Nitric oxide

{{short description|Colorless gas with the formula NO}} {{distinguish|nitrous oxide}} {{About|a molecule of one nitrogen atom and one oxygen atom|other chemical combinations of nitrogen and oxygen|nitrogen oxide|the use of nitric oxide as a medication or in biology|Biological functions of nitric oxide}} {{Chembox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 477001381 | Name = | ImageFile = Nitric-oxide-2D.svg | ImageClass = skin-invert-image | ImageFile_Ref = {{chemboximage|correct|??}} | ImageSize = 121 | ImageName = Skeletal formula of nitric oxide with bond length | ImageFileL1 = Nitric oxide.svg | ImageClassL1 = skin-invert-image | ImageNameL1 = Skeletal formula showing two lone pairs and one three-electron bond | ImageFileR1 = Nitric-oxide-3D-vdW.png | ImageClassR1 = bg-transparent | ImageFileR1_Ref = {{chemboximage|correct|??}} | ImageNameR1 = Space-filling model of nitric oxide | IUPACName = Nitrogen monoxide<ref name="Nomenclature_2005" /> | SystematicName = Oxidonitrogen(•)<ref>{{cite web|title = Nitric Oxide (CHEBI:16480)|url = https://www.ebi.ac.uk/chebi/searchId.do?chebiId=16480|work = Chemical Entities of Biological Interest (ChEBI)|location = UK|publisher = European Bioinformatics Institute}}</ref> (additive) | OtherNames = Nitrogen oxide<br/>Nitrogen(II) oxide<br />Oxonitrogen<br />Nitrogen monoxide | Section1 = {{Chembox Identifiers | IUPHAR_ligand = 2509 | CASNo = 10102-43-9 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 1200689 | CASNo_Ref = {{cascite|correct|CAS}} | PubChem = 145068 | ChemSpiderID = 127983 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | UNII = 31C4KY9ESH | UNII_Ref = {{fdacite|correct|FDA}} | EINECS = 233-271-0 | UNNumber = 1660 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00435 | KEGG = D00074 | KEGG_Ref = {{keggcite|correct|kegg}} | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 16480 | RTECS = QX0525000 | Gmelin = 451 | 3DMet = B00122

| SMILES = [N]=O | StdInChI = 1S/NO/c1-2 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | InChI = 1/NO/c1-2 | StdInChIKey = MWUXSHHQAYIFBG-UHFFFAOYSA-N | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | InChIKey = MWUXSHHQAYIFBG-UHFFFAOYAI }} | Section2 = {{Chembox Properties | N=1 | O=1 | Appearance = Colourless gas | Density = 1.3402 g/L | MeltingPtC = −164 | BoilingPtC = −152 | Solubility = 0.0098 g / 100&nbsp;mL (0&nbsp;°C) <br /> 0.0056&nbsp;g / 100&nbsp;mL (20&nbsp;°C) | RefractIndex = 1.0002697 }} | Section3 = {{Chembox Structure | MolShape = linear (point group C_∞''v'') }} | Section4 = | Section5 = {{Chembox Thermochemistry | DeltaHf = +90.29 kJ/mol | Entropy = 210.76 J/(K·mol) }} | Section6 = {{Chembox Pharmacology | ATCCode_prefix = R07 | ATCCode_suffix = AX01 | Licence_EU=yes | AdminRoutes = Inhalation | Bioavail = good | Metabolism = via pulmonary capillary bed | HalfLife = 2–6 seconds }} | Section7 = {{Chembox Hazards | ExternalSDS = [https://web.archive.org/web/20201102102334/https://www.boconline.co.uk/en/images/sg-088-nitric-oxide-v1.2_tcm410-39637.pdf External SDS] | MainHazards = Very toxic, corrosive, oxidizer<ref name="SDS">{{cite web| url=https://www.boconline.co.uk/en/images/sg-088-nitric-oxide-v1.2_tcm410-39637.pdf| title=Safety Data Sheet - Nitric Oxide, compressed - Registration Dossier| access-date=2020-11-02}}</ref> | GHSPictograms = {{GHS03}}{{GHS05}}{{GHS06}}<ref name="ECHA">{{cite web| url=https://echa.europa.eu/registration-dossier/-/registered-dossier/24163/1| title=Nitrogen monoxide - Registration Dossier - ECHA| access-date=2020-11-02}}{{Dead link|date=January 2026 |bot=InternetArchiveBot }}</ref><ref name=SDS/> | GHSSignalWord = Danger | HPhrases = {{H-phrases|270|330|314}}<ref name=ECHA/><ref name=SDS/> | PPhrases = {{P-phrases|244|260|220|280|304+340+315|303+361+353+315|305+351+338+315|370+376|403|405}}<ref name=ECHA/><ref name=SDS/> | NFPA-H = 3 | NFPA-F = 0 | NFPA-R = 3 | NFPA-S = OX | LC50 = 315&nbsp;ppm (rabbit, 15&nbsp;min)<br/>854&nbsp;ppm (rat, 4&nbsp;h)<br/>2500&nbsp;ppm (mouse, 12&nbsp;min)<ref name=IDLH>{{IDLH|10102439|Nitric oxide}}</ref> | LCLo = 320&nbsp;ppm (mouse)<ref name=IDLH/> }} | Section8 = {{Chembox Related | OtherFunction_label = nitrogen oxides | OtherFunction = Dinitrogen pentoxide<br /> Dinitrogen tetroxide<br /> Dinitrogen trioxide<br /> Nitrogen dioxide<br /> Nitrous oxide<br/> Nitroxyl (reduced form)<br/> Hydroxylamine (hydrogenated form) }} }}

