a r t i c l e
i n f o
Article history:
Received 20 April 2011
Received in revised form 5 August 2011
Accepted 17 August 2011
Available online 25 August 2011
Keywords:
RAFT polymerisation
Block copolymers
Star polymers
Graft polymers
Hyperbranched polymers
Dendrimer
a b s t r a c t
Reversible addition fragmentation chain transfer (RAFT) polymerization has made a huge
impact in macromolecular design. The rst block copolymers were described early on,
followed by star polymers and then graft polymers. In the last ve years, the types of architectures available have become more and more complex. Star and graft polymers now
have block structures within their branches, or a range of different branches can be found
growing from one core or backbone. Even the synthesis of hyperbranched polymers can
be positively inuenced by RAFT polymerization, allowing end group control or control
over the branching density. The creative combination of RAFT polymerization with other
polymerization techniques, such as ATRP or ring-opening polymerization, has extended the
array of available architectures. In addition, dendrimers were incorporated either as star
core or endfunctionalities. A range of synthetic chemistry pathways have been utilized and
combined with polymer chemistry, pathways such as click chemistry. These combinations
have allowed the creation of novel structures. RAFT processes have been combined with
natural polymers and other naturally occurring building blocks, including carbohydrates,
polysaccharides, cyclodextrins, proteins and peptides. The result from the intertwining
of natural and synthetic materials has resulted in the formation of hybrid biopolymers.
Following these developments over the last few years, it is remarkable to see that RAFT
polymerization has grown from a lab curiosity to a polymerization tool that is now been
used with condence in material design. Most of the described synthetic procedures in the
literature in recent years, which incorporate RAFT polymerization, have been undertaken
in order to design advanced materials.
2011 Elsevier Ltd. All rights reserved.
Corresponding author. Tel.: +61 2 9385 4344; fax: +61 2 9385 6250.
E-mail address: m.stenzel@unsw.edu.au (M.H. Stenzel).
Abbreviations: 2VP, 2-vinylpyridine; AA, acrylic acid; AAGP, acrylamido glucopyranose; AAm, acrylamide; AcOSty, p-acetoxystyrene; AGA, acryloyl glucosamine; AIG, 3-O-acryloyl-1,2:5,6-di-O-isopropylidene--d-glucofuranose; AN, acrylonitrile; APMA, 2-aminopropyl methacrylamide hydrochloride;
AzA, aziodopropylacrylamide; BA, n-butyl acrylate; BFA, 2-(N-butyl peruorooctaneuorosulfonamido)ethyl acrylate; BIS, methylene bisacrylamide;
BISTRIS, bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane; BMA, n-butyl methacrylate; BzMA, benzyl methacrylate; DEA, N,N-diethylacrylamide;
DEAEMA, 2-(diethylamino) ethyl methacrylate; DIPAMA, N,N-(diisopropylamino)ethyl methacrylate; DMA, N,N-dimethyl acrylamide; DMAEA, 2(dimethylamino)ethyl acrylate; DMAEMA, 2-(dimethylamino)ethyl methacrylate; DMAPMA, 2-(dimethylamino)propyl methacrylate; DTT, dithiothritol;
EA, ethyl acrylate; EGDMA, ethylene glycol dimethacrylate; FDA, 1,1,2,2-tetrahydroperuorodecyl acrylate; FPMA, pentauorophenyl methacrylate; GMA, glycidyl methacrylate; HEA, 2-hydroxyethyl acrylate; HEMA, 2-hydroxyethyl methacrylate; HPA, 2-hydroxypropyl acrylamide; HPMA,
2-hydroxypropyl methacrylamide; iBor, isobornyl acrylate; IP, isoprene; LA, d,l-lactide; LBAM, 2-lactobionamidoethyl methacrylamide; MA, methyl
acrylate; MAA, methacrylic acid; MAGO, 6-O-methacryloyl--d-glucoside; MAGP, methacrylamido glucopyranose; MAn, maleic anhydride; MIGC11, 3 (1 ,2 :5 ,6 -di-O-isopropylidene--d-glucofuranosyl)-11-methacrylamido undecanoate; MIGC5, 3 -(1 ,2 :5 ,6 -di-O-isopropylidene--d-glucofuranosyl)0079-6700/$ see front matter 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.progpolymsci.2011.08.004
39
Contents
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2.
3.
4.
5.
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H-shaped B2 AB2 , dumb-bell (pom-pom), ring diblock, starblock (AB)n , amongst many other designs (Fig. 1).
These novel properties arise from the ability of complex architectures to show signicantly different solution
behaviors as well as from their ability to self-assemble
40
Fig. 1. Examples of various complex architectures that can be achieved utilizing two independent blocks (A and B) or segments or a homopolymer structure:
(a) linear; (b) graft; (c) brush or comb; (d) ring; (e) star An Bn ; (f) star-block (AB)n ; (g) AB2 star; (h) palm tree ABn ; (i) dumb-bell (pom-pom); and (j) H-shaped
B2 AB2 .
into structures of higher order. By coordinating the structure and composition of polymers, materials possessing a
diverse array of attributes can be formed and utilized in a
wide range of applications.
With the rise of controlled/living [1] radical polymerization techniques, pathways were created that allowed
access to many polymer architectures, the range of
structures possible only limited by the creativity and imagination of the researcher. Reversible addition fragmentation
chain transfer (RAFT) [2] is one of the very successful
polymerization tools that allows this goal to be achieved
[36]. It should be mentioned here that RAFT polymerization is equivalent to MADIX (macromolecular design
41
Fig. 2. A simple example regarding the formation of a diblock copolymer. Using RAFT polymerization to form a homopolymer and chain extending the
macromolecule with a different monomer to yield the desired block copolymer.
42
Fig. 3. The formation of a block copolymer via the chain extension of a macro-RAFT. The various initiation, propagation and termination steps have been
highlighted.
[51] (Copyright, Wiley-VCH, 2008).
RAFT agent and initiator), must allow for the highest yield
of pure homopolymer to be obtained, with minimal termination effects and other side reactions taking place, to
ensure the vast majority of the polymer chains are capped
with the RAFT end group. In order to achieve this desired
outcome, one approach would be to use a high concentration of RAFT agent with minimal initiator present. Although
on the surface this would be the ideal solution, it invariably results in long retardation periods and drawn out (or
minimal) polymerization reactions taking place [59]. As
previously mentioned, using high concentrations of initiator may lead to a prevalence of termination reactions
and dead polymer chains, while too little may see reaction times extended to very long reactions times or, if the
systems are not totally free of contaminants, i.e., oxygen, a
complete loss of radicals, halting propagation in its tracks.
Although termination reactions can never be completely
avoided, by carefully choosing the correct parameters, they
can be severely limited. One way to do this is to stop
the polymerization when only a small percentage of the
available monomer has been polymerized, i.e., stop the
reactions at low conversions. While this can be an advantageous strategy, it may lead to the loss/waste of monomer,
which becomes especially important when a monomer is
not commercially available and/or requires extensive synthesis and purication processes to be made.
Along with radical termination processes, other pathways exist that can cause the destruction of the RAFT agent.
