Stimuli-responsive cationic terpolymers by RAFT polymerization: Synthesis, characterization, and protein interaction studies (original) (raw)
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Materials Research, 2014
Poly(2-(dimethylamino)ethylmethacrylate-b-methymethacrylate) (PDMAEMA-b-PMMA) poly(2-(dimethylamino)ethylmethacrylate-b-vinylcaprolactam-b-(2-(dimethylamino)ethyl methacrylate) (PDMAEMA-b-PVCL-b-PDMAEMA) and poly(vinylcaprolactam-b-(2-(dimethylamino) ethylmethacrylate-b-vinylcaprolactam) (PVCL-b-PDMAEMA-b-PVCL) block copolymers were obtained by reversible addition-fragmentation chain transfer (RAFT) polymerization, and the effect of the solution pH on the particle size was investigated. In the case of PDMAEMA-b-PMMA, PDMAEMA was first synthesized using 2-cyanoprop-2-yl dithiobenzoate (CPDB) as a chain transfer agent (CTA), which was subsequently used for the RAFT polymerization of MMA. The triblock copolymers were obtained using PDMAEMA or PVCL as macro-CTAs prepared using dibenzyl trithiocarbonate (DBTTC) as a bifunctional RAFT agent. The structure and formation of the copolymers was confirmed through 1 H NMR and SEC analysis. The particle size varied considerably depending on the pH of the aqueous solutions of copolymers indicating that these materials could be potential candidates for biomedical applications.
Polymers, 2019
Thermo-responsive polymers and copolymers derivatives of oligo(ethylene glycol) methyl ether methacrylate (Mn = 300 g mol−1) (OEGMA) and di(ethylene glycol) methyl ether methacrylate (DEGMA) have been synthesized by reversible addition fragmentation chain transfer polymerization (RAFT) using 5-amino-4-methyl-4-(propylthiocarbonothioylthio)-5-oxopentanoic acid (APP) as chain transfer agent (CTA). The monomer conversion was evaluated by hydrogen nuclear magnetic resonance (1H-NMR); number average molecular weights (Mn), weight average molecular weight (Mw), and dispersity (Đ) were obtained by gel permeation chromatography (GPC); glass transition temperature (Tg) was evaluated by modulated differential scanning calorimetry (DSC), cloud point temperature (Tcp) was measured and compared by turbidimetry and dynamic light scattering (DLS). The effect of polymer composition and concentration on the Tcp, either in water or in phosphate buffer saline (PBS), was studied. The values of Tcp usin...
Polymers
In this work, we report the synthesis of novel triple hydrophilic statistical terpolymers consisting of three different methacrylate monomers with varying degrees of responsivity to solution conditions. Terpolymers of the type poly(di(ethylene glycol) methyl ether methacrylate-co-2-(dimethylamino)ethylmethacrylate-co-oligoethylene glycol methyl ether methacrylate), P(DEGMA-co-DMAEMA-co-OEGMA), and of different compositions, were prepared by using the RAFT methodology. Their molecular characterization was carried out using size exclusion chromatography (SEC) and spectroscopic techniques, including 1H-NMR and ATR-FTIR. Studies in dilute aqueous media by dynamic and electrophoretic light scattering (DLS and ELS) show their potential responsiveness regarding changes in temperature, pH, and kosmotropic salt concentration. Finally, the change in hydrophilic/hydrophobic balance of the formed terpolymer nanoparticles during heating and cooling was studied using fluorescence spectroscopy (FS...
Macromolecules, 2011
RAFT polymerization of a "more activated monomer" (MAM) -N,N-dimethylacrylamide (DMAm)has been successfully achieved in aqueous solution using an acid/base switchable pyridyl-substituted dithiocarbamate RAFT agent. The effect of strength (pK a ) and stoichiometry of the acid used to switch the RAFT agent on the molecular weight and dispersity of PDMAm were examined, making use of high-throughput protocol. Best control was achieved with a stoichiometric amount of the strongest acid investigated, p-toluenesulfonic acid monohydrate. Use of weaker acids (higher pKa) or less than stoichiometric amounts of acid with respect to RAFT agent resulted in broader molecular weight distributions. These results can be rationalized in terms of the extent of protonation of the pyridine nitrogen of the RAFT agent (pK a ~3.13). The preparation of unimodal low dispersity block copolymers 2 of PDMAm with the "less-activated" monomers (LAMs) N-vinylcarbazole (NVC), vinyl acetate (VAc) and N-vinylpyrrolidone (NVP) demonstrated the fidelity of the RAFT end group in these experiments and provides a further example of the utility of switchable RAFT polymerization.
