Alpha hydroxycarboxylic acid

{{Short description|Class of chemical compounds}} thumb|140px|right|Structural formulae of α-, β- and γ-hydroxy acids '''Alpha hydroxy carboxylic acids''', or '''α-hydroxy carboxylic acids''' ('''AHAs'''), are a group of carboxylic acids featuring a hydroxy group located ''one'' carbon atom away from the acid group. This structural aspect distinguishes them from beta hydroxy acids, where the functional groups are separated by ''two'' carbon atoms.<ref>{{Ullmann |doi=10.1002/14356007.a13_507|title=Hydroxycarboxylic Acids, Aliphatic |year=2000 |last1=Miltenberger |first1=Karlheinz |isbn=3527306730}}</ref> Notable AHAs include glycolic acid, lactic acid, mandelic acid, and citric acid.

α-Hydroxy acids are stronger acids compared to their non-alpha hydroxy counterparts, a property enhanced by internal hydrogen bonding.<ref>{{cite book |title=Data for Biochemical Research |vauthors=Dawson RM, etal |date=1959 |publisher=Clarendon Press |location=Oxford}}</ref><ref>Handbook of Chemistry and Physics, CRC Press, 58th edition, page D147 (1977)</ref><ref group=note>The strength of the hydrogen bonding is reflected also in the Proton nuclear magnetic resonance-spectrum of these compounds: instead of giving rise to a contribution to the broad signal of rapidly exchanged protons (between COOH, OH, NH, etc) in 2-phenyl-2-hydroxyacetic acid (mandelic acid) the proton on the alpha carbon and the proton trapped in the internal hydrogen bridge show a nice pair of doublets instead a singlet (H on alpha-C) and the formentioned broad signal of exchangable protons. So on the NMR-time scale the exchange equilibrium for the alpha-hydroxy group is frozen.</ref> AHAs serve a dual purpose: industrially, they are utilized as additives in animal feed and as precursors for polymer synthesis.<ref name=":5">{{cite journal |last1=Casalini |first1=Tommaso |last2=Rossi |first2=Filippo |last3=Castrovinci |first3=Andrea |last4=Perale |first4=Giuseppe |date=2019 |title=A Perspective on Polylactic Acid-Based Polymers Use for Nanoparticles Synthesis and Applications |journal=Frontiers in Bioengineering and Biotechnology |volume=7 |article-number=259 |doi=10.3389/fbioe.2019.00259 |issn=2296-4185 |pmc=6797553 |pmid=31681741 |doi-access=free}}</ref><ref name=":6">{{cite journal |last1=Storti |first1=G. |last2=Lattuada |first2=M. |date=2017-01-01 |editor-last=Perale |editor-first=Giuseppe |editor2-last=Hilborn |editor2-first=Jöns |title=8 - Synthesis of bioresorbable polymers for medical applications |url=https://www.sciencedirect.com/science/article/pii/B9780081002629000082 |journal=Bioresorbable Polymers for Biomedical Applications |language=en |publisher=Woodhead Publishing |pages=153–179 |doi=10.1016/b978-0-08-100262-9.00008-2 |isbn=978-0-08-100262-9 |access-date=2023-04-01|url-access=subscription }}</ref><ref name=":3">{{cite journal |last1=Samantaray |first1=Paresh Kumar |last2=Little |first2=Alastair |last3=Haddleton |first3=David M. |last4=McNally |first4=Tony |last5=Tan |first5=Bowen |last6=Sun |first6=Zhaoyang |last7=Huang |first7=Weijie |last8=Ji |first8=Yang |last9=Wan |first9=Chaoying |date=2020 |title=Poly(glycolic acid) (PGA): a versatile building block expanding high performance and sustainable bioplastic applications |url=http://xlink.rsc.org/?DOI=D0GC01394C |journal=Green Chemistry |language=en |volume=22 |issue=13 |pages=4055–4081 |doi=10.1039/D0GC01394C |issn=1463-9262 |s2cid=219749282|url-access=subscription }}</ref><ref name=":4">{{Cite journal |last1=Herold |first1=B. C. |last2=Scordi-Bello |first2=I. |last3=Cheshenko |first3=N. |last4=Marcellino |first4=D. |last5=Dzuzelewski |first5=M. |last6=Francois |first6=F. |last7=Morin |first7=R. |last8=Casullo |first8=V. Mas |last9=Anderson |first9=R. A. |last10=Chany |first10=C. |last11=Waller |first11=D. P. |last12=Zaneveld |first12=L. J. D. |last13=Klotman |first13=M. E. |date=2002-11-15 |title=Mandelic Acid Condensation Polymer: Novel Candidate Microbicide for Prevention of Human Immunodeficiency Virus and Herpes Simplex Virus Entry |journal=Journal of Virology |language=en |volume=76 |issue=22 |pages=11236–11244 |doi=10.1128/JVI.76.22.11236-11244.2002 |issn=0022-538X |pmc=136750 |pmid=12388683}}</ref> In cosmetics, they are commonly used for their ability to chemically exfoliate the skin.<ref name=":1">{{Cite journal |last=Nutrition |first=Center for Food Safety and Applied |date=2022-11-22 |title=Alpha Hydroxy Acids |url=https://www.fda.gov/cosmetics/cosmetic-ingredients/alpha-hydroxy-acids |journal=FDA |language=en}}</ref>

