Nitroxyl

Names
IUPAC name

Azanone

Systematic IUPAC name

Oxidanimine[1]

Other names

Hydrogen nitroxide

Hydrogen oxonitrate(I)
Hyponitrous acid monomer
Nitronous oxide

Nitrosyl hydride

Identifiers

CAS Number

* 14332-28-6 Y

3D model (JSmol)

* Interactive image

ChEMBL |

* ChEMBL1200689 Y

ChemSpider |

* 920 Y

MeSH | Nitroxyl

PubChem CID

* 945

UNII |

* GFQ4MMS07W Y

InChI

* InChI=1S/HNO/c1-2/h1H Y

Key: ODUCDPQEXGNKDN-UHFFFAOYSA-N Y

SMILES

* N=O

Properties

Chemical formula

| HNO
Molar mass | 31.014 g·mol−1
log P | 0.74
Structure

Coordination geometry

| Digonal

Molecular shape

| Bent
Thermochemistry

Heat capacity (C)

| 33.88 J K−1 mol−1

Std molar
entropy (S⦵298)

| 220.91 J K−1 mol−1

Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Infobox references

Chemical compound

Nitroxyl (common name) or azanone (IUPAC name)[2] is the chemical compound HNO. It is well known in the gas phase.[3][4] Nitroxyl can be formed as a short-lived intermediate in the solution phase. The conjugate base, NO−, nitroxide anion, is the reduced form of nitric oxide (NO) and is isoelectronic with dioxygen. The bond dissociation energy of H−NO is 49.5 kcal/mol (207 kJ/mol), which is unusually weak for a bond to the hydrogen atom.

## Generation

[edit]

Nitroxyl is produced from the reagents Angeli's salt (Na2N2O3) and Piloty's acid (PhSO2NHOH).[5] 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.[6] HNO is generated via organic oxidation of cyclohexanone oxime with lead tetraacetate to form 1-nitrosocyclohexyl acetate:[7]

Nitrosocyclohexyl acetate

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.[8]

Alkali metals react with nitric oxide to give salts of the form MNO (M = metal).[9] However, generation of the (unstable) free acid from these salts is not entirely straightforward (see below).

## Reactions

[edit]

Nitroxyl is a weak acid, with pKa 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 = 4.9×104 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 Ka 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 pKa is about 23. On the other hand, when deprotonating triplet HNO to obtain triplet NO−, the pKa is about −1.8.[10][11]

Nitroxyl rapidly decomposes by a bimolecular pathway to nitrous oxide (k at 298 K = 8×106 M s):[10]

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:[11]

HNO + RSH → RS(O)NH2

## Detection

[edit]

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.[12]

## Medicinal chemistry

[edit]

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]

## See also

[edit]

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

## References

[edit]

