Dual-Pathway Strategy for Click-Type Functionalization and Programmable Polymer Deconstruction

Developing polymeric materials that combine precise, modular functionalization with programmed backbone degradability remains an outstanding challenge in macromolecular engineering. Herein, we present a molecular design strategy that integrates orthogonal postpolymerization modification with selective, stimulus-responsive backbone degradability within a single macromolecular platform. The ring-opening polymerization of 1,2-dithiolanes introduces cleavable disulfide linkages into polymer backbones, providing a powerful route to degradable materials under biologically relevant reducing conditions. By incorporating a β-triketone (TK) moiety into an α-lipoic-acid-derived 1,2-dithiolane, we synthesized triketone-lipoic acid (TKLA), a dual-functional monomer that combines click-type, catalyst-free amine ligation with programmed backbone degradability. Leveraging photoinduced electron/energy-transfer reversible addition-fragmentation chain-transfer (PET-RAFT) copolymerization of TKLA with acrylate and acrylamide monomers, we accessed well-defined copolymers containing both pendant TK groups and disulfide-rich backbones in a single synthetic step. Under mild conditions, TK-bearing copolymers react quantitatively with a broad scope of amines to form β,β'-diketoenamines (DKEs), enabling modular installation of hydrophilic, hydrophobic, charged, and bioactive substituents. Importantly, these DKE moieties are not static but participate in associative transamination, allowing dynamic exchange and reconfiguration of installed functionalities. Meanwhile, the disulfide-containing backbones fragment cleanly and selectively under reducing environments, affording controlled deconstruction while preserving, or transforming, the appended side-chain chemistry. Overall, the integration of efficient, chemoselective β-triketone-amine condensation with LA-based degradability within a single monomer framework establishes a molecular design strategy for constructing functional, recyclable, and stimuli-responsive polymer architectures.