Synthesis, Characterization, Computational, DNA Binding and Cleavage Studies of Cu (II), Co (II), and Ni (II) Metal Complexes Derived N'-[(E)-(3-hydroxynaphthalen-2-yl) methylidene] pyridine-4-carbohydrazide

We describe the synthesis, detailed characterization, and biological assessment of new Cu (II), Co (II), and Ni (II) complexes formed from a hydrazone Schiff base ligand. Structural analysis using multiple spectroscopic and analytical methods confirmed an octahedral geometry, with metal ions coordinated through the azomethine nitrogen and hydroxyl oxygen atoms. DNA-binding behaviour was examined by UV–Vis absorption spectroscopy, viscosity studies, and thermal denaturation experiments, indicating a classical intercalative mode of binding, with binding constants reaching 4.43 × 10⁶ M⁻¹. Agarose gel electrophoresis showed that these complexes efficiently promote oxidative cleavage of plasmid DNA, an effect associated with reactive oxygen species generated by the redox-active metal centres. Molecular docking studies revealed strong interactions of the complexes, especially those of Co (II) and Ni (II), with DNA binding sites. Furthermore, DFT calculations shows the electronic structures and frontier molecular orbitals of the complexes, which correlate well with their observed biological activity. Collectively, these findings indicate that the synthesized metal complexes are promising DNA-targeted therapeutic candidates with substantial potential for biological applications.