New Bicyclic Benzylidene Oxazole Pyrimidines: Synthesis, Docking, Dynamics, and Adsorption Studies on Fe(110) and Cu(111)

Abstract This study reports the successful synthesis of a novel series of bicyclic benzylidene oxazole pyrimidine derivatives namely (Z)-6-benzoyl-2-benzylidene-5,7-diphenyl-5H-oxazolo[3,2-a]pyrimidin-3(2H)-one (C1), (Z)-6-benzoyl-2-(3,4-dimethoxybenzylidene)-5,7-diphenyl-5H-oxazolo[3,2-a]pyrimidin-3(2H)-one (C2), and (Z)-6-benzoyl-2-(4-fluorobenzylidene)-5,7-diphenyl-5H-oxazolo[3,2-a]pyrimidin-3(2H)-one (C3) via a one-pot Hantzsch heterocyclization and Knoevenagel condensation. The compounds were characterized by FTIR, ¹H-NMR, and ¹³C-NMR spectroscopy, supported by theoretical calculations. Quantum chemical simulations using B3LYP/6-311G+(d,p) provided insights into electronic properties, including HOMO-LUMO gaps, MEP surfaces, Fukui functions, and topological parameters. Monte Carlo (MC) simulations evaluated adsorption behavior on Fe(110) and Cu(111), with C2 exhibiting the strongest binding affinity. Drug-likeness and toxicity assessments classified the compounds in the 2nd toxicity class, with C1 being BBB toxic, C2immunotoxic, and C3 neurotoxic and BBB toxic. Molecular docking (MD) studies indicated C1 as a potent COX-2 inhibitor (-10.137 XP GScore), stabilized by π⋅⋅⋅πinteractions, while C2 showed strong hydrogen bonding in the NF-κB pathway. Molecular dynamics simulations confirmed the stability of the COX-2-C1 complex, highlighting key ligand-protein interactions. These findings suggest C1as a promising COX-2 inhibitor and C2 as a potential NF-κB modulator, offering insights for future drug development.