Solute-solvent interactions, electrostatic & covalent surface analysis, and pharmacokinetic studies via in-silico simulation on diethyl 3-hydroxyglutarate: Anti-hypercholesterolemia activity

Abstract

In this study, theoretical investigations of the anti-hypercholesterolemia molecule diethyl 3-hydroxyglutarate (D3HG) have been carried out using DFT techniques. Vibrational spectral analyses were utilized for the structural determination after the compound's stability was identified through DFT optimization. As per the QTAIM findings, the highest electron density and electron distribution asymmetry were found at O4C9 and O510 in the molecule D3HG. Under the topological evaluation, the covalent and electrostatic interactions were assessed by Laplacian electron density (∇2ρ(r)) and reduced density gradient (RDG). Studies of solvent effects on electronic absorptions, molecular electrostatic potentials, global reactive descriptors, and Fukui functions have been analysed to understand better the mechanism causing chemical responsiveness. First-order hyperpolarizability (β) and natural bond orbital (NBO) stability calculations were also included. Solvatochromic correlations are used to approximate the referred molecule's reactions to polar and non-polar solutions as well as the solute-solvent interactions. Using Lipinski's rule, the molecule's drug-likeness study was carried out; pharmacokinetics and the D3HG molecule's interactions with iso-enzymes were also explored. A molecular docking study also demonstrates the efficacy of the title molecule to have anti-hypercholesterolemia activity.