Facile, Controlled, Room-Temperature RAFT Polymerization of N-isopropylacrylamide

Poly(N-isopropyl acrylamide) is a thermoresponsive polymer that has been widely investigated for drug delivery. Herein, we report conditions facilitating the controlled, room-temperature RAFT polymerization of N-isopropylacrylamide (NIPAM). The key to success is the appropriate choice of both a suitable RAFT chain transfer agent (CTA) and initiating species. We show that the use of 2-dodecylsulfanylthiocarbonylsulfanyl-2-methyl propionic acid, a trithiocarbonate RAFT CTA, in conjunction with the room-temperature azo initiator 2,2‘-azobis(4-methoxy-2,4-dimethylvaleronitrile), in DMF, at 25 °C, yields conditions leading to NIPAM homopolymerizations which bear all of the characteristics of a controlled/“living” polymerization. We also demonstrate facile size exclusion chromatographic analysis of PNIPAM samples in DMF at 60 °C, directly on aliquots withdrawn during the polymerizations, which avoids the problems previously reported in the literature