It is widely known that peroxides can destroy the thiocarbonate group due to oxidation [60], these may be found in
a number of common laboratory solvents, e.g., 1,4-dioxane
and THF. Several studies have looked at the removal of the
RAFT agent on purpose, in order to produce desired end
group functionalities [6163], but the RAFT agent can also
be lost inadvertently in an unwanted process. Heat, light
and pH can result in the loss of the RAFT end groups. Caution
not only needs to be taken during RAFT polymerizations to
stop the loss of the RAFT end group functionalities, but also
during the storage of the resulting polymeric products, e.g.,
leaving a RAFT produced polymer exposed to sunlight for
an extended period can remove the end groups due to the
inherent UV radiation [64]. Some speciality RAFT agents
or monomers may also cause unwanted reactions. A good
illustration of this comes from the work completed by the
Davis group where monomers and RAFT agents incorporating disulde moieties (based on pyridyl disulde) were
produced. In this case there is the risk that side reactions
involving disulde exchange could take place, once again
removing the RAFT agent from use [22,6567].
Although the majority of RAFT polymerizations use
additional azo-initiators to form block copolymers, ionizing radiation can also be used to initiate the reaction [68],
be it from a gamma source [69], or a microwave [70,71]. Roy
et al. were able to form well dened block copolymers from
acrylamide and acrylate monomers using a single mode
microwave reactor and with dramatically decreased reaction times (as low as 2 min), when compared to reactions
which relied on conventional heating. Ambient temperature RAFT polymerizations have also been carried out using
mild long-wave radiation and an appropriate photoinitiator [7274].
43
44
45
46
Fig. 4. Various RAFT agents used in the formation of block copolymers as listed in Table 1.
47
48
summarize most of the structures reported in the literature in regular updates [3,5,6]. (Note that some details,
such as concentrations, initiators used, reaction times, etc.,
are absent. This table is only to serve as a guide to the
reader in regards to the different structures that are possible. Should the reader require full experimental details,
they are directed to the complete reference paper.)
2.1.2. Cross-linked micelles
Finally, in the last part of this section we shall look at
a specic architecture of block copolymers, cross-linked
micelles. These are formed from amphiphilic polymers,
that have self-assembled in a micellar structure and,
after cross-linking, the structure has been locked, i.e., the
micelles cannot dissociate into the constituent unimers.
With RAFT polymers the cross-linking can take place either
in the core [23,162165], the shell [43,48,166168] or at
the nexus between the block copolymer blocks [169,170].
A number of different cross-linking techniques exist.
A range of different chemistries have been investigated
[171,172]. Most commonly, micelles are cross-linked via
the addition of a bifunctional reactive agent. Cross-linking
can be carried out using a radical pathway following the
addition of a divinyl cross-linker [48,100,165,173]. The
RAFT polymers undergo chain extension with the addition
of the fresh divinyl monomer creating triblock structures.
The reactions of both vinyl groups introduce crosslinks
between the various chains.
An interesting example of the radical approach was
performed by Zhang et al. who produced a nucleoside containing block copolymer, poly(polyethylene
glycol
methyl
ether
methacrylate)-b-poly(5 -Omethacryloyluridine) and after self-assembly cross-linked
the structure using the degradable compound bis(2methacryloyloxyethyl)disulde [165]. The synthesis
produced coreshell nanoparticles, which could degrade
under reductive conditions. The resulting core-crosslinked micelles readily hydrolyzed into free block copolymers in the presence of dithiothritol (DTT), in less than 1 h.
Another unusual way of cross-linking, presented
by the Wooley group, includes the synthesis of norbonene containing block copolymers. 4-(5 -Norbornene2 -methoxy)-2,3,5,6-tetrauorostyrene was polymerized
via RAFT leading to block copolymers with a polystyrene
blocks and randomly distributed norbonene side groups in
the second block. Ring-opening metathesis polymerization
led to core-cross-linked nanoparticles [176].
Examples of micelles prepared from polymers, formed
via RAFT and cross-linked using bifunctional reactive
agents are the most common structures encountered in
Fig. 5. Selected examples of neutral monomers: maleic anhydride (MAn), styrene (STY), methyl methacrylate (MMA), 4-vinylpyridine (4VP), 4vinylbenzyl chloride (VBC), pentauorostyrene (PFSty), N-vinylpyrrolidone (NVP), isoprene (IP), methyl acrylate (MA), N,N-dimethylacrylmide (DMA),
2-hydroxypropyl methacrylamide (HPMA), N-acryloylpiperidine (NAP), N-acryloylmorpholine (NAM), 2,5-dibromo-3-vinylthiophene (DBrVT), lauryl
methacrylate (LMA), n-butyl methacrylate (BMA), tert-butyl acrylate (t-BA), 2-hydroxyethyl methacrylate (HEMA), 2-hydroxyethyl acrylate (HEA), glycidyl methacrylate (GMA), vinyl chloroacetate (VClAc), vinyl acetate (VAc), pentauorophenyl methacrylate (FPMA), pentauorophenyl acrylate (PFPA)
N-vinylphthalimide (NVPH), polyethylene glycol methyl ether methacrylate (PEGMEMA), polyethylene glycol methyl ether acrylate (PEGEMA), trimethylsilylpropargyl methacrylate (TMSPMA), tert-butyldimethylsilyl methacrylate (tBSiMA) -methacryloxypropyltrimethoxysilane (MASi), aziodopropylacrylamide (AzA), 5-{1,3-dihydro-3,3-dimethyl-6-nitrospiro[2H-1-benzopyran-2,2 -(2H)-indole]}ethyl acrylate (DHNBA), 9-acryloyloxy-[3,3-bis(4methoxyphenyl)]-3H-naphtho[2,1-b]pyran (APNP), N-acryloyl-l-phenylalanine methyl ester (l-Phe-OMe), N-acryloyl-4-trans-hydroxy-l-proline (AHP),
6-acryloylaminohexanoic acid-1-adamantylamide (AAHA), 3-acrylamidophenylboronic acid (APBA) 2-(2-pyridyldisulde)ethylmethacrylate (PDSEMA)
4-(acrylamide)azobenzene (AAzB), vinyltriphenyl amine (p-HT).
49
Fig. 7. Examples of pH responsive monomers: acrylic acid (AA), acrylamide (AAm), 4-vinylbenzoic acid (4VBA), N,N-(diisopropylamino)ethyl methacrylate (DIPAMA), 2-cinnamoyloxyethyl acrylate (COEA), 2-(dimethylamino)ethyl methacrylate (DMAEMA), 2-(diethylamino)ethyl methacrylate (DEAEMA),
propylacrylic acid (PrAA), N-acryloylvaline (NACV), l-phenylalanine acrylamide (AP).
Fig. 8. Examples of thermoresponsive monomers: N-isopropylacrylamide (NIPAAm), N-(2-methacryloyloxyethyl) pyrrolidone (NAOEP), N,Ndiethylacrylamide (DEA), 2-hydroxypropyl acrylate (HPA), N-acryloyl-l-proline methyl ester (NAPME).
50
51
Table 1
Examples for block copolymer structures that can be formed using various monomer units, which can be neutral or ionic in nature and responsive to
changes in pH and temperature. The RAFT agents and monomers may be found in Figs. 48.
