View source for Chemistry:Nitric oxide

{{short description|Colorless gas with the formula NO}}
{{Chembox
| Verifiedfields = changed
| Watchedfields  = changed
| verifiedrevid  = 477001381
| Name           = 
| ImageFile      = Nitric-oxide-2D.svg
| ImageFile_Ref  = {{chemboximage|correct|??}}
| ImageSize      = 121
| ImageName      = Skeletal formula of nitric oxide with bond length
| ImageFileL1    = Nitric oxide.svg
| ImageNameL1    = Skeletal formula showing two lone pairs and one three-electron bond
| ImageFileR1    = Nitric-oxide-3D-vdW.png
| 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|point group]] C<sub>∞''v''</sub>)
}}
| 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 = [[Biology:Inhalation|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 = {{Unbulleted list
  | Fatal if inhaled
  | Causes severe burns
  | Causes eye damage
  | Corrosive to the respiratory tract}}<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 = {{GHS04}}{{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}}</ref><ref name=SDS/>
| GHSSignalWord = Danger
| HPhrases = {{H-phrases|270|280|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;[[Minute|min]])<br/>854&nbsp;ppm (rat, 4&nbsp;[[Hour|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 = [[Chemistry:Dinitrogen pentoxide|Dinitrogen pentoxide]]<br />
[[Chemistry:Dinitrogen tetroxide|Dinitrogen tetroxide]]<br />
[[Chemistry:Dinitrogen trioxide|Dinitrogen trioxide]]<br />
[[Chemistry:Nitrogen dioxide|Nitrogen dioxide]]<br />
[[Chemistry:Nitrous oxide|Nitrous oxide]]<br/>
Nitroxyl (reduced form)<br/>
[[Chemistry:Hydroxylamine|Hydroxylamine]] (hydrogenated form)
}}
}}

'''Nitric oxide''' ('''nitrogen 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 [[Biology:Free radical|free radical]]: it has an [[Chemistry:Unpaired electron|unpaired electron]], which is sometimes denoted by a dot in its [[Chemistry:Chemical formula|chemical formula]] (<sup>•</sup>N=O or <sup>•</sup>NO).  Nitric oxide is also a heteronuclear [[Chemistry:Diatomic molecule|diatomic molecule]], a class of molecules whose study spawned early modern [[Chemistry:Molecular orbital theory|theories of chemical bonding]].<ref name="G&E" />

An important [[Chemistry:Reaction intermediate|intermediate]] in [[Engineering:Chemical industry|industrial chemistry]], nitric oxide forms in combustion systems and can be generated by lightning in thunderstorms. 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>

Nitric oxide should not be confused with [[Chemistry:Nitrogen dioxide|nitrogen dioxide]] (NO<sub>2</sub>), a brown gas and major air pollutant, or with [[Chemistry:Nitrous oxide|nitrous oxide]] (N<sub>2</sub>O), an [[Chemistry:General anaesthetic|anesthetic]] gas.<ref name="G&E"/>

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

The ground state electronic configuration of NO is, in united atom notation:<ref>{{cite book |last1=Berkowitz |first1=Joseph |title=Photoabsorption, Photoionization, and Photoelectron Spectroscopy |date=1979 |publisher=Academic Press |page=231 |doi=10.1016/B978-0-12-091650-4.50012-8 |url=https://doi.org/10.1016/B978-0-12-091650-4.50012-8}}</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''<sub>O</sub> and 1''s''<sub>N</sub> 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 (X ²Π) in its ground state whose degeneracy is split in the fine structure from spin-orbit coupling with a total momentum ''J''={{frac|3|2}} or ''J''={{frac|1|2}}.

