Ring-opening polymerization of lactide catalyzed using metal-coordinated enzyme-like amino acid assemblies

Polylactide (PLA), a biocompatible and biodegradable polymer, is widely used in diverse biomedical applications. However, the industry standard for converting lactide into PLA involves toxic tin (Sn)-based catalysts. To mitigate the use of these harmful catalysts, other environmentally benign metal-containing agents for efficient lactide polymerization have been studied, but these alternatives are hindered by complex synthesis processes, reactivity issues, and selectivity limitations. To overcome these shortcomings, we explored the catalytic activity of Cu-(Phe)₂ and Zn-(Phe)₂ metal-amino acid co-assemblies as potential catalysts of the ring-opening polymerization (ROP) of lactide into PLA. Catalytic activity of the assemblies was monitored at different temperatures and solvents using ¹H-NMR spectroscopy to determine the catalytic parameters. Notably, Zn-(Phe)₂ achieved >99% conversion of lactide to PLA within 12 h in toluene under reflux conditions and was found to have first-order kinetics, whereas Cu-(Phe)₂ exhibited significantly lower catalytic activity. Following Zn-(Phe)₂-mediated catalysis, the resulting PLA had an average molecular weight of 128 kDa and a dispersity index of 1.25 as determined by gel permeation chromatography. Taken together, our minimalistic approach expands the realm of metal-amino acid-based supramolecular catalytic nanomaterials useful in the ROP of lactide. This advancement shows promise for the future design of simplified biocatalysts in both industrial and biomedical applications.