NITROSYL CYANIDE, A PUTATIVE METABOLIC OXIDATION-PRODUCT OF THE ALCOHOL-DETERRENT AGENT CYANAMIDE

When incubated with catalase/glucose-glucose oxidase, C-13-labeled cya namide gave rise not only to C-13-labeled cyanide, but also to C-13-la beled CO2. Moreover, a time dependent formation of nitrite was observe d when cyanamide was oxidized in this system. These results suggested that the initial product of cyanamide oxidation, viz. N-hydroxycyanami de, was being further oxidized by catalase/H2O2 to nitrosyl cyanide (O =N-C equivalent to N). Theoretically, nitrosyl cyanide can hydrolyze t o the four end-products detected in the oxidative metabolism of cyanam ide in vitro, viz. nitroxyl, cyanide, nitrite, and CO2 Accordingly, bo th unlabeled and C-13-labeled nitrosyl cyanide were synthesized by the low temperature (-40 to -50 degrees) nitrosylation of K-(18-crown-6)c yanide with nitrosyl tetrafluoroborate. The product, a faint blue liqu id 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/deh ydration product of nitroxyl, while cyanide was detected in the aqueou s solution, as measured colorimetrically. [C-13]CO2 was analyzed by GC /MS. An oxidative biotransformation pathway for cyanamide that account s for all the products detected and involving both N-hydroxycyanamide and nitrosyl cyanide as tandem intermediates is proposed.