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 CuCl or Cu(NO)·2.5 HO yielded the monomeric [Cu(Py(OMe)BTh))(NO)]NO·1.5 MeOH, (1·1.5 MeOH) complex or the dimeric [Cu(Py(OMe)BTh)Cl] (2), respectively, with the nuclearity of the complex dependent on the starting Cu(II) salt. Reaction between the methyl substituted ligand and Cu(NO)·2.5 HO resulted in the isolation of Cu(Py(Me)BTh)(NO)·0.5 THF (3·0.5 THF). Complexes 1-3 were fully characterized. Cyclic voltammetry measurements were performed on all three complexes as well as on [Cu(PyBTh)(HO)](BF) (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. 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)(NO)(HO) and Cu(PyBIm)(BF). The differences in the observed toxicities suggests the importance of the ligand and its substituents in modulating cell death.