +0.11 % +0.12 % -0.08 % -0.05 % 0.35888
Ni-41Cr-1Mo +0.04 % +0.21 % -0.05 % -0.05 % 0.35927
Ni-43Cr-1Mo +0.09 % +0.06 % -0.08 % -0.02 % 0.35948
Ni-44Cr-1Mo -0.03 % +0.03 % -0.08 % -0.05 % 0.36010

With the results of structural studies agree well the changes in the mechanical and physical
properties of experimental alloys of the system Ni-Cr. So, the occurrence of tetragonal
distortions in the solid solution due to the long-range order decreases the maximum impact
strength in exactly those alloys in which there is the highest degree of long-range order - in the
alloys with 35 and 48 at% chromium (Fig. 29). Fig. 29 also shows that when the aging time is
10 000 h the toughness of alloys with elevated chromium content (~ 43 and ~ 44 wt%) is
higher than that in alloys with lower chromium content (~ 38 and ~ 39 wt%), but after
exposure 40 000 h the situation is reverse. It is connected, apparently, with the formation the
regions of long-range ordering around of precipitates the - phase.

Self-Organization of the Nanocrystalline Structure and Radiation Resistance 151

Figure 29. Dependence of impact strength Ni-Cr alloys from chromium content after annealing
at 450C [6].
Character of the electrical resistivity changes of the system Ni-Cr alloys also confirms the
results of electron microscopic studies [16], which showed that the no equilibrium state of the
system Ni-Cr alloys manifests itself during aging in different ways. If in the alloys with 32
and 44 wt% chromium at 450C occur drastic structural changes, in the alloys with 41 wt%
chrome like as if nothing happened. To elucidate the structural transformations have been
conducted experimental determinations of the electrical resistivity of alloys in the initial state
and after aging at 450C for 4000, 10000 and 40000 h [17]. Electrical resistivity was
measured at room temperature for the same samples before and after aging.
The results of electrical resistance measurements are shown in Fig. 30. The analysis
shows that the electrical resistivity is in good agreement with the structural features of alloys
Ni-Cr-Mo. The higher after quenching in comparison with other alloys electrical resistivity of
the alloy Ni-32Cr-1Mo is connected, apparently, with higher degree of short-range ordering.
In accordance with this assumption in solid solution of the alloy Ni-32Cr-1Mo should be
more pairs of unlike atoms after quenching than in the alloys with higher amounts of
chromium. The significant and monotonic decrease in the electrical resistivity with increasing
of aging time at 450C of the alloy Ni-32Cr-1Mo is caused by increasing the long-range order
extent in solid solution.

V. P. Kolotushkin and A. A. Parfenov 152

Figure 30. Resistivity of alloys Ni-Cr-Mo after quenching and aging at 450C [17].
As far as the distance from the stoichiometric Ni
2
Cr grows the character of electrical
resistivity changes in the system Ni-Cr alloys is complicated by competition between short-
and long-range ordering and discontinuous decomposition with the formation of - phase.
Long-range order of alloys with approaching to the boundary of the cupola of ordering in
the process of aging is becoming less and less intensive, and in these alloys occurs only short-
range order. In the alloys outside the "cupola" of ordering apparently due to the changes the
mechanism of disintegration of solid solution, the course of the electrical resistivity curves is
more complicated. A significant role in the changes of the electrical resistivity starts to play
the decomposition. The elucidation more details of these changes is not the purpose of this
study. One can only note a few facts. Reduction of resistivity in the alloys with higher
chromium content is due to intensive precipitation - phase and the subsequent nucleation of
long-range order domains in interlamel space. Somewhat unexpected increase in the values of
resistivity in the alloy Ni-44Cr-1Mo for the first 10 000 h of aging may be caused by short-
range ordering connected with the intense precipitation - phase. In further with increasing
the aging time up to 40 000 h the resistance of the alloy Ni-44Cr-1Mo decreases during the
formation of the Ni
2
Cr superstructure in the interlamel space.
For further investigation, it should be noted that the degree of long-range order, which
was estimated on the decrease of electrical resistivity, is minimal in the alloys, which are on
the content of chromium are close to the right boundary of the "cupola" ordering on phase
diagram of the system Ni-Cr. Significance and meaning of this phenomenon will be clarified
during the discussion the results of further research.
The changes of the electrical resistivity (Fig. 31) associated with structural changes at
450C, are apparently caused by dependence of the electron density of the system Ni-Cr
alloys from chromium content. In alloy, which is close to stoichiometric, electrical resistivity
during the aging has dropped after 4 000 h of exposure due to long-range ordering. In alloys
with higher chromium content character of changes of the electrical resistivity is more
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 153
complicated because it is influenced by several factors, in particular, the need a more
prolonged exposure for the beginning of long-range ordering.


Annealing time:
- 4 000 h,
- 10 000 h,
- 40 000 h
Figure 31. Relative change of alloys Ni-Cr-Mo resistivity after aging at 450C.
In the paper [18] have been suggested that the change in electrical resistance with the
formation of alloys based on transition metals is determined by the redistribution of electrons
between atoms. According to this hypothesis, the chromium atoms give a portion of their
conduction electrons, which pass to d - subshells of nickel atoms. Such a transition should
lead to an increase in the binding energy of atoms.
During the short-range ordering in solid solution increases the number of pairs of unlike
atoms. The free energy of the electron cloud decreases due to the transfer of electrons in a
stable state, this is accompanied by the release of energy H
mix
<0. Number of conduction
electrons decreases, as well the electrical resistivity increases.
If we increase the content of chromium in the alloys, then due to increasing tendency of
alloys to the disintegration with the formation of pairs of like atoms, the relative amount of
chromium, transferred their valence electrons to the nickel atoms is reduced. Accordingly, the
number of conduction electrons increases as well the electrical resistivity of the alloy
decreases.
In the process of long-range ordering in solid solution alloys Ni-Cr-Mo is formed not a
pairs of Ni-Cr, but superstructure, based on its triad of Ni-Ni-Cr. In this case, the number of
atoms of chromium, referred from solid solution to the superstructure is less than during the
formation of short-range ordering. In this case, respectively, the number of conduction
electrons increases and the electrical resistivity of alloys decrease.
V. P. Kolotushkin and A. A. Parfenov 154
Decrease in the electrical resistivity due to aging at 450C for 40 000 h was found in all
the experimental alloys Ni-Cr-Mo, but the minimum relative change in the electrical
resistivity occurs in alloys with chromium content in the interval 38 - 41 wt%.
So the results of structural studies and the definition of the electrical resistivity showed in
the good agreement with the hypothesis of exchange interaction of electrons of the nickel and
chromium atoms the minimum relative structural and physical changes in alloys with
chromium content in the interval 38 - 41 wt%.

3.2.3. Crystal Lattice Distortions and Recombination of Point Defects
Since the purpose of this study is to understand the role of changes in the structure in
improving of radiation resistance of materials, as well as the causes and mechanisms that
cause such an increase it is necessary to clarify the changes of physical properties with the
peculiarities which arise with rearrangement of atoms in the crystal lattice.
The appearance of tetragonal distortions in the crystal lattice of the Ni-Cr alloys in the
process of prolonged annealing at 450C have been reliably confirmed by X-ray studies of
structure and measuring the density of alloys. First of all, it was found that the absolute values
of the lattice constant in all the alloys after annealing at 300 C have higher values than after
aging at 450 C (Fig. 32 [8]). This means that in all the studied alloys of the system Ni-Cr,
which more or less display a tendency to short-range ordering and long-range ordering in the
process of the formation of order there is a decrease of the atomic volume or the lattice
contraction. The difference of the lattice periods after annealing at 300 and 450 C is maximal
for close-stoichiometric alloys and decreases with increasing chromium content up to 42
at%.


- matrix, aging at 300 C;
, - the matrix, aging at 450 C;
- superstructure Ni
2
Cr
Figure 32. The lattice periods of alloys Ni-Cr-Mo.
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 155
Aging at 300C for 40 000 h of studied alloys Ni-Cr-Mo, as was shown in [3, 6],
practically does not change their phase composition as compared to the state after quenching.
Was found only the initial - phase. However, in the solid solution of alloys, apparently in
connection with the annealing of quenched vacancies, there were the signs of short-range
ordering [8], as indicated by the comparison of the Bragg peaks (331) for the alloy Ni-41Cr-
1Mo at two temperatures (Fig. 33). It is seen that the lattice parameter of the alloy as a result
of short-range ordering at 450C decreased d/d (4x10
-4
) and the width of the reflections
increased ( 20 %). Qualitatively such changes manifest themselves in all other samples.


Figure 33. Comparison of the alloy Ni-41Cr-1Mo (331) reflections after annealing at 300 and 450C,
40 000 h.
The lattice compression was also discovered [19] by hydrostatic weighing in water with
preliminary evacuation the air, thermostatting, and with correction for buoyant force of the
suspension and the temperature correction to the density of water. The total error of
determining the density is 0,01 g/cm
3
. The density of experimental alloys after quenching
and after prolonged aging was determined (Table 9). In the alloys with chromium content
from 41 to 44 wt% the density increase due to short- and long range ordering was
compensated by its decrease due to precipitation of - phase.
Effect of annealing temperature on the density is observed more clearly in alloys with 32
and 39 wt% Cr (Table 9). In the Ni-32Cr-1Mo alloy located near the stoichiometric phase
Ni
2
Cr the raising of annealing temperature from 300 to 450C led to a significant increase in
density due to the formation of a superstructure Ni
2
Cr. In the alloys with 43 and especially 44
wt% chromium discontinuous disintegration of solid solution occurs at the grain boundaries.
At the first stage of disintegration in some parts of the grain boundaries there is a formation of
- phase in the form of plates. The plates of - phase are formed to the discontinuous
disintegration cell. The formation of cells occurs very rapidly, and in adjacent with plates of
- phase enriched by nickel interlamel space the particles of phase Ni
2
Cr are formed.


V. P. Kolotushkin and A. A. Parfenov 156
Table 9. Density of Ni-Cr alloys after annealing at 300-450C, 40 000 h

Alloys
Annealing
temperature,
Sample Weight
in air (g)
Alloy density (g/cm
3
)
- - 8.91
- - 7.20

Ni-32Cr-1Mo

300 0.47505 8.22
400 1.15615 8.23
450 0.58670 8.34

Ni-39Cr-1Mo

300 0.58625 8.09
400 0.59115 8.11
450 0.45520 8.13

Ni-41Cr-1Mo

300 0.36330 8.08
400 0.95355 8.02
450 0.52045 8.00
Ni-44Cr-1Mo

400 0.45730 7.99
450 0.44530 8.00

Increasing the chromium content from ~ 32 to ~ 44 wt% in the investigated alloys is
accompanied during annealing at 300 and 450 C uniform increasing in the lattice parameter
(Fig. 32. An increase the parameter is accompanied by decrease in the density because the
density of chromium less than the density of nickel (Table 9), and the size of chromium atom
by about 2.4 % larger than the size of the nickel atom.


Figure 34. Dependence of relative changes in density and lattice constants of alloys Ni-Cr-Mo on the
content of chromium with increasing aging temperature from 300 to 450C, 40 000 h.
With increasing chromium content from about 32 to 41 wt% the propensity of alloys
Ni-Cr-Mo to long range ordering decreases [3, 6, 8]. Simultaneously with the decrease in the
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 157
propensity to long range ordering increases the propensity to the disintegration of solid
solution with the formation of - phase. Character of change in the lattice parameter and the
density of alloys Ni-Cr-Mo with aging (Fig. 34) confirm these trends. The increase in the
density ( > 0) due to the formation of long-range ordering domains, with increasing
chromium content decreases and becomes minimum at short-range order alloys. Since the
beginning of the selection - phase the density become lower than the initial ( <0). At the
simultaneous formation of discontinuous disintegration cells and concomitant formation of
long-range ordering domains in the transition from ordering to disintegration region in which
long-range order does not occur, i.e. stage of short-range ordering is not transferred to the
stage of the long-range ordering the change in density close to zero.
Thus, the chromium content in the range ~ 39 - 41 wt% for alloys of Ni-Cr at 450C is
a transition or critical. Within this interval, at reasonable times of aging there is only short-
range ordering. In the microstructure of these alloys is observed only diffraction tweed
contrast which is evidence of short-range order. At this stage, oscillation period of the
fragments of contrast, i.e. zones of enrichment and depletion of nickel in the matrix is 5 nm.
It is known that in solid solutions, whose formation is accompanied by the increase in the
number of unlike pairs of atoms, i.e. ordering, there is the release of heat (negative deviations
from Raoult's law). In solid solutions whose formation is accompanied by a decrease in the
number of unlike pairs i.e. disintegration of solid solutions, there is the heat absorption
(positive deviations from Raoult's law). For this reason, the enthalpy of mixing H
mix
is
sometimes called the enthalpy of ordering if it is negative or enthalpy of decomposition if it is
positive. In the critical range of the chromium content the enthalpy of mixing H
mix
should be
close to zero.
The aging process at a temperature of ~ 450C in alloys with chromium content ~ 39 - 41
wt% stops at the stage of formation of crystalline domains size 2.5 nm i.e. at the stage that
is intermediate between the homogeneous and micro domain short-range order. This step
should be to call, according to the size of areas, "nanodomain short-range order". A
characteristic feature of the nanodomain short-range order is close to zero enthalpy of mixing
H
mix
. The nanodomain short-range order should have a positive impact on improving the
radiation resistance of alloys by increasing the recombination of vacancies and interstitials in
the border zones of the nanodomains.
This also implies that with a glance the heterogeneity of chemical composition, the alloys
in the concentration range of ~ 39-41 wt% chromium are in a no equilibrium metastable state.
Solid solution of these alloys has the concentration and density of components fluctuations,
availability and the development of which is crucial for increasing radiation resistance of
materials.
To determine the effect of short-and long-range order on the recombination of point
defects was conducted 5 MeV electron irradiation [20] of nickel alloy with 32 wt% chromium
in the states after quenching (short-range order) and after annealing at 450C for 40 000 h
(long-range order). In analyzing the structure was used the method of positron annihilation by
measuring the angular distribution of annihilation photons. Changes in the shape of the
spectra due to the capture of positrons by defects were characterized by standard S - and W -
parameters. S - and W - parameters were determined as the ratio of the coincidence rate sum
in the angle range of from 0 to 3.5 mrad and 10 to 20 mrad to the total rate of coincidences,
respectively. When positrons are trapped by vacancy-type defects or dislocations, the value of
V. P. Kolotushkin and A. A. Parfenov 158
S - parameter increases and W decreases, i.e. increases the probability of annihilation of
positrons with conduction electrons, and decreases the probability of annihilation with the
electrons of the ion core.
Fig. 35 shows the dependence of parameter S, proportional to the number of vacancies in
the matrix of the irradiated alloy from the electron fluence.


- long-range ordering
- short-range ordering [20]
Figure 35. Effect of short-and long-range ordering on the accumulation of vacancies in the irradiated at
200 C 5 MeV electrons alloy Ni-32Cr-1Mo:
It is seen that with increasing electron fluence the number of vacancies in which the
positrons annihilate is increased. However for the alloy in a state of short range ordering at a
fluence of ~ 2x10
22
m
-2
the growth of S - parameter is slowing, and the values of S -
parameters reach saturation. This means that the emerging vacancies during irradiation of the
alloy in a state of short-range ordering recombine with the interstitial atoms. At the same time
for the alloy in a state of long-range ordering the growth of values S - parameter at irradiation
continues, i.e. vacancies in the matrix continues to accumulate.
This experiment shows that the tetragonal distortions that occur in the matrix during the
formation of short-range order nanodomains are effective traps for point defects. From this
experiment should also be an important conclusion: when the alloy is given in a stable state,
for example by long-range ordering, the alloy can not provide the high recombination of
vacancies and interstitials.
At the same time the recombination accelerating of vacancies and interstitials is
observed, as determined by the study of experienced Ni-Cr alloys in no equilibrium
metastable alloys, removed from the composition of the stoichiometric phase Ni
2
Cr and
having approximately the same inclination as to ordering and to phase separation, i.e. near to
zero enthalpy of mixing of solid solution. Due to nonstoichiometric of composition and near-
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 159
zero enthalpy of mixing in the structure of these alloys during neutron irradiation does not
occur long-range ordering and is observed only short-range order.
Study of physical mechanisms of radiation damage of materials and the ways of
increasing resistance to embrittlement and swelling is the most important problem of radiation
material science, and in this regard, understanding of dependence the recombination of point
defects on the effects of short-range ordering is of considerable interest.
In the process of the study of ordering alloys of system Ni-Cr with near-zero enthalpy of
mixing was found that their evolution during neutron irradiation is stopped at the stage of
formation of tweed contrast with the period of oscillation of zones nickel enriched 5 nm. It
is known that due to the high surface energy such small particles have high catalytic activity
[21]. The number of constituent atoms in an isolated metal particle is small, so the distance
between the energy levels of electrons = E
F
/N (E
F
Fermi energy, N the number of
atoms in a particle) comparable to the thermal energy k
B
. Activity of small metal particles
begins to appear when in size close to k
B
. This allows us to estimate the size for which
show catalytic properties of the particle.
In accordance with the algorithm proposed in [22], were determined for metals used in
nuclear industry (Table 10), parameters for calculating the number of atoms in a particle: the
number of electrons in 1
3


A
Z
n
m

24
10 6022 , 0 =
(1),

where Z - number of conduction electrons,
m
- bulk density (g/cm
3
), - relative atomic mass;
radius of a sphere whose volume is equal to the amount paid for a conduction electron

3
1
4
3

=
n
r
S

(2)

and the Fermi energy of metals

( )
2
0
1 , 50
a r

E
S
F
=
(3),

where
0
- Bohr radius = 0.529 .

Table 10. Initial data for calculating the number of atoms in the particle [9]

Element Z (g/cm
3
) n, 10
22
cm
-3
r
s
, r
s
/
0

F
, eV
Ti 2 4.51 11.34 1.28 2.42 8.55
V 2 6.1 14.42 1.18 2.23 10,07
Cr 1 7.19 8.33 1.42 2.68 6.98
Fe 2 7.87 16.97 1.12 2.12 11.15
Ni 2 8.9 18.26 1.09 2.06 11.81
V. P. Kolotushkin and A. A. Parfenov 160
Calculating the number of atoms N = E
F
/k
B
T in the isolated metal particle from the atoms
of transition elements gives, in accordance with the Fermi energy, defined by (3), the values
shown in Table 11.

Table 11. Assessment of the number of atoms for some transition metals in accordance
with the catalytic activity

The number of atoms in a particle (at temperature*, C), = E
F
/ k
B
T
Temperature* 20 100 200 300 400 500 600 700 800
E
l
e
m
e
n
t

Ti 342 267 214 174 147 128 114 102 93
V 423 330 264 216 182 158 141 126 115
Cr 279 218 174 142 120 104 93 83 76
Fe 446 348 279 228 192 166 149 133 121
Ni 472 369 295 241 204 176 157 141 128

With such quantity of the atoms a linear particle size is 2 - 4 nm and, therefore, in this
size range should significantly change the physical and the catalytic properties of small
particles of these atoms.
The evaluation shows that short-range order nanodomains with an average size 2 -3 nm
formed in alloys of nickel and chromium under irradiation with neutrons are the particle of
size at which is actively manifest catalytic properties. Short-range order nanodomains form
homogeneously distributed in the matrix system or a sub lattice of the catalytically active sites
that interact with vacancies and interstitials. With the linear size of the nanodomains 2 - 3
nm, the number of the atoms in them in the system Ni-Cr amounts 150 - 250 for a
temperature of 600 K [9]. One can assume that consolidation of point defects in the zone of
influence of nanodomains short-range ordering is an effective factor in the recombination
accelerating and increasing radiation resistance of the alloys.


4. DISCUSSION: SELF-ORGANIZATION OF THE NANOCRYSTALLINE
STRUCTURE OF TRANSITION METALS

Now back to the unusual results of the experiment on neutron irradiation, in which was
discovered a more long incubation period to maintain a stable structure of the alloy Ni-42Cr-
1Mo compared with other materials. On the diagram state of the system Ni-Cr figurative
point of radiation-resistant alloy Ni-42Cr-1Mo is located in the region of metastable alloys,
which have enthalpy of mixing close to zero (H
mix
0). Due to this the alloy Ni-42Cr-1Mo
affects only short-range order during prolonged radiation and thermal aging. Less radiation
resistant alloy Ni-47Cr-1Mo alloy lies in the region of alloys which subjected to
discontinuous disintegration at exposed to prolonged thermal aging and therefore in
conditions of the reactor are more inclined to transition to stable structural condition. Over the
stabilization of the structure there should be accelerated accumulation of dislocation loops.
Mechanism of the recombination accelerating in alloys of system Ni-Cr of type Ni-42Cr-
1Mo with near-zero enthalpy of mixing is as follows. In the alloys with the structure of short-
range order (38 - 41 wt% Cr) the changes in the displacement cascade of the composition of
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 161
matrix entails the formation of the local areas short-range ordering. If in the local region
begins short-range ordering, then the adjacent areas of the matrix are enriched with
chromium. In the chromium-enriched areas begins to form discontinuous disintegration. In
this case, the surrounding matrix is enriched with nickel. In these areas begins to form short-
range ordering, etc. Short-range ordering and the short-range disintegration help each other,
and the as a result no one phase is not formed, which corresponds to the spinodal condition.
This mechanism suggests that the processes in the metastable structure, leading to the
appearance of nuclei of new phases are competing. However, it seems obvious that if for the
nucleation of short-range order is necessary only tendency to minimize of the system free
energy, for the formation of clusters should be further upward diffusion. From this point of
view, the formation of clusters (zones of Guinier - Preston) are less likely than the emergence
of short-range order nanodomains, since during the nucleation of short-range order
nanodomains the energy gain will be greater..
However, the tetragonal distortions move over the matrix due to the fact that in the
displacement cascades the formed nanodomains of short-range ordering and disintegration are
destroyed and re-formed in another place. As a result of differences in lattice constant and the
density of the FCC phase and the nanodomains short-range order in the alloys appear the
mobile local distortions that significantly accelerate the recombination of the surrounding
radiation-induced point defects.
Ordered arrangement of the short-range order nanodomains with an interval of 5 nm
allows evaluate them as an ordered structure of traps of vacancies and interstitials.
The short-range order nanodomains form crystalline structure, but do not have time to
form long-range order domains of the superstructure due to failure in displacement cascades
and the near-zero enthalpy of mixing. During the formation of nanodomains the surrounding
volume is depleted with one of the components, creating a periodic change in chemical
composition. Such zones are constantly shuffled and placed on a matrix, which ultimately
ensures the presence of traps and recombination of point defects in any point of the matrix,
where the formation of displacement cascade would not have happened with the
corresponding appearance of an excess concentration of vacancies and interstitials. In these
processes, the dynamic equilibrium of ordering and disordering is the decisive factor that
controls the structural transformations.
Such is the concept of maximal radiation resistance of the metastable alloys.
It is known that in the presence of distortions in the crystal lattice the interstitial atoms
tend to get into the stretched spaces, and vacancies on the contrary, in tight. Therefore,
existing and emerging after quenching and aging in the alloys Ni-Cr-Mo fluctuations of
concentration and density represent a system or sub lattice of short-range order nanodomains
- traps for vacancies and interstitials.
In the process of neutron irradiation the primary knocked atoms destroy the integrity of
the nanodomains, takes place a process similar to hardening of the alloy - there is a local
disordering. Alloy tends to decrease the free energy and again is locally ordered; then again in
the displacement cascade is destroyed etc. Thus, the behavior of the atomic structure of the
alloy under neutron irradiation becomes in the local points the character of the continuous
reversible change from ordering to disordering and vice versa, i.e. the character of dynamic
equilibrium.
The orientation and shift of the dynamic equilibrium of the metastable alloy in the
direction of the order or disorder is determined by the alloy composition, i.e. electron density
V. P. Kolotushkin and A. A. Parfenov 162
and other physical characteristics, as well as the parameters of an open system. With the
change in the physical characteristics of the alloy appears to be changed the effectiveness of
interaction of vacancies and interstitials with the crystal lattice. We can assume that the rate
of ordering of the alloy must be equal to the rate of disorder in the neutron field or be a few
below it. Such a preponderance of the rate of disorder in the neutron field is required in order
to prevent the transformation of the metastable solid solution through the ordering in the
stable.
Calculating the number of displaced atoms in the dislocation loops according to the
formula N=0,141d
2
, where d - the average size of dislocation loops, - the average
concentration showed: in the alloy Ni-42Cr-1Mo after neutron irradiation dose of ~ 32 dpa
the number of displaced atoms in the loops, i.e. the number of the not recombined interstitials
was approximately two times less than in the alloy Ni-47Cr-1Mo.
One can with certainty assume that the advantages of alloys of Ni-42Cr-1Mo, as a stable
during neutron irradiation material, are based on the metastability of the structure derived
from a tendency to short-range order. The above analysis also suggests that the development
of the traps associated with the short-range ordering nanodomains, is the most effective
mechanism for improving radiation resistance at temperature of 350C.
Thus, the analysis of the results of neutron and electron irradiation clearly demonstrates
that the alloys in a metastable state having a tendency to the short-range order much more
slowly accumulate radiation damages compared to the more stable alloys in the state of long-
range ordering, and especially in comparison with the austenitic steels.
The obtained experimental facts indicate that in assessing the number of secondary
radiation defects must be taken into account as the conditions for the appearance of point
defects and the effectiveness of the conditions for their recombination. The higher the rate of
the creation the displacements in the core, the greater number of vacancies and interstitials
per unit of time are created in the crystal lattice of the alloy. And, in its turn, the higher the
rate of ordering of the structure, the greater amount of point defects recombines in a time unit.
The equality of these rates will provide the dynamic equilibrium of the structure during
neutron irradiation.
The analysis of own and literature data shows that the established mechanism of
accelerated recombination of point defects is effective not only in radiation-resistant alloys
system of Ni-Cr, but also in the alloys with the others system components. The use of
radiation-resistant alloys of different systems is predetermined by operating temperature
range in which in structure of the alloy are formed the short-range order nanodomains.
Different classes of materials of active zones have the different temperature ranges of
use. For example, alloys based on nickel-chromium are suitable to 400C, iron-based alloys
with the chromium - approximately 550C. At higher temperatures, are perspective ternary
alloys based on vanadium with titanium and chromium, which can provide a more stringent
operating conditions arising from the 2 - 3-fold reduce the amount of the core of fast reactors
per unit of installed capacity.
Thus in accordance with the proposed phenomenological model the alloys that are
resistant to neutron irradiation in a specific temperature range necessary to select in the range
of compositions with the enthalpy of mixing, which is close to zero. This implies that the
alloys have the metastable structure of short-range ordering and about the same penchant for
Self-Organization of the Nanocrystalline Structure and Radiation Resistance 163
ordering and phase separation, i.e. structure that as the swing periodically inclined then to
ordering then to the disintegration.
The distinctive feature of short-range ordering nanodomains as the traps for vacancies
and interstitials is that they are formed from atoms of the components of the matrix, however,
such atoms can be either in the a disordered state or in a state of short-range order. And the
transition from one state to another in the open system of neutron irradiation is carried out
continuously. Under the influence of the temperature the matrix is ordered, creating the traps
and under the influence of the neutron flux - becomes disordered, losing the traps. And these
"the swing" is working as long as the active zone works. This feature of the behavior of solid
solution of the metastable alloys with the near-zero enthalpy of mixing we call "the self-
organization of the nanocrystalline structure" of transition metal alloys under the influence of
temperature and radiation.


CONCLUSION

The analysis of experimental results of the study the structure-phase state of the austenitic
steels, nickel-based alloys after quenching and aging, neutron irradiation at temperatures of
300 - 350C and by electrons with the 5 MeV allows us to make the following conclusions.