'''Nitric oxide''' ('''nitrogen oxide''', '''nitrogen mono-oxide''', or '''nitrogen monoxide'''<ref name="Nomenclature_2005">{{cite book |title=Nomenclature of Inorganic Chemistry, IUPAC Recommendations <!-- |title-link=IUPAC nomenclature of inorganic chemistry 2005 --> |url=http://old.iupac.org/publications/books/rbook/Red_Book_2005.pdf |publisher=International Union of Pure and Applied Chemistry |year=2005 |page=69}}</ref>) is a colorless gas with the formula '''{{chem|NO}}'''. It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its chemical formula (^•N=O or ^•NO). Nitric oxide is also a heteronuclear diatomic molecule, a class of molecules whose study spawned early modern theories of chemical bonding.<ref name="G&E" />

An important intermediate in industrial chemistry, nitric oxide forms in combustion systems and can be generated by lightning in thunderstorms. High temperatures of hydrogen combustion in an oxygen-rich environment, with atmospheric nitrogen present, can also result in breaking of N≡N bonds, forming toxic NOx if no exhaust scrubbing is done.<ref>{{Cite journal |last=Lewis|first=Alastair C.|date=2021-07-22|title=Optimising air quality co-benefits in a hydrogen economy: a case for hydrogen-specific standards for NOx emissions|journal=Environmental Science: Atmospheres|language=en|volume=1|issue=5|pages=201–207|doi=10.1039/D1EA00037C|s2cid=236732702|issn=2634-3606|doi-access=free|bibcode=2021ESAt....1..201L}}</ref>In mammals, including humans, nitric oxide is a signaling molecule in many physiological and pathological processes.<ref>{{cite journal |pmid=10390607 |year=1999 |last1=Hou |first1=Y. C. |last2=Janczuk |first2=A. |last3=Wang |first3=P. G. |title=Current trends in the development of nitric oxide donors |volume=5 |issue=6 |pages=417–441 |journal=Current Pharmaceutical Design|doi=10.2174/138161280506230110111042 }}</ref> It was proclaimed the "Molecule of the Year" in 1992.<ref name="pmid1361684">{{cite journal |author1=Culotta, Elizabeth |author2=Koshland, Daniel E. Jr. | year = 1992 | title = NO news is good news | journal = Science | volume = 258 | issue = 5090 | pages = 1862–1864 | doi = 10.1126/science.1361684 | pmid = 1361684 |bibcode=1992Sci...258.1862C }}</ref> The 1998 Nobel Prize in Physiology or Medicine was awarded for discovering nitric oxide's role as a cardiovascular signalling molecule.<ref>{{Cite web |title=The Nobel Prize in Physiology or Medicine 1998 |url=https://www.nobelprize.org/prizes/medicine/1998/summary/ |access-date=2022-06-17 |website=NobelPrize.org |language=en-US}}</ref> Its impact extends beyond biology, with applications in medicine, such as the development of sildenafil (Viagra), and in industry, including semiconductor manufacturing.<ref>{{Cite web |last=Reporter |first=Kashmira Gander |date=2020-04-07 |title=How the Gas That Gave Us Viagra Could Help Treat Coronavirus Patients |url=https://www.newsweek.com/what-nitric-oxide-how-gas-that-gave-us-viagra-could-help-treat-coronavirus-patients-1496520 |access-date=2024-08-29 |website=Newsweek |language=en}}</ref><ref>{{Cite web |title=Nitric Oxide in Semiconductor Manufacturing: Unveiling the Silent Powerhouse Shaping Our Hi-Tech Future {{!}} Plasma Futures |url=https://plasmafutures.com/2024/01/30/nitric-oxide-in-semiconductor-manufacturing-unveiling-the-silent-powerhouse-shaping-our-hi-tech-future/#:~:text=Etching%20Processes:%20Nitric%20oxide's%20utility,create%20intricate%20patterns%20and%20structures. |access-date=2024-08-29 |language=en-US}}</ref>

