Synthesis of Precursors and Reactivity Studies ofNitrosocarbonyl Intermediates

Nitroxyl;Nitrosocarbonyl Intermediates;Chemistry

Nourian, SagharToscano, John P. ;

Johns Hopkins University

关键词: Nitroxyl;    Nitrosocarbonyl Intermediates;    Chemistry;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/60871/NOURIAN-DISSERTATION-2017.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Nitroxyl (HNO), a potential heart failure therapeutic, is a reactive species that spontaneously dimerizes to yield hyponitrous acid, which dehydrates to generate nitrous oxide (N2O).Due to its inherent chemical reactivity, HNO cannot be used directly, and therefore, donors are required for its in situ generation.Here, we report N-substituted hydroxamic acids with pyrazolone leaving groups (NHPY) and O-substituted hydroxamic acids with pyrazolone leaving groups (OHPY) as novel precursors to nitrosocarbonyl intermediates, which subsequently provide HNO.Nitrosocarbonyls are transient electrophiles that react with nucleophiles, including water, to produce HNO.We found that pyrazolones are efficient nitrosocarbonyl traps under physiologically relevant conditions, undergoing an N-selective nitrosocarbonyl aldol reaction.This trapping reaction has been used to confirm the involvement of nitrosocarbonyls as intermediates in the observed chemistry.Time-resolved infrared (TRIR) spectroscopy is a powerful tool for studying photochemically generated reactive intermediates in solution.Applying this technique, we examined the reactivity of a photo-generated nitrosocarbonyl intermediate with a pyrazolone and reported the rate constant for this trapping reaction.