nitroxyl

Nitroxyl is produced from the reagents Angeli's salt (Na₂N₂O₃) and Piloty's acid (PhSO₂NHOH).{{cite journal|title=Prodrugs of Nitroxyl as Potential Aldehyde Dehydrogenase Inhibitors vis-a-vis Vascular Smooth Muscle Relaxants |last1=Nagasawa |first1=H. T. |last2=Kawle |first2=S. P. |last3=Elberling |first3=J. A. |last4=DeMaster|first4=E. G. |last5=Fukuto |first5=J. M. |journal=J. Med. Chem. |volume=38 |issue=11 |pages=1865–1871 |doi=10.1021/jm00011a005|pmid=7783118 |year=1995 }} Other notable studies on the production of HNO exploit cycloadducts of acyl nitroso species, which are known to decompose via hydrolysis to HNO and acyl acid. Upon photolysis these compounds release the acyl nitroso species which then further decompose.{{cite journal|title=Direct observation of an acyl nitroso species in solution by time-resolved IR spectrocopy|last1=Cohen|first1= A. D.|last2=Zeng|first2= B.-B. |last3=King |first3=S. B. |last4=Toscano |first4=J. P. |journal=J. Am. Chem. Soc. |date=2003 |volume=125 |issue=6|pages=1444–1445|doi=10.1021/ja028978e |pmid=12568581}}

HNO is generated via organic oxidation of cyclohexanone oxime with lead tetraacetate to form 1-nitrosocyclohexyl acetate:{{cite journal|title=Hydrolysis of Acyloxy Nitroso Compounds Yields Nitroxyl (HNO) |first1=Xin |last1=Sha |first2=T. Scott |last2=Isbell |first3=Rakesh P. |last3=Patel |first4=Cynthia S. |last4=Day |first5=S. Bruce |last5=King |journal=J. Am. Chem. Soc.|date=2006|volume=128|issue=30 |pages= 9687–9692 |doi= 10.1021/ja062365a|pmid=16866522 }}

Image:Nitrosocyclohexyl acetate.png

This compound can be hydrolyzed under basic conditions in a phosphate buffer to HNO, acetic acid, and cyclohexanone.

Dichloramine reacts with the hydroxide ion, which is always present in water, to yield nitroxyl and the chloride ion.{{cite book|last1=White|first1=George Clifford|title=The handbook of chlorination|date=1986|publisher=Van Nostrand Reinhold|location=New York|isbn=978-0-442-29285-0|pages=169|edition=2nd}}

Alkali metals react with nitric oxide to give salts of the form {{awrap|MNO (M {{=}} metal)}}.{{cite encyclopedia|first=P. W.|last=Schenk|entry=Nitrogen: Sodium nitroxyl|pages=514–515|chapter-url=https://archive.org/details/Handbook_of_Preparative_Inorganic_Chemistry_1_2_Brauer/page/n537|via=the Internet Archive|year=1963|publisher=Academic Press|location=NY, NY|lccn=63-14307|title=Handbook of Preparative Inorganic Chemistry|volume=1|edition=2nd|editor-first=Georg|editor-last=Brauer|translator-first=Reed F.|translator-last=Riley}} However, generation of the (unstable) free acid from these salts is not entirely straightforward (see below).

Nitroxyl is a weak acid, with pK_a of about 11, the conjugate base being the triplet state of NO⁻, sometimes called nitroxide. Nitroxyl itself, however, is a singlet ground state. Thus, deprotonation of nitroxyl uniquely involves the forbidden spin crossing from the singlet state starting material to triplet state product:

:¹HNO + B⁻ → ³NO⁻ + BH

Due to the spin-forbidden nature of deprotonation, proton abstraction is many orders of magnitude slower (k = {{val|4.9e4|u=M⁻¹ s⁻¹}} for deprotonation by OH⁻) than what one would expect for a heteroatom proton-transfer process (processes that are so fast that they are sometimes diffusion-controlled).

The K_a of starting from or ending with the electronic excited states has also been determined. When process of deprotonating singlet state HNO to obtain singlet state NO⁻ has a pK_a is about 23. On the other hand, when deprotonating triplet HNO to obtain triplet NO⁻, the pK_a is about −1.8.{{cite journal|author1=Bianco, C. L. |author2=Toscano, J. P. |author3=Bartberger, M. D. |author4=Fukuto, J. M. |title=The chemical biology of HNO signaling|journal=Archives of Biochemistry and Biophysics|year=2017|volume=617|pages=129–136|doi=10.1016/j.abb.2016.08.014|pmid=27555493|pmc=5318259}}

Nitroxyl rapidly decomposes by a bimolecular pathway to nitrous oxide (k at 298 K = {{val|8e6|u=M s}}):{{cite journal|author1=Shafirovich, V. |author2=Lymar, S. V. |title=Nitroxyl and its anion in aqueous solutions: Spin states, protic equilibria, and reactivities toward oxygen and nitric oxide|journal=Proceedings of the National Academy of Sciences of the United States of America|year=2002|volume=99, 7340|issue=11|pages=7340–7345|doi=10.1073/pnas.112202099|pmid=12032284|pmc=124232|doi-access=free}}

:2 HNO → N₂O + H₂O

The reaction proceeds via dimerization to hyponitrous acid, H₂N₂O₂, which subsequently undergoes dehydration. Therefore, HNO is generally prepared in situ as described above.

Nitroxyl is very reactive towards nucleophiles, including thiols. The initial adduct rearranges to a sulfinamide:

:HNO + RSH → RS(O)NH₂

In biological samples, nitroxyl can be detected using fluorescent sensors, many of which are based on the reduction of copper(II) to copper(I) with concomitant increase in fluorescence.{{cite journal|title=Metal-Based Optical Probes for Live Cell Imaging of Nitroxyl (HNO) |first1=Pablo |last1=Rivera-Fuentes |first2=Stephen J. |last2=Lippard |journal=Acc. Chem. Res.|date=2015|volume=38|issue=11 |pages= 2427–2434 |doi= 10.1021/acs.accounts.5b00388|pmid=26550842 |hdl=1721.1/107934 |hdl-access=free }}

Nitroxyl donors, known as nitroso compounds, show potential in the treatment of heart failure and ongoing research is focused on finding new molecules for this task. {{Citation needed|date=February 2024}}

• Nitroxyl radicals (also called aminoxyl radicals) — chemical species containing the R₂N−O^• functional group

{{Reflist}}

{{Nitric oxide signaling}}

{{Hydrogen compounds}}

{{Molecules detected in outer space}}

{{Oxidation states of nitrogen}}

Category:Aldehyde dehydrogenase inhibitors

Category:Hydrogen compounds

Category:Triatomic molecules

Category:Nitrogen oxoacids

Category:Oxygen compounds