Entry Block 1
Block 2
Solventb
Reference
R18
R1
R5
R2
R19
R19
R3
R3
R10
R14
R1
R9
R1
R2
R5
R4
R20
R21
R22
R20
R25
R26
70
60
40, 50
60
70
80, 125
70
70
65
80
70
90
60, 60/80
60
60
70
70
80, 90
30
70
70/microwave
90/110
Toluene
H2 O
Toluene
DMF:H2 O (95:5)
Dioxane
Dioxane
DMAc
THF
DMF
Toluene
Dioxane
Bulk, dioxane
Dioxane
Acetonitrile, dioxane
Toluene
Dichloroethane
Bulk, dioxane
Benzene
Dioxane
Trioxane
Solvent mixtures
[129]
[123]
[130]
[79]
[131]
[132]
[91]
[22]
[133]
[134]
[135]
[136]
[137]
[138]
[50]
[81]
[139]
[36]
[73]
[140]
[141]
[142]
R3
R3
R3
R19
R16
R16
Various
70
70
80
80, 60
60
Various, N-methyl-2-pyrrolidone
H2 O:EtOH (2:1), H2 O
Acetate buffer (pH 5.2)
Benzene, benzene:NaOH(aq) (1:1)
Dioxane, DMF
Dioxane
[143]
[105]
[144]
[145]
[146]
[147]
R3
R3
R3
R6
R3
70
70, 60
70
80
70
[107]
[148]
[77]
[149]
R7
R3
R1
R8
R9
R22
R10
R19
R10
70
70
80
60
80, 70
30
110, 90
80
60
Dioxane
Dioxane
Dioxane
DMF
THF
MeOH
Bulk, THF
tert-Butanol
Chlorobenzene, DMF
[114]
[23]
[124]
[76]
[112]
[72]
[16]
[150]
[151]
R3
R1
R12
R1
R6
R6
R3
70, 25
70, 80
70, 30
80
60
70
60
H2 O (pH 4.5)
Dioxane
H2 O (pH 6.5), H2 O (pH 4.8)
THF
DMF
THF
Water/dioxane
[38]
[152]
[30]
[153]
[154]
[104]
[155]
R5
R5
R23
R11
R15
R1
R24
R19
20
70
70
30
80
90, 60
70
60
[156]
[157]
[45]
[101]
[158]
[159]
[160]
[161]
Where two temperatures are shown the former relates to the synthesis of the rst segment, the latter relates to the formation of the second segment.
Where two solvents are shown the former relates to the synthesis of the rst segment, the latter relates to the formation of the second segment.
-Cyclodextrin was also introduced to produce an inclusion complex with the adamantane units.
Later converted into HMPA units.
Later converted into acrylic acid.
Uses a photoinitiator for both reactions.
52
Fig. 9. The formation of triblock copolymers adopting three different chain extension strategies: Pathway 1 sequential chain extensions (the example
yielding a ABC triblock copolymer); Pathway 2 the use of a compound containing two RAFT agents tethered together (the examples given shows two
RAFT agents linked via the Z-groups (left) or the R-groups (right) showing the formation of ABA triblock copolymer) or Pathway 3 RAFT agents possessing
two leaving groups (the example showing the formation of a ABA triblock copolymer).
53
Fig. 10. Difunctional RAFT agents which are connected via a linker through either the Z group (R27, R28) or R group (R29, R30, R31) allowing the formation
of ABA (Fig. 9.2a) and BAB (Fig. 9.2b) block copolymers.
were prepared by RAFT via the cross-linking of linear triblock copolymer precursors possessing two active polymer
ends. These were interconnected via cross-linking to form
three-dimensional networks.
Another co-network was formed using R29,
for the preparation of end-linked semiuorinated
amphiphilic polymer co-networks based on 2,2,2triuoroethyl methacrylate (hydrophobic monomer)
and 2-(dimethylamino)ethyl methacrylate (DMAEMA,
hydrophilic monomer) [190]. Ethylene glycol dimethacrylate (EGDMA) served as the cross-linker. Various ABA
and BAB copolymers were synthesized (where A was
the uorinated block and the B block was comprised of
DMAEMA), with the co-networks characterised in terms of
their degrees of swelling in THF and in water as a function
of the solution pH.
Following on from Fig. 9, Pathway 2, the third route
(Fig. 9, Pathway 3) employs RAFT agents which possess
two leaving groups. A selection of these difunctional RAFT
agents are shown in Fig. 11. The majority of work has used
R32, including Ran et al. who used it in the photopolymerizations of STY and BA [197]. The macro-RAFT agent
of PS successfully controlled the polymerization of BA with
PDI values for the nal products being between 1.12 and
1.14. Liu et al. modied R32 to include two pyridyldisulde
groups [67]. After producing telechelic triblock copolymers
with oligo(ethyleneglycol)acrylate and STY, micelles were
formed and the presence of the disulde groups within the
micelle corona was proven by UVvis spectroscopy. The
pyridyldisulde groups were then used to functionalize the
54
Fig. 11. Difunctional RAFT agents which can be used to produce triblock copolymers according to the procedure in displayed Fig. 9.3.
micelles with a thiol bearing model peptide, reduced glutathione, and a thiol modied uorophore, rhodamine B,
under mild reaction conditions.
As with other synthetic routes designed to produce
block copolymers, amphiphilic copolymers can be formed
using this technique. For example, Vekataraman and Wooley produced ABA and BAB triblock copolymers with
di(ethylene glycol) 2-ethylhexyl ether acrylate and t-BA
[198].
A lot of the amphiphilic systems, based on Fig. 9, Pathway 3, utilize NIPAAm, focussing on its thermoresponsive
behavior (LCST). The aggregation behavior of the thermoresponsive polymers was the primary focus for most
of the studies. For example, Fu et al. used well-dened
naphthalene end-capped STY and NIPAAm amphiphilic
triblock copolymers, coupled with transmission electron
microscopy (TEM), to look at the various aggregates formed
in water and DMF mixtures [199]. Nykaenen et al. described
the synthesis of styrene and NIPAAm triblock copolymers
and their self-assembly and phase behavior in bulk [200].
The self-assembly and phase behavior in bulk of the triblock
copolymers, as well as selected blends with low molecular
weight NIPAAm homopolymers were studied using TEM.
Classical lamellar, cylindrical, spherical, and bicontinuous
double gyroid morphologies were observed in the dried
state. In aqueous solutions, the glassy PS domains act as
physical cross-links, and hydrogels were therefore, formed.
With their ABA triblock copolymers of STY (A block) and
NIPAAm (B block), Zhou et al. formed micelle like aggregates with PS blocks as the cores and PNIPAAm rings as
the coronas [201]. The hydrolysis of the trithiocarbonate
group led the rings in the corona to be cut into open linear
coils.
Qu et al. obtained an unusual structure with their
amphiphilic thermo-responsive ABA triblock copolymer
with MMA (A blocks), and NIPAMM (copolymerized with
PEGMEMA for the B block) [33]. The copolymer dispersed
in water and self-assembled into nanoscaled micelles in
a owerlike arrangement at room temperature. Notably,
there was no copolymer precipitation observed at the LCST,
which is advantageous in regards to the in vivo use of the
micelle. The micelles loaded with folic acid as a model
drug showed a promising thermo-responsive drug release
behavior.
Zhou et al. looked at a series of novel pH and temperature responsive triblock copolymers with stearyl
methacrylate and NIPAAm, the latter as the center block,
using R32 [202]. By varying the organic solvent used in
the self-assembly procedure and adjusting the copolymer
composition, multiple morphologies ranging from vesicles
to coreshell spherical aggregates and pearl-necklace-like
aggregates were obtained.
Kirkland et al. used NIPAAm to form narrowly dispersed,
temperature-responsive BAB block copolymers capable of
forming physical gels under physiological conditions [203].
