Photochemistry of 2-Azido-1-methylimidazole in Aqueous Solutions. Observation of the 1-Methyl-2-imidazolylnitrenium Ion

Irradiation of 2-azido-1-methylimidazole ( 12 ) in aqueous solution gives products from two reaction channels. One pathway involves a ring opening typical of azidoheterocycles. The observed products are glyoxal bis-hydrate, the methylammonium ion, and cyanamide; a glyoxal bis-oxime is presumed to be the intermediate initially formed in the ring opening. The other pathway leads to products that retain the five-membered ring, the 2-amino-4,5-dihydro-4,5-dihydroxy-1-methylimidazolium ion 3, its monophosphate ester 6 when the irradiation is carried out in phosphate buffer, and glutathione adducts 7 and 8 when glutathione (GSH) is present. These products have been previously observed in the reactions of 2-hydroxylamino-1-methylimidazole in aqueous solution, and arise from reaction of the 1-methyl-2-imidazolylnitrenium ion ( 2 + ) with water, phosphate, and GSH. This pathway is therefore proposed to involve formation of the cation 2 + via protonation of the singlet 1-methyl-2-imidazolylnitrene 13 formed upon irradiation of the azide. A single transient species undergoing exponential decay with λ max at 230−235 nm is observed with flash photolysis. This transient is assigned to 2 + on the basis of the pH dependence of the yields of products, and especially because of the correspondence of k 2 (GS - ): k s ratios measured directly with flash photolysis and by competition kinetics starting from the hydroxylaminoimidazole. The cation 2 + has a lifetime in water of 100 ms, and shows a high selectivity for GSH with k 2 (GS - ) = 3 × 10 7 M - 1 s - 1 . There is evidence that this class of nitrenium ion is formed upon reductive metabolism of 2-nitroimidazoles. Thus this class of drugs is capable of producing a relatively long-lived electrophile in biological systems.