Editing Zwitterion

{{Short description|Molecule containing an equal number of positive and negative functional groups}}

In [[chemistry]], a '''zwitterion''' ({{IPAc-en|ˈ|t|s|v|ɪ|t|ə|ˌ|r|aɪ|ə|n}} {{respell|TSVIT|ə|ry|ən}}; {{etymology|de|{{wikt-lang|de|Zwitter}} ''{{IPA|de|ˈtsvɪtɐ|}}''<nowiki />|[[hermaphrodite]]}}), also called an '''inner salt''' or '''dipolar ion''',<ref>{{cite web |date=2015-11-03 |title=Zwitterion |url=https://chem.libretexts.org/Ancillary_Materials/Reference/Organic_Chemistry_Glossary/Zwitterion |access-date=2022-02-11 |website=Chemistry LibreTexts |language=en |archive-date=2023-06-21 |archive-url=https://web.archive.org/web/20230621214448/https://chem.libretexts.org/Ancillary_Materials/Reference/Organic_Chemistry_Glossary/Zwitterion |url-status=live}}</ref> is a [[molecule]] that contains an equal number of positively and negatively charged [[functional group]]s.<ref Name=Skoog>{{cite book |last1=Skoog|first1=Douglas A. |last2=West|first2=Donald M. |last3=Holler|first3=F. James |last4=Crouch|first4=Stanley R. |title=Fundamentals of Analytical Chemistry |date=2004 |publisher=Thomson/Brooks/Cole |isbn=0-03-035523-0 |pages=231, 385, 419, 460 |edition=8th}}
:{{cite book |last1=Skoog |first1=Douglas A. |last2=West |first2=Donald M. |last3=Holler |first3=F. James |display-authors=0 |title=Fundamentals of Analytical Chemistry |edition=9th |date=2013 |pages=415–416 |isbn=978-1-285-60719-1}}</ref>
(1,2-[[dipolar compound]]s, such as [[ylide]]s, are sometimes excluded from the definition.<ref name=GoldBook>{{GoldBookRef|title=Zwitterionic compounds/zwitterions|file=Z06752}}</ref>)

Some zwitterions, such as [[amino acid]] zwitterions, are in [[equilibrium chemistry|chemical equilibrium]] with an uncharged "parent" molecule. [[Betaine]]s are zwitterions that cannot [[Isomerization|isomerize]] to an all-neutral form, such as when the positive charge is located on a [[quaternary ammonium]] group. Similarly, a molecule containing a [[phosphonium]] group and a [[carboxylate]] group cannot isomerize.

==Amino acids==
[[File:Amino Acid Zwitterion Structural Formulae V.1.svg|thumb|280px|An [[amino acid]] contains both acidic (carboxylic acid fragment) and basic (amine fragment) centres. The isomer on the right is a zwitterion.]]

[[tautomer|Tautomerism]] of amino acids follows this stoichiometry:
:{{chem2|RCH(NH2)CO2H <-> RCH(N+H3)CO2-}}
The ratio of the concentrations of the two species in solution is independent of [[pH]].