The NIPAAm (B blocks), was copolymerized in the presence
of R32 with DMA (the A block). At concentrations as low
as 7.5 wt.%, the copolymers formed reversible physical gels
above the phase transition temperature of PNIPPAm. The
mechanical properties of the gel were found to be similar
to those of the naturally occurring collagen.
Nuopponen et al. controlled the tacticity of their
ABA stereoblock polymers with atactic PNIPAAm as a
hydrophilic block (either A or B) and a non-water-soluble
block consisting of isotactic PNIPAAm, using R32 in the
absence, or presence, of yttrium triuoromethanesulfonate, respectively [204]. Both the atactic and isotactic
PNIPAAm macromolecules were successfully used as
macro-RAFT agents.
Xiao et al. produced a functional coilrodcoil triblock
copolymer containing a rigid teruorene unit (rod) and
PNIPAAm for the exible coil using a teruorene-based
dithioester as the RAFT agent [205]. The temperatureresponsive optical properties were investigated with the
aid of dynamic light scattering and uorescence techniques. The copolymers have a potential to be used as
responsive uorescent probes in facile detection of dyelabelled biopolymers.
2.1.4. Conclusions to 2.1
The cornucopia of block copolymers reported so
far shows the versatility of the chain extension of a
macro-RAFT agent to generate these architectures. After
considering suitable experimental conditions, the choices
seem limitless. However, there are still restrictions such as
the order of the preparation, which requires starting the
synthesis with the block that forms the most stable radicals. This can have implications with the position of the
55
56
Fig. 12. The various pathways for producing block copolymers via the combination of RAFT with other, mutually exclusive polymerization techniques. Five
possible pathways are envisaged wherein the polymer blocks are formed using RAFT polymerization (solid spheres) or another technique (blank spheres)
either via successive or concurrent polymerizations.
57
58
way to form block copolymers it to employ a difunctional compound that can take part in a non-RAFT process.
The product, a macro-RAFT agent, can then be redeployed for the controlled synthesis of a vinyl monomer,
Fig. 12, Pathway 2. The reverse process is also viable
with the RAFT polymerization performed rst, followed
by the mutually exclusive process Fig. 12, Pathway
4. A good example of these routes is the combination
of either ROP [14,17,26,92,102,103,245252] or ROMP
[207,253,254] with RAFT.
The most heavily researched area, using Fig. 12, Pathway 2, is with ROP (using metal catalyzed [170,255,256],
enzymatic [206] or anionic routes [103]). This route allows
for the formation of copolymers incorporating biodegradable polymers such as PCL [17,26,49,102,103,248,257] or
PLA [14,92,169,170,245247,249]. These polymers can act
as templates, e.g., in the formation of nano-cages [170], and
can be easily removed in the correct environment, such as
acidic solutions.
A number of different block copolymers have been
produced using Fig. 12, Pathway 2. Mespouille used 2(benzylsulfanylthiocarbonylsulfanyl)ethanol, the terminal
hydroxyl unit acting as the initiator for the ROP of LA.
The thus formed macro-RAFT agent was then successfully
deployed for the controlled polymerization of NIPAAm. The
process showed high conversions (>99%) and the products
exhibited low PDI values (1.19) [258]. The same process was reported almost simultaneously by Hales et al.,
who further investigated the self-assembly and crosslinking of the aggregates [169]. In a similar approach Ting
et al. were able to produce hollow poly(6-O-acryloyl-Rd-galactopyranose) (PAGP) nano-spheres [170]. Initially,
an amphiphilic block copolymer, PLA-b-PAGP, was synthesized using a PLA macro-RAFT agent. The block copolymers
self-assembled in aqueous solution to form micelles with
pendent galactose moieties covering the surface. The
micelles were cross-linked at the nexus of the copolymer using hexandiol diacrylate, creating stable aggregates.
Aminolysis with hexylamine allowed removal of the lactide
core without any detrimental effect on the glycopolymer
units, to produce hollow nano-cages.
Following in their footsteps, Saeed et al. found a facile
route to biocompatible poly(lactic acid-co-glycolic acid)b-poly(ethylene glycol methacrylate) copolymers utilizing
ROP and applying the polymer as a macro-RAFT agent
for ethylene glycol methacrylate (Fig. 13) [255]. A series
of polymers with various co-monomer content and block
length were synthesized with low polydispersities. All the
block co-polymers formed micelles in aqueous solutions
and were able to encapsulate model drugs (carboxyuorescein and uorescein isothiocyanate).
While most catalytic system employed do not lead
to any regularity within the PLA, the group of OReilly
managed to synthesize recently homochiral PLA using a
functional RAFT agent as initiating species, which was used
to prepare block copolymers [259].
As mentioned in the section above, RAFT and ATRP
can be combined to generate block copolymers with
monomers possessing disparate reactivities. P(t-BA)-bPVAc were obtained by Petruczok et al. in a three step
process [260]. Initially t-BA was polymerized via ATRP, the
59
60
Fig. 13. The formation of biocompatible micelles using a combination of RAFT and ROP.
[255] (Copyright, Royal Society of Chemistry, 2009).
61
Fig. 14. The combination of RAFT and ATRP to yield block copolymers. Either route can be taken to yield the desired products.
[275] (Copyright, Royal Society of Chemistry, 2008).
62
63
Fig. 16. Various glycomonomers used for the formation of block copolymers. 3-O-Acryloyl-1,2:5,6-di-O-isopropylidene--d-glucofuranose (AIG)
[88], 3-O-methacryloyl-1,2:5,6-di-O-isopropylidene--d-glucofuranose (MIG) [85,86,88], 3 -(1 ,2 :5 ,6 -di-O-isopropylidene--d-glucofuranosyl)-6methacrylamido hexanoate (MIGC5 when n = 5) [88], 3 -(1 ,2 :5 ,6 -di-O-isopropylidene--d-glucofuranosyl)-11-methacrylamido undecanoate (MIGC11
when n = 10) [88], 6-O-methacryloyl--d-glucoside (MAGO) [281], acrylamidoglucopyranose (AAGP) [47], 2 -(4-vinyl-[1,2,3]-triazol-1-yl)ethyl-O-d-mannpyranoside (VTEMP) [284], 3-O-methacryloyl-1,2:3,4-di-O-isopropylidene-d-galactopyranose (MIGP) [87], 6-O-p-Vinylbenzyl-1,2:3,4-di-Oidopropylidene-d-galactopyranose (VDIGP) [291], 2-(-d-galactosyloxy)ethyl methacrylate (GEMA) [281], methacrylamidoglucopyranose (MAGP) [32],
2-(2 ,3 ,4 ,6 -tetra-O-acetyl--d-glucopyranosyloxy)ethyl methacrylate(AGPM) [255], 2-lactobionamidoethyl methacrylamide (LBAM) [292].
[32] (Copyright, John Wiley & Sons, 2009); [85] (Copyright, John Wiley & Sons, 2007); [86] (Copyright, John Wiley & Sons, 2007); [87] (Copyright, Elsevier,
2007); [88] (Copyright, Wiley-VCH, 2007); [255] (Copyright, Royal Society of Chemistry, 2009); [281] (Copyright, Royal Society of Chemistry, 2008); [283]
(Copyright, Wiley-VCH, 2007); [284] (Copyright, Wiley-VCH, 2010); [291] (Copyright, John Wiley & Sons, 2008); [292] (Copyright, American Chemical
Society, 2009).
