Controlled Synthesis of Lipoate Homopolymers via Reversible Addition–Fragmentation Chain Transfer Polymerization

Polylipoates (PLp), derived from α-lipoic acid, are promising polymers for developing biocompatible, stimuli-responsive, and fully (closed-loop) recyclable materials. However, their synthesis is hindered by two key challenges: the high propensity of lipoate propagating radicals to undergo backbiting during polymerization, and the tendency for polymers to spontaneously depolymerize due to a low ceiling temperature. In this study, we demonstrate that reversible addition-fragmentation chain transfer (RAFT) polymerization overcomes these challenges and can be used to synthesize PLp homopolymers with a high degree of control. This was confirmed by a linear relationship between molecular weight (M_n) and monomer conversion, as well as first-order polymerization kinetics, characteristics not achievable with conventional radical polymerization. By adjusting the RAFT agent feed ratio, the M_n of homopolymer PLps was precisely controlled with an M_n ranging from 3.6 to 62.6 kg mol^-1. RAFT polymerization provided stable end-groups that effectively suppressed the spontaneous depolymerization of PLp. Polymers synthesized using RAFT agents remained intact for over 2 weeks in both solution and bulk, while those prepared under traditional radical conditions showed substantial degradation. Moreover, the trithiocarbonate end-group enabled light-triggered, on-demand depolymerization back to the original monomer. RAFT was also successfully extended to the synthesis of degradable block copolymers. Together, these results demonstrate that RAFT offers a simple, accessible, and proven strategy to address key challenges in PLp synthesis and long-term stability.