Novel Mixed-Ligand Co(II), Ni(II), and Cu(II) Complexes of Azo-Schiff Bases with 1,10-Phenanthroline and Metformin: Synthesis, Characterization, Molecular Docking, and Antibacterial Evaluation

In this study, two azo-Schiff base ligands were synthesized via condensation of vanillin and 4-(dimethylamino)benzaldehyde with 4-aminoazobenzene. Mixed-ligand complexes of Co(II), Ni(II), and Cu(II) were synthesized using 1,10-phenanthroline (Phen) and metformin (Met), affording twelve complexes with a metal-to-ligand ratio of 1:2. The synthesized ligands and their complexes were characterized using FT-IR, 1H-NMR, UV-Vis spectroscopy, atomic absorption spectroscopy (AAS), elemental analysis (C, H, N), molar conductivity, thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electron microscopy (SEM). XRD analysis revealed an average crystallite size of 56 nm using Scherrer's equation. Spectral data confirmed coordination through the azomethine and azo nitrogen atoms, while electronic spectra and magnetic measurements supported octahedral geometry around the metal ion. The effective magnetic moments were 3.91-4.25 B.M. for Co(II), 2.654-2.899 B.M. for Ni(II), and 1.65-1.721 B.M. for Cu(II) complexes. Molar conductivity values (135-170 Ω-1cm2mol-1) indicated that complexes behave as 1:2 electrolytes. TGA confirmed the presence of water of crystallization, whereas SEM revealed aggregated nanostructures with particle sizes of 130-270 nm. Molecular docking studies against the bacterial protein (1JIK) and acetylcholinesterase (1B41) showed favorable binding affinities, with ligand L2 exhibiting the highest affinity toward the acetylcholinesterase target (-9.494 kcal/mol). Antibacterial evaluation against Escherichia coli and Staphylococcus aureus demonstrated enhanced activity of the complexes compared with the free ligand, with complex 5 showing the highest inhibition zones (22 and 20 mm, respectively). The combined experimental and molecular docking results highlight the potential of these mixed-ligand complexes as promising bioactive coordination compounds.