Nitric oxide should not be confused with nitrogen dioxide (NO₂), a brown gas and major air pollutant, or with nitrous oxide (N₂O), an anaesthetic gas.<ref name="G&E"/>

==History==

Nitric oxide (NO) was first identified by Joseph Priestley in the late 18th century, originally seen as merely a toxic byproduct of combustion and an environmental pollutant.<ref>{{Cite journal |last=Gillman |first=Mark A. |date=June 2019 |title=Mini-Review: A Brief History of Nitrous Oxide (N2O) Use in Neuropsychiatry |journal=Current Drug Abuse Reviews |volume=11 |issue=1 |pages=12–20 |doi=10.2174/1874473711666181008163107 |issn=1874-4737 |pmc=6637098 |pmid=30829177}}</ref> Its biological significance was later uncovered in the 1980s when researchers Robert F. Furchgott, Louis J. Ignarro, and Ferid Murad discovered its critical role as a vasodilator in the cardiovascular system, a breakthrough that earned them the 1998 Nobel Prize in Physiology or Medicine.<ref>{{cite journal |last1=Lancaster |first1=Jack R. |title=Historical origins of the discovery of mammalian nitric oxide (nitrogen monoxide) production/physiology/pathophysiology |journal=Biochemical Pharmacology |date=June 2020 |volume=176 |article-number=113793 |doi=10.1016/j.bcp.2020.113793 |pmid=31923387 }}</ref>

==Physical properties== ===Electronic configuration===

The ground-state electronic configuration of NO in united-atom notation is<ref>{{cite book |doi=10.1016/B978-0-12-091650-4.50012-8 |chapter=Partial Cross Sections |title=Photoabsorption, Photoionization, and Photoelectron Spectroscopy |date=1979 |last1=Berkowitz |first1=Joseph |pages=155–357 |isbn=978-0-12-091650-4 }}</ref> <math display="block"> (1\sigma)^2 (2\sigma)^2 (3\sigma)^2 (4\sigma^*)^2 (5\sigma)^2 (1\pi)^4 (2\pi^*)^1. </math> The first two orbitals are actually pure atomic 1''s''_O and 1''s''_N from oxygen and nitrogen respectively and therefore are usually not noted in the united-atom notation. Orbitals noted with an asterisk are antibonding. The ordering of 5σ and 1π according to their binding energies is subject to discussion. Removal of a 1π electron leads to 6 states whose energies span over a range starting at a lower level than a 5σ electron an extending to a higher level. This is due to the different orbital momentum couplings between a 1π and a 2π electron.

The lone electron in the 2π orbital makes NO a doublet {{nobr|(''X''{{tsp}}²Π)}} in its ground state, whose degeneracy is split in the fine structure from spin–orbit coupling with a total momentum {{nobr|''J'' {{=}} 3/2}} or {{nobr|''J'' {{=}} 1/2}}.

