Understanding the Ring-Opening Reaction of α-Amino Acid N-Carboxyanhydride in an Amine-Mediated Living Polymerization: A DFT Study

• Published in: Macromolecular chemistry and physics 2010-08, Vol.211 (15), p.1708-1711
• Main Authors: Ling, Jun, Huang, Yanxin
• Format: Article
• Language: English
• Subjects: Aminoacid polymers; Applied sciences; calculations; density functional theory; Exact sciences and technology; peptides; Physicochemistry of polymers; polymerization mechanism; Synthetic biopolymers; transition states
• ISSN: 1022-1352; 1521-3935
• DOI: 10.1002/macp.201000115

The primary‐amine‐initiated polymerization of α‐amino acid N‐carboxyanhydride (NCA) is a widely‐used and promising way to synthesize polypeptide‐involved materials with various applications. The nucleophilic attack mechanism, also known as normal amine mechanism of ring opening reaction of NCA is investigated in detail by means of the DFT calculation in this work. Three steps, i.e., addition, ring opening and decarboxylation are discussed. The addition of C5 carbonyl group of NCA by NH2 group of initiator requires the highest activation energy (≈60 kcal · mol−1) and is regarded as the rate‐determining step. These results are compatible with the experimental studies reported previously and provide an inside view of the normal amine mechanism. The detailed polymerization mechanism of α‐amino acid N‐carboxyanhydride initiated by primary amines is calculated using density functional theory. Separate addition, ring‐opening and decarboxylation steps are involved in a monomer ring‐opening cycle; the addition step is rate‐determining.