Nitric oxide 235287 226144255 2008-07-17T00:45:50Z 66.139.123.182 {{Chembox new | Name = Nitric oxide | ImageFile = Nitric-oxide-2D.png | ImageSize = 150px | ImageName = Nitric oxide | ImageFile1 = Nitric-oxide-3D-vdW.png | ImageSize1 = 150px | ImageName1 = Nitric oxide | Section1 = {{Chembox Identifiers | CASNo = 10102-43-9 }} | Section2 = {{Chembox Properties | Formula = NO | MolarMass = 30.0061 | Appearance = colourless gas | Density = 1.3 × 10<sup>3</sup> kg m<sup>−3</sup> (liquid)<br /> 1.34 g dm<sup>−3</sup> (vapour) | MeltingPt = −163.6°C (109.6 K) (-262.48°F) | BoilingPt = −151.7°C (121.4 K) (-241.06°F) }} | Section7 = {{Chembox Hazards | EUClass = Toxic ('''T'''), corrosive ('''C''') | NFPA-H = 3 | Flammability=0 | NFPA-F = | NFPA-R = 2 | Other=OX | RPhrases = {{R23}}, {{R24}}, {{R25}}, {{R34}}, {{R44}} | SPhrases = {{S23}}, {{S36}}, {{S37}}, {{S39}} }} }} '''Nitric oxide''' or '''Nitrogen monoxide''' is a [[chemical compound]] with [[chemical formula]] [[Nitrogen|N]][[Oxygen|O]]. This [[gas]] is an important [[signaling molecule]] in the body of [[mammal]]s, including [[human]]s, and is an extremely important intermediate in the [[chemical industry]]. It is also a [[toxic]] [[air pollutant]] produced by [[automobile]] [[engine]]s and [[power plant]]s. NO is an important messenger molecule involved in many physiological and pathological processes within the mammalian body both beneficial and detrimental. <ref>Hou Y.C., Janczuk A. and Wang P.G. (1999): Current trends in the development of nitric oxide donors. Curr. Pharm. Des. June, 5 (6): 417- 471</ref>. Appropriate levels of NO production are important in protecting an organ such as the liver from ischemic damage. However sustained levels of NO production result in direct tissue toxicity and contribute to the vascular collapse associated with septic shock, whereas chronic expression of NO is associated with various carcinomas and inflammatory conditions including juvenile diabetes, multiple sclerosis, arthritis and ulcerative colitis. <ref>Tylor B.S., Kion Y.M., Wang Q.I., Sharpio R.A., Billiar T.R. and Geller D.A. (1997): Nitric oxide down regulates hepatocyte-inducible nitric oxide synthase gene expression. Arch. Surg. 1, (32). Nov.; 1177-1182.</ref> Nitric oxide should not be confused with [[nitrous oxide]] (N<sub>2</sub>O), a [[general anaesthetic]], or with [[nitrogen dioxide]] (NO<sub>2</sub>) which is another poisonous air pollutant. The nitric oxide molecule is a [[free radical]], which is relevant to understanding its high reactivity. It reacts with the [[ozone]] in air to form [[nitrogen dioxide]], signalled by the appearance of the reddish-brown color. Despite being a startlingly simple molecule, NO is a fundamental player in the fields of [[neuroscience]], [[physiology]], and [[immunology]], and was proclaimed “[[Molecule of the Year]]” in 1992<ref name="undefined">{{cite journal | author = Elizabeth Culotta and Daniel E. Koshland Jr | year = 1992 | month = December | title = NO news is good news. (nitric oxide; includes information about other significant advances & discoveries of 1992) (Molecule of the Year). | journal = Science | volume = 258 | issue = 5090 | pages = 1862–1864 | doi = 10.1126/science.1361684 | pmid = 1361684 }}</ref> == Production environmental effects == From a thermodynamic perspective, NO is unstable with respect to O<sub>2</sub> and N<sub>2</sub>, although this conversion is very slow at ambient temperatures in the absence of a [[catalyst]]. Because the heat of formation of NO is [[endothermic]], its synthesis