RAFT Synthesis of Water-Soluble, Stimuli-Responsive (Co)polymers and Post-Polymerization End Group Modification Via the Thiol-ene Reaction
A series of water-soluble, stimuli-responsive (co)polymers was synthesized via the reversible addition-fragmentation chain transfer (RAFT) polymerization. The end group of a RAFT polymer, poly(N -isopropylacrylamide), was modified to ene or yne function via thiol-ene click chemistry. The ene or yne end group subsequently underwent thiol-ene or thiol-yne addition affording mono- or di-functional end group. First, three methacrylic monomers containing 2 or 3 pendent tertiary amine functional groups, 1,3-bis(dimethylamino)propan-2-ylmethacrylate ( M1 ), 1-(bis(3-(dimethylamino)propyl)amino)propan-2-yl methacrylate (M2 ), and 2-((2-(2-(dimethylamino)ethoxy)ethyl)methylamino)ethyl acrylate (M3 ), were synthesized via an acylation reaction between methacryloyl chloride and the corresponding aminoalcohol. All of these three monomers were successfully homopolymerized under RAFT conditions with 1-methyl-l-cyanoethyl dithiobenzoate (CPDB) as chain transfer agent (CTA). For each monomer, homopolymerization using two different CTA:Initiator ratio was conducted. The effect of the CTA:Initiator ratio on the kinetics is in agreement with the prediction by RAFT mechanism. The stimuli-responsive properties of poly M1 , polyM2 , and polyM3 in aqueous solution were tested and all the homopolymers shows reversible thermo-responsive and pH-responsive properties. Second, a monomer with excellent biocompatibility, 2-(methacryloyloxy)ethyl phosphorylcholine (MPC), was homopolymerized in water via RAFT polymerization mediated by 4-cyanopentanoic acid dithiobenzoate (CTP). The prepared MPC homopolymer was used as a macro-CTA in the RAFT polymerization of four stimuli-responsive monomers, N,N -diethylacrylamide (DEAm ), 4-vinylbenzoic acid (VBZ ) N -(3-sulfopropyl)-N -methacrylooxyethyl- N,N -dimethylammonium betaine (DMAPS ), and the newly synthesized N,N -di-n -propylbenzylvinylamine (DnPBVA ), yielding a series of water-soluble, stimuli-responsive AB diblock copolymers. The stimuli-responsive properties of there copolymers were examined by a combination of 1 H NMR spectroscopy and dynamic light scattering. The results show that aggregates with varied sizes formed upon application of the corresponding stimulus (change of pH, temperature, or electrolyte concentration). And the removal of the stimulus caused the dissociation of the aggregates, proving the reversibility of the stimuli-responsive property. Finally, a well-defined precursor homopolymer of N -Isopropylacrylamide (NIPAm ) was prepared using RAFT polymerization in DMF at 70°C employing the CPDB as CTA. The dithiobenzoate end-groups were subsequently modified to give ene or yne functional end groups via a thiol-ene click reaction catalyzed using a combination of octylamine and dimethylphenylphosphine to induce a thio-Michael reaction with either allyl methacrylate or propargyl acrylate. The conversion of the end-group was near quantitative according to 1 H NMR spectroscopy. The ene and yne groups were then reacted quantitatively via radical thiol-ene and radical thiol-yne reactions under UV-irradiation with three representative thiols yielding the mono and bis-end functional NIPAm homopolymers. The lower critical solution temperatures (LCST) were then determined for all NIPAm homopolymers using a combination of optical measurements and dynamic light scattering. Results show that the LCST varies depending on the chemical nature of the end-groups with measured values lying in the range 26-35°C.