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
6
H
8
O
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
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 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 through various processes in many plants and animals.

Industrial preparation

The outdated but historically significant industrial synthesis of ascorbic acid from glucose via the Reichstein process Synthesis ascorbic acid.svg
The outdated but historically significant 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 biotechnological process, first developed in China in the 1960s but further developed in the 1990s, bypassing 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 the 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 by 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 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 the reaction of ascorbic acid with iodate and iodide in acid solution. Electrolyzing the potassium iodide solution produces iodine, which reacts with ascorbic acid. The end of the process is determined by potentiometric titration like 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 with atomic number 53 (I)

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.

<span class="mw-page-title-main">Norman Haworth</span> British chemist (1883–1950)

Sir Walter Norman Haworth FRS was a British chemist best known for his groundbreaking work on ascorbic acid while working at the University of Birmingham. He received the 1937 Nobel Prize in Chemistry "for his investigations on carbohydrates and vitamin C". The prize was shared with Swiss chemist Paul Karrer for his work on other vitamins.

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.

A scavenger in chemistry is a chemical substance added to a mixture in order to remove or de-activate impurities and unwanted reaction products, for example oxygen, to make sure that they will not cause any unfavorable reactions. Their use is wide-ranged:

<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.

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

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Further reading