Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Alloxan: Difference between pages

| Verifiedfields = changed

| verifiedrevid = 477247988

| ImageFileL1 =Alloxan, skeletal formula.svg

| ImageSizeL1 =130

| ImageCaptionL1 = Alloxan

| ImageFileR1 =Alloxan hydrate structure.png

| ImageSizeR1 =110

| ImageCaptionR1 = Alloxan hydrate

| PIN = 5,5-Dihydroxypyrimidine-2,4,6(1''H'',3''H'',5''H'')-trione

| OtherNames = 5,5-Dihydroxybarbituric acid

|Section1={{Chembox Identifiers

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| UNII_Comment = (anhydrous)

| UNII1_Ref = {{fdacite|correct|FDA}}

| UNII1 = O2AAP9F8B6

| UNII1_Comment = (monohydrate)

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 76451

| CASNo_Comment = (Anhydrous)

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo = 50-71-5

| CASNo1 = 3237-50-1

| CASNo1_Comment = (monohydrate)

| CASNo1_Ref = {{cascite|correct|CAS}}

| EC_number = 200-062-0

| PubChem = 5781

| SMILES = C1(=O)C(=O)NC(=O)NC1=O

| MeSHName = Alloxan

}}

|Section2={{Chembox Properties

| Formula = C₄H₄N₂O₅

| MolarMass = 160.07 g/mol

| Appearance = pale yellow solid

| Density = 1.639 g/cm³ (anhydrous)

| MeltingPtC = 254

| MeltingPt_notes = (decomposition)

| BoilingPt =

| Solubility = 0.29 g/100 mL<ref name=OS/>

}}

|Section3={{Chembox Hazards

| ExternalSDS = [http://www.palomar.edu/ehs/Chemistry%20MSDS/ALLOXAN%20MONOHYDRATE.pdf MSDS]

| MainHazards =

| FlashPt =

| AutoignitionPt =

}}

'''Alloxan''', sometimes referred to as '''alloxan hydrate''', is an [[organic compound]] with the formula OC(N(H)CO)₂C(OH)₂. It is classified as a derivative of [[pyrimidine]]. The [[anhydrous]] derivative OC(N(H)CO)₂CO is also known, as well as a dimeric derivative. These are some of the earliest known organic compounds. They exhibit a variety of biological activities.

==History and literature==

The compound was discovered by Justus von Liebig and Friedrich Wöhler. It is one of the oldest named organic compounds. It was originally prepared in 1818 by [[Luigi Valentino Brugnatelli]] (1761-1818)<ref>[[Luigi Valentino Brugnatelli]]; also cited as: Luigi Gaspari Brugnatelli and Luigi Vincenzo Brugnatelli.</ref><ref>See:

* Gaspare Brugnatelli (1818) [http://babel.hathitrust.org/cgi/pt?id=chi.097296757;view=1up;seq=123 "Sopra i cangiamenti che avvengono nell' ossiurico (ac. urico) trattato coll' ossisettonoso (ac. nitroso)"] (On the changes that occur in uric acid (uric acid) treated with nitric acid (nitric acid)), ''Giornale di Fisica, Chimica, Storia Naturale, Medicina, ed Arti'', 2nd series, '''1''' : 117-129. Brugnatelli called it ''ossieritrico'' (erythric acid) [p. 117].

* (Gaspard Brugnatelli) (1818) [http://babel.hathitrust.org/cgi/pt?id=ien.35556014128250;view=1up;seq=205 "Sur un acide nouveau obtenu en traitant l'acide urique par acid nitrique"] (On a new acide obtained by treating uric acid with nitric acid), ''Annales de Chimie et de Physique'', 2nd series, '''8''' : 201-204.</ref> and was named in 1838 by [[Friedrich Wöhler|Wöhler]] and [[Justus von Liebig|Liebig]].<ref>F. Wöhler und J. Liebig (1838) [http://babel.hathitrust.org/cgi/pt?id=uva.x002457907;view=1up;seq=613 "Untersuchungen über die Natur der Harnsäure"] (Investigations into the nature of uric acid), ''Annalen der Chemie und Pharmacie'', '''26''' : 241-340. Alloxan is named on p. 252 and its preparation and properties appear on pp. 256 ff.</ref> The name "Alloxan" emerged from an amalgamation of the words "[[allantoin]]" and "Oxalsäure" ([[oxalic acid]]). The alloxan model of diabetes was first described in rabbits by Dunn, Sheehan and McLetchie in 1943.<ref>{{cite journal |author1=Dunn, J. S. |author2=Sheehan, H. L. |author3=McLetchie, N. G. B. | title = Necrosis of Islets of Langerhans Produced Experimentally | journal = Lancet | year = 1943 | volume = 241 | issue = 6242 | pages = 484–487 | doi = 10.1016/S0140-6736(00)42072-6 }}</ref> The name is derived from [[allantoin]], a product of [[uric acid]] excreted by the [[fetus]] into the [[allantois]], and [[oxaluric acid]] derived from [[oxalic acid]] and [[urea]], found in [[urine]].

