Products of reductions of 2-nitroimidazoles

Abstract

Reductions under neutral conditions of misonidazole (l-(2'-hydroxy-3'-methoxypropyl)-2-nitroimidazole) and 1 -methyl-2-nitroimidazole have been studied with radiation chemical, electrochemical, and chemical (zinc/ammonium chloride) techniques. Major products accounting for 70-85% of the reduction mixture have been identified as the cis:trans isomers of 4 (1-substituted 2-amino-4,5-dihydro-4,5-dihydroxyimidazolium ions). These have been independently synthesized by the reaction

4,5-Dihydro-4,5-dihydroxyimidazoles as products of the reduction of 2-nitroimidazoles. HPLC assay and demonstration of equilibrium transfer of glyoxal to guanine

“…Our analyses have supported the latter viewpoint, the dihydroimidazoles 3 being able to react to give glyoxal derivatives (10). This species 3 is in fact the adduct of glyoxal and a monosubstituted guanidinium ion, with the equilibrium in aqueous solution lying well to the adduct side (10). We have moreover found that yields of 3 are high, the two isomers accounting for 80-90% of the initial nitroimidazole when reductions are carried out in the absence of other strong nucleophiles (10,20).…”

“…Moreover, there has been some discussion (17,23) as to whether the reduction mixture actually contains free glyoxal or simply some species capable of reacting with the added reagent to form the glyoxal derivative. Our analyses have supported the latter viewpoint, the dihydroimidazoles 3 being able to react to give glyoxal derivatives (10). This species 3 is in fact the adduct of glyoxal and a monosubstituted guanidinium ion, with the equilibrium in aqueous solution lying well to the adduct side (10).…”

“…Work in our laboratory, however, has shown that such compounds are unstable at neutral pH (6,10,19,20), with half-lives ranging from 2-15 min (21,22). The major products of their further reaction have been identified as the cis and trans 2-amino-4,5-dihydro-4,5-dihydroxyirnidazolium ions 3 (10,20,21 c R = CH2CONHCH2C6H5 (Benznidazole) tives of aldehydes and ketones. Such experiments have been found to result in the appropriate derivatives of the two-carbon dialdehyde glyoxal (7,12,17,(23)(24)(25)(26).…”

Effects of halide (X) and sulfoxide (R2SO) replacement within the ruthenium(II) nitroimidazole complexes, RuX2(R2SO)m, (nitroimidazole)n, m = 1-3, n = 1 or 2: their characterization, solution chemistry, radiosensitizing activity, and related properties

“…seen for the nitroimidazoles or Ru(I1) complexes that w e have used. For 4-nitroimidazoles, the toxicity:electron affinity trend was attributed to depletion of thiols (24); certain radiosensitizers are thought to act by binding free, non-protein sulfhydryl groups (NPSH) which normally have a protective effect in irradiated cells (25). Of the complexes listed, only 5 and 6 under hypoxic conditions deplete non-protein thiol levels (26) but this is presumed to result from the presence of the dissociated miso and De-miso ligands; these ligands, 4-N021m, and SR-2508 (out of all the 2-NO2-and 4-N021m derivatives used), were the only free ligands found to deplete thiols (26).…”

Electrochemical Reduction of 2-Nitroimidazole in Aqueous Mixed Medium

“…Their reactivities, and thus cytotoxicities, are modulated by aromatic ring substituents as well as by the pH of the medium. 8 Although nitro reduction and redox behavior are crucial for all biological activity, there are still no conclusive studies about the electrochemistry of 2-nitroimidazole. In fact, electrochemical studies about 2-nitroimidazole derivatives are restricted almost exclusively to work where electrocatalytic reduction on gold and modified gold electrodes is described.…”