Quantum mechanical and molecular mechanics based computational study on 4′,5,7-tetrahydroxydihydroflavonol-6-C-β-glucopyranoside exhibit its chemical reactivity with nonlinear optical activity and multifunctional drug candidature

Quantum Mechanical and Molecular Mechanics (QM/MM) based computations have been carried out using density functional theory (DFT) at B3LYP/6-31 + G(d,p) level and molecular docking approach to investigate the electronic structure properties and biological activities of 4′,5,7-tetrahydroxydihydroflavonol-6-C-β-glucopyranoside, a naturally occurring compound reportedly isolated from Ulmus wallichiana stem bark for exploring its multifaceted potential applications. Frequency calculations and spectroscopic analysis reveal that the vibrational, NMR, and UV-vis spectral characteristic parameters are in good agreement with the reported experimental results, thereby validating the applied theoretical approach. The MESP surface analysis exhibits that electrophilic regions are located around the oxygen atoms of carbonyl and hydroxyl groups, whereas the nucleophilic regions are located around the hydrogen atoms, which are well-suited for molecular recognition through electrostatic potential, as in the case of drug receptor interactions, while a HOMO-LUMO band gap of 4.31 eV suggests good chemical reactivity in the titled compound. The dipole moment and first-order hyperpolarizability of the titled compound are about 5.58 times the dipole moment and about 19.404 times the first-order hyperpolarizability of the prototype molecule, urea which is favoured by the low HOMO-LUMO energy gap, suggesting that it can have potential NLO application. DOS spectrum indicates that HOMO & LUMO are localized on the phenolic and aromatic fragments contributing to the site-specific bioactivity, having antibonding electron interactions. The MM calculations reveal that the titled compound possesses strong binding affinity of −9.6 kcal mol⁻¹ against the Parkin protein, along with promising binding affinities against Osteoporosis, Japanese Encephalitis, Alzheimer’s, Hepatitis B, and Type-2 diabetes protein receptors, predicting it to be a multifunctional drug candidate. Furthermore, ADMET predictions classified the molecule to have favourable drug-like properties and low toxicity risks. The findings of the present study predict the titled natural compound to be a potential multifunctional drug candidate with non-linear optical activity.