Editing Superoxide

{{short description|Any chemical compound containing an O2 ion (charge –1)}}
{{Chembox
| ImageFile1 = superoxide.svg
| ImageCaption1 = [[Lewis structure]] of superoxide. The six outer-shell electrons of each [[oxygen]] atom are shown in black; one electron pair is shared (middle); the unpaired electron is shown in the upper-left; and the additional electron conferring a negative charge is shown in red.
| ImageSize1 = 100px
| IUPACName = Superoxide
| SystematicName = Dioxidan-2-idylide
| OtherNames = Hyperoxide, Dioxide(1−)
|Section1={{Chembox Identifiers
| CASNo = 11062-77-4 
| CASNo_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 0S9K0E25FL
| ChEBI = 18421
| Gmelin = 487
| KEGG = C00704
| PubChem = 5359597
| ChemSpiderID = 4514331
| SMILES = O=[O-]
| StdInChI = InChI=1S/O2/c1-2/q-1
| StdInChIKey = MXDZWXWHPVATGF-UHFFFAOYSA-N
 }}
|Section2={{Chembox Properties
| Formula = {{chem2|O2-}}
| O=2
| ConjugateAcid = [[Hydroperoxyl]]
 }}
}}

In [[chemistry]], a '''superoxide''' is a [[Chemical compound|compound]] that contains the superoxide [[ion]], which has the chemical formula {{chem2|O2-}}.<ref>{{cite journal|last1=Hayyan|first1=M.|last2=Hashim|first2=M.A.|last3=Al Nashef|first3=I.M.|title=Superoxide Ion: Generation and Chemical Implications|journal=Chem. Rev.|date=2016|volume=116|issue=5|pages=3029–3085|doi=10.1021/acs.chemrev.5b00407|pmid=26875845|doi-access=free}}</ref> The systematic name of the anion is '''dioxide(1&minus;)'''. The [[reactive oxygen species|reactive oxygen ion]] superoxide is particularly important as the product of the one-electron [[redox|reduction]] of [[dioxygen]] {{chem2|O2}}, which occurs widely in nature.<ref>Sawyer, D. T. ''Superoxide Chemistry'', McGraw-Hill, {{doi|10.1036/1097-8542.669650}}</ref> [[Oxygen|Molecular oxygen]] (dioxygen) is a [[diradical]] containing two [[unpaired electron]]s, and superoxide results from the addition of an electron which fills one of the two [[Degenerate energy level|degenerate]] [[molecular orbital]]s, leaving a charged ionic species with a single unpaired electron and a net negative charge of −1. Both dioxygen and the superoxide anion are [[free radicals]] that exhibit [[paramagnetism]].<ref name="Valko" /> Superoxide was historically also known as "'''hyperoxide'''".<ref>{{cite journal|doi = 10.1021/acs.chemrev.5b00407|title = Superoxide Ion: Generation and Chemical Implications|year = 2016|last1 = Hayyan|first1 = Maan|last2 = Hashim|first2 = Mohd Ali|last3 = Alnashef|first3 = Inas M.|journal = Chemical Reviews|volume = 116|issue = 5|pages = 3029–3085|pmid = 26875845|doi-access = free}}</ref>

==Salts==

Superoxide forms salts with [[alkali metal]]s and [[alkaline earth metal]]s. The salts [[sodium superoxide]] ({{chem2|NaO2}}), [[potassium superoxide]] ({{chem2|KO2}}), [[rubidium superoxide]] ({{chem2|RbO2}}) and [[caesium superoxide]] ({{chem2|CsO2}}) are prepared by the reaction of {{chem2|O2}} with the respective alkali metal.<ref>{{cite book|last1=Holleman|first1=A.F.|title=Inorganic chemistry|date=2001|publisher=Academic Press, W. de Gruyter|location=San Diego, CA & Berlin|isbn=0-12-352651-5|edition=1st English|editor-first=Nils|editor-last=Wiberg}}</ref><ref>{{cite journal|title= The Preparation of Calcium Superoxide from Calcium Peroxide Diperoxyhydrate|first1=E.|last1=Vernon Ballou|first2=Peter|last2=C. Wood|first3=LeRoy|last3=A. Spitze|first4=Theodore|last4=Wydeven|date=1 July 1977|journal=Ind. Eng. Chem. Prod. Res. Dev.|volume=16|issue=2 |pages=180–186 |doi=10.1021/i360062a015}}</ref>

