Synthesis, characterization and comparative biological activity of a novel set of Cu(II) complexes containing azole-based ligand frames

The synthesis and spectroscopic characterization of three complexes containing a substituted 2-(2-pyridyl)benzothiazole (PyBTh) group in the ligand frame are reported along with the comparative biological activity. The ligands have been substituted at the 6-position with either a methoxy (Py(OMe)BTh) or a methyl group (Py(Me)BTh). Reaction of Py(OMe)BTh with either CuCl2 or Cu(NO3)(2)<middle dot>2.5 H2O yielded the monomeric [Cu(Py(OMe)BTh))(2)(NO3)]NO3<middle dot>1.5 MeOH, (1<middle dot>1.5 MeOH) complex or the dimeric [Cu(Py(OMe)BTh)Cl-2](2) (2), respectively, with the nuclearity of the complex dependent on the starting Cu(II) salt. Reaction between the methyl substituted ligand and Cu(NO3)(2)<middle dot>2.5 H2O resulted in the isolation of Cu(Py(Me)BTh)(NO3)(2)<middle dot>0.5 THF (3<middle dot>0.5 THF). Complexes 1-3 were fully characterized. Cyclic voltammetry measurements were performed on all three complexes as well as on [Cu(PyBTh)(2)(H2O)](BF4)(2) (4), a compound previously reported by us which contains the unsubstituted 2-(2-pyridyl)benzothiazole ligand. The biological activity was studied and included concentration dependent DNA binding and cleavage, antibacterial activity, and cancer cell toxicity. All complexes exhibited DNA cleavage activity, however 2 and 4 were found to be the most potent. Mechanistic studies revealed that the nuclease activity is dependent on an oxidative mechanism reliant principally on O-2(-). Antibacterial studies revealed complex 4 was more potent compared to 1-3. Cancer cell toxicity studies were carried out on HeLa, PC-3, and MCF7 cells with 1-4, Cu(QBTh)(NO3)(2)(H2O) and Cu(PyBIm)(3)(BF4)(2). The differences in the observed toxicities suggests the importance of the ligand and its substituents in modulating cell death.