Electrochemical characteristics of nitro-heterocyclic compounds of biological interest. I. The influence of solvent.

The electrochemical properties of three nitroimidazoles, a nitropyrazole, a nitrofuran and three nitrobenzenoid compounds have been extensively investigated in a range of solvents. The reduction pathway for the nitro group is independent of the cyclic function to which it is attached, but is strongly influenced by the nature of the solvent. In aqueous media, generally, a single, irreversible 4-electron reduction occurs to give the hydroxylamine. In aprotic media (dimethylformamide, methylene chloride or dimethylsulphoxide), a reversible one-electron reduction takes place to form a stable nitro radical anion. At more negative values, a further 3-electron reduction occurs, irreversibly to give the hydroxylamine. In mixed aqueous-organic systems, intermediate behaviour is found, with the reversibility of the RNO2/RNO.-2 couple increasing with addition of organic medium. The control of the reduction pathway, by changing the electrolytic medium is discussed in relation to the biological activities of the drugs and identification of the short-lived reduction intermediate responsible for DNA damage.