In silico Investigations on Structure, Reactivity Indices, NLO properties, and Bio-evaluation of 1-benzyl-2-phenyl-1H-benzimidazole Derivatives using DFT and Molecular Docking Approaches

Abstract

Six 1-benzyl-2-phenyl-1H-benzimidazole derivatives, A1-A6, were modeled computationally, and equilibrium optimization was carried out at the B3LYP/6-31G** level of theory. The geometrical parameters, IR, UV-Vis, and molecular reactive properties were predicted on the basis of density functional theory (DFT) calculations. The electron-donating/accepting power (𝜔−/𝜔+) calculated were 4.71/1.18, 5.675/1.766, and 4.785/1.210 eV for A1, A2, and A3, respectively, indicating good electron donors; while A4 and A5 were calculated to be 8.13/3.60 and 9.284/4.744 eV, respectively signifying good electron acceptors in line with chemical hardness (μ), electrophilicity (ω) values and MEP analysis. The NLO behavior of compounds A1-A3 was greater than that of the standard NLO material urea gives the most reactive sites in the molecules. Docking analysis revealed that binding affinities for the six compounds A1-A6 were -8.3 to -9.0 kcal/mol and -9.2 to -10.0 kcal/mol for APO-liver alcohol dehydrogenase inhibitor (PDB IP: 5ADH) and antihypertensive protein hydrolase inhibitor (PDB IP: 4XX3), respectively; thus could possess good antioxidant and antihypertensive properties.