Nanomaterials, 2019
Polymerization through reversible addition-fragmentation chain-transfer (RAFT) polymerization has been extensively employed for the production of polymers with controlled molar mass, complex architectures and copolymer composition distributions intended for biomedical and pharmaceutical applications. In the present work, RAFT miniemulsion copolymerizations of methyl methacrylate with acrylic acid and methacrylic acid were conducted to prepare hydrophilic polymer nanoparticles and compare cell uptake results after bioconjugation with bovine serum albumin (BSA), used as a model biomolecule. Obtained results indicate that the RAFT agent 2-cyano-propyl-dithiobenzoate allowed for successful free radical controlled methyl methacrylate copolymerizations and performed better when methacrylic acid was used as comonomer. Results also indicate that poly(methyl methacrylate-co-methacrylic acid) nanoparticles prepared by RAFT copolymerization and bioconjugated with BSA were exceptionally well accepted by cells, when compared to the other produced polymer nanoparticles because cellular uptake levels were much higher for particles prepared in presence of methacrylic acid, which can probably be associated to its high hydrophilicity.
Macromolecular Chemistry and Physics, 2006
RAFT polymerization was used to prepare PMMA-b-PNIPAM copolymers. Two different chain transfer agents, tBDB and MCPDB, were used to mediate the sequential polymerizations. Micellar solutions and gels were prepared from the resulting copolymers in aqueous solution. When heated above T c of PNIPAM (about 31 8C), DLS revealed that PNIPAM coronas collapsed, resulting in aggre-gation of the original micelles. The micellar gels underwent syneresis above T c as water was expelled from the ordered gel structure, the lattice periodicity of which was determined by SANS. A large decrease in lattice spacing was observed above T c. The gel became more viscoelastic at high temperature, as revealed by shear rheometry which showed a large increase in G 00 .
Advanced Drug Delivery Reviews, 2015
RAFT-mediated polymerization, providing control over polymer length and architecture as well as facilitating post polymerization modification of end groups, has been applied to virtually every facet of biomedical materials research. RAFT polymers have seen particularly extensive use in drug delivery research. Facile generation of functional and telechelic polymers permits straightforward conjugation to many therapeutic compounds while synthesis of amphiphilic block copolymers via RAFT allows for the generation of selfassembled structures capable of carrying therapeutic payloads. With the large and growing body of literature employing RAFT polymers as drug delivery aids and vehicles, concern over the potential toxicity of RAFT derived polymers has been raised. While literature exploring this complication is relatively limited, the emerging consensus may be summed up in three parts: toxicity of polymers generated with dithiobenzoate RAFT agents is observed at high concentrations but not with polymers generated with trithiocarbonate RAFT agents; even for polymers generated with dithiobenzoate RAFT agents, most reported applications call for concentrations well below the toxicity threshold; and RAFT end-groups may be easily removed via any of a variety of techniques that leave the polymer with no intrinsic toxicity attributable to the mechanism of polymerization. The low toxicity of RAFT-derived polymers and the ability to remove end groups via straightforward and scalable processes make RAFT technology a valuable tool for practically any application in which a polymer of defined molecular weight and architecture is desired.
Macromolecules, 2016
RAFT solution polymerization of N-(2-(methacryoyloxy)ethyl)pyrrolidone (NMEP) in ethanol at 70°C was conducted to produce a series of PNMEP homopolymers with mean degrees of polymerization (DP) varying from 31 to 467. Turbidimetry was used to assess their inverse temperature solubility behavior in dilute aqueous solution, with an LCST of approximately 55°C being observed in the high molecular weight limit. Then a poly(glycerol monomethacylate) (PGMA) macro-CTA with a mean DP of 63 was chain-extended with NMEP using a RAFT aqueous dispersion polymerization formulation at 70°C. The target PNMEP DP was systematically varied from 100 up to 6000 to generate a series of PGMA 63 − PNMEP x diblock copolymers. High conversions (≥92%) could be achieved when targeting up to x = 5000. GPC analysis confirmed high blocking efficiencies and a linear evolution in M n with increasing PNMEP DP. A gradual increase in M w /M n was also observed when targeting higher DPs. However, this problem could be minimized (M w /M n < 1.50) by utilizing a higher purity grade of NMEP (98% vs 96%). This suggests that the broader molecular weight distributions observed at higher DPs are simply the result of a dimethacrylate impurity causing light branching, rather than an intrinsic side reaction such as chain transfer to polymer. Kinetic studies confirmed that the RAFT aqueous dispersion polymerization of NMEP was approximately four times faster than the RAFT solution polymerization of NMEP in ethanol when targeting the same DP in each case. This is perhaps surprising because both 1 H NMR and SAXS studies indicate that the core-forming PNMEP chains remain relatively solvated at 70°C in the latter formulation. Moreover, dissolution of the initial PGMA 63 −PNMEP x particles occurs on cooling from 70 to 20°C as the PNMEP block passes through its LCST. Hence this RAFT aqueous dispersion polymerization formulation offers an efficient route to a high molecular weight water-soluble polymer in a rather convenient low-viscosity form. Finally, the relatively expensive PGMA macro-CTA was replaced with a poly(methacrylic acid) (PMAA) macro-CTA. High conversions were also achieved for PMAA 85 −PNMEP x diblock copolymers prepared via RAFT aqueous dispersion polymerization for x ≤ 4000. Again, better control was achieved when using the 98% purity NMEP monomer in such syntheses.