1) The formation in the solid solution of nickel-based alloys of the short-range order
nanodomains as the traps of vacancies and interstitials with the period 5 nm and
concentration 10
24
m
-3
is the most effective way to ensure the radiation resistance.
2) The crystal structure of the short-range order nanodomains is formed in the process
of the neutron irradiation under the influence of radiation enhanced temperature,
while under the influence of irradiation is destroyed.
3) The effect of "the self-organization of the nanocrystalline structure" of alloys,
inclined to short-range ordering during neutron irradiation consists in the permanent
formation in the solid solution of the short-range order nanodomains, being destroyed
in the displacement cascades.
4) In accordance with the proposed phenomenological model the alloys that are
resistant to neutron irradiation in the specific temperature range should be selected in
the range of compositions with the enthalpy of mixing which is close to zero. This
implies that the alloys have the metastable structure of short-range order and about
the same penchant to the ordering and phase separation.
5) A necessary condition for the minimal accumulation of secondary radiation-induced
defects in the alloys is the lagging speed of short-range ordering from the rate of
disorder in the neutron field, which prevents the formation of stable phases and the
shift of the solid solution state to the stability.
6) The choice of alloy components with the metastable structure for the operation in
conditions of specific open system should be determined by its parameters, that is the
temperature and intensity of irradiation, as well as the relevant physical
characteristics of the material.


V. P. Kolotushkin and A. A. Parfenov 164
REFERENCES

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In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0
Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc.






Chapter 4



TRANSITION METAL COMPLEXES OF SCHIFF BASE
LIGANDS OF 3-FORMYLSALICYLIC ACID:
SYNTHETIC PATHWAYS AND USEFUL PROPERTIES


Saikat Sarkar
1
and Kamalendu Dey
2

1
Department of Chemistry, Santipur College, Santipur,
Nadia, West Bengal, India
2
Department of Cheistry, University of Kalyani, Kalyani,
Nadia, West Bengal, India


ABSTRACT

The contributions of transition metal complexes of 3-formylsalicylic acid and
varieties of Schiff base ligands based on it have been vividly reviewed and discussed.
The mode of reactions along with the structural topologies with such variety of ligands
having a wide range of donor atoms such as N, S, O, P are typically commented. The
metal complexes of such privileged ligands show many interesting polymeric /
supramolecular coordination architectures involving different weak forces e.g. C-H.,
. etc. interactions. The synthesis and practical properties of the complexes of various
nuclearities of the Schiff bases derived from 3-formylsalicylic acid with monoamines,
diamines, polyamines and substituted amines are discussed systematically. Such
transition metal coordination complexes, due to their intriguing topologies, have found
their applications in magnetism, catalysis, biological activities, solid state properties,
charge transfer and useful materials. A few non-transition metal complexes have also
been disussed for comparison.





1
E-mail addresses: saikat_s@rediffmail.com (S. Sarkar)
2
Email address: kdey_chem@rediffmail.com (K.Dey) Former Professor of Chemistry and UGC Emeritus Fellow.
Saikat Sarkar and Kamalendu Dey 166
1. INTRODUCTION

In 1864 Hugo Schiff [1] first described the reaction between an aldehyde and an amine
lead to a condensation product called Schiff base according to his name. Modern chemists
still prepare Schiff bases, and now-a-days active and well-designed Schiff bases are being
prepared. Schiff bases may also act as ligands to form metal complexes coordinating metal
centres through imine nitrogen(s) and other groups usually linked to aldehyde, and they can
also stabilize them in various oxidation states, enabling the use of such complexes for a large
variety of useful catalytic transformations and recently they are considered as privileged
ligands [2].
Many simple organic aldehydes were used to react with variety of amines to produce a
large number of Schiff base ligands. 3-Formylsalicylic acid (Figure 1.1), first synthesized by
Duff and Bills [3], has been extensively utilized as an efficient precursor for the synthesis of
numerous multidentate Schiff base ligands. 3-Formylsalicylic acid, itself, may also act as a
ligand for the synthesis of many metal complexes.


Figure 1.1.


2. METAL COMPLEXES OF 3-FORMYLSALICYLIC ACID

3-Formylsalicylic acid, owing to the presence of three different binding groups (viz. -
COOH, -CHO and -OH) may act as monobasic bidentate (like salicylaldehyde), dibasic
bidentate (like salicylic acid) or dibasic phenoxy oxygen bridged tridentate ligand [4-6].
Dey et al. [6] had synthesized anionic complexes of V(IV)O and V(V)O with H
2
fsa of the
types (NH
4
)
2
[VO(fsa)
2
].2H
2
O and NH
4
[VO(fsa)(OH)
2
(H
2
O)].
The IR spectra [4,7] of the complexes suggest that both OH and COOH groups
participate in chelate formation after deprotonation and the ligand behaves as a dibasic
bidentate fashion. The electronic spectra of the V(IV)O and V(V)O have been measured and
compared with the previously reported low-symmetry oxovanadium complexes [8,9] of
hydroxy acids. Qualitative band assignments suggest that the geometry of these V(IV)O and
V(V)O complexes are intermediate between square pyramid and bi-pyramid.
Binuclear Cu(II) complexes of the types Cu
2
Cl
2
(fsa)H
2
O, Cu
2
Cl
2
(Hfsa)
2
H
2
O,
Cu
2
(CH
3
COO)
2
(Hfsa)
2
.H
2
O and Cu
2
(fsa)
2
.3H
2
O were prepared and characterized by Dey and
coworkers [10]. Binuclear Ni(II) complexes of H
2
fsa are also known [11].
Encapsulation of metal complexes inside microporous supports has emerged as a general
technique to increase and control selectivity of catalysis [12]. Zeolites can play as effective
and attaractive supports for encapsulation as they are thermally and chemically stable having
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 167
a regular, crystalline framework. Besides, because of their similarities with the
metalloenzymes, the encapsulated complexes are expected to mimic enzyme active site for
catalytic reactions such as oxidation [13,14], hydrogenation [15], dehalogenation [16], etc.
Considering the above characteristics Xavier et al. [17] synthesized and characterized Y
zeolite encapsulated Co(II), Ni(II) and Cu(II) complexes of 3-formylsalicylic acid which were
used as a novel solid catalysts for the partial oxidation of benzyl alcohol and ethyl benzene.
Encapsulated Cu(II) complexe has been found to be more efficient than the other two
complexes for the oxidation reaction.
However, thorough investigations on the metal complexes of H
2
fsa are yet to be done.


3. METAL COMPLEXES OF LIGANDS DERIVED FROM
3-FORMYLSALICYLIC ACID

The formyl group (-CHO) of H
2
fsa can easily be condensed with different monoamines,
aminoalcohols, aminophenols, aminothiol, aminothiophenol, suphanilamides, diamines and
polyamines leading to different types of Schiff bases. Most of these Schiff bases were
synthesized and their versatility as ligands has been investigated over the past several years
by different group of workers. The accounts of which are given below under appropriate
headings covering the salient features of the topics.


3.1. Mono-, Bi- And Polynuclear Complexes of the Schiff Base Ligands
Derived by the Condensation of 3-Formylsalicylic Acid with
Monoamines, Aminoalcohols, Aminoacids, etc.

Condensation reactions of appropriate amino compounds and 3-formylsalicylic acid (1:1
molar ratio) lead to the formation of corresponding Schiff base ligands (Scheme 1.1).

Scheme 1.1.
Saikat Sarkar and Kamalendu Dey 168
Depending on the nature of R, the Schiff base ligands can act as a monobasic bidentate
(Figure 1.2), dibasic tridentate (Figure 1.3) and phenoxo-bridged dibasic tridentate (Figure
1.4) ligand. Most of the transition and non-transition metals form these types of complexes
[18-23].


Figure 1.2.

Figure 1.3.

Figure 1.4.
Magnetic moment values of the Fe(II) and Fe(III) complexes of H
2
fsaan and H
2
fsaana
show that the complexes belong to the ionic or outer-level covalent category [7]. Some
V(IV)O and V(V)O complexes of dibasic tridentate Schiff bases, H
3
fsagly and H
2
fsaana have
also been prepared and characterized [9]. The complexes synthesized are of the types,
[(Hfsagly)VO(H
2
O)], [(Hfsagly)VO(H
2
O)(Py)], [(Hfsaana)VO(H
2
O)], [(Hfsaana)VO(H
2
O)
(OH)] and [(Hfsagly)VO(OH)]
2
. The structures of the complexes have been discussed on the
basis of elemental analyses, magnetic moments and spectroscopic (IR, UV-Vis.) data. The
V(IV)O complexes are paramagnetic with magnetic moment ranging from 1.77-1.81 B.M.,
which is close to the spin-only value of 1.73 B.M. for a d
1
system. A square-pyramidal
geometry has been assigned to the [(Hfsagly)VO(H
2
O)] and [(Hfsaana)VO(H
2
O)] complexes
and their electronic spectra are interpreted using the ordering of vanadium d orbitals, i.e.
d
xy
<d
xz
, d
yz
<d
x
2
-y
2
<d
z
2
proposed by Vanquickenborne and McGlynn [11,24]. The other
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 169
complexes found to be diamagnetic. The electronic spectrum of the dimeric compound in
nujol mull shows one broad band around 17000 cm
-1
which may be considered as metal
ligand charge transfer [18,25].
Dey et al. [10] reported the synthesis and characterization of Cu(II) complexes of
H
2
fsama, H
2
fsaan and H
2
fsaeao. All of these complexes except one are binuclear with
subnormal magnetic moments at room temperature. Using g
av
= 2.2 and a value of 6 x 10
6

c.g.s. units for TIP (temperature independent paramagnetism), the energy separation between
singlet and triplet states, i.e. 2 J, have been calculated using Bleaney and Bowers equation
[19,26] which support the occurrence of strong antiferromagnetic spin-exchange interaction
between the two Cu(II) centres. Similar Cu(II) complexes have also been described by
Tanaka et al. [11,27].
Sugar borne Schiff bases and their metal complexes can play wide variety of roles in
different fields like, metal-base affinity chromatography materials [28], chiral homogeneous
catalysts [29], metal chelators for clinical use [30], etc. Inspite of the above facts, the field of
sugar-metal chemistry is still unexplored vividly. Keeping the facts in mind, Adam and Hall
synthesized a new sugar containing Schiff base ligand and its Cu(II) complex [31]. Methyl
3,4,6-tri-o-actyl-2-amino-2-deoxy--D-glucopyranoside hydrobromide on condensation with
H
2
fsa gives the Schiff base which on reaction with copper(II) acetate afforded Cu(II) complex
in alcoholic solution. From detail study of mass spectrometry and ESR spectra it has been
concluded that the complex has binuclear Cu(II) structure. The overall reactions are shown in
Scheme 1.2.


Scheme 1.2.
Saikat Sarkar and Kamalendu Dey 170
Other complexes of this type with first and second row transition metal ions have also
been synthesized. Some boron derivatives of this ligand are also known [32]. Amine
containing polysaccharides on reaction with such aldehydes also produce Schiff base which
on treatment with the metal salts also give metal complexes [33].
3-Formylsalicylic acid (H
2
fsa) on reaction with 2-aminothiophenol in methanol yielded
benzothiazoline [34-36], (H
2
chpbzn) which remains in equilibrium with its corresponding
Schiff base form, H
3
mpcsalim, in solution (Figure 1.5).
However, in the solid state the benzothiazoline structure has been suggested from the
infrared spectroscopic data. The absence of
CHO
,
C=N
and
SH
at 1660 cm
-1
, ~1600 cm
-1
and
~2600 cm
-1
respectively support the benzothiazoline structure [37].


Figure 1.5.
Some complexes of Cu(II), Ni(II), Zn(II), Pd(II) and U(VI)O
2
have been synthesized by
the treatment of the benzothiazoline solution with the corresponding metal salts [34]. In these
complexes, the Schiff base actually functions as a tridentate NSO donor ligand. Based on
physico-chemical data the authors proposed following monomeric structures for Zn(II) and
U(VI)O
2
complexes (Figure 1.6) but sulphur-bridged dimeric structures for Cu(II), Ni(II) and
Pd(II) complexes (Figure 1.7) [34]. Crystallographic studies of such complexes will be of
much interest.


Figure 1.6.
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 171

Figure 1.7.


Scheme 1.3.

Scheme 1.4.
Recently Dey et al. synthesized many new metal complexes and organometallic
compounds by the reaction of benzothiazoline (H
2
chpbzn) with (-C
5
H
5
)
2
TiCl
2
, (-C-
5
H
5
)
2
ZrCl
2
, CrCl
3
.6H
2
O, FeCl
3
, VOSO
4
.2H
2
O, VOCl
3
, Ni(OAc)
2
.4H
2
O, Na
2
PdCl
4
, Me
2
TlCl,
Ph
2
TlCl, BiCl
3
and SbCl
3
under varied reaction conditions [36]. During complexation, the
Saikat Sarkar and Kamalendu Dey 172
Schiff base (H
3
mpcsalim) involves in its dianionic form utilizing NSO donor set of atoms,
except in case of Bi(III) and Sb(III), where the benzothiazoline acts as a unidentate neutral N-
donor ligand. Such Lewis basic behaviour of benzothiazoline is very rarely encountered in
literature [35,38-40]. The reactions are summarized in the Schemes 1.3-1.5.


Scheme 1.5.


Scheme 1.6.
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 173
As proposed by Nag et al. [34] sulphur-bridged dimeric structures have been proposed
for Ni(II), Pd(II) and V(IV)O complexes. Corresponding molybdenum (III, IV, V, VI)
complexes are also known [41].
The reaction of [(Hmpcsalim)Ti(-C
5
H
5
)
2
Cl] with Me
3
SiE (where E stands for SMe,
NMe
2
, N
3
and CCPh) affording new organotitanium(IV) compounds have also been
discussed (Scheme 1.6).
Due to immense importance of benzothiazoline type of ligand in coordination chemistry,
Dey and co-workers [42] have shown interest to synthesize a new benzothiazolidine
compound and studied similar types of reactions with different metal salts. The reaction of 3-
formylsalicylic acid with 2-aminoethanethiol produces the thiazolidine (H
2
chptz) compound
which shares equilibrium in solution with its corresponding Schiff base form (H
3
mcsalim)
(Figure 1.8).


Figure 1.8.
The reaction of this thiazolidine with Me
2
SnCl
2
is very interesting. It gives NSO chelated
organotin(IV) compound having trigonal bipyramidal geometry (Figure 1.9). Similar type
organotin(IV) complex with benzothiazoline (Figure 1.10) has also been reported.

Figure 1.9.

Saikat Sarkar and Kamalendu Dey 174

Figure 1.10.
The
1
H NMR spectra of organotin(IV) complex [(Hmcsalim)SnMe
2
] (Figure 1.9)
displays the Sn-CH
3
protons as one sharp singlet at 0.89 ppm. The observed
3
J (
119
Sn-CH
3
),
2
J (
117
Sn-CH
3
) and
3
J (
119
Sn-N=CH
+
) values (74.5, 72.1, 38.8) respectively are within the
ranges reported for other trigonal bipyramidal (CH
3
)
2
Sn(IV) chelate complexes with two
methyl groups in the cis-configuration [43].
The dimeric Cu(II) complex also draws our attention. The ESR data of the complex in
polycrystalline and solution phase (DMF) at room temperature (300 K) exhibits four lines
(
63
Cu, I = 3/2) slightly anisotropic spectra at higher magnetic field. At liquid nitrogen
temperature (77 K) the spectrum shows axial type with g


(2.280) and g

(2.091) with respect


to DPPH marker. The trend g

> g

> g
e
(2.0048) suggests that the unpaired electron is
localized in d
x
2
-y
2
[44,45].
The cyclic voltammogram (CV) of the Cu(II) complex exhibits one quasi-reversible
redox couple at E
1/2
= 0.16 V (E
p
= 150 mv) and an irreversible peak at 0.8 V vs. SCE. First
response is reductive due to Cu
II

Cu
I
and the second one is oxidative Cu
II

Cu
III
.
Dey et al. [46] very recently synthesized a new hydrazone ligand, 3-carboxy-2-
hydroxybenzaldehydemorpholine N-thiohydrazone (H
2
chbmth) by the condensation of H
2
fsa
and morpholine N-thiohydrazide (Hmth) and studied its reactions with 3d and 4d transition
metal salts. The thiohydrazone ligand remained as thioketo form in the solid state. However,
in solution, thioketo and small amount of thiolo tautomeric forms (H
2
chbmth and H
3
chbmthol
respectively) may remain in equilibrium (Figure 1.11). Depending on the pHs of the reaction
medium and the nature of the metal salts used, the ligand is found to act as monobasic
tridentate, dibasic tridentate, monobasic bidentate and neutral bidentate fashion.


Figure 1.11.
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 175
The dimeric Cu(II) complex, [Cu(Hchbmthol)]
2
(scheme 1.7) is found to show low
magnetic moment (1.44 B.M.) which might be due to spin-coupling resulting from super
exchange through the bridging sulphur (oxygen) atom or metal-metal bonding as observed
earlier on similar such complexes [47-49]. The decrease in the magnetic moment with the
decrease in the temperature indicates the presence of antiferromagnetic coupling between the
two centres.


Scheme 1.7.
Using the idea of an easy route for the synthesis of immobilized transition metal
complexes by the reaction of polymer-anchored ligand with metal ions, recently, Syamal et
al. [50,51] have reported the synthesis and characterization of Cu(II), Ni(II), Co(II), Fe(III),
Zn(II), Cd(II), Mn(II), Mo(VI), Zr(IV) and U(VI)O
2
complexes of polystyrene supported
resin containing Schiff base derived by the reaction of chloromethylated polystyrene, 3-
formylsalicylic acid and ethanolamine (Scheme 1.8).
The reaction of PS-Cl and H
2
fsa in 1:4 molar ratio leads to the 100 % conversion to PS-
FSal, which does not contain any chlorine. But the same reaction in the ratio 1:<4 always
resulted the product containing chlorine. These types of polymer-assisted complexes might
have wide range of applications [52-54] based on their physico-chemical properties.
The same group of workers extended their idea to synthesize polystyrene-anchored mixed
Schiff bases and their coordination complexes [55,56,57] in view of their numerous
applications in organic synthesis [58], biological systems [53], catalysis [59] and analytical
chemistry [60]. They designed the mixed Schiff base having H
2
fsa as one component fixed
which are shown in Scheme 1.9.

Scheme 1.8.
Saikat Sarkar and Kamalendu Dey 176


Scheme 1.9.
The Maurya group of researchers also synthesized many polymer bound Schiff base
metal complexes and studied their immense catalytic applications [61-64]. Schiff bases have
been derived by the condensation reaction of 3-formylsalicylic acid with 2-aminoethanol, 3-
aminoethanol, 2-amino-2-methylpropanol, -alanine,
D,L
-alanine,
L
-isoleucine and o-
hydroxybenzylamine. Then, the polymer bound oxovanadium, oxomolybdenum and copper
complexes have been synthesized, characterized and employed as efficient catalysts in
various oxidation reactions. The recycling studies also indicated the reusability of such
catalysts for atleast three times without any significant loss in their potential catalytic activity.
Recent research of Maurya et al. has shown a new gateway for the desulfurization of
various organo-sulfur compounds to their corresponding sulfones using polymer bound
oxovanadium(IV) and oxovanadium(V) complexes [65]. The desulfurization process is
deadly required in petroleum industry. The general mechanism (Scheme 1.10) of oxidation
has also been proposed based on UV-Vis, EPR,
51
V NMR and DFT study.

Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 177

Scheme 1.10.


Scheme 1.11.
The immobilization of H
2
fsa on the surface of amino group containing silica gel phases
and the use of such phases for the extraction of different metal ions from aqueous solution
using batch equilibrium has been reported by Mahmoud et al. [66,67]. The synthesis of silica
gel bound H
2
fsa has been shown in the Scheme 1.11.
The selectivity of the different phases is evaluated by atomic absorption spectroscopy and
found with highest exchange capacity of 0.95-0.96 mmol/g for Fe(III) ion. A method for the
recycling of immobilized silica gel after metal extraction has also been demonstrated for
practical utility.
Saikat Sarkar and Kamalendu Dey 178
The synthesis and reactivity of a Cu(II) complex of N-4-acetophenyl-3-carboxy-
salicylaldimines (Figure 1.12) has been studied [68] to build up a hierarchy for similar type
metal complexes of N-substituted salicylaldimine.


Figure 1.12.
Further condensation of the ketone parts of the Schiff base and its Cu(II) complex
generates new ketimine center which leads to transamination reaction. The reaction involves
exchange of amine parts in the Schiff bases with the added amines and in situ complexation
of the freshly generated Schiff bases with Cu(II) ion present in solution.
Mononuclear complexes of Co(II), Ni(II) and Cu(II) with the Schiff base derived from
H
2
fsa and hydroxylamine hydrochloride have been characterized by infrared spectra, thermal
analysis and molar conductance studies [69]. The Co(II) and Cu(II) complexes are found to
be paramagnetic while Ni(II) exhibits diamagnetism.
The Schiff base ligand formed by the condensation of H
2
fsa and 2-
(aminomethyl)pyridine have been first investigated by Coppola et al. [70] by fast atom
bombardment mass spectrometry and metastable ion studies.
Monomeric [Cu(Hfsagly)].2H
2
O and trimeric [Cu
3
(fsagly)
2
].6H
2
O are prepared by the
reaction of CuCl
2
.2H
2
O, H
2
fsa, gycine and Na
2
CO
3
in Cu: H
3
fsagly as 1:1 and 2:1 ratio
respectively. The spectroscopic (IR, UV-Vis.) and magnetic studies proposed the trimeric
Cu(II) complex as [Cu(H
2
O)
6
][Cu
2
(fsagly)
2
] with uncoordinated glycinato O. A strong
antiferromagnetic coupling is observed in [Cu
2
(fsagly)
2
]
2-
unit with J = -185 cm
-1
[71].
The coordination chemistry of alkaline earth metals with such ligands received far less
attention than that with transition metal ions. Keeping this in view Erxleben and co-workers
[72,73] tried to synthesize Mg (3s
2
) complex with the Schiff base ligand, H
3
fsagly. The
Mg(II) complex is prepared by the substitution reaction of the corresponding Zn(II) complex
in DMSO. It is found that Zn(II) is susceptible to substitution by Mg(II) when DMSO is used
as the non-aqueous solvent. But the presence of small amount of water decrease the yield of
the Mg-complex mainly owing to the high affinity of Mg(II) for aqua ligand. The whole
observation (Scheme 1.12) has been monitored by
1
H NMR spectroscopy.
Presently the homo- and heteropolymetallic complexes are of much interest due to their
unique physico-chemical properties associated with metal-metal interactions [74,75]. Several
synthetic routes have been proposed for their synthesis, one being consists of the ingenious
use of compartmental ligands. The newly synthesized unsymmetrical polydentate Schiff base,
3-[N-2-(pyridylether)fomimidoyl]salicylic acid (H
2
fsapea), derived by the reaction of H
2
fsa
and 2-(2-aminoethyl)pyridine in ethanol in 1:1 molar ratio, belonging to this compartmental
behaviour category, is used to synthesize a series of bi-[76-79] and tri-nuclear [77,78] Cu(II)
complexes. The 3d-4f hexanuclear cluster compounds [76] are also cited using dinuclear
species as precursor.
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 179

Scheme 1.12.
In all these complexes ligand utilizes two different adjacent coordination sites, N
2
O and
O
2
and favours the formation of polymetallic systems containing phenoxo groups as
exogenous bridges.
Variable temperature magnetic susceptibility measurements for the chloro- bridged
dicopper complex, [Cu(Hpefdsa)
2
Cl
2
], show the presence of very weak ferromagnetic
coupling between the Cu(II) ions with J = 0.15 cm
-1
. But the antiferromagnetic coupling
between the two Cu(II) centres is observed in [Cu
2
(pefdsa)
2
] (J = -617 cm
-1
) and trimeric
Cu(II) complex [Cu
3
(pefdsa)
2
](ClO
4
)
2
with J = -228 cm
-1
. The Scheme 1.13 shows synthetic
routes for preparation of some of the bi- and tri-nuclear complexes.
But to explain the magnetic behaviour of the hexanuclear clusters {Cu
4
Ln
2
}, the clusters
may be taken as two individual {Cu
II
Ln
III
Cu
II
} triads. A weak antiferromagnetic Cu(II)-Cu(II)
interaction through the closed shell rare earth ion is noticed for {Cu
4
La
2
} complex having
J
CuCu
= -3.13 cm
-1
. Inspite of antiferromagnetic coupling, the {Cu
4
Gd
2
} complex shows
ferromagnetic Gd(III)-Cu(II) interaction with J
GdCu
= 6.0 cm
-1
, which is attributed to the
coupling between the Gd(III)Cu(II) ground configuration and the Gd(III)Cu(II) charge-
transfer excited configuration in which the electron is transferred from the slightly occupied
3d type copper orbital towards an empty 5d type gadolinium orbital. The Gd(III)-Cu(II)
interaction is quite peculiar in the sense that owing to the contraction of 4f orbitals, the usual
mechanisms involving 4f-3d overlap densities are inoperative [76,77].
In this connection the work of Tuna et al. [79] may be mentioned, who for the first time
reported a pentanuclear complex of {Cu
II
Cu
II
Mn
II
Cu
II
Cu
II
} moiety with the ligand H
2
fsapea
having novel magnetic properties. The IR spectrum of the complex shows two bands at 1564
and 1439 cm
-1
, attributed to the
COO
stretching modes, which are characteristic of the
bridging carboxylate groups.
The variable temperature magnetic susceptibility measurements indicate the presence of
antiferromagnetic interactions within the {Cu
II
Cu
II
Mn
II
Cu
II
Cu
II
} pentanuclear entity. The
bridging capability of the phenolic oxygen between the Cu(II) and Mn(II) ions in {Cu
4
Mn}
system might be responsible for the most probable exchange pathway for the
antiferromagnetic coupling. On the basis of the above discussion and considering the
electronic spectra the following structure for the pentanuclear complex may be proposed
(Figure 1.13). However, only x-ray structure can say the last word.


Saikat Sarkar and Kamalendu Dey 180

Scheme 1.13.

Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 181

Figure 1.13.
In continuation of this study, a new oxalato bridged dinuclear Cu(II) complex of the same
ligand, H
2
fsapea (Figure 1.14), and phenolato bridged dinuclear Cu(II) complex of the ligand
derived from H
2
fsa and N,N-dimethyl-1,3-propanediamine (Figure 1.15) has been reported
[80]. Both the complexes are crystallographically characterized and show strong
antiferromagnetic coupling interaction between the two Cu(II) centres.


Figure 1.14.


Figure 1.15.
Two dinuclear Zn(II) complexes (Figure 1.16) of unsymmetrical binucleating Schiff base
ligand 3-{N-[2-(dimethylamino)ethyl]iminomethyl}salicylic acid (H
2
fsadmen) (Figure 1.17)
have been synthesized by the reaction of ZnX
2
(X = NO
3
-
, CH
3
COO
-
) with H
2
fsa and N,N-
Saikat Sarkar and Kamalendu Dey 182
dimethylethylenediamine at neutral or slightly acidic pH [81]. In the nitrate complex,
[Zn
2
(Hfsadmen)
2
(H
2
O)
2
](NO
3
)
2
.2H
2
O the centrosymmetric Zn(II) ions are bridged by two
phenolato oxygens. Further coordination sites of the ligand are the imine nitrogen and
carboxylate oxygen, while the amino nitrogens of the ligand side arms are protonated. The
basic structure of the acetato analogue, [Zn
2
(Hfsadmen)
2
(CH
3
COO)
2
].6H
2
O is identical to
that of nitrate complex except the water ligands coordinated to Zn(II) ions in the former have
been replaced by acetate ion in the later.


Figure 1.16.


Figure 1.17.
On dissolution in DMSO or DMF these dizinc complexes are converted into mononuclear
species [Zn(Hfsadmen)]
+
and the cleavage is accompanied by migration of the ammonium
proton to the carboxylate group and coordination of the amino nitrogen to zinc. Reaction of
[Zn
2
(Hfsadmen)
2
(CH
3
COO)
2
].6H
2
O with 1(N) NaOH at pH 9.9 produces yellow cubes of
tetranuclear zinc complex, [Zn
4
(fsadmen)
4
].6.5H
2
O that is found to show asymmetry in
coordination around the four zinc centres having N
2
O
3
and N
2
O
4
coordination environments
and located at the corners of a nearly square-planar rectangle.
In contrast to H
2
fsadmen the Schiff base 3-[N-(2-pyridylmethyl)iminomethyl]-salicylic
acid (H
2
fsapma) (Figure 1.18) (formed by H
2
fsa and 2-picolylamine) forms the mononuclear
complex with zinc in acid medium (Figure 1.19). The ligand H
2
fsapma bind Zn(II) via
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 183
deprotonated phenolic oxygen, the imine nitrogen and pyridine nitrogen while the carboxylate
group remains free.


