Further evidence for redox activation of the plasmid – dirhenium(III) complexes interactions

Abstract

The DNA-interactions in vitro are still necessary investigations for determination of the possible anticancer properties of the compounds, candidates for application in cancer therapy. The aim of the present work was to realize if the interaction of cis-dicarboxylates of dirhenium(III), with pivalato- (I), isobutirato- (II) and adamanthyl- (III) ligands cleaves the plasmid in the same manner and what is the influence of the ligands on this process. For experiments we used the prokaryotic plasmid which is good model to analyze DNA-cleaving ability of different substances that exists in supercoiled conformation and turns to nicked and linear forms. It was shown that gradual conversion of the supercoiled Form I to a mixture of supercoiled (Form I) and nicked (Form II) DNA takes place and increasing amounts of Form II are produced with higher concentrations of I–III under increasing of concentration that showed the DNA-cleaving abilities of all investigated dirhenium complexes. This process was taking place with different intensity in the range I ˃ II ˃ III, that demonstrates the influence of the organic radical on the cleaving activity of the dirhenium(III) complexes. Under hydrogen peroxide conditions, I and II showed close results, demonstrating more intensive process of cleaving, including formation of the linear plasmid (Form III) under higher concentration, witnessing about redox-activation of the DNA-cleaving reaction. Cleaving activity of III was approximately the same in all experiments, that was demonstrated only by decreasing of the supercoiled form I and increasing of the nicked form II of the plasmid and by absolutely absence of the linear form III of the plasmid. The electrophoresis mobility shift assays showed that rhenium cluster compounds have nuclease activity and confirmed that natural DNA may be their target in the living cells. The conclusion was made that the mechanism of DNA-cleavage reaction of the dirhenium(III) complexes is multiple in which the electron donating (withdrawing) effects of the ligands and catalytic activity of the metal core should be taken in consideration.