Synthesis, structural elucidation, electronic properties, and biomolecular docking studies of halogen-substituted aminobenzohydrazone Schiff base ligands

Abstract

Three halogenated Schiff base ligands (H₂L¹−H₂L³) with ONO donor sets were synthesized from 4-aminobenzohydrazide and dihalogenated salicylaldehydes (Cl, Br, I). Their structures were confirmed using multiple spectroscopic methods (FT-IR, ¹H/¹³C NMR), and the molecular structure of H₂L¹ was definitively determined by single-crystal XRD. Intermolecular interactions were explored via Hirshfeld surface analysis. Molecular orbital (MO), molecular electrostatic potential (MEP), natural bond orbital (NBO), and natural population analysis (NPA) revealed the electronic distribution and donor-acceptor interactions, demonstrating a clear substituent effect where the halogen identity systematically influenced the electron density and molecular polarity. Molecular docking simulations revealed that the ligands interact favorably with DNA and bovine serum albumin (BSA) through hydrogen bonding and hydrophobic contacts, with DNA binding predominantly occurring within the grooves, highlighting their potential for strong biomolecular interactions.