The in situ DNA-damaging capacity of berenil (1) has been investigated using an electrochemical approach employing double stranded (ds) DNA-modified glassy carbon electrode biosensors. Electrochemical voltammetric sensing of damage caused by 1 to dsDNA was monitored by the appearance of peaks diagnostic of the oxidation of guanine and adenine. When 1 was incorporated directly onto the biosensor surface, DNA damage could be observed at concentrations of additive as low as 10 μM. In contrast, when the dsDNA-modified biosensor was exposed to 1, in acetate buffer solution, the method was much less sensitive and DNA damage could be detected only in the presence of 100 μM berenil. When mixed solutions of 1 and single stranded (ss) DNA, polyguanylic acid or polyadenylic acid were submitted to voltammetric study, the oxidation signals of the respective bases decreased in a concentration-dependent manner and the major variation of the adenine current peak indicated preferential binding of 1 to adenine. The electrochemical results were in close agreement with those deriving from a differential scanning calorimetric study of the DNA-berenil complex.

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2:8, 0.18 mol L −1 , pH 9.6͒ and aprotic ͓dimethylformamide ͑DMF͒ + tetrabutylammonium perchlorate ͑TBAP͒, 0.1 mol L −1 ͔ media. The primary reduction behavior in aprotic medium was typical of nitroaromatics along with an additional wave related to the reduction of the acrylate function. Kinetic analysis carried out in aprotic and aqueous basic media pointed out to the high stability of the electrogenerated nitro radical anion, especially in DMF + TBAP. Reduced ͑GSH͒ and oxidized ͑GSSG͒ gluthatione in phosphate buffer influenced the reduction behavior of 1, due mainly to protonation effects. Direct reduction of 1, in the presence of GSH, led to a transient nitroso-GS adduct. In the presence of GSSG, hydrogen-bondingassociated GSSG-hydroxylamine was the main product. Electrochemical studies of 1, in the presence of oxygen, showed no chemical reactivity between O 2 and 1-•. These electrochemical results help in the understanding of the anticancer activity of 1 that can be considered a bioreductive agent with a glutathione depleting function.

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