Electrochemical characteristics of nitroheterocyclic compounds of biological interest. V. Measurement and comparison of nitro radical lifetimes.

Using mixed aqueous/dimethylformamide solvents we have generated nitro radical anions by electrochemical reduction of nitroaromatic compounds. Six drugs have been examined: metronidazole, nitrofurazone, nifuroxime, chloramphenicol, M&B 4998 and 4(5)-nitroimidazole, chosen to represent a variety of ring structures and a range of reduction potentials. Analysis of the cyclic voltammetric response as a function of scan rate and dimethylformamide content yields information on the reactivity of RNO2.-. A kinetic analysis of the return-to-forward peak current ratio based on a theoretical treatment was employed. Second-order kinetics for the decay of RNO2.- for all six drugs examined was established. By extrapolation, first half-lives in purely aqueous media were found to increase in the order: nitrofurazone, nifuroxime, chloramphenicol, metronidazole and M&B 4998 (from 8.9 x 10(-2) seconds for nitrofurazone to 98s for M&B 4998 at a radical anion concentration of 1 x 10(-6) mol/dm3). Comparison with reduction potentials showed that as the lifetime of RNO2.- increased, the drug became progressively less electron-affinic (reduced at more negative potentials). The reactivity of RNO2.- was also examined in relation to the DNA damaging capability following electrochemical reduction of these nitroaromatic drugs.