Chemistry of ascorbic acid

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L-Ascorbic acid
L-Ascorbic acid.svg
Ascorbic-acid-from-xtal-1997-3D-balls.png
Names
IUPAC name
(5R)-[(1S)-1,2-Dihydroxyethyl]-3,4-dihydroxyfuran-2(5H)-one
Other names
Vitamin C
Identifiers
3D model (JSmol)
  • Interactive image
  • Interactive image
ChEBI
ChEMBL
ChemSpider
EC Number 200-066-2
  • 4781
KEGG
  • D00018 ☑Y
PubChem CID
  • 5785
UNII
  • PQ6CK8PD0R ☑Y
Properties
C6H8O6
Molar mass 176.12 g·mol−1
Appearance White or light yellow solid
Density 1.65 g/cm3
Melting point 190 to 192 °C (374 to 378 °F; 463 to 465 K) decomposes
330 g/L
Solubility in ethanol 20 g/L
Solubility in glycerol 10 g/L
Solubility in propylene glycol 50 g/L
Solubility in other solvents insoluble in diethyl ether, chloroform, benzene, petroleum ether, oils, fats
Acidity (pKa) 4.10 (first), 11.6 (second)
Pharmacology
A11GA01 (WHO) G01AD03 (WHO), S01XA15 (WHO)
Hazards
Safety data sheet JT Baker
NFPA 704
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g., canola oil Health code 1: Exposure would cause irritation but only minor residual injury. E.g., turpentine Reactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogen Special hazards (white): no codeNFPA 704 four-colored diamond
1
1
0
Lethal dose or concentration (LD, LC):
LD50 (median dose)
11.9 g/kg (oral, rat)[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
‹See TfM›☒N verify (what is ☑Y‹See TfM›☒N ?)
Infobox references

Ascorbic acid is an organic compound with formula C
6
H
8
O
6
, originally called hexuronic acid. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. It is a mild reducing agent.

Ascorbic acid exists as two enantiomers (mirror-image isomers), commonly denoted "L" (for "levo") and "D" (for "dextro"). The L isomer is the one most often ecountered: it occurs naturally in many foods, and is one form ("vitamer") of vitamin C, an essential nutrient for humans and many animals. Deficiency of vitamin C causes scurvy, formerly a major disease of sailors in long sea voyages. It is used in as a food additive and a dietary supplement for its antioxidant properties. The "D" form can be made chemical synthesis but has no significant biological role.

History

The antiscorbutic properties of certain foods were demonstrated in the 18th century by James Lind. In 1907, Axel Holst and Theodor Frølich discovered that the antiscorbutic factor was a water-soluble chemical substance, distinct from the one that prevented beriberi. Between 1928 to 1932, Albert Szent-Györgyi isolated a candidate for this substance, which he called it "hexuronic acid", first from plants and later from animal adrenal glands. In 1932 Charles Glen King confirmed that it was indeed the antiscorbutic factor.

In 1933, sugar chemist Walter Norman Haworth, working with samples of "hexuronic acid" that Szent-Györgyi had isolated from paprika and sent him in the previous year, deduced the correct structure and optical-isomeric nature of the compound, and in 1934 reported its first synthesis.[2][3] In reference to the compound's antiscorbutic properties, Haworth and Szent-Györgyi proposed to rename it "a-scorbic acid" for the compound, and later specifically L-ascorbic acid.[4] Because of their work, in 1937 the Nobel Prizes for chemistry and medicine were awarded to Haworth and Szent-Györgyi, respectively.

Chemical properties

Acidity

Ascorbic acid is a vinylogous carboxylic acid and forms the ascorbate anion when deprotonated on one of the hydroxyls. This property is characteristic of reductones: enediols with a carbonyl group adjacent to the enediol group, namely with the group –C(OH)=C(OH)–C(=O)–. The ascorbate anion is stabilized by electron delocalization that results from resonance between two forms:

Ascorbate resonance.png

For this reason, ascorbic acid is much more acidic than would be expected if the compound contained only isolated hydroxyl groups.

Salts

The ascorbate anion forms salts, such as sodium ascorbate, calcium ascorbate, and potassium ascorbate.

