DNA cleavage studies of mononuclear and dinuclear copper(II) complexes with benzothiazolesulfonamide ligands

Abstract

Copper-based transition metal complexes performing single- and double-strand scission of DNA have been studied. The dinuclear complexes [Cu(2)(L)(2)(OCH(3))(2)(NH(3))(2)] and [Cu(2)(L)(2)(OCH(3))(2)(DMSO)(2)] are more active than the corresponding mononuclear [Cu(L)(2)(py)(2)] (where HL= N-(4-methylbenzothiazol-2-yl)benzenesulfonamide), suggesting that the dinuclearity is an important factor in the oxidative cleavage of DNA. The cleavage efficiency of the complexes depends on the reducing agent used in the process, the tandem ascorbate/H(2)O(2) being the most efficient. PAGE analyses have shown that these complexes cleave DNA without sequence selectivity. The DNA degradation process takes place mainly by C1' oxidation, but C4' and C5' oxidations cannot be ruled out as minor pathways. These copper complexes preferably oxidize guanine under mild conditions, but under more drastic conditions the oxidation reactivity appears to be T>G>C>A, suggesting the intervention of hydroxyl radicals as active species.

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

“…The slight suppression of cleavage may be ascribed to the affinity of sodium azide for transition metals [68]. Addition of superoxide dismutase (superoxide scavenger) to the reaction mixture show no significant quenching of the cleavage reaction revealing that superoxide anion is not also the active species (not shown) [68]. Thus no freely diffusible oxygen intermediate or hydroxyl radical is involved in the strand scission and hence a simple diffusible radical mechanism is ruled out.…”

“…9C); this reveals that 1 O 2 is not the activated oxygen intermediate responsible for the cleavage. The slight suppression of cleavage may be ascribed to the affinity of sodium azide for transition metals [68]. Addition of superoxide dismutase (superoxide scavenger) to the reaction mixture show no significant quenching of the cleavage reaction revealing that superoxide anion is not also the active species (not shown) [68].…”

The interaction of native DNA with Zn(II) and Cu(II) complexes of 5-triethyl ammonium methyl salicylidene orto-phenylendiimine

“…In particular, copper(II) complexes in the presence of oxidizing or reducing agents are able to cleave DNA. Research on DNA cleavage by synthetic copper complexes is of considerable interest because of their efficacy as anti-tumour agents [10][11][12][13].…”

Mono-, Trinuclear Nickel(ii) and Copper(ii) Dioxime Complexes: Synthesis, Characterization, Catecholase and Catalase-Like Activities, Dna Cleavage Studies

“…oxidative strand cleavage by abstraction of sugar hydrogen atom(s), hydrolytic cleavage involving the phosphate group, and by base oxidations primarily directed at the guanine base. 34 Although there are reports [35][36][37][38] of copper complexes cleaving DNA hydrolytically or in an oxidative manner in the presence of a reducing agent, the chemistry of copper complexes showing visible light-induced photocleavage is virtually unexplored. 34,39,40 We have previously described the preparation and DNA cleavage properties of oxime ligands which are capable of chelating two metal ions and in which the coordinating moieties are separated by 1,10-phenanthroline.…”