Chemistry of ascorbic acid

Last updated
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)
ChEBI
ChEMBL
ChemSpider
EC Number
  • 200-066-2
E number E300 (antioxidants, ...)
KEGG
PubChem CID
UNII
  • InChI=1S/C6H8O6/c7-1-2(8)5-3(9)4(10)6(11)12-5/h2,5,7-10H,1H2/t2-,5+/m0/s1 X mark.svgN
    Key: CIWBSHSKHKDKBQ-JLAZNSOCSA-N X mark.svgN
  • OC=1C(OC(=O)C=1O)[C@@H](O)CO
  • C([C@@H]([C@@H]1C(=C(C(=O)O1)O)O)O)O
Properties
C6H8O6
Molar mass 176.124 g·mol−1
AppearanceWhite 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 Insoluble in diethyl ether, chloroform, benzene, petroleum ether, oils, fats
Solubility in ethanol 20 g/L
Solubility in glycerol 10 g/L
Solubility in propylene glycol 50 g/L
Acidity (pKa)4.10 (first), 11.6 (second)
Pharmacology
A11GA01 ( WHO ) G01AD03 ( WHO ), S01XA15 ( WHO )
Hazards
NFPA 704 (fire diamond)
NFPA 704.svgHealth 1: Exposure would cause irritation but only minor residual injury. E.g. turpentineFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
1
1
0
Lethal dose or concentration (LD, LC):
11.9 g/kg (oral, rat) [1]
Safety data sheet (SDS) JT Baker
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

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

Contents

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 encountered: 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 as a food additive and a dietary supplement for its antioxidant properties. The "d" form can be made via 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 and 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 two Nobel Prizes: in Chemistry and in Physiology or Medicine were awarded to Haworth and Szent-Györgyi, respectively.

Chemical properties

Acidity

Ascorbic acid is a furan-based lactone of 2-ketogluconic acid. It contains an adjacent enediol adjacent to the carbonyl. This −C(OH)=C(OH)−C(=O)− structural pattern is characteristic of reductones, and increases the acidity of one of the enol hydroxyl groups. The deprotonated conjugate base is the ascorbate anion, which 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 L-Semidehydroascorbinsaure.svg
Semidehydroascorbate acid radical
Dehydroascorbic acid Dehydroascorbic acid 2.svg
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
6H
7O−
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 antioxidant food additives.

Other reactions

It creates volatile compounds when mixed with glucose and amino acids at 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] the US, [10] Australia, and New Zealand. [11]

Dietary supplement

Another major use of l-ascorbic acid is as a dietary supplement. It is on the World Health Organization's List of Essential Medicines. [12]

Niche, non-food uses

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

Seventy percent of the world's supply of ascorbic acid is produced in China. [20] 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 hypochlorite  – bleaching 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%. [21]

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 70% of world's ascorbic acid. [20] Researchers are exploring means for one-step fermentation. [22] [23]

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. [24]

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

Related Research Articles

Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants are frequently added to industrial products, such as polymers, fuels, and lubricants, to extend their usable lifetimes. Foods are also treated with antioxidants to forestall spoilage, in particular the rancidification of oils and fats. In cells, antioxidants such as glutathione, mycothiol or bacillithiol, and enzyme systems like superoxide dismutase, can prevent damage from oxidative stress.

<span class="mw-page-title-main">Iodine</span> Chemical element, symbol I and atomic number 53

Iodine is a chemical element; it has symbol I and atomic number 53. The heaviest of the stable halogens, it exists at standard conditions as a semi-lustrous, non-metallic solid that melts to form a deep violet liquid at 114 °C (237 °F), and boils to a violet gas at 184 °C (363 °F). The element was discovered by the French chemist Bernard Courtois in 1811 and was named two years later by Joseph Louis Gay-Lussac, after the Ancient Greek Ιώδης, meaning 'violet'.

<span class="mw-page-title-main">Titration</span> Laboratory method for determining the concentration of an analyte

Titration is a common laboratory method of quantitative chemical analysis to determine the concentration of an identified analyte. A reagent, termed the titrant or titrator, is prepared as a standard solution of known concentration and volume. The titrant reacts with a solution of analyte to determine the analyte's concentration. The volume of titrant that reacted with the analyte is termed the titration volume.

<span class="mw-page-title-main">Vitamin C</span> Essential nutrient found in citrus fruits and other foods

Vitamin C is a water-soluble vitamin found in citrus and other fruits, berries and vegetables. It is also a generic prescription medication and in some countries is sold as a non-prescription dietary supplement. As a therapy, it is used to prevent and treat scurvy, a disease caused by vitamin C deficiency.

