Synthesis of Novel Diazeniumdiolate and Sydnonate-N-oxide Products

Daisy, Sophia Kwende
Nitric oxide (NO) is known to react with carbanions and secondary amines as a cis-dimeric molecule (cis-N2O2) to form useful NO-donor reagents known as NONOates. Rare examples for trans-N2O2 addition are also known. Active methylene-group containing α-alkylcarboxylates undergo trans-N2O2 addition leading to the formation of sydnonate-N-oxide salts. The diazeniumdiolate and sydnonate-N-oxide products exhibit varying levels of stability in aqueous media, and some of them are capable of releasing NO under physiological conditions. Such compounds are of great recent interest as pro-drugs for NO-delivery in the treatment of heart diseases. Interestingly, the two classes of products also exhibit high-energy density properties and are potential monopropellants. In this project, we synthesized new diazeniumdiolate and sydnonate-N-oxide products, and studied their decomposition properties. Methyl cyanoacetate reacts with NO in the presence of ammonium hydroxide and alkali hydroxides forming an unstable and reactive diazeniumdiolate. The poorly characterized product decomposes in aqueous solutions releasing NO and forming a stable sydnonate-N-oxide. The final product is stable, and is characterized by UV-Vis, IR and NMR spectroscopic data, and single crystal X-ray diffraction analysis as potassium trimethyl 1,3-dinitrilopropenyl-1,2,3-tricarboxylate. The release of NO from the less stable diazeniumdiolate in aqueous media at pH 7.4 under ambient conditions is verified by the trapping of the free radical with the well-known NO-trapping reagent Fe(MGD)2. EPR spectral data measured for the NO adduct of Fe(MGD)2 exhibits the expected three-line pattern.
Journal Title
Journal ISSN
Volume Title
University of Wyoming Libraries