===Dipole===

The dipole of NO has been measured experimentally to 0.15740&nbsp;D and is oriented from O to N (⁻NO⁺) due to the transfer of negative electronic charge from oxygen to nitrogen.<ref>{{cite journal |first1=A. R. |last1=Hoy |first2=J. W. C. |last2=Johns |first3=A. R. W. |last3=McKellar |title=Stark Spectroscopy with the CO Laser: Dipole Moments, Hyperfine Structure, and Level Crossing Effects in the Fundamental Band of NO |journal=Canadian Journal of Physics |date=1975 |volume=53 |issue=19 |pages=2029–2039 |doi=10.1139/p75-254 |bibcode=1975CaJPh..53.2029H }}</ref>

==Reactions== ===With di- and triatomic molecules=== Upon condensing to a liquid, nitric oxide dimerizes to colorless dinitrogen dioxide (O=N&ndash;N=O), but the association is weak and reversible. The N–N distance in crystalline NO is 218&nbsp;pm, nearly twice the N–O distance. Condensation in a highly polar environment instead gives the red alternant isomer O=N&ndash;O⁺=N⁻.<ref name=G&E/>

Since the heat of formation of ^•NO is endothermic, NO can be decomposed to the elements. Catalytic converters in cars exploit this reaction: : 2 ^•NO → O₂ + N₂

When exposed to oxygen, nitric oxide converts into nitrogen dioxide: : 2 ^•NO + O₂ → 2 ^•NO₂

This reaction is thought to occur via the intermediates ONOO^• and the red compound ONOONO.<ref name="Galliker Kissner Nauser Koppenol pp. 6161–6168">{{cite journal | last1=Galliker | first1=Benedikt | last2=Kissner | first2=Reinhard | last3=Nauser | first3=Thomas | last4=Koppenol | first4=Willem H. | display-authors=1 | title=Intermediates in the Autoxidation of Nitrogen Monoxide | journal=Chemistry - A European Journal | volume=15 | issue=25 | date=2009 | issn=0947-6539 | doi=10.1002/chem.200801819 | pages=6161–6168| pmid=19437472 }}</ref>

In water, nitric oxide reacts with oxygen to form nitrous acid (HNO₂). The reaction is thought to proceed via the following stoichiometry:

: 4 ^•NO + O₂ + 2 H₂O → 4 HNO₂

Nitric oxide reacts with fluorine, chlorine, and bromine to form the nitrosyl halides, such as nitrosyl chloride: : 2 ^•NO + Cl₂ → 2 NOCl

With NO₂, also a radical, NO combines to form the intensely blue dinitrogen trioxide:<ref name=G&E/> : ^•NO + ^•NO₂ {{eqm}} ON−NO₂

===Organic chemistry=== {{Redirect-confuse|Traube reaction|Traube purine synthesis}} Nitric oxide rarely sees organic chemistry use. Most reactions with it produce complex mixtures of salts, separable only through careful recrystallization.<ref name=Radicals>{{cite book|pages=165–166|title=Stable Radicals|editor-first=Robin&nbsp;G.|editor-last=Hicks|publisher=Wiley|year=2010|isbn=978-0-470-77083-2|chapter=The nitrogen oxides|first=D.&nbsp;Scott|last=Bohle}}</ref>

The addition of a nitric oxide moiety to another molecule is often referred to as ''nitrosylation''. The '''Traube reaction''' is the addition of a two equivalents of nitric oxide onto an enolate, giving a diazeniumdiolate (also called a ''nitrosohydroxylamine'').<ref>{{cite journal |title= Synthesis of Diazeniumdiolates from the Reactions of Nitric Oxide with Enolates |first1= Navamoney |last1= Arulsamy |first2= D. Scott |last2= Bohle |journal= J. Org. Chem. |year= 2006 |volume= 71 |issue= 2 |pages= 572–581 |doi= 10.1021/jo051998p |pmid= 16408967 }}</ref> The product can undergo a subsequent retro-aldol reaction, giving an overall process similar to the haloform reaction. For example, nitric oxide reacts with acetone and an alkoxide to form a diazeniumdiolate on each α position, with subsequent loss of methyl acetate as a by-product:<ref>{{cite journal |doi=10.1002/jlac.18983000108 |title=Ueber Synthesen stickstoffhaltiger Verbindungen mit Hülfe des Stickoxyds |year=1898 |last1=Traube |first1=Wilhelm |journal=Justus Liebig's Annalen der Chemie |volume=300 |issue=1 |pages=81–128 |language=de |url=https://zenodo.org/record/1427495 }}</ref>

: class=skin-invert-image|400px|Traube reaction

This reaction, which was discovered around 1898, remains of interest in nitric oxide prodrug research. Nitric oxide can also react directly with sodium methoxide, ultimately forming sodium formate and nitrous oxide by way of an ''N''-methoxydiazeniumdiolate.<ref>{{cite journal |doi=10.1021/jo7020423 |title=Nitric Oxide Reacts with Methoxide |year=2008 |last1=Derosa |first1=Frank |last2=Keefer |first2=Larry K. |last3=Hrabie |first3=Joseph A. |journal=The Journal of Organic Chemistry |volume=73 |pages=1139–1142 |pmid=18184006 |issue=3}}</ref>

