title: Reexamination of the aqueous chemistry of N-Nitroso-3-hydroxymorpholine, a metabolite of the carcinogen N-nitrosomorpholine.
abstract: N-Nitroso-3-hydroperoxymorpholine was synthesized in 12 steps starting from a commercially available serine derivative and was subsequently characterized by elemental analysis, one-dimensional (1)H and (13)C NMR spectroscopy, and homonuclear and heteronuclear two-dimensional methods. Treatment of the hydroperoxide with triarylphosphine or trialkylphosphine in CD(2)Cl(2) or CD(3)CN yields N-nitroso-3-hydroxymorpholine, a putative metabolite of the carcinogen N-nitrosomorpholine, as indicated by (1)H and (13)C NMR spectroscopy. A study of the decomposition of N-nitroso-3-hydroxymorpholine in aqueous buffer solution, ionic strength 1 M (KCl), at 25 degrees C is reported. The kinetics of decay obey a three term rate law, with terms for a hydrogen ion-dependent, pH-independent, and hydroxide ion-dependent reactions, similar to what has been reported for other alpha-hydroxynitrosamines. The stability of this compound is similar to that of alpha-hydroxynitrosopiperidine reported previously. The reaction of 3-hydroxymorpholine in aqueous solution, 25 degrees C, pH 6.6, yields (2-hydroxy-ethoxy)acetaldehyde (62%), acetaldehyde (26%), and glycolaldehyde (26%), based on analysis of the dintrophenylhydrazine derivatives. Both the stability and the products of decay of N-nitroso-3-hydroxymorpholine that are reported here contrast strongly with a previous description.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA.
authors.forename: Hyun-Joong
authors.initials: HJ
authors.lastname: Kim
authors.forename: James C
authors.initials: JC
authors.lastname: Fishbein
mesh_terms: D002273:Carcinogens / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009025:Morpholines / Q000737:chemistry*; D009602:Nitrosamines / Q000737:chemistry*; D014867:Water
chemical_list: D002273:Carcinogens; D009025:Morpholines; C481058:N-nitroso-3-hydroxymorpholine; D009602:Nitrosamines; D014867:Water