Reactions of nitroimidazoles with free radicals--enhancement of reaction by u.v. irradiation

The free-radical reactivity of the nitroimidazole derivatives metronidazole, misonidazole, benznidazole and ornidazole was investigated by observing their effect on the polymerization of acrylamide in aqueous solution. Free-radical polymerization was initiated by the thermal decomposition of potassium peroxydisulphate at 50 degrees C. Measurement of the polymerization rate showed an inhibitory effect of the nitroimidazoles which was greatly enhanced when the system was irradiated with u.v. light near their absorption maximum of 320-325 nm. Analysis of the competitive kinetics of the system enabled calculation of the rate constant for reaction of the ground state and photoexcited nitroimidazole with the polyacrylamide free radicals. No significant difference between the various nitroimidazoles could be found in the dark reaction, but in the u.v.-irradiated system the order of reactivity (misonidazole greater than benznidazole greater than metronidazole approximately equal to ornidazole) was the same as the reported relative mutagenic, cytotoxic and radiosensitizing potency of the compounds. These results imply that the excited states of the nitroimidazoles are important to their activity in radical-radical reactions.