Alloxan

Alloxan[1]
IUPAC name 1,3-Diazinane-2,4,5,6-tetrone
Other names Mesoxalylurea 5-Oxobarbituric acid
Identifiers
CAS number	50-71-5 Y, 2244-11-3 (Monohydrate)
PubChem	5781
ChemSpider	5577 Y
UNII	6SW5YHA5NG Y
MeSH	Alloxan
ChEMBL	CHEMBL1096009 Y, CHEMBL1697709
Jmol-3D images	Image 1
SMILES O=C1C(=O)NC(=O)NC1=O
InChI InChI=1S/C4H2N2O4/c7-1-2(8)5-4(10)6-3(1)9/h(H2,5,6,8,9,10) Y Key: HIMXGTXNXJYFGB-UHFFFAOYSA-N Y InChI=1/C4H2N2O4/c7-1-2(8)5-4(10)6-3(1)9/h(H2,5,6,8,9,10) Key: HIMXGTXNXJYFGB-UHFFFAOYAQ
Properties
Molecular formula	C4H2N2O4
Molar mass	142.07 g/mol
Melting point	256 °C (decomposition)
Solubility in water	Freely soluble
Hazards
MSDS	MSDS
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Alloxan (2,4,5,6-tetraoxypyrimidine; 2,4,5,6-pyrimidinetetrone) is an oxygenated pyrimidine derivative. It is present as alloxan hydrate in aqueous solution.

History

Alloxan was originally isolated in 1818 by Brugnatelli and was named in 1838 by Wöhler and Liebig. The name "Alloxan" emerged from an amalgamation of the words "Allantoin" and "Oxalsäure" (oxalic acid).

Biological effects

Alloxan is a toxic glucose analogue, which selectively destroys insulin-producing cells in the pancreas (that is beta cells) when administered to rodents 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 thiols, 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 radicals formed in this redox reaction. One study suggests that alloxan does not cause diabetes in humans.^[2] Others found a significant difference in alloxan plasma levels in children with and without diabetes Type 1. ^[3]

Discovery

The compound was discovered by Justus von Liebig and Friedrich Wöhler following the discovery of urea in 1828 and is one of the oldest named organic compounds that exist. The alloxan model of diabetes was first described in rabbits by Dunn, Sheehan and McLetchie in 1943.^[4]

Etymology

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.

Synthesis

The original preparation for alloxan was by oxidation of uric acid by nitric acid. In another method the monohydrate is prepared by oxidation of barbituric acid by chromium trioxide ^[5]

Alloxan is a strong oxidizing agent and it forms a hemiacetal with its reduced reaction product dialuric acid (in which a carbonyl group is reduced to a hydroxyl group) which is called alloxantin.^[6]

Alloxane (left) with dialuric acid (right) and alloxantin (center)

Commercial use

Alloxane is a raw material for the production of the purple dye murexide. Carl Wilhelm Scheele discovered the dye in 1776. Murexide is the product of the complex in-situ multistep reaction of alloxantin and gaseous ammonia. Murexide results from the condensation of the unisolated intermediate uramil with alloxan, liberated during the course of the reaction.

Murexide dye (right) from reaction of alloxantin (left)

Scheele sourced uric acid from human calculi (such as kidney stones) and called the compound lithic acid. William Prout investigated the compound in 1818 and he used boa constrictor excrement with up to 90% ammonium acid urate.

Liebig and Wöhler in the nineteenth century coined the name murexide for the dye after the Trunculus Murex which is the source of the Tyrian purple of antiquity.

Primo Levi in his novel The Periodic Table in chapter Nitrogen considers pythons as a source for alloxane on behalf of a lipstick producer but he is turned down by the director of the Turin zoo because the zoo already has lucrative contracts with cosmetics companies.

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. 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).

However, alloxan is not toxic to the human beta-cell, even in very high doses, probably due to differing glucose uptake mechanisms in humans and rodents.^[7][8]Alloxan is, however, toxic to the liver and the kidneys in high doses.^{[citation needed]}

References

1. ^ Merck Index, 11th Edition, 281.
2. ^ Lenzen, S: The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 51, 216-226, 2008 (Review)
3. ^ A. Mrozikiewicz, D. Kielstrokczewska-Mrozikiewicz, Z. Lstrokowicki, E. Chmara, K. Korzeniowska and P. M. Mrozikiewicz: Blood levels of alloxan in children with insulin-dependent diabetes mellitus. Acta Diabetologica 31, 236-237, 1994 (Rapid report)
4. ^ Dunn JS, Sheehan HL, McLetchie NGB (1943). "Necrosis of islets of Langerhans produced experimentally". Lancet 241 (6242): 484–487. doi:10.1016/S0140-6736(00)42072-6. 
5. ^ Alloxan monohydrate Submitted by A. V. Holmgren and Wilhelm Wenner1. Checked by T. L. Cairns and R. W. Upson. Organic Syntheses, Coll. Vol. 4, p.23 (1963); Vol. 32, p.6 (1952).Link
6. ^ Alloxantin dihydrate R. Stuart Tipson Organic Syntheses, Coll. Vol. 4, p.25; Vol. 33, p.3 Online article
7. ^ Tyrberg B, Andersson A, Borg L (2001). "Species differences in susceptibility of transplanted and cultured pancreatic islets to the beta-cell toxin alloxan". Gen Comp Endocrinol 122 (3): 238–51. doi:10.1006/gcen.2001.7638. PMID 11356036. 
8. ^ Eizirik D, Pipeleers D, Ling Z, Welsh N, Hellerström C, Andersson A (1994). "Major species differences between humans and rodents in the susceptibility to pancreatic beta-cell injury". Proc Natl Acad Sci U S A 91 (20): 9253–6. doi:10.1073/pnas.91.20.9253. PMID 7937750. 

External links

• Alloxan diabetes, a discovery, albeit a minor one, N.G.B. McLetchie
• The history and chemistry of the Murexide dye