64
Table 2
The synthesis of sugar containing block copolymers using the glycomonomers shown in Fig. 16, with experimental details and associated references.
Entry
First block
Second block
RAFT agent
T ( C)a
Solventb
Reference
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
NIPAAm
NIPAAm
NIPAAm
NIPAAm
GEMA
GEMA
MAMGIc
DEAEMA
MIG
3-MDF
AAGP
VTEMP
MIGP
VDIGP
AGPM
APMA
MAGP
AIG
MIG
MIGC5
MIGC11
DMAEMA
BA
BMA
MIG
BMA
BMA
NIPAAm
NIPAAm
DMAEMA
NIPAAm
PEGMEMA (n = 2)
LBAM
5 -O-Methacryloyl uridine
R1
R1
R1
R1
R3
R3
R3
R3
R2
R2
R5
R3
R1 or R2
R10
R1
R3
R3
95
95
95
95
70
?
?
70
70
70
60
60
60
90, 60
70, 65
70
60, 70
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
EtOH:H2 O (9:1)
DMF
DMF
1,4-Dioxane
H2 Oc
H2 Oc
EtOH, H2 O/DMSO
H2 O:MeOH (2:1), DMAC
DMF
Toluene, THF
MeOH, EtOH
H2 O:dioxane (2:1), H2 O:DMF (16:1)
DMAc/H2 O (9:1), DMSO
[88]
[88]
[88]
[88]
[281]
[281]
[281]
[86]
[85]
[85]
[47]
[284]
[87]
[291]
[89]
[292]
[32]
Where two temperatures are quoted the rst is used for the formation of the homopolymer and the second is for the construction of the block copolymer.
Where two solvent systems are shown the rst is in relation to the formation of the homopolymer and the second relates to the construction of the
block copolymer.
c
Mini emulsion systems.
b
65
66
Fig. 17. Two disparate homopolymer chains, possessing complimentary functionalities, which can combine to yield a block copolymer with the functional
groups combined at the nexus between the two chains.
Fig. 18. The coupling of azide and alkyne functionalized homopolymers via the copper catalyzed Huisgencycloaddition to form a block copolymer with a
mid-chain triazole ring.
Fig. 19. Modied compounds that incorporate alkyne groups which can be attached to complimentary azide containing compounds.
Fig. 20. RAFT agents functionalized with azidegroups which can be attached to complimentary alkyne containing compounds.
67
Table 3
Examples of block copolymers formed using the Cu(I) Huisgencycloaddition approach. The components used can be seen in Figs. 19 and 20.
Entry
1
2
3
4
5
6
7
8
9
10
11
12
Polymer 1
Polymer 2
Polymer
Azide component
PVAc
C7
1-(3-Azidopropyl)pyrrole-terminated
poly(isobutylene)
PMMA
C8
PMMA
C8
PMMA
C8
Mono azide PEG
(1000 g mol1 )
PBA/PEGMEA/PNIPAAm
C9
PVAc
C10
PVAc
C11
PS capped with azide after ATRP polymerization
P2VP
C6
Polymer
Poly(6-O-methacryloyl mannose)
PNIPAAm
Alkyne component
C1
C2
[288]
[326]
PAA
PDMA
PHEMA
P4VP
C2
C2
C2
C2
[323]
[323]
[323]
[329]
PCL/PLA
PS
Alkyne terminated PCL
Poly(N-acryloyl-l-valineN -methylamide)
Poly(3-(triethoxysilyl)propyl methacrylate)-block-PS
C4
C3
[327]
[324]
[252]
[328]
[325]
Reference
C2
C5
68
Fig. 21. The thiol-ene addition of a homopolymer possessing a single thiol unit to a another chain having free alkene moiety.
Table 4
Examples where block copolymers have been synthesized using other click approaches.
Polymer 1
Polymer 2
Polymer
Clickable functionality
Polymer
Clickable functionality
PNIPAM
PiBor
PS
PiBor
PiBor
PiBor
PS
PS
PS
PCL
PCL
PS
PS
PEG
Terminal thiol
Terminal cyclopentadiene
trans,trans-2,4-Hexadien-1-ol
Terminal cyclopentadiene
Terminal cyclopentadiene
Terminal cyclopentadiene
Azide
Click reaction
Reference
[322]
[334]
[250]
[335]
[335]
[336]
[337]
69
are sufciently electron decient, but that are able to control the molecular weights for a large array of monomers.
In the literature the polymers have been limited to STY and
iBor. New agents are currently being developed, including sulfonyldithioformate based RAFT agents [334]. These
were shown to undergo hetero DielsAlder with cyclopentadiene based polymers, although the only examples given
utilized PS and PiBor, so further work is required. Although
there seems to a limitation with the number of viable
monomers for the electron decient RAFT agents, a whole
multitude of polymers can be functionalized with the
appropriate diene, e.g., cyclopentadiene, by performing
facile reactions such as esterications.
A creative approach has been recently reported by Voit
et al. They formed a peptide bond via Staudinger ligation by
reacting two blocks, one with a phosphine-containing ester
functionality and one with a terminal azide group [337].
Although based on older chemistry practices, the use of
the click chemistry processes will continue to grow as the
feasibility of the routes is examined and discussed further.
2.5.3.1. Conclusion to 2.5. In theory, preparations of block
copolymers via click reaction seem to address a lot of
shortcomings of many other reactions. Limitations of block
copolymerization via chain extension of a macro-RAFT
agent include rm rules on the order in which the blocks
are prepared. In addition, block copolymers cannot be
prepared from two monomers with very disparate reactivities. Click reactions can indeed overcome these limitations
and several examples demonstrated the success of such
an approach. The rst prerequisite is the high purity of
both polymers in terms of the functional groups on the
ends of the polymer chains. This means that during the
polymerization with a RAFT agent, which carries, for example an azide group, loss of reactive groups should be
avoided. This might mean that side reactions should be
suppressed by careful selection of reaction conditions and
that the functional group should not react in a radical
process. The latter is often difcult to achieve and it is
known that certain groups such as azides might undergo
reaction with the monomer as highlighted above. Even
if the endfunctionality is high, subsequent click reaction
requires the exact stoichiometry of the two blocks to eliminate the need for further purication. This introduces
an element of uncertainty. It is therefore, not surprising that many click reactions lead to block copolymers
with PDIs higher than the homopolymers prior to reaction. According to the theory, the conjugation of two
polymers should result in a narrowing of the molecular weight distribution. Furthermore, most examples on
block copolymer synthesis via click chemistry deal with
rather short polymers, barely higher than 10,000 g mol1 .
The number of reports on successful synthesis procedures is probably inverse proportional to the molecular
weight of both blocks. Often the reaction is incomplete
at higher molecular weights. This can be understood in
terms of chain mobility and the necessary diffusion of
the two reactive chain ends towards each other. While
this process is already difcult, the actual occurring reaction is hampered by the rate of the click reaction. It is
therefore not surprising that a report on a high-molecular
70
R
S
S
Z
S
S
Z
Z
S
S
S
S
Z
R
Z
S
S
R
Fig. 23. Comparison of star synthesis using the core-rst strategy via Z-group (left) and R-group (right) approach.
