Synthesis, DNA binding profile and DNA cleavage pathway of divalent metal complexes

Abstract

Complexes of dipyridylamine based ligand with an anthracene moiety containing divalent metal ions Co(II), Cu(II), Ni(II), Zn(II) and Cd(II) were characterized structurally. The experimental results showed that they can induce considerable oxidative DNA cleavage in the presence of hydrogen peroxide and dioxygen. The Zn(II) complex did not show any appreciable cleavage activity, whereas the Cd(II) and Ni(II) complexes were moderately active. On the other hand, Cu(II) and Co(II) complex showed the formation of a significant quantity of linear DNA resulting from the double-strand breaks. Mechanistic studies revealed the involvement of HO center dot and the superoxide anion to be the reactive species in the scission process in aerobic media. A mechanism involving either the Fenton or the Haber-Weiss reaction was proposed for the DNA cleavage mediated by these complexes. The Cu(II) complex could also cleave the double stranded calf thymus DNA (ds DNA) in the presence of activators, most likely via an oxidative mechanism, whereas the activity of the other complexes was negligible under similar reaction conditions. The kinetic aspects of ds DNA cleavage with the Cu(II) are detailed. The interaction of the five metal complexes with ds DNA was investigated by UV absorption and linear dichroism studies, and the mode of complexes binding to ds DNA is proposed.