Esters

Ascorbic acid can also react with organic acids as an alcohol forming esters such as ascorbyl palmitate and ascorbyl stearate.

Nucleophilic attack

Nucleophilic attack of ascorbic acid on a proton results in a 1,3-diketone:

Ascorbic diketone.png

Oxidation

Semidehydroascorbate acid radical
Dehydroascorbic acid

The ascorbate ion is the predominant species at typical biological pH values. It is a mild reducing agent and antioxidant. It is oxidized with loss of one electron to form a radical cation and then with loss of a second electron to form dehydroascorbic acid. It typically reacts with oxidants of the reactive oxygen species, such as the hydroxyl radical.

Ascorbic acid is special because it can transfer a single electron, owing to the resonance-stabilized nature of its own radical ion, called semidehydroascorbate. The net reaction is:

RO + C
6
H
7
O
6
→ RO + C6H7O
6
→ ROH + C6H6O6[5]

On exposure to oxygen, ascorbic acid will undergo further oxidative decomposition to various products including diketogulonic acid, xylonic acid, threonic acid and oxalic acid.[6]

Reactive oxygen species are damaging to animals and plants at the molecular level due to their possible interaction with nucleic acids, proteins, and lipids. Sometimes these radicals initiate chain reactions. Ascorbate can terminate these chain radical reactions by electron transfer. The oxidized forms of ascorbate are relatively unreactive and do not cause cellular damage.

However, being a good electron donor, excess ascorbate in the presence of free metal ions can not only promote but also initiate free radical reactions, thus making it a potentially dangerous pro-oxidative compound in certain metabolic contexts.

Ascorbic acid and its sodium, potassium, and calcium salts are commonly used as antioxidant food additives. These compounds are water-soluble and, thus, cannot protect fats from oxidation: For this purpose, the fat-soluble esters of ascorbic acid with long-chain fatty acids (ascorbyl palmitate or ascorbyl stearate) can be used as food antioxidants.

Other reactions

It creates volatile compounds when mixed with glucose and amino acids in 90 °C.[7]

It is a cofactor in tyrosine oxidation.[8]

Uses

Food additive

The main use of L-ascorbic acid and its salts is as food additives, mostly to combat oxidation. It is approved for this purpose in the EU with E number E300,[9] USA,[10], Australia, and New Zealand)[11]

Dietary supplement

Another major use of L-ascorbic acid is as dietary supplement.

Niche, non-food uses

  • Ascorbic acid is easily oxidized and so is used as a reductant in photographic developer solutions (among others) and as a preservative.
  • In fluorescence microscopy and related fluorescence-based techniques, ascorbic acid can be used as an antioxidant to increase fluorescent signal and chemically retard dye photobleaching.[12]
  • It is also commonly used to remove dissolved metal stains, such as iron, from fiberglass swimming pool surfaces.
  • In plastic manufacturing, ascorbic acid can be used to assemble molecular chains more quickly and with less waste than traditional synthesis methods.[13]
  • Heroin users are known to use ascorbic acid as a means to convert heroin base to a water-soluble salt so that it can be injected.[14]
  • As justified by its reaction with iodine, it is used to negate the effects of iodine tablets in water purification. It reacts with the sterilized water, removing the taste, color, and smell of the iodine. This is why it is often sold as a second set of tablets in most sporting goods stores as Portable Aqua-Neutralizing Tablets, along with the potassium iodide tablets.
  • Intravenous high-dose ascorbate is being used as a chemotherapeutic and biological response modifying agent.[15] Currently it is still under clinical trials.[16]

Synthesis

Natural biosynthesis of vitamin C occurs in many plants, and animals, by a variety of processes.

Industrial preparation

The outdated, but historically important industrial synthesis of ascorbic acid from glucose via the Reichstein process.

