Mixed-ligand copper(II) phenolate complexes: Synthesis, spectral characterization, phosphate-hydrolysis, antioxidant, DNA interaction and cytotoxic studies

• Eight mixed-ligand copper(II) complexes have been synthesized and characterized.
• Binding studies revealed the intercalative/groove binding of complexes with CT-DNA.
• The mechanism of DNA cleavage indicate the involvement of ROS.
• Cytotoxicity studies show the death of cancer cells via apoptosis.
• The complexes with hydrophobic CH3 substituent show higher biological activity.

A series of phenol-based mixed-ligand copper(II) complexes of the type [CuL1–4(diimine)] (1–8), where L1–4 = N1,N2-bis(5-substituted-2-hydroxybenzylidene)-1,2-ethylene/phenylenediimine and diimine = 2,2′-bipyridyl (bpy) or 1,10-phenanthroline (phen), have been isolated and fully characterized by analytical and spectral techniques. Electronic spectra of complexes suggest Cu(II) cation has a d9 electronic configuration, adopting distorted octahedral geometry with axial elongation, due to Jahn–Teller effect. Electrochemical studies of complexes evidenced one-electron irreversible reduction wave in the cathodic region. The observed rate constant (k) values for the hydrolysis of 4-nitrophenylphosphate (4-NPP) are in the range of 0.25–3.82 × 10−2 min−1. The obtained room temperature magnetic moment values (1.79–1.90 BM) lies within the range observed for octahedral copper(II) complexes. Antioxidant studies revealed that these complexes possess considerable radical scavenging potency against DPPH. The binding studies of complexes with calf thymus DNA (CT-DNA) revealed intercalation with minor-groove binding, and the complex 4 exhibits highest binding activity than the other complexes. The cleavage activity on supercoiled pBR322 DNA revealed the involvement of hydroxyl radical and singlet-oxygen as reactive oxygen species, and complexes encourage binding to minor-groove. Further, the cytotoxicity of complex 4 on human hepatocellular liver carcinoma HepG2 cell line implies the cell death through apoptosis.

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