3. Branched polymers
3.1. Star polymers
Similar to other star synthesis techniques, there are
two different avenues to synthesize star polymers: armrst and core rst. The RAFT process however, represents
a unique case since the core-rst method can be further
divided into two processes. Initially, the star synthesis via
core-rst technique was favored but in recent years there is
a stronger focus on arm-rst techniques. This shift in interest may be due to the increasing attention of the end group
chemistry of the RAFT made polymer and the emergence
of efcient click chemistries.
3.1.1. Star polymers via core-rst strategy
RAFT polymerization is unique between all the star
synthesis techniques because the core-rst strategy can
be further subdivided into two strategies: the R-group
approach and the Z-group approach. The core-rst strategy usually refers to the attachment of multiple initiating
sites with the number of arms equivalent to the number
71
72
I.
Initiator
2I
II.
I + M
Pn
III.
RAFT process
Z
Z
S
Z
Pn
Pn
S
S
R
S
Z
Z
S
S
S
S
Pn
R
S
Z
S
linear
macroRAFT
S
Z
S
S
An
S
S
Z
S
S
Z
S
S
S
S
Z
S
Z
S
R
Pn
Termination reactions
S
S
S
R
S
Z
S
Z
S
S
S
S
Z
S
R
An
S
Z
S
S
Pn
Z
S
An
S
Z
Pn
Z
S
Pn
Pn
Pn
Z
S
Z
S
An
S
S
S
R
An
S
S
S
An
S
Z
Pn
Z
S
An
targeted product
S
S
IV.
growth of arms
Pn
s
Fig. 25. Schematic drawing of the synthesis of star polymers via R-group approach.
73
Table 5
Star polymers via R-group approach (N = number of arms).
N
Type of core
1,1,1Tris(hydroxymethyl)ethane,
pentaerythriol
Benzene
RAFT group
Arms
Polymerization T ( C)
solvent
Reference
PVAc
Bulk
60
[349]
Dioxane
65
[359]
110
[353]
PVPi
PVND
PVAG
PS
PEGA
Benzene
PS
Bulk
60
PMA
Benzene
PMA
Toluene
65
[356]
PAcOSty
Toluene
60
[362]
Benzene
PVBC
Bulk
120
[282]
Benzene
PNVP
Bulk
60
[351]
Pentaerythritol
PNIPAAm
DMF
70
[361]
Pentaerythritol
PS
PMMA
PS-b-PDMAEMA
Bulk
80
[363]
Pentaerythritol
PNVC
Dioxane
60
[352]
Pentaerythritol
PtBBPMA
Toluene
70
[358]
Porphyrine
PDEA
Dioxane
70
[364]
Ruthenium
tris(bipyridyl)
complex
PNIPAAm
Chlorobenzene
70
[365,366]
P(Styrylcoumarin)
74
Table 5 (Continued)
N
Type of core
RAFT group
Arms
Polymerization
solvent
PMMA
Toluene
Europium tris
(-diketenate)
complex
PS-co-PBEVB
PBEVB
Benzene
PS
PS
T ( C)
Reference
70
[367]
Bulk
80
100
120
[345]
Bulk
35
[368]
O
S
Triphenylene
NH O
C H
S
Dendrimer
PtBA
70
110
PNIPAAm
THF
100
[350]
PS
THF
120
[354]
65
[360]
100
[355]
70
[357]
105
[102]
16
Dendrimer
16
16
16
PMA
Hyperbranched
-caprolactone
(-CL)
DMAEMA
Toluene
Dendrimer
PS
THF
PMA
16
19
Dentritic core
with already
existing 16
P(EO-THF)
arms
PMMA
Dioxane
Dendrimer/PCL
PDMAEMA
THF
75
76
I.
Initiator
2I
II.
P1
+ M
S
S
S
S
Z
S
S
R
R
R
+ Pn
R
Pm
R
S
S
Z
S
S
R
S Pn
R
S
S
S
S
S
S Pn
S
S
Z
S
R
S
S
R
Pm
+ M
R
R
S
R
S
S
S
S
R
S
S
Z
S
Pn
S
S
S
S
S
Z
S
R
S
S
R
Pn
Pm
targeted product
Dn+m
Fig. 26. Schematic drawing of the synthesis of star polymers via Z-group approach.
R
S
S
S
R
Fig. 27. Schematic drawing of the hindered accessibility of the RAFT group during the synthesis of star polymers using the Z-group approach caused by
the shielding effect of the growing polymer arms.
[369] (Copyright, American Chemical Society, 2007).
77
Table 6
Star polymers prepared via RAFT process using Z-group approach (N = number of arms).
N
Type of core
Thiourethaneisocyanurate
RAFT group
Arms
Polymerization
solvent
T ( C)
Reference
PS
Bulk
60
[386]
PVAc
Bulk
60
[349]
PS
Bulk
60
[379]
PS
BA
PAGA
PBA
PS
Bulk
Bulk
Water
Bulk
Bulk
60
60
60
60
80
[387]
[387]
[384]
[375]
[372]
VAc
Bulk
60
[388]
PS
Dioxane
75
[382]
PNIPAAm
Dioxane
60
1,1,1-Tris(hydroxy
methyl)ethane
1,1,1-Tris(hydroxy
methyl)ethane
S
O
1,1,1-Tris(hydroxy
methyl)ethane
S
S
1,1,1-Tris(hydroxy
methyl)ethane
1,1,1-Tris(hydroxy
methyl)ethane
PS
Bulk
80
[372]
1,3,5-Triazine
PS
Bulk
115
[389]
PS-b-PNIPAAm
THF
70
VAc
Bulk
60
Pentaerythritol
90
VPr
[390]
Pentaerythritol
PS
Bulk
110
[353]
PMA
PtBA
PS
PNIPAAM
P(l-Phe-OMe)
PBA
PS
Bulk
Toluene
Toluene
DMF
Dioxane
Bulk
Bulk
60
60
60
60
60
60
80
[353]
[391]
[391]
[392]
[383]
[375]
[372]
VAc
Bulk
60
[349]
PNVC
Dioxane
60
[393]
S
O
Pentaerythritol
S
S
Pentaerythritol
78
Table 6 (Continued)
N
Type of core
RAFT group
Arms
Polymerization
solvent
T ( C)
Reference
PVAc
Bulk
60
[388]
PNVC
Dioxane
60
[352]
S
O
Pentaerythritol
S
S
Pentaerythritol
PNVC
Dioxane
60
[352]
Pentaerythritol
STY
Bulk
80
[372]
Polypseudorotaxanes
PNIPAAm
DMF
60
[385]
BISTRIS-PCL-b-PLA
PDMAEMA
Dioxane
80
[26]
Dendrimer
PS
Bulk
60
[379]
PS
BA
Bulk
60
60
[387]
[387]
P(l-Phe-OMe)
Dioxane
60
[383]
PS
PS
Bulk
Bulk
80
80
[374]
[372]
PBA
Bulk
60
[375]
PMA
PBA
PDA
Bulk
Bulk
Bulk
60
60
60
[373]
[373]
[373]
PS
Bulk
80
[374]
PS
Bulk
80
[372]
PS
Dioxane
75
[381]
PPEGA
PSPPEGA
Dioxane
Dioxane
70
70
PS
Bulk
60
[369]
PS
PS
PEA
PAGA
PHEA
Bulk
Bulk
Bulk
Water
DMSO
100
120
60
65
60
[369]
[369]
[369]
[173]
[173]
Dipentaerythritol
Dipentaerythritol
Dipentaerythritol
Dendrimer
-Cyclodextrin
79
Table 6 (Continued)
N
Type of core
12
Hyperbranched
polyester
12
Dendrimer
RAFT group
Arms
Polymerization
solvent
T ( C)
Reference
STY
Bulk
60
[378]
STY
Bulk
110
[394]
PS
Bulk
60
[379]
PBA
Bulk
60
[387]
NIPAAm
Dioxane
65
[395]
S
O
S
12
17
Dendrimer
Hyperbranched
polyglycerol
DMAEA
70
17
Hyperbranched
polyglycerol
EA
Bulk
80
[396]
16/65
Hyperbranched
polyglycerol
STY
Bulk
120
[370]
60/110
Hyperbranched with
PS arms
PBA
Toluene
80
[371]
polymerization is the addition of linear RAFT agent. Assuming an efcient chain-transfer between the macro-radical
and the linear macro-RAFT agent, the molecular weight
was a direct indication of the molecular weight of each
arm and, in return, the number of arms [372,375]. Despite
optimization of all the parameters, some tailing could not
be eliminated and the authors concluded that this must
be solely due to the shielding effect, which hinders the
chain transfer close to the core. Monte Carlo simulations
were used, conrming the presence of the shielding effect,
which becomes more pronounced with larger, or longer
polymer arms [376,377]. The authors also predicted that a
star RAFT agent that has the RAFT groups located a greater
distance from the core may witness less unwanted termination. Indeed, a hyperbranched core [378] with the same
number of arms as a well-dened dendritic core [379] did
prevent further growth of the arm after a monomer conversion of 20% while the dendritic core allowed the controlled
growth of the star polymer to higher conversions. Systems,
such as the star polymer which has been prepared by the
initial ROP followed by the attachment of a RAFT agent on
each PLA arm [26], should then not be affected by shieldingeffects. Shielding effects should therefore, be inuenced by
parameters that might determine chain mobility such as
the solvent present in a reaction [380].
