Synthesis of linear amphiphilic tetrablock quaterpolymers with dual stimulus response through the combination of ATRP and RAFT by a click chemistry site transformation approach

Well-defined linear amphiphilic tetrablock quaterpolymers with dual stimulus response, poly(ethylene glycol)-b-poly(styrene)-b-poly(N-isopropylacrylamide)-b-poly(2-(dimethylamino)ethyl methacrylate) (PEG-b-PS-b-PNIPAM-b-PDMAEMA), were successfully synthesized through the combination of ATRP and RAFT by a click chemistry site transformation approach. Bromine-terminated diblock copolymer PEG-b-PS-Br was first prepared by ATRP of styrene initiated with macro-initiator PEG-Br, which was prepared from the esterification of PEG and 2-bromoisobutyryl bromide. PEG-b-PS-Br can then be converted into the azido-terminated diblock copolymer, PEG-b-PS-N3, by nucleophilic substitutions. Site transformation of PEG-b-PS-N3 into a macro-chain transfer agent (CTA) for RAFT polymerization was accomplished using a copper-catalyzed click chemistry approach. Afterwards, the novel linear tetrablock quaterpolymers, PEG-b-PS-b-PNIPAM-b-PDMAEMA, were synthesized by successive RAFT polymerizations of NIPAM and DMAEMA. The polymerization data indicated that both RAFT processes were well controlled. The structures of the linear amphiphilic tetrablock quaterpolymers and the corresponding precursors were characterized by 1H NMR, FTIR and GPC. Containing thermoresponsive PNIPAM and pH-responsive PDMAEMA blocks, the obtained amphiphilic PEG-b-PS-b-PNIPAM-b-PDMAEMA tetrablock quaterpolymers self-assembled into spherical micelles with hydrophobic PS cores and hydrophilic PEG/PNIPAM/PDMAEMA shells at acidic pH and room temperature but self-assembled into PS/PDMAEMA-core micelles at alkaline pH and room temperature, and PS/PNIPAM-core micelles at acidic pH and elevated temperatures.