from molecular nitrogen and oxygen requires elevated temperatures, >1000°C. A major natural source is [[lightning]]. The use of [[internal combustion engine]]s has drastically increased the presence of nitric oxide in the environment. One purpose of [[catalytic converter]]s in cars is to minimize NO emission by catalytic reversion to O<sub>2</sub> and N<sub>2</sub>. Nitric oxide in the air may convert to [[nitric acid]], which has been implicated in [[acid rain]]. Furthermore, both NO and NO<sub>2</sub> participate in [[ozone layer depletion]]. Nitric oxide is a small highly diffusible gas and a ubiquitous bioactive molecule. == Mechanism of action == There are several mechanisms by which NO has been demonstrated to affect the biology of living cells. These include oxidation of iron containing proteins such as ribonucleotide reductase and aconitase, activation of the soluble guanylate cyclase, ADP ribosylation of proteins, protein sulphhydryl group [[nitrosylation]], and iron regulatory factor activation. <ref>Shami P.J., Moore J.O., Cockerman J.P., Halhorn W.J., Misukonis M.A., and Weinberg J.B. (1995): Nitric oxide modulation of the growth and differentiation of freshly isolated acute non-lymphocytic leukaemia cells. Leukaemia Research; 19(8): 527 - 534.</ref> NO has been demonstrated to activate NFkB in peripheral blood mononuclear cells, an important transcription factor in iNOS gene expression in response to inflammation. <ref>Kaibori M., Sakitani K., Oda M., Kamiyama Y., Masu Y. and Okumura T.(1999). Immunosuppressant FK56 inhibits iNOS gene expression at a step of NK-Kappa B activation in rat hepatocytes. J. Hepatol. Jan; 30 (6): 1138-1145.</ref>. It was found that NO acts through the stimulation of the soluble guanylate cyclase which is a heterodimeric enzyme with subsequent formation of cyclic GMP. Cyclic GMP activates protein kinases and leads ultimately to the dephosphorylation of the myosine light chain. <ref>Denninger J.W. and Marletta M.A. (1999): Guanylate cyclase and the No/cGMP singling pathway. Biochem. Biophys. Acta, May; 1411 (2-3): 334-356.</ref> == Technical applications == Although NO has relatively few direct uses, it is produced on a massive scale as an intermediate in the [[Ostwald process]] for the synthesis of [[nitric acid]] from [[ammonia]]. In 2005, the US alone produced 6M metric tons of nitric acid.<ref>“Production: Growth is the Norm” Chemical and Engineering News, July 1 0, 2006, p. 59.</ref> It finds use in the [[semiconductor]] industry for various processes. In one of its applications it is used along with [[nitrous oxide]] to form oxynitride gates in [[CMOS]] devices. === Miscellaneous applications === Nitric oxide can be used for detecting surface radicals on polymers. Quenching of surface [[Radical (chemistry)|radical]]s with nitric oxide results in incorporation of nitrogen, which can be quantified by means of [[X-ray photoelectron spectroscopy]]. == Biological functions == {{main|Endothelium-derived relaxing factor}} NO is one of the few gaseous signaling molecules known. It is a key [[vertebrate]] [[signal transduction|biological messenger]], playing a role in a variety of biological processes. Nitric oxide, known as the '[[endothelium-derived relaxing factor]]', or 'EDRF', is biosynthesised endogenously from [[arginine]] and [[oxygen]] by various [[nitric oxide synthase]] (NOS) [[enzyme]]s and by reduction of inorganic nitrate. The [[endothelium]] (inner lining) of [[blood vessel]]s use nitric oxide to signal the surrounding [[smooth muscle]] to relax, thus resulting in [[vasodilation]] and increasing blood flow. 