Figure 1.18.


Figure 1.19.
When a solution of the above zinc complex is brought to pH 8.9 with 0.5(N) NaOH,
deprotonation of the carboxyl (-COOH) group results to form a tetranuclear compound
[Zn
4
(fsapma)
4
].4.5H
2
O with a cubane like {Zn
4
(o-phenolato)
4
} core situated around a
crystallographic two-fold axis of symmetry.
Two tetranuclear Cu(II) assembly complexes comprised of one dimetallic di(3-
iminomethylsalicylato)dicopper(II) core and two monometallic Cu(II) auxiliaries attached to
the imino nitrogens of the dinuclear core through an alkane chain have been reported [82].
The synthetic route to the preparation is shown by the Scheme 1.14. One Cu(II) complex,
[Cu
4
(LigA)](PF
6
)
4
.2CH
3
CN.3H
2
O has one di(2-pyridylethyl)amine copper(II) as the
monometallic auxiliary and the other Cu(II) complex [Cu
4
(LigB)](ClO
4
)
4
.CH
3
OH has
1,4,8,11-tetraazacyclotetradecanecopper(II) as the monometallic auxiliary.
The cryomagnetic property suggests that the bimetallic core and the monometallic
auxiliaries are magnetically independent of each other, and a strong antiferromagnetic
interaction operates within the bimetallic core to achieve a perfect coupling above 100 K.
This is also supported by the previous magnetic studies of the similar complexes [83].
[Cu
4
(LigA)](PF
6
)
4
.2CH
3
CN.3H
2
O in acetonitrile shows a two-electron reduction at 0.08
V (vs. SCE) followed by a one electron reduction at 0.42 V. Together with EPR studies for
electrolyzed solutions, it is shown that the two monometallic auxiliaries are reduced at 0.08
V, followed by an intramolecular electron transfer from one of the reduced auxiliaries to the
bimetallic core and by the second reduction at the resulting monometallic Cu(II) centre at
0.42 V: {Cu(II)-Cu
2
(II,II)-Cu(II)}/ {Cu(I)-Cu
2
(II,II)-Cu(I)}{Cu(I)-Cu
2
(I,II)-Cu(II)}/
Saikat Sarkar and Kamalendu Dey 184
{Cu(I)-Cu
2
(I,II)-Cu(I)}. The cyclic voltammogram (CV) of [Cu
4
(LigB)](ClO
4
)
4
.CH
3
OH in
DMSO shows two couples at0.68 and 0.99 V attributable to the stepwise reduction:
{Cu(II)-Cu
2
(II,II)-Cu(II)}/{Cu(II)-Cu
2
(I,II)-Cu(II)}/{Cu(I)-Cu
2
(I,II)-Cu(I)}. The tetranuclear
complex, [Cu
4
(LigA)](PF
6
)
4
is reduced with ascorbic acid to {Cu(I)-Cu
2
(I,II)-Cu(I)} species,
whereas [Cu
4
(LigB)](ClO
4
)
4
does not undergo reduction with ascorbic acid.


Scheme 1.14.
The syntheses and structure determination of mixed valence pentanuclear manganese
complex [{Mn
II
Mn
III
(fsatren)}
2
Mn
II
(H
2
O)
4
].n(sol) where, H
6
fsatren is tris-[(2-hydroxy-3-
carboxybenzylidene)aminoethyl]amine and sol is H
2
O or MeOH and hexanuclear cobalt
complex [Co
4
II
Co
2
III
(fsaea)
2
(OMe)
4
(NO
3
)
2
(OAc)
2
(MeOH)
2
] where, H
3
fsaea is 3-[N-(2-
hydroxyethyl)formimidoyl]salicylaldehyde by T. Shiga and H. Oshio is also worth
mentioning [84]. It is clear from the crystal structure that [Mn
3
II
Mn
2
III
] complex has a linear
pentanuclear core bridged by phenoxo and carboxyl group and [Co
4
II
Co
2
III
] complex has a
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 185
face shared incomplete tetra cubane core bridged by
3
-MeO
-
, phenoxo, alkoxo and carboxyl
groups. An antiferromagnetic interaction between the Mn(II) ions in [Mn
3
II
Mn
2
III
] complex
and a ferromagnetic interaction between Co(II) ions in [Co
4
II
Co
2
III
] complex have been
proved by magnetic susceptibility studies. The structures of both the complexes are show
below (Figure 1.20).


Figure 1.20.
The technique complex as a ligand was also successfully used by R-J. Tao et al. [85] to
synthesize a 1D chain coordination polymer having chemical formula {[Cu
4
L
2
(H
2
O)].H
2
O}
n
where, H
4
L is 2-hydroxy-3-[(E)-({2-[(2-hydroxybenzoyl)imino]ethyl}imono)methyl]benzoic
acid. The polymer has been synthesized by the assembly reaction of precursor complex
K
2
CuL. 1.5 H
2
O and Cu(CH
3
COO)
2
. H
2
O in 1:1 molar ratio. The x-ray crystal structure has
shown that the polymeric chain structure has been formed by dissymmetrical tetranuclear
units and the Cu-Cu antiferromagnetic interactions have also been observed.
Double stranded monohelical complexes with exclusive M-helicity of divalent iron,
nickel, cobalt and zinc have been synthesized from an unsymmetrical chiral Schiff base
ligand, prepared by a two-step reaction of 3-formylsalicylic acid and (1R, 2R)-
diaminocyclohexane in alcoholic solvents [86]. The 1:1 condensation product was shown to
exist as a zwitterion in the solid state having pleated weak hydrogen bonding interactions.
The chiral ligand behaves as a monobasic tridentate donor system having carboxylic acid
group remains free in all the complexes. But the same ligand reacts in distinctly different way
to bind with divalent copper, in which the ligand was shown to be transformed into a
symmetric tetradentate salen type ligand with uncoordinated carboxylic acid groups.
Another most interesting diazine tetratopic helicand ligand (H
4
L) was synthesized by the
condensation of 3-formylsalicylic acid and hydrazine and the ligand was used to synthesize a
novel chiral coordination polymer which was built up from tetranuclear helicates connected
by Na ions [87]. The anionic helicates results from the self-assembly process involving the
heterotopic helicand and Co(II) and Fe(III) ions. It was reported that the tetratopic helicand
offers two different types of binding domains: one with only oxygen donor atoms and the
other one with N and O donor atoms. The two metal ions were connected by the phenoxo
bridging oxygen atoms which belong to the two chelating moieties and the oxygen of the
carboxyl group helps to build the helical motif through subsequent coordination to a third
Saikat Sarkar and Kamalendu Dey 186
metal ion. The crystal structure of the coordination polymer shows that the polymer consists
of triple-stranded dianionic helicates, [L
3
Co
2
II
Fe
2
III
]
2-
, and the three ligands twisted along N-N
single bonds. The variable temperature magnetic moment values indicate the spin states of
different metals ions. The perspective view [Figure 1.21 (a)] and the space-filling
representation [Figure 1.21 (b)] of the coordination polymer with M helicity is shown below.


Figure 1.21.
3.2. Binuclear Complexes of 3-Formylsalicylic Acid Oxime

Metal condensed compounds are of much interest due to their physico-chemical
properties arise from the interaction of the metal centres in close proximity. Generally
complex ligands having one or more sites capable of donating other metal ions are used to
synthesize metal-condensed compounds. Complex ligands with cis-dioximate groups within
the molecular framework are of particular interest [88-99] because the dioximate-bridge is
known as a good magnetic mediator between a pair of metal ions.
3-Formylsalicylic acid oxime (H
3
fsaox) is obtained [100] by the reaction of 3-
formylsalicylic acid and hydroxylamine hydrochloride in presence of NaHCO
3
.
The ligand H
3
fsaox on reaction with Cu(II) and Ni(II) salts gives the following binuclear
complexes [Cu
2
(Hfsaox)
2
]0.5H
2
O, Na[Cu
2
(Hfsaox)(fsaox)].3H
2
O, [Ni
2
(Hfsaox)
2
].2.5H
2
O,
[Ni
2
(Hfsaox)
2
(H
2
O)
4
].8H
2
O. The x-ray structure shows that Na[Cu
2
(Hfsaox)(fsaox)].3H
2
O
has a cis-arrangement of the two ligands providing dissimilar {CuN
2
O
2
} and {CuO
4
}
chromophores sharing the two phenolic oxygen atoms. The N
2
O
2
cavity has a hydrogen-
bonded N-O
.
H
.
O-N linkage as the lateral chain and the Cu(II) in this site has a square-
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 187
pyramidal geometry with a water molecule at the axial site. The Cu(II) at O
4
cavity has a
planar geometry.
[Ni
2
(Hfsaox)
2
].2.5H
2
O has a trans- configuration with respect to its two ligands and each
Ni(II) has a six-coordinate geometry with two H
2
O molecules at the axial sites. The
interconversion among the dinuclear Cu(II) and Ni(II) complexes have been established by
pH adjustment (Scheme 1.15 & 1.16).


Scheme 1.15.


Scheme 1.16.

3.3. Mononuclear Complexes of the Schiff Base Ligands Derived by the
Condensation of 3-Formylsalicylic Acid with Diamines

3-Formylsalicylic acid (H
2
fsa) on reaction with diamines in 2:1 molar ratio produces
different types of Schiff base ligands as shown in the Scheme 1.17.
Saikat Sarkar and Kamalendu Dey 188

Scheme 1.17.
These Schiff bases are capable of acting as dibasic tetradentate ligands having N
2
O
2

donor with COOH groups being remained free in the complexes except in the complexes of
U(VI)O
2
and Eu(III) ions. For these ions the ligands generally act as a tetrabasic tetradentate
O
2
O
2
donor system. Such ligands form numerous numbers of mononuclear complexes with
different transition, non-transition and lanthanide metal ions [101-117]. The corresponding
disodium salt has also been reported [118]. The general structures have been shown below in
the Figures 1.22-1.25.


Figure 1.22. Figure 1.23. Figure 1.24. Figure 1.25.
The complexes have been characterized by the help of elemental analyses, molecular
weights, magnetic moments, and molar conductance, UV-Vis., IR, ESR, CD and
1
H NMR
spectral data [119-156]. The x-ray crystal structures of some of the complexes have also been
determined [157-160].
Mononuclear complexes of Cu(II), Ni(II) and U(VI)O
2
with the Schiff base, H
4
fsadmtp,
derived by the condensation H
2
fsa and 1,5-diamino-3-thiapentane (dmtp) have been
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 189
synthesized and properly characterized. In the complexes, Ni(II) and Cu(II) lie in inner N
2
SO
2

site while U(VI)O
2
takes the outer O
2
O
2
site.
It is interesting to mention here that Kahn and co-workers [161,162] studied some spin
crossover, high-spin, low-spin Co(II) complexes with Schiff base derived from H
2
fsa and
ethylenediamine (en). The magnetic behaviour of [Co(H
2
fsaen)L] [161,162] and
[Co(H
2
fsaen)L
2
] [161,163] species clearly suggests that, in both kinds of compounds, the
lowest high-spin (S = 3/2) and low-spin (S = 1/2) states are very close in energy. Indeed,
though the
M
.T products (
M
= molar magnetic susceptibility) related to
[Co(H
2
fsaen)(EtOH)] and [Co(H
2
fsaen)(4-t-BuPy)] (where, 4-t-BuPy is 4-tert-butylpyridine)
follow, in a wide temperature range, a Curie-law characteristic of low-spin form, the slight
increase of
M
.T with temperature that is observed above ~200 K for the former complex and
~250 K for the later seems to indicate the beginning of an occupation of excited high-spin
levels. Likewise in the six-fold coordinated complexes, the ligand field appeared to
approximate the conditions suitable for the pairing of electrons: in [Co(H
2
fsaen)(3-MePy)
2
],
Co(II) is found to retain an essentially high-spin state from 300-4 K, while in [Co(H
2
fsaen)(
Py)
2
] and [Co(H
2
fsaen)(H
2
O)] it exhibited thermally induced quartet doublet spin
transitions. It is worth nothing that these transitions are very abrupt, in contrast to the
previously reported for other Co(II) complexes, which are generally of the continuous type
[164-173].
Again Thuery and Zarembowitch show the influence of the apical Lewis bases on the
spin state of the metal ion in order to forecast the nature of the L ligands that would likely to
spin-crossover compounds [174]. The Co(II) complexes of the type [Co(H
2
fsaen)L
n
] (where L
is a substituted pyridine) shows a wide range of magnetic properties . The Five-coordinate (n
=1) species with L = 2-MePy recognized a spin-quartet ground state, and its magnetic
property was described using a rhombic spin Hamiltonian ((D
2
+ 3E
2
)
1/2
= 16.7 cm
-1,
g = 2.04)
with additional temperature independent paramagnetism (N

= 211 x 10
-6
cm
3
mol
-1
). The L =
3-OHPy adduct has undergone a kinetically controlled S = 3/2 S = 1/2 crossover, while
retaining an essentially high-spin character and the cobalt complex with L = 4-MePy is in the
low-spin state even at room temperature.
The six-coordinate species (n = 2) with L = 3-MePy, 3-NH
2
Py and 3,5-Me
2
Py present a
predominant high-spin character. The effect of the nature of the apical ligands on the spin-
state of Co(II) is discussed in terms of -donor ability, orientation of the pyridine ring and
steric requirements [173,175-180].
Recently Tuna et al. [181] has reported a five-coordinate Co(II) complex containing a
photosensitive ligand which displays a thermally-induced S = 1/2 S = 3/2 conversion at
high temperature. The schematic representation of the preparation of the complex is shown
(Scheme 1.18).
The coordination of trans-1-(4-methylphenyl)-2-(4-pyridyl)ethene (t-MeSPy) is proved
by electronic spectral data which corresponds to the t-MeSPy -* absorption in the room
temperature around 315 nm (~31750 cm
-1
) [182,183].
Like other transition metal ions [112] a stable Hg(II) complex of the ligand H
4
fsapnol has
been formed by the reaction of HgCl
2
solution with the corresponding Schiff base H
4
fsapnol.
But the elemental anlyses show metal-ligand ratio as 2:1. This 2:1 complex, further on
treatment with KI solution, a transient red colouration is formed which ultimately gives a
greenish-yellow solution (with excess of KI solution) with the separation of a yellow
crystalline compound, identified as [Hg(H
2
fsapnol)] [19].
Saikat Sarkar and Kamalendu Dey 190

Scheme 1.18.
The above observation may be explained by assuming that each Schiff base molecule in
these metal chelates is also associated with one HgCl radical by displacing a hydrogen atom
in the free hydroxyl group. The Hg-O bond thus formed in the 2:1 complex is not so strong as
Hg-N bond [184,185] and as such the (>CHO.HgCl) group may easily be effected by KI
solution producing K
2
HgI
4
and [Hg(H
2
fsapnol)] (Scheme 1.19).


Scheme 1.19.
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 191
H
4
fsaen may act as compartmental ligand; the inner compartment consists of N
2
O
2
and
outer compartment O
2
O
2
donor atoms. For transition elements it uses generally the inner
N
2
O
2
coordination site while for lanthanoids (e.g. Eu(III)) it can form complexes using outer
O
2
O
2
site [113,186]. Recently both Cu(II) and Eu(III) complexes have been investigated
[186] by photo-acoustic (PA) and fluorescence spectroscopy. The outside and inside
coordination sphere shows different ligand field strength. The emission spectrum of
[Eu(H
2
fsaen)(H
2
O)
2
]Cl.H
2
O (Figure 1.26) shows four characteristic emissions of Eu(III) ( =
594, 614, 650 and 701 nm) attributable to the
5
D
0
to
7
F
1
,
7
F
2
,
7
F
3
and
7
F
4
transitions
respectively.


Figure 1.26.
The Schiff bases derived from 3-formylsalicylic acid and diamines also formed
heterochelates [106], involving quadridentate Schiff base ligands and bidentate ligands (L-L)
of the type, [M(Lig)(L-L)] (where M = Co(III), Cr(III) or Mn(III) and L-L = acac
-
, gly
-
, etc.)
(Scheme 1.20).
The same workers also reported some mixed ligand complexes of Co(III) of the type
[Co(H
2
fsaen)L
2
]X.2H
2
O. All the mixed ligand complexes were characterized with the help of
elemental analyses, molar conductances, magnetic moment values, UV-Vis., IR and
1
H NMR
spectroscopic data [187-202].


From the above observations it may be concluded that the reaction of [Co(H
2
fsaen)] with
bidentate chelating agents and oxygen to give Co(III) mixed ligand chelates in which the
dibasic quadridentate Schiff base has been rearranged from a planar to a twisted conformation
by the displacement of only one oxygen atom from equatorial plane to the planar isomer.
The Schiff bases H
4
fsaen and H
4
fsatn do not give any mixed ligand complex with Co(II)
ions, instead they produce square planar Co(II) chelates of the type Na
2
[Co(fsaen)] and
Na
2
[Co(fsatn)] respectively. These compounds are characterized with help of elemental
analyses, magnetic moment value and spectroscopic data [203-206].

Saikat Sarkar and Kamalendu Dey 192

Scheme 1.20.
The Schiff bases have been employed to synthesize varieties of oxomolybdenum (V and
VI) complexes. Detailed characterization data are also available [207-213].
Non-planar configurations of the quadridentate Schiff bases are also observed in the
Mo(VI)O
2
complexes (Figure 1.27) as discussed above.


Figure 1.27.
The tendency of the group MoO
2
to assume a cis-configuration forced the essentially
planar ligand to occupy the non-planar geometry. This aspect had been discussed earlier
[209,214]. The
1
H NMR spectral data also support this view [209-214]. 3-Formylsalicylic
acid (H
2
fsa), on treatement with boric acid, formed 3-formylsalicylato salt [215]. Thus the
Schiff bases H
4
fsaen and H
4
fsatn yielded tri-coordinated boron complexes [216]. These
complexes might have some importance in view of their industrial utility [217], biological
uses [218] and activities [219-221]. The syntheses are depicted in the Scheme 1.21.

Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 193

Scheme 1.21.
The compound as shown above is interesting in the sense that it has potentiality of being
used as a precursor for further novel syntheses. Thus it smoothly reacts with Ph
2
BCl (1:1
molar ratio) in thf at around 5
o
C in di-nitrogen atmosphere and yielded a new organo boron
derivative (Scheme 1.22).


Scheme 1.22.
The compound on reaction with Ni(OAc)
2
.4H
2
O in thf at room temperature, yielded
another novel organoboron derivative containing Ni(II) (Scheme 1.23). The study of the
reaction of Ni(II) complex with lanthanide ions will be of much interest.


Scheme 1.23.
Saikat Sarkar and Kamalendu Dey 194
Analogously Pd(II) and Pt(II) derivatives were also synthesized [222]. The corresponding
compound [Na(H
2
fsatn)B(OH)
2
] had also been prepared (Figure 1.28).


Figure 1.28.
All these compounds are solid and coloured. They are stable in air and also in their
solutions. However, the aqueous solutions of the complexes are hydrolysed on prolonged
standing and the solution turned strongly basic probably due to liberation of NaOH upon
hydrolysis.

Scheme 1.24.
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 195

Scheme 1.25.
The low values of molar conductance for boron chelates in the solvents suggest their non-
electrolytic nature. However, the conductance value in water, measured after 2 h of
dissolution, increased sufficiently indicating thereby extensive hydrolysis.
The electronic absorption spectral band positions and their molar extinction co-efficients,
when compared with the spectra of the ligands, suggest for complex formation [220,223].
The complex [Ni(fsaen){B(OH)
2
BPh
2
}] is characterized with the help of elemental
analyses, magnetic moment, UV-Vis., IR and
1
H NMR spectroscopic data [224-231].
Dey and Nandi [232] have successfully synthesized a new 1,2,3 trisubstituted benzene
derivative by using mononuclear Ni(II) complex of the Schiff base ligand, H
4
fsaen. Here
metal ions play the vital role in protecting the reactive groups.
Dey et,al. [233,234]

and Dilworth et al. [235] have synthesized lithio and silyl-
derivatives of several quadridentate Schiff base ligands and also studied their reactions
leading to new synthesis of coordination complexes, organo-derivatives of boron, titanium,
zirconium, tin and organo-oxoderivatives of phosphorus (see later discussion).
Saikat Sarkar and Kamalendu Dey 196
Lithio or silyl derivative of mononuclear complex, N,N'-ethylenebis{(3-
carboxy)salicylideneiminato}nickel(II) is easily converted to different organic compounds
and are shown in the following scheme (Scheme 1.24):
The free carboxylic acid group of mononuclear complex [Ni(H
2
fsaen)] had also been
converted to the corresponding acyl chloride functionality, which on Fridel-Craft acylation
with suitable substrates followed by normal work-up produced different organic compounds
which is shown in the Scheme 1.25.


3.4 Organoderivatives of the Schiff Base Ligands Derived From 3-
Formylsalicylic Acid and Diamines

Cobalt-carbon -bond [236,237] is found in vitamin B
12
-coenzyme. The Co(III) ion
containing a coordinated carbanion [238] in such organometallic complexes stimulated the
interests to synthesize and characterize a wide variety of organocobalt complexes with other
ligands [239-242]. Organoderivatives of dibasic tetradentate ligand with different metal ions
are also known [102,105]. Dey et al. synthesized organotin(IV) [102] and organocobalt(III)
complexes [105] of dibasic tetradentate ligands H
4
fsaen and H
4
fsapnol having general
formula shown below (Figure 1.29).

Figure 1.29.
The organoderivatives are hydrolyzed easily with aqueous mineral acids, and the light
remarkably accelerates this. This photo lability represents connection between the present
complexes and that of the corrinoids [243,244]. All the diamagnetic Co(III) complexes are
characterized by elemental analyses, thermogravimetric analysis, magnetic moments and
spectroscopic (electronic and IR) data [102,105,245-247].


3.5 Electrochemical Behaviour of the Complexes of Schiff Base Derived
From 3-Formylsalicylic Acid and Diamine

Complexes in which a ligand can bind two metal centres in close proximity are of much
interest in particular in electrochemical field. Such complexes have attracted growing
attention because of their ability to illuminate the redox properties of such complexes, which,
for instance are connected with the function of metalloenzymes incorporating two metal ions
in close proximity to the active site.
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 197
The electrochemical behaviour of a series of mononuclear and dinuclear complexes of
Ni(II), Cu(II) and U(VI)O
2
ions have been studied with the Schiff base H
4
fsaen. The
hexadentate H
4
fsaen ligand has an outer O
2
O
2
and an inner N
2
O
2
coordination site. The redox
properties of the metal ions in these two different and adjacent chambers have been
investigated [248].
It is observed that the reduction of metal centre in the N
2
O
2
compartment is greater than
that of in the O
2
O
2
compartment. The redox properties of such complexes have also been
compared with the ligand H
4
aapen derived by the condensation of o-acetoacetylphenol and
ethylenediamine and it has been seen that the H
4
fsaen complexes are in general easier to
reduce than the corresponding H
4
aapen complex [249,250].


3.6. Binuclear Complexes of the Schiff Base Ligands Derived from
3-Formylsalicylic Acid and Diamines

The chemistry of polymetallic Schiff base complexes is subject of considerable interest.
Ligands derived from the reaction of 3-formylsalicylic acid (H
2
fsa) and different diamines
have one inner N
2
O
2
core and outer O
2
O
2
coordination site capable of binding two similar or
dissimilar metal ions in these two closely placed chambers. Such homo- or heterobimetallic
complexes are useful in homogeneous catalysis [251] and biochemical field [252,253],
particularly in connection with metalloenzymes which involve two metal ions at their active
site [254]. Specially, the recognition that super oxide dismutase [255] and cytochrome
oxidase [256] contain two kinds of metal ions has stimulated an interest in heterodinuclear
complexes.
Two magnetic centres whenever brought into close proximity our natural inclination is to
assume that, like bar magnets, they will arrange themselves so that they couple
antiferromagnetically, and thus reduce the overall magnetism of the dimer. This spin-
exchange phenomenon is thus common to such bimetallic complexes [74].
Another interest in heterodinuclear complexes is to find new reactivities or functions
associated with such hetero centres where distinct features of the constituting metal ions are
accumulated or amplified to give rise to unprecedented cooperative effects [257,258]. The
potential of this polynuclear area can be gauged from the appearance of many reviews in the
literature [259-261]. All these considerations have led the investigators to investigate the
synthesis and characterization of polynuclear metal complexes with special emphasis on
hetero-polynuclear complexes.
The hydrolysis of bis(p-nitrophenyl phosphate) (BNPP) and p-nitrophenyl phosphate
(NPP) was observed to be catalyzed by the heterodinuclear Cu(II)-La(III) complex in 50%
aqueous DMSO at 35 C [262]. It was also reported that the Cu(II)-La(III) complex exhibited
a relatively higher catalytic function on NPP hydrolysis, while the hydrolysis of BNPP was
slightly more efficient in the presence of mononuclear La(III) complex.
The Schiff base H
4
fsaen and its homologous ligands having two dissimilar coordination
sites, N
2
O
2
and O
2
O
2
can form dinuclear complexes [11,263-272] sharing the bridging
phenolic oxygens [11,263]. When only transition metal ions participate in the heterodinuclear
complex, then those transition metal ions, which are higher in the Irving-Williams order,
occupy the N
2
O
2
site and those metal ions that are lower in that series occupy the outer O
2
O
2

site [265-272]. Further, during the synthesis of heterodinuclear complexes containing
Saikat Sarkar and Kamalendu Dey 198
transitions metal ions and lanthanoids, the O
2
O
2
site prefer to bind with the lanthanoids
[273,274].
The synthesis of Co-Ln [275] complexes (Ln = La, Nd or Gd) has been carried out by a
step-wise reaction, that is mono-nuclear Co(II) complex is isolated as [Co(H
2
fsaen)(Py)
2
] and
subject to reaction with a Ln(III) ion. The Co(II)-Ln(III) complexes are
[CoLa(fsaen)(CH
3
OH)(NO
3
)], [CoNd(fsaen)(H
2
O)
2
(NO
3
)], [CoGd(fsaen)(H
2
O)(NO
3
)]. In
these complexes the cobalt ion is bound at the N
2
O
2
-site and the lanthanoid ion at the O
2
O
2

site. All these complexes are quite stable in air and fully characterized with the help of
elemental analyses, molar conductivity, UV-Vis. and IR spectroscopic data [276-285].
At liquid nitrogen temperature the configuration around the cobalt is dependent upon the
nature of the base. It is suggested that substrates possessing N- and O-donor groups such as 2-
aminoethanol is specifically bind at the cobalt-lanthanoid centre via 'N' to the cobalt and 'O' to
the lanthanoid ion.
Cu(II) salts also give Cu(II)-Ln(III) hetero-binuclear complexes (Ln = La, Pr, Nd, Sm,
Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb or Lu) with the Schiff base ligands such as H
4
fsaen and
H
4
fsapn [273]

. These complexes have also been fully characterized with the help of physico-
chemical and spectroscopic data [27,286-292].
The frequencies of ligand field bands, due to Cu(II) ion bound to the N
2
O
2
site i.e.
[CuN
2
O
2
] chromophore, on forming a binuclear complex with a lanthanide ion at the
coordination site O
2
O
2
, are higher than those of mono-nuclear complexes of Cu(II) with same
ligand [263]. Such a blue shift of the d-d band may be attributed to the enhanced planarity of
the [CuN
2
O
2
] chromophore on forming a binuclear complex with a lanthanoid ion at the
coordination site.
When the complexes are dissolved in Py, DMSO or DMF, the d-d band frequency
decreases in order of the solvent DMSO>DMF>Py for the binuclear complexes where- as it
decreases in order of DMF>DMSO>Py for mononuclear complexes [273]. These trends is
due to the different affinities of solvent molecules for Cu(II) and Ln(III) ions.
The absorption spectra and circular dichroism (C.D.) spectra of Cu(II)-Gd(III)

[282, 293]
hetero-binuclear complexes suggest that substrates with a nitrogeneous and oxygeneous
groups (amino alcohols, amino acids, 8-quinolinol, amino acid esters) were specifically bound
to Cu(II)-Gd(III) centre, with the nitrogen to the copper and with the oxygen to the
gadolinium.
The V(IV)O also gives different binuclear complexes with rare earth(III) ions with the
Schiff base ligand H
4
fsaen [294]. The general formula of these complexes is
[VOLn(fsaen)(NO
3
)(H
2
O)
n
](m-n)H
2
O. where Ln = La, Pr, Eu, Gd, Tb.
The V(IV)O ion and Eu(III) ion in the respective mono-nuclear complexes is bound at the
O
2
O
2
site of the ligand, where as in the V(IV)O-Ln(III) complexes V(IV)O ion is bound at the
N
2
O
2
site and Ln(III) ion at the O
2
O
2
site because Ln(III) ion is more hard than V(IV)O ion,
strongly prefers oxygen donor atoms.
Dinuclear Cu(II)-M(II) (where M = Co, Ni, Cu, Zn, Mg, Ca and Ba) and Cu(II)-Fe(III)
heterodinuclear complexes [287] of N,N'-bis(3-carboxysalicylidene)-1,1-dibenzyl-
ethylenediamine, (H
4
fsadb) have been prepared and characterized [26,195, 264,265,269,295].
Other complexes of the series are also known. e.g. [CuM(fsadb].nH
2
O where M = Co, Ni, Cu,
Zn, Mg, Ca, Ba and [CuFe(fsadb)].3/2H
2
O. The magnetic susceptibilities, measured in the
temperature range 78-300K, indicate antiferromagnetic spin-exchange interactions operating
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 199
between metal ions. The Cu(II/I) redox potentials of the hetero metal complexes are much
lower as compared to that of [Cu(H
2
fsadb)H
2
O].
The binucleating ligand H
4
fsaen has formed Cu(II)-Me
2
Sn(IV) and Co(II)-Me
2
Sn(IV)
complexes of the type [MSn(CH
3
)
2
(fsaen)] (M = Cu, Co), where the Cu(II) or Co(II) ion is
bound at the inner N
2
O
2
site and the Sn(IV) ion at the outer O
2
O
2
site with two methyl groups
at the axial positions. Both complexes are fairly stable towards atmospheric moisture in the
solid state but decomposes into a mononuclear complex [M(H
2
fsaen)] by a trace amount of
water when dissolved in solution. Spectroscopic investigations on the Cu-Sn complex in
pyridine reveals that the coordination of pyridine to the Cu(II) is sterically hindered by the
methyl groups attached to the neighbouring Sn(IV) ion. In the case of Co-Sn complex such a
steric effect of methyl groups is not pronounced enough to hinder the coordination of pyridine
to the axial site of the Co(II). ESR spectra at liquid nitrogen temperature reveals that the
Co(II) ion adopts a penta-coordinate structure at room temperature and a hexa-coordinate
structure near liquid nitrogen temperature with pyridine molecule at the axial site [296].
Recently a side-off septadentate Schiff base ligand has been synthesized by the reaction
of H
2
fsa and bis(2-aminophenyl)disulphide (apds) [297]. Though the ligand contains eight
donor atoms (N
2
S
2
O
4
), it, however, acts as a septadentate side-off ligand leaving one
disulphide sulphur atom. Thio-ether is not a good ligand to bind class a metal ions [298] and
in this ligand it is located in an internal position within the complexing side chains as shown
in the Scheme 1.26.


