The interaction of nitroaromatic drugs with aminothiols

The effect of cysteamine and glutathione addition on the redox behaviour of metronidazole, chloramphenicol, M&B 4998, nitrofurazone, and nifuroxime has been studied by electrochemical techniques. The presence of thiol influences the redox behaviour of the nitro compound in a number of ways. In aqueous media, the single-step nitro/hydroxylamine reduction shows a decrease in current and a shift to more positive potentials, which is assigned to the thiol acting as the reducing agent, but only after the formation of the nitro radical anion. In addition, the reversible RNO/RNHOH couple is greatly diminished or removed. In a dimethylformamide/H2O solvent, the nitro radical anion can be selectively generated. The effect of thiol addition on the stability of the radical anion is strongly dependent on the drug, the identity of the thiol, and the concentration of the supporting electrolyte. The presence of thiol can result in an increase or a decrease in the lifetime of the radical with no apparent correlation with the redox couple of the nitro compound, or can act as an oxidizing agent and regenerate the original nitro compound. These disparate routes by which thiol can modify the redox characteristics of nitro compounds suggest that the traditional role of thiol as a radical scavenger needs to be extended.