In addition to advancements in terms of understanding
the mechanics involved when synthesizing star polymers,
there has been a clear push to utilize star polymers in var-
with [M], [I] and [RAFT] the initial monomer, initiator and
RAFT agent concentration, respectively, d the number of
chain generated during termination process, f the initiator
efciency, kd the initiator decomposition rate coefcient
and Mmonomer and MRAFT agent are the molecular weights of
80
81
Fig. 28. Schematic approach to star polymers; (a) macroRAFT and crosslinker are soluble in solvent; (b) macroRAFT is soluble in solvent, but the polymer
of crosslinker and co-monomer are incompatible with solvent causing preassembly into star-shaped structure; (c) pre-assembly prior core-cross-linking
using an amphiphilic block copolymer and subsequent core-crosslinking of star-like micelle.
crosslinker
S
n+1 m
1.2
8 hours
16 hours
24 hours
36 hours
48 hours
1.0
0.8
n+1
S
m
R
X
X
X
X
n+1
S
m
n+1
S
m
S
R
R X
0.6
X R
0.4
X X X X
X X X X
S
Z
X
X
X
X
R
0.2
0.0
-1
Fig. 29. Synthesis of polystyrene star polymers via arm-rst approach and molecular weight distribution after different polymerization times.
[397] (Copyright, Royal Society of Chemistry, 2003).
82
R
X
O
O
nO
CN
S
O
S
NC
nO
CN
S
S
soluble in ethanol/THF
soluble in solvent
insoluble in solvent
X
X
X X X X
!
X
X R
X X X X
X
X
X
X
R
Fig. 30. Synthesis of well-dened star polymers via arm-rst strategy facilitated by suitable solvent choice.
[404] (Copyright, John Wiley & Sons, 2006).
83
azide-alkyne Huisgen cycloaddition requires the modication of proteins in order to introduce alkyne or azides
moieties. BSA has therefore been modied with three
alkyne moieties, which were then linked with PNIPAAm,
which was obtained by polymerization in the presence of
an azide containing RAFT agent [419].
In contrast to star polymer synthesis via click chemistry as described in the section above, the molecular
weight of the polymers that were clicked or reacted
to the core by other efcient synthetic approaches were
usually much higher. For example the PVP arms, which
were reacted with lysozyme, had molecular weights up
to 33,000 g mol1 leading to seven-arms star polymers
with substantial molecular weights [420]. The difference
between these approaches is the spacing between the two
functional groups.
3.1.2.5. Supramolecular star polymers. The interest in noncovalent bonds to create complex molecules has been a
popular topic for many years now for the synthesis of star
polymers. RAFT agents with bypyridyl functionalities were
used for the polymerization of PNIPAAm and PS and upon
mixing the polymers with ruthenium ions, star-shaped
metallopolymers were created with a ruthenium core and
PNIPAAm and PS arms and a combination of both, respectively.
Hetero-complementary H-Bonding RAFT agents, one
with thymine and one with diaminopyridine, were
employed to generate supramolecular PVAc 3-arm stars
(Fig. 32) [421]. Interestingly this supramolecular approach
was sufciently powerful to create a star polymer from
polymers with substantial molecular weights of 6000 and
20,000 g mol1 . Although ionic bonding between a charged
RAFT agent and an oppositely charged core should t into
this category, it has not been utilized yet using the arm rst
strategy, but only the core-rst strategy [368] and as a pathway to introduce an building block to generate miktoarm
stars [422].
3.1.2.6. Conclusion to 3.1.2. The synthesis of star polymers
via arm-rst strategies using radical crosslinking strategies has seen increased activity over the last few years.
The versatility of this technique and the simplicity from
a mechanistic point of view saw a shift in favor from the
core-rst to the arm-rst strategy. Although experimen-
84
Fig. 32. Synthesis of heterocomplementary H-bonding xanthate RAFT agent, followed by polymerization of VAc and the supramolecular assembly of the
blocks to a three-arm star polymer.
[421] (Copyright, Wiley-VCH, 2009).
RAFT agents to a tetrafunctional core while the remaining two functional groups were used for single-electron
transfer-mediated living radical polymerization (SET-LRP)
[423] or for anionic polymerizations.
Three arm-star polymers were prepared based on
ABC triblock copolymers, in which the second block, B,
consisted of only one reactive repeating unit. Monomers
which cannot undergo homopolymerization such as maleic
anhydride [424] or hydroxyethylene cinnamate [425] were
employed to achieve An B1 Cm structures. The reactive B
block underwent reaction with end functionalized polymers leading to three-arm star polymers [424,425] or can
be used directly as the initiator for the polymerization of
the third arm [28].
Click chemistry was soon utilized to extend the scope
of this approach. Due to the orthogonality of click chemistry, a series of different arms can be grown from the core
without interfering with the polymerization, as shown in
the synthesis of (PS)(PCL)(PMA)(PEO) ABCD 4-miktoarm
star polymer [426] or (PCL)2 (PBA) A2 B three arms stars
[327]. Other type of click reactions employed includes the
aldehydeaminooxy click reaction, which has been used to
prepare An Bn star polymers [401,402].
A very versatile tool to generate miktoarm star polymers
is supramolecular chemistry. Simply by mixing different
arms, a whole library of different types of star polymers
can be created. Non-covalent ligandmetal complexation
between bypyridyl terminated polymers and ruthenium
complex created A2 B type miktoarm stars [427]. An array
of A2 B miktoarm star polymers, with molecular weights up
to 20,000 g mol1 , were obtained using heterocomplementary H-bonding RAFT agents [428].
