Synthesis, purification and mutagenicity of 2-hydroxyamino-3-methylimidazolo[4,5-f] quinoline

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Abstract
Synthesis of 2-hydroxyamino-3-methylimidazolo [4,5-f]quinoline ( N -hydroxy-IQ), a reactive metabolite of 2-amino-3-methylimidazolo[4,5-f]quinoline (IQ), was achieved by a modification of an earlier method. N -Hydroxy-IQ was purified by a two-step procedure involving C 18 Sep-Pack and semi-preparative h.p.l.c. Additional h.p.l.c. methods were developed to monitor the synthesis of N -hydroxy-IQ, and to measure IQ and other IQ derivatives on the same h.p.l.c. profile. The structure of N -hydroxy-IQ was confirmed by mass spectral analysis following derivatization to azoxy-IQ, phenyl-azoxy-IQ and acetoxy-acetamido-IQ, and by chemical reactivity studies. Mutagenicity studies with the nitroreductase-deficient strain of Salmonella TA98 showed that N -hydroxy-IQ is directly mutagenic, having a specific activity of 2 × 10 4 revertants/nmol. The data confirm that N -hydroxy-IQ is a mutagenic metabolite of IQ and further implicate the hydroxylamine in the carcinogenkity of IQ.