The alkali salts of {{chem2|O2-}} are orange-yellow in color and quite stable, if they are kept dry. Upon dissolution of these salts in water, however, the dissolved {{chem2|O2-}} undergoes [[disproportionation]] (dismutation) extremely rapidly (in a [[pH]]-dependent manner):<ref>{{Cotton&Wilkinson5th|page=461}}</ref>

:{{chem2|4 O2- + 2 H2O → 3 O2 + 4 OH-}}

This reaction (with moisture and carbon dioxide in exhaled air) is the basis of the use of [[potassium superoxide]] as an oxygen source in [[chemical oxygen generator]]s, such as those used on the [[Space Shuttle]] and on [[submarine]]s. Superoxides are also used in [[firefighter]]s' [[oxygen tank]]s to provide a readily available source of oxygen. In this process, {{chem2|O2-}} acts as a [[acid-base reaction theories|Brønsted base]], initially forming the [[hydroperoxyl]] radical ({{chem2|HO2}}).

The superoxide anion, {{chem2|O2-}}, and its protonated form, [[hydroperoxyl]], are in [[chemical equilibrium|equilibrium]] in an [[aqueous solution]]:<ref name="pka">{{cite journal |url=https://openlibrary.org/b/OL14350787M/Reactivity_of_HO2_O2_Radicals_in_Aqueous_Solution |title=Reactivity of HO<sub>2</sub>/O<sub>2</sub><sup>−</sup> Radicals in Aqueous Solution |journal=J. Phys. Chem. Ref. Data |date=1985 |volume=14 |issue=4 |pages=1041–1091 |doi=10.1063/1.555739 |bibcode=1985JPCRD..14.1041B |url-access=<!-- free -->|last1=Bielski |first1=Benon H. J. |last2=Cabelli |first2=Diane E. |last3=Arudi |first3=Ravindra L. |last4=Ross |first4=Alberta B.}}</ref>
:{{chem2|O2- + H2O ⇌ HO2 + OH-}}

Given that the hydroperoxyl radical has a [[pKa|p''K''<sub>a</sub>]] of around 4.8,<ref>{{cite web|url=http://www.sens.org/files/pdf/manu10.pdf|title={{chem|HO|2|•}}: the forgotten radical Abstract|archive-url=https://web.archive.org/web/20170808150022/http://www.sens.org/files/pdf/manu10.pdf|archive-date=2017-08-08|url-status=dead}}</ref> superoxide predominantly exists in the anionic form at neutral pH.

Potassium superoxide is soluble in [[dimethyl sulfoxide]] (facilitated by [[crown ether]]s) and is stable as long as protons are not available. Superoxide can also be generated in [[aprotic]] solvents by [[cyclic voltammetry]].

Superoxide salts also decompose in the solid state, but this process requires heating:

:{{chem2|2 NaO2 → Na2O2 + O2}}

==Biology==
Superoxide is common in biology, reflecting the pervasiveness of O<sub>2</sub> and its ease of reduction.  Superoxide is implicated in a number of biological processes, some with negative connotations, and some with beneficial effects.<ref>{{cite journal |doi=10.1371/journal.pbio.1000556|doi-access=free |title=A Mitochondrial Superoxide Signal Triggers Increased Longevity in ''Caenorhabditis elegans'' |date=2010 |last1=Yang |first1=Wen |last2=Hekimi |first2=Siegfried |journal=PLOS Biology |volume=8 |issue=12 |pages=e1000556 |pmid=21151885 }}</ref>

