Biodegradable Poly(disulfide)s Derived from RAFT Polymerization: Monomer Scope, Glutathione Degradation, and Tunable Thermal Responses

Telechelic, RAFT (reversible addition–fragmentation chain transfer)-derived macromonomers with a pyridyl disulfide end-group were converted into high molecular weight, disulfide-linked polymers using a polycondensation, step-growth procedure. The applicability of the method to polycondense a library of macromonomers with different functionalities including (meth)­acrylates and acrylamides was investigated. Side-chain sterics were found to be important as nonlinear poly­(ethylene glycol) analogues, which proved incompatible with this synthetic methodology, as were methacrylates due to their pendant methyl group. This method was used to incorporate disulfide bonds into poly­(N-isopropylacrylamide), pNIPAM, precursors to give dual-responsive (thermo- and redox) materials. These polymers were shown to selectively degrade in the presence of intracellular concentrations of glutathione but be stable at low concentrations. Due to the molecular weight-dependent cloud point of pNIPAM, the lower critical solution temperature behavior could be switched off by a glutathione gradient without a temperature change: an isothermal transition.