Click to Self-immolation: A "Click" Functionalization Strategy towards Triggerable Self-Immolative Homopolymers and Block Copolymers

Angew Chem Int Ed Engl. 2024 Jan 15;63(3):e202317063. doi: 10.1002/anie.202317063. Epub 2023 Dec 8.

Abstract

Self-immolative polymers (SIPs) are a class of degradable macromolecules that undergo stimuli-triggered head-to-tail depolymerization. However, a general approach to readily end-functionalize SIP precursors for programmed degradation remains elusive, restricting access to complex, functional SIP-based materials. Here we present a "click to self-immolation" strategy based on aroyl azide-capped SIP precursors, enabling the facile construction of diverse SIPs with different trigger units through a Curtius rearrangement and alcohol/thiol-isocyanate "click" reaction. This strategy is also applied to polymer-polymer coupling to access fully depolymerizable block copolymer amphiphiles, even combining different SIP backbones. Our results demonstrate that the depolymerization can be actuated efficiently under physiologically-relevant conditions by the removal of the trigger units and ensuing self-immolation of the p-aminobenzyl carbonate linkage, indicating promise for controlled release applications involving nanoparticles and hydrogels.

Keywords: Block Copolymer; Click Chemistry; Functionalization; Self-Immolative Polymer; Stimuli-Responsive.