===Dipole===

The dipole of NO has been measured experimentally to  0.15740 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 |url=https://doi.org/10.1139/p75-254}}</ref>

==Reactions==
===With di- and triatomic molecules===
Upon condensing to a liquid, nitric oxide [[Chemistry:Dimer|dimerizes]] to [[Chemistry:Dinitrogen dioxide|dinitrogen dioxide]], but the association is weak and reversible.  The N–N distance in crystalline NO is 218&nbsp;pm, nearly twice the N–O distance.<ref name=G&E/>

Since the heat of formation of <sup>•</sup>NO is endothermic, NO can be decomposed to the elements.  [[Chemistry:Catalytic converter|Catalytic converter]]s in cars exploit this reaction:
: 2 NO  →  O<sub>2</sub> +  N<sub>2</sub>

When exposed to [[Chemistry:Oxygen|oxygen]], nitric oxide converts into [[Chemistry:Nitrogen dioxide|nitrogen dioxide]]:
: 2 NO + O<sub>2</sub> → 2 NO<sub>2</sub>

This reaction is thought to occur via the intermediates ONOO<sup>•</sup> 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 [[Chemistry:Nitrous acid|nitrous acid]] (HNO<sub>2</sub>). The reaction is thought to proceed via the following [[Chemistry:Stoichiometry|stoichiometry]]:

: 4 NO + O<sub>2</sub> + 2 H<sub>2</sub>O → 4 HNO<sub>2</sub>

Nitric oxide reacts with [[Chemistry:Fluorine|fluorine]], [[Chemistry:Chlorine|chlorine]], and [[Chemistry:Bromine|bromine]] to form the nitrosyl halides, such as [[Chemistry:Nitrosyl chloride|nitrosyl chloride]]:
: 2 NO + Cl<sub>2</sub> → 2 NOCl

With NO<sub>2</sub>, also a radical, NO combines to form the intensely blue [[Chemistry:Dinitrogen trioxide|dinitrogen trioxide]]:<ref name=G&E/>
: NO + NO<sub>2</sub> {{eqm}} ON−NO<sub>2</sub>

===Organic chemistry===
The addition of a nitric oxide [[Chemistry:Moiety|moiety]] to another molecule is often referred to as ''[[Chemistry:Nitrosylation|nitrosylation]]''. The '''Traube reaction'''<ref>{{confused|Traube purine synthesis}}</ref> is the [[Chemistry:Addition reaction|addition]] of a two [[Chemistry:Equivalent|equivalent]]s of nitric oxide onto an [[Chemistry:Enolate|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-[[Chemistry:Aldol reaction|aldol reaction]], giving an overall process similar to the [[Chemistry:Haloform reaction|haloform reaction]]. For example, nitric oxide reacts with [[Chemistry:Acetone|acetone]] and an [[Chemistry:Alkoxide|alkoxide]] to form a diazeniumdiolate on each α position, with subsequent loss of [[Chemistry:Methyl acetate|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>

: [[File:TraubeReaction.svg|400px|Traube reaction]]

This reaction, which was discovered around 1898, remains of interest in nitric oxide [[Chemistry:Prodrug|prodrug]] research. Nitric oxide can also react directly with [[Chemistry:Sodium methoxide|sodium methoxide]], ultimately forming [[Chemistry:Sodium formate|sodium formate]] and [[Chemistry:Nitrous oxide|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>

===Coordination complexes===
Nitric oxide reacts with [[Chemistry:Transition metal|transition metal]]s 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 [[Chemistry:Ammonia|ammonia]] at 750–900&nbsp;°C (normally at 850&nbsp;°C) with [[Chemistry:Platinum|platinum]] as [[Chemistry:Catalyst|catalyst]] in the [[Chemistry:Ostwald process|Ostwald process]]:

:4 NH<sub>3</sub> + 5 O<sub>2</sub> → 4 NO + 6 H<sub>2</sub>O

The uncatalyzed endothermic reaction of [[Chemistry:Oxygen|oxygen]] (O<sub>2</sub>) and [[Chemistry:Nitrogen|nitrogen]] (N<sub>2</sub>), which is effected at high temperature (>2000&nbsp;°C) by lightning has not been developed into a practical commercial synthesis (see [[Chemistry:Birkeland–Eyde process|Birkeland–Eyde process]]):
:N<sub>2</sub> + O<sub>2</sub> → 2 NO

