Design, synthesis, and biological insights of a novel imidazole-based heterocycle: A combined spectroscopic and DFT approach

A new imidazole-based heterocycle, 4-(2-(2-(4-isopropylphenyl)-4,5-diphenyl- 1H -imidazol-1-yl)ethyl)morpholine, was synthesized via a one-pot multicomponent reaction and its structure was confirmed by FT-IR, ¹H NMR, and ¹ ³C NMR spectroscopy. The vibrational characteristics associated with aromatic and aliphatic functionalities exhibited excellent agreement between the experimental and DFT-predicted IR spectra at the B3LYP/6–311 ++G(d,p) level. The GIAO-calculated NMR chemical shifts closely matched the experimental values, confirming the electronic environment around the heteroaromatic core. Geometry optimization revealed a rigid π-conjugated imidazole ring system connected to a flexible morpholine-ethylene chain with energetically favorable conformers at −180° and +60°. NBO analysis demonstrated strong π→π* and n→π* delocalization, contributing to enhanced electronic stabilization. FMO and MEP analyses indicated a favorable charge distribution for receptor binding, while the calculated first-order hyperpolarizability suggests that the compound possesses moderate nonlinear optical (NLO) properties. The synthesized compound also exhibited significant in vitro cytotoxic activity against A549 human lung cancer cells in the MTT assay, indicating its potential as an anticancer agent. Molecular docking against PI3Kα showed a high binding affinity (−9.8 kcal/mol) with diverse interactions, including π–cation, π–anion, hydrogen bonding, and hydrophobic contacts. Furthermore, 200 ns molecular dynamics simulations confirmed the stability of the protein–ligand complex (RMSD 2–3.5 Å). ADMET predictions indicated favorable drug-like characteristics; however, potential toxicity suggests that further structural optimization is warranted. Overall, the excellent agreement between experimental and theoretical studies, together with the promising cytotoxic, computational, and physicochemical properties, highlights this multifunctional imidazole derivative as a promising lead for anticancer drug development and advanced material application.