Stable reduction product of misonidazole.
The predominant stable product (greater than 80%) of the anaerobic radiation chemical reduction (pH 7, formate, N2O) of misonidazole (MISO) has been identified as the cyclic guanidinium ion MISO-DDI, a 4,5-dihydro-4,5-dihydroxyimidazolium ion. This cation was prepared as its sulfate salt by the reaction of glyoxal and the appropriate N-substituted guanidinium sulfate. Its formation during MISO reduction was established by NMR spectral comparison and by derivatization as glyoxal bis-oxime, which was formed in 86% yield in fully reduced systems. The toxicity of pure MISO-DDI X sulfate was examined in vivo (C3H mice) and in vitro (CHO cells). This product is less toxic than the parent MISO and free glyoxal. A reactive, short-lived, intermediate is suggested as the agent responsible for the toxicity of MISO under hypoxic conditions.