==Occurrence== Aldonic acids, a type of sugar acid, are a class of naturally occurring hydroxycarboxylic acids. They have the general chemical formula, HO2C(CHOH)''n''CH2OH. Gluconic acid, a particularly common aldonic acid, the oxidized derivative of glucose.

2-Hydroxy-4-(methylthio)butyric acid is an intermediate in the biosynthesis of 3-dimethylsulfoniopropionate, precursor to natural dimethyl sulfide.<ref name=":22">{{cite journal |last1=Curson |first1=Andrew R. J. |last2=Liu |first2=Ji |last3=Bermejo Martínez |first3=Ana |last4=Green |first4=Robert T. |last5=Chan |first5=Yohan |last6=Carrión |first6=Ornella |last7=Williams |first7=Beth T. |last8=Zhang |first8=Sheng-Hui |last9=Yang |first9=Gui-Peng |last10=Bulman Page |first10=Philip C. |last11=Zhang |first11=Xiao-Hua |last12=Todd |first12=Jonathan D. |year=2017 |title=Dimethylsulfoniopropionate biosynthesis in marine bacteria and identification of the key gene in this process |url=https://ueaeprints.uea.ac.uk/id/eprint/62649/1/Todd_Figure_1.pdf |journal=Nature Microbiology |volume=2 |issue=5 |page=17009 |doi=10.1038/nmicrobiol.2017.9 |pmid=28191900 |s2cid=21460292}}</ref>

==Synthesis== One common synthesis hydrolyzes the relatively common α-halocarboxylic acids to produce 2-hydroxycarboxylic acids. For instance, glycolic acid is typically produced industrially from chloroacetic acid through base hydrolysis and acid workup:<ref name="Ullmann" /> :{{chem2|R\sCH(Cl)CO2H + H2O -> R\sCH(OH)CO2H + HCl}}

Another synthetic pathway adds hydrogen cyanide to ketones or aldehydes, with acidic hydrolysis of the cyanohydrin intermediate:<ref>{{Cite book |last1=Vollhardt |first1=K Peter C |title=Organic chemistry: structure and function |last2=Schore |first2=Neil Eric |date=2018-01-29 |isbn=9781319079451 |edition=8th |publisher=W. H. Freeman, Macmillan Learning |location=New York |oclc=1007924903 |name-list-style=vanc}}</ref> :{{chem2|R\sCHO + HCN -> R\sCH(OH)CN}} :{{chem2|R\sCH(OH)CN + 2H2O -> R\sCH(OH)CO2H + NH3}}

