Experimental and theoretical studies of salophen Schiff base ligands derived from 4-nitro-o-phenylenediamine: Docking and ADME studies, structural integrity, and functional properties of DNA and BSA

A series of mono-imine salophen Schiff base ligands— L1 (( E )-2-(((2-amino-5-nitrophenyl)imino)methyl)-6-ethoxyphenol), L2 (( E )-2-(((2-amino-5-nitrophenyl)imino)methyl)-6-methoxyphenol), and L3 (( E )-2-(((2-amino-5-nitrophenyl)imino)methyl)-4-bromophenol)—were synthesized via a 1:1 M ratio condensation of 4-nitro- o -phenylenediamine with various salicylaldehyde derivatives, 3-ethoxysalicylaldehyde, 3-methoxysalicylaldehyde, and 5-bromosalicylaldehyde, respectively. The electron-withdrawing nitro group was found to be critical, selectively yielding tridentate mono-imine products instead of the typical tetradentate di-imine salophen ligands. The molecular structure of L1 was explored by single-crystal X-ray diffraction (SC-XRD), revealing a non-planar enol tautomer stabilized by intramolecular O–H⋯N and N–H⋯N hydrogen bonds. Crystal packing analysis and Hirshfeld surface studies showed intermolecular O–H⋯N, N–H⋯O, and C–H⋯O interactions stabilize the lattice. Electrochemical analysis via cyclic voltammetry revealed a quasi-reversible reduction process associated with the nitro group in all ligands. The optimized structures obtained from DFT calculations were examined to explore their electronic properties and potential biological relevance. Frontier molecular orbitals (HOMO–LUMO), molecular electrostatic potential (MEP) maps, and natural bond orbital (NBO) analyses provided insights into charge distribution, reactive sites, and donor–acceptor interactions within the ligands. Docking simulations using AutoDock Vina (version 1.1.2) demonstrated that L1 , L2 , and L3 interact effectively with the active sites of DNA and bovine serum albumin (BSA), highlighting their possible influence on protein function and ligand bioavailability. To complement these findings, a pharmacokinetic assessment was conducted using the SwissADME tool. This in silico analysis predicted high gastrointestinal (GI) absorption and favorable drug-likeness for all ligands, collectively underscoring their strong potential as candidates for oral therapeutic agents. • Mono-imine salophen ligands synthesized via nitro-group-directed condensation. • Non-planar enol tautomer stabilized by intramolecular H-bonding (SC-XRD). • Quasi-reversible nitro reduction revealed by cyclic voltammetry. • DFT and docking show strong DNA/BSA binding and electronic properties.