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 signal molecule between adjacent cells and within cells.<ref name="stryer">{{cite book | last = Stryer| first = Lubert| title = Biochemistry, 4th Edition| publisher = W.H. Freeman and Company | date = 1995| pages = pp. 732| isbn = 0-7167-2009-4 }}</ref> The production of nitric oxide is elevated in populations living at high-altitudes, which helps these people avoid [[Hypoxia (medical)|hypoxia]]. Effects include blood vessel dilatation, [[neurotransmitter|neurotransmission]] (see [[Gasotransmitters]]), modulation of the [[hair|hair cycle]], and [[erection|penile erections]]. [[Glyceryl trinitrate (pharmacology)|Nitroglycerin]] and [[amyl nitrite]] serve as vasodilators because they are converted to nitric oxide in the body. Sildenafil, popularly known by the trade name [[Sildenafil|Viagra]], stimulates erections primarily by enhancing signaling through the nitric oxide pathway in the penis. Nitric oxide (NO) contributes to vessel homeostasis by inhibiting vascular smooth muscle contraction and growth, platelet aggregation, and leukocyte adhesion to the endothelium. In humans, a high-salt intake was demonstrated to attenuate NO production. <ref>[http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=223997&Ausgabe=228460&ArtikelNr=63555]</ref> Nitric oxide is also generated by [[macrophage]]s and [[neutrophil]]s as part of the human [[immune response]]. Nitric oxide is toxic to [[bacteria]] and other human [[pathogens]]. In response, however, many bacterial pathogens have evolved mechanisms for nitric oxide resistance.<ref>{{cite book |author=C. A. Janeway, et al. |title=Immunobiology: the immune system in health and disease |publisher=Garland Science |location=New York |year=2005 |edition=6th ed. |isbn=0-8153-4101-6 |oclc= |doi= }}</ref> Nitric oxide can contribute to [[reperfusion injury]] when an excessive amount produced during reperfusion (following a period of [[ischemia]]) reacts with [[superoxide]] to produce the damaging [[radical (chemistry)|free radical]] [[peroxynitrite]]. In contrast, inhaled nitric oxide has been shown to help survival and recovery from [[paraquat]] poisoning, which produces lung tissue damaging superoxide and hinders NOS metabolism. In plants, nitric oxide can be produced by any of four routes: (i)L-arginine-dependent nitric oxide synthase <ref>{{cite journal |author=Corpas et al.|title=Cellular and subcellular localization of endogenous nitric oxide in young and senescent pea plants|journal=Plant Physiology|volume=136 |issue=1 |pages=2722–33 |year=2004|doi=10.1104/pp.104.042812|pmid=15347796}}</ref>, <ref>{{cite journal |author=Corpas et al.|title=Constitutive arginine-dependent nitric oxide synthase activity in different organs of pea seedlings during plant development|journal=Planta|volume=224|issue=2 |pages=246–54|year=2006|doi=10.1007/s00425-005-0205-9}}</ref>,<ref>{{cite journal |author=Valderrama et al.|title=Nitrosative stress in plants|journal=FEBS Lett|volume=581|issue=3 |pages=453–61|year=2007|doi=10.1016/j.febslet.2007.01.006}}</ref>,(although the existence animal NOS homologs in plants is debated)<ref>{{cite journal |author=Corpas et al.|title=Enzymatic sources of nitric oxide in plant cells – beyond one protein–one function|journal=New Phytologist|volume=162|issue= |pages=246–7|year=2004|doi=10.1111/j.1469-8137.2004.01058.x}}</ref>,(ii) by plasma membrane-bound [[nitrate reductase]], (iii) by mitochondrial electron transport chain, or (iv) by non-enzymatic reactions. It is a signaling molecule, acts mainly against oxidative stress and also plays a role in plant pathogen interactions. Treating cut flowers and other plants with nitric oxide has been shown to lengthen the time before wilting.