Thioester-Functional Polyacrylamides: Rapid Selective Backbone Degradation Triggers Solubility Switch Based on Aqueous Lower Critical Solution Temperature/Upper Critical Solution Temperature

Radical ring-opening polymerization is a clever strategy to incorporate cleavable linkages into otherwise nondegradable vinyl polymers. However, conventional systems suffer from slow copolymerization, harsh nonselective degradation conditions, and limited application potential because the degradation products (often oligomers or polymers themselves) have properties like those of the intact species. This work presents fast selective degradation accompanied by a drastic change in a key property, aqueous solubility. Thionolactone dibenzo[c,e]oxepane-5-thione was found to copolymerize radically with a range of primary, secondary, and tertiary neutral and zwitterionic acrylamides with rapid incorporation of degradable biphenyl thiocarboxylate repeat units. Intact copolymers displayed temperature-responsive (lower critical solution temperature or upper critical solution temperature-type) aqueous solubility behavior, tunable through the molar composition and (exploiting the non-azeotropic copolymerization behavior) comonomer sequence. Various conditions led to selective and complete degradation of the backbone thioesters through hydrolysis, aminolysis, transthioesterification (including under physiological conditions), and oxidative hydrolysis, which drastically increased aqueous solubility. Polymers containing as little as 8 mol % thioester repeat units underwent a temperature-independent insoluble–soluble transition upon degradation with cysteine or potassium persulfate. Insoluble polymers were used to block syringe filters, which allowed flow of degradant solutions only, relevant to lab-on-a-chip, sensing, and embolic biomedical applications.