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Issue 26, 2020
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Understanding ring-closing and racemization to prepare α-amino acid NCA and NTA monomers: a DFT study

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Abstract

Polypeptides and polypeptoids are promising materials in biomedical applications bearing α-amino acid repeating units, which are prepared from ring-opening polymerizations of α-amino acid N-carboxyanhydride (NCA) or N-thiocarboxyanydride (NTA) monomers. Detailed studies on monomer synthetic routes are essential to explore new α-amino acid NCA and NTA monomers as well as the corresponding poly(α-amino acid) materials. In this contribution, density functional theory (DFT) is applied to investigate the mechanism of the Leuchs approach including two possible pathways, precursor structure and racemization in the ring-closing reaction. According to DFT calculations, pathway 2 is preferred with lower ΔG than pathway 1, and the rate-determining step is recognized as an SN2 substitution with releasing equivalent halogenated hydrocarbon, which explains our experimental observations. Racemization results from the reaction between the NTA monomer and a strong protonic acid, which can be suppressed by low temperature and short reaction time. Racemization is inhibited by steric hindrance in those NTAs of α-amino acids containing high bulkiness at the β-carbon, such as leucine-NTA.

Graphical abstract: Understanding ring-closing and racemization to prepare α-amino acid NCA and NTA monomers: a DFT study

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Supplementary files

Article information


Submitted
01 Mar 2020
Accepted
09 Jun 2020
First published
09 Jun 2020

Phys. Chem. Chem. Phys., 2020,22, 14868-14874
Article type
Paper

Understanding ring-closing and racemization to prepare α-amino acid NCA and NTA monomers: a DFT study

T. Bai, B. Shen, D. Cai, Y. Luo, P. Zhou, J. Xia, B. Zheng, K. Zhang, R. Xie, X. Ni, M. Xu, J. Ling and J. Sun, Phys. Chem. Chem. Phys., 2020, 22, 14868
DOI: 10.1039/D0CP01174F

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