Engineering Pathway-Dependent Two-Dimensional Nanosheets from Polypeptoid Diblock Copolymers via ROPISA

Polymerization-induced self-assembly (PISA) is an efficient method for fabricating nanoassemblies with diverse morphologies. In particular, ring-opening polymerization-induced self-assembly (ROPISA) of α-amino acid N-carboxyanhydrides has enabled the in situ synthesis of biodegradable nanostructures. Despite their structural similarity, N-substituted glycine-N-carboxyanhydrides (NNCAs) have rarely been explored for ROPISA, and their assembly mechanisms remain poorly understood. In this study, we report the first ROPISA of N-octyl glycine-N-carboxyanhydrides (NOG-NCAs) utilizing α-methoxy-ω-amino poly(ethylene glycol) (mPEG-NH2) as the macromolecular initiator. In the selective solvent acetonitrile, two-dimensional nanosheets of poly(ethylene glycol)-b-poly(N-octyl glycine) (PEG-b-PNOG) were prepared via a pathway-dependent assembly process. The nanosheet thickness could be tuned by adjusting the degree of polymerization (DP) of the PNOG block, while varying the DP of the PEG block yielded a range of morphologies, including fibrous, rodlike, and sheet-like assemblies. Higher temperatures increased nanosheet width, whereas rapid polymerization in the presence of a catalyst led to kinetic trapping, yielding less-defined nanoparticles. In contrast, ROPISA in 1,4-dioxane─a lower polarity selective solvent─followed a thermodynamically controlled pathway. This study established a one-step preparation of biocompatible two-dimensional (2D) polypeptoid nanosheets and demonstrated solvent polarity as a key determinant of kinetic versus thermodynamic assembly pathways.