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|ɚ|ˌ|aɪ|ɔː|n|}} {{respell|TSVIT|ər|EYE|awn}}; {{etymology|de|{{wikt-lang|de|Zwitter}} ''{{IPA|de|ˈtsvɪtɐ|}}''<nowiki />|hermaphrodite}}), also called an '''inner salt''' or '''dipolar ion''' is a molecule that contains an equal number of positively and negatively charged functional groups.<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 |publisher=Cengage Learning |isbn=978-1-285-60719-1}}</ref> (1,2-dipolar compounds, such as ylides, 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 chemical equilibrium with an uncharged "parent" molecule. Betaines are zwitterions that cannot 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.

Because tautomers are different compounds, they have distinct structures. By detecting each, the equilibrium between the zwitterion and its uncharged tautomer can be assessed.<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 |bibcode= 1997JAChS.119.4999N }}</ref>

==Examples== <gallery mode="packed"> File:Amino Acid Zwitterion Structural Formulae V.1.svg|An amino acid 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 H4EDTA </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 |bibcode= 1960AcCry..13..320S | 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, C7H7NO2, by neutron diffraction |journal=Acta Crystallographica C |date=1985 |volume=41 |issue=3 |pages=441–443 |doi=10.1107/S0108270185004206 |bibcode=1985AcCrC..41..441B }}</ref>

In the solid state, H4EDTA 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 |bibcode= 1972AcCrB..28..781C }}</ref>

==Case studies== thumb|140px|pyridoxal phosphate Vitamin B6, also known as pyridoxal phosphate, exists as the zwitterion in aqueous solution.<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 |url=http://scholarbank.nus.edu.sg/handle/10635/95196 }}</ref>

===Amino acids=== The amino acids are a particularly important family of zwitterions. The zwitterions arise by tautomerism, which 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. The zwitterionic form in the solid state is stabilized by 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|bibcode=1972AcCrB..28.1827J |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> 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 |bibcode=1997JAChS.11911988P }}</ref>

===Betaines and similar compounds=== The compound trimethylglycine, named as "betaine", contain the same structural motif, a quaternary nitrogen atom with a carboxylate group attached to it via a –CH2– link. 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; 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|url-access=subscription}}</ref> and pulmonary surfactants 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>

===Nucleotides=== Containing both amines or imines and phosphoric acid groups, the nucleotides such as AMP, ADP, and ATP exist significantly as zwitterions, although the positive and negative charges are not necessarily balanced.<ref>{{cite journal |last1=Kaszubowski |first1=Oskar |last2=Ślepokura |first2=Katarzyna |title=Post-crystallization Rearrangement of Crystal Architecture, Intermolecular Interactions, and Nucleotide Conformation in Adenosine Monophosphates Crystals Induced by Single Crystal-to-Single Crystal Dehydration |journal=Crystal Growth & Design |date=2025 |volume=25 |issue=12 |pages=4586–4600 |doi=10.1021/acs.cgd.5c00490|doi-access=free }}</ref>

==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|pmid= 37118028 |s2cid= 235220781 }}</ref> Donor-acceptor entities are of vast use in photochemistry (photoinduced electron transfer), organic electronics, switching and sensing.

==See also== *Amphoterism *Azomethine ylide

==References== {{reflist}}

Category:Zwitterions