Electron-Affinic Sensitization: VI. A Pulse Radiolysis and ESR Comparison of Some 2- and 5-Nitroimidazoles

Abstract

The nitroimidazoles are effective radiosensitizers for both hypoxic bacterial and mammalian cells and are currently under clinical investigation as adjuncts in radiotherapy. It is known that the 2-nitroimidazoles are biologically more efficient than the 5-nitro derivatives. This paper reports on some aspects of the radiation chemistry of one biologically important example of each class, together with results obtained with other related derivatives. Metronidazole (a 5-nitroimidazole) and Ro-07-0582 (a 2-nitroimidazole) react rapidly with both $e{}_{{\rm aq}}{}^{-}$ and OH to produce transient absorbing species which decay by second-order kinetics. Both compounds accept electrons from the radical anion of thymine at near diffusion-controlled rates, but not from neutral thymine radicals formed by H and OH attack. From a study of one-electron transfer reactions involving p-nitroacetophenone as an electron acceptor it is shown that the electron affinity of the 2-nitroimidazole structure is...