Scheme 1.26.
This ligand forms several complexes with the inner N
2
SO
2
with copper ions and outer
O
2
O
2
site having transition/non-transition metal ions. The dinuclear copper complex exhibits
subnormal magnetic moment due to spin-exchange. The complexes have been characterized
by the usual physico-chemical methods and the proposed structures are given in the Figures
1.30 to 1.32.


Figure 1.30.
Saikat Sarkar and Kamalendu Dey 200

Figure 1.31.


Figure 1.32.
Nag et al. [299] has also synthesized some mono and heterodinuclear transition metal
complexes with a polydentate Schiff base ligand derived from H
2
fsa and 1,2-bis(o-
aminophenylthio)ethane.
The complexes [CoMn(fasen)(Py)
3
], [CoMn(fsapn)(Py)
3
] and [CoFe(fsapn)(Py)
3
] [Figure
1.33] have been synthesized and characterized [268]. Cryomagnetic data indicate no spin-
exchange interaction operating between the low-spin Co(II) and the high-spin Mn(II) or Fe(II)
ions.


Figure 1.33.

Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 201

Scheme1.27.
Dey et al. have shown that [Ni(H
2
fsaen)] has been successfully silylated or lithiated [224]
to get [Ni{(SiMe
3
)
2
fsaen}] and [{(Li)
2
fsaen}] which in turn react with R
2
MX
2
(R = CH
3
,
C
6
H
5
, -C
5
H
5
; M = Sn, Ti; X = Cl), R
2
BCl (R = C
6
H
5
), RPCl
2
(R = CH
3
, C
6
H
5
) and POCl
3
to
yield the complex of the type [Ni(M)
2
R
2
fsaen], [Ni(BR
2
)
2
fsaen], [Ni(PR)fsaen] and
[Ni(POCl)fsaen] (Scheme 1.27). All the complexes have been properly characterized.
Similarly mononuclear complexes of Ni(II), Pd(II) and Sn(IV) upon silylation coupled
with desilylation and reaction with R
2
SnCl
2
afforded many new organotin(IV) complexes
[300] (Figure 1.34).


Figure 1.34.
A magnetically important Cu(II)-V(IV)O heterodinuclear complex [CuVO(fsaen)CH
3
OH]
has been synthesized and confirmed by molecular structure [301]. In this complex copper ion
Saikat Sarkar and Kamalendu Dey 202
is five-fold coordinated to two nitrogens, two phenolic oxygens and the oxygen of methanol
molecule and the vanadium ion is also five-fold coordinated to two phenolic oxygens, two
carboxylic oxygens and the oxygen of the vanadyl group. The metallic ions and the oxygen of
the methanol and of the vanadyl group are in a mirror plane for the two square-pyramids
CuN
2
O
3
and VO
5
. These pyramids point in the same direction. The nature of intramolecular
interaction has been explained easily by the orthogonality of the magnetic orbitals centered on
Cu(II) and V(IV)O metallic ions, antisymmetric and symmetric respectively, with regard to
mirror plane . The magnetic behaviour of the complex is studied in the temperature 4-300 K
which reveals an intramolecular ferromagnetic coupling characterized by a ground triplet
state separated by around J = 118 cm
-1
from the excited singlet state. The magnitude of the
ferromagnetic interaction is interpreted from considerations of overlap density between the
magnetic orbitals (Figure 1.35).


Figure 1.35.
Casellato et al. has reported [302] the synthesis and characterization of a new
heptadentate compartmental Schiff base ligand (H
4
fsadmtp) synthesized by the condensation
of H
2
fsa and 1,5-diamino-3-thiapentane (dmtp) in methanol. The ligand contains an inner
N
2
SO
2
and an outer O
2
O
2
sites and gives homo- and heterodinuclear complexes with Cu(II),
Ni(II) and U(VI)O
2
. The syntheses of the complexes have been shown in the Scheme 1.28.
Perovskite type oxides (La
x
MO
y
) are known to be efficient in catalysis for oxidation
reactions [303-307]. Initially, they have been synthesized by grinding a stoichiometric
mixture of rare earth oxide and a metal oxide, and heating subsequently at 800-1000 C [308].
Unfortunately, this method generates highly heterogeneous solids with a poorly controlled
stoichiometry. An improvement for the synthesis of such perovskite compounds has been
observed by using the process of thermal decomposition of heterodinuclear complexes with
Schiff base as a ligand [309]. Cations of the heterodinuclear complexes of the type
[LaM(fsaen)]NO
3
.H
2
O (M = Ni(II), Co(II), Fe(II)) is first exchanged with the interlamellar
cation of montmorillonite, and subsequent thermal decomposition of the derivative under
oxygen at ca. 500-600 C produces a clay-perovskite oxide (La
x
MO
y
) type nano-composite
[310-312].


Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 203

Scheme1.28.

3.7. Mono- and Binuclear Complexes of the Schiff Base Ligands Derived by
the Condensation of 3-Formylsalicylic Acid with Polyamines

Cassellato et al. [21,313] have reported the synthesis of some new potentially
heptadentate compartmental ligands by the reaction of 3-formylsalicylic acid (H
2
fsa) with
diethylenetriamine (H
4
fsadien) (Figure 1.36) or bis-3-aminopropylphenylphosphine
(H
4
fsaappp) (Figure 1.37).
Saikat Sarkar and Kamalendu Dey 204

Figure 1.36.


Figure 1.37.
Both the ligands form mononuclear, homo- and heterodinuclear complexes with some
metal salts. The schematic representations of the preparation of such metal complexes with
H
4
fsadien are given below (Scheme 1.29 & 1.30).
The potentially heptadentate H
4
fsaappp ligand contains an inner N
2
O
2
P and outer O
2
O
2

coordination sites which can bind two similar or dissimilar metal ions in close proximity. This
Schiff base ligand forms mononuclear complexes with Ni(II) while analogous compounds of
Cu(II) and U(VI)O
2
are not formed. But in any case the binuclear species have been obtained.
The structures of the homo- and heterodinuclear complexes are shown in Figures 1.38 and
1.39.
Weak and strong antiferromagnetic spin-exchange has been observed in homodinuclear
Ni
2
and Cu
2
complexes respectively. The homodinuclear Cu
2
complexes have also been
employed in the oxidation of 3,5-di-t-butylcatechol (3,5-DTBC) to 3,5-di-t-butylquinone (3,5-
DTBQ). The electrochemical behaviour of the homo- and heterodinuclear complexes has also
been recorded.

Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 205

Scheme 1.29.
Dey et al. [314] synthesized and studied some mononuclear complexes of some oxo-
cations like U(VI)O
2
, V(IV)O and V(V)O with the Schiff base ligand H
4
fsadien. All the
V(IV)O complexes are paramagnetic with the
eff
ranging from 1.67-1.73 B.M., which are
quite close to spin-only value for one unpaired electron with no significant interaction
between the neighbouring vanadium ions [315,316]. On the contrary V(V)O and U(VI)O
2
are
found to be diamagnetic as expected for these ions having d
0
configuration [315,316].

Saikat Sarkar and Kamalendu Dey 206

Scheme 1.30.


Figure 1.38.

Figure 1.39.
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 207
The U(VI)O
2
complex, [(H
4
fsadien)UO
2
(NO
3
)
2
] is non-conducting in DMSO (
M
= 5.8
ohm
-1
cm
2
mol
-1
) but on prolonged standing (about 3 days) the molar conductance value is
increased and attained value of 58.5 ohm
-1
cm
2
mol
-1
. This is rationalized by the following
equation and it shows the formation of a 1:2 electrolyte in solution.



From these observations the structure of the V(IV)O and U(VI)O
2
complexes have been
proposed as in Figures 1.40 and 1.41.


Figure 1.40.


Figure 1.41.
Recently the same group of researchers thoroughly discussed the formation of
mononuclear [317], homo- and heterodinuclear [318] complexes with the same Schiff base
ligand H
4
fsadien. It has been observed that the reaction of H
4
fsadien with CoCl
2
.6H
2
O,
Ni(OAc)
2
.4H
2
O, Cu(OAc)
2
.H
2
O, Zn(OAc)
2
.2H
2
O, Na
2
MoO
4
.2H
2
O, WO
2
(acac)
2
,
(NH
4
)
2
[MoOCl
5
], (PyH)
2
[Mo(SCN)
6
], FeSO
4
.7H
2
O and FeCl
3
.6H
2
O under varied reaction
conditions led to the formation of mononuclear complexes.
On the basis of elemental analyses, molecular weights, magnetic moment values, molar
conductances and spectroscopic (IR, UV-Vis. and
1
H NMR) data the structure of the
complexes of [(H
2
fsadien)M] has been proposed as shown in Figure 1.42.


Figure 1.42.
Saikat Sarkar and Kamalendu Dey 208
The presence of cis-MoO
2
/WO
2
moiety in the complexes [(H
2
fsadien)MoO
2
] and
[(H
2
fsadien)WO
2
] (Figure 1.43) is confirmed by the presence of bands around 910-940 cm
-1

and 900-930 cm
-1
region respectively in the IR spectrum [319].


Figure 1.43.
The formation of homo- and heterodinuclear complexes has been achieved by reacting
the mononuclear Co(II) complex, [(H
2
fsadien)Co] as precursor with suitable metal salts.
The silylation and lithiation of the complex [(H
2
fsadien)Co] having two free COOH
groups with Me
3
SiCl or trimethylsilyl N,N
/
-diphenylurea (TDPU) and LiOH yielded
disilylated and dilithiated product which then smoothly reacts with (-C
5
H
5
)
2
TiCl
2
, (-
C
5
H
5
)
2
ZrCl
2
, Me
2
SnCl
2
, Ph
2
SnCl
2
and MX
2
.nH
2
O (where, M = Ni(II), Cu(II), Co(II), Pd(II),
V(IV)O and X = Cl
-
or CH
3
COO
-
) leading to the formation of some homo- and
heterodinuclear complexes including some organo-derivatives. The reaction of H
4
fsadien with
FeCl
3
.6H
2
O and Co(NO
3
)
2
.6H
2
O in access of oxygen also yields diiron and dicobalt
complexes. In all the mononuclear complexes the ligand functions either as dibasic
tetradentate (N
2
O
2
donor) or pentadentate (N
3
O
2
donor) ligand. On the other hand, in the
homo- and hetero-dinuclear complexes the ligand functions either as dibasic hexadentate
(N
2
O
2
inner and O
2
O
2
outer compartment) ligand. The Scheme 1.31 shows the sequences of
the reactions.
Coordination supramolecules of Mn(II), Ni(II) and Cd(II) with a new symmetrical N
4
O
2

hexadentate Schiff base ligand has been reported by Sarkar et al. [320]. The hexadentate
ligand was synthesized by the condensation of 3-formylsalicylic acid and triethylenetetramine
in 2:1 molar ratio and the metal complexes was synthesized using in situ condensation
reaction. The crystal structures shows that the 1D, 2D and 3D supramolecules have been
formed by different weak force interactions like H-bonding, . stacking and C-H.
interactions. Solid-state properties (e.g. electrical conductivity at different temperatures and
optical properties) of the Ni(II) and Mn(II) complexes have also been studied and depending
on the temperature, the conductivity of the complexes is found to be insulating and
semiconducting (intrinsic and extrinsic) in nature. The optical band gap (E
gd
) of Mn(II) and
Ni(II) complexes was found to be 2.57 and 2.30 eV, respectively. The representative 1D and
Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 209
2D crystal structures and the perspective view of the Mn(II) complex are shown below
[Figure 1.44, 1.45 and 1.46].


Scheme 1.31.


Figure 1.44.

Saikat Sarkar and Kamalendu Dey 210

Figure 1.45.

Figure 1.46.
Some other mononuclear transition and non-transition metal complexes have also been
synthesized and reported by the same group of researchers [321]. The Schiff base ligand and
most of the complexes have been screened in vitro to judge their antibacterial (Escherichia
coli and Staphylococcus aureus) and antifungal (Aspergillus niger and Pencillium
chrysogenum) activities and was found as efficient agent.


ACKNOWLEDGMENT

S.S. is thankful to UGC, ERO, Kolkata for providing financial assistance (No. F. PSW-
107/09-10 (ERO) dt. 08-10-09.) and K.D is thankful to the UGC, New Delhi for awarding
Emeritus Fellowship and Financial grants.

Transition Metal Complexes of Schiff Base Ligands of 3-Formylsalicylic Acid 211
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In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0
Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc.






Chapter 5



STRUCTURAL AND MAGNETIC CHARACTERIZATION
OF CU-PICOLINATE AND CU-QUINALDINATE
MOLECULAR SYSTEMS


Bogumia urowska
*

Faculty of Chemistry, University of Wroclaw, Wroclaw, Poland


ABSTRACT

Review article concerns information on a synthesis, structural and magnetic
characterization of the copper(II) compounds based on two classes of carboxylate ligands
containing heterocyclic nitrogen atom of pyridine and quinoline, e.g. pyridine-2-
carboxylate (2-picolinate, 2-pic) and quinoline-2-carboxylate (2-quinaldinate, 2-qic),
respectively. Such compounds are products of a direct reaction of picolinate or
quinaldynate acids with copper(II) salts and hydrolytic or non hydrolytic decomposition
of the some ligands. Picolinate ion forms polymeric compounds of the general formula
{[Cu(2-pic)
2
]2H
2
O}
n
, [Cu(2-pic)
2
Br
2
][(2-picH)
2
], {[Cu
2
(2-pic)
3
(H
2
O)]X}
n
, where X =
ClO
4
, BF
4
or NO
3
. The compound of the formula [Cu(2-pic)
2
] exists in three
polymorphic forms: monomeric with Cu(N
2
O
2
) chromophore and two polymeric (1D) of
the same Cu(N
2
O
4
) chromophore. With halide ions isostructural polymeric (2D)
compounds of the formula [Cu(2-pic)X], X= Cl or Br are formed of Cu(N
2
O
2
X
chromophore. However, quinaldynate ion forms compounds of the stoichiometries: two
isomeric forms of [Cu(2-qic)
2
H
2
O], which involve the same CuN
2
O
3
chromophore
(distortion isomers), and [Cu(2-qic)X], X = Cl or Br. The chloride and bromide
polymeric (2D) [Cu(2-qic)X] compounds, which crystal structure consists of two
different chromophore [Cu(N
2
O
2
X] and Cu(O
2
X
2
) are isostructural. Crystal structure of
these copper-picolinate and copper-quinaldinate systems, indicate that carboxylate group
in both ligands offers a variety of coordination modes leading to the formation of
mononuclear and polynuclear compounds. The monomeric form of [Cu(2-pic)
2
] is an
example of a square-planar copper(II) compound in which structure is achieved by
important - stacking intermolecular interaction, which leads to 1D network. Polymeric
Cu-picolinate and Cu-quinaldynate systems, based on syn-anti or out-of-plane
carboxylates (COO) and di- or monohalogenes bridges (Cl, Br) are interesting material to

*
E-mail: zurowska@wchuwr.pl
Bogumia urowska 222
magnetic investigations and magneto-structural correlations, because included
magnetically couplet copper(II) centers. This work presented also the role of non-
covalent interactions (- stacking, hydrogen bonds), stabilizing structures, in
transmission of the magnetic interactions. The magnitude of the exchange interactions
between copper(II) centers are discussed on the basis of the molecular and crystal
structures, in terms of bond properties and well-known theories and thesis of the
exchange being base explanation of the magnetic properties.


INTRODUCTION

The structure, bond properties, and magnetic behavior of copper(II) compounds are
continuous interest in inorganic and bioinorganic chemistry [1-5]. The copper ions as centers
of the active sites of various metaloproteins, play an essential role in biological processes
such as electron transfer, oxidation catalysis and dioxygen transport [6-8]. Generally, the
research of the relationship between structure and magnetic properties are important for the
understand of the fundamental factors responsible for magnetic properties [9-13] and,
furthermore, allows for modeling and understanding of the mechanisms of many bioinorganic
processes. The copper(II) complexes are the best systems to investigation the magnetic
interaction between metal centers, because of the d
9
(one unpaired electron) electronic
structure.
The copper(II) complexes characterize a structural diversity, largely related to a Cu(II) d
9

system. It enables the creation the compounds with different coordination number i.e. 4, 5 and
6, and stereochemistry [14-17]; (distorted) octahedral, distorted trigonal bipyramidal,
(distorted) square pyramidal, (distorted) square planar, (distorted) tetrahedral complexes have
been observed [for example 18-26]. However, because of the influence of the Jahn-Teller
effect square-planar-based geometries are usually preferred [27]. Steric constraints are
known to generate tetrahedral geometries. Copper(II) with regard on plasticity effect and
results from the Jahn-Teller distortion of coordination sphere, yields a polymorphic and
isomers forms [16, 26, 28]. Generally, the symmetry of the coordination polyhedron around
Cu(II) appears to be determined by subtle factors. The shape of the coordination polyhedron
is determined to a much greater extent by ligand constraints, steric hindrance, or the donor
properties of the ligand.
Copper(II) complexes are well-known from the ability of the creation of interesting
structurally and magnetically di- and polynuclear species with poli- (for example e.g. COO
-
,
CO
3
2-
C
2
O
4
2-
and

NCS
-
) [for example 29-35] and monoatomic bridges (for example e.g. -
OH, OCH
3
and Cl) [for example 36-39]. These compounds provide a substantial knowledge
to several scientific areas, including bioinorganic chemistry, solid-state physics, molecular
magnetism and material science. Particularly interesting is the phenomenon of interaction
between metal centers, which is important for physics of magnetic materials [40, 41]. On the
other hand, the study of the molecular magnetism in correlation with the structure of the
mono- and polynuclear complexes allow to know of the role of the mono- and polymetallic
active sites in biological systems [42, 43]. Many polynuclear complexes relevance as models
for active sites of biomolecules.
Among copper (II) complexes synthesis, structural and magnetic investigations of
copper(II) carboxylates have been the object of special interest [44-48]. The chemistry of
Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 223
these compounds, particularly those including N-heterocyclic donor atom has been in recent
years the subject of many studies [44,45]. The reason of this interest are their numerous
applications in diverse areas such as pharmaceuticals, fungicides, catalysts, gas occlusion
compounds and solvent extraction processes. Moreover, the attention of, bioinorganic
chemists has been directed towards the synthesis and characterization of copper(II)
carboxylates with N-donor ligands to model the active sites in metalloenzymes [49].
The carboxylate groups are the versatile ligands, able to generate diverse compounds,
mono-, di- and polynuclear] with interesting magnetic properties. The study of the magnetic
interactions in these compounds permit, on the one hand, the creation of the new magnetic
materials and building of the model systems, on the other hand. These models serve the
explanation of the role of the mono- and polymetallic active sites in protein, because some
carboxylate group play essential role as the ligands in many metalloenzymes.
It is worth to mention that the study of the magnetic interactions between the copper
centers occurring in the crystal network through non-covalent bonds (-, hydrogen bonds)
permit the knowledge of the mechanism of this interactions in the biological molecules. In
addition, polynuclear metal carboxylates are good candidates for the investigation of
exchange-coupling interaction between adjacent metal ions.
The structurally and magnetically interesting group of the d
9
carboxylate systems with
low molecular weight are the copper(II) complexes, derivatives of pyridine and quinoline, e.g.
pyridine-2-carboxylate (2-picolinate, 2-pic) and quinoline-2-carboxylate (2-quinaldinate, 2-
qic), respectively. Among these species, polymeric compounds have in their structure rare
conformations of the carboxylate group (syn-anti and out-of-plane). It is worth to mention,
that the including in the copper picolinate and quinaldynate systems, the halogene bridges is
unusual and leads to structurally and magnetically interesting polymeric complexes.
This review article presents and summarize, known in literature until now, the results of
the synthetic study, structural and magnetic analysis of the mono- and polinuclear copper(II)-
picolinate and the copper-quinaldynate systems. Magneto-structural correlations, based on
known theories and thesis, explain character of the magnetic interactions occurring through
the carboxylate and halogene bridges, as well as through weak non-covalent bonds (-
stacking, hydrogen bonds) in presented systems.


1. THE PICOLINATE AND QUINALDINATE COMPLEXES

1.1. Coordination Properties of the Picolinate and Quinaldinate Acids

Among the carboxylate compounds, containing heterocyclic donor atom, the interesting
group are (stanowi), 2-picolinate (pyridine-2-carboxylate, 2-Hpic)) and 2-quinaldinate
(quinoline-2-carboxylate, 2-Hqic) acids (Figure 1), which contain both O- and N- donor
atoms. These acids coordinated usually in deprotonated form.

Bogumia urowska 224
N COOH
N COOH
Hqic Hpic 2- 2-

Figure 1. Scheme of the structure of picolinate (2-Hpic) and quinaldinate (2-Hqic) acids.
The broad spectrum of the physiological effects of 2-picolinic acid and its derivatives on
the activity functions of both animal and plant organisms has been attributed to their ability to
form complexes with transition metals. The picolinate acid is known to form complexes of
the type M(2-pic)
2
(H
2
O)
n
with n = 0, 2 or 4 and M = Mn, Fe, Co, Ni, Cu, Zn, Cd, Mg and Hg
[50-60]. The X-ray crystal analysis of these compounds shows that the ligand acts
predominantly as N,O-chelating agent with water molecule occupying the crystal lattice
(Figure 3). Also a number of Mn-2-picolinate complexes with high nuclearity have been
reported [61].

Figure 2. Crystal structure of the Cu(2-pic)
2
2H
2
O (1) [52].
N
O
O
M
C
N
O
O
M
C
M
M
N
O
O
M
C
N
O
O
M
C
M
M
N
O
O
M
C
M

Figure 3. Scheme of the coordination mode of the picolinate anion.
Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 225
The multidentate picolinate ion is versatile ligand, coordinating in variety modes, namely
acts as N,O-, O,O-chelate, or O,O-bridge. (Fig 3). Despite its coordination modes, a chelating
five-membered ring is invariably formed.
The O,O-chelate carboxylate group forms symmetric and asymmetric chelate, and finally
monodentate complexes (Figure 4).

N
C
O
O
M
O
O
C
N
M
N
C
O
M
O

Figure 4. Coordination modes of the carboxylate.
The 2-quinaldynic acid (2-Hqic) shows also a strong N,O-chelating properties [62-71].
The 2-picolinate and 2-quinaldinate acids indicate the ability of the existing not only in
deprotonated form but also as zwitterion (Figure 5) [72, 73]. In this case the negative charge
is spread over the O-C-O group while the positive charge, formally located on the nitrogen
atom, is delocalized over the pyridine ring. The ligands acting as zwitterions coordinate to
one carboxylic oxygen, however, nitrogen atom interacts with oxygen atom through hydrogen
N-HO bonds [73].

N
H
C
O
O
N
H
C
O
O
2-Hqic
Hpic 2-

Figure 5. The 2-picolinate and 2-quinaldinate acids as zwitterions.
The neutral acid molecule is demonstrated in the structure [Cu(2-pic)
2
Br
2
][(2-pic)
2
-H] in
which nitrogen atom from [(2-pic-H)
2
]
2+
cation interacts with [Cu(2-pic)
2
Br
2
]
2-
through
intermolecular N-HBr hydrogen bond (Figure 6) [74].
The X-ray analysis of the Cu-picolinate and Cu-quinaldinate systems indicate not only a
strong N,O-chelating ability these ligands but also ability the carboxylate -O-C-O- group to
bridge between metal centers [75-81]. The inclusion in the structure containing the bridging
carboxylate groups also the bridging halogene ions (Cl, Br) leads to structurally and
magnetically interesting polymeric complexes (Part 3) [75, 76, 79].

Bogumia urowska 226

Figure 6. The molecular structure of [Cu(2-pic)
2
Br
2
][(2-picH)
2
] (3) [74].