Sufficiently basic secondary amines undergo a Traube-like reaction to give NONOates.<ref>{{cite journal |author1=Joseph A. Hrabie |author2=John R. Klose |author3=David A. Wink |author4=Larry K. Keefer | title = New nitric oxide-releasing zwitterions derived from polyamines | journal = J. Org. Chem. | volume = 58 | issue = 6 | year = 1993 | pages = 1472–1476 | doi = 10.1021/jo00058a030}}</ref> However, very few nucleophiles undergo the Traube reaction, either failing to adduce NO or immediately decomposing with nitrous oxide release.<ref name=Radicals/>

===Coordination complexes=== {{Main|Metal nitrosyl}} Nitric oxide reacts with transition metals to give complexes called metal nitrosyls. The most common bonding mode of nitric oxide is the terminal linear type (M−NO).<ref name=G&E>{{Greenwood&Earnshaw2nd}}</ref> Alternatively, nitric oxide can serve as a one-electron pseudohalide. In such complexes, the M−N−O group is characterized by an angle between 120° and 140°. The NO group can also bridge between metal centers through the nitrogen atom in a variety of geometries.

==Production and preparation== In commercial settings, nitric oxide is produced by the oxidation of ammonia at 750–900&nbsp;°C (normally at 850&nbsp;°C) with platinum as catalyst in the Ostwald process:

:4 NH₃ + 5 O₂ → 4 ^•NO + 6 H₂O

The uncatalyzed endothermic reaction of oxygen (O₂) and nitrogen (N₂), which is effected at high temperature (>2000&nbsp;°C) by lightning has not been developed into a practical commercial synthesis (see Birkeland–Eyde process): :N₂ + O₂ → 2 ^•NO

===Laboratory methods=== In the laboratory, nitric oxide is conveniently generated by reduction of dilute nitric acid with copper: :8 HNO₃ + 3 Cu → 3 Cu(NO₃)₂ + 4 H₂O + 2 ^•NO

An alternative route involves the reduction of nitrous acid in the form of sodium nitrite or potassium nitrite: : 2 NaNO₂ + 2 NaI + 2 H₂SO₄ → I₂ + 2 Na₂SO₄ + 2 H₂O + 2 ^•NO : 2 NaNO₂ + 2 FeSO₄ + 3 H₂SO₄ → Fe₂(SO₄)₃ + 2 NaHSO₄ + 2 H₂O + 2 ^•NO : 3 KNO₂ + KNO₃ + Cr₂O₃ → 2 K₂CrO₄ + 4 ^•NO

The iron(II) sulfate route is simple and has been used in undergraduate laboratory experiments.

So-called NONOate compounds are also used for nitric oxide generation, especially in biological laboratories. However, other Traube adducts may decompose to instead give nitrous oxide.<ref>{{cite journal|journal=Nature|department=Correspondence|date=22 February 2001|title=Oxide formation: reaction details studied, reported in brief|first=Howard|last=Maskill|volume=409|issue=6823 |page=977|doi=10.1038/35059310 |doi-access=free|pmid=11234042 |bibcode=2001Natur.409..977M }}</ref>

==Detection and assay== [[File:The production and diffusion of nitric oxide (NO) (white) in the cytoplasm (green) of clusters of conifer cells one hour after mechanical agitation.jpg|thumb|250px|Nitric oxide (white) in conifer cells, visualized using DAF-2 DA (diaminofluorescein diacetate)]]

Nitric oxide concentration can be determined using a chemiluminescent reaction involving ozone.<ref>{{cite journal |title=Homogeneous chemiluminescent measurement of nitric oxide with ozone. Implications for continuous selective monitoring of gaseous air pollutants|year=1970 |last1=Fontijn |first1=Arthur |last2=Sabadell |first2=Alberto J. |last3=Ronco |first3=Richard J. |journal=Analytical Chemistry |volume=42 |issue=6 |pages=575–579 |doi=10.1021/ac60288a034}}</ref> A sample containing nitric oxide is mixed with a large quantity of ozone. The nitric oxide reacts with the ozone to produce oxygen and nitrogen dioxide, accompanied with emission of light (chemiluminescence): : ^•NO + O₃ → ^•NO₂ + O₂ + ''hν'' which can be measured with a photodetector. The amount of light produced is proportional to the amount of nitric oxide in the sample.

