Kinetic studies of four types of nitroheterocyclic radicals by pulse radiolysis. Correlation of pharmacological properties to decay rates
- Institut de Biologie Physico-Chimique, CNRS, URA 1089, Paris (France)
The chemical properties of the nitro radical of four types of nitroheterocyclic compounds, nitrofurans, 2-nitroimidazoles, 4(5)-nitroimidazoles, 5-nitroimidazoles, having radiosensitizing and cytotoxic properties, have been studied by pulse radiolysis. The acid-base equilibria involving the nitro radical, the imidazole ring and some residues on the heterocycle have been determined. The pH-dependence of the rate of the disproportionation reaction of the nitro radical have been extensively studied. While the nitro radical derived from nitrofurans, 4- and 5-nitroimidazoles had a second-order decay, those of the 2-nitroimidazoles were found to decay through simultaneous first-order and second-order processes. Intrinsic second-order rate constants of the decay of the radical species in its various acidic and basic forms, could be determined. The intrinsic rate constants that determine the overall decay rates in the physiologically important 6 to 7.5 pH-range could be related to the one-electron redox potential E7(1). The implication of such chemical properties to enzyme-catalyzed reduction processes and to the mechanisms of radiosensitization and cytotoxicity of nitroheterocyclic compounds are briefly discussed. Pharmacological properties such as in vitro radiosensitization efficiency or metabolic reduction rates could be related to two of the nitro radical intrinsic disproportionation rates.
- OSTI ID:
- 7054920
- Journal Information:
- Free Radical Biology and Medicine; (USA), Journal Name: Free Radical Biology and Medicine; (USA) Vol. 8:2; ISSN FRBME; ISSN 0891-5849
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
400600* -- Radiation Chemistry
CHEMICAL PROPERTIES
CHEMICAL RADIATION EFFECTS
CHEMICAL REACTIONS
CHEMISTRY
DECOMPOSITION
KINETICS
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIATION CHEMISTRY
RADIATION EFFECTS
RADICALS
RADIOLYSIS
RADIOSENSITIVITY
REDOX POTENTIAL