It has been suggested, on the basis of theoretical analysis,  that the zwitterion is stabilized in aqueous solution by [[hydrogen bonding]] with solvent water molecules.<ref>{{cite journal |title= On the Number of Water Molecules Necessary to Stabilize the Glycine Zwitterion |first1= Jan H. |last1= Jensen |first2= Mark S. |last2= Gordon |journal= Journal of the American Chemical Society |year= 1995 |volume= 117 |issue= 31 |pages= 8159–8170 |doi= 10.1021/ja00136a013 |url= https://lib.dr.iastate.edu/cgi/viewcontent.cgi?article=1283&context=chem_pubs |access-date= 2020-08-28 |archive-date= 2020-12-02 |archive-url= https://web.archive.org/web/20201202083526/https://lib.dr.iastate.edu/cgi/viewcontent.cgi?article=1283&context=chem_pubs |url-status= live }}</ref> Analysis of [[neutron diffraction]] data for [[glycine]]  showed that it was in the zwitterionic form in the solid state and confirmed the presence of hydrogen bonds.<ref>{{cite journal|last1=Jönsson|first1=P.-G.|last2=Kvick|first2=Å.|year=1972|journal=Acta Crystallographica Section B|title=Precision neutron diffraction structure determination of protein and nucleic acid components. III. The crystal and molecular structure of the amino acid α-glycine|volume=28|pages=1827–1833|doi=10.1107/S0567740872005096|issue=6|url=http://journals.iucr.org/b/issues/1972/06/00/a09113/a09113.pdf|access-date=2019-09-03|archive-date=2020-03-14|archive-url=https://web.archive.org/web/20200314030331/http://journals.iucr.org/b/issues/1972/06/00/a09113/a09113.pdf|url-status=live}}</ref> Theoretical calculations have been used to show that zwitterions may also be present in the gas phase for some cases different from the simple carboxylic acid-to-amine transfer.<ref>{{cite journal|last1=Price|first1=William D.|last2=Jockusch|first2=Rebecca A. |last3=Williams|first3=Evan R. |year=1997|title=Is Arginine a Zwitterion in the Gas Phase?|journal=Journal of the American Chemical Society |volume=119 |issue=49 |pages=11988–11989 |doi=10.1021/ja9711627 |pmid=16479267 |pmc=1364450 }}</ref> 

The [[Proteinogenic amino acid|p''K''<sub>a</sub> values]] for deprotonation of the common amino acids span the approximate range {{val|2.15|0.2}}. This is also consistent with the zwitterion being the predominant isomer that is present in an aqueous solution. For comparison, the simple carboxylic acid [[propionic acid]] ({{chem2|CH3CH2CO2H}}) has a p''K''<sub>a</sub> value of 4.88.

==Other compounds==
<gallery mode="packed">
File:Zwitterion Structural Formulae V.1.svg|[[Sulfamic acid]] isomers, with the zwitterion (right)
File:Anthranilsäure.svg|[[Anthranilic acid]]
File:EDTA-xtal-2D-skeletal.png|Structure of [[EDTA|H<sub>4</sub>EDTA]]
File:Psilocybin, Kekulé, skeletal formula of canonical psilocybin.svg| [[Psilocybin]]
</gallery>
[[Sulfamic acid]] crystallizes in the zwitterion form.<ref name="Sass">{{ cite journal | first= R. L.|last= Sass |date=1960 | title = A neutron diffraction study on the crystal structure of sulfamic acid | journal = Acta Crystallographica | volume = 13 | issue = 4 | pages = 320–324 | doi = 10.1107/S0365110X60000789 | doi-access = free }}</ref>

In crystals of [[anthranilic acid]] there are two molecules in the [[unit cell]]. One molecule is in the zwitterion form, the other is not.<ref>{{cite journal |last1=Brown |first1=C. J. |last2=Ehrenberg |first2=M. |title=Anthranilic acid, C<sub>7</sub>H<sub>7</sub>NO<sub>2</sub>, by neutron diffraction |journal=Acta Crystallographica C |date=1985 |volume=41 |issue=3 |pages=441–443 |doi=10.1107/S0108270185004206}}</ref>

In the solid state, [[EDTA|H<sub>4</sub>EDTA]] is a zwitterion with two protons having been transferred from carboxylic acid groups to the nitrogen atoms.<ref>{{cite journal |first= Par Michel |last= Cotrait |title= La structure cristalline de l'acide éthylènediamine tétraacétique, EDTA |trans-title=The crystalline structure of ethylenediamine tetraacetic acid, EDTA |year= 1972 |journal= Acta Crystallographica B |volume= 28 |issue= 3 |pages= 781–785 |doi= 10.1107/S056774087200319X}}</ref>

In [[psilocybin]], the proton on the dimethyl amino group is [[lability#chemistry|labile]] and may jump to the phosphate group to form a compound which is not a zwitterion.

