Synthesis and crystal structure of new monometallic Ni(ii) and Co(ii) complexes with an asymmetrical aroylhydrazone: effects of the complexes on DNA/protein binding property, molecular docking, and in vitro anticancer activity

Abstract

Two novel complexes, NiL₂phen·CH₃CN (1) and CoL₂phen·CH₃CN (2) (HL = 2-acetonaphthone salicylylhydrazone, phen = 1,10-phenanthroline) were synthesized and characterized by spectroscopy (IR, ESI-MS) and elemental analysis. The structures for the complexes were determined by X-ray crystallography proving the 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. Interaction of the ligand HL along with the corresponding copper complexes 1 and 2 with herring sperm DNA (HS–DNA) has been estimated by absorption and emission titration methods which revealed that the compounds interacted with HS–DNA through intercalation. Binding of the compounds with bovine serum albumin (BSA) protein investigated using UV-visible, fluorescence and synchronous fluorescence spectroscopic methods indicated that there occurred strong binding of nickel and cobalt complexes to BSA over the ligand HL. The alterations in the secondary structure of the protein by the complexes were confirmed by synchronous and three dimensional fluorescence spectroscopic studies. The interaction of the Ni(II) complex with DNA/BSA also has been supported by molecular docking studies. Further, the ligand HL and corresponding Ni(II) and Co(II) have been tested for their scavenging effect towards DPPH, NO, OH and O₂⁻ radicals. An in vitro cytotoxicity study of the complexes found significant activity against human breast (HeLa) and lung (A549) cancer cell lines, with the best results for Ni(II) complex, where the IC₅₀ values are of 34.93 ± 2.05 and 29.19 ± 1.10 μM respectively after 24 h of incubation.