Other methods of testing include electroanalysis (amperometric approach), where ·NO reacts with an electrode to induce a current or voltage change. The detection of NO radicals in biological tissues is particularly difficult due to the short lifetime and concentration of these radicals in tissues. One of the few practical methods is spin trapping of nitric oxide with iron-dithiocarbamate complexes and subsequent detection of the mono-nitrosyl-iron complex with electron paramagnetic resonance (EPR).<ref>{{cite book |last1=Vanin |first1=A |last2=Huisman |first2=A |last3=Van Faassen |first3=E |title=Nitric Oxide, Part D: Oxide Detection, Mitochondria and Cell Functions, and Peroxynitrite Reactions |chapter=Iron dithiocarbamate as spin trap for nitric oxide detection: Pitfalls and successes |year=2002 |volume=359 |pages=[https://archive.org/details/nitricoxide0000unse/page/27 27–42] |pmid=12481557 |doi=10.1016/S0076-6879(02)59169-2 |series=Methods in Enzymology |isbn=978-0-12-182262-0 |chapter-url=https://archive.org/details/nitricoxide0000unse/page/27 }}</ref><ref>{{cite journal |last1=Nagano |first1=T |last2=Yoshimura |first2=T |year=2002 |title=Bioimaging of nitric oxide |journal=Chemical Reviews |volume=102 |issue=4 |pages=1235–1270 |doi=10.1021/cr010152s |pmid=11942795}}</ref>

A group of fluorescent dye indicators that are also available in acetylated form for intracellular measurements exist. The most common compound is 4,5-diaminofluorescein (DAF-2).<ref name="undefined">{{cite journal | vauthors=Kojima H, Nakatsubo N, Kikuchi K, Kawahara S, Kirino Y, Nagoshi H, Hirata Y, Nagano T | year = 1998 | title = Detection and imaging of nitric oxide with novel fluorescent indicators: diaminofluoresceins | journal = Anal. Chem. | volume = 70 | issue = 13 | pages = 2446–2453| pmid = 9666719 | doi = 10.1021/ac9801723 }}</ref>

== Environmental effects == {{Main|NOx}}

=== Acid rain deposition === Nitric oxide reacts with the hydroperoxyl radical ({{chem|HO|2|•}}) to form nitrogen dioxide (NO₂), which then can react with a hydroxyl radical (HO^•) to produce nitric acid (HNO₃): : ^•NO + {{chem|HO|2|•}} → ^•NO₂ + HO^• : ^•NO₂ + HO^• → HNO₃ Nitric acid, along with sulfuric acid, contributes to acid rain deposition.

=== Ozone depletion === ^•NO participates in ozone layer depletion. Nitric oxide reacts with stratospheric ozone to form O₂ and nitrogen dioxide: : ^•NO + O₃ → ^•NO₂ + O₂

This reaction is also utilized to measure concentrations of ^•NO in control volumes.

=== Precursor to NO₂ === As seen in the acid deposition section, nitric oxide can transform into nitrogen dioxide (this can happen with the hydroperoxy radical, {{chem|HO|2|•}}, or diatomic oxygen, O₂). Symptoms of short-term nitrogen dioxide exposure include nausea, dyspnea and headache. Long-term effects could include impaired immune and respiratory function.<ref>{{Cite web|url = https://www.cdc.gov/niosh/ipcsneng/neng0930.html|title = Centers for Disease Control and Prevention|date=1 July 2014 |access-date = 10 December 2015|website =NIOSH }}</ref>

==Biological functions== {{Main|Biological functions of nitric oxide}} NO is a gaseous signaling molecule.<ref>{{Cite journal|last1=Liu|first1=Hongying|last2=Weng|first2=Lingyan|last3=Yang|first3=Chi|date=2017-03-28|title=A review on nanomaterial-based electrochemical sensors for H₂O₂, H₂S and NO inside cells or released by cells|journal=Microchimica Acta|volume=184|issue=5|pages=1267–1283|doi=10.1007/s00604-017-2179-2|s2cid=21308802|issn=0026-3672}}</ref> It is a key vertebrate biological messenger, playing a role in a variety of biological processes.<ref>Weller, Richard, [https://www.ted.com/talks/richard_weller_could_the_sun_be_good_for_your_heart Could the sun be good for your heart?] TedxGlasgow. Filmed March 2012, posted January 2013</ref> It is a bioproduct in almost all types of organisms, including bacteria, plants, fungi, and animal cells.<ref>Roszer, T (2012) The Biology of Subcellular Nitric Oxide. {{ISBN|978-94-007-2818-9}}</ref>