1.2. Synthesis of Copper (II) Picolinate and Quinaldinate Complexes

The literature survey indicate that the picolinate and quinaldinate complexes of the
Cu(II) are formed not only in the direct reaction of the copper(II) salts with appropriate
carboxylate acid [50, 53, 69, 74, 77] but also are the product of the hydrolytic and non
hydrolytic processes of the degradation of the some ligands [52, 82-84].
In Table 1 known in the literature 2-picolinate and 2-quinaldinate complexes of Cu(II)
are presented.
The complex of the stoichiometry {[Cu(2-pic)
2
]2H
2
O}
n
is the product of the direct
reaction [50, 53] of the Cu(II) salt with 2-picolinic acid (1) or hydrolytic degradation
pyridyne-2-carbonitrile (2) [52]. The picolinate 3, 5, 10 and 11, and quinaldinate 12, 14 and
15 complexes are the products of the direct reaction of copper(II) salts with picolinic (2-Hpic)
or quinaldinic (2-qic) acids, respectively. However, the picolinate (4, 6) and quinaldinate (13)
complexes are the product of the oxidative P-dephosphorylation reaction of R-CH
2
P(O)(OEt)
2

phosphonate ligand leading to transformation of this ligand to R-COOH, according to
scheme [83]:

R-CH
2
-P(O)(OEt)
2
R-COOH + OHP(OEt)
2
,

where R = C
5
H
4
N or R = C
9
H
6
N. Final products of this process are copper(II) complexes with
2-pic or 2-qic ligands.
Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 227
These complexes cannot be obtained directly in the reaction of the copper(II) salts with
picolinic and quinolinic acid. These complexes are formed only in the oxidative degradation
of the phosphonate ligands. However, the complexes 10, 12 and 14 are formed in both above
reactions. The complexes 7, 8 and 9 of formula {[Cu
2
(2-pic)
3
(H
2
O)]X}
n
, where X = ClO
4
,
BF
4
or NO
3
, were prepared

by taking advantage

of the carboxylate bridge of the
metalloligand [Cu(2-pic)
2
].

Table 1. Cu(II) complexes with pyridyne-2-carboxylate and quinoline-2-carboxylate

Compound
a
Structure Chromophore Ref.
1

2
3
4
5
6
7

8

9

10
11
12
13
14

15

{[Cu(2-pic)
2
]2H
2
O}
n
{[Cu(2-pic)
2
]2H
2
O}
n

[Cu(2-pic)
2
Br
2
][(2-pic-H)
2
]
[Cu(2-pic)
2
]
[Cu(2-pic)
2
]
n
[Cu(2-pic)
2
]
n
{[Cu
2
(2-pic)
3
(H
2
O)]ClO
4
}
n

{[Cu
2
(2-pic)
3
(H
2
O)]BF
4
}
n


{[Cu
2
(2-pic)
3
(H
2
O)]NO
3
}
n


[Cu(2-pic)Cl]
n
[Cu(2-pic)Br]
n

[Cu(2-qic)
2
H
2
O]
[Cu(2-qic)
2
H
2
O]

[Cu(2-qic)Cl]
n

[Cu(2-qic)Br]
n

polimer (1D)
polimer (1D)
monomer
monomer
polimer (1D)
polimer (1D)
polimer (2D)

polimer (2D)

polimer (1D)

polimer (2D)
polimer (1D)
monomer
monomer
polimer (2D)

polimer (1D)

Cu(N
2
O
4
)
Cu(N
2
O
4
)
Cu(N
2
O
2
Br
2
)
Cu(N
2
O
2
)
Cu(N
2
O
2
O
2
)
Cu(N
2
O
2
O
2
)
CuO
4
, CuN
2
O
3

CuN
2
O
4
CuO
4
, CuN
2
O
3

CuN
2
O
4
CuNO
4
, CuN
2
O
4

Cu(N
2
O
2
Cl)
Cu(N
2
O
2
Br)
Cu(N
2
O
3
)
Cu(N
2
O
3
)
Cu(N
2
O
2
Cl)
Cu(O
2
Cl
2
)
Cu(N
2
O
2
Br)
Cu(O
2
Br
2
)
[50, 52]
[53]
[74]
[83]
[77]
[78, 83]
[80]

[80]

[80]

[75, 81, 83]
[79]
[69]
[83]
[76, 83]

[79]



1.3. Polymorphic and Isomeric Forms

The polymeric complexes 1 and 2 of formula {[Cu(2-pic)
2
]2H
2
O}
n
(Figure 2 and 7) are
polymorphic forms, in which the copper(II) ions are a doubly out-of-plane carboxylate
bridged along the a axis. The adjacent polymeric chains are joined by the lattice water chains
leading to a 2D sheet. The crystallographic parameters for both polymorphic forms are
presented in Table 2.

Bogumia urowska 228

Figure 7. Crystal structure of the [Cu(2-pic)
2
2H
2
O]
n
(2) [53].

Table 2. Crystallographic parameters for polymorphic forms of the {[Cu(2-
pic)
2
]2H
2
O}
n
[52, 53]

Compounds {[Cu(2-pic)
2
]2H
2
O}
n
(1) {[Cu(2-pic)
2
]2H
2
O}
n
(2)
Crystal system triclinic triclinic
Space group
P1 P1
a() 5.090(2) 5.172(1)
b() 7.480(4) 7.654(2)
c() 9.067(6) 9.175(2)
(
o
) 75.89(5) 74.92(3)
(
o
) 84.94(5) 84.22(3)
(
o
) 71.96(4) 71.69(3)
Z 1 1

The complexes 4, 5, and 6 are polymorphic forms of the [Cu(2-pic)
2
]. The
crystallographic parameters are presented in Table 3.






Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 229
Table 3. Crystallographic parameters for polymorphic forms of the
Cu(2-pic)
2
[77, 78, 83]

Compounds Cu(2-pic)
2
(4) [Cu(2-pic)
2
]
n
(5) [Cu(2-pic)
2
]
n
(6)
Space group P2
1
/c P2
1
/c
P1
Crystal system monoclinic monoclinic triclinic
a() 3.6975(7) 5.163(1) 5.178(3)
b() 11.9890(19) 24.658(1) 7.614(6)
c()
11.8886(19)
8.452(1) 8.109(6)
(
o
) 90 90 67.06
(
o
) 91.108(14) 92.22(1) 73.81(6)
(
o
) 90 90 71.74(6)
Z 2 4 1

The structure of 4, 5 and 6 is shown in Figure 8 and 9.

Cu1
C1
C2
C3
C4
C5
C6
O1
O2
N1

(A) (B)
Figure. 8. (a) The molecular structure of the [Cu(2-pic)
2
] (4); (b) - stacking interactions in the crystal
lattice of the compound 4 [83].
The [Cu(2-pic)
2
] (4) compound is monomeric. The crystal packing is mainly due to short
stacking (3.27 ) between pyridine rings belonging to different molecules giving rise to a
mono-dimensional polymeric network arrangement, resulting the Cu-Cu contacts of
3.8975(7) . The structures of 5 and 6 are the one-dimensional polymeric chains. Each Cu(II)
ion is connected to the two adjacent metal ions by two out-of-plane carboxylate bridges,
creating a polymeric chain along the a axis in which the CuCu distance within the chain is
3.6975(7) and 5.163(1) for 5 and 6 respectively. The Cu(2-pic)
2
molecule as a whole, are
nearly planar and forms obliquely stacked planes. The essential difference between structures
5 and 6 results from the Cu-O apical distances, which are 2.745(8) - 2.770(8), 2,737(4) ,
respectively. These differences in distances are responsible for observed magnetic properties
(see Part 5.1.1 )
Bogumia urowska 230

(A) (B)
Figure 9. The molecular structure of the [Cu(2-pic)
2
]
n
5 (a) and 6 (b) [77, 78].
These compounds are the coordination isomers, with the different coordination number,
which are 4 for 4, and 4+2 for 5 and 6, and these last are also called polymeric isomers [16].


Figure 10. The molecular structure of Cu(2-qic)
2
H
2
O (12) [69].
The monomeric compounds with quinaldinate ion 12 and 13 of formula [Cu(2-qic)
2
H
2
O]
are isomeric forms, in which 5-coordinated copper centers (CuN
2
O
3
) differ from each other
the geometry of the coordination sphere (geometrical distortion). This is the result of the
plasticity coordination sphere of the copper(II) and their ability to receive differ
stereochemistry.


2. INTRODUCTION TO THE MAGNETISM OF THE MAGNETIC
EXCHANGE COUPLED SYSTEMS

In transition metal complexes containing more than one metal atom with unpaired
electrons, the observed magnetic behavior often differs from the predicted sum of the
Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 231
properties of the component units. This phenomenon is due to a coupling of the electron spins
and is termed intramolecular anti- or ferromagnetism, depending upon whether antiparallel or
parallel spin coupling, respectively, is found in the ground state.
In numerous transition metal complexes magnetic interactions between metal centers is
transmitted through mono-(e.g. Cl, Br, -OH, OCH
3
) or multiatomic bridges (e.g. OCO, N
3
XCN, X=O, S, Se). In these compounds metal-metal distance is 3-5 . For monoatomic
bridges this distance is about 3 , and for polyatomic bridges is about 5 [85]. Therefore
magnetic interactions do not result from direct metal-metal interaction, but occur through
bridging ligand. These intramolecular interactions, because of the large distances, are often
termed as superexchange.
In experimental studies, the energy of the magnetic interaction of magnetic centers
through the bridge for copper(II) dimers between the local spins S
i
and S
j
for atoms i and j is
given by Heisenberg Hamiltonian [69, 88]: H = -2JS
i
S
j
, where J is exchange parameter,
called also isotropic interaction parameter. Positive values of J indicate a triplet ground state
(ferromagnetic coupling), while for negative values, the singled state is lower in energy
(antiferromagnetic coupling). Generalizing, this expression for many interacting of the
magnetic centers within a molecule is received: H = -2 J
ij
S
i
S
j
.
Much experimental and theoretical works in recent decades have been done on the
mechanism of this exchange coupling. Mechanism of magnetic coupling have been described
by Goodenougha [87] in terms of the overlap of the d orbitals on one metal ions with the s
and p orbitals on a bridging anion and with the d orbitals on the other metal. According to the
conception of Kahn [9] and Alvarez [88], on strength of the observed antiferromagnetic
coupling decides the magnitude of the overlap of the magnetic orbitals (build up from the d
orbitals of the metal and p orbitals of the ligand atom on the appropriate symmetry). Maximal
overlap leads to strong antiferromagnetic coupling. When the overlap between magnetic
orbitals is zero, the antiferromagnetic contribution is also zero and the coupling is purely
ferromagnetic. The overlap criterion of the orbitals is confirmed by Hay theory [89], which
on the basis of the calculations for Cu(II) dimers, based on theory of molecular orbitals, state,
that the increase of the electron density on the orbital bridging ligand leads to increase of the
antiferromagnetic coupling (increase of the value |J|). However, decrease of the electron
density leads to decrease antiferromagnetic coupling`(decrease of the value |J|). This
conclusion confirms Hodgson, Hatfield and other [90]. According to Kahn theory, the
exchange coupling is the sum of the ferromagnetic (F) and antiferromagnetic (AF)
contributions i.e. J = J
F
+ J
AF
. In this model the value of J
AF
is proportional to the square of
the integral overlap (S
2
) [91, 92]. Therefore, the magnitude of antiferromagnetic interaction is
governed primarily by the overlap of two magnetic orbitals centered on the nearest neighbor
copper(II) ions. The magnitude of the antiferromagnetic interaction is more sensitive on
change of the structural parameters, deciding on degree of the overlap of the magnetic.
orbitals. At very unfavorable structural conditions of the overlap, the coupling will be
ferromagnetic (J
AF
0).
Summing up, mechanism superexchange interactions between metal centers through
bridging ligands for coupled systems is based on concept overlap of the two magnetic orbitals
and delocalization of the electron density unpaired electron in direction of the orbital of the
bridging ligands. This factors decides on the sign and magnitude of interactions expressed by
J parameter. In other words, the magnitude of the ground spin with regard to the excited spin
Bogumia urowska 232
is explained in a topologic way from the map of the overlap density. The symmetry of the
metal orbitals, that contains the unpaired electron density, and the symmetry of the bridging
atom about this overlap decides.


3. MAGNETO-STRUCTURAL CORRELATIONS

Magneto-structural correlation based on investigation of the influence a topological way
(geometry of the bridge, stereochemistry of the central ion) occurring between metallic
centers through the bridged ligand, permits to determine magnetic orbitals of the central ions
and the ligands involved in magnetic interaction. Knowledge of the geometry of the
superexchange permits the explanation of the sign and magnitude of the magnetic exchange
parameter, J.
Due to known of the plasticity of the coordination sphere, the Cu(II) adopts in the
complexes different stereochemistry with coordination number: 4, 4+1 or 4+2 with four
atoms in plane and eventually with one or two in axial position, leading to square-planar or
tetragonal pyramid (SP) structure or tetragonal distortion octahedron, respectively. In these
three cases, unpaired electron is on a d(x
2
-y
2
) orbital however, for 4+1 trigonal bipyramid
(TBP), on dz
2
orbital. For geometry between SP and TBP, unpaired electron is on a d(x
2
-y
2
)
orbital with some admixture of a dz
2
. Stereochemistry of the copper(II) ions as well as
geometry of the bridge have essential meaning for explanation of the magnetic properties for
coupled systems.


4. ROLE OF THE CARBOXYLATE AND HALOGENE BRIDGES
IN TRANSMISSION OF MAGNETIC EXCHANGE

4.1. The Conformation of the Carboxylate Bridges

Copper(II) carboxylates are structurally a very diverse group of coordination compounds
due to the various coordination behavior displaying distinct bonding modes towards metal
centers such as monodentate and chelate, as well as bridging ligands (Figure 3). Different
coordination behavior of the carboxylato group lead to the formation of the mono- di- and
polynuclear structures. Carboxylate can assume many types of bridging conformations, the
most important being monoatomic and triatomic syn-syn, syn-anti and anti-anti (Figure 11).
Different conformations are responsible for observed magnetic properties which are from
strongly coupled to moderate or weak antiferromagnetic and even ferromagnetic ones.
Copper(II) compounds in which carboxylate group adopts syn-syn conformation, exhibit
strong antiferromagnetic coupling (singlet-triplet distance is about 300 cm
-1
) [29]. The
classical example is dimeric copper(II) acetate [Cu(CH
3
COO)H
2
O]
2
[93], for which singlet-
triplet distance is -284 cm
-1
. Weak antyferro- or ferromagnetic interactions are observed for
complexes, in which carboxylate group adopts syn-anti conformation [see e.g. 75, 76, 79, 85,
94-97]. For anti-anti conformation weak or moderately antiferromagnetic coupling is
observed [98-100]. For the coupling through monoatomic bridge interactions are very weak
antiferromagnetic [101, 102]. It is worth to mention, that in spite of large Cu-Cu distances in
Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 233
the complexes with syn-anti conformation, anti-anti is more favorable for transmission of the
coupling. This shows that the 2p orbitals of the oxygens are favorable oriented to give more
effective overlap with magnetic copper orbitals. It is interesting, that the complexes with
bridging carboxylate group in syn-anti and anti-anti conformation are ever rare, because anti
electron pair on the oxygen atom indicates a lower basicity than the syn ones [103, 104].
Therefore, the largest group are these, which adopt syn-syn conformation.


Figure 11. Conformations of the carboxylate group.

4.2. The Carboxylate Bridges Syn-Anti Type

Generally, the weak ferro- and antyferromagnetic interactions observed in copper(II)
complexes, which copper centers are connected carboxylate bridges in syn-anti conformation,
is result this conformation leading to poor overlap of the magnetic orbitals. The structural
features of the bridge, geometry of the coordination sphere and manner of the coordination,
which may be (Fig 12): equatorial-equatorial (Type I), axial-equatorial (Type II) and axial-
axial (Type III) type, are additional factors responsible for the kind and magnitude of the
magnetic interactions.

C
R
Cu
Cu
O
O
R
C
Cu
Cu
O
O
R
C
Cu
Cu
O
O
Typ I Typ II Typ III

Figure 12. Relative orientation of d(x
2
-y
2
) magnetic orbitals of copper(II) and 2p orbitals of oxygen for
carboxylate bridge in syn-anti conformation.
C
R
Cu Cu
O O
R
C
C
R O
C
R
O O
Cu
Cu
C
R
C
R
C
R O
O
Cu Cu
Cu
O
C
R
O
Cu
_
syn syn
syn anti
_ anti anti
_
monoatomowe
wiazanie
Bogumia urowska 234
Generally, as it has been stated by several authors and also substantiated by DFT
calculation [32] syn-anti Cu-O-C-O-Cu carboxylate bridge leads to weak magnetic
interactions because 2p orbitals of oxygen atoms belonging to the magnetic orbitals centered
on Cu(II) ions are unfavorably oriented to give a significant overlap.
Figure 12 presents mutually orientation of the magnetic orbitals of Cu(II) and 2p orbitals
of oxygen resulting into weak antyferromagnetic (I), weak ferromagnetic (II) and near zero
interactions.
Very important factor which has an influence on magnitude of superexchange coupling is
non-planarity of the Cu-O-C-O-Cu bridge (an out-of-phase exchange pathway), measured by
the dihedral angle. For high dihedral angles the overlap of the magnetic orbitals is reduced,
which implies a reduction of the antiferromagnetic contribution and, consequently,
ferromagnetism is dominant. The strongest ferromagnetic coupling is expected for a dihedral
angle of 90
o
[80].


4.3. The Carboxylate Bridge Out-of-Plane Type

The interesting group of the copper(II) carboxylate are rare complexes in which
carboxylate group bridges in out-of-plane type (Figure 13) leading to very weak
antiferromagnetic interactions. [77, 78, 105].

C R
O
O
Cu
Cu

Cu
Cu
C R
O
O

(A) (B)
Figure 13. (a) Single carboxylate bridge of out-of-plane type; (b) Relative orientation of the d(x
2
-y
2
)
magnetic orbitals of Cu(II) and 2p orbitals of oxygen atoms of carboxylate group.
In this type of complexes, the magnetic orbitals of the Cu(II) interact through orthogonal
2p orbitals of the oxygen atom. Generally, magnetic coupling for all known out-of-plane
polynuclear compounds is relatively weak, because of the near-orthogonality of magnetic
orbitals, as it has been shown for carboxylato [77, 78], chlorido- [37, 106], carbonato- [107]
or oximato- [108] bridged compounds. In this case of the magnetic interactions in apical-
equatorial bond modes, the orthogonality of magnetic orbitals leads to a coupling which must
be very weakly antiferromagnetic or weak ferromagnetic and even near zero.


Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 235
4.4. Halogene Bridges (Cl, Br)

The halogene bridges, beside the carboxylate bridges, play essential role in transmission
of the magnetic interactions. These bridges included in the structure of the carboxylate
derivatives of the pyridine and quinoline, build interesting polymeric structures (Part.5.2.1. )
[76, 79].
In the past two decades the copper(II) complexes containing single (-Cl) and double (-
Cl)
2
bridges have been the object of numerous theoretical analysis [89] and magneto-
structural correlations [37, 106, 109]. In the majority of known halogene-bridges di- and
polinuclear Cu(II) complexes, the bridges are out-of-plane type (apical-equatorial bond mode)
with bridging angle about 90
o
. (Figure 14, Type I). This conformation leads to very weak
ferro-and antyferromagnetic interactions, characterizing small value of the coupling
parameter |J | [37, 106].

Cu
Cu
Cl

Cu
Cu
Cl

Cu
Cu
Cl

Type I Type II Type III

Cu
Cu
Cl

Type IV
Figure 14. Bridging type for Cu(-Cl)Cu system.
Exceptional in respect of topology of chloro- bridge, reported so far, are three structurally
and magnetically characterized copper(II) complexes with linear and near linear Cu-Cl-Cu
bridge of apical-apical mode ( Figure 14, Type II) [110, 111], which leads to weak
ferromagnetic interactions and these with equatorial-apical bridge (Figure 14, Type III) [76]
for which moderately strong antiferromagnetic coupling is observed. The type IV (equatorial-
equatorial bridge) is rare and rather characterize other bridging ligands [112].


Bogumia urowska 236
5. STRUCTURE AND MAGNETIC PROPERTIES OF THE POLYMERIC CU-
PICOLINATE AND CU-QUINALDINATE SYSTEMS

Structures of the polymeric picolinate and quinaldinate complexes presented in the
literature are based on, depending on the compounds (Table 1), carboxylate bridges out-of-
plane (5 and 6) and syn-anti type (7, 8, 9, 10, 11, 14, and 15). Additionally, in the structure
of 10, 11, 14 and 15 halogene bridges (Cl or Br) are included.


5.1. Picolinate Complexes

5.1.1. Structure and Magnetic Exchange through Out-of-Plane Carboxylate Bridges
Molecular structure of 5 and 6 compounds of formula Cu(2-qic)
2
H
2
O as it is seen from
Figure 9 and as mentioned in Part 1.3. is an infinite linear one-dimensional (1D) polymeric
chains [Cu(2-pic)
2
]
n
results from the fact that the copper(II) ions are sequentially doubly
bridged by carboxylate groups [77, 78]. The structures are stabilized by weak C-HO
hydrogen bonds (Part 6). Coordination polyhedron around the copper can be described as a
strongly distorted octahedron (4+2). Both compounds are parallel-planar type with out-of-
plane carboxylate bridges (Figure 14, Type I). The magnetic behavior of these picolinate
complexes can be explained as a results of the magnetic exchange within the chains through
long Cu-O axial bond (2.737(4) and 2,745(8)-2.770(8) for 5 and 6, respectively).
The small values of the exchange parameters J for 5 and 6 of -0.73 and -1.04 cm
-1
,
respectively, are in accordance with the expection for this out-of-plane type bridges with the
orthogonality of the orbitals (Figure 15).

Cu
Cu

Cl
Cu(2)
Cl

Figure 15. Bridging type for Cu(-Cl)Cu system.
On magnitude values of J obtained decides not only topology of the bridges, causing the
weak delocalization of the spin density unpaired electron located on the dx
2
-y
2
orbital in
direction an axial position of the bridging oxygen, but also significant axial bond Cu-O
distance. Sequence of |J | (5) < |J | (6) is in accordance with difference of the Cu-O axial
distance (d
cu-o
(5) > d
cu-o
(6)) observed. Both compounds are example of the influence the
axial bond on the magnetic properties and indicates that the magnetic interactions may be
transmitted, through long apical ligand distance. Weak interactions between copper(II)
Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 237
centers through out-of-plane carboxylate bridge has been observed for other complexes (J
from 0.5 to -1 cm
-1
) with long axial distance (2.28-2.68 ) [108]. Comparison between the
J values for [Cu(2-pic)
2
]
n
(5 and 6) and for out-of-plane single carboxylate bridged
compounds [105], reveals that the monocarboxylato-bridged series exhibit weaker
antiferromagnetic coupling. This is consistent with the simple orbital model proposed by
Kahn et al. [116, 117], in which magnetic coupling is proportional to the square of the
overlapping integral. So, for mono-out-of-plane bridged copper(II) compounds, the values of
coupling constant are smaller due to a decreasing number of the bridging groups.

5.1.2. Structure and Magnetic Exchange through Syn-Anti Carboxylate and Halogene
(Cl, Br) Bridges
Molecular structure of the polynuclear complexes of formula: {[Cu
2
(2-pic)
3
(H
2
O)]ClO
4
}
n
(7) , {[Cu
2
(2-pic)
3
(H
2
O)]BF
4
}
n
(8), {[Cu
2
(2-pic)
3
(H
2
O)]NO
3
}
n
(9) contains syn-anti
carboxylate bridges [80]. These complexes were synthesized by taking advantage of the
carboxylate bridge of metalloligand [Cu(2-pic)
2
] building block. Isomorphous 7 and 8
complexes are constructed by fish backbone chains through syn-anti (equatorial-equatorial)
carboxylate bridges, which are linked to one another by syn-anti (equatorial-axial)
carboxylate-bridges, giving rise to a rectangular grid-like two-dimensional net [80] (Figure
16, 17).



Figure 16. Metallocycle formed in the complex 7 and 8 [80].

Bogumia urowska 238

Figure 17. Two-dimensional layer in the complex 7 [80].
The magnitude of the magnetic coupling in 7 and 8 through carboxylate bridges defines
the exchange parameters J (chain) and J (side), respectively, according to scheme (Figure
18):


Figure 18. Magnetic exchange scheme in the complexes 7 and 8 [80].
The values of the superexchange parameters, assuming J = J = J, are J = 1.74 cm
-1
, J
= 0.19 cm
-1
for 7, and J = 0.99 cm
-1
, J = 0.25 cm
-1
for 8. The difference between two values
J and J for 7 and 8 is a result of the difference of the dihedral angles in the Cu-O-C-O-Cu
carboxylate bridge. Because, in the backbone of the chain (J) the dihedral angle (48.5
o
),
which is measure of non-planarity bridge, is greater from this (31.6
o
) in the side chain (J'), the
stronger ferromagnetic coupling (J > J) in 7 is observed. The same arguments explain the
stronger exchange coupling (J > J) observed in 8, where the dihedral angle is 48.0
o
and 31.8
o
,
respectively.
The structure of 9 is one-dimensional polymeric chain formed by alternating syn-anti
carboxylate-bridges (Figure 19).

Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 239

Figure 19. Alternating chain in 9 [80].
The geometry of the Cu(1) is intermediate between square pyramid and trigonal
bipyramid (Adison parameter [115] is 0.47). In contrast, the arrangement about Cu(2) is an
elongated octahedral. Therefore, it was assumed, that both copper(II) atoms are connected
through equatorial-equatorial syn-anti carboxylate bridges [80].
The magnitude of the magnetic coupling in 9 through carboxylate bridges defines the
exchange parameters J and J, according to scheme (Figure 20):


Figure 20. Magnetic exchange scheme in complex 9 [80].
The obtained the value of the parameter J and J is 1,19 cm
-1
. This value is very close to
that observed for compounds 7 and 8, where very similar syn-anti carboxylate bridges are
present [80].
The structure of the polymeric complex [Cu(2-pic)Cl]
n
(10) is presented in Figure 21
[75]. The element of the structure is the Cu
4
cluster. Namely, each carboxylate group links in
syn-anti conformation two copper centers, forming a 16-membered ring (-Cu-O-C-O-)
4
. Each
copper(II) ion of an individual tetrameric units is connected to others through a
dichlorobridge (-Cl
2
) resulting in the layer (2D) structure. The copper is five- coordinate
with CuNO
2
Cl
2
chromophore (4+1). Consideration of the O(1a) atom, included in
semicoordination leads to 4+1+1
*
type coordination. Local CuNO
2
Cl
2
geometry involves a
very distorted five-coordinate stereochemistry, intermediate between two idealized
geometries: square-pyramidal and trigonal-bipyramidal, as indicates structural index = 0.39
[115].

Bogumia urowska 240
C1
C2
C3
C4
C5
C6
N1
Cl1
Cu1
O1
O2
O1a
Cl1a
O2a

(A) (B)
Figure 21. The fragment of Cu(2-pic)Cl structure (10); (b) The view of the layer structure (2D) of
[Cu(2-pic)Cl]
n
[75].
The [Cu(2-pic)Br]
n
complex (Figure 22) is izostructural with [Cu(2-pic)Cl]
n
. Hydrogen
contacts of C-H-X (X = Br or Cl, respectively)) type stabilize the structure of 10 and 11.


(A) (B)
Figure 22. The fragment of [Cu(2-pic)Br]
n
structure (11); (b) The view of the layer structure (2D) of
[Cu(2-pic)Br]
n
[79].
The bridges Cu-O-C-O-Cu in 10 and 11 indicate the same structural features. The
parameter is 0.39, indicating the same stereochemistry. However, reliably some structural
differences in halogene bridges, essential with magnetic point of view, are observed. Namely,
The Cu-Cu distances in dimeric units are 4.446(2) and 3.676(2) for 10 and 11,
respectively. The bridging distances Cu-Br (2.390(1) and 2.849(1) ) are longer than these
Cu-Cl (2.242(4) and 2.756(4) ). Bridging angle Cu-X-Cu are 90.79(2)
o
and 87.9(1)
o
for
X=Cl and Br, respectively. The magnitude of the magnetic coupling through dihalogene and
Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 241
carboxylate bridges defines the exchange parameters J and J , respectively, according to
scheme presented in Figure 23.

Figure 23. Scheme of magnetic exchange in complexes 10 and 11.
They are J = 15 and 8.31 cm
-1
for 10 and 11, respectively, and J = 0.38 and 0.34 cm
-1

for 10 and 11, respectively. The results obtained indicates that the magnetic interactions
inside of the layer is ferromagnetic, and ferromagnetic interaction through chloride-bridge is
larger than through bromido-bridge, according to sequence: J(Cl) > J(Br).
Weak ferromagnetic interactions through the carboxylate bridge observed for 10 and 11
complexes is results of the syn-anti conformation and low site symmetry of the chromophore
group (C
2v
), which causing a weak delocalization of the spin density towards the 2p oxygen
orbital of the COO bridge. Additionally, non-planarity of the Cu-O-C-O-Cu bridge leads to
stronger ferromagnetic coupling.


