title: Nitrosyl cyanide, a putative metabolic oxidation product of the alcohol-deterrent agent cyanamide.
abstract: When incubated with catalase/glucose-glucose oxidase, 13C-labeled cyanamide gave rise not only to 13C-labeled cyanide, but also to 13C-labeled CO2. Moreover, a time-dependent formation of nitrite was observed when cyanamide was oxidized in this system. These results suggested that the initial product of cyanamide oxidation, viz. N-hydroxycyanamide, was being further oxidized by catalase/H2O2 to nitrosyl cyanide (O = N-C = N). Theoretically, nitrosyl cyanide can hydrolyze to the four end-products detected in the oxidative metabolism of cyanamide in vitro, viz. nitroxyl, cyanide, nitrite, and CO2. Accordingly, both unlabeled and 13C-labeled nitrosyl cyanide were synthesized by the low temperature (-40 to -50 degrees) nitrosylation of K-(18-crown-6)cyanide with nitrosyl tetrafluoroborate. The product, a faint blue liquid at this temperature, was transferred as a gas to phosphate-buffered solution, pH 7.4, where it was solvolyzed. Analysis of the headspace by gas chromatography showed the presence of N2O, the dimerization/dehydration product of nitroxyl, while cyanide was detected in the aqueous solution, as measured colorimetrically. [13C]CO2 was analyzed by GC/MS. An oxidative biotransformation pathway for cyanamide that accounts for all the products detected and involving both N-hydroxycyanamide and nitrosyl cyanide as tandem intermediates is proposed.
authors.affiliation: Medical Research Laboratories, DVA Medical Center, University of Minnesota, Minneapolis 55417, USA.
authors.forename: F N
authors.initials: FN
authors.lastname: Shirota
authors.forename: D J
authors.initials: DJ
authors.lastname: Goon
authors.forename: E G
authors.initials: EG
authors.lastname: DeMaster
authors.forename: H T
authors.initials: HT
authors.lastname: Nagasawa
mesh_terms: D000427:Alcohol Deterrents / Q000737:chemistry*; D002247:Carbon Isotopes; D003484:Cyanamide / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009589:Nitrogen Oxides / Q000737:chemistry*; D010084:Oxidation-Reduction
chemical_list: D000427:Alcohol Deterrents; D002247:Carbon Isotopes; D009589:Nitrogen Oxides; D003484:Cyanamide; C099974:nitrosyl cyanide