Hydrolysis of Acyloxy Nitroso Compounds Yields Nitroxyl (HNO)

Nitroxyl (HNO/NO-), the reduced form of nitric oxide, has gained attention based on its separate
chemistry and biology from nitric oxide. The inherent reactivity of HNO requires new and mechanistically
unique donors for the detailed study of HNO chemistry and biology. Oxidation of cyclohexanone oxime
with lead tetraacetate yields 1-nitrosocyclohexyl acetate, whereas oxidation of oximes in the presence of
excess carboxylic acid gives various acyloxy nitroso compounds. These bright blue compounds exist as
monomers as indicated by their infrared, proton, and carbon NMR spectra, and X-ray crystallographic
analysis reveals the nitroso groups possess a “nitroxyl-like” bent configuration. Hydrolysis of these
compounds produces nitrous oxide, the dimerization and dehydration product of HNO, and provides evidence
for the intermediacy of HNO. Both thiols and oxidative metal complexes inhibit nitrous oxide formation.
Hydrolysis of these compounds in the presence of ferric heme complexes forms ferrous nitrosyl complexes
providing further evidence for the intermediacy of HNO. Kinetic analysis shows that the rate of hydrolysis
depends on pH and the structure of the acyl group of the acyloxy nitroso compound. These compounds
relax pre-constricted rat aortic rings similar to known HNO donors. Together, these results identify acyloxy
nitroso compounds as a new class of HNO donors.