5.2. Quinaldinate Complexes

5.2.1. Magnetic Exchange through Syn-Anti Carboxylate and Halogene (Cl, Br)
Bridges
The crystal structure of the [Cu(2-qic)Cl]
n
(14) consist of copper(II) ions sequentially
bridged through carboxylate groups in the syn-anti conformation forming an infinite one-
dimensional zigzak chain with two alternating non-equivalent copper(II) chromophores:
CuO
2
Cl
2
on square-planar geometry and CuN
2
O
2
Cl on geometry involves a very distorted
five-coordinate stereochemistry, intermediate between two idealized geometries: square-
pyramidal and trigonal-bipyramidal, as indicates structural index = 0.64 [115]. The
neighbouring chains are linked by linear mono-chloride atoms (bridging angle Cu-Cl-Cu is
180
o
) link adjacent chains, forming a ribbon type structure (1D).


(A)
Figure 24. Continued.
Bogumia urowska 242

(B)
Figure 24. (a) The fragment of [Cu(2-qic)Cl]
n
structure (14); (b) View of ribbon type structure (1D) of
[Cu(2-qic)Cl]
n
[76].
The planes of the quinoline rings are stacked, and additionally, the contacts C-HCl
stabilize the crystal structure (Figure 25).


Figure 25. Arrangement of the [Cu(2-qic)Br]
n
(14) ribbons of the compound 14 in the crystal lattice .
Hydrogen contacts of C-HO and C-HBr type are shown with dashed lines [79].
The [Cu(2-pic)Br]
n
(15) is izostructural with [Cu(2-pic)Cl]
n
(14). Similarly as in the case
picolinate complexes (10 and 11) the some structural differences in halogene bridges are
observed. The distances Cu-Cu in bridged unit Cu(-X)Cu is 4.860(3) (X=Cl) and 5.149(2)
(X=Br). The bridging distances Cu-X are 2.376(2) and 2.515(4) (X=Cl), and 2.490(2)
and 2.659(2) (X=Br).
The crystal structure of Cu(2-qic)Cl suggests that two kinds of coupling parameters must
be considered to interpret the magnetic properties, according to the scheme presented in Fig
26.

Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 243
J
2 J
2
J
2
J
2
J
2
J
1
J
1
J
2
Cu
Cu
Cu
Cu

Figure 26. Scheme of the magnetic exchange in complexes 14 and 15.
where J
1
and J
2
are the constants for exchange coupling via the mono--chlorobridge (or
bromide bridge) in the dimeric unit and the carboxylate bridge in the chain, respectively. The
values parameters coupling are for Cu(2-qic)Cl) (14): J
1
= -57 cm
-1
, J
2
= 0.37 cm
-1
, and for
Cu(2-qic)Br) (15): J
1
= -102,5 cm
-1
, J
2
= 0.37 cm
-1
.


5.3. Magneto-Structural Correlation for Halogene Bridges

As it is seen from the Table 2, the coupling between metallic centers in the complexes 14
and 15 in the chain (carboxylate bridge) is ferromagnetic, however, between the chains
(halogene bridge) is moderately antiferromagnetic and |J| (Cl) > |J| (Br) sequence is
observed.
One of the major problem that remains open in magnetochemistry research is to discover
the factors which determine whether the magnetic interactions in singly and doubly
chlorobridged copper systems will be antiferromagnetic or ferromagnetic. For such systems
some theoretical analyses [91] have been presented.

5.3.1. Monohalogene Bridges
From the Table 3 it is seen, that antiferromagnetic coupling between copper(II) centers
through mono-chloride and bromide bridges is dominating in Cu(2-pic)Cl (10) and Cu(2-
pic)Br (11). It is worth to emphasize that the antiferromagnetic coupling is the strongest one
observed for halogeno-bridged systems up to now. The structures of the complexes with
linear Cu-Cl-Cu bridges are known, but besides carboxylate compound 14 [78], only two
with other ligands including linear 16 [11o] and near linear (177.35
o
) (17) [111] were
characterized magnetically.
For the complexes including linear Cu-Cl-Cu systems with bridging angle of 180
o

moderately strong antiferromagnetic (14) and very weak interactions are observed. As results
with Table 4, presented structural parameters for linear and nearly linear Cu(-Cl)Cu bridges
in correlation with coupling parameters J, bridging angle directly not determined
magnitude of the coupling through chloride-bridge. Also such parameters as Cu-Cu and Cu-
Cl distances and structural parameter , have not larger influence on value of J parameter.



Table 4. Coupling parameters J and symmetry of the chromophore group for the chloride (10, 14) complexes and its
bromide analogs (11, 15)



Compound


Type of bridge
a)
Coupling parameter J (cm
-1
)

Chromophore Group Symmetry

Reference
(-X)
2
(-X) OCO
J
1
(cm
-1
) J
2
(cm
-1
)
Cu(2-pic)Cl (10) 15.0 0.38 Cu(N
2
O
2
Cl) C
4v
D
3h
(C
2v
) [75]
Cu(2-pic)Br (11) 8.31 0.34 Cu(N
2
O
2
Br) C
4v
D
3h
(C
2v
) [79]
Cu(2-qic)Cl (14) -57.0 0.37 Cu(N
2
O
2
Cl)
Cu(O
2
Cl
2
)
C
4v
D
3h
(C
2v
)
D
4h

[76]
Cu(2-qic)Br (15)

-102.5 0.37 Cu(N
2
O
2
Br)
Cu(O
2
Br
2
)
C
4v
D
3h
(C
2v
)
D
4h

[79]
X= Cl lub Br;

Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 245
Table 5. Structural and magnetic parameters for complexes with linear
bridge Cu(-Cl)Cu

Compound
a
CuCu
()
R
()
Cu-Cl-Cu
(
o
)

symmetry
J
(cm
-1
)
Ref.
Cu(2-qic)Cl (14) 4.86 2.51, 2.65 180 0.64
b
(C
2v
) -57.0 [76]
[Cu(tach)
2
Cl]
5+
(16) 5.3 2.34, 2.65 180 0.07 (D
4h
) -0.86 [110]
Cu
2
(-Cl)(L)
2
(ClO
4
)
3
(17) 2.75, 2.71 177.35 0.06 (D
4h
)
0.03 (D
4h
)
-1.30 [111]
a) R- Cu-Cl distance, - Adison parameter [119]
b) concern of Cu(2)
c) -bridging angle

Chloride bridges in 16 and 17 compounds belong to II type (axial-axial), however, the
compound 14 to type III (axial-equatorial) (Figure 14). Fig 27 shows the scheme of the
bridges and mutual orientation of the copper(II) magnetic orbitals and 2p ligand orbitals for
above complexes.


O
O
Cl
Cu(1)
Cl
Cu(2)
O
N
O
N

Cu(2)
O
O
O
O
Cl
Cu(1)
N
N
Cl Cl

Cl
N
N
N
N
N N
Cu
N
N
Cu

N
N
Cl
N
N
N
N
N
N
Cu
Cu

Cu(2-qic)Cl (14) [Cu(tach)
2
Cl]
5+
(16)
Figure 27. Relative orientation of magnetic orbitals in Cu(2-qic)Cl (14) and [Cu(tach)
2
Cl]
5+
(16).
According to Kahns theory [116, 117] the sign and magnitude of the magnetic exchange
coupling are very sensitive to the orientation of the unpaired electrons on metal ions.
Different geometries usually result in different energies (and orientation). Such a different
orientation of the d orbitals in the cited compounds must be responsible for the magnetic
behavior.
The explanation of the magnetic properties of the 14 and 16 and 17 is based on
determination of the superexchange geometry and topology of the spin density of the
unpaired electron. From Adison structural parameters [115] it is evident, that the geometry of
the copper(II) coordination sphere in 16 and 17 is near square pyramid (D
4h
), in which axial
position occupy chloride atom. In this case weak delocalization of the spin density in
Bogumia urowska 246
direction of the axial position is expected. So, in spite of bridging angle of 180
o
, in 16 and 17
compounds of an axial(apical)-axial(apical) type only weak antiferromagnetic coupling
through chloro-bridge is observed. Stronger coupling observed in 14 is a result of
significantly delocalization of the spin density of the copper magnetic orbital in direction of
the equatorial position occupied by a chloride atom. Then, the Cu(1)-Cl(1)
eq
pathway in 14 is
more effective in allowing for the spin delocalization than Cu-Cl
ax
, pathway in the mono-
chloro-bridged dimers 16 and 17 of an axial(apical)-axial(apical) type, an increase of the
exchange transmitted through the bridging chloride ion in 14 is expected. On the other hand,
the distortion from a square-pyramidal towards a trigonal-bipyramidal copper coordination
geometry ( = 64) is expected to increase the spin density on the bridge. For this distortion,
magnetic orbital of copper(II), on which is localized the spin density of the unpaired electron,
is dx
2
-y
2
with admixture of the dz
2
. Then partial delocalization of the spin density on 2p
orbital of the chloride atom in axial position occurs. This is consistent with relationship
between Addison structural parameter and the magnitude of the constant coupling |J|,
observed for other systems with chloride-bridged connecting five-coordinated copper centers
[37, 106]. Generally, the Adison parameter plays an important role in determination of
magnetic interaction. It has been pointed out that the greater is this parameter, the higher is
the spin delocalization on the bridge, consequently, the stronger is the antiferromagnetic
coupling and vice-versa. Namely, this confirms the Hays theory [89], which on the basis of
calculations on a hypothetical mono-chloro-bridged copper(II) dimer predicts an increase of
the antiferromagnetic coupling as such a distortion proceeds. However, the parameter has a
minor influence on the relatively superexchange interaction in 14 compound. Mutual
orientation of the equatorial plane of Cu(1) and Cu(2) (Fig 27) is mainly responsible for the
observed strength of the magnetic interaction.
In summary, for 14 compound better overlap of the copper magnetic orbitals with ligand
orbitals leads to, the stronger antiferromagnetic coupling, compared with 16 and 17
compounds. So, the electronic and structural features of the linear Cu-Cl-Cu bridge in 14 are
favorable for the propagation of strong interaction. These features also explain strong
antiferromagnetic coupling observed in bromide analog Cu(2-qic)Br (15), J = -102.5 cm
-1
.

5.3.2. Dihalogene Bridges
Although there is not simple correlation in the case of chloride bridges, Hatfield [109]
has obtained interesting magneto-structural correlations which show that the sign and the
strength of coupling occurring through the bridging chloride ions in di- and polynuclear
copper(II) complexes depend critically on the structural parameter /R
o
, where is the Cu-
Cl-Cu bridging angle and R
o
the longer Cu-Cl distance (out-of-plane) within the bridge. For
bromide bridges this correlation is not observed [79, 118, 119]. Alves et all. [120] presented
correlation in a variety of chloro-bridged copper(II) dimers. The empirically established
correlation between J and /R
o
leads to conclusion that for the values lower than 32.6
o

-1
,
and higher than 35
o

-1
the antiferromagnetic magnetic exchange is observed, whereas the
ferromagnetic coupling appears when the value of this structural parameter is intermediate
between these two values. Ferromagnetic coupling through dichloro-bridge in Cu(2-pic)Cl
(14) is well correlated with the calculated structural parameter (J = 15 cm
-1
, /R
o
=33.2
o

-1
).

However, in the case of dibromo-bridged copper(II) compound Cu(2-pic)Br (11) the
exchange value J does not correlate with /R
o
. Namely, for /R
o
< 32.6, i.e. 31.9
o

-1

Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 247
ferromagnetic exchange was found (J = 8.32 cm
-1
). Thus, values of the exchange coupling do
not correlate with the bridging angle or bridging distance R
o
. It is in accordance with earlier
observations [118, 119] which indicate that there is no simple magneto-structural correlation
for bromo-bridged dimmers as it was found for dichloro-bridged copper(II) complexes.

5.3.3. Correlation between J(Br) and J(Cl)
The larger antiferromagnetic interaction in [Cu(2-qic)Br]
n
(15) through the bromide
bridge (J = -102.5 cm
-1
) than that observed in [Cu(2-qic)Cl]
n
(14) through the chloride bridge
(J = -57 cm
-1
), in spite of a longer CuCu distance (5.149(2) ) in the bromide bridging unit
than that of the chloride compound (4.860(3) ), may be explained on the basis of the fact,
that the magnetic orbital of bromide atom contacts easier with the copper atom than that of
chloride (the orbitals 3p of the bromide atom, in contrary to 2p orbitals of chloride atom are
energetically nearier of the 3d orbitals of copper atom). In other words, the contribution of the
orbital overlap between Cu(II) and bridging chloride atom, suggesting that the spin density
localized on the bridging Br atom is a larger than that on the bridging Cl atom. Relationship |J
| (Br) > |J | (Cl) is consistent with the value of the exchange constant observed for other
antiferromagnetic monohalide bridging compounds [118, 119].
The dihalido-bridges (-Cl)
2
transmit the ferromagnetic exchange with J = 8.31 and 15.0
cm
-1
in [Cu(2-pic)Cl]
n
(10) and [Cu(2-pic)Br]
n
(11), respectively. Thus, in contrary to
relation |J| (Br) > |J | (Cl) obtained for [Cu(2-qic)Br]
n
(15) and the chloride analog, the
sequence |J | (Cl) > |J| (Br) is observed for 10 and 11. According to Kahn theory: J = J
F
+ J
AF

[91-94]. Because the magnetic orbital of bromide atom contacts easier with copper atom than
chloride, the antiferromagnetic contribution J
AF
in J should be larger in the case of bromide
compounds. This model may explain the observed increase of |J| along the sequence Cl, Br
of briding atoms in Cu(2-pic)X and, Br, Cl of bridging atoms in Cu(2-qic)X. Concluding, the
superexchange pathway Cu-Br-Cu is more favorable for propagation of magnetic interactions
than Cu-Cl-Cu, and generally relationship is observed [79, 125], for the antiferromagnetic
coupling: 2J
AF
(Cl) J
AF
(Br), and for ferromagnetic interaction: J
F
(Cl) 2J
F
(Br).


6. MAGNETIC INTERACTIONS THROUGH NON-COVALENT
INTERACTIONS (H-BOND AND - STACKING)

Studies of very weak non-covalent intermolecular interactions, such as hydrogen bonds
[126, 127], - stacking of aromatic rings [128-131] are of fundamental importance not only
for further development of inorganic supramolecular chemistry and prediction of crystal
structure, but these contacts also generate interesting supramolecular properties, such as
electrical, optical and magnetic ones [132], and play a major role in the functioning of
biological macromolecules [133, 134]. Tabl. 6 shown exchange coupling parameters zJ (z is
the number of nearest neighbors) obtained for Cu(2-pic)
2
(4, 5, 6) and Cu(2-qic)
2
H
2
O (12,
13) complexes.




Bogumia urowska 248
Table 6. Parameters of the magnetic coupling in 4, 5, 6, 12 and 13 complexes

Compound Type
interactions

zJ (cm
-1
) Oddziaywanie
poprzez mostek
out-of-plane
-O-C-O-
J (cm
-1
)
Ref.

Cu(2-pic)
2
(4) - stacking
C-HO
-0.76
-0.47
[83, 135]
[Cu(2-pic)
2
]
n
(5) C-HO -0.06 -0.73 [77]
[Cu(2-pic)
2
]
n
(6) C-HO 0.34 -1.04 [78, 83]
Cu(2-qic)
2
H
2
O (12) O-HO -0.25 [83, 135]
Cu(2-qic)
2
H
2
O (13) O-HO -0.23 [135]


6.1. Mononuclear Systems

The crystal structures of the [Cu(2-pic)
2
Br
2
][(2-pic-H)
2
] picolinate complex (3) (Fig 6)
indicate that the molecules are isolated in the crystal lattice and for that reason the magnetic
interactions between copper centers are not observed.
As it was mentioned earlier (Figure 8) intermolecular short (3.27 ) - stacking
interactions in Cu(2-pic)
2
(4) lead to one-dimensional (1D) network arrangement (Fig 8),
resulting a Cu-Cu contacts of 3.6975(7) . Further hydrogen bonds, additionally stabilizing
structure, link Cu(2-pic)
2
molecule leading to three-dimensional network. Crystal packing of
4 is presented in Figure 28.


Figure 28. The crystal structure of Cu(2-pca)
2
(4). Hydrogen bonds are shown with dashed line [83].
Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 249
The obtained exchange coupling constants J = -0.76 cm
-1
, responsible for the -
stacking and zJ

= -0.47 cm
-1
, responsible for the hydrogen bonds interactions, indicate
stronger antiferromagnetic coupling through the - stacking. In 4 an interaction through an
offset - stacking (1.73 ) between the pyridine molecules occurs (Figure 29) with a
perfectly planar copper complex, allowing for the optimal stacking interaction. The mutual
positions of coplanar pyridine rings show a very small value of the interplane distance (3.27
) and often observed centroid-centroid distance of 3.70 . However, the angle between the
centre-centre line and the normal to the plane, of about 30
o
, is large. For centroid-centroid
distances up to 3.8 , being approximately the maximum distance for which - interactions
are accepted, this displacement angle, observed for pyridine molecule, lies around 20
o
. This
angle corresponds to a horizontal displacement of 1.30 .

Magnetic interaction through - stacking can have very weak antiferromagnetic [135-
138] or weak ferromagnetic [139, 140] character. Influence of the structural factor, such as
Cu-Cu (R) distance, centroid-centroid distance R, distance between planes R
2
, offset R
1
and
displacement angle , as also influence of electronic factors (participation of and
electrons of the aromatic rings and d copper(II) ions) on magnitude and sign of J has been
for several complexes the subject of the discussion [135]. Analysis of the structure and
magnetic interactions in these complexes suggests that the interplane and offset distances are
substantial parameters which could influence on the strength of magnetic exchange coupling
between copper(II) centers. So, both short interplane and relatively large offset distances
could be responsible for a larger antiferromagnetic exchange through - stacking interaction
observed in 4.

)
R
1
R
2
R
N
N
Cu
Cu
R

Figure 29. Geometry of the pyridyl rings in Cu(2-pca)
2
(4); R = 3.70 , R
1
= 1.73 , R
2
= 3.27 , =
30
o
[134].
The crystal structure of the Cu(2-qic)
2
H
2
O (12) (Figure 30), which molecular structure is
depicted on Figure 10, present the layer (2D), created by strong O-HO hydrogen bonds
(OO The spectroscopic studies of the complexes 12 and isomer 13, for which lack of the X-
ray data, indicate that the structure of 13 is also stabilized by strong O-HO hydrogen
bonds.
Bogumia urowska 250

Figure 30. The crystal structure of Cu(2-qic)
2
H
2
O (12). Hydrogen bonds are shown with dashed line
[141].
The coupling parameters of zJ = -0.25 (12) and -0.23 cm
-1
(13) indicate the weak
antiferromagnetic coupling transmitted by H-bonds [141].
Polynuclear systems. The molecular structures of isomeric forms of [Cu(2-pic)
2
]
n
5 and 6
are one-dimensional chains (1D) formed by double out-of-plane carboxylate bridges (Figure
9). The weak C-HO hydrogen bonds and contacts link the chains forming two-dimensional
(2D) network (Figure 31, 32).


(A) (B)
Figure 31.The crystal structure of Cu(2-pic)
2
(5). (a) Corrugated layers formed by planar molecules of
Cu(2-pic)
2
of adjacent chains; (b) The layer (2D). Hydrogen bonds of C-HO type are shown with
dashed lines [77].
Exchange coupling parameters indicate weak antiferromagnetic (zJ= -0.06 cm
-1
) in 5 and
weak ferromagnetic (zJ= 0.34 cm
-1
) in 6 interactions through hydrogen bonds. These
interactions are weaker than those transmitted through out-of-plane bridges (Table 5).
The role that hydrogen bonds play in the transmission of magnetic interactions is still not
completely understood. For many years, hydrogen bonds have been reported to propagate
essentially antiferromagnetic interactions between metal centers in variety of transition metal
complexes [142]. Even Cu dimer with O-HO distance of 2.32 with high J value of -90
a
b
Structural and Magnetic Characterization of Cu-Picolinate and Cu-Quinaldinate 251
cm
-1
has been reported [143]. Recent theoretical studies have been able to rationalize the
antiferromagnetic coupling between copper(II) complexes mediated by hydrogen bonds
[143].

(A) (B)
Figure 32. The crystal structure of Cu(2-pca)
2
(6);(a) Layers formed by planar molecules of Cu(2-pca)
2

of adjacent chains; (b) The layer (2D). Hydrogen bonds of C-HO type are shown with dashed line
[78].
In recent years, ferromagnetically coupled hydrogen bond systems are growing
exponentially, either some supramolecular copper structures, or even some organic radicals
interactions has been observed but the mechanism of these interactions is not completely
understood [143-148].
Although the ligands (2-pic) are the same in 5 and 6 complexes and the Cu(II) ions are
doubly bridged by carboxylate out-of-plane bridges, the packing of the two complexes is
different (Figure 31, 32). In these compounds difference in H-bond networks are responsible
for different magnetic properties (F and AF). Both compounds show C-HO intermolecular
hydrogen bonds with similar OH distance in the range 2.43-2.49 and 2.40-2.49 in 5 and
6, respectively. However, the relative CO donoracceptor separations in C-HO
hydrogen bonds in 5 are shorter (3.161-3.278 ) than those (3.287-3.419 ) in compound 6.
The shorter Cu-O distance in 5 (1.944(7 ) than this in 6 (1.957(3) ) is also observed. On
the other hand, the relative bond angles C-HO in 5 of 150
o
and 166
o
are more favourable
for transmission of the magnetic interaction through the H-bonds than those in compound
6 (140
o
, 137
o
, 143
o
). The above structural factors could explain the differences in the sign of
the superexchange coupling observed in compounds 5 and 6, because the stronger coupling
correspond to the shorter hydrogen bonded donoracceptor distance [W] and shorter
distance between copper ions and oxygen atom included in H-bond. These conclusions
confirm earlier investigations [143, 144].
The crystal structure of the [Cu(2-pic)
2
Cl] (9) and izostructural [Cu(2-pic)Br] (11) (Fig
25) indicates that the magnetic interactions may be transmitted through non-covalent
interactions (H-bond network and - stacking). However, lack of model do not permit the
calculation of J parameter, characterizing these interactions.


Bogumia urowska 252
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In: Transition Metals: Characteristics, Properties and Uses ISBN 978-1-61324-559-0
Editor: Ajay Kumar Mishra 2012 Nova Science Publishers, Inc.






Chapter 6



REVIEW: TRANSITION METALS IN MEDICINE


Hanan F. Abdel-Halim
Pharmaceutical Chemistry Department, Faculty of Pharmacy,
Misr International University, Cairo, Egypt


INTRODUCTION

Opportunities exist to exploit inorganic chemistry in the discovery and development of
pharmaceuticals. Preparation of model compounds, synthesis of potential medicinal agents
and imaging agents are the new area of pharmaceutical researches[1]. This involves the
synthesis of metal complexes, usually of relatively small molecule ligands, which in some
way mimic the naturally occurring metallomolecules, or which have desirable properties such
as solubility, stability in vivo, selective absorption into certain tissues, are the main core of
studying metals in medicine.
Fear of metal toxicity is a limiting factor, but may be, in part, a matter of perception. Not
all metals are bad and not all metals are "heavy metals", yet, even essential metals are toxic at
certain levels and in some chemical forms [2,3]. The key is to understand and to control the
interaction of the metal with the living system. Metal metabolism is emerging as an exciting
area of cell biology and a potential site for therapeutic interventions where normal metal
metabolism appears to maintain free metal ion concentrations at a very low level and to
deliver metals very selectively to their sites of action, while maintaining tight control over
their reactivity [3].
The unique properties of metal complexes may offer advantages in the discovery and
development of new drugs. These unique properties include redox activity, Lewis acidity,
electrophilicity, access to cationic/anionic/radical species, flexible bond orders, unique
geometries, easily accessed structure/activity variations, and magnetic, spectroscopic, and
radioactive signatures. The fundamental properties of metals and of metal-ligand chelation
chemistry remain an important area for research. Examples include regulation of spin
relaxation processes, complex stability, ligand exchange kinetics, and other physico- chemical
properties (electrochemical potentials, fluorescence quantum yields, ligand pKa values,
etc.).[3] Metals can be useful probes of cellular function. Understanding these interactions is
Hanan F. Abdel-Halim 264
paving the way toward rational design of metallopharmaceticals and implementation of new
co-therapies.
Metal complexes can be potent and highly selective ligands of cell surface receptors. As
metal complexation is the basis for chelation therapy and to rectify abnormal metal
accumulations or toxic metal exposures (e.g., iron overload; lead, cadmium, and mercury
poisoning),improving chelator designs are needed to enhance selectivity, affinity, stability,
renal clearance, and oral activity, while maintaining low toxicity and low cost.
Ligand must be designed to optimize desired metal complex properties (e.g:
thermodynamic and kinetic stability, hydrolytic stability, catalytic activity, molecular weight,
charge, lipophilicity, water solubility, targeting functionalization, and ligand metabolism).In
addition, the essential transition metal ions are accumulated by cells, to be used as required
cofactors, and to catalyze cytotoxic reactions in which several families of proteins are
emerging to control the activity of intracellular metal ions and to help confine them to vital
roles. These include integral transmembrane transporters, metalloregulatory sensors, and
metallochaperone proteins [soluble metal receptor proteins] that protect and guide metal ions
to targets [3].
In this review we try to present the importance of some examples of transition metals in
the treatment of certain diseases and their role in avoid these diseases.


METTALOENZYMES

Metals play roles in approximately one-third of the known enzymes. Metals may be a co-
factor or they may be incorporated into the molecule, and these are known as
metalloenzymes. Amino Acids in peptide linkage posses groups that can form coordinate-
covalent bonds with the metal atom , the free amino and carboxyl group bind to the metal
affecting the enzymes structure resulting in its active conformation [4].
The metalloproteins are part of enzymatic systems, have structural functions, and use the
protein to be transported to their target site in the organism. In enzymes, the metals participate
in catalytic processes as:

constituents of enzyme active sites.
stabilizers of enzyme tertiary or quaternary structure.
contributors in forming weak bonding complexes with the substrate that can carrying
out the orientation of the substrate for reactions.
Stabilizers for charged transition states.

