Synthesis, Characterization, and In-Silico Exploration of N-Salicylideneaniline Schiff Base Derivatives: DFT, Antioxidant activity and Molecular Docking Studies

Abstract

This study reports the synthesis of three N-salicylideneaniline Schiff base derivatives: N-(2 hydroxybenzylidene)-m-chloroaniline (HBMC), N-(2-hydroxybenzylidene)-m-nitroaniline (HBMN), and N-(2-hydroxybenzylidene)-m-methoxyaniline (HBMM). Characterization was achieved through a combination of spectroscopic techniques (FT-IR, 1H NMR, UV-Vis) and density functional theory (DFT-B3LYP) calculations, demonstrating strong agreement between experimental and theoretical data. Computational methods were employed to investigate potential antioxidant mechanisms. Calculations of bond dissociation energies (BDEs), ionization potentials (IPs), proton dissociation energies (PDEs), proton affinities (PAs), and electron transfer energies (ETEs) in various solvents revealed a solvent-dependent shift. The Single Proton Loss Electron Transfer (SPLET) mechanism appears dominant in polar environments, while the Hydrogen Atom Transfer (HAT) mechanism is favored in the gas phase. HBMC exhibited the most promising profile for radical scavenging among the investigated compounds. In silico ADME-Tox analysis revealed favorable pharmacokinetic properties and compliance with drug-likeness criteria for all three derivatives, indicating potential for good oral bioavailability. Molecular docking studies further highlighted their potential as inhibitors of the UQCRB protein, with HBMM demonstrating the strongest binding affinity (-7.68 kcal/mol).