<ref>Judy Siegel-Itzkovich. [http://www.studentbmj.com/issues/99/09/news/313.php Viagra makes flowers stand up straight]. ''[[Student BMJ]]'', September 1999.</ref> A biologically important reaction of nitric oxide is S-[[nitrosylation]], the conversion of [[thiol]] groups, including [[cysteine]] residues in proteins, to form S-nitrosothiols (RSNOs). S-[[Nitrosylation]] is a mechanism for dynamic, post-translational regulation of most or all major classes of protein. == Use in Pediatric Intensive Care == Nitric Oxide/Oxygen blends are used in critical care to promote capillary and pulmonary dilation to treat Primary Pulmonary Hypertension in neonatal patients<ref>{{cite journal |author=Finer NN, Barrington KJ |title=Nitric oxide for respiratory failure in infants born at or near term |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD000399 |year=2006 |pmid=17054129 |doi=10.1002/14651858.CD000399.pub2 }}</ref><ref>{{cite journal |author=Chotigeat U, Khorana M, Kanjanapattanakul W |title=Inhaled nitric oxide in newborns with severe hypoxic respiratory failure |journal=J Med Assoc Thai |volume=90 |issue=2 |pages=266–71 |year=2007 |month=February |pmid=17375630 }}</ref> post meconium aspiration and related to birth defect. These are often a last-resort gas mixture before the use of [[ECMO]]. NO therapy has the potential to significantly increase the quality of life and in some cases save the lives of infants at risk for pulmonary vascular disease. <ref>Hayward C.S., Kelly R.P. and Macdonald P.S. (1999): Inhaled nitric oxide in cardiology practice. Cadio. Vasc. Res. Aug.; 15, 43 (3): 628 - 638.</ref> == Reactions == *When exposed to [[oxygen]], NO is converted into [[nitrogen dioxide]]. : 2NO + O<sub>2</sub> → 2NO<sub>2</sub> :This conversion has been speculated as occurring via the ONOONO intermediate. In water, NO react with oxygen and water to form HNO<sub>2</sub> or [[nitrous acid]]. The reaction is thought to proceed via the following stoichiometry: : 4 NO + O<sub>2</sub> + 2 H<sub>2</sub>O → 4 HNO<sub>2</sub> * NO will react with [[fluorine]], [[chlorine]], and [[bromine]] to from the XNO species, known as the nitrosyl halides, such as [[nitrosyl chloride]]. Nitrosyl iodide can form but is an extremely short lived species and tends to reform I<sub>2</sub>. : 2NO + Cl<sub>2</sub> → 2NOCl *[[Nitroxyl]] (HNO) is the reduced form of nitric oxide. *Nitric oxide reacts with [[acetone]] and an [[alkoxide]] to a ''diazeniumdiolate'' or ''nitrosohydroxylamine'' and [[Methyl acetate]] <ref>''Ueber Synthesen stickstoffhaltiger Verbindungen mit Hülfe des Stickoxyds'' [[Justus Liebig's Annalen der Chemie]] Volume 300, Issue 1, Date: '''1898''', Pages: 81-128 [[Wilhelm Traube]] {{DOI|10.1002/jlac.18983000108}}</ref>: :[[Image:TraubeReaction.svg|400px|Traube reaction]] :This is a very old reaction (1898) but of interest today in NO [[prodrug]] research. Nitric oxide can also react directly with sodium methoxide, forming [[sodium formate]] and [[nitrous oxide]] <ref>''Nitric Oxide Reacts with Methoxide'' Frank DeRosa, Larry K. Keefer, and Joseph A. Hrabie [[J. Org. Chem.]] '''2008''', 73, 1139-1142 {{DOI|10.1021/jo7020423}}</ref>. === Preparation === * As stated above, nitric oxide is produced industrially by the direct reaction of O<sub>2</sub> and N<sub>2</sub> at high temperatures. In