As constituents of active sites, metal cations with unpaired electrons mediate oxidation
reduction (redox) processes by reversible changes in their oxidation state, transferring or
receiving electrons to or from the substrate and co-factor. For example, human superoxide
dismutases reduce one superoxide anion to hydrogen peroxide, and oxidize a second
superoxide anion to generate molecular oxygen by means of either Cu or Mn present in the
active site of the cytosolic or mitochondrial enzyme, respectively. The presence of metals
bound to lipids, nucleic acids, and carbohydrates is well documented, but the biochemical
functions of the metals present in these molecules is unclear.
ac
w
st
di
ov
th
co
im
an
pr
co
co
th
be
de
un
m
m
sy
be
st
ch
sy
cl
m
m
pr
Fi
th
su
w
w
Because m
ccepting an el
with anionic a
tructure and fu
isrupt this ele
verall effectiv
Nucleases
hat contain a
omplexes, wh
mportant signi
nd in the deve
ropose a simp
ontain, recent
ontaining two
hese complex
enzimidazolyl
erivatives, and
nderstand the
multinuclear
metallonuclease
ynthetic multi
etween metal
tudies and com
hemistry that p
ynthetic metal
leavage (Fig
metallonuclease
multinuclear m
rinciples of co

igure 1. DNA h
Transition
hey mimic the
ubstrate. Meta
with more than
whatever molec
R
metals resembl
lectron pair to
and neutral li
unction but m
ectron flow th
veness of the m
which are me
variety of d
ich can media
ificance in elu
elopment of t
ple mechanism
progress has e
or more Fe (I
xes include
l- and pyridyl
d their conjug
e differences
metallonuclea
es; the rela
inuclear meta
sites and lig
mparison must
provides insig
llonucleases m
gure 1).In a
es and the cha
metallonuclease
oordination an
hydrolytic cleav
state is a key
e structure of
al's larger size
n one ligand. M
cule the metal
Review: Transi
le protons (H
+
o form a chem
igands. This
makes the enzy
hat the metal w
metalloenzyme
etalloenzymes
different meta
ate phosphodie
ucidation of t
the biomacrom
m for these en
extended to th
III), Zn (II), C
natural and
l-based organi
gates to polyp
in structure
ases; the
ationship betw
llonucleases;
gands in the c
t be illustrated
ght into how ch
may lead to the
addition, the
allenges that sh
es with DNA
nd enzymatic c
vage catalyzed b
y role in the
f the substrat
e relative to p
Metals typica
l interacts with
ition Metals in
+
) in that they
mical bond, th
characteristic
yme it is part
would normal
e.
s that have a w
al ions, there
ester bond cle
the catalytic m
molecule - tar
nzymes due to
he design of sy
u (II), Co (II/I
d non-natural
ic molecules,
peptides or o
and compos
design stra
ween the stru
and the coo
courses of ph
d. Indeed, ther
hanges in met
e same overall
e solvation
hould be faced
A sequence or
chemistry [5,6
by synthetic mu
competitive i
tes transition
protons is com
lly react with
h. If a metal is
n Medicine
y are electroph
hey may act a
c of metals i
of pH depend
lly help facili
wide variety o
fore, design
eavage via hyd
mechanisms f
rgeted drugs.
o the variation
ynthetic multin
III), or Ln (III
l organic m
azamacrocyc
ligonucleotide
ition between
ategies of
uctures and n
operativities b
hospodiester l
re are features
tal ions and lig
l outcome of p
effect of
d toward the d
structure sele
].
ultinuclear meta
nhibition of m
state in the r
mpensated for
two, four, or
s bound with tw
hiles that are
as general aci
is helpful in
dent. Changes
tate and thus
of active site
and synthesis
drolytic pathw
for the natural
Despite the d
n of metal ion
nuclear metall
I/IV) ions. The
molecules, i.e
lic and amino
es. Owing to
n natural and
synthetic m
nucleolytic ac
between metal
inkage hydro
s that converg
gands of both n
phosphodieste
synthetic m
development o
ectivity by ap

llonucleases.
metalloenzym
reaction of en
by their abili
r six ligands. A
wo ligands it w
265
capable of
ids to react
enzymatic
s in pH can
inhibit the
motifs and
s of metal
ways, are of
l nucleases
difficulty to
ns that they
lonucleases
e ligands in
e., mainly
ocarboxylic
be able to
d synthetic
multinuclear
ctivities of
l sites, and
lysis, deep
e about the
natural and
r backbone
multinuclear
of synthetic
pplying the
mes because
nzyme and
ity to react
A ligand is
will form a
26
lin
of
m
po
T
pr
im
to
re
(s
pH
di
ox
sy
re
tr
ac
re
an
m
of
di
tr
ne
re
se
pr
is
ni
w
to
m
66
near complex
f a square that
metal sits in th
ossess groups
he free amino
rotein to a sp
mportant in th
ogether and he
As transiti
eactions of act
superoxide,
H and chelatio
ioxygen and
xidative dama
ystems the co
eactions appea
ransport prote
ctive metals [
eaction of any
ntioxidant is a



Chromium
metabolism, bu
f risk factors a
Insufficien
iabetes and
riglycerides, to
Severe sig
europathy that
Chromium
eceptor numbe
ensitivity [10-
revent weight
s better absorb
icotinic acid).
well. Chromiu
olerance factor
mechanism of a

. So that, if th
t is planer or i
he center of a
s with the abil
o and carboxy
pecific, active
hat metals pla
elp establish an
on metal cata
tivated oxygen
;
on govern the
oxy-radicals
age to phosph
oncentrations
ars to be relat
eins (ferritin,
[7].Antioxidan
y substance w
any substance
is not only a
ut also, its diet
associated with
t dietary intak
cardiovascula
otal cholestero
gns of diabet
t were refracto
improves in
er, and phosp
-12]. Research
gain associat
bed than othe
Other forms
um is an esse
r." Despite th
action is not k
Hanan
e metal reacts
t will form a t
an octahedron
lity to bind to
l groups in a p
e conformation
ay a role in b
n active confo
alysis is recog
n species (par
hydrogen per
e reactivity of
and therefo
holipids, DNA
of redox-act
tively low. Ho
transferrin, c
nt has been d
with dioxygen
that

hinders a
CH
an essential el
tary intake is
h diabetes and
ke of chromiu
ar diseases
ol, reduced HD
tes including
ory to insulin w
nsulin functio
phorylation of
h has shown
ted with the u
er forms, in w
of chromium,
ential nutrient
his, chromium
known [13-16]
F. Abdel-Hal
s with four liga
tetrahedral stru
n. Amino acid
o the metal re
protein can bi
n. The fact th
bringing remo
ormation of the
gnized as bein
rtially-reduced
roxide H
2
O
2
;
the transition
ore influence
A, and other b
ive transition
owever, under
ceruloplasmin,
described as a
n. The more
free radical re
HROMIUM
lement requir
often sub opt
d cardiovascul
um leads to inc
including ele
DL-cholesterol
weight loss,
were treated b
n by increas
f the insulin
that chromiu
use of the diab
which, chromi
, such as chro
t forming the
m remains the
.
im
ands the meta
ucture, and wh
ds in their pep
esulting in coo
ind to the met
hat metals bin
ote parts of th
e enzyme.
ng integral to
d forms of dio
hydroxyl radi
n metals as we
the apparent
iomolecules i
n metals capa
r certain cond
, etc.) may f
any substance
mechanistic

d
eaction
ed for normal
timal in the pr
lar diseases.
creases in risk
evated circul
l, and impaire
glucose into
by supplement
ing insulin b
receptor lead
um(III) picolin
betic drug as c
ium is bound
omium glycina
e active com
only essential
l will be set in
hen six ligand
ptide linkage
ordinate-coval
tal and this ma
nd to several
he amino acid
o the generatio
oxygen or ox
ical OH) ,facto
e mentioned b
t mechanisms
is initiated. In
able of cataly
ditions metal s
furnish additio
that interfere
definition stat
l carbohydrate
revention and
k factors assoc
lating insulin
d immune fun
olerance and
tal chromium
binding to ce
ing to increas
nate (Figure 2
chromium pol
to vitamin B
ate chelate, m
mponent of th
l transition m
n the center
ds react, the
in proteins
lent bonds.
ay bind the
ligands is
d sequence
on and the
xy-radicals
ors such as
before, with
by which
n biological
yzing these
storage and
onal redox
es

with the
tes that an
e and lipid
alleviation
ciated with
n, glucose,
nction.
peripheral
[8, 9].
lls, insulin
sed insulin
2) helps to
ynicotinate
B3, known(
ay work as
e "glucose
metal whose
Fi
so
to
ar
th
an
at
de
ef
or
tr
ef
pr
ph
an
ca
ne
di
th
co
ty
fu
nu
m
igure 2. Chromi
While the t
olubility , Cr (
oxic systemica
re uncertain, th
hrough cell m
nd the difficu
ttributable to
etoxification p
ffect. While re
r near the cell
If Cr (VI)
ransported int
fficiently by a
roteins and DN
hosphate back
nd larger pept
an be dissocia



Copper is
eeded to abso
ismutase (SOD
he body runs
ollagen (the
yrosinase, whi
unction.
Copper com
umber of body
maintain and re
R
ium (III) picolin
toxicity of chr
(VI) compoun
ally than Cr (
his variation i
embranes and
ulty of absorb
the Cr(VI) f
process when
eduction of Cr
nucleus of tar
is reduced to
to cells and
an anion transp
NA, this creat
kbone of DNA
tides and prote
ated with chela
an essential t
orb and utiliz
D) [22]. Copp
on. Synthesis
"glue" that
ich plays a rol
mbines with c
y functions, o
epair connecti
Review: Transi
nate.
romium comp
nds, which are
III) compoun
in toxicity may
d its subseque
bing Cr(III) b
form as the r
it occurs at a
r(VI) may ser
rget organs[17
o Cr (III) ext
so toxicity is
port system it
tes adducts inv
A, N-7 of guan
ein molecules
ators, such as E
C
trace element
ze iron. It is
per is needed
s of some ho
holds connec
le in the produ
certain protein
thers help to f
ive tissues [23
ition Metals in
pounds are var
powerful oxid
ds. Although
y be related to
ent intracellula
y any route.
reduction of C
distance from
rve to activate
7-20] .
tracellularly, t
s not observe
is reduced ins
volving the six
nine, and amin
. These ternar
EDTA.
COPPER
t present in th
s also part of
to make aden
ormones requi
ctive tissue t
uction of skin
ns to produce e
form cross-lin
3]. References
n Medicine
ried due to the
dizing agents
mechanisms
o the ease with
ar reduction to
The toxicity
Cr (VI) is co
m the target sit
chromium to
this form of t
ed[21]. As C
side the cells t
x coordination
no acids, such
ry DNA comp
he diet and in
f the antioxid
nosine triphosp
ires copper, a
together). In
pigment (mel
enzymes that
nks in collagen
s and further r
e oxidation st
appear to be m
of biological
h which Cr (V
o reactive inte
of chromium
onsidered to
te for toxic or
xicity if it tak
the metal is n
Cr(VI) enters
to Cr(III) whi
n sites of Cr(II
as cysteine, g
plexes are very
n the human
dantenzyme,
phate (ATP),
as does the sy
addition, th
anin), require
act as catalyst
n and elastin a
reading may b
267
ate and the
much more
interaction
VI) can pass
ermediates,
m is mainly
serve as a
r genotoxic
kes place in
not readily
cells very
ch binds to
II) with the
glutathione,
y stable but
body. It is
superoxide
the energy
ynthesis of
e enzyme,
s copper to
ts to help a
and thereby
be available
26
fo
es
fa
go
a
su
co
m
of
co
an
fo
po
al
co
dr
co
Fu
ib
pr
Fi
th
co
pr
an
68
or this article.
specially impo
actor leading t
It appears
oes beyond a
wide range o
usceptibility o
opper plays a
mediated dama
Copper has
f chest wound
opper helps pr
nti-ulcer and
or treating co
ossess anti-in
lways have s
ompounds, it h
rugs are their
It has been
opper tryptop
urther, it has
buprofen and
romote norma

igure 3. Copper
Copper has
hat are not the
opper [25]. T
rocesses invol
nd diabetes ar
To view refer
ortant for the h
to an increased
clear that the
decrease in th
of disturbance
of lipoproteins
a vital role in
age and disease
s also been us
ds and the pu
revent inflamm
anti-inflamma
onvulsions and
nflammatory a
significantly
has been hypo
copper chelate
n demonstrated
phanate (Figur
been shown
enefenamic a
al wound heali
r aspirinate.
s a role in the
mselves anti-c
The hypothes
lving copper-d
re diseases of
Hanan
rences and fur
heart and arter
d risk of devel
decrease in a
he activity of c
s in other ant
s and heart tis
the protectio
e.
sed as a medic
urifying of dri
mation in arth
atory medicine
d epilepsy. W
activity, and
stronger acti
othesized that
es[24].
d that copper c
re 4), marked
n that, wherea
acid suppress
ing while at th
prevention of
convulsants ex
sis that coppe
dependent enz
f specific tissu
F. Abdel-Hal
rther reading y
ries. Research
loping coronar
antioxidant pr
copper-depend
tioxidant enzy
sue to peroxid
on of the card
cine for thous
inking water.
hritis and simil
es containing
With the know
the finding t
vity and hav
the active for
complexes su
dly increase
as non-steroid
wound healin
he same time r
f seizures. It w
xhibit anticon
er complexes
zymes and tha
ues in disrepa
im
you must purc
suggests that
ry heart diseas
rotection caus
dent antioxida
yme systems.
dation, provid
diovascular sy
sands of years
Recently, res
lar diseases. R
copper, and
wledge that m
that these co
ve lower tox
rm of many po
ch as copper a
healing rate
dal anti-inflam
ng, copper co
retaining anti-i
was discovered
vulsant activit
s facilitate or
at arthritis, ulc
ir. The coroll
chase this arti
copper deficie
se.
ed by copper
ant enzymes b
as well as inc
ding strong ev
ystem from fr
s including the
search has ind
Research is go
its use in rad
many copper
opper complex
xicity than th
opular anti-inf
aspirinate (Fig
of ulcers an
mmatory drug
omplexes of t
inflammatory
d that organic c
ty when comp
r promote tis
cers, seizures,
ary to this hy
cle. This is
ency is one
deficiency
by inducing
creases the
idence that
ree -radical
e treatment
dicated that
ing on into
diology and
complexes
xes almost
heir parent
flammatory
gure 3) and
nd wounds.
gs, such as
these drugs
activity.
compounds
plexed with
ssue repair
, neoplasia,
ypothesis is
th
dy
Fi
su
or
in
re
ra
im
th
su
th
th
ca
th
tr
ra
be
m
in
m
ti
of
as
ar
en
tr
th
re
nu
ca
de
fu
bl
hat the loss o
ysfunction tha

igure 4. Copper
Treating fo
ucceeded. Rec
rganic comple
ncreased survi
evert to norma
Copper me
adiation reco
mmunocompet
his activity ap
uperoxide, or
he capability o
hese with non-
apability. Sinc
here would be
reating patient
adiation, and a
Copper ha
etween zinc a
major contribut
nvestigators h
minimization o
ssues followin
f copper comp
s a means o
rteriosclerosis
Ceruloplas
nzyme that o
ransport in the
hroughout the
esult. Due to
umerous symp
ause of myelo
evelopment).
unctions, dimi
lood vessels, i
R
r reduction o
at may be reve
r tryptophanate.
or facial epith
cently research
exes of copp
ival rate. Thes
al cells.
etallo-organic
overy activit
tence and reco
ppears to be ti
"free," radical
of breaking th
-toxic doses o
ce these comp
merit in usin
s undergoing
astronauts und
as also a dire
and copper - w
ting factor to t
has shown th
of damage to
ng myocardial
plexes. These
f preventing
), coronary he
min is the m
xidizes Fe
2+

e plasma in as
body ,theref
its broad ran
ptoms. The m
odysplasia (w
Other sympto
inished pigme
irregular heart
Review: Transi
of copper-depe
ersed with cop
.
helioma with a
h on the treatm
er markedly
se copper com
complexes h
ties. They
overy from ra
ied to the abi
ls liberated by
he bonds of n
of pharmaceuti
lexes may als
ng copper com
ionizing radia
dertaking space
ct effect on t
with more emp
the etiology o
hat copper co
the aorta and
l infarction. T
and other stu
and controll
eart disease, ao
ajor copper-c
(ferrous iron)
ssociation wit
fore, if copper
nge of activit
most common
when a blood
oms include
ent in skin and
t beat , increa
ition Metals in
endent enzym
pper complex t
a mixture of c
ment of solid tu
decreased tum
mplexes did no
have been sho
are capable
adiation induc
ility of certain
y ionizing rad
atural copper
ical copper co
o have anticar
mplexes in the
ation therapy f
e travel.
the control o
phasis on cop
of coronary he
omplexes also
heart muscle
This action is b
udies suggest t
ing such dis
ortic aneurysm
arrying protei
) into Fe
3+
(f
th transferrin,
r levels are t
ties in the bo
symptom of
profile has in
weakness and
d hair, osteop
ased levels of
n Medicine
me-mediated p
therapy [26].
copper chlorid
umors with no
mor growth a
ot kill cancer
own to have r
of causing
ed tissue chan
n copper com
iation. In addi
enzymes in t
omplexes resto
rcinogenic act
treatment of
for their cance
f cholesterol,
pper deficiency
art disease. Su
o can have
e as oxygenate
based on the a
the use of cop
eases as athe
ms and myocar
in in the bloo
ferric iron), th
which carrie
too low, iron
ody, copper d
copper deficie
ndicators of p
d fatigue, po
orosis, proble
LDL choleste
processes lead
de and lecithin
on-toxic doses
and metastasi
cells but caus
radiation prot
g rapid rec
nges. The mec
mplexes to dea
ition, since ra
the body, supp
ores the lost ti
tivity, it is sug
cancer and in
er, accidental e
a metabolic
y than zinc ex
ubsequent wo
a valuable r
ed blood repe
anti-inflamma
pper dietary su
erosclerosis (
rdial infarction
od. Ceruloplas
herefore assis
es iron in the
deficiency an
deficiency can
ency is anemi
possible future
or immune a
ems with joint
erol and decre
269
ds to tissue
n has been
s of various
s and thus
sed them to
tection and
covery of
chanism of
activate the
adiation has
plementing
issue-repair
ggested that
n particular,
exposure to
imbalance
xcess - is a
rk by other
role in the
erfuses into
atory action
upplements
(a form of
n [27].
smin as an
sting in its
ferric state
nemia may
n result in
ia and as a
e leukemia
and thyroid
ts, ruptured
ased levels
Hanan F. Abdel-Halim 270
of HDL cholesterol, resulting in an increase in cardiovascular disease risk [28,29]. It has also
been demonstrated that copper deficiency significantly increases the susceptibility of
lipoproteins and cardiovascular tissues to lipid peroxidation, thus increasing the risk of
cardiovascular disease [30-34]. and breathing problems.
Copper is also involved in normalized function of many enzymes, such as cytochrome c
oxidase, which is complex IV in mitochondrial electron transport chain, ceruloplasmin, Cu/Zn
superoxide dismutase, and in amine oxidases[35,36]. These enzymes catalyze reactions for
oxidative phosphorylation, iron transportation, antioxidant and free radical scavenging and
neutralization, and neurotransmitter synthesis, respectively [37].
It has long been suspected that free radicals may play a role in iron- and copper-induced
cell toxicity because of the powerful prooxidant action of iron and copper salts in vitro. In the
presence of available cellular reductants, iron or copper in low molecular weight forms may
play a catalytic role in the initiation of free radical reactions. The resulting oxyradicals have
the potential to damage cellular lipids, nucleic acids, proteins, and carbohydrates, resulting in
wide-ranging impairment in cellular function and integrity. However, cells are endowed with
antioxidants, scavenging enzymes, repair processes that act to counteract the effects of free
radical production. Thus, the net effect of metal-induced free radicals on cellular function will
depend on the balance between radical production and the cytoprotective systems As a result,
there may be a rate of free radical production that must be exceeded before cellular injury
occurs.
Despite the importance role of Cu (II) complexes as we mentiond above, we must clarify
that copper (II)ion has a critical role in chronic neurologic diseases. The amyloid precursor
protein (APP) of Alzheimer's disease or a synthetic peptide representing its copper-binding
site reduced bound copper (II) to copper (I). This copper ion-mediated redox reaction led to
disulfide bond formation in APP, which indicated that free sulfhydryl groups of APP were
involved. Neither superoxide nor hydrogen peroxide had an effect on the kinetics of copper
(II) reduction. The reduction of copper (II) to copper (I) by APP involves an electron-transfer
reaction and could enhance the production of hydroxyl radicals, which could then attack
nearby sites. Thus, copper-mediated toxicity may contribute to neurodegeneration in
Alzheimer's disease [38].
Zinc and vitamin C supplements are strong antagonists of copper status and absorption.
In the case of zinc, numerous studies have shown that relatively small increases in dietary
zinc significantly lower copper absorption [39, 40]. This antagonism has been utilized as a
treatment of Wilson's disease.
Copper complexes like copper salicylate have been extensively studied for their anti-
inflammatory and antioxidant activity, as well as their ability to mimic the superoxide-radical
scavenging activity of superoxide dismutase.
Numerous researchers have examined the paradoxical role of copper in the process of
inflammation, and they have determined that the increase in serum copper is a physiological
response to inflammation, rather than a promoter of it [41]. In fact, the main copper
containing enzyme, ceruloplasmin, is significantly elevated in inflammatory conditions and
has anti -inflammatory activity [42] .Additionally, it has been shown that copper deficiency
increases the severity of experimentally-induced inflammation,[43] and that dietary copper
must be increased to maintain adequate copper status [44] .
The therapeutic potency and safety of the copper complexes of aspirin (acetyl-salicylic
acid) and salicylic acid is much better than for aspirin itself or for other copper compounds
Review: Transition Metals in Medicine 271
such as copper acetate. These complexes are 5 to 8 times more effective than aspirin but less
toxic. The therapeutic index (the margin between effectiveness and toxic effects) has been
stated as being significantly greater than for other anti-inflammatory drugs.
While aspirin and other anti-inflammatory drugs cause or aggravate ulcers and gastro-
intestinal bleeding and distress, the copper complexes have a better ulcer-healing effect than
commonly used anti-inflammatory ulcer drugs. Harmful effects of aspirin, salicylic acid and
similar drugs apparently arise because they bind copper in the stomach and intestines wall and
cause a localised copper deficiency in these tissues. This then causes connective tissue
disintegration with bleeding and ulcers. Copper salicylate supplies the necessary copper in a
useable form to heal these lesions. Then we can say that patients who are allergic to
salicylates are mainly reacting because of copper deficiency.
In addition copper salicylate has also good anti-cancer and anti-convulsive properties
suitable for treatment of epilepsy and possibly Parkinson's disease. After the liver the brain is
the second-highest copper-containing organ. There are at least 6 important copper-dependent
enzymes in the brain.
Experimental evidence showed that copper complexes can cause established tumor cells
to re-differentiate into normal cells and it has been suggested that the future use of copper
complexes to treat neoplastic diseases has some exciting possibilities [45].
Wearing copper bracelets is a time-tested anti-inflammatory, in contrast, copper
salicylates were found to be the best copper complex for the treatment of arthritic pain [46,
47].
Prion diseases such as Creutzfeldt-Jakob or "mad cow" disease, and also Alzheimers and
Parkinsons disease are related to the accumulation of wrongly folded and entangled prion
proteins. It has now been shown that this may be due to a copper deficiency in the brain, and
that copper stabilises prions and helps them to fold correctly [48].
In addition to copper salicylate complexes also a salicylate complex with zinc and boron
is a good healing remedy. This has been called the Schweitzer Formula, and is formed from
zinc (oxide or carbonate), boron (boric acid) and salicylic acid. It has been used as an
antibiotic, disinfectant, fungicide, and anti-inflammatory agent.
The Schweitzer Formula was developed 1915, in addition to any kind of infection or
inflammation, it has been used in cancer treatment, to improve the immune response and
blood oxygenation. Applied externally it is claimed to heal injuries and skin diseases,
including acne, scarring varicose veins and varicose ulcers.
The decrease in antioxidant protection caused by copper deficiency goes beyond a
decrease in the activity of copper-dependent antioxidant enzymes by inducing a wide range of
disturbances in other antioxidant enzyme systems. Copper plays a vital role in the protection
of the cardiovascular system from free -radical mediated damage and disease.[49] Thus, it
appears clear that adequate copper is vital for optimal functioning of many antioxidant
enzymes, both copper dependent and otherwise, in varied organs and tissues.
Lysyl Oxidase, which is involved in the synthesis of the collagen that constitutes much of
bone and connective tissue, is a copper dependent enzyme. Insufficient copper intake has also
been shown to lower bone calcium levels during long-term deficiency [50].
With the essential role that copper plays in maintaining bone health, it is surprising how
little attention has been given to copper's role in bone diseases, estrogens, which have a
beneficial effect on preventing post-menopausal bone loss, have been shown to raise the level
of ceruloplasmin (the main copper transport protein) two to three fold, providing a possible
Hanan F. Abdel-Halim 272
explanation for how estrogen positively influences bone health, as well as cardiovascular
health [51].
Copper plays another role in the development of cancer in which is somewhat similar to
its role in cardiovascular disease. Numerous copper complexes that demonstrate SOD-
mimetic properties, including copper salicylate, have been shown to possess anticancer,
anticarcinogenic, and antimutagenic effects both in vitro and in vivo [52].
With cancer copper serum levels behave similar to those described for atherosclerosis.
Various studies show a beneficial effect of copper on cancer. However, if growing tumours
are present, then copper is needed to form new blood vessels. Therefore one form of cancer
therapy creates artificial copper deficiency by removing copper with a molybdenum
compound, and high amounts of zinc may be used to prevent the absorption of copper. It has
now been shown that in the long-term this so-called anti-angiogenesis therapy does more
harm than good by stressing tumours and inducing them to spread [53].
The main metabolic defect of cancer cells, according to researchers, is a deficiency of the
enzyme cytochrome oxidase. This causes a blockage in the cellular respiration or oxidative
energy production of the affected cells. Cytochrome oxidase is a copper dependent enzyme
and additional copper might be beneficial. In the final stages of this oxidative energy
production cytochrome oxidase transfers electrons to copper (II) and iron (III) to form copper
(I) and iron (II). In the last step these electrons are then transferred to oxygen, which now can
attract hydrogen ions to form water. In cancer cells this electron transfer is blocked and
energy is inefficiently produced by converting glucose into lactic acid.
Due to copper deficiency this electron transfer is defective in Menkes disease, a genetic
disorder of early childhood. This is sometimes called Menkes kinky hair disease because such
babies have very fragile hair; they also have abnormal brain development and a low body
temperature. They are very floppy, lack energy and usually will not survive beyond 3 years of
age.


