Synthesis, solvent-solute interactions (polar and non-polar), spectroscopic insights, topological aspects, Fukui functions, molecular docking, ADME, and donor-acceptor investigations of 2-(trifluoromethyl)benzimidazole: A promising candidate for antitumor pharmacotherapy

Abstract

The favorite heteroatom-containing compound, 2-(trifluoromethyl) benzimidazole (2TFMBI), was synthesized and experimentally characterized using spectroscopic techniques. Density Functional Theory (DFT) with B3LYP/6–311++G(d,p) basis set was employed to simulate geometrical parameters, vibrational spectra, electronic spectra, chemical shifts, and other properties of 2TFMBI. Solvent effects, including aprotic polar (aniline and DMSO), protic polar (methanol and water), and non-polar (carbon tetrachloride, chloroform, cyclohexane, and toluene), on electronic properties, frontier molecular orbitals (FMO), and Molecular Electrostatic Potential Surface (MESP) were analyzed. Additionally, Natural Bond Orbital (NBO) and Mulliken population analysis were simulated to better understand the structural aspects of 2TFMBI. The energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) confirms the compound's high reactivity and charge transfer. In-silico Absorption, Distribution, Metabolism, and Excretion (ADME) indices were determined to have potential pharmacokinetic attributes and biological properties. A set of topological analyses, including Electron Localization Function (ELF), Local Orbital Locator (LOL), Non-Covalent Interaction (NCI), Reduced Density Gradient (RDG), and Quantum Theory of Atoms in Molecules (QTAIM) was performed to reveal weak interactions within the compound, spanning both chemical functionalities and delocalized zones. Furthermore, molecular docking analysis was performed to examine the potential biological activity against tumor-inducing proteins H-RASGTP and H-RASGDP, endorsing the antitumor efficacy of 2TFMBI.