the laboratory, it is conveniently generated by reduction of nitric acid: : 8[[Nitric acid|HNO<sub>3</sub>]] + 3[[Copper|Cu]] → 3Cu(NO<sub>3</sub>)<sub>2</sub> + 4H<sub>2</sub>O + 2NO * or by the reduction of nitrous acid: : 2 [[Sodium nitrite|NaNO<sub>2</sub>]] + 2 NaI + 2 H<sub>2</sub>SO<sub>4</sub> → I<sub>2</sub> + 4 [[Sodium bisulfate|NaHSO<sub>4</sub>]] + 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>(l) + [[Potassium nitrate|KNO<sub>3</sub>]] (l) + Cr<sub>2</sub>O<sub>3</sub>(s) → 2 K<sub>2</sub>CrO<sub>4</sub>(s) + 4 NO (g) :The iron(II) sulfate route is simple and has been used in undergraduate laboratory experiments. * Commercially, NO is produced by the oxidation of ammonia at 750°C to 900°C (normally at 850°C) in the presence of platinum as catalyst: : 4NH<sub>3</sub> + 5O<sub>2</sub> → 4NO + 6H<sub>2</sub>O :The uncatalyzed [[endothermic]] reaction of [[Oxygen|O<sub>2</sub>]] and [[Nitrogen|N<sub>2</sub>]] which is performed at high temperature (>2000°C) with lightning has not been developed into a practical commercial synthesis: : N<sub>2</sub> + O<sub>2</sub> → 2NO == Coordination Chemistry == {{main|metal nitrosyl}} NO forms complexes with all [[transition metal]]s to give complexes called [[metal nitrosyl]]s. The most common bonding mode of NO is the terminal linear type (M-NO). The angle of the M-N-O group can vary from 160-180° but are still termed as "linear". In this case the NO group is formally considered a 3-electron donor. In the case of a bent M-N-O conformation the NO group can be considered a one electron donor.<ref>Catherine E. Housecroft and Alan G. Sharpe: "Inorganic Chemistry", page 570. Pearson Education Limited 2001, 2005</ref>. Alternatively, one can view such complexes as derived from NO<sup>+</sup>, which is isoelectronic with CO. Nitric oxide can serve as a one-electron pseudohalide. In such complexes, the M-N-O group is characterized by an angle between 120-140°. The NO group can also bridge between metal centers through the nitrogen atom in a variety of geometries. == Measurement of nitric oxide concentration == The concentration of nitric oxide can be determined using a simple [[chemiluminescence|chemiluminescent reaction]] involving [[ozone]]:<ref>Fontijn, A., A. J. Sabadell and R. J. Ronco (1970). "Homogeneous chemiluminescent measurement of nitric oxide with ozone." Analytical Chemistry 42(6): 575-579.</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]]. This reaction also produces [[light]] (chemiluminescence), which can be measured with a [[photodetector]]. The amount of light produced is proportional to the amount of nitric oxide in the sample. : NO + O<sub>3</sub> → NO<sub>2</sub> + O<sub>2</sub> + light Other methods of testing include [[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]] of nitric oxide with iron-[[dithiocarbamate]] complexes and subsequent detection of the mono-nitrosyl-iron complex with [[Electron Paramagnetic Resonance]] (EPR).<ref>Vanin A. F.; Huisman A.; van Faassen E.E.; Methods in Enzymology vol 359 (2002) 27 - 42</ref><ref> Nagano T.; Yoshimura T.; "Bioimaging of nitric oxide", Chemical Reviews vol 102 (2002) 1235 - 1269.</ref> A group of [[fluorescent dye]] indicators exist that are also available in [[acetyl]]ated form for intracellular measurements. The most common compound is [[4,5-diaminofluorescein]] (DAF-2).