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MSE 598/494 Bio-inspired Materials and Biomaterials MSE 598/494 Bio-inspired Materials and Biomaterials
Instructor: Ximin He
TA: Xiying Chen Email: xchen128@asu.edu
2014-04-18
Lecture 17-18
Self-assembly I
Self-assembled Structure
What you will learn in the next 75 minutes
Self-assembly
1. Molecular clefts, cages
2. Enzyme mimics
3. Self-assembled liposome-like systems
4. Ion-channel mimics
5. Base pairing structures
6. DNA-DNA structures
7. Bioinspired frameworks (Option for Lit Rev Presentation)
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Self-assembly
Multifunctional building blocks are assembled into larger molecular
entities showing considerable sophistication in both their function and
form.
Natural self-assembly processes:
Protein folding,
the assembly of DNA,
the formation of bilayers, micelles, and vesicless
Synthetic self-assembly:
Self-assembly structures prepared by the bottomup approach
Arise from supramolecular chemistry, when it became a subdescipline of
chemistry
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Supramolecular Chemistry
History:
Originate from
Weak bonds: 1873, van de Waals force; 1950, Hydrogen bond
DNA : nucleic acid double helix are held together by base pairing
Enzyme: interaction with substrate
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Supramolecular Chemistry
History:
In 1894, Herman Fischer:
enzyme-substrate interactions a lock and key
the fundamental principles of molecular
recognition and host-guest chemistry
Nobel Prize in 1987: D. J. Cram, J.-M. Lehn, and
C. J. Pedersen
in particular for the development of selective "host-
guest" complexes, in which a host molecule recognizes
and selectively binds a certain guest
Supramolecular Chemistry
Definition: The domain of chemistry beyond that of molecules and
focuses on the chemical systems made up of a discrete number of
assembled molecular subunits or components.
Traditional Chemistry covalent bonds
Supramolecular Chemistry the weaker and reversible noncovalent
interactions between molecules
Concepts studied:
molecular self-assembly, folding,
molecular recognition, host-guest chemistry,
mechanically-interlocked molecular architectures,
dynamic covalent chemistry
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Self-Assembly
Study Subjects:
The spontaneous and often selective inclusion of numerous neutral and
charged (both cationic and anionic) guests in the cavities of a wide range
of cage-like synthetic hosts (often referred to as container molecules or
assemblies
Synthetic structures based on noncovalent interactions, such
as micelles and microemulsions
Glue between building blocks:
weaker noncovalent interactions
hydrogen bonding (in nature: carbohydrates, amino acids, nucleic acids)
metal coordination,
- stacking,
-cation and -anion interactions,
electrostatic interactions (ionion, iondipole, dipoledipole)
Design and Assembly of Supramolecular Systems
Molecular and ionic
complementarity
Influencing parameters:
Steric and electronic information
inherent in molecular/ionic
building blocks
Preparation of bioinspired
systems:
1. fully synthetic
components
2. naturally occurring
molecules (DNA, etc)
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1. MOLECULAR CLEFTS, CAPSULES, AND CAGES
Nature uses molecular (and ionic) encapsulation:
enzymes, proteasomes, and viral capsids
1. Host: deep cavity-like structures
2. Guest: can be single molecule or large entities
3. Inclusion process associated with combination of
Selective guest uptake (sometimes associated with chiral recognition)
Induced high catalytic activity
Concentration and guest storage of particular guests (including toxic
species)
Molecular/ionic guest transport processes
Alteration of guest reactivity: e.g. a carboxylate group when encapsulated
in lysozyme becomes capable of hydrolyzing a polysaccharide in water
Research Focus: Syntheses for larger cage-like molecules and assemblies (metal
or metal-free structures)
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K
+
1) Organic Cage Systems
Large variety of cage or cage-like systems:
Simple self-assembling micelles that can act as primitive hosts,
large container systems capable of including a nanoscale guest or
multiple smaller guests
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1. Closed cages: Cryptand, fullerene
2. Fully organic closed and open cages
based on preformed macrocyclic scaffolds
1) natural cyclodextrins
2) synthetic cyclic derivatives based on
calixarene, resorcinarene, and
curcurbit[n]uril rings
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1) Organic Cage Systems organic synthesis
Trinacrene
High performance:
a suitable host for a range of organic,
organometallic, and inorganic guests
Low yield:
prepared in a conventional four-step synthesis
starting from furan and hexabromobenzene in an
overall yield of less than 0.01%!
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1) Organic Cage Systems templating
Cavitand
water soluble
spontaneously forms a self-assembled dimeric capsule in the presence
of different hydrophobic templating guests, i.e. highly complementary
rigid steroids and flexible straight-chain hydrocarbons
weak C-H- interactions
hydrophobic effect
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1) Organic Cage Systems reversible imine linkage
Exist in solution in equilibrium with their precursors namely, the
corresponding carbonyl (aldehyde or ketone) and amine derivatives
The equilibrium corresponds to the reversible hydrolysis or solvolysis
of the imine linkage
Allow the generation of cages in fewer steps and in higher yield
Dynamic covalent synthesis: imine-linked, fully covalent nanocubes
1) Organic Cage Systems reversible imine linkage
Dynamic covalent synthesis:
imine-linked, fully covalent nanocubes
4: diamine (1,4-phenylenediamine or benzidine), in an 8:12 ratio in
chloroform containing trifluoroacetic acid as catalyst
90% yield
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2) Metallosupramolecular Cage Systems - Fe
Metal ions are incorporated in the framework of the cage structures
Show inclusion behavior that resembles that exhibited by biological
systems
Example: Fe(II) was demonstrated to interact in acetonitrile with the
quaterpyridine-derived ligand
the assembly of an 8
+
charged tetrahedral shaped cation of type
[Fe
4
L
6
]
8+
, which was found to spontaneously encapsulate the polyatomic
anions BF
4

