Studies on DNA damage and induction of SOS repair by novel multifunctional bioreducible compounds. I. A metronidazole adduct of dirhodium (II) tetraacetate

A novel bifunctional hypoxia-selective compound [Rh2(O2CCH3)4.2C6N3O3H9] has been synthesized and its genotoxic and potential mutagenic effects studied with reference to those of dirhodium tetraacetate (RAc) and metronidazole. The properties of the two functional components have been examined by comparing its oxic genotoxicity, a measure of the DNA damage induced by RAc, with its anoxic genotoxicity by electrochemical reduction, a measure of DNA damage resulting from the combined activity of reduced nitro group intermediates and RAc. The induction of DNA SOS repair has also been studied as well as the strand-breaking ability of the compound using viscometry. The genotoxic effects observed are proportional to the drug concentration over the range tested and the compound exhibits a high selective toxicity differential to hypoxic bacteria. The strand-breaking and mutagenic properties are governed by the metronidazole component and other effects, such as inhibition of DNA synthesis, are governed by the RAc component.