Ring opening functionalization of thiolactone homopolymers for ROS scavenging

In this research, we explored the synthesis and application of thiolactone acrylamide (TLA) polymers for neutralizing reactive oxygen species (ROS), produced as a result of traumatic brain injury (TBI). We synthesized well‐defined TLA polymers using RAFT (reversible addition‐fragmentation chain transfer) polymerization across a range of monomer‐to‐chain transfer agent ([M]0/[CTA]0) ratios to achieve a range of molar masses. Polymerizations were carried out using a trithiocarbonate CTA (chain transfer agent) with AIBN (azobisisobutyronitrile) as the initiator in N'N‐dimethylacetamide (DMAc) at 60 °C. Kinetic studies indicated a linear increase in molar mass with conversion, pseudo‐first‐order kinetics, and molar mass values that are consistent with theoretical predictions. Furthermore, the polymerizations exhibited a decrease in molar mass dispersity with conversion. We then investigated ring opening of the thiolactone residues with isoserinol (ISOH), which was followed by thiol‐ene reactions of the resultant thiol groups with methacrylamide to yield a series of copolymers with different thiol‐to‐thioether ratios. The resulting polymers demonstrated varying levels of ROS neutralization. Higher thiol concentrations lead to more rapid neutralization while thioether residues provided sustained neutralization activity.