Polymerization of N‑Carboxyanhydride in Cosolvents: The Balance between the Polymerization Rate and Molecular Weight Control

• Published in: Macromolecules Vol. 56; no. 17; pp. 7023 - 7031
• Main Authors: Li, Qinyuan, Lan, Yingjia, Wang, Wanying, Ji, Guonan, Li, Xiaohong, Song, Ziyuan
• Format: Journal Article
• Language: English
• Published: American Chemical Society 12-09-2023
• ISSN: 0024-9297; 1520-5835
• DOI: 10.1021/acs.macromol.3c00704

The recent advances in accelerated cooperative covalent polymerization (CCP) of N-carboxyanhydrides (NCAs) in dichloromethane or chloroform benefit the preparation of polypeptide materials by minimizing side reactions and simplifying the synthetic procedure. However, CCP sometimes produces ill-defined polypeptides, mainly due to the two-stage kinetics. Herein, we report the use of a cosolvent system to regulate the polymerization behavior, which enables the preparation of polypeptides in a fast and controlled manner. Specifically, the mixing of polar solvents, such as N,N-dimethylformamide, with chloroform altered the kinetics profile and increased the monomer solubility. Considering the [M]0-dependent kinetics in the cosolvent, polypeptides were synthesized with an accelerated rate that was comparable with that in chloroform but with an improved molecular weight distribution. We believe this work not only improves our understanding of the solvent impact on NCA polymerization but also offers a simple and effective strategy for preparing various polypeptide materials.