==Theoretical studies==
[[Image:Pyridoxal-phosphate.svg|thumb|140px|pyridoxal phosphate]]
Insight to the equilibrium in solution may be gained from the results of theoretical calculations. For example, pyridoxal phosphate, a form of [[vitamin B6|vitamin B<sub>6</sub>]], in aqueous solution is predicted to have an equilibrium favoring a tautomeric form in which a proton is transferred from the phenolic -OH group to the nitrogen atom.<ref>{{cite journal |last1=Kiruba |first1=G. S. M. |last2=Ming |first2=Wah Wong |title=Tautomeric Equilibria of Pyridoxal-5′-phosphate and 3-Hydroxypyridine Derivatives: A Theoretical Study of Solvation Effects|journal=Journal of Organic Chemistry |date=2003 |volume=68 |issue=7 |pages=2874–2881 |doi=10.1021/jo0266792|pmid=12662064 }}</ref>

Because tautomers are different compounds, they sometimes have different enough structures that they can be detected independently in their mixture. This allows experimental analysis of the equilibrium.<ref>{{cite journal |title= Theoretical and Experimental Studies of the Zwitterion ⇌ Neutral Form Equilibrium of Ampholytes in Pure Solvents and Mixtures |first1= Peter I. |last1= Nagy |first2= Krisztina |last2= Takács-Novák |journal= J. Am. Chem. Soc. |year= 1997 |volume= 119 |issue= 21 |pages= 4999–5006 |doi= 10.1021/ja963512f }}</ref>

==Betaines and similar compounds==
The compound [[trimethylglycine]], which was isolated from [[sugar beet]], was named as "betaine". Later, other compounds were discovered that contain the same structural motif, a [[Quaternary (chemistry)|quaternary]] nitrogen atom with a [[carboxylate]] group attached to it via a [[Methylene group|–CH<sub>2</sub>–]] link. At the present time, all compounds whose structure includes this motif are known as betaines. Betaines do not isomerize because the chemical groups attached to the nitrogen atom are not [[labile]]. These compounds may be classed as permanent zwitterions, as isomerisation to a molecule with no electrical charges does not occur, or is very slow.<ref>{{cite book|last1=Nelson |first1=D. L. |last2=Cox |first2=M. M. |title=Lehninger, Principles of Biochemistry |edition=3rd |publisher=Worth Publishing |location=New York |date=2000 |isbn=1-57259-153-6}}</ref>
 
Other examples of permanent zwitterions include phosphatidylcholines, which also contain a quaternary nitrogen atom, but with a negatively-charged phosphate group in place of a carboxylate group; [[Polysulfobetaine|sulfobetaines]], which contain a quaternary nitrogen atom and a negatively charged sulfonate group;<ref>{{Cite journal|last1=Gonenne|first1=Amnon|last2=Ernst|first2=Robert|date=1978-06-15|title=Solubilization of membrane proteins by sulfobetaines, novel zwitterionic surfactants|url=https://dx.doi.org/10.1016/0003-2697%2878%2990565-1|journal=Analytical Biochemistry|language=en|volume=87|issue=1|pages=28–38|doi=10.1016/0003-2697(78)90565-1|pmid=677454 |issn=0003-2697}}</ref> and [[pulmonary surfactant]]s such as [[dipalmitoylphosphatidylcholine]]. Lauramidopropyl betaine is the major component of cocamidopropyl betaine.

<gallery widths="200">
File:Betaine Formula V.1.svg|[[Trimethylglycine]] (trivial name betaine)
File:1-Oleoyl-2-almitoyl-phosphatidylcholine Structural Formulae V.1.png|Example of a [[phosphatidylcholine]]
File:Cocamidopropyl betaine.svg|[[cocamidopropyl betaine]]
</gallery>

==Conjugated zwitterions==
Strongly polarized conjugated compounds (conjugated zwitterions) are typically very reactive, share [[diradical]] character, activate strong bonds and small molecules, and serve as transient intermediates in catalysis.<ref>{{cite journal |title=Charge frustration in ligand design and functional group transfer. |first1= Dominik |last1= Munz |first2= Meyer |last2= Karsten |journal= Nat. Rev. Chem. |year= 2021 |volume= 5 |issue= 6 |pages= 422–439 |doi= 10.1038/s41570-021-00276-3|s2cid= 235220781 }}</ref> Donor-acceptor entities are of vast use in photochemistry ([[photoinduced electron transfer]]), [[organic electronics]], switching and [[Reichardt's dye|sensing]].

==See also==
*[[Amphoterism]]
*[[Azomethine ylide]]

==References==
{{reflist}}

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[[Category:Zwitterions| ]]