Post-polymerization 'click' end-capping of polyglyoxylate self-immolative polymers

Abstract

Post-polymerization modification is a powerful tool for expanding the functionality and tuning the properties of self-immolative polymers (SIPs), typically through reactions of the polymer repeat units. Herein, we investigate the use of post-polymerization 'click' reactions to attach stimuli-responsive end-caps to poly(ethyl glyoxylate) (PEtG) SIPs. Two classes of alkyne-terminated polymers were synthesized, with the alkyne attached to the PEtG either by an acetal or carbonate bridge. These PEtGs were treated with azide-functionalized self-immolative linker precursors via the copper(i) catalyzed azide-alkyne cycloaddition reaction to afford PEtGs end-capped with cleavable self-immolative triazole (SIT) linkers. Our results demonstrate that degradation of the PEtGs can be initiated by cleavage of the SIT end-caps, and that successful cleavage depends strongly on the moiety that connects the SIT linker to the PEtG backbone. Through depolymerization studies on the polymers and a series of small molecule model compounds, we examined in detail the mechanistic features of this system. Additionally, we demonstrate that this modular chemistry is versatile for introducing different stimuli-responsive end-caps to a single pre-synthesized PEtG.