Biological Evaluation of 2-Hydroxy-1-Naphthaldehyde Based Ligand and Its Metal Complexes: Synthesis, Characterization, Density Functional Theory, and Docking Studies

Schiff base metal complexes continue to attract considerable attention due to their tunable coordination geometries and promising biological applications. In this study, Co(II), Ni(II), Cu(II), Zn(II), and Pd(II) complexes of 1-(((4H-1,2,4-triazol-yl)imino)methyl)naphthalen-2-ol (HNAT) were designed and well characterized using spectroscopy, analytical, and computational methods. Based on analytic and spectroscopic techniques, the geometry of the complexes is confirmed, which indicates octahedral for Co(II), square planar for Ni(II), Cu(II), Pd(II), and tetrahedral for Zn(II) complexes. The proposed geometries were further supported by DFT calculations. The powder X-ray diffraction patterns show that the ligand and its complexes are crystalline. The crystallite sizes of the ligand and its metal complexes [Co(II), Ni(II), Cu(II), Zn(II), and Pd(II)] were determined as about 44, 24, 48, 23, 35, and 31 nm, respectively, which are considered nanocrystalline. The PXRD pattern of the ligand is quite different compared to the metal complexes, indicating the existence of new crystalline phases with the formation of new complexes. DNA-binding studies ensured that Cu(II) complex has significantly high Kb value, suggesting its strong ability to interact with DNA, which enhances effective π–π stacking with DNA base pairs. In addition, the antimicrobial activity of the Ni(II) complex displayed broad spectrum activity with MIC of 3.65, 4.51, 4.44, and 4.86 µg/mL against K. pneumoniae and E. coli, S. aureus, and S. epidermidis. In addition, cytotoxicity of Cu(II) and Zn(II) complexes showed high activity against HepG-2, MCF-7, and HeLa cell lines. The EGFR (PDB: 4HJO) molecular docking indicated the greatest binding affinity with the Cu(II) complex (−10.32 kcal mol−1), which was consistent with the experimental findings. These results demonstrate the potential of metal complexes in the treatment process and also give structure-activity information to use in designing new drugs.