Click to Self‐immolation: A “Click” Functionalization Strategy towards Triggerable Self‐Immolative Homopolymers and Block Copolymers

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.