Eighty percent of the world's supply of ascorbic acid is produced in China.[17] Ascorbic acid is prepared in industry from glucose in a method based on the historical Reichstein process. In the first of a five-step process, glucose is catalytically hydrogenated to sorbitol, which is then oxidized by the microorganism Acetobacter suboxydans to sorbose. Only one of the six hydroxy groups is oxidized by this enzymatic reaction. From this point, two routes are available. Treatment of the product with acetone in the presence of an acid catalyst converts four of the remaining hydroxyl groups to acetals. The unprotected hydroxyl group is oxidized to the carboxylic acid by reaction with the catalytic oxidant TEMPO (regenerated by sodium hypochloritebleaching solution). Historically, industrial preparation via the Reichstein process used potassium permanganate as the bleaching solution. Acid-catalyzed hydrolysis of this product performs the dual function of removing the two acetal groups and ring-closing lactonization. This step yields ascorbic acid. Each of the five steps has a yield larger than 90%.[18]

A more biotechnological process, first developed in China in the 1960s, but further developed in the 1990s, bypasses the use of acetone-protecting groups. A second genetically modified microbe species, such as mutant Erwinia, among others, oxidises sorbose into 2-ketogluconic acid (2-KGA), which can then undergo ring-closing lactonization via dehydration. This method is used in the predominant process used by the ascorbic acid industry in China, which supplies 80% of world's ascorbic acid.[19] American and Chinese researchers are competing to engineer a mutant that can carry out a one-pot fermentation directly from glucose to 2-KGA, bypassing both the need for a second fermentation and the need to reduce glucose to sorbitol.[20]

There exists a D-ascorbic acid, which does not occur in nature but can be synthesized artificially. To be specific, L-ascorbate is known to participate in many specific enzyme reactions that require the correct enantiomer (L-ascorbate and not D-ascorbate).[citation needed] L-Ascorbic acid has a specific rotation of [α]20
D
 = +23°.[21]

Determination

The traditional way to analyze the ascorbic acid content is the process of titration with an oxidizing agent, and several procedures have been developed.

The popular iodometry approach uses iodine in the presence of a starch indicator. Iodine is reduced by ascorbic acid, and, when all the ascorbic acid has reacted, the iodine is then in excess, forming a blue-black complex with the starch indicator. This indicates the end-point of the titration.

As an alternative, ascorbic acid can be treated with iodine in excess, followed by back titration with sodium thiosulfate using starch as an indicator.[22]

This iodometric method has been revised to exploit reaction of ascorbic acid with iodate and iodide in acid solution. Electrolyzing the solution of potassium iodide produces iodine, which reacts with ascorbic acid. The end of process is determined by potentiometric titration in a manner similar to Karl Fischer titration. The amount of ascorbic acid can be calculated by Faraday's law.

Another alternative uses N-bromosuccinimide (NBS) as the oxidizing agent, in the presence of potassium iodide and starch. The NBS first oxidizes the ascorbic acid; when the latter is exhausted, the NBS liberates the iodine from the potassium iodide, which then forms the blue-black complex with starch.