===Laboratory methods===
In the laboratory, nitric oxide is conveniently generated by reduction of dilute [[Chemistry:Nitric acid|nitric acid]] with [[Chemistry:Copper|copper]]:
:8 HNO<sub>3</sub> + 3 Cu → 3 Cu(NO<sub>3</sub>)<sub>2</sub> + 4 H<sub>2</sub>O + 2 NO

An alternative route involves the reduction of nitrous acid in the form of [[Chemistry:Sodium nitrite|sodium nitrite]] or [[Chemistry:Potassium nitrite|potassium nitrite]]:
: 2 NaNO<sub>2</sub> + 2 NaI + 2 H<sub>2</sub>SO<sub>4</sub> → I<sub>2</sub> + 2 Na<sub>2</sub>SO<sub>4</sub> + 2 H<sub>2</sub>O + 2 NO
: 2 NaNO<sub>2</sub> + 2 FeSO<sub>4</sub> + 3 H<sub>2</sub>SO<sub>4</sub> → Fe<sub>2</sub>(SO<sub>4</sub>)<sub>3</sub> + 2 NaHSO<sub>4</sub> + 2 H<sub>2</sub>O + 2 NO
: 3 KNO<sub>2</sub> + KNO<sub>3</sub> + Cr<sub>2</sub>O<sub>3</sub> → 2 K<sub>2</sub>CrO<sub>4</sub> + 4 NO

The iron(II) sulfate route is simple and has been used in undergraduate laboratory experiments. So-called [[Chemistry:NONOate|NONOate]] compounds are also used for nitric oxide generation.

==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 [[Biology:Pinophyta|conifer]] cells, visualized using DAF-2 DA (diaminofluorescein diacetate)]]

Nitric oxide concentration can be determined using a [[Physics:Chemiluminescence|chemiluminescent reaction]] involving [[Chemistry:Ozone|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 [[Chemistry:Oxygen|oxygen]] and [[Chemistry:Nitrogen dioxide|nitrogen dioxide]], accompanied with emission of [[Physics:Light|light]] ([[Physics:Chemiluminescence|chemiluminescence]]):
: NO + O<sub>3</sub> → NO<sub>2</sub> + O<sub>2</sub> + ''hν''
which can be measured with a [[Physics:Photodetector|photodetector]]. The amount of light produced is proportional to the amount of nitric oxide in the sample.

Other methods of testing include [[Chemistry:Electrochemistry|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|spin trapping]] of nitric oxide with iron-[[Chemistry:Dithiocarbamate|dithiocarbamate]] complexes and subsequent detection of the mono-nitrosyl-iron complex with [[Physics:Electron paramagnetic resonance|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=9780121822620 |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|Earth:NOx}}

=== Acid rain deposition ===
Nitric oxide reacts with the [[Chemistry:Hydroperoxyl|hydroperoxyl radical]] ({{chem|HO|2|•}}) to form nitrogen dioxide (NO<sub>2</sub>), which then can react with a hydroxyl radical (<sup>[[Chemistry:Hydroxyl radical|•]]</sup>[[Chemistry:Hydroxyl radical|OH]]) to produce [[Chemistry:Nitric acid|nitric acid]] (HNO<sub>3</sub>):
: <sup>•</sup>NO + {{chem|HO|2|•}} → <sup>•</sup>NO<sub>2</sub> + <sup>•</sup>OH
: <sup>•</sup>NO<sub>2</sub> +  <sup>•</sup>OH → HNO<sub>3</sub>
Nitric acid, along with [[Chemistry:Sulfuric acid|sulfuric acid]], contributes to [[Earth:Acid rain|acid rain]] deposition.

=== Ozone depletion ===
<sup>•</sup>NO participates in ozone layer depletion. Nitric oxide reacts with stratospheric [[Chemistry:Ozone|ozone]] to form O<sub>2</sub> and nitrogen dioxide:
: <sup>•</sup>NO + O<sub>3</sub> → NO<sub>2</sub> + O<sub>2</sub>

This reaction is also utilized to measure concentrations  of <sup>•</sup>NO in control volumes.

