Structural elucidation, biological significance and computational approach of Copper(ii), Nickel(ii) and Cobalt(ii) with bidentate schiff base of N-(Napthalene-1-ylmethylene)isonicotinohydrazide

Abstract The increasing prevalence of antibiotic-resistant bacteria and oxidative stress-related diseases underscores the need for novel therapeutic agents with potential dual functionality. In this research, a schiff base ligand, N-(Napthalene-1-ylmethylene)isonicotinohydrazide, was synthesized and complexed with Copper(II), Nickel(II), and Cobalt(II) ions. Characterization of the compounds using various spectroscopic and analytical techniques confirmed successful complex formation and structural stability. Antibacterial testing through the disc diffusion method revealed that the Ni(II) complex exhibited the highest antibacterial activity, with significant inhibition against Staphylococcus aureus , Bacillus subtilis , Escherichia coli , and Shigella flexneri . The antioxidant activity, evaluated via DPPH radical scavenging, showed that the Cu(II) complex was the most effective with an IC 50 value of 187.81 ± 1.42 µg/mL. Molecular docking studies against DNA gyrase (PDB ID: 7P2M) predicted the Ni(II) complex as the best binder (–9.9 kcal/mol), suggesting strong initial affinity. Complementary molecular dynamic simulations further demonstrated that Cu(II) and Co(II) complexes maintained the most stable protein-ligand interactions under dynamic conditions, highlighting their potential as robust inhibitors. ADMET predictions indicated favorable pharmacokinetic and toxicity profiles, though recognized as preliminary. DFT calculations confirmed stable geometries and showed a reduction of the HOMO–LUMO energy gap from 4.21 eV (ligand) to 2.85 eV (Ni complex), consistent with enhanced reactivity and biological activity. Mapping of electron density and atomic charge analysis identified potential nucleophilic attack sites, reinforcing the complexes’ therapeutic potential in combating bacterial infections and oxidative stress.