In chemistry, a reducing agent is a chemical species that "donates" an electron to an electron recipient . Examples of substances that are common reducing agents include hydrogen, the alkali metals, formic acid, oxalic acid, and sulfite compounds.

Redoxon is the brand name of the first artificially synthesized ascorbic acid. Redoxon was first marketed to the general public by Roche in 1934, making it the first mass-manufactured synthetic vitamin in history. The brand is now owned by German pharmaceutical company Bayer and is sold in many countries.

Iodometry, known as iodometric titration, is a method of volumetric chemical analysis, a redox titration where the appearance or disappearance of elementary iodine indicates the end point.

<span class="mw-page-title-main">Organic peroxides</span> Organic compounds of the form R–O–O–R’

In organic chemistry, organic peroxides are organic compounds containing the peroxide functional group. If the R′ is hydrogen, the compounds are called hydroperoxides, which are discussed in that article. The O−O bond of peroxides easily breaks, producing free radicals of the form RO•. Thus, organic peroxides are useful as initiators for some types of polymerization, such as the acrylic, unsaturated polyester, and vinyl ester resins used in glass-reinforced plastics. MEKP and benzoyl peroxide are commonly used for this purpose. However, the same property also means that organic peroxides can explosively combust. Organic peroxides, like their inorganic counterparts, are often powerful bleaching agents.

<span class="mw-page-title-main">Mineral ascorbates</span>

Mineral ascorbates are a group of salts of ascorbic acid. They are composed of a mineral cation bonded to ascorbate.

Irwin Stone (1907–1984) was an American biochemist, chemical engineer, and writer. He was the first to use ascorbic acid in the food processing industry as a preservative, and originated and published the hypothesis that humans require much larger amounts of Vitamin C for optimal health than is necessary to prevent scurvy.

<span class="mw-page-title-main">Ascorbyl palmitate</span> Chemical compound

Ascorbyl palmitate is an ester formed from ascorbic acid and palmitic acid creating a fat-soluble form of vitamin C. In addition to its use as a source of vitamin C, it is also used as an antioxidant food additive. It is approved for use as a food additive in the EU, the U.S., Canada, Australia, and New Zealand.

Ascorbyl stearate (C24H42O7) is an ester formed from ascorbic acid and stearic acid. In addition to its use as a source of vitamin C, it is used as an antioxidant food additive in margarine (E number E305). The USDA limits its use to 0.02% individually or in conjunction with other antioxidants.

<span class="mw-page-title-main">Sodium ascorbate</span> Chemical compound

Sodium ascorbate is one of a number of mineral salts of ascorbic acid (vitamin C). The molecular formula of this chemical compound is C6H7NaO6. As the sodium salt of ascorbic acid, it is known as a mineral ascorbate. It has not been demonstrated to be more bioavailable than any other form of vitamin C supplement.

<span class="mw-page-title-main">Potassium ascorbate</span> Chemical compound

Potassium ascorbate is a compound with formula KC6H7O6. It is the potassium salt of ascorbic acid (vitamin C) and a mineral ascorbate. As a food additive, it has E number E303, INS number 303. Although it is not a permitted food additive in the UK, USA and the EU, it is approved for use in Australia and New Zealand. According to some studies, it has shown a strong antioxidant activity and antitumoral properties.

<span class="mw-page-title-main">Potassium iodate</span> Chemical compound

Potassium iodate (KIO3) is an ionic inorganic compound with the formula KIO3. It is a white salt that is soluble in water.

<span class="mw-page-title-main">Dichlorophenolindophenol</span> Chemical compound

2,6-Dichlorophenolindophenol is a chemical compound used as a redox dye. When oxidized, DCPIP is blue with a maximal absorption at 600 nm; when reduced, DCPIP is colorless.

<span class="mw-page-title-main">Dough conditioner</span>

A dough conditioner, flour treatment agent, improving agent or bread improver is any ingredient or chemical added to bread dough to strengthen its texture or otherwise improve it in some way. Dough conditioners may include enzymes, yeast nutrients, mineral salts, oxidants and reductants, bleaching agents and emulsifiers. They are food additives combined with flour to improve baking functionality. Flour treatment agents are used to increase the speed of dough rising and to improve the strength and workability of the dough.

Unlike its lighter congeners, the halogen iodine forms a number of stable organic compounds, in which iodine exhibits higher formal oxidation states than -1 or coordination number exceeding 1. These are the hypervalent organoiodines, often called iodanes after the IUPAC rule used to name them.

