Synthesis and multidimensional investigation of a tetra-substituted imidazole derivative: Spectroscopy, DFT/NLO properties, toxicity analysis, molecular docking, and dynamics simulation

A novel tetra-substituted imidazole derivative <b>(BDIM)</b> was synthesized via a one-pot, four-component condensation reaction using BF₃ as a Lewis acid catalyst. The experimental FT-IR,¹H- and ¹³C-NMR spectra show a very good match with the DFT-calculated results, which proves that the optimized molecular geometry and electronic structure are correct. The strong correlation between the experimental and theoretical spectral parameters supports the proposed molecular structure and shows that the computational method used is reliable. NBO analysis revealed strong π→π* (13.26-22.43 kcal mol^-1) and n→π* (23.93-35.85 kcal mol^-1) interactions, indicating extensive π-conjugation and intramolecular charge transfer. Moderate n→σ* delocalization (∼7.7 kcal mol^-1) further contributes to overall molecular stability. The frontier molecular orbital (FMO) calculations gave a HOMO-LUMO energy gap of 3.11 eV, and the compound displayed high nonlinear optical (NLO) activity with a first-order hyperpolarizability (β₀) of 1.399 × 10^-³⁰esu, suggesting strong potential for optoelectronic applications. Molecular electrostatic potential (MEP) and Mulliken charge analyses highlighted reactive regions suitable for further functionalization. Molecular docking and molecular dynamics (MD) simulations were performed to evaluate the interaction of the synthesized imidazole derivative BDIM with key SARS-CoV-2 target proteins 6WCF, 6Y84, and 6LU7, compared with hydroxychloroquine and native ligands. Docking results showed that <b>BDIM</b> exhibited strong binding affinities of -9.7, -7.8, and -8.1 kcal/mol, respectively, surpassing hydroxychloroquine and comparable to the native ligands. The 6WCF-BDIM complex, showing the highest affinity, was further analyzed by MD simulations for 100 ns. The analysis revealed potential risks of neurotoxicity, respiratory toxicity, blood-brain barrier penetration, and GABA receptor interaction, while showing low probabilities for hepatotoxicity, nephrotoxicity, mutagenicity, and carcinogenicity.