The Missing Lactam-Thermoresponsive and Biocompatible Poly(N-vinylpiperidone) Polymers by Xanthate-Mediated RAFT Polymerization

A new polymer poly(N-vinylpiperidone) (PVPip) (2x, MnNMR 4.5−83 kDa) has been prepared by reversible addition−fragmentation chain-transfer (RAFT) polymerization using a xanthate as a chain-transfer agent. These polymers all exhibited sharp reversible cloud points (in the range 87 and 68 °C) which depended on the molecular weight of the polymer and showed no apparent hysteresis. Furthermore, cytotoxicity studies of the PVPip showed that the polymer is noncytotoxic. Chain extension of PVPip62 with vinyl acetate afforded well-defined amphiphilic diblock copolymers: poly(N-vinylpiperidone)x-block-poly(vinyl acetate)y (PVPipx-b-PVAcy) (for 3, x:y = 62:21; for 4, x:y = 62:32). Both 3 and 4 exhibit phase transitions of 62 and 55 °C, respectively, in water, with the latter showing evidence of a slight hysteresis. Direct dissolution of 3 in nanopure water at 1 mg/mL gave spherical micelles (ca. 24 nm), as confirmed by DLS, TEM, and AFM analysis, which could be reversibly disassembled upon heating above the cloud point of the diblock. The block copolymer 4 was hydrolyzed under basic conditions to give the double hydrophilic biocompatible diblock copolymer poly(N-vinylpiperidone)62-block-poly(vinyl alcohol)32 (5).