Insights into structural, vibrational, and chemical shift characteristics, solvents impact (polar and nonpolar) on electronic properties and reactive sites, ADMET predictions, and ligand-protein interactions for antiviral drugs safrole and isosafrole: An in-silico approach

Abstract

The safrole and isosafrole are constitutional isomers that have been theoretically characterized utilizing Density Functional Theory (DFT) employed with the B3LYP/6-311++G(d,p) basis set to simulate geometrical parameters, vibrational aspects, electronic properties, and chemical shifts and explored the solvent effect on electronic spectra of safrole and isosafrole in different solvents, including polar solvents such as acetone, Dimethyl sulfoxide (DMSO), and methanol, nonpolar solvents such as chloroform, cyclohexane, and toluene, and the gas phase using Time Dependent-Density Functional Theory (TD-DFT) methods. In addition, Natural Orbital (NBO), Mulliken population analysis, and Molecular Electrostatic Potential (MEP) surface have been simulated to understand better the reactive sites in the molecular structures of safrole and isosafrole. The frontier molecular orbitals (FMO) energy gaps of safrole and isosafrole were simulated in polar and nonpolar solvents, confirming the safrole and isosafrole kinetic stability and chemical reactivity. The in-silico ADMET indices were utilized to ascertain the probable pharmacokinetic and biological features of safrole and isosafrole. A molecular docking investigation was also conducted to investigate the potential biological activity of safrole and isosafrole against the SARS-CoV-2 spike protein, providing more support for its antiviral efficacy.