Solid acid-catalyzed green synthesis of bis-Schiff bases: Spectroscopic, DFT, molecular docking, and ADMET studies

This research examines the green synthesis of bis-Schiff bases with benzyl substitutions at 3,4-dimethoxy and 3,4,5-trimethoxy positions through solvent-free microwave-assisted condensation between para-phenylenediamine and 3,4-dimethoxybenzaldehyde (I) and 3,4,5-trimethoxybenzaldehyde (II), using sulfated-TiO₂ as a solid acid catalyst. The structures were confirmed through various physicochemical and spectroscopic techniques, including IR, ¹H NMR, ¹³C NMR, and SC-XRD. The compound II crystallized in the monoclinic system (space group of P-2₁/c). The primary objective was to explore the geometry using both experimental methods and density functional theory (DFT) with the B3LYP/6–311 G (d,p) level. A comparison of experimental (FT-IR, NMR, SC-XRD) and simulated data showed strong agreement. Additionally, Hirshfeld analysis, ELF, LOL, and RDG topological studies were performed. Docking simulations on the 2V54 monkeypox target protein revealed binding affinities, with compounds I and II. The target protein had a binding energy of 4.83 and −4.98 kcal/mol with I and II. ADMET predictions further demonstrated the pharmacological profile of the synthesized compounds.