DFT, MM and ADMET integrated computations on a naturally occurring biomolecule (Luteolin-7-O-β-d-glucoside) and its interaction with various protein-receptors reveal its phase-dependent nonlinear optical and multifunctional drug activity

Abstract

This study presents a comprehensive computational investigation of Luteolin-7-O-β-d-glucoside, a flavonoid glycoside isolated from Cucumis sativus L. (cucumber) seeds, using integrated density functional theory (DFT), molecular mechanics (MM), and ADMET analysis. DFT calculations at the B3LYP/6–31+G(d,p) level are performed to analyze spectroscopic properties (IR, NMR, UV–Visible), nonlinear optical characteristics, frontier molecular orbitals, molecular electrostatic potential surface and thermodynamic parameters. The optimized structure exhibited 150 vibrational modes with no imaginary frequencies. IR and NMR spectra for the titled molecule show good agreement between calculated and experimental spectroscopic data. UV–vis spectrum is reported, and its analysis revealed maximum absorption at 357.50 nm with a transition energy of 3.47 eV and oscillator strength 0.433. Electronic structure analysis demonstrates a narrow HOMO-LUMO gap (0.146 au), indicating high chemical reactivity and charge-transfer capacity. Remarkable phase-dependent NLO characteristics are observed, with first-order hyperpolarizability values 70 times higher than that of the reference molecule urea in the gas phase and 206 times higher in ethanol solution. Molecular docking studies against seven physiologically relevant proteins reveal strong binding affinities and optimal interaction against hepatitis B viral capsid with final intermolecular energy of −13.53 kcal/mol and binding free energy of −10.25 kcal/mol at 30 nM inhibition constant. ADMET analysis indicates favourable safety profiles with moderate bioavailability. The integrated computational approach demonstrates that Luteolin-7-O-β-d-glucoside may be explored as a potential multifunctional drug candidate for hepatitis B, Alzheimer's disease, cancer, type 2 Diabetes and other metabolic diseases, along with nonlinear optical applications that dominate in the liquid phase.