Further specialized synthetic routes are the reaction of dilithiated carboxylic acids with oxygen, followed by neutralization...<ref>{{March6th|page=813}}</ref> :{{chem2|R\sCHLiCO2Li + O2 → R\sCH(O2Li)CO2Li}} :{{chem2|R\sCH(O2Li)CO2Li + H+ -> R\sCH(OH)CO2H + 2Li+ + ...}} ...and the Cannizzaro oxidation of α-keto aldehydes:<ref>{{March6th|page=1864}}</ref> :{{chem2|R\sC(O)CHO + 2OH− -> R\sCH(OH)CO2− + H2O}}

==Uses== The synthesis and utilization of polymers based on lactic acid, including polylactic acid (PLA) and its cyclic ester lactide, are used in the creation of biodegradable materials such as medical implants, drug delivery systems, and sutures.<ref name=":6" /> Similarly, glycolic acid serves as a foundation for the development of poly(glycolic acid), spelled polyglycolide (PGA), a polymer distinguished by its high crystallinity, thermal stability, and mechanical strength, despite its synthetic origins.<ref name=":5" /> Both PLA and PGA are fully biodegradable.<ref name=":3" />

Furthermore, mandelic acid, another alpha hydroxy acid, when combined with sulfuric acid produces "SAMMA", obtained via condensation with sulfuric acid.<ref name=":4" /> Early laboratory work performed in 2002 and 2007 against notable pathogens such as the human immunodeficiency virus (HIV) and the herpes simplex virus (HSV) suggest SAMMA warrants further investigation as a topical microbicide to prevent vaginal sexually-transmitted infection transmission.<ref name=":4" /><ref>{{Cite journal |last1=Chang |first1=Theresa L. |last2=Teleshova |first2=Natalia |last3=Rapista |first3=Aprille |last4=Paluch |first4=Maciej |last5=Anderson |first5=Robert A. |last6=Waller |first6=Donald P. |last7=Zaneveld |first7=Lourens J.D. |last8=Granelli-Piperno |first8=Angela |last9=Klotman |first9=Mary E. |date=2007-10-02 |title=SAMMA, a mandelic acid condensation polymer, inhibits dendritic cell-mediated HIV transmission |journal=FEBS Letters |language=en |volume=581 |issue=24 |pages=4596–4602 |doi=10.1016/j.febslet.2007.08.048 |issn=0014-5793 |pmc=2018605 |pmid=17825297 |bibcode=2007FEBSL.581.4596C }}</ref>

2-Hydroxy-4-(methylthio)butyric acid, alpha hydroxy carboxylic acid, is used commercially in a racemic mixture to substitute for methionine in animal feed.<ref>{{cite journal |last1=Lemme |first1=A. |last2=Hoehler |first2=D. |last3=Brennan |first3=JJ |last4=Mannion |first4=PF |year=2002 |title=Relative effectiveness of methionine hydroxy analog compared to DL-methionine in broiler chickens |journal=Poultry Science |volume=81 |issue=6 |pages=838–845 |doi=10.1093/ps/81.6.838 |pmid=12079051 |doi-access=free}}</ref>

