title: "Catch-and-release" of HNO with pyrazolones.
abstract: A new and versatile class of HNO donors, the (hydroxylamino)pyrazolone (HAPY) series of HNO donors utilizing pyrazolone (PY) leaving groups, is described. HNO, the smallest N-based aldehyde equivalent, is used as a reagent along with a variety of PY compounds to synthesize the desired HAPY donors in what can be considered an N-selective HNO-aldol reaction in up to quantitative yields. The bimolecular rate constant of HNO with PY in pH 7.4 phosphate buffer at 37 °C can reach 8 × 10(5) M(-1) s(-1). In (1)H NMR experiments, the HAPY compounds generate HNO quantitatively (trapped as a phosphine aza-ylide) with half-lives spanning 3 orders of magnitude (minutes to days) under physiologically relevant conditions. B3LYP/6-31G* calculations confirm the energetically favorable reactions between HNO and the PY enol and enolate, whereas HNO release is expected to occur through the oxyanion (OHN-PY) of each HAPY compound. HNO has been shown to provide functional support to failing hearts.
authors.affiliation: Department of Chemistry, 3400 North Charles Street, Johns Hopkins University , Baltimore, Maryland 21218, United States.
authors.forename: Daryl A
authors.initials: DA
authors.lastname: Guthrie
authors.forename: Anthony
authors.initials: A
authors.lastname: Ho
authors.forename: Cyrus G
authors.initials: CG
authors.lastname: Takahashi
authors.forename: Anthony
authors.initials: A
authors.lastname: Collins
authors.forename: Matthew
authors.initials: M
authors.lastname: Morris
authors.forename: John P
authors.initials: JP
authors.lastname: Toscano
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000737:chemistry*; D047069:Pyrazolones / Q000737:chemistry*
chemical_list: D009589:Nitrogen Oxides; D047069:Pyrazolones; C038362:pyrazolone