KINETIC-STUDIES OF 4 TYPES OF NITROHETEROCYCLIC RADICALS BY PULSE-RADIOLYSIS - CORRELATION OF PHARMACOLOGICAL PROPERTIES TO DECAY-RATES

被引：39

作者：

GUISSANI, A ^{[1
]}

HENRY, Y ^{[1
]}

LOUGMANI, N ^{[1
]}

HICKEL, B ^{[1
]}

机构：

[1] INST BIOL PHYSCHIM,BIOPHYS LAB,CNRS,URA 1089,13 RUE PIERRE & MARIE CURIE,F-75005 PARIS,FRANCE

来源：

FREE RADICAL BIOLOGY AND MEDICINE | 1990年 / 8卷 / 02期

关键词：

Decay rates; Disproportion; Free radicals; Nitro radical; Nitroheterocycles; pK values; Pulse radiolysis;

D O I：

10.1016/0891-5849(90)90090-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 thephysiologically 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. © 1990.

引用

页码：173 / 189

页数：17

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