Electrochemical Characteristics of Nitroheterocyclic Compounds of Biological Interest. V. Measurement and Comparison of Nitro Radical Lifetimes

Summary

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 × 10⁻² seconds for nitrofurazone to 98 s for M&B 4998 at a radical anion concentration of 1 × 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.