Crystal structure, chemical reactivity, kinetic and thermodynamic studies of new ligand derived from 4-hydroxycoumarin: Interaction with SARS-CoV-2

J Mol Struct. 2020 Dec 15:1222:128918. doi: 10.1016/j.molstruc.2020.128918. Epub 2020 Jul 16.

Abstract

Currently, Covid-19 pandemic infects staggering number of people around the globe and causes a high rate of mortality. In order to fight this disease, a new coumarin derivative ligand (4-[(pyridin-3-ylmethyl) amino]-2H-chromen-2-one) (LTA) has been synthesized and characterized by single-crystal X-ray diffraction, NMR, ATR, UV-Visible and cyclic voltammetry. Chemical reactivity, kinetic and thermodynamic studies were investigated using DFT method. The possible binding mode between LTA and Main protease (Mpro) of SARS-CoV-2 and their reactivity were studied using molecular docking simulation. Single crystal X-ray diffraction showed that LTA crystallizes in a monoclinic system with P2 1 space group. The reactivity descriptors such as nucleophilic index confirm that LTA is more nucleophile, inducing complexation with binding species like biomolecules. The kinetic and thermodynamic parameters showed that the mechanism of crystal formation is moderately exothermic. The binding energy of the SARS-CoV-2/Mpro-LTA complex and the calculated inhibition constant using docking simulation showed that the active LTA molecule has the ability to inhibit SARS-CoV-2.

Keywords: Chemical reactivity; Coumarin derivative; Crystal structure; Interaction SARS-CoV-2/Mpro-LTA; Thermodynamic properties.