, PF
6

, [FeCl
4
]

from solution.
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cationic metallosupramolecular cage
[Fe
4
L
6
(FeCl4)]
5+
an [FeCl
4
]

anion occupies the center of the


tetrahedron
selective for Fe(III) species, [FeCl
4
], over
Fe(II) analog, [FeCl
4
]
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2) Metallosupramolecular Cage Systems - Fe
enlarged internal volume of 844
3
encapsulate four tetrahydrofuran solvent molecules in the solid state
as opposed to 174
3
volume in the smaller phenylene-spaced
analog which included a single tetrahydrofuran molecule
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neutral metallosupramolecular cage
[Fe4L6(THF)4]5+
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2) Metallosupramolecular Cage Systems -Ni or Zn & Fe
[Fe
8
(M-L)
6
]
16+
(M = Ni)
internal volume=1340
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uptake 3 coronene molecules
2) Metallosupramolecular Cage Systems Pd, Cu
2+
a series of M
12
L
24
spherical assemblies
displays cuboctahedral symmetry
(diameter of 2.6 nm)
M
24
L
48
spherical assemblies, mass of
>20,000 Da, diameter of 4.0 nm.
nanocage of composition [Pd
12
L
24
]
24+
Confirmed by X-ray diffraction
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2. ENZYME MIMICS AND MODELS
Substrate selectivity of enzymes nature of the cavity
Dimensions
Lipophilicity
The presence or absence of
complementary functional groups
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Goals of synthetic enzyme mimics:
as an aid for defining the active site of a natural system & for probing
potential mode of action
to probe the possibility of producing a functioning catalyst system for
application in the real world.
2. ENZYME MIMICS AND MODELS - Carbonic anhydrase
Carbonic anhydrase II is an enzyme that reversibly converts carbon
dioxide into the bicarbonate ion.
maintain acid-base balance in blood and other tissues and to help transport
carbon dioxide out of tissues
The active site incorporates a zinc ion bound to three histidines and a water
molecule, such that a distorted tetrahedral coordination geometry is present
Feature:
pKa = 7 Readily deprotonated under
physiological conditions
Deprotonation is promoted by the Lewis
acidity of the zinc center and bound water
(part of a hydrogen bonded network within
the cavity)
employed to model the active site of carbonic
anhydrase
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2. ENZYME MIMICS AND MODELS - Carbonic anhydrase
Most of the studies have focused on the role of the Zn(II)OH

group
for the hydration of CO
2
& the reverse process, the dehydration of
HCO
3
Mimics:
1. Using tripodal (substituted) tris(pyrazolyl)borate ligand to form complexes
of type [ZnL(OH)]+ (pKa =6.5)
2. Using triaza-macrocycle,1,5,9-triazacyclododecane to form [ZnL(H2O]2+
Catalytic enhancement of both the hydration of CO
2
and the dehydration of
HCO
3
3. SELF-ASSEMBLED LIPOSOME-LIKE SYSTEMS
Bilayer structures self-assembly process
Importance: the delivery of both therapeutic (drugs, genes) and
diagnostic agents
Bionanoscience: the self-assembly of liposomes and caposomes using
polymers
demonstration of forming bilayer structures through the use of small
amphiphilic components
Various shapes
By cryo-TEM
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an amphiphilic dendrimer with a cross-
sectional view of a spherical dendrimersome.
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4. ION CHANNEL MIMICS
The passage of ions across cell membranes
crucial to cellular vitality
Ion Channel Mimics:
Self-assembled pyrogalloarene cages and
nanotubes:
With sufficiently long alkyl chains
extending from the metallocage core, these
assemblies display an excellent ability to
insert into phospholipid bilayers and act as
protein channel mimics
conductance measurements to ion channel
behavior greatest selectivity toward Na+
among Na+, K+, and Cs+ ions.
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5. BASE-PAIRING STRUCTURES
WatsonCrick base pairing is central to the structure and function of DNA
reliable base-pairing interactions
strength of the double helical structure over nanometer dimensions
Base pairing mimics: a synthetic nucleotide
coordination of Ag+ by the central imidazole nucleosides.
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imidazoleAgimidazole bonds
double helix
determined through 107/109Ag15N heteronuclear correlation NMR
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6. DNARNA STRUCTURES
Using DNA and RNA as building blocks
RNA
stronger interactions between base pairs than DNA and can give more
thermally robust structures
slightly more stable to acidic environments than DNA
tRNA and DNA heteroduplex formation to give a triangular unit
that assembles into a large discrete dodecahedron
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6. DNARNA STRUCTURES
(a) Formation of a triangle through base-pairing interactions;
(b) linking strands bringing two units together to form the prism;
(c) reinforcement of the linking strands;
(d) metallation of the prism (Cu
+
or Ag
+
)
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DNA orgigami
developed a computer program to generate a continuous single-
stranded DNA sequence that, along with smaller DNA fragments that
act as staples, would self-assemble into the desired shape.
3D 2D
Summary
Self-assembly
1. Molecular clefts, cages
2. Enzyme mimics
3. Self-assembled liposome-like systems
4. Ion-channel mimics
5. Base pairing structures
6. DNA-DNA structures
7. Bioinspired frameworks (Option for Lit Rev Presentation
and Original Research)
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Reading Sources
Self-assembly for elctronics, drug delivery, etc
Prof. Samuel Stupp, Northwestern Univ
DNA Origami:
Prof. William Shih, Harvard
Prof. Peng Yin, Harvard
Prof. Hao Yan, ASU
Aarhus University Center for DNA Nanotechnology
(Option for Lit Rev Presentation and Original Research)