Alloxan was used in the production of the purple dye [[murexide]], discovered by [[Carl Wilhelm Scheele]] in 1776. Murexide is the product of the complex ''in-situ'' multistep reaction of alloxantin and gaseous [[ammonia]].{{cn|date=January 2021}} Murexide results from the condensation of the unisolated intermediate uramil with alloxan, liberated during the course of the reaction.

:[[Image:Murexide dye.png|thumb|left|527px|Murexide dye (right) from reaction of alloxantin (left)]]{{clear left}}

Scheele sourced [[uric acid]] from human [[calculus (medicine)|calculi]] (such as [[kidney stone]]s) and called the compound lithic acid. [[William Prout]] investigated the compound in 1818 and he used [[boa (genus)|boa constrictor]] excrement with up to 90% ammonium acid urate.

In the chapter "Nitrogen" of his memoir [[The Periodic Table (short story collection)|''The Periodic Table'']], [[Primo Levi]] tells of his futile attempt to make alloxan for a cosmetics manufacturer who has read that it can cause permanent reddening of the lips. Levi considers the droppings of [[Pythonidae|pythons]] as a source for uric acid for making alloxan, but he is turned down by the director of the [[Turin]] zoo because the zoo already has lucrative contracts with pharmaceutical companies, so he is obliged to use [[chicken]]s as his source of uric acid. The synthesis fails, however, "and the alloxan and its resonant name remained a resonant name."<ref>Primo Levi, ''The Periodic Table'' (New York: Schocken, 1984), translated by Raymond Rosenthal, 183.</ref>

==Synthesis==

It was originally obtained by oxidation of [[uric acid]] by [[nitric acid]]. It is prepared by oxidation of [[barbituric acid]] by [[chromium trioxide]].<ref>{{OrgSynth | author = Holmgren, A. V. |author2=Wenner, W. | title = Alloxan monohydrate | year = 1952 | volume = 32 | pages = 6 | collvol = 4 | collvolpages = 23 | prep = CV4P0023 }}</ref>

A dimeric derivative '''alloxantin''' can be prepared by partial reduction of alloxan with hydrogen sulfide.<ref name=OS>{{OrgSynth | author = Tipson, R. S. | title = Alloxantin dihydrate | year = 1953 | volume = 33 | pages = 3 | collvol = 4 | collvolpages = 25 | prep = CV4P0025 }}</ref>

:[[Image:Alloxane chemistry.png|thumb|left|400px|Alloxane (left) with dialuric acid (center) and alloxantin (right)]]{{clear left}}

==Biological effects==

Alloxan is a toxic [[glucose]] analogue, which selectively destroys [[insulin]]-producing cells in the [[pancreas]] (that is, [[beta cell]]s) when administered to [[rodent]]s and many other animal species. This causes an insulin-dependent [[diabetes mellitus]] (called "alloxan diabetes") in these animals, with characteristics similar to type 1 diabetes in humans. Alloxan is selectively toxic to insulin-producing pancreatic beta cells because it preferentially accumulates in beta cells through uptake via the [[GLUT2]] glucose transporter. Alloxan, in the presence of intracellular [[thiol]]s, generates [[reactive oxygen species]] (ROS) in a cyclic reaction with its reduction product, [[dialuric acid]]. The beta cell toxic action of alloxan is initiated by [[free radical]]s formed in this [[redox reaction]]. Studies suggests that alloxan does not cause diabetes in humans.<ref name="literature1">{{cite journal | author = Lenzen, S. | title = The Mechanisms of Alloxan- and Streptozotocin-induced Diabetes | journal = Diabetologia | year = 2008 | volume = 51 | issue = 2 | pages = 216–226 | pmid = 18087688 | doi=10.1007/s00125-007-0886-7| doi-access = free }}</ref> Others found a significant difference in alloxan plasma levels in children with and without diabetes Type 1.<ref name="literature2">{{cite journal |author1=Mrozikiewicz, A. |author2=Kielstrokczewska-Mrozikiewicz, D. |author3=Lstrokowicki, Z. |author4=Chmara, E. |author5=Korzeniowska, K. |author6=Mrozikiewicz, P. M. | title = Blood Levels of Alloxan in Children with Insulin-dependent Diabetes Mellitus | journal = Acta Diabetologica | year = 1994 | volume = 31 | issue = 4 | pages = 236–237 | pmid = 7888696 |doi=10.1007/bf00571958 |s2cid=12726659 }}</ref>