See also

Notes and references

  1. ^ Safety (MSDS) data for ascorbic acid. Oxford University
  2. ^ Story of Vitamin C's chemical discovery. Profiles.nlm.nih.gov. Retrieved on 2012-12-04.
  3. ^ Davies, Michael B.; Austin, John; Partridge, David A. (1991). Vitamin C: Its Chemistry and Biochemistry. The Royal Society of Chemistry. p. 48. ISBN 0-85186-333-7.
  4. ^ Svirbelf, Joseph Louis; Szent-Györgyi, Albert (April 25, 1932), The Chemical Nature Of Vitamin C (PDF). Part of the National Library of Medicine collection. Accessed January 2007
  5. ^ R, Caspi (Aug 19, 2009), "MetaCyc Compound: monodehydroascorbate radical", MetaCyc, retrieved 2014-12-08
  6. ^ https://books.google.com/books?id=AJW37Xc3uiAC&pg=PA311&dq=decomposition+of+ascorbic+acid
  7. ^ Seck, S.; Crouzet, J. (1981). "Formation of Volatile Compounds in Sugar-Phenylalanine and Ascorbic Acid-Phenylalanine Model Systems during Heat Treatment". Journal of Food Science. 46 (3): 790–793. doi:10.1111/j.1365-2621.1981.tb15349.x.
  8. ^ Sealock, R. R.; Goodland, R. L.; Sumerwell, W. N.; Brierly, J. M. (1952). "The Role of Ascorbic Acid in the Oxidation of l-Tyrosine by Guinea Pig Liver Extracts" (PDF). Journal of Biological Chemistry. 196 (2): 761–767. PMID 12981016.
  9. ^ UK Food Standards Agency: "Current EU approved additives and their E Numbers". Retrieved 2011-10-27.
  10. ^ US Food and Drug Administration: "Listing of Food Additives Status Part I". Archived from the original on 2012-01-17. Retrieved 2011-10-27.
  11. ^ Australia New Zealand Food Standards Code"Standard 1.2.4 – Labelling of ingredients". Retrieved 2011-10-27.
  12. ^ Widengren, J.; Chmyrov, A.; Eggeling, C.; Löfdahl, P.-Å.; Seidel, C. A. (2007). "Strategies to Improve Photostabilities in Ultrasensitive Fluorescence Spectroscopy". The Journal of Physical Chemistry A. 111 (3): 429–440. doi:10.1021/jp0646325. PMID 17228891.
  13. ^ Vitamin C, water have benefits for plastic manufacturing, Reliable Plant Magazine, 2007, archived from the original on 2007-09-27, retrieved 2007-06-25
  14. ^ Beynon, C. M.; McVeigh, J.; Chandler, M.; Wareing, M.; Bellis, M. A. (2007). "The Impact of Citrate Introduction at UK Syringe Exchange Programmes: A Retrospective Cohort Study in Cheshire and Merseyside, UK". Harm Reduction Journal. 4 (1): 21. doi:10.1186/1477-7517-4-21. PMC 2245922. PMID 18072971.
  15. ^ "The Riordan IVC Protocol for Adjunctive Cancer Care: Intravenous Ascorbate as a Chemotherapeutic and Biological Response Modifying Agent" (PDF). Riordan Clinic Research Institut. February 2013. Retrieved 2 February 2014.
  16. ^ "High-Dose Vitamin C (PDQ®): Human/Clinical Studies". National Cancer Institute. Retrieved 2 February 2014.
  17. ^ Weiss, Rick (May 20, 2007), "Tainted Chinese Imports Common", Washington Post, retrieved 2010-04-25
  18. ^ Eggersdorfer, M.; et al., "Vitamins", Ullmann's Encyclopedia of Industrial Chemistry, Weinheim: Wiley-VCH, doi:10.1002/14356007.a27_443
  19. ^ China's grip on key food additive / The Christian Science Monitor. CSMonitor.com (2007-07-20). Retrieved on 2012-12-04.
  20. ^ BASF’s description of vitamin C—developments in production methods Archived January 30, 2012, at the Wayback Machine.. competition-commission.org.uk
  21. ^ Davies, Michael B.; Austin, John A.; Partridge, David A. (1991). Vitamin C : its chemistry and biochemistry. Cambridge [Cambridgeshire]: Royal Society of Chemistry. ISBN 9780851863337.
  22. ^ "A Simple Test for Vitamin C" (PDF). School Science Review. 83 (305): 131. 2002. Archived from the original (PDF) on July 4, 2016.

Further reading

  • Clayden; Greeves; Warren; Wothers (2001), Organic Chemistry, Oxford University Press, ISBN 0-19-850346-6.
  • Davies, Michael B.; Austin, John; Partridge, David A., Vitamin C: Its Chemistry and Biochemistry, Royal Society of Chemistry, ISBN 0-85186-333-7.
  • Coultate, T. P., Food: The Chemistry of Its Components (3rd ed.), Royal Society of Chemistry, ISBN 0-85404-513-9.
  • Gruenwald, J.; Brendler, T.; Jaenicke, C., eds. (2004), PDR for Herbal Medicines (3rd ed.), Montvale, New Jersey: Thomson PDR.
  • McMurry, John (2008), Organic Chemistry (7e ed.), Thomson Learning, ISBN 978-0-495-11628-8.

External links

  • International Chemical Safety Card 0379
  • SIDS Initial Assessment Report for L-Ascorbic acid from the Organisation for Economic Co-operation and Development (OECD)
  • IPCS Poisons Information Monograph (PIM) 046
  • Interactive 3D-structure of vitamin C with details on the x-ray structure
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