Like hydroperoxyl, superoxide is classified as [[reactive oxygen species]].<ref name="Valko">{{cite journal |last1=Valko |first1 = M. |last2=Leibfritz |first2=D. |last3=Moncol |first3=J. |last4=Cronin |first4=MTD. |last5=Mazur |first5=M. |last6=Telser |first6=J. |journal=International Journal of Biochemistry & Cell Biology |title=Free radicals and antioxidants in normal physiological functions and human disease |volume=39 |issue=1 |pages=44–84 |date=August 2007 |pmid=16978905 |doi=10.1016/j.biocel.2006.07.001}}</ref> It is generated by the [[immune system]] to kill invading [[microorganism]]s. In [[phagocyte]]s, superoxide is produced in large quantities by the [[enzyme]] [[NADPH oxidase]] for use in oxygen-dependent killing mechanisms of invading pathogens. Mutations in the gene coding for the NADPH oxidase cause an immunodeficiency syndrome called [[chronic granulomatous disease]], characterized by extreme susceptibility to infection, especially [[catalase]]-[[Catalase#Bacterial identification (catalase test)|positive]] organisms. In turn, micro-organisms genetically engineered to lack the superoxide-scavenging enzyme [[superoxide dismutase]] (SOD) lose [[virulence]]. Superoxide is also deleterious when produced as a byproduct of [[mitochondria]]l [[cellular respiration|respiration]] (most notably by [[Complex I]] and [[Complex III]]), as well as several other enzymes, for example [[xanthine oxidase]],<ref name="pmid17640558">{{cite journal |last1=Muller |first1=F. L. |last2=Lustgarten |first2=M. S. |last3=Jang |first3=Y. |last4=Richardson <first4=A. |last5=Van Remmen |first5=H. | title = Trends in oxidative aging theories. | journal = Free Radic. Biol. Med. | volume = 43 | issue = 4 | pages = 477–503 | year = 2007 | pmid = 17640558 | doi =10.1016/j.freeradbiomed.2007.03.034}}</ref> which can catalyze the transfer of electrons directly to molecular oxygen under strongly reducing conditions.

Because superoxide is toxic at high concentrations, nearly all aerobic organisms express SOD. SOD efficiently catalyzes the [[disproportionation]] of superoxide:
:{{chem2|2 HO2 → O2 + H2O2}}
Other proteins that can be both oxidized and reduced by superoxide (such as [[Oxyhemoglobin|hemoglobin]]) have weak SOD-like activity. Genetic inactivation ("[[Gene knockout|knockout]]") of SOD produces deleterious [[phenotype]]s in organisms ranging from bacteria to mice and have provided important clues as to the mechanisms of toxicity of superoxide in vivo.

[[Yeast]] lacking both mitochondrial and cytosolic SOD grow very poorly in air, but quite well under anaerobic conditions. Absence of cytosolic SOD causes a dramatic increase in mutagenesis and genomic instability. Mice lacking mitochondrial SOD (MnSOD) die around 21 days after birth due to neurodegeneration, cardiomyopathy, and lactic acidosis.<ref name="pmid17640558"/> Mice lacking cytosolic SOD (CuZnSOD) are viable but suffer from multiple pathologies, including reduced lifespan, [[Hepatocellular carcinoma|liver cancer]], [[muscle atrophy]], [[cataracts]], thymic involution, haemolytic anemia, and a very rapid age-dependent decline in female fertility.<ref name="pmid17640558"/>

Superoxide may contribute to the pathogenesis of many diseases (the evidence is particularly strong for [[radiation]] poisoning and [[hyperoxia|hyperoxic]] injury), and perhaps also to [[aging]] via the oxidative damage that it inflicts on cells. While the action of superoxide in the pathogenesis of some conditions is strong (for instance, mice and rats overexpressing CuZnSOD or MnSOD are more resistant to strokes and heart attacks), the role of superoxide in aging must be regarded as unproven, for now. In [[model organism]]s (yeast, the fruit fly Drosophila, and mice), genetically [[Gene knockout|knocking out]] CuZnSOD shortens lifespan and accelerates certain features of aging: ([[cataracts]], [[muscle atrophy]], [[macular degeneration]], and [[thymic involution]]). But the converse, increasing the levels of CuZnSOD, does not seem to consistently increase lifespan (except perhaps in ''[[Drosophila]]'').<ref name="pmid17640558"/> The most widely accepted view is that oxidative damage (resulting from multiple causes, including superoxide) is but one of several factors limiting lifespan.

