Organic Acid Promoted Controlled Ring-Opening Polymerization of α‑Amino Acid-Derived N‑thiocarboxyanhydrides (NTAs) toward Well-defined Polypeptides

• Published in: ACS macro letters Vol. 7; no. 10; pp. 1272 - 1277
• Main Authors: Siefker, David, Williams, Ajah Z, Stanley, George G, Zhang, Donghui
• Format: Journal Article
• Language: English
• Published: American Chemical Society 16.10.2018
• ISSN: 2161-1653; 2161-1653
• DOI: 10.1021/acsmacrolett.8b00743

Weak organic acids (i.e., acetic acid) in conjunction with primary amine initiators have enabled controlled ring-opening polymerization of α-amino-acid derived N-thiocarboxyanhydrides (NTAs) bearing N–H proton in a polar solvent (CH2Cl2) at room temperature, producing well-defined polypeptides with tailorable molecular weight (M n = 3.2–57 kg·mol–1) and narrow molecular weight distribution (PDI = 1.02–1.12). The pK a of the organic acids and the nature of the reaction medium were found to be important for the polymerization to proceed in a controlled manner. The polymerization was shown to occur by a normal amine mechanism. The acetic acid is proposed to promote the polymerization of NTAs by accelerating the elimination of COS from the carbamate propagating intermediate to form the active amino propagating species and reducing side reactions by modulating the relative abundance of the active amino propagating species via acid–base equilibrium. The reactions do not require the use of rigorously anhydrous solvent and can be conducted in air owing to the enhanced hydrolytic stability of NTAs.