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Download file“Catch-and-Release” of HNO with Pyrazolones
journal contribution
posted on 2015-02-06, 00:00 authored by Daryl
A. Guthrie, Anthony Ho, Cyrus G. Takahashi, Anthony Collins, Matthew Morris, John P. ToscanoA 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 × 105 M–1 s–1. In 1H 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.