===Impact upon beta cells===

Because it selectively kills the [[insulin]]-producing [[beta-cells]] found in the pancreas, alloxan is used to induce [[diabetes]] in laboratory animals.<ref>{{cite journal | author = Danilova I.G. |author2=Sarapultsev P.A. |author3=Medvedeva S.U. |author4=Gette I.F. |author5=Bulavintceva T.S. |author6=Sarapultsev A.P. | year = 2014 | title = Morphological Restructuring of Myocardium During the Early Phase of Experimental Diabetes Mellitus | journal = Anat. Rec. | volume = 298| issue = 2| pages = 396–407| doi = 10.1002/ar.23052 | pmid = 25251897 | hdl = 10995/73117 | s2cid = 205412167 | hdl-access = free }}</ref><ref>{{Cite book |url=https://www.taylorfrancis.com/books/mono/10.1201/9781420093278/experimental-surgical-models-laboratory-rat-veronica-di-loreto-alfredo-rigalli |title=Experimental Surgical Models in the Laboratory Rat |date=2009-05-12 |publisher=CRC Press |isbn=978-0-429-14721-0 |editor2=Loreto, Veronica Di |editor1=Alfredo Rigalli |location=Boca Raton |doi=10.1201/9781420093278}}</ref> This occurs most likely because of selective uptake of the compound due to its structural similarity to [[glucose]] as well as the beta-cell's highly efficient uptake mechanism (GLUT2). In addition, alloxan has a high affinity to SH-containing cellular compounds and, as a result, reduces glutathione content. Furthermore, alloxan inhibits glucokinase, a SH-containing protein essential for insulin secretion induced by glucose.<ref>{{cite journal | author = Szkudelski T | year = 2001 | title = The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas | journal = Physiol Res | volume = 50 | issue = 6 | pages = 536–546 | pmid = 11829314 }}</ref>

Most studies have shown that alloxan is not toxic to the human beta-cell, even in very high doses, probably because of differing glucose uptake mechanisms in humans and rodents.<ref>{{cite journal |author1=Tyrberg, B. |author2=Andersson, A. |author3=Borg, L. A. | title = Species Differences in Susceptibility of Transplanted and Cultured Pancreatic Islets to the β-Cell Toxin Alloxan | journal = General and Comparative Endocrinology | year = 2001 | volume = 122 | issue = 3 | pages = 238–251 | pmid = 11356036 | doi = 10.1006/gcen.2001.7638 }}</ref><ref>{{cite journal |author1=Eizirik, D. L. |author2=Pipeleers, D. G. |author3=Ling, Z. |author4=Welsh, N. |author5=Hellerström, C. |author6=Andersson, A. | title = Major Species Differences between Humans and Rodents in the Susceptibility to Pancreatic β-Cell Injury | journal = Proceedings of the National Academy of Sciences of the United States of America| year = 1994 | volume = 91 | issue = 20 | pages = 9253–9256 | pmid = 7937750 | doi = 10.1073/pnas.91.20.9253 | pmc=44790|bibcode=1994PNAS...91.9253E |doi-access=free }}</ref>

Alloxan is, however, toxic to the [[liver]] and the [[kidneys]] in high doses.

==See also==

* [[Streptozotocin]]

==References==

{{Reflist}}

==External links==

*{{cite journal | author = McLetchie, N. G. | url = http://www.rcpe.ac.uk/journal/issue/journal_32_2/L%20Paper%209HistAllox.pdf | title = Alloxan Diabetes, a Discovery, albeit a Minor one | journal = [[Journal of the Royal College of Physicians of Edinburgh]] | year = 2002 | volume = 32 | issue = 2 | pages = 134–142 | pmid = 12434795 }}

*[http://www.chriscooksey.demon.co.uk/murexide/index.html The history and chemistry of the Murexide dye] {{Webarchive|url=https://web.archive.org/web/20130505133028/http://www.chriscooksey.demon.co.uk/murexide/index.html |date=2013-05-05 }}

[[Category:Pyrimidines]]

[[Category:Lactams]]

[[Category:Ureas]]

[[Category:Conjugated ketones]]