Ni(II) Complexes with Mixed Ligands, Reduced N₂O₂ Schiff Bases and β-Diketones: Redox Modulation, ROS Generation and...

This study addresses the development of nickel(II) complexes with potential antiproliferative activity. Two novel hydrogenated Schiff base ligands (N₂O₂-type), L1 and L2, were synthesized using environmentally friendly routes within a green chemistry framework and fully characterized. These ligands were coordinated to Ni(II) to obtain mixed octahedral complexes of general formulae [Ni(N₂O₂)(NO₃)₂] and [Ni(N₂O₂)(O-O)]NO₃, where O-O denotes β-diketones (acetylacetonate and fluorinated analogs). Structural, spectroscopic, and electrochemical characterization, including cyclic voltammetry, was performed to evaluate the effect of ligand substitution on redox properties. Antiproliferative activity was assessed in HeLa cells. The results show that all complexes exhibit octahedral geometry, while [Ni(N₂O₂)(O-O)]NO₃ complexes behave as 1:1 electrolytes, with redox potentials influenced by electron-withdrawing fluorinated substituents on the secondary ligand. Complexes containing fluorinated diketones and the methoxy-substituted L1 ligand displayed enhanced antiproliferative effects compared to non-fluorinated and unsubstituted analogues. Mechanistic studies suggest apoptosis induction associated with early caspase-3 activation, likely mediated by reactive oxygen species. Overall, ligand electronic effects play a key role in modulating redox behavior and biological activity in these nickel(II) complexes.