Creatinine nitrosation to yield 5-oxocreatinine 5-oxime and 1-methyl-5-oxohydantoin 5-oxime: reaction rates, identification of syn and anti oxime isomers, and their interconversion by nitrite
1993
Mirvish, S.S. | Deshpande, A. | Haight, R. | Nickols, J. | McWilliams, N. | Babcook, D.M. | Morris, C.R.
Aqueous nitrosation of creatinine (CRN) yields 5-oxocreatinine 5-oxime (OCNO) and 1-methyl-5-oxohydantoin 5-oxime (MOHO). Nitrosation of OCNO yields MOHO. Because further nitrosation of MOHO yields methylurea, which can be nitrosated to give the carcinogen methylnitrosourea, the CRN to OCNO to MOHO reactions were reinvestigated. On treatment of CRN with six batches of nitrite at pH 1, MOHO yield but not OCNO yield dropped sharply as the nitrite level was reduced. MOHO yield was 0.8% from CRN and 11.2% from OCNO under similar conditions. For CRN and OCNO nitrosation by single batches of nitrite, the pH maximum was 2.7-3.0 and third-order kinetics were followed, with reaction rates proportional to [nitrite]. OCNO showed pKa values of 2.7 and 8.9. For OCNO nitrosation, the stoichiometric and real rate constants were, respectively, 17 and 0.4 times those for CRN nitrosation. Four products of a OCNO nitrosation experiment were separated by HPLC and provisionally identified as syn- and anti-OCNO and syn- and anti-MOHO, with a predominance of the antiisomers. Nitrite catalyzed the isomerization of all four oximes (a novel effect of nitrite). Nitrosation of CRN to give methylnitrosourea may be too slow and complex to present a hazard.
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