Straightforward Synthesis, Spectroscopic Characterizations, Molecular Docking, Molecular Dynamics Simulations, and Comprehensive DFT Calculations of Novel Tetrazole 1,5 and 2,5-Disubstituted Tetrazole Scaffolds

Abstract

New 1,5- and 2,5-disubstituted tetrazole derivatives were successfully synthesized under phase-transfer catalysis conditions in good to excellent yields (21%–97%). The structures of the obtained compounds were confirmed by ¹H and ¹³C NMR spectroscopy, as well as single-crystal X-ray diffraction analysis. Density functional theory calculations performed at the B3LYP/DNP 3.5 level showed that compound F possesses the smallest HOMO–LUMO energy gap (3.390 eV), suggesting enhanced chemical reactivity. Monte Carlo/SAA simulations demonstrated strong adsorption tendencies on metallic surfaces, particularly for compound 1j on the Fe(110) surface, with an adsorption energy of −229.944 kcal mol⁻¹. Molecular docking investigations against Abl kinase targets demonstrated favorable binding affinities, with docking scores reaching −11.7 and −8.3 kcal mol⁻¹ for the most active derivatives. In addition, 100 ns molecular dynamics simulations confirmed the stability of the 2HZI–3d and 4TWP–2j complexes throughout the simulation period. These findings highlight the potential of the synthesized tetrazole derivatives as promising candidates for further biological and corrosion-related applications.