<ref name="undefined">{{cite journal | author = Kojima H, Nakatsubo N, Kikuchi K, Kawahara S, Kirino Y, Nagoshi H, Hirata Y, Nagano T | year = 1998 | month = | title = Detection and imaging of nitric oxide with novel fluorescent indicators: diaminofluoresceins | journal = Anal. Chem. | volume = 70 | issue = 13 | pages = 2446–2453| pmid = 9666719 | url = | doi = 10.1021/ac9801723 }}</ref> ==Supplements== Nitric oxide has become a supplement for [[bodybuilder]]s. [[GNC]] sells an oral "nitric oxide" product targeted for bodybuilders, which is claimed to dramatically increase muscle growth, but this claim is unproven. == References == <references/> == Further reading == * Butler A. and Nicholson R.; " Life, death and NO." Cambridge 2003. ISBN-13: 978-0-85404-686-7. * Corpas FJ et al “Constitutive arginine-dependent nitric oxide synthase activity in different organs of pea seedlings during plant development” Planta 2006 224(2):246-54. * Corpas FJ, del Río LA, Barroso JB. "Need of biomarkers of nitrosative stress in plants" Trends Plant Sci. 2007 12(10):436-8. * van Faassen, E. E.; Vanin, A. F. (eds); " Radicals for life: The various forms of Nitric Oxide." Elsevier, Amsterdam 2007. ISBN-13: 978-0-444-52236-8. * F.A. Cotton, G. Wilkinson, C.A. Murillo, M. Bochmann; ''Advanced Inorganic Chemistry'', 6th ed. Wiley-Interscience, New York, 1999. * K.J. Gupta , M. Stoimenova, and W. M. Kaiser "In higher plants, only root mitochondria, but not leaf mitochondria reduce nitrite to NO, ''in vitro'' and in situ" Journal of Experimental Botany 2005 56(420):2601-2609. * E.Planchet, K.J. Gupta, M .Sonada & W.M.Kaiser (2005) "Nitric oxide emission from tobacco leaves and cell suspensions: rate limiting factors and evidence for the involvement of mitochondrial electron transport"The Plant Journal 41 (5), 732-743. * Stöhr, C.; Stremlau, S. "Formation and possible roles of nitric oxide in plant roots" Journal of Experimental Botany 2006 57(3):463-470. * Pacher, P.; Beckman, J. S.; Liaudet, L.; “Nitric Oxide and Peroxynitrite: in Health and disease” Physiological Reviews 2007, volume 87(1), page 315-424. PMID 17237348. * Valderrama et al. "Nitrosative stress in plants" FEBS Lett. 2007 581(3):453-61. == External links == * [http://www.npi.gov.au/database/substance-info/profiles/67.html National Pollutant Inventory - Oxides of nitrogen Fact Sheet] * [http://www.nobel.se/medicine/laureates/1998/index.html 1998 Nobel Prize in Physiology/Medicine for discovery of NO's role in cardiovascular regulation] * [http://www.diabetesincontrol.com/annodyne/burkeseries.php Nitric Oxide and its Role in Diabetes, Wound Healing and Peripheral Neuropathy] * [http://mattson.creighton.edu/NOx/index.html Microscale Gas Chemistry: Experiments with Nitrogen Oxides] * [http://www.livescience.com/humanbiology/060817_brain_boot.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] * [http://www.sciencedaily.com/releases/2007/11/071121213845.htm New Discoveries About Nitric Oxide Can Provide Drugs For Schizophrenia] * [http://www.mmmp.org/MMMP/public/biomap/viewBiomap.mmmp?id=65 Biomap on nitric oxide biochemistry] * [http://www.mmmp.org/MMMP/public/biomap/viewBiomap.mmmp?id=63 Biomap on nitric oxide biology & cancer] [[Category:Oxides]] [[Category:Nitrogen compounds]] [[Category:Neurotransmitters]] [[Category:Nitrogen metabolism]] [[ar:أكسيد نيتريك]] [[cs:Oxid dusnatý]] [[da:Nitrogenmonoxid]] [[de:Stickstoffmonoxid]] [[es:Óxido de nitrógeno (II)]] [[fr:Monoxyde d'azote]] [[ko:일산화 질소]] [[it:Monossido di azoto]] [[hu:Nitrogén-monoxid]] [[nl:Stikstofmonoxide]] [[ja:一酸化窒素]] [[pl:Tlenek azotu(II)]] [[pt:Óxido nítrico]] [[ro:Monoxid de azot]] [[ru:Оксид азота(II)]] [[sk:Oxid dusnatý]] [[sr:Азот-моноксид]] [[fi:Typpioksidi]] [[sv:Kväveoxid]] [[zh-yue:一氧化氮]] [[zh:一氧化氮]]