Oxidative DNA Cleavage by Zn(X-BDPA)(NO3)2Complexes (X=F, H, and Me): Effect of Different Ligand Substituents

Abstract

Metal complexes have a large potential in biological and medicinal applications because of their cationic character, modularity, reactivity, redox chemistry, photoreactions and defined three dimensional structures. Particularly, the catalytic effects of various metal complexes on the nucleic acids cleavage has been a subject for an intensive study. As a recent example, oxidative DNA cleavage by [M(2,2'dipyridylamine)2(NO3)n] x+ (M = Cd, Cu, Ni and Zn, n = 1, 2, x = 0, 1) metal complexes has been reported. The cleavage has been shown to depend on the nature of the central metal: Zn performed the fastest and Ni the slowest in double stranded DNA cleavage. Another report showed that (N,N'ethylenediaminediacetato) M(II) complexes (M = Cu, Co, Ni, Zn) cleaved plasmid DNA in the presence of hydrogen peroxide. The Cu(II) complex was more efficient in DNA cleavage than the Zn and Ni complexes; the different amounts of OH radicals among the complexes were responsible for their different efficiencies. In this study, we report the cleavage of supercoiled pgem7zf-nisin DNA (referred to as pgem DNA) by Zn(X-BDPA) (NO3)2 complexes (Figure 1). 6 As shown in the structure, the ligand possesses Me or F at the position of X. The presence of Me or F represents an electron donating or withdrawing group, respectively, resulting in a different electron density on the complex in each case (see Supporting Information for the syntheses and characterizations of three ligands and their metal complexes). Figure 2 depicts the time-dependent appearance of nicked circular and linear pgem DNA with respect to the incubation time. The amount of super coiled pgem DNA decreased with incubation time for all three complexes. After 40 minutes of incubation, no super coiled DNA was left for the Zn(X-BDPA)(NO3)2 complexes, where X represents H or Me. The appearance of linear DNA was also noted for the X = Me complex after 35 minutes of incubation. The band corresponding to linear DNA appeared after 50 minutes incubation for the complex with X = H.