1. ^ "Nitroxyl". PubChem. Retrieved August 24, 2022.
2. ^ Doctorovich, F.; Bikiel, D.; Pellegrino, J.; Suárez, S. A.; Larsen, A.; Martí, M. A. (2011). "Nitroxyl (azanone) trapping by metalloporphyrins". Coordination Chemistry Reviews. 255 (23–24): 2764–2784. doi:10.1016/j.ccr.2011.04.012. hdl:11336/68714.
3. ^ Greenwood, Norman N.; Earnshaw, Alan (1997). Chemistry of the Elements (2nd ed.). Butterworth-Heinemann. ISBN 978-0-08-037941-8.
4. ^ Wiberg, Egon; Holleman, Arnold Frederick (2001). Inorganic Chemistry. Elsevier. ISBN 978-0-12-352651-9.
5. ^ Nagasawa, H. T.; Kawle, S. P.; Elberling, J. A.; DeMaster, E. G.; Fukuto, J. M. (1995). "Prodrugs of Nitroxyl as Potential Aldehyde Dehydrogenase Inhibitors vis-a-vis Vascular Smooth Muscle Relaxants". J. Med. Chem. 38 (11): 1865–1871. doi:10.1021/jm00011a005. PMID 7783118.
6. ^ Cohen, A. D.; Zeng, B.-B.; King, S. B.; Toscano, J. P. (2003). "Direct observation of an acyl nitroso species in solution by time-resolved IR spectrocopy". J. Am. Chem. Soc. 125 (6): 1444–1445. doi:10.1021/ja028978e. PMID 12568581.
7. ^ Sha, Xin; Isbell, T. Scott; Patel, Rakesh P.; Day, Cynthia S.; King, S. Bruce (2006). "Hydrolysis of Acyloxy Nitroso Compounds Yields Nitroxyl (HNO)". J. Am. Chem. Soc. 128 (30): 9687–9692. doi:10.1021/ja062365a. PMID 16866522.
8. ^ White, George Clifford (1986). The handbook of chlorination (2nd ed.). New York: Van Nostrand Reinhold. p. 169\. ISBN 978-0-442-29285-0.
9. ^ Schenk, P. W. (1963). "Nitrogen: Sodium nitroxyl". In Brauer, Georg (ed.). Handbook of Preparative Inorganic Chemistry. Vol. 1\. Translated by Riley, Reed F. (2nd ed.). NY, NY: Academic Press. pp. 514–515. LCCN 63-14307 - via the Internet Archive.
10. ^ a b Shafirovich, V.; Lymar, S. V. (2002). "Nitroxyl and its anion in aqueous solutions: Spin states, protic equilibria, and reactivities toward oxygen and nitric oxide". Proceedings of the National Academy of Sciences of the United States of America. 99, 7340 (11): 7340–7345. doi:10.1073/pnas.112202099. PMC 124232. PMID 12032284.
11. ^ a b Bianco, C. L.; Toscano, J. P.; Bartberger, M. D.; Fukuto, J. M. (2017). "The chemical biology of HNO signaling". Archives of Biochemistry and Biophysics. 617: 129–136. doi:10.1016/j.abb.2016.08.014. PMC 5318259. PMID 27555493.
12. ^ Rivera-Fuentes, Pablo; Lippard, Stephen J. (2015). "Metal-Based Optical Probes for Live Cell Imaging of Nitroxyl (HNO)". Acc. Chem. Res. 38 (11): 2427–2434. doi:10.1021/acs.accounts.5b00388. hdl:1721.1/107934. PMID 26550842.

* v
* t
* e

Nitric oxide signaling modulators

Forms|

* Nitroxyl anion (NO−; oxonitrate(1-), hyponitrite anion)
* Nitric oxide (NO⋅; nitrogen monoxide)
* Nitrosonium (NO+; nitrosyl cation)

Targets|

| sGC|

* Activators/stimulators: Ataciguat
* BAY 41-2272
* BAY 41-8543
* BAY 60-4552
* BI-703704
* Cinaciguat (BAY 58-2667)
* GSK-2181236A
* Praliciguat
* Riociguat
* Vericiguat

* Inhibitors: ODQ

|

NO donors
(prodrugs)|

* Nitrates: Diethylene glycol dinitrate (DEGDN)
* Erythritol tetranitrate (ETN)
* Ethylene glycol dinitrate (EGDN; nitroglycol)
* Isosorbide mononitrate (ISMN)
* Isosorbide dinitrate (ISDN)
* Itramin tosilate
* Mannitol hexanitrate
* Naproxcinod (nitronaproxen; AZD-3582, HCT-3012)
* NCX-466
* NCX-2216
* NCX-4016
* NCX 4040
* NCX-4215
* Nicorandil
* Nipradilol (K-351)
* Nitrate (NO−

* Nitroatorvastatin (NCX-6560)
* Nitroflurbiprofen (HCT-1026)
* Nitrofluvastatin
* Nitroglycerin (glyceryl trinitrate (GTN))
* Nitropravastatin (NCX-6550)
* Pentaerithrityl tetranitrate (PETN)
* Propatylnitrate
* Propylene glycol dinitrate (PGDN)
* Sodium trioxodinitrate (Angeli's salt)
* Tenitramine
* Trolnitrate

* Nitroso compounds/nitrites: Nitrite (NO−
2); O-Nitroso compounds (alkyl nitrites): Amyl nitrite (isoamyl nitrite, isopentyl nitrite)
* Cyclohexyl nitrite
* Ethyl nitrite
* Hexyl nitrite
* Isobutyl nitrite (2-methylpropyl nitrite)
* Isopropyl nitrite
* Methyl nitrite
* n-Butyl nitrite
* Pentyl nitrite
* tert-Butyl nitrite; S-Nitroso compounds (thionitrites): LA810
* S-Nitrosoalbumin (SNALB)
* S-Nitrosated AR545C
* S-Nitroso-N-acetylcysteine (SNAC)
* S-Nitroso-N-acetylpenicillamine (SNAP)
* S-Nitroso-N-valerylpenicillamine (SNVP)
* S-Nitrosocaptopril (SNO-Cap)
* S-Nitrosocysteine (SNC, CysNO, SNO-Cys)
* S-Nitrosodiclofenac
* S-Nitrosoglutathione (GSNO, SNOG)
* SNO-t-PA
* SNO-vWF; N-Nitroso compounds (e.g., nitrosamines): SIN-1A