Nitric oxide, an endothelium-derived relaxing factor (EDRF), is biosynthesized endogenously from <small>L</small>-arginine, oxygen, and NADPH by various nitric oxide synthase (NOS) enzymes.<ref name="Perez 2598–2607.e1">{{Cite journal|last1=Perez|first1=Krystle M.|last2=Laughon|first2=Matthew|date=November 2015|title=Sildenafil in Term and Premature Infants: A Systematic Review|journal=Clinical Therapeutics|volume=37|issue=11|pages=2598–2607.e1|doi=10.1016/j.clinthera.2015.07.019|pmid=26490498|issn=0149-2918}}</ref> Reduction of inorganic nitrate may also make nitric oxide.<ref name="stryer" /> One of the main enzymatic targets of nitric oxide is guanylyl cyclase.<ref name="Hancock-2010">{{Cite book|title=Cell signalling|last=Hancock |first=John T. |date=2010|publisher=Oxford University Press|isbn=978-0-19-923210-9|edition= 3rd|location=Oxford|oclc=444336556}}</ref> The binding of nitric oxide to the heme region of the enzyme leads to activation, in the presence of iron.<ref name="Hancock-2010" /> Nitric oxide is highly reactive (having a lifetime of a few seconds), yet diffuses freely across membranes. These attributes make nitric oxide ideal for a transient paracrine (between adjacent cells) and autocrine (within a single cell) signaling molecule.<ref name="stryer">{{cite book|last = Stryer| first = Lubert| title = Biochemistry |edition=4th| publisher = W.H. Freeman and Company|year = 1995| page = 732| isbn = 978-0-7167-2009-6}}</ref> Once nitric oxide is converted to nitrates and nitrites by oxygen and water, cell signaling is deactivated.<ref name="Hancock-2010" />

The endothelium (inner lining) of blood vessels uses nitric oxide to signal the surrounding smooth muscle to relax, resulting in vasodilation and increasing blood flow.<ref name="stryer" /> Sildenafil (Viagra) is a drug that uses the nitric oxide pathway. Sildenafil does not produce nitric oxide, but enhances the signals that are downstream of the nitric oxide pathway by protecting cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, allowing for the signal to be enhanced, and thus vasodilation.<ref name="Perez 2598–2607.e1"/> Another endogenous gaseous transmitter, hydrogen sulfide (H₂S) works with NO to induce vasodilation and angiogenesis in a cooperative manner.<ref>{{Cite journal|last1=Szabo|first1=Csaba|last2=Coletta|first2=Ciro|last3=Chao|first3=Celia|last4=Módis|first4=Katalin|last5=Szczesny|first5=Bartosz|last6=Papapetropoulos|first6=Andreas|last7=Hellmich|first7=Mark R.|date=2013-07-23|title=Tumor-derived hydrogen sulfide, produced by cystathionine-β-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=110|issue=30|pages=12474–12479|doi=10.1073/pnas.1306241110|issn=1091-6490|pmc=3725060|pmid=23836652|bibcode=2013PNAS..11012474S|doi-access=free}}</ref><ref name="Altaany 879–888">{{Cite journal|last1=Altaany|first1=Zaid|last2=Yang|first2=Guangdong|last3=Wang|first3=Rui|date=July 2013|title=Crosstalk between hydrogen sulfide and nitric oxide in endothelial cells|journal=Journal of Cellular and Molecular Medicine|volume=17|issue=7|pages=879–888|doi=10.1111/jcmm.12077|issn=1582-4934|pmc=3822893|pmid=23742697}}</ref>

Nasal breathing produces higher levels of exhaled nitric oxide compared to oral breathing.<ref>{{cite journal |last1=Yasuda |first1=Yoshifumi |last2=Itoh |first2=Tomonori |last3=Miyamura |first3=Miharu |last4=Nishino |first4=Hitoo |title=Comparison of Exhaled Nitric Qxide and Cardiocrespiratory Indices between Nasal and Oral Breathing during Submaximal Exercise in Humans |journal=The Japanese Journal of Physiology |date=1997 |volume=47 |issue=5 |pages=465–470 |doi=10.2170/jjphysiol.47.465 |pmid=9504133 }}</ref>