The binding of {{chem2|O2}} by reduced ({{chem2|[[iron|Fe]](2+)}}) [[heme]] proteins involves formation of Fe(III) superoxide complex.<ref>
{{cite book
|first1=Gereon M.
|last1=Yee 
|first2=William B. 
|last2=Tolman 
|editor1-first=Peter M.H. |editor1-last=Kroneck |editor2-first=Martha E. |editor2-last=Sosa Torres
|title=Sustaining Life on Planet Earth: Metalloenzymes Mastering Dioxygen and Other Chewy Gases
|series=Metal Ions in Life Sciences
|volume=15
|year=2015
|publisher=Springer
|chapter=Chapter 5, Section 2.2.2 ''Fe(III)-Superoxo Intermediates''
|pages=141–144
|doi=10.1007/978-3-319-12415-5_5
|pmid=25707468 
|isbn=978-3-319-12414-8 
}}
</ref>

===Assay in biological systems===
The assay of superoxide in biological systems is complicated by its short half-life.<ref name="pmid8074285">{{cite journal | last1 = Rapoport | first1 = R. | last2 = Hanukoglu | first2 = I. | last3 = Sklan | first3 = D. | title = A fluorimetric assay for hydrogen peroxide, suitable for NAD(P)H-dependent superoxide generating redox systems. | journal = Anal Biochem | volume = 218 | issue = 2 | pages = 309–13 |date=May 1994 | doi = 10.1006/abio.1994.1183 | pmid = 8074285 | s2cid = 40487242 | url = https://zenodo.org/record/890715}}</ref> One approach that has been used in quantitative assays converts superoxide to [[hydrogen peroxide]], which is relatively stable. Hydrogen peroxide is then assayed by a fluorimetric method.<ref name="pmid8074285" /> As a free radical, superoxide has a strong [[Electron paramagnetic resonance|EPR]] signal, and it is possible to detect superoxide directly using this method. For practical purposes, this can be achieved only in vitro under non-physiological conditions, such as high pH (which slows the spontaneous dismutation) with the enzyme [[xanthine oxidase]]. Researchers have developed a series of tool compounds termed "[[spin trap]]s" that can react with superoxide, forming a meta-stable radical ([[half-life]] 1–15 minutes), which can be more readily detected by EPR. Superoxide spin-trapping was initially carried out with [[DMPO]], but phosphorus derivatives with improved half-lives, such as [[DEPPMPO]] and [[DIPPMPO]], have become more widely used.{{citation needed|date=October 2019}}

==Bonding and structure==
Superoxides are compounds in which the [[oxidation number]] of oxygen is −{{frac|2}}. Whereas molecular oxygen (dioxygen) is a [[diradical]] containing two [[unpaired electron]]s, the addition of a second electron fills one of its two [[Degenerate energy level|degenerate]] [[molecular orbital]]s, leaving a charged ionic species with single unpaired electron and a net negative charge of −1. Both dioxygen and the superoxide anion are [[free radicals]] that exhibit [[paramagnetism]].

The derivatives of dioxygen have characteristic O–O distances that correlate with the [[bond order|order]] of the O–O bond.
{| class="wikitable"
! Dioxygen compound || name || O–O distance ([[angstrom|Å]])|| O–O bond order
|-
| {{chem2|O2+}}|| [[dioxygenyl]] cation||1.12||2.5
|-
| {{chem2|O2}}||di[[oxygen]]||1.21||2
|-
| {{chem2|O2-}} || superoxide || 1.28||1.5<ref>{{cite journal | last1 = Abrahams | first1 = S. C. | last2 = Kalnajs | first2 = J. | year = 1955 | title = The Crystal Structure of α-Potassium Superoxide | journal = Acta Crystallographica | volume = 8 | issue = 8| pages = 503–506 | doi = 10.1107/S0365110X55001540 | doi-access = free| bibcode = 1955AcCry...8..503A }}</ref>
|-
| {{chem2|O2(2-)}} || [[peroxide]]|| 1.49||1
|-
|}

==See also==
* [[Oxygen]], {{chem2|O2}}
* [[Ozonide]], {{chem2|O3−}}
* [[Peroxide]], {{chem2|O2(2-)}}
* [[Oxide]], {{chem2|O(2−)}}
* [[Dioxygenyl]], {{chem2|O2+}}
*[[Antimycin A]] – used in fishery management, this compound produces large quantities of this free radical.
*[[Paraquat]] – used as a herbicide, this compound produces large quantities of this free radical.
* [[Xanthine oxidase]] – This form of the enzyme xanthine dehydrogenase produces large amounts of superoxide.

==References==
{{reflist}}

{{oxygen compounds}}

[[Category:Anions]]
[[Category:Oxygen compounds]]
[[Category:Oxyanions]]
[[Category:Immune system]]
[[Category:Superoxides| ]]
[[Category:Free radicals]]
[[Category:Reactive oxygen species]]