* Nitrosyl compounds: Metal nitrosyl complexes: Roussin's black salt
* Roussin's red salt
* Sodium nitroprusside (SNP)

* NONOates (diazeniumdiolates): Diethylamine/NO (DEA/NO)
* Diethylenetriamine/NO (DETA/NO)
* GLO/NO
* JS-K
* Methylamine hexamethylene methylamine/NO (MAHMA/NO)
* PROLI/NO
* Spermine/NO (SPER/NO)
* V-PYRRO/NO

* Heterocyclic compounds: Furoxans: Furoxan
* REC15/2739; Sydnonimines: Feprosidnine
* Linsidomine (SIN-1)
* Molsidomine (SIN-10)
* Sydnonimine

* Unsorted: Cimlanod
* FK-409
* FR144220
* FR146881
* N-Acetyl-N-acetoxy-4-chlorobenzenesulfonamide

Enzyme
(inhibitors)|

| NOS|

| nNOS|

* 3-Bromo-7-nitroindazole
* 3-Chloroindazole
* 3-Chloro-5-nitroindazole
* 5-Nitroindazole
* 6-Nitroindazole
* 7-Nitroindazole
* A-84643
* Aminoguanidine (pimagedine)
* ARL-17477
* Indazole
* N5-(1-Iminoethyl)-L-ornithine (L-NIO)
* Nω-Methyl-L-arginine (L-NMA)
* Nω-Propyl-L-arginine (L-NPA)
* Nitroarginine (NNA, NOARG)
* Pentamidine isethionate
* TRIM

|

iNOS|

* 1-Amino-2-hydroxyguanidine
* 2-Ethylaminoguanidine
* 2-Iminopiperidine
* 1400W
* AEITU
* Aminoguanidine (pimagedine)
* AMT
* AR-C 102222
* BYK-191023
* Canavanine
* Cindunistat (SD-6010)
* EITU
* IPTU
* MITU
* N5-(1-Iminoethyl)-L-ornithine (L-NIO)
* N6-(1-Iminoethyl)-L-lysine (L-NIL)
* Nω-Methyl-L-arginine (L-NMA)
* Ronopterin (VAS-203)
* TRIM

eNOS|

* Aminoguanidine (pimagedine)
* N5-(1-Iminoethyl)-L-ornithine (L-NIO)
* Nω-Methyl-L-arginine (L-NMA)
* Nitroarginine (NNA, NOARG)

Unsorted|

* Asymmetric dimethylarginine (ADMA)
* CKD-712
* Guanidinoethyldisulfide (GED)
* GW-273629
* Indospicine
* KD-7040
* Nitroarginine methyl ester (NAME)
* NCX-456
* NXN-462
* ONO-1714
* VAS-2381

Arginase|

* ABH
* Nω-Hydroxy-L-arginine (NOHA)
* chlorogenic acid
* ginseng
* epicatechin
* ornithine
* norvaline
* lysine
* alpha aminoacids

CAMK|

* Calmidazolium
* W-7

Others|

* Precursors: L-Arginine
* Nω-Hydroxy-L-arginine (NOHA)

* Cofactors: NADPH
* FAD
* FMN
* Heme
* BH4
* CaM
* O2
* Ca2+

* Indirect/downstream NO modulators: ACE inhibitors/AT-II receptor antagonists (e.g., captopril, losartan)
* ETB receptor antagonists (e.g., bosentan)
* L-Type calcium channel blockers (e.g., dihydropyridines: nifedipine)
* Nebivolol (beta blocker)
* PDE5 inhibitors (e.g., sildenafil)
* non-selective PDE inhibitors (e.g., caffeine)
* PDE9 inhibitors (e.g., paraxanthine)
* cGMP preferring PDE inhibitors (e.g., sildenafil, paraxanthine, tadalafil)
* Statins (e.g., simvastatin)

