Functionalization of Methacrylate Polymers with Thiooximes: A Robust Postpolymerization Modification Reaction and a Method for the Preparation of H2S-Releasing Polymers

The effectiveness of thiooxime formation as a postpolymerization modification reaction was evaluated. To this end, methacrylate polymers bearing pendant aldehyde functionality were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(4-formylbenzoyloxy)ethyl methacrylate. Polymer side-chain derivatizations with tert-butylhydrazide, O-benzylhydroxylamine, and S-aroylthiohydroxylamine (SATHA) were shown to be quantitative, forming the corresponding hydrazone, oxime, and thiooxime, respectively. This work represents the first example of thiooxime formation on polymers, achieving high conversions under mild conditions. In response to thiol functionality, S-aroylthiooximes decomposed to release H2S: an endogenous signaling gas with significant therapeutic potential. H2S release from the resulting thiooxime-functionalized polymers was observed in the presence of cysteine and glutathione; moreover, degradation kinetics could be controlled by tuning the electronics at the para position of the corresponding SATHA-derived ring. In addition to generating polymers capable of controlled H2S release, this methodology also enables thiol-triggered degradation of pendant functionalities at neutral pH.