== Occupational safety and health == In the U.S., the Occupational Safety and Health Administration (OSHA) has set the legal limit (permissible exposure limit) for nitric oxide exposure in the workplace as 25&nbsp;ppm (30&nbsp;mg/m³) over an 8-hour workday. The National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit (REL) of 25&nbsp;ppm (30&nbsp;mg/m³) over an 8-hour workday. At levels of 100&nbsp;ppm, nitric oxide is immediately dangerous to life and health.<ref>{{Cite web|title = Nitric oxide |url = https://www.cdc.gov/niosh/npg/npgd0448.html|website = National Institute for Occupational Safety and Health |access-date = 2015-11-20}}</ref>

== Explosion hazard == Liquid nitrogen oxide is very sensitive to detonation even in the absence of fuel, and can be initiated as readily as nitroglycerin. Detonation of the endothermic liquid oxide close to its boiling point ({{convert|&minus;152|°C|°F K|1|disp=or}}) generated a 100 kbar pulse and fragmented the test equipment. It is the simplest molecule that is capable of detonation in all three phases. The liquid oxide is sensitive and may explode during distillation, and this has been the cause of industrial accidents.<ref>{{cite book |last=Urben |first=Peter |title=Bretherick's Handbook of Reactive Chemical Hazards |date=2017 |publisher=Elsevier Science |isbn=978-0-08-100971-0 }}{{pn|date=February 2025}}</ref> Gaseous nitric oxide detonates at about {{convert|2300|m/s|km/h mph|-2}}, but as a solid it can reach a detonation velocity of {{convert|6100|m/s|km/h mph|-2}}.<ref>{{cite journal |last1=Ribovich |first1=John |last2=Murphy |first2=John |last3=Watson |first3=Richard |title=Detonation studies with nitric oxide, nitrous oxide, nitrogen tetroxide, carbon monoxide, and ethylene |journal=Journal of Hazardous Materials |date=1975 |volume=1 |issue=4 |pages=275–287 |doi=10.1016/0304-3894(75)80001-X |bibcode=1975JHzM....1..275R }}</ref>

==References== '''Notes ''' {{Reflist}}

==Further reading== * {{cite book |last1=Butler |first1=Anthony R. |last2=Nicholson |first2=Rosslyn |title=Life, Death and Nitric Oxide |date=2003 |publisher=Royal Society of Chemistry |isbn=978-0-85404-686-7 }} * {{cite book |last1=Faassen |first1=Ernst van |last2=Vanin |first2=Anatoly |title=Radicals for Life: The Various Forms of Nitric Oxide |date=2011 |publisher=Elsevier |isbn=978-0-08-048959-9 }} * {{cite book |last1=Ignarro |first1=Louis J. |title=Nitric Oxide: Biology and Pathobiology |date=2000 |publisher=Academic Press |isbn=978-0-08-052503-7 }}

==External links== * [http://www.inchem.org/documents/icsc/icsc/eics1311.htm International Chemical Safety Card 1311] * {{cite web|url= http://www.diabetesincontrol.com/nitric-oxide-and-its-role-in-health-and-diabetes-2/ |title=Nitric oxide and its role in health and diabetes |work=Diabetes In Control. A free weekly diabetes newsletter for Medical Professionals. |date=21 October 2015 }} * [http://mattson.creighton.edu/NOx/index.html Microscale Gas Chemistry: Experiments with Nitrogen Oxides] {{Webarchive|url=https://web.archive.org/web/20100615045842/http://mattson.creighton.edu/NOx/index.html |date=2010-06-15 }} * {{cite news |last1=Leonard |first1=Abigail W |title=Your Brain Boots Up Like a Computer |url=https://www.livescience.com/980-brain-boots-computer.html |work=livescience.com |date=17 August 2006 }} * [http://www.podiatrytoday.com/article/5164 Assessing The Potential of Nitric Oxide in the Diabetic Foot] * {{cite press release |title=New Discoveries About Nitric Oxide Can Provide Drugs For Schizophrenia |url=https://www.sciencedaily.com/releases/2007/11/071121213845.htm |work=ScienceDaily |publisher=Göteborg University |date=23 November 2007 }}

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