See also: Receptor/signaling modulators

* v
* t
* e

Hydrogen compounds

* H3AsO3
* H3AsO4
* HArF
* HAt
* HSO3F
* H[BF4]
* HBr
* HBrO
* HBrO2
* HBrO3
* HBrO4
* HCl
* HClO
* HClO2
* HClO3
* HClO4
* HCN
* HCNO
* H2CrO4/H2Cr2O7
* H2CO3
* H2CS3
* HF
* HFO
* HI
* HIO
* HIO2
* HIO3
* HIO4
* HMnO4
* H2MnO4
* H2MoO4
* HNC
* NaHCO3
* HNCO
* HNO
* HNO2
* HNO3
* H2N2O2
* HNO5S
* H3NSO3
* H2O
* H2O2
* H2O3
* H2O4
* H2O5
* H3PO2
* H3PO3
* H3PO4
* H4P2O7
* H5P3O10
* H2[PtCl6]
* H2S
* H2S2
* H2Se
* H2SeO3
* H2SeO4
* H4SiO4
* H2[SiF6]
* HSCN
* HNCS
* H2SO3
* H2SO4
* H2SO5
* H2S2O3
* H3O
* H2S2O6
* H2S2O7
* H2S2O8
* CF3SO3H
* H2Te
* H2TeO3
* H6TeO6
* H4TiO4
* H2Po
* H[Co(CO)4]

* v
* t
* e

Molecules detected in outer space

Molecules|

| Diatomic|

* Aluminium monochloride
* Aluminium monofluoride
* Aluminium(II) oxide
* Argonium
* Carbon cation
* Carbon monophosphide
* Carbon monosulfide
* Carbon monoxide
* Cyano radical
* Diatomic carbon
* Fluoromethylidynium
* Helium hydride ion
* Hydrogen chloride
* Hydrogen fluoride
* Hydrogen (molecular)
* Hydroxyl radical
* Iron(II) oxide
* Magnesium monohydride
* Methylidyne radical
* Nitric oxide
* Nitrogen (molecular)
* Imidogen
* Sulfur mononitride
* Oxygen (molecular)
* Phosphorus monoxide
* Phosphorus mononitride
* Potassium chloride
* Silicon carbide
* Silicon monoxide
* Silicon monosulfide
* Sodium chloride
* Sodium iodide
* Sulfanyl
* Sulfur monoxide
* Titanium(II) oxide

|
|

Triatomic|

* Aluminium(I) hydroxide
* Aluminium isocyanide
* Amino radical
* Carbon dioxide
* Carbonyl sulfide
* CCP radical
* Chloronium
* Diazenylium
* Dicarbon monoxide
* Disilicon carbide
* Ethynyl radical
* Formyl radical
* Hydrogen cyanide (HCN)
* Hydrogen isocyanide (HNC)
* Hydrogen sulfide
* Hydroperoxyl
* Iron cyanide
* Isoformyl
* Magnesium cyanide
* Magnesium isocyanide
* Methylene
* N2H+
* Nitrous oxide
* Nitroxyl
* Ozone
* Methylidynephosphane
* Potassium cyanide
* Trihydrogen cation
* Sodium cyanide
* Sodium hydroxide
* Silicon carbonitride
* c-Silicon dicarbide
* SiNC
* Sulfur dioxide
* Thioformyl
* Thioxoethenylidene
* Titanium dioxide
* Tricarbon
* Water

Four
atoms|

* Acetylene
* Ammonia
* Isocyanic acid
* Cyanoethynyl
* Formaldehyde
* Fulminic acid
* HCCN
* Hydrogen peroxide
* Hydromagnesium isocyanide
* Isocyanic acid
* Isothiocyanic acid
* Ketenyl
* Methylene amidogen
* Methyl cation
* Methyl radical
* Propynylidyne
* Protonated carbon dioxide
* Protonated hydrogen cyanide
* Silicon tricarbide
* Thioformaldehyde
* Tricarbon monoxide
* Tricarbon monosulfide
* Thiocyanic acid

Five
atoms|

* Ammonium ion
* Butadiynyl
* Carbodiimide
* Cyanamide
* Cyanoacetylene
* Cyanoformaldehyde
* Cyanomethyl
* Cyclopropenylidene
* Formic acid
* Isocyanoacetylene
* Ketene
* Methane
* Methoxy radical
* Methylenimine
* Propadienylidene
* Protonated formaldehyde
* Silane
* Silicon-carbide cluster

