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

TL;DR

This paper introduces a new polymer design that allows for both precise chemical modifications and controlled breakdown under specific conditions.

Contribution

A dual-functional monomer combining click-type functionalization and stimulus-responsive degradability in one platform.

Findings

The TKLA monomer enables catalyst-free amine ligation and disulfide-based degradability in a single step.

Copolymers with TK and disulfide groups show modular functionalization and selective backbone fragmentation under reducing conditions.

The system supports dynamic reconfiguration of functionalities and controlled deconstruction of polymer structures.

Abstract

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.

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