ZINC

Zinc (Zn) is a trace element essential for cell proliferation and differentiation. It is a
structural constituent of enzymes and proteins, including metabolic enzymes, transcription
factors, and cellular signaling proteins. There is increasing evidence for a direct signaling
function of Zn at all levels of cellular signal transduction [54]. Zinc is an important element in
preventing free radical formation, in protecting biological structures from damage and in
correcting the immune functions. Zinc deficiency produces growth retardation, anorexia,
delayed sexual maturation and iron-deficiency anemia [55].
Zinc is often used for the prevention or treatment of common colds and sinusitis
(inflammation of sinuses due to an infection), ulcers, sickle cell disease, celiac disease,
memory impairment and acne [56,57 ].
Zinc is found in many common vitamin supplements and is also found in denture creams
[56, 58]. There is also increasing evidence that zinc plays an important role in protein
biosynthesis and utilization. The addition of small amounts of zinc to a diet containing
suboptimal amounts of a vegetable protein causes a pronounced increase in protein utilization
and growth. This defect may result from a failure in adequate RNA synthesis. Zinc apparently
Review: Transition Metals in Medicine 273
inhibits the enzyme ribonuclease. Thus, in zinc deficiency, excessive destruction of RNA
could occur. Zinc-binding proteins, such as metallothioneins (MTs), belong to the family of
intra-cellular metal binding proteins that are present in virtually all living organisms and they
play a key role in the Zn effect upon the immune system. Metallothioneins are protective
against stress and increase in ageing [59]. Zinc plays major biological roles in the organism
such as its role as catalyst, and as structural and regulatory ion [60]. The dysregulation of
apoptosis is central to pathogenic mechanisms in many diseases such as neurodegenerative
disorders, acquired immune deficiency syndrome, autoimmune disease and cancers [61, 62].
Increased apoptosis in vivo may occur as direct or indirect consequence of a decrease in
intracellular Zn concentrations. Therefore, cellular Zn is described as an inhibitor of
apoptosis, while its depletion induces death in many cell lines [63]. In ageing MTs
preferentially bind Zn rather than copper and they are unable to release Zn. Indeed, during
ageing the stress like-condition is persistent provoking sequester of intracellular Zn with
subsequent low Zn ion bioavailability for immune efficiency and for the activity of Zn-
dependent enzymes and proteins [60, 64]. Low Zn ion bioavailability and high MTs levels are
present in aging and stress . A low Zn ion bioavailability may also trigger impaired cognitive
functions, via altered thyroid hormones turnover [60].
Unlike other first-row transition metals (e.g., Sc
2+
, Ti
2+
, V
2+
, Cr
2+
, Mn
2+
, Fe
2+
, Co
2+
, Ni
2+

and Cu
2+
), the zinc ion (Zn
2+
) contains a filled d orbital (d
10
) and therefore does not
participate in redox reactions but rather functions as a Lewis acid to accept a pair of electrons
[65].
This lack of redox activity makes Zn
2+
a stable ion in a biological medium whose
potential is in constant flux. Therefore, the zinc ion is an ideal metal cofactor for reactions
that require a redox-stable ion to function as a Lewis acidtype catalyst [66] such as
proteolysis and the hydration of carbon dioxide. Furthermore, due to the filled d-shell
orbitals, Zn
2+
has ligand-field stabilization energy of zero [67].
In all liganding geometries, and hence no geometry is inherently more stable than
another. This lack of an energetic barrier to a multiplicity of equally accessible coordination
geometries can be used by zinc metalloenzymes to alter the reactivity of the metal ion and
may be an important factor in the ability of Zn
2+
to catalyze chemical transformations
accompanied by changes in the metal coordination geometry. Nevertheless, in all zinc
metalloenzymes studied to date, the binding geometry observed most often is a slightly
distorted tetrahedral (Scheme 1) with the metal ion coordinating three or four protein side
chains. However, five-coordinate distorted trigonal bipyramidal geometry has been observed
in the metal sites of Zn-substituted astacin [68].
A final important property of Zn
2+
that makes it well suited as a catalytic cofactor is that
ligand exchange is rapid [69], allowing for the rapid product dissociation required for
efficient turnover.
Zinc is classified as a "borderline" metal, meaning that Zn
2+
does not consistently act
either "hard" (not very polarizable) or "soft" (highly polarizable) and does not have a strong
preference for coordinating with oxygen, nitrogen or sulfur atoms [70]. In protein zinc-
binding sites, the zinc ion is coordinated by different combinations of protein side chains,
including the nitrogen of histidine, the oxygen of aspartate or glutamate and the sulfur of
cysteine.
27
In
In
w
si
en
le
nu
as
in
ph
th
or
of
Sc
us
be
be
in
co
74
In zinc pro
n a catalytic zi
n a cocatalytic
where one play
ite [71].
Finally, in
nzyme in a ma
ead to a loss o
umber of zinc
s described lat
As unders
ncreases, the
henotypes can
A unique f
hat is, the zinc
r four protein
f [74-77]:

an acti
polariz
stabiliz

cheme.1. Zinc m
In structur
sually in a tetr
Cysteine is
eing present in
In contrast
etween the pro
n a rigid sec
omplexes ens
oteins, the maj
inc site, the zi
c zinc site, th
ys a catalytic r
structural zin
anner analogo
of enzymatic a
c proteins has
ter [72,73] .
standing of th
connection b
n be establishe
feature for a c
c-binding poly
ligands act as
vated water m
zation of the ca
zation of the n
mettaloenzymes
ral zinc sites,
rahedral geom
s by far the lig
n many cases
t to catalytic z
otein zinc liga
condary struc
sure both loca
Hanan
jor role of the
inc ion directly
here are sever
role and the o
nc sites, the zin
ous to disulfide
activity. A sy
established di
he biochemica
between the d
ed.
atalytic zinc s
yhedron conta
powerful elec
molecule for nu
arbonyl of the
negative charg
s.
the metal io
metry, so that s
gand observed
and aspartate
zinc sites, thes
ands, and the l
cture. The hig
al and overal
F. Abdel-Hal
e zinc ion can
y participates
ral metal ions
ther metal ion
nc ion mainly
e bonds. In all
stematic analy
istinct feature
al role of zinc
detailed bioch
site is the exis
ains at least on
ctrophilic cata
ucleophilic att
e scissile bond
ge in the transi
n is coordina
olvent is exclu
d most freque
being present
se sites conta
ligands can be
gh stability c
ll structural s
im
be catalytic,
in the bond-m
s bound in pr
ns enhance the
y stabilizes the
l cases, remov
ysis of the str
s of catalytic
c in these bio
hemical funct
stence of an op
ne water mole
alyst by provid
tack.
d .
tion state.
ated by four a
uded as an inn
ently in these
in one case [7
in no regular
e located on a
constants of
stability simil
cocatalytic or
making or -bre
roximity to on
e catalytic acti
e tertiary struc
val of the boun
ructure and fu
and structural
ological macro
tions and ph
pen coordinat
ecule in additi
ding all or a co

amino acid si
ner sphere liga
sites, with his
75, 79].
pattern of spa
flexible loop
these tetrade
lar to that pr
r structural.
eaking step.
ne another,
ivity of the
cture of the
nd zinc can
nction of a
l zinc sites,
omolecules
hysiological
ion sphere;
ion to three
ombination
ide chains,
and [78].
stidine also
acer length
rather than
entate zinc
rovided by
di
of
lo
us
ac
ne
be
co
en
re
fo
am
ch
be
ag
su
tr
fo
an
Z
ab
us
m
zi
of
isulfides [78].
f functions.
Zinc defici
oss or defects
sed as a treatm
crodermatitis
ervosa and bu
ecause a wid
oordinate dire
nzyme.
Zinc has b
edox-active tr
ormation of

O
mounts of iro
hemistry accor







Reaction 2
een suggested
gents

(AH
2
),
uperoxide via
The proces
ransition metal
orm

OH .
Zinc can a
nhydrase. Her
n-OH group.
bility to act as
sed by many e
Recent clin
malnutrition an
inc

content in
f zinc deficie
R
This enables p
iency can caus
leading to re
ment of many
enteropathica
ulimia nervos
de range of
ctly to the me
been shown in
ransition meta
OH from H
2
O
n or copper to
rding to the

fo
is commonly
d that trace a
such as asco
the metal-cata
ss of protein

l to an enzyme
also perform a
re the metal bi
The zinc me
s an electrophi
enzymes [81].
nical and expe
nd diarrheal di
virtually all t
ency. Compe
Review: Transi
proteins conta
se retardation,
eproductive fa
y illnesses and
a (inflammatio
a [80].Catalyt
functional g
etal, displacing
n numerous sy
als iron and
O
2

and superox
o

catalyze for
ollowing reacti
y

known as the
amounts

of so
orbate, can c
alyzed Haber-
oxidation is i
e to form a co
a different rol
inds H
2
O and
etal serves as
ile or as the so

erimental findi
isease.

Becaus
types of foods
nsatory

mech
ition Metals in
aining structur
, cessation of
ailure. Zinc su
d disorders, in
on of the ski
tic zinc sites
groups (i.e., s
g the zinc-wat
ystems to anta
copper with
xide. There

is
rmation of

OH
ions [81].
e Haber-Weiss
oluble iron or
catalyze the
Weiss

reaction
initiated by th
oordination com
le in enzymes
makes it acid
a nucleophile
ource of a nuc
ings have rein
se there is a st
s, insufficient
hanisms opera
n Medicine
ral zinc atoms
growth, impa
upplementatio
ncluding dwarf
in and the sm
provide conv
sulfonamides
ter in the activ
agonize the ca
respect

to th
s a well know
H from H
2
O
2
s reaction and
r copper in th
formation of
n (Fenton reac
he binding of
mplex

that can
s like the role
dic enough to l
e to the subst
cleophilic gro
forced the

link
trong associat
protein

intake
ating in mon
to perform a w
ired wound he
on has success
fism, sexual i
mall intestine)
venient targets
or hydroxam
ve site and inh
atalytic prope
heir abilities t
wn requiremen
and O
2
-
throu
d is relatively s
he presence o
f hydroxyl

rad
ction (reaction
f a reduced re
n then react w
it performs i
lose a proton
trate. Since zi
up it is incorp
k among zinc
tion between p
e may often be
nogastric spec
275
wide range
ealing, hair
sfully been
mmaturity,
), anorexia
s for drugs
mates) can
hibiting the
rties

of the
to promote
nt for trace
ugh Fenton
(1)
(2)
(3)
(4)
(5)
(6)
slow. It

has
of reducing
dical from
n 6).


edox-active

ith H
2
O
2
to
in carbonic
and form a
inc has the
porated and
deficiency,
protein and
e the cause
cies during
Hanan F. Abdel-Halim 276
malnutrition

are less effective for the absorption of transition divalent

elements such as zinc,
which remain bound to ligands of dietary

or endogenous origin. Both protein and zinc
deficiencies are

strong negative determinants for normal cellular immunity. Zinc deficiency

may impair the absorption of water and electrolytes, delaying

the termination of normally
self-limiting gastrointestinal disease

episodes.
As zinc has an antioxidant and anti-inflammatory action in the uterus. Improvement in
micro-vessel circulation by zinc may help prevent cramping and pain. Since strong uterine
contractions temporarily reduce or stop the blood supply to the uterus, thus depriving the
uterus of oxygen resulting in contractions and pain, perhaps improvement in micro-vessel
circulation by zinc treatment is sufficient to prevent cramping and pain. Ischemia is partly
caused by reperfusion, which results in the release of much active oxygen species which can
cause tissue damage and pain. Thus, much of the discomfort of dysmenorrhea is likely to be
due to these free oxygen radicals. The enzyme which inactivates these oxygen species is
dismutase. Copperzinc dismutase is present in the uterus [82] and zinc treatment allows for
more adequate levels of this enzyme which in turn could relieve cramping and pain. Zinc is
an effective anti-inflammatory and antioxidant agent, and it can readily down regulate
inflammatory cytokines [83]. Zinc protects plasma cell membranes preventing damage to
cells by a wide variety of cytotoxic agents in a dose dependent manner extending far above
physiologic concentrations.


GOLD

For decades, gold salts have been utilized for the treatment of inflammatory rheumatoid
arthritis [84].Although their exact mechanism of action is not clearly understood, gold salts
decrease the inflammation of the joint lining, thereby preventing destruction of bone and
cartilage. It is quite likely that the mechanism by which gold anti-rheumatic drugs modulate
the immune response is multifactorial. Their therapeutic activity may be derived from an
ability of gold to undergo facile ligand exchange with biological thiolates, particularly those
with low pKa values, resulting in the inhibition of activity of several different enzymes. Gold
(I) can chelate thiol peptides with two or more cysteine residues thus affecting antigen
presentation [85].While some gold compounds can affect the cellular redox balance.
Additionally, it has also been proposed that golds anti-arthritic activity may be due to its
ability to release peptides from major histocompatibility complex-class II (MHC-II) proteins
[86].
Among the non-platinum antitumor drugs, gold complexes have recently gained
considerable attention due to their strong antiproliferative potency. In many cases the cell
growth inhibiting effects could be related to anti-mitochondrial effects making gold species
interesting drug candidates with a mode of action different from that of the platinum agents.
The spectrum of gold complexes described as antiproliferative compounds comprises a broad
variety of different species including many phosphine complexes as well as gold in different
oxidation states[87].
Auranofin - Au - oral rheumatoid arthritis drug (Figure 5) , has a triethylphosphinegold
unit, is just as effective, as Disodium aurothiomalate AuSCH(CO
2
Na)CH
2
CO
2
Na (Figure 6)
is a coordination complex used to treat rheumatoid arthritis.The injectable thiolate complexes
ar
st
au
th
he
af
T
T
pr
Fi
Fi
A
is
en
G
re polymers c
tructures Au-S
urothiomalate
hiolate drugs
exameric 1 :
ffinity for thio
herefore Au(1
hiolate exchan
robably not th

igure 5. Aurano

ig 6. Disodium
Albumin c
Au(1) in the cy
s mobile withi
nzyme glutath
GSH-Px-Se-Au
R
containing lin
S-Au-S- with
usually conta
have been cr
1 Au(1) thiola
olate S compar
1) binds to D
nge reactions
he pharmacolo
ofin.
aurothiomalate
can transfer A
ytoplasm. Glut
n the cell due
hione peroxida
u-SG [93].
Review: Transi
near Au (1)
h succinoyl gr
ains a slight e
rystallized, bu
ate complex h
red to thioethe
NA very wea
on Au(1) are
gically-active
e.
Au(1) into cell
tathione is kno
e to dynamic e
ase by bindin
ition Metals in
and bridging
roups attached
excess of thiol
ut the X-ray
has been repo
er S, and a mu
akly and is no
facile [90] an
species.
ls,specific me
own to bind to
exchange react
ng to the activ
n Medicine
thiolate sulf
d to the sulfur
late over gold
crystal struct
orted [89]. Go
uch lower affin
ot usually car
d therefore th
etal transport
o intracellular
tions. This co
ve site selenoc
furs, in chain
r atoms.[88]. F
d. None of the
ture of a rela
ld(1) has a m
nity for N and
cinogenic or
e administered


proteins, [91]
Au(1) [92] an
mplex can inh
cysteine residu
277
n or cyclic
Formulated
e injectable
ated cyclic
much higher
d 0 ligands.
mutagenic.
d drugs are
], transport
nd the gold
hibit the Se
ue forming
Hanan F. Abdel-Halim 278
Under the oxidative conditions that exist in inflamed joints, oxidation of Au(1) to Au(III)
is likely formed. The formation of Au(III) may be responsible for some of the side-effects of
gold therapy [94]. Gold(III) has a remarkable ability to deprotonate peptide amide bonds even
at highly acidic pH values. The tripeptide Gly-Gly-His, for example, readily forms a square-
planar complex with Au(III) at (pH 2) via binding to the terminal amino group, two
deprotonated amide nitrogens and imidazole N of His. [95]. Ultimately much gold is
deposited in lysosomes of cells but the chemical form of it is not known. It is not metallic Au,
but probably a protein complex. Here gold may inhibit lysosomal enzymes which are
responsible for destruction of joint tissue [96].
As Gold(III) is isoelectronic and isostructural with Platinum (II), it was suggested that
gold compounds may also be useful as anticancer. Although the screening of Auranofin and
Auranofin analogues yielded a limited spectrum of activity [97,98] organogold(III)
DAMP(DAMP = o-C
6
H
4
CH
2
NME2) complexes[99,100] and triphenylphosphine-gold (I)
complexes have shown significant activity . The work conducted on the latter compounds led
to the development of bis(diphos)gold(I) complexes [101,102]. Mononuclear gold(III)
complexes, organogold(III) compounds and dinuclear oxobridged gold(III) complexes were
evaluated in several human tumor cell-lines [103]. and novel targets proposed include the
mitochondrial membrane, cysteine proteases (notably caspases and cathepsins) and
thioredoxin reductase [104,106].
In 2011 researchers synthesis and study new gold(III) complexes 5-aryl-3-(pyridin-2-yl)-
4,5-dihydropyrazole-1- carbothioamide . The cytotoxicity was tested by MTT assay. The
results indicate that some complexes have higher cytotoxicity than cisplatin against HeLa cell
line. The study suggests that the substituent groups on benzene have important effect on
cytotoxicity [107].


VANADIUM

Vanadium is a curious trace element which seems to be required by the body in relatively
tiny amounts. There is nevertheless increasing excitement about its potential therapeutic
value. Low blood levels of vanadium have been associated with increases in cholesterol and
blood sugar, and it is also believed by some researchers that the mineral may play a role in
maintaining the vital balance between sodium and potassium in cells. These characteristics of
vanadium have led to speculation that it may act as a protector against heart disease, cancer
and especially diabetes.
Some nutritional therapists have rushed to embrace vanadium's potential, insisting that
high dose vanadium supplements can reduce levels of fasting blood sugar and reducing
cellular inflammation [108,109 ], as well as those of low density lipids (LDLs), the so-called
"bad cholesterol" which is strongly associated with atherosclerosis (hardening of the arteries)
[110].
The initial use of vanadium to treat diabetes was in 1899 [111]. The ability of sodium
vanadate (NaVO3) to lower blood glucose levels has been tested. The result was very
promising in lowering sugar levels, with no side effects [112].
Vanadyl sulfate (VOSO4) soon replaced sodium vanadate in animal testing due to the
decreased toxicity of vanadyl compared to vanadate . Also, much of the vanadate
ad
fo
th
7)
T
T
Fi
in
m
am
in
m
va
an
ca
pr
co
ho
co
tr
(v
so
oc
an
de
ar
th
vi
sp
to
in
va
pr
dministered is
ocus off of van
he major treatm
) was the first
here is also a
here are differ

igure 7. Bis(ma
Vanadium
ncrease cell vo
mimic the horm
mino acids an
ncreasing cell
muscles look b
anadium may
nd fight age-r
apacity and ab
Vanadium
roperties in e
omplex exert
owever exerts
ombination w
reatment of hu
Most of th
vanadate) prob
olution. In van
ccur simultane
nd decameric
epending on v
re not taken in
hat, particularl
ivo [119]. In
pectroscopy st
o the iceberg
nteresting one
anadium spec
romoted effec
R
s found in the
nadium comp
ment for the d
t vanadium co
an increase in
rences in distr
altolato)oxovana
became popu
olume and thu
mone insulin
nd blood suga
volume, vana
bigger and ful
also be impor
related loss o
bility to enhan
salts and com
experimental
ed antitumor
s much more
with its low to
uman malignan
e biological im
bably due to
nadium (+5)
eously in equi
(V10) and,
vanadium conc
n consideratio
ly V10, they m
vitro effects
tudies. Allego
phenomena:
e, but clearly
cies and the in
ts.
Review: Transi
e vanadyl form
lexes for treat
disease [111,1
omplex prepare
uptake and t
ribution of ion
adium (BMOV)
ular with bod
us was hoped
in the body, v
ar, into our mu
adium has bee
ller but even
rtant for bone
of bone. This
ce calcium me
mplexes have
carcinogenes
effects in tu
e potent . Th
oxicity provid
nt diseases [11
mportance of
similarities b
solutions diff
ilibrium such
in same case
centration, pH
on in the majo
may also influ
can be conv
orically, vanad
there is alway
y it is the es
nteractions wi
ition Metals in
m [111]. The
tment of diabe
113]. Bis(malt
ed that has inc
tolerability ass
nic verses com
).
dybuilders las
to also boost
vanadium is b
uscle cells, w
en suggested b
result in mus
formation, wh
effect seems
etabolism [115
been widely i
is. Vanadyl
umor bearing
hese beneficia
de evidence su
18].
vanadium is a
etween the ph
ferent oligome
as monomeri
s, with differ
H and ionic stre
ority of the bi
uence enzyme
veniently ana
date studies in
ys an invisibl
ssential part n
ith the system
n Medicine
discovery of
etes, as hormo
tolato)oxi-van
creased effect
sociated with
mplex forms of
st decade bec
muscle mass
believed to he
which leads to
by some expe
scle growth. S
hich could hel
to be due to
5-117].
investigated fo
sulfate, cyste
g rats. The V
al effects of
uggest its pos
associated wit
hosphate and
eric (n=1 to 1
c (V1), dimer
rent states of
ength. Many o
ological studi
e activity not
alysed combin
n biological sy
le part that p
needed to pr
m before attem
insulin in 192
one supplemen
nadium (BMO
tiveness again
the complex
f vanadyl.

cause of its p
.Due to its p
elp shuttle nut
greater cell v
rts to not only
Some evidenc
lp maintain bo
o an enzyme-s
for their antica
eine and V(II
V(III)-cysteine
the above co
ssible applica
th the +5 oxid
vanadate che
0) vanadate s
ric (V2), tetram
protonation a
of these vanad
ies, although i
only in vitro
ning kinetic w
ystems can be
robably is no
ecisely chara
mpting to unde
279
22 took the
nts became
OV) (Figure
st diabetes.
[113,114].
potential to
potential to
trients, like
volume. By
y make the
ce suggests
one density
stimulating
arcinogenic
II)-cysteine
e complex,
omplex, in
ation in the
dation state
emistries in
species can
meric (V4)
and forms,
date species
it is known
but also in
with NMR
e compared
ot the most
acterize the
erstand the
Hanan F. Abdel-Halim 280
Among vanadate oligomers, decameric vanadate (V10), which may occur upon medium
acidification, is considered as the vanadate oligomer with more biochemical relevance.
Although unstable at physiologic pH, the slow rate of decameric vanadate decomposition
allows studying its effects in biochemical systems [119,120]. In fact, it was suggested that
even at physiological pH values an eventual local acidification of a vanadate solution will
induce the formation of (V10) species. Once formed, decameric vanadate disintegration is in
general slow enough to allow the study of its effects even in the micromolar range. Besides, it
may become inaccessible to decomposition due to their stabilization upon binding to target
proteins such as sarcoplasmic reticulum Ca
2+
-ATPase or actin [121]. Additionally, recently
described in vivo toxicological studies demonstrated that decameric vanadate species are
responsible for a strong increase in lipid peroxidation and oxidative stress markers, thus
contributing to oxidative stress responses upon vanadate intoxication and pointing out to the
importance of vanadate speciation on the evaluation of vanadium toxicity . The degree of
toxicity depends on the mode of administration such as intraperitoneal or intravenous, and of
course to the vanadate species such as decavanadate [122,123]. Other studies included the use
of decavanadate as a probe in comprehension of muscle contraction and calcium homeostasis
[119]. Actually, we are investigating the mechanisms of cell death induced by vanadate [122]
and the effects of insulin-mimetic vanadium compounds in the activity of sarcoplasmic
reticulum calcium pump . We believe that these recent advances in vanadium toxicology and
pharmacology allow a better understanding of the role of the versatile vanadium in biological
systems [124].
Vanadium is widely known for its toxic effects; however it is vestigial in muscles and
other tissues and is considered an essential oligoelement for humans. Its biological role is far
from a clear identification. Vanadium is present in petroleum, coal and gasoline, used as
alloys and catalysts for industry and is well known for its environmental and biological
impact (Nriagu, 1998). In spite of the emerging interest in the pharmacological effects of
some vanadium compounds, for instance as an insulin-mimetic in the treatment of diabetes,
the toxicology of vanadium constitutes an area of increasing interest (Aureliano, 2007).
Recently, it was reviewed some medicinal applications of vanadium focusing structure-
activity relationship of antidiabetic vanadium complexes, vanadium compounds as anti-
tumour drugs and anti-parasitic agents, and osteogenic action of vanadium complexes in order
to make vanadium compounds available and safe for clinical use. Milestones in the history of
Vanadium Biochemistry are also the review chapters about the redox profile of vanadium, the
biological role of vanadium in bromoperoxidases and the oxovanadates interactions with
lipidic structures (Aureliano, 2007).
Most of the biological importance of vanadium is associated with the +5 oxidation state
(vanadate) probably due to similarities between the phosphate and vanadate chemistries in
solution. In vanadium (+5) solutions different oligomeric (n=1 to 10) vanadate species can
occur simultaneously in equilibrium such as monomeric (V1), dimeric (V2), tetrameric (V4)
and decameric (V10) and, in same cases, with different states of protonation and forms,
depending on vanadium concentration, pH and ionic strength. Many of these vanadate species
are not taken in consideration in the majority of the biological studies, although it is known
that, particularly V10, they may also influence enzyme activity not only but also (Aureliano,
2007). effects can be conveniently analysed combining kinetic with NMR spectroscopy
studies. Allegorically, vanadate studies in biological systems can be compared to the iceberg
phenomena: there is always an invisible part that probably is not the most interesting one, but
Review: Transition Metals in Medicine 281
clearly it is the essential part needed to precisely characterize the vanadium species and the
interactions with the system before attempting to understand the promoted effects.
Among vanadate oligomers, decameric vanadate (V10), which may occur upon medium
acidification, is considered as the vanadate oligomer with more biochemical relevance.
Although unstable at physiologic pH, the slow rate of decameric vanadate decomposition
allows studying its effects in biochemical systems (Aureliano and Gndara, 2005, Aureliano
2007). In fact, it was suggested that even at physiological pH values an eventual local
acidification of a vanadate solution will induce the formation of V10 species. Once formed,
decameric vanadate disintegration is in general slow enough to allow the study of its effects
even in the micromolar range. Besides, it may become inaccessible to decomposition due to
their stabilization upon binding to target proteins such as sarcoplasmic reticulum Ca
2+
-
ATPase or actin (Ramos et al, 2006). Additionally, recently described toxicological studies
demonstrated that decameric vanadate species are responsible for a strong increase in lipid
peroxidation and oxidative stress markers, thus contributing to oxidative stress responses
upon vanadate intoxication and pointing out to the importance of vanadate speciation on the
evaluation of vanadium toxicity (Soares et al, 2007a). The degree of toxicity depends on the
mode of administration such as intraperitoneal or intravenous, and of course to the vanadate
species such as decavanadate.
One of the most important recent results was the observation that decameric vanadate
also affects mitochondrial oxygen consumption at the nM range of concentration (Soares et
al, 2007b). In another line of research, the effects of vanadate on the mineralization of a fish
bone-derived cell line were studied and compared to that of insulin, being suggested that it
stimulates growth and prevents mineralization through multiple processes involving
regulation that may or may not depend upon the activation of insulin stimulated pathways
(Tiago et al, 2008). Other studies included the use of decavanadate as a probe in
comprehension of muscle contraction (Tiago et al, 2004, 2007) and calcium homeostasis
(Aureliano et al, 2007). Actually, we are investigating the mechanisms of cell death induced
by vanadate (Soares et al, 2008) and the effects of insulin-mimetic vanadium compounds in
the activity of sarcoplasmic reticulum calcium pump (Aureliano et al, 2008). We believe that
these recent advances in vanadium toxicology and pharmacology allow a better understanding
of the role of the versatile vanadium in biological systems (Kustin et al, 2007).


IRON

Hemoglobin, which is the principal oxygen carrier in humans has four sub-units in which
the iron(II) ion is coordinated by the planar, macrocyclic ligand protoporphyrin IX and the
imidazole nitrogen atom of a histidine residue[125].
Each ferrous iron within hemoglobin provides one binding site for O
2
(Figure 8)

. Thus a
single hemoglobin molecule has the capacity to combine with four molecules of oxygen.
Hemoglobin binds oxygen in a cooperative fashion; occupation of one binding site enhances
the affinity of another binding site for oxygen in the molecule[126,127].

28
Fi
ha
as
fo
pr
co
m
so
ce
fa
sp
to
in
of
Fi
ac
82
igure 8. Structu
The sixth c
as only one su
s, without it, th
or the formatio
ressure of ox
ooperativity
myoglobin[128
olubility and p
enter and the
acilitates the p
In both hem
pecies contain
o the fact that
n the plane of t
iron atom l
f higher crysta

igure 9. Rubred
Rubredoxin
ctive site cont
ure of Heme b, i
coordination si
uch unit. The
he iron(II) wo
on of HbO
2
is
xygen in the l
effect which
8].A combina
prevents aggre
presence of
peroxidation re
moglobin and
ns iron(III). It
the iron(II) is
the porphyrin
lies above the
al field splittin
doxin.
n is an electro
tains an iron
Hanan
in the protein.
ite contains a
active site is l
ould be irrever
such that oxy
lungs or in m
h allows for
ation of a hy
egation of hem
a relatively p
eaction.
myoglobin it
is now known
in the low-sp
ring, but in th
plane of the r
ng and smaller
on-carrier foun
ion which is
F. Abdel-Hal
water molecu
located in an h
rsibly oxidised
ygen is taken u
muscle. In he
r easy oxyg
ydrophobic b
min, tentative d
polar site clos
is sometimes
n that the diam
pin state. In ox
he paramagnet
ring. The chan
r ionic radius o
nd in sulfur-m
coordinated b
im
ule or a dioxyg
hydrophobic p
d to iron(III). T
up or released
emoglobin the
gen transfer
binding pocke
donation of an
se to the iron
incorrectly st
magnetic natur
xyhemoglobin
tic deoxyhemo
nge in spin sta
of Fe
2+
in the o

metabolizing b
by the sulphur

gen molecule.
pocket. This is
The equilibriu
depending on
e four sub-un
from hemo
et, which inc
n axial ligand t
n-oxo center p
tated that the o
re of these spe
n the iron atom
oglobin ,
ate is a coopera
oxy- moiety [
acteria and ar
r atoms of fou
myoglobin
s important
um constant
n the partial
its show a
oglobin to
creases the
to the Fe3+
presumably
oxygenated
ecies is due
m is located
ative effect
128].
rchaea. The
ur cysteine
Review: Transition Metals in Medicine 283
residues forming an almost regular tetrahedron. Rubredoxins perform one-electron transfer
processes. The oxidation state of the iron atom changes between the +2 and +3 states. In both
oxidation states the metal is high spin, which helps to minimize structural changes.
Iron is transported by transferrin (Figure 10) whose binding site consists of two tyrosines,
one aspartic acid and one histidine[129].


Figure 10.The Amino Acids that bind and hold iron in a N-terminus Transferrin lobe.
Iron tris(bipyridine) Polymeric Metal Complexes is useful in biological applications
because they are labile and may alter their inner coordination sphere in response to changes in
pH and temperature or the presence of reactive oxygen species [130]. This presents a new
triggered release