Six
atoms|

* Acetonitrile
* Cyanobutadiynyl radical
* E-Cyanomethanimine
* Cyclopropenone
* Diacetylene
* Ethylene
* Formamide
* HC4N
* Ketenimine
* Methanethiol
* Methanol
* Methyl isocyanide
* Pentynylidyne
* Propynal
* Protonated cyanoacetylene

Seven
atoms|

* Acetaldehyde
* Acrylonitrile
* Vinyl cyanide
* Cyanodiacetylene
* Ethylene oxide
* Glycolonitrile
* Hexatriynyl radical
* Propyne
* Methylamine
* Methyl isocyanate
* Vinyl alcohol

Eight
atoms|

* Acetic acid
* Aminoacetonitrile
* Cyanoallene
* Ethanimine
* Glycolaldehyde
* Hexapentaenylidene
* Methylcyanoacetylene
* Methyl formate
* Acrolein

Nine
atoms|

* Acetamide
* Cyanohexatriyne
* Dimethyl ether
* Ethanol
* Methyldiacetylene
* Octatetraynyl radical
* Propene
* Ethanethiol
* Propionitrile
* N-Methylformamide

Ten
atoms
or more|

* Acetone
* Benzene
* Benzonitrile
* Buckminsterfullerene (C60, C60+, fullerene, buckyball)
* C70 fullerene
* Cyanodecapentayne
* Ethylene glycol
* Ethyl formate
* Methyl acetate
* Methyl-cyano-diacetylene
* Methyltriacetylene
* Propionaldehyde
* Butyronitrile
* Pyrimidine
* Heptatrienyl radical

Deuterated
molecules|

* Ammonia
* Ammonium ion
* Formaldehyde
* Formyl radical
* Heavy water
* Hydrogen cyanide
* Hydrogen deuteride
* Hydrogen isocyanide
* Propyne
* N2D+
* Trihydrogen cation

Unconfirmed|

* Anthracene
* Dihydroxyacetone
* Methoxyethane
* Glycine
* Graphene
* Hemolithin
* H2NCO+
* Linear C5
* Naphthalene cation
* Phosphine
* Pyrene
* Silylidyne

Related|

* Abiogenesis
* Astrobiology
* Astrochemistry
* Atomic and molecular astrophysics
* Chemical formula
* Circumstellar dust
* Circumstellar envelope
* Cosmic dust
* Cosmic ray
* Cosmochemistry
* Diffuse interstellar band
* Earliest known life forms
* Extraterrestrial life
* Extraterrestrial liquid water
* Forbidden mechanism
* Homochirality
* Intergalactic dust
* Interplanetary medium
* Interstellar medium
* Photodissociation region
* Iron–sulfur world theory
* Kerogen
* Molecules in stars
* Nexus for Exoplanet System Science
* Organic compound
* Outer space
* PAH world hypothesis
* Pseudo-panspermia
* Polycyclic aromatic hydrocarbon (PAH)
* RNA world hypothesis
* Spectroscopy
* Tholin

* Category:Astrochemistry
* Outer space portal
* Astronomy portal
* Chemistry portal

* v
* t
* e

Nitrogen species

Hydrides|

* NH3
* NH4+
* NH2−
* N3−
* NH2OH
* N2H4
* HN3
* N3−
* NH5 (?)

Organic|

* NR3
* >C=NR
* -CONR2
* -CN
* HCN
* CN−
* (CN)2
* H2NCN
* HOCN
* HNCO
* HNCS
* CH2N2
* -NO
* -NO2

Oxides|

* NO / (NO)2
* N2O3
* HNO2 / NO−
2 / NO+
* NO2 / (NO2)2
* N2O5
* HNO3 / NO−
3 / NO+

* NO3
* HNO / (HON)2 / N2O2−
2 / N2O
* H2NNO2
* HO2NO / ONOO−
* HO2NO2 / O2NOO−
* NO3−

* H4N2O4 / N2O2−

Halides|

* NF
* NF2
* NF3
* NF5 (?)
* NCl3
* NBr3
* NI3
* FN3
* ClN3
* BrN3
* IN3
* NH2F
* N2F2
* NH2Cl
* NHF2
* NHCl2
* NHBr2
* NHI2

Oxidation states|

−3, −2, −1, 0, +1, +2, +3, +4, +5 (a strongly acidic oxide)
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