Hydrazone-oxime Ni(II) complexes: crystal structures, DNA binding, DNA cleavage and topoisomerase inhibition

Two novel square-planar Ni(II) complexes, [Ni(HL1)]ClO4 and [Ni(HL2)]ClO4, were synthesized from hydrazone-oxime Schiff base ligands and characterized by elemental analyses, FT-IR, UV-Vis,1H NMR spectroscopies and single-crystal X-ray diffraction. Structural analyses, confirmed the formations of the mononuclear Ni(II) centers in distorted square-planar geometries. Hirshfeld surface analyses highlighted dominant van der Waals and hydrogen-bonding interactions contributing to crystal stabilities. The DNA-binding affinities of the complexes were investigated via UV-Vis spectroscopy and molecular docking, revealing a minor groove binding with moderate affinity. DNA cleavage assays under both oxidative and hydrolytic conditions demonstrated time- and concentration-dependent activities. Topoisomerase inhibition studies indicated that both complexes act as Topo I catalytic inhibitors, while [Ni(HL1)]ClO4 additionally functioned as a Topo IIα poison. These findings demonstrate that hydrazone-oxime Ni(II) complexes can simultaneously modulate DNA structure and enzymatic function, offering valuable insight into the design of multifunctional coordination compounds.