α-Hydroxy acids, such as glycolic acid, lactic acid, citric acid, and mandelic acid, serve as precursors in organic synthesis, playing a role in the industrial-scale preparation of various compounds.<ref name="Ullmann">{{cite journal |vauthors=Miltenberger K |date=2000 |title=Hydroxycarboxylic Acids, Aliphatic |journal=Ullmann's Encyclopedia of Industrial Chemistry |doi=10.1002/14356007.a13_507 |isbn=978-3527306732}}</ref><ref>{{cite journal |vauthors=Ritzer E, Sundermann R |date=2000 |title=Hydroxycarboxylic Acids, Aromatic |journal=Ullmann's Encyclopedia of Industrial Chemistry |doi=10.1002/14356007.a13_519 |isbn=978-3527306732}}</ref> These acids are used when synthesizing aldehydes through oxidative cleavage.<ref>{{cite journal |vauthors=Ôeda H |date=1934 |title=Oxidation of some α-hydroxy-acids with lead tetraacetate |journal=Bulletin of the Chemical Society of Japan |volume=9 |issue=1 |pages=8–14 |doi=10.1246/bcsj.9.8 |doi-access=free}}</ref><ref>{{cite journal |vauthors=Nwaukwa S, Keehn P |date=1982 |title=Oxidative cleavage of α-diols, α-diones, α-hydroxy-ketones and α-hydroxy- and α-keto acids with calcium hypochlorite [Ca(OCl)2] |journal=Tetrahedron Letters |volume=23 |issue=31 |pages=3135–3138 |doi=10.1016/S0040-4039(00)88578-0}}</ref> α-Hydroxy acids are particularly prone to acid-catalyzed decarbonylation, yielding carbon monoxide, a ketone or aldehyde, and water as by-products.<ref>{{Cite book |title=Principles of organic synthesis. |vauthors=Chandler NR |date=1993 |publisher=Blackie Academic & Professional |others=Coxon, J. M. (James Morriss), 1941- |isbn=978-0751401264 |edition=3rd. |location=London |oclc=27813843}}</ref>

== Safety == Alpha hydroxy acids are generally safe when used on the skin as a cosmetic agent using the recommended dosage. The most common side-effects are mild skin irritations, redness and flaking.<ref name=":1" /> The United States Food and Drug Administration (FDA) and Cosmetic Ingredient Review expert panels both suggest that alpha hydroxy acids are safe to use as long as they are sold at low concentrations, pH levels greater than 3.5, and include thorough safety instructions.<ref name=":1" />

The FDA has warned consumers that care should be taken when using alpha hydroxy acids after an industry-sponsored study found that they can increase the likelihood of sunburns.<ref name=":1" /> This effect is reversible after stopping the use of alpha hydroxy acids. Other sources suggest that glycolic acid, in particular, may protect from sun damage.<ref name=":1" />

==Further reading== * {{cite journal | vauthors = Atzori L, Brundu MA, Orru A, Biggio P | title = Glycolic acid peeling in the treatment of acne | journal = Journal of the European Academy of Dermatology and Venereology | volume = 12 | issue = 2 | pages = 119–22 | date = March 1999 | pmid = 10343939 | doi = 10.1111/j.1468-3083.1999.tb01000.x | s2cid = 9721678 }} * {{cite journal |title=Alpha Hydroxy Acids for Skin Care |journal=Cosmetic Dermatology, Supplement |date=October 1994 |pages=1–6}} * {{cite journal |vauthors=Kalla G, Garg A, Kachhawa D |title=Chemical peeling--glycolic acid versus trichloroacetic acid in melasma |journal=Indian Journal of Dermatology, Venereology and Leprology |volume=67 |issue=2 |pages=82–4 |year=2001 |pmid=17664715}} * {{cite journal |vauthors=Kempers S, Katz HI, Wildnauer R, Green B |title=An evaluation of the effect of an alpha hydroxy acid-blend skin cream in the cosmetic improvement of symptoms of moderate to severe xerosis, epidermolytic hyperkeratosis, and ichthyosis |journal=Cutis |volume=61 |issue=6 |pages=347–50 |date=June 1998 |pmid=9640557}}

== Notes == {{reflist|group=note}}

== References == <references>  </references>

== External links == * [https://web.archive.org/web/20140401202214/http://www.fda.gov/Cosmetics/ProductsIngredients/Ingredients/ucm107940.htm U.S. Food and Drug Administration: Alpha Hydroxy Acids in Cosmetics]

Category:Alpha hydroxycarboxylic acids Category:Cosmetics chemicals Category:Skin whitening