Ni(ii) and Co(ii) complexes of an asymmetrical aroylhydrazone: synthesis, molecular structures, DNA binding, protein interaction, radical scavenging and cytotoxic activity

Abstract

Two new nickel(II) and cobalt(II) benzhydrazone complexes having the general formula [ML₂phen·3CH₃OH] (where M = Ni and Co, L = 2-acetonaphthonebenzoylhydrazone, phen = 1,10-phenanthroline) have been synthesized via the reaction of Ni(OAc)₂·4H₂O and CoCl₂·6H₂O with 2 equivalents of HL and 1 equivalent of phen ligands in a MeOH/THF mixed medium. Both complexes have been characterized by single-crystal X-ray crystallography methods, which reveals a distorted octahedral coordination environment around the metal center with an MN₄O₂ chromophore [M = Ni(II) and Co(II)], with the hydrazone ligand acting as a monoanionic bidentate N,O-donor. These complexes exhibit quasi-reversible one-electron reduction responses (Ni^II–Ni^I, Co^II–Co^I) within the E_1/2 at −0.808 and −0.767 V versus Ag/AgCl reference. The DNA-binding interactions of the complexes with herring sperm DNA have been investigated by UV-vis absorption, emission and viscosity measurements, which reveal that the complexes could interact with DNA via intercalation. The protein binding interactions of the complexes with BSA were investigated by UV-vis, fluorescence and synchronous fluorescence methods, which indicate strong binding of the complexes with BSA and a static quenching mechanism was observed. The Ni(II) complex displays higher DNA and BSA-binding affinity than the corresponding Co(II) analogue, which is expected of its smaller size. Moreover, the potential for free-radical scavenging of all the complexes was also determined using DPPH, hydroxyl and nitric oxide radicals under in vitro conditions, showing that the complexes are more effective in arresting the formation of hydroxyl than nitric oxide or DPPH radicals. Cytotoxicity experiments reveal that the two complexes both exhibit cytotoxic effects against human hepatocellular carcinoma cell line SMMC-7721 and human lung adenocarcinoma cell line A549.