3.1.3.1. Conclusion to 3.1.3. Since the synthesis of
miktoarm-arm star polymers requires the combination of
several techniques, the impact of RAFT polymerization is
not immediately evident although it certainly expanded
the scope of synthetic approaches available to researchers.
3.2. Graft and comb polymers
Graft and comb polymers are closely related to each
other. They both consist of a backbone with branches
attached [11]. Comb polymers have, however, higher
branching density and the chemistry of the backbone
should be similar to that of the branch. The synthesis
of both architectures via RAFT polymerization is equivalent and in the following chapter we will only use the
term graft polymers, not only because most polymers
described in the literature are indeed graft polymers, but
also for convenience. Graft polymers polymers with a
linear backbone and a number of branches along this
chain can be prepared in a similar fashion to star polymers using the attachment of RAFT agents along a linear
polymer chain the backbone. The branches grow from
the RAFT agent anchor points in a controlled fashion.
Branches were also prepared using other polymerization
techniques by combing the RAFT process with a non-RAFT
technique. A one-step approach is the random copolymerization of a macro-monomer with another monomer
forming the branch structure in situ with the growing backbone. In recent years, click chemistry has been utilized
more and more in order to create well-dened graft polymers (Fig. 33).
3.2.1. Graft polymers via the attachment of a RAFT agent
to the backbone
Similar to the synthesis of star polymers, RAFT polymerization is unique regarding the attachment of the chain
transfer agent, which can be carried out via the R-group and
Z-group. Everything discussed earlier regarding the mechanism of the two approaches, advantages and disadvantage,
are valid. Moreover, the presence of usually signicantly
more RAFT agent on one backbone can magnify problems,
such as the increased occurrence of side reactions.
3.2.1.1. Graft polymers via R-group approach. The rst graft
polymer described via RAFT polymerization, in this case
essentially a comb polymer, was based on poly(vinylbenzyl
chloride), which was modied with RAFT functionalities
(Fig. 34) [429]. Similar to star polymers a fraction of linear polymers with RAFT endfunctionalities were observed,
appearing as shoulders in the molecular weight distribution. The event is however, overshadowed by signicant
combcomb termination events, which at high conversions
even led to insoluble network polymers.
These experimental results are in agreement with theoretical predications outlined in the star polymer synthesis
section. The typically higher number of branches in a graft
polymer compared to a star polymer magnies the termi-
85
86
R-group approach
S
S S
Z
S S
Z
S S
Z
S
Z
S
S S
S S
Z
S
Z
S
S
R
S S
R
S S
R
S S
R
S S
S S
S S
S R
I
S
S
S
Z
S
S R
Macromonomer technique
Z
N3
X
S
S
87
Fig. 34. Synthetic route to graft polymers (left), and evolution of the molecular weight distribution with time (right) for PS combs (vinylbenzyldithiobenzoate concentration = 55 mol.%; T = 60 C; t = 4, 8, 12, or 16 h; [AIBN] = 1.2 mmol L1 ; benzyl dithiobenzoate moiety concentration = 16.3 mmol L1 ), comb
precursor = 38,600 g mol1 .
[429] (Copyright, John Wiley & Sons, 2002).
3.2.1.2. Graft polymers via the Z-group approach. The Zgroup approach to graft polymers faces similar difculties
to the star synthesis such as steric shielding leading to
the increased occurrence of termination reactions of two
linear macro radicals. PS branches were grown from cellulose resulting in monomodal distributions. The hydrolysis
of arms however revealed that the growth of each branch
deviates even further from the expected value than during the star synthesis. Some branches already reached a
signicant length, other RAFT agents still remained inactivate [444,445]. Synthesis of graft polymers via Z-group
88
Fig. 35. Grafting of NIPAAm from pullulan via R-group approach (PulSTS: pullulan macroRAFT agent; NgPul: pullulan-graft-PNIPAAm).
[437] (Copyright, American Chemical Society, 2008).
S
HN
O
S
NH
AgNO3
89
S
n
S
O
HN
90
S
S
R
S
S
AIBN
S
Z
S R
R
R
S
S
Z
Z
S
Z
S R
S
R
S
R
AIBN
S
R
R
R
S
R
S
SB
BS
BS
SB
S
Z
S
BS
B
Aminloysis
SB
BS
BS
BS
SB
SB
BS
BS
BS
BS
BS
SB
Fig. 37. Synthetic strategies to hyperbranched polymers.
BS
S
Z
R
S
91
polymers were attained via self-condensing vinyl copolymerization [490] (Fig. 37, middle).
Controlling the distance between two branching points
can introduce some regularity to the otherwise broad
molecular weight distribution of the branched polymer.
Telechelic AB2 -polymers with one functionality at one end
that is capable of reacting with two complementary functionalities on the opposite chain end can be employed in
a self-condensing process. Polymers made via the RAFT
process have already an in-built thiol end group, which is
readily available after aminolysis [492]. This thiol group
can then react with two bromide functionalities in the position [493], a -double pyridyl disulde end-groups
[494] or an -alkyne, which can react with two thiol
functionalities [495]. The latter approach was applied to
block copolymers leading to branched polymers with an
amphiphilic structure between two branching points [496]
(Fig. 37, bottom).
3.3.1. Conclusions to 3.3
The use of RAFT agents in the synthesis of hyperbranched polymers is reasonably new, but it made a
signicant impact. The aim of this approach is not so
much the design of a product with narrow molecular
weight distribution. After all, most hyperbranched polymers described here have high PDIs. It is more the
avoidance of gelation, the control over the end groups on
each branch and the control over the distance between two
branching points that sparked the interest in this area. It
would be desirable in the future to see more investigation into the properties of these materials and their use
in different applications.
3.4. Dendritic polymers
The rst dendritic polymer via RAFT polymerization
was described using poly(benzyl ether) monodendrons of
the second generation ([G-2]) or third generation ([G-3]),
which were modied with a RAFT agent in a R-group
approach (Fig. 38). Subsequent polymerization of NIPAAm
led to thermo-responsive micelles [497]. Using a symmet-
92
Fig. 39. Complex polymer architectures prepared by combination of RAFT with other techniques.
5. Conclusions
5.2. Recent developments
5.1. Experimental advice
What advice should be given for a novice in the area
of RAFT polymerization? RAFT polymerization seems to be
robust in the presence of many functional groups, but at
the same time can degenerate quickly in the presence of
other inuences. Heat, light and peroxides, which are often
present in some solvents, as well as alkaline groups such as
amines, can deplete the RAFT agent. However, this sensitivity of RAFT agents bear at the same time the opportunity to
convert the RAFT groups after the polymerization has been
completed. Considering these inuences, the next important step is to keep the radical concentration as low as
possible. Every mechanism discussed above includes side
reactions. These termination reactions often lead to the loss
of the RAFT groups and ultimately result in broader molec-
Despite certain difculties such as the occurrence of termination reactions, RAFT polymerization was shown to be a
versatile tool to access a range of different complex architectures. Especially the broader range of monomers that
can be polymerized in a controlled manner as well as the
robustness of the process in the presence of a range of functional groups makes the RAFT process unique and advantageous. It might have become clear in each chapter that there
are often signicant challenges to overcome. Although
there are some limitations, the power of RAFT polymerization lies certainly in its robustness. The array of monomers
is endless and some monomers can only be polymerized via
RAFT polymerization in a unique manner. This robustness
also allows the creative combination of RAFT polymerization with other materials and other techniques.
93
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