Elucidating the Racemization Mechanism of Aliphatic and Aromatic Amino Acids by In Silico Tools

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Aug 12

PMID 37569252

Authors

Mateo S Andino

Jose R Mora

Jose L Paz

Edgar A Marquez

Yunierkis Perez-Castillo

Guillermin Aguero-Chapin

Affiliations

Soon will be listed here.

Abstract

The racemization of biomolecules in the active site can reduce the biological activity of drugs, and the mechanism involved in this process is still not fully comprehended. The present study investigates the impact of aromaticity on racemization using advanced theoretical techniques based on density functional theory. Calculations were performed at the ωb97xd/6-311++g(d,p) level of theory. A compelling explanation for the observed aromatic stabilization via resonance is put forward, involving a carbanion intermediate. The analysis, employing Hammett's parameters, convincingly supports the presence of a negative charge within the transition state of aromatic compounds. Moreover, the combined utilization of natural bond orbital (NBO) analysis and intrinsic reaction coordinate (IRC) calculations confirms the pronounced stabilization of electron distribution within the carbanion intermediate. To enhance our understanding of the racemization process, a thorough examination of the evolution of NBO charges and Wiberg bond indices (WBIs) at all points along the IRC profile is performed. This approach offers valuable insights into the synchronicity parameters governing the racemization reactions.

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