=== Precursor to NO<sub>2</sub> ===
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, O<sub>2</sub>). 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|Biology: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 H<sub>2</sub>O<sub>2</sub>, H<sub>2</sub>S 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 [[Biology:Vertebrate|vertebrate]] [[Biology:Signal transduction|biological messenger]], playing a role in a variety of biological processes.<ref>Weller, Richard, [http://www.ted.com/talks/richard_weller_could_the_sun_be_good_for_your_heart.html Could the sun be good for your heart?] {{Webarchive|url=https://web.archive.org/web/20140216052804/http://www.ted.com/talks/richard_weller_could_the_sun_be_good_for_your_heart.html |date=2014-02-16 }} 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 [[Chemistry:Endothelium-derived relaxing factor|endothelium-derived relaxing factor]] (EDRF), is biosynthesized endogenously from [[Chemistry:Arginine|<small>L</small>-arginine]], [[Chemistry:Oxygen|oxygen]], and NADPH by various [[Biology:Nitric oxide synthase|nitric oxide synthase]] (NOS) [[Biology:Enzyme|enzyme]]s.<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 [[Biology:Guanylate cyclase|guanylyl cyclase]].<ref name="Hancock-2010">{{Cite book|title=Cell signalling|last=T.|first=Hancock, John|date=2010|publisher=Oxford University Press|isbn=9780199232109|edition= 3rd|location=Oxford|oclc=444336556}}</ref> The binding of nitric oxide to the [[Biology:Heme|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 [[Biology:Endothelium|endothelium]] (inner lining) of [[Biology:Blood vessel|blood vessel]]s uses nitric oxide to signal the surrounding [[Biology:Smooth muscle|smooth muscle]] to relax, resulting in [[Medicine:Vasodilation|vasodilation]] and increasing blood flow.<ref name="stryer" /> [[Chemistry:Sildenafil|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 [[Chemistry:Cyclic guanosine monophosphate|cyclic guanosine monophosphate]] (cGMP) from degradation by [[Biology:CGMP-specific phosphodiesterase type 5|cGMP-specific phosphodiesterase type 5]] (PDE5) in the corpus cavernosum, allowing for the signal to be enhanced, and thus [[Medicine:Vasodilation|vasodilation]].<ref name="Perez 2598–2607.e1"/> Another endogenous gaseous transmitter, [[Chemistry:Hydrogen sulfide|hydrogen sulfide (H<sub>2</sub>S)]] 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 nitric oxide within the body, while [[Medicine:Mouth breathing|oral breathing]] does not.<ref>{{cite journal|doi=10.2170/jjphysiol.47.465|doi-access=free|issn=0021-521X|first1=Yoshifumi|last1=Yasuda|first2=Tomonori|last2=Itoh|first3=Miharu|last3=Miyamura|first4=Hitoo|last4=Nishino|journal=Japanese Journal of Physiology|year=1997|volume=47|issue=5|url=https://www.jstage.jst.go.jp/article/jjphysiol/47/5/47_5_465/_article/-char/ja/|pages=465–470|title=Comparison of Exhaled Nitric Oxide and Cardiorespiratory Indices between Nasal and Oral Breathing during Submaximal Exercise in Humans|pmid=9504133 |access-date=2022-11-17}}
</ref><ref>{{Cite web|last=Dahl|first=Melissa|date=2011-01-11|title='Mouth-breathing' gross, harmful to your health|url=http://www.nbcnews.com/healthmain/mouth-breathing-gross-harmful-your-health-1C6437430|access-date=2021-09-06|website=NBC News|language=en}}</ref>