The Reichstein process in chemistry is a combined chemical and microbial method for the production of ascorbic acid from D-glucose that takes place in several steps. This process was devised by Nobel Prize winner Tadeusz Reichstein and his colleagues in 1933 while working in the laboratory of the ETH in Zürich.

References

  1. ↑ Safety (MSDS) data for ascorbic acid. University of Oxford
  2. ↑ Story of Vitamin C's chemical discovery. Profiles.nlm.nih.gov. Retrieved on 2012-12-04.
  3. ↑ Davies MB, Austin J, Partridge DA (1991). Vitamin C: Its Chemistry and Biochemistry. The Royal Society of Chemistry. p. 48. ISBN   0-85186-333-7.
  4. ↑ Svirbelf JL, Szent-Györgyi A (April 25, 1932). "The Chemical Nature Of Vitamin C" (PDF). Science. 75 (1944): 357–8. Bibcode:1932Sci....75..357K. doi:10.1126/science.75.1944.357-a. PMID   17750032. S2CID   33277683.. Part of the National Library of Medicine collection. Accessed January 2007
  5. ↑ Caspi R (Aug 19, 2009). "MetaCyc Compound: monodehydroascorbate radical". MetaCyc. Retrieved 2014-12-08.
  6. ↑ Gaonkar AG, McPherson A (2016-04-19). Ingredient Interactions: Effects on Food Quality, Second Edition. CRC Press. ISBN   9781420028133.
  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 RR, Goodland RL, Sumerwell WN, Brierly JM (May 1952). "The role of ascorbic acid in the oxidation of L-Tyrosine by guinea pig liver extracts" (PDF). The Journal of Biological Chemistry. 196 (2): 761–7. doi: 10.1016/S0021-9258(19)52407-3 . 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". Food and Drug Administration . 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". 8 September 2011. Retrieved 2011-10-27.
  12. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl: 10665/371090 . WHO/MHP/HPS/EML/2023.02.
  13. ↑ Widengren J, Chmyrov A, Eggeling C, Löfdahl PA, Seidel CA (January 2007). "Strategies to improve photostabilities in ultrasensitive fluorescence spectroscopy". The Journal of Physical Chemistry A. 111 (3): 429–40. Bibcode:2007JPCA..111..429W. doi:10.1021/jp0646325. PMID   17228891.
  14. ↑ Vitamin C, water have benefits for plastic manufacturing. Reliable Plant Magazine. 2007. Archived from the original on 2007-09-27. Retrieved 2007-06-25.
  15. ↑ Beynon CM, McVeigh J, Chandler M, Wareing M, Bellis MA (December 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.
  16. ↑ "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. Archived (PDF) from the original on 2022-10-09. Retrieved 2 February 2014.
  17. ↑ "High-Dose Vitamin C (PDQ): Human/Clinical Studies". National Cancer Institute. 2013-02-08. Retrieved 2 February 2014.
  18. ↑ Strom JG, Jun HW (1993). "Effect of urine pH and ascorbic acid on the rate of conversion of methenamine to formaldehyde". Biopharmaceutics & Drug Disposition. 14 (1): 61–69. doi:10.1002/bdd.2510140106. PMID   8427945. S2CID   11151179.
  19. ↑ Nahata MC, Cummins BA, McLeod DC, Schondelmeyer SW, Butler R (1982). "Effect of urinary acidifiers on formaldehyde concentration and efficacy with methenamine therapy". European Journal of Clinical Pharmacology. 22 (3): 281–284. doi:10.1007/bf00545228. PMID   7106162. S2CID   31796137.
  20. 1 2 "Vantage Market Research: Global Vitamin C Market Size & Share to Surpass $1.8 Bn by 2028". Globe Newswire (Press release). 8 November 2022. Retrieved 21 December 2023.
  21. ↑ Eggersdorfer, M., et al. "Vitamins". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a27_443. ISBN   978-3527306732.
  22. ↑ Zhou M, Bi Y, Ding M, Yuan Y (2021). "One-Step Biosynthesis of Vitamin C in Saccharomyces cerevisiae". Front Microbiol. 12: 643472. doi: 10.3389/fmicb.2021.643472 . PMC   7947327 . PMID   33717042.
  23. ↑ Tian YS, Deng YD, Zhang WH, Yu-Wang, Xu J, et al. (August 2022). "Metabolic engineering of Escherichia coli for direct production of vitamin C from D-glucose". Biotechnol Biofuels Bioprod. 15 (1): 86. doi: 10.1186/s13068-022-02184-0 . PMC   9396866 . PMID   35996146.
  24. ↑ "A Simple Test for Vitamin C" (PDF). School Science Review. 83 (305): 131. 2002. Archived from the original (PDF) on July 4, 2016.

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