Dinuclear μ‐Phenoxo and μ‐Hydroxo Bridged Copper Complexes Exhibiting Oxidation of Phenols and Isoelectronic Compounds: Cytotoxicity and Evidences for Cellular Apoptosis

Abstract

The compartmental pentadentate ligands HLR (where R=Me, OMe, tBu) have been utilized for the synthesis of dinuclear hydroxo and phenolato bridged copper complexes viz. [Cu2(LMe)(μ‐OPh)(μ‐OH](ClO4)2]CH3CN; (1), [Cu2(LOMe)(μ‐OPh)(μ‐OH)(μ‐OH2)](ClO4)2.CH3CN; (2) and [Cu2(LtBu)(μ‐OPh)(μ‐OH)(OH2)](ClO4)2; (3). All the three complexes were characterized by various spectroscopic techniques. Tyrosinase activity was studied by insitu reaction of Cu(I) and ligands exploiting 2,4‐di‐tert‐butyl phenol as substrate. The phenolic substrate (2,4‐DTBP) underwent radical mediated C−C coupling reaction with no insertion of molecular oxygen in contrast to the oxidative aromatic hydroxylation reaction. The catalytic activities of complexes 1–3 on diphenols and related substrate molecules were investigated and all three complexes efficiently oxidize 3,5‐di‐tert‐butylcatechol. Treatment of copper complexes on o‐aminophenol and o‐phenylene diamine resulted in the oxidative coupling of substrate molecules, leading to the formation of phenoxazinone and diaminophenazine respectively. Furthermore, oxidative properties of reported copper complexes were studied in relevance to their ability in inducing apoptotic cell death. Remarkably, all three copper complexes (1, 2 and 3) exhibited excellent cytotoxic activity towards MCF‐7 cell lines (human breast cancer cell lines) with IC50 values of 1.6 μM, 2.0 μM and 0.65 μM respectively and carried out self activated DNA cleavage of plasmid pUC18 DNA.