== Occupational safety and health ==
In the U.S., the [[Organization:Occupational Safety and Health Administration|Occupational Safety and Health Administration]] (OSHA) has set the legal limit ([[Earth:Permissible exposure limit|permissible exposure limit]]) for nitric oxide exposure in the workplace as 25&nbsp;ppm (30&nbsp;mg/m<sup>3</sup>) over an 8-hour workday. The [[Organization:National Institute for Occupational Safety and Health|National Institute for Occupational Safety and Health]] (NIOSH) has set a [[Earth:Recommended exposure limit|recommended exposure limit]] (REL) of 25&nbsp;ppm (30&nbsp;mg/m<sup>3</sup>) 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 b.p. (-152°C) 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|title=Bretherick's Handbook of Reactive Chemical Hazards {{!}} ScienceDirect|url=https://www.sciencedirect.com/book/9780081009710/brethericks-handbook-of-reactive-chemical-hazards|access-date=2022-02-23|isbn=9780081009710 |language=en |last1=Urben |first1=Peter |date=22 May 2017 |publisher=Elsevier Science }}</ref> Gaseous nitric oxide detonates at about 2300 m/s, but as a solid it can reach a detonation velocity of 6100 m/s.<ref>{{Cite journal|last1=Ribovich|first1=John|last2=Murphy|first2=John|last3=Watson|first3=Richard|date=1975-01-01|title=Detonation studies with nitric oxide, nitrous oxide, nitrogen tetroxide, carbon monoxide, and ethylene|url=https://dx.doi.org/10.1016/0304-3894%2875%2980001-X|journal=Journal of Hazardous Materials|language=en|volume=1|issue=4|pages=275–287|doi=10.1016/0304-3894(75)80001-X|issn=0304-3894}}</ref>

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

'''Further reading'''
* Butler A. and Nicholson R.; [https://books.google.com/books?id=0d1Z0m76YeYC "Life, death and NO."] Cambridge 2003. {{ISBN|978-0-85404-686-7}}.
* van Faassen, E. E.; Vanin, A. F. (eds); [https://books.google.com/books?id=UJ4glFNEcn0C "Radicals for life: The various forms of Nitric Oxide."] Elsevier, Amsterdam 2007. {{ISBN|978-0-444-52236-8}}.
* Ignarro, L. J. (ed.); [https://books.google.com/books?id=h5FugARr4bgC "Nitric oxide:biology and pathobiology."] Academic Press, San Diego 2000. {{ISBN|0-12-370420-0}}.

==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 |date=21 October 2015 }}
* [http://mattson.creighton.edu/NOx/index.html Microscale Gas Chemistry: Experiments with Nitrogen Oxides]
* [http://www.livescience.com/980-brain-boots-computer.html Your Brain Boots Up Like a Computer] – new insights about the biological role of nitric oxide.
* [http://www.podiatrytoday.com/article/5164 Assessing The Potential of Nitric Oxide in the Diabetic Foot]
* [https://www.sciencedaily.com/releases/2007/11/071121213845.htm New Discoveries About Nitric Oxide Can Provide Drugs For Schizophrenia]
* [https://web.archive.org/web/20090930092625/http://ull.chemistry.uakron.edu/erd/Chemicals/8000/6828.html Nitric Oxide at the Chemical Database]
* {{cite web | title=Immediately Dangerous to Life or Health Concentrations (IDLH): Nitric oxide | website=National Institute for Occupational Safety and Health | date=2 November 2018 | url=https://www.cdc.gov/niosh/idlh/10102439.html }}

{{nitrogen compounds}}
{{Oxides}}
{{Neurotransmitters}}
{{Nitric oxide signaling}}
{{Glutamatergics}}
{{GABAAR PAMs}}
{{Other respiratory system products}}
{{Molecules detected in outer space}}
{{oxygen compounds}}

{{DEFAULTSORT:Nitric Oxide}}

[[Category:Free radicals]]
[[Category:Gaseous signaling molecules]]
[[Category:GABAA receptor positive allosteric modulators]]
[[Category:Nitrogen oxides]]
[[Category:Neurotransmitters]]
[[Category:Nitrogen cycle]]
[[Category:NMDA receptor antagonists]]
[[Category:Orphan drugs]]
[[Category:Diatomic molecules]]

{{Sourceattribution|Nitric oxide}}