Polymers with a thermally triggered phase transition are important in the design of materials for biological applications, where their behavior can be used to trigger release or (dis)assembly events. Despite their advantages, a system with tunable thermal response, end-group reactive sites, low toxicity, and controlled main-chain degradability has not been realized, yet this would be a significant advance. The versatile new poly(oligo(ethylene glycol) vinyl acetate)s are presented with excellent control over their molecular properties obtained through RAFT/MADIX polymerization. Furthermore, we demonstrate structure-controlled thermal transitions, conjugation to human lysozyme through the retained end-group, and moreover show that this class of polymers can uniquely be copolymerized with 2-methylene-1,3-dioxepane (MDO) to generate polymers in which the degradability and cloud point can be independently tuned to create materials that display the same cloud point but degrade differently.
Thiolactones
allow catalyst-free polymer synthesis and modification
under stoichiometric conditions at mild temperatures, without the
need for tedious and costly purification steps. However, there is
a need for simple and general methods for the preparation of functional
thiolactones. We have developed a modular platform for γ-thiolactone
synthesis based on free-radical xanthate addition to alkenes. Because
of the ready availability of a great variety of functional vinyl,
allyl, and maleimido derivatives, numerous substituents (exemplified
here through alkyl, perfluoroalkyl, diethyl phosphonate, and N-substituted
succinimidyl groups) could be efficiently attached to the γ-position
of the thiolactone ring. A second substituent may be added in the
α-position by proper selection of the xanthate leaving group.
In all cases the target thiolactone was obtained in good yield from
the xanthate:alkene monoadduct by consecutive Chugaev elimination
and cyclization. The potential of these new substituted thiolactone
building blocks for polymer chemistry was demonstrated via an amine–thiol–ene
conjugation strategy which resulted in successful end-functionalization
of amino-terminated polymers and a thiol–acrylate step-growth
polymerization to prepare functional poly(ester amide)s. This versatile
method for making functional thiolactones should find broad applications
as a means to prepare new materials with original properties.
The development of innovative, easy
to implement strategies for
polymer synthesis and modification contributes to pushing back the
limits of macromolecular engineering. In this context, thiolactones
were highlighted as a new powerful “click” strategy
involving an amine–thiol–ene conjugation. In order to
further explore the potential of thiolactone chemistry for the field
of reversible-deactivation radical polymerization (RDRP), we have
developed a toolbox of γ-thiolactone-based RDRP agents including
xanthates, bromides, and an alkoxyamine. These RDRP agents were used
for the polymerization of more activated and less activated monomers
using appropriate RDRP techniques such as RAFT/MADIX, ATRP, and NMP.
Well-defined thiolactone-terminated polymers were obtained and characterized
for different degrees of polymerizations. An example of thiolactone–telechelic
PNIPAM using a thiolactone-based xanthate and an ω-end-chain
cyclization strategy was reported. The great reactivity of the thiolactone
end-group for postpolymerization modification was proven using primary
amines such as benzylamine or propargylamine, which ring-opened the
thiolactone with subsequent thiol–thiolsulfonate reaction to
scavenge the generated thiol. The original S-naphthalene
ethanethiosulfonate was used to give fluorescence properties to the
polymers.
Anionic polymerization of butadiene or/and styrene is performed with lithium initiators, functional or not. The polymer chains are subsequently transferred to magnesium. The resulting polymeryl-magnesium compounds were combined with {(Me 2 Si(C 13 H 8 ) 2 )Nd(μ-BH 4 )[(μ-BH 4 )Li(THF)]} 2 metallocene complex to act as macromolecular chain transfer agents (macroCTAs) in coordinative chain transfer polymerization (CCTP) of ethylene (E) or its copolymerization (CCTcoP) with butadiene (B). Block copolymers were produced for the first time by this switch from anionic polymerization to CCTP. Hard and soft blocks such as PB, polystyrene (PS), poly(styrene-co-butadiene) (SBR) obtained by anionic polymerization and PE or poly(ethylene-cobutadiene) (EBR) produced by CCT(co)P were combined and the corresponding structures were characterized.
Block copolymers based on ethylene (E) and butadiene (B) were prepared using the ansa-bis(fluorenyl) complex {Me 2 Si(C 13 H 8 ) 2 Nd(BH 4 ) 2 Li(THF)} 2 in combination with (n-Bu)(n-Oct)Mg (BOMAG) as a chain-transfer agent. The diblock copolymers incorporating a soft poly(ethylene-cobutadiene) segment, called ethylene butadiene rubber (EBR), and a hard polyethylene (PE) one were obtained by simply adjusting the different feeds of monomers during the polymerization. The soluble EBR block was formed first by feeding the catalytic system dissolved in toluene at 70 °C with a mixture of ethylene and butadiene (E/B molar ratio 80 : 20).Then the feeding was stopped leading to the consumption of a large part of the residual monomers. The reactor was finally fed with ethylene to form the PE block. By varying the molar mass of the latter, it is shown that the resulting soft-b-hard block copolymers can self-assemble simultaneously to the growth of the PE block in agreement with a polymerizationinduced self-assembly (PISA) mechanism. The self-assembly is discussed considering the reaction conditions, the crystallization of the PE block, and the polymerization mechanism involved.
A modular
platform based on free-radical xanthate addition to alkenes
enables access to a large series of functional γ-thiolactones.
This methodology includes two different pathways based on xanthate
chemistry involving radical addition and Chugaev elimination steps.
The first method uses the addition of an ester-functionalized xanthate
to various commercially functional alkenes, whereas the second one
is based on the addition of functional xanthates to an ester-functionalized
alkene. In both cases, a series of xanthate/alkene monoadducts was
obtained, and their thermolysis and subsequent cyclization led to
a library of functional γ-thiolactones in moderate to good yield.
For a few cases where it may not be possible to directly incorporate
some targeted functional groups via the proposed process involving
free radicals and high temperature, a bromo-functionalized thiolactone
was used as a starting material for chemical transformations.
The concepts of polymer–peptide
conjugation and self-assembly
were applied to antimicrobial peptides (AMPs) in the development of
a targeted antimalaria drug delivery construct. This study describes
the synthesis of α-acetal, ω-xanthate heterotelechelic
poly(N-vinylpyrrolidone) (PVP) via reversible addition–fragmentation
chain transfer (RAFT)-mediated polymerization, followed by postpolymerization
deprotection to yield α-aldehyde, ω-thiol heterotelechelic
PVP. A specific targeting peptide, GSRSKGT, for Plasmodium
falciparum-infected erythrocytes was used to sparsely
decorate the α-chain ends via reductive amination while cyclic
decapeptides from the tyrocidine group were conjugated to the ω-chain
end via thiol–ene Michael addition. The resultant constructs
were self-assembled into micellar nanoaggregates whose sizes and morphologies
were determined by dynamic light scattering (DLS) and transmission
electron microscopy (TEM). The in vitro activity and selectivity of
the conjugates were evaluated against intraerythrocytic P. falciparum parasites.
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