DNA/protein interaction and cytotoxic activity of imidazole terpyridine derived Cu(II)/Zn(II) metal complexes

Two imidazole terpyridine (itpy) based complexes, [Cu(itpy)(OAc)(H2O)]NO3·H2O (1) and [Zn(itpy)(OAc)]OAc (2) have been synthesised and characterized. The crystal structure of complex 1 shows distorted octahedral geometry with an anti-parallel stacking arrangement. The interactions of the two complexes with Calf thymus DNA (ctDNA) have been studied using absorption titration and circular dichroism. Complex 1 shows coordinate binding to DNA bases, and complex 2 shows an intercalative mode of binding with DNA. Complex 1 cleaves the DNA via an oxidative pathway in the presence of additives, because of the presence of a redox active copper(II) centre. However, complex 2 cleaves DNA hydrolytically. Interactions of the two complexes with bovine serum albumin have been studied using fluorescence quenching and circular dichroism experiments. Circular dichroic analysis reveals that both the complexes strongly influence the secondary structure of the protein. Fluorescence quenching experiments indicate that there are different binding sites for complexes 1 and 2 on the protein. Furthermore, the complexes show potential cytotoxicity towards the A549 lung cancer cell line. Both the complexes have been found to induce apoptosis.