Chemistry of ascorbic acid

Ascorbic acidis anorganic compoundwith formulaC6H8O6, originally calledhexuronic 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 mildreducing agent.
Ascorbic acid exists as twoenantiomers(mirror-imageisomers), commonly denoted "l" (for "levo") and "d" (for "dextro"). Thelisomer is the one most often encountered: it occurs naturally in many foods, and is one form ("vitamer") ofvitamin C, an essential nutrient for humans and many animals. Deficiency of vitamin C causesscurvy, formerly a major disease of sailors in long sea voyages. It is used as afood additiveand adietary supplementfor itsantioxidantproperties. The "d" form (erythorbic acid) can be made by chemical synthesis, but has no significant biological role.
Theantiscorbuticproperties of certain foods were demonstrated in the 18th century byJames Lind. In 1907,Axel HolstandTheodor Frølichdiscovered that the antiscorbutic factor was a water-soluble chemical substance, distinct from the one that preventedberiberi. Between 1928 and 1932,Albert Szent-Györgyiisolated a candidate for this substance, which he called "hexuronic acid", first from plants and later from animal adrenal glands. In 1932Charles Glen Kingconfirmed that it was indeed the antiscorbutic factor.
In 1933, sugar chemistWalter Norman Haworth, working with samples of "hexuronic acid" that Szent-Györgyi had isolated frompaprikaand sent him in the previous year, deduced the correct structure and optical-isomeric nature of the compound, and in 1934 reported its first synthesis.In reference to the compound's antiscorbutic properties, Haworth and Szent-Györgyi proposed to rename it "a-scorbic acid" for the compound, and later specificallyl-ascorbic acid.Because of their work, in 1937 twoNobel Prizes: in Chemistry and in Physiology or Medicine were awarded to Haworth and Szent-Györgyi, respectively.
Ascorbic acid is afuran-basedlactoneof2-ketogluconic acid. It contains an adjacentenedioladjacent to thecarbonyl. This −C(OH)=C(OH)−C(=O)− structural pattern is characteristic ofreductones, and increases the acidity of one of the enolhydroxyl groups. The deprotonatedconjugate baseis theascorbateanion, which is stabilized by electron delocalization that results fromresonancebetween two forms:
For this reason, ascorbic acid is much more acidic than would be expected if the compound contained only isolated hydroxyl groups.
The ascorbate anion formssalts, such assodium ascorbate,calcium ascorbate, andpotassium ascorbate.
Ascorbic acid can also react with organic acids as analcoholformingesterssuch asascorbyl palmitateandascorbyl stearate.
Nucleophilic attackof ascorbic acid on a proton results in a 1,3-diketone:
The ascorbate ion is the predominant species at typical biological pH values. It is a mildreducing agentandantioxidant, typically reacting with oxidants of thereactive oxygen species, such as thehydroxyl radical.
Reactive oxygen species are damaging to animals and plants at the molecular level due to their possible interaction withnucleic acids, proteins, and lipids. Sometimes these radicals initiate chain reactions. Ascorbate can terminate these chain radical reactions byelectron transfer. The oxidized forms of ascorbate are relatively unreactive and do not cause cellular damage.
Ascorbic acid and its sodium, potassium, and calciumsaltsare commonly used asantioxidantfood additives. These compounds are water-soluble and, thus, cannot protectfatsfrom oxidation: For this purpose, the fat-solubleestersof ascorbic acid with long-chainfatty acids(ascorbyl palmitate or ascorbyl stearate) can be used as antioxidant food additives. Sodium-dependent active transport process enables absorption of Ascorbic acid from the intestine.
Ascorbate readily donates a hydrogen atom tofree radicals, forming theradical anionsemidehydroascorbate (also known as monodehydroascorbate), a resonance-stabilizedsemitrione:
Loss of an electron from semidehydroascorbate to produce the 1,2,3-tricarbonyl pseudodehydroascorbate is thermodynamically disfavored, which helps prevent propagation of free radical chain reactions such asautoxidation:
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.
Semidehydroascorbate oxidation instead occurs in conjunction with hydration, yielding the bicyclichemiketaldehydroascorbate. In particular, semidehydroascorbate undergoes disproportionation to ascorbate and dehydroascorbate:
Aqueous solutions of dehydroascorbate are unstable, undergoing hydrolysis with a half-life of 5–15 minutes at 37 °C (99 °F). Decomposition products includediketogulonic acid,xylonic acid,threonic acidandoxalic acid.
It creates volatile compounds when mixed withglucoseandamino acidsat 90 °C.
It is a cofactor intyrosineoxidation, though because a crude extract of animal liver is used, it is unclear which reaction catalyzed by which enzyme is being helped here.For known roles in enzymatic reactions, seeVitamin C § Pharmacodynamics.
Because it reduces iron(III) and chelates iron ions, it enhances the oral absorption of non-heme iron.This property also applies to its enantiomer.
In 1958, it was discovered that ascorbic acid can be converted tooxalate, a key component of calcium oxalatekidney stones.The process begins with the formation ofdehydroascorbic acid(DHA) from the ascorbyl radical. While DHA can be recycled back to ascorbic acid, a portion irreversibly degrades to 2,3-diketogulonic acid (DKG), which then breaks down to both oxalate and the sugarsL-erythruloseandthreosone.Research conducted in the 1960s suggested ascorbic acid could substantially contribute to urinary oxalate content (possibly over 40%), but these estimates have been questioned due to methodological limitations.Subsequent large cohort studies have yielded conflicting results regarding the link between vitamin C intake and kidney stone formation. The overall clinical significance of ascorbic acid consumption to kidney stone risk, however, remains inconclusive, although several studies have suggested a potential association, especially with high-dose supplementation in men.
The main use ofl-ascorbic acid and its salts is as food additives, mostly to combat oxidation and prevent discoloration of the product during storage.It is approved for this purpose in the EU withE numberE300,the US,Australia, and New Zealand.
The "d" enantiomer (erythorbic acid) shares all of the non-biological chemical properties with the more commonlenantiomer. As a result, it is an equally effective food antioxidant, and is also approved in processed foods.
Another major use ofl-ascorbic acid is as adietary supplement. It is on theWorld Health Organization's List of Essential Medicines.Its deficiency over a prolonged period of time could cause scurvy, which is characterized by fatigue, widespread weakness in connective tissues and capillary fragility.It affects multiple organ systems due to its role in the biochemical reactions of connective tissue synthesis.
Naturalbiosynthesis of vitamin Coccurs through various processes in many plants and animals.
Seventy percent of the world's supply of ascorbic acid is produced in China.Ascorbic acid is prepared in industry fromglucosein a method based on the historicalReichstein process. In the first of a five-step process, glucose is catalyticallyhydrogenatedtosorbitol, which is thenoxidizedby themicroorganismAcetobactersuboxydanstosorbose. Only one of the six hydroxy groups is oxidized by this enzymatic reaction. From this point, two routes are available. Treatment of the product withacetonein the presence of an acidcatalystconverts four of the remaininghydroxylgroups toacetals. The unprotected hydroxyl group is oxidized to the carboxylic acid by reaction with the catalytic oxidantTEMPO(regenerated bysodium hypochlorite–bleachingsolution). Historically, industrial preparation via the Reichstein process usedpotassium permanganateas the bleaching solution. Acid-catalyzed hydrolysis of this product performs the dual function of removing the two acetal groups andring-closing lactonization. This step yields ascorbic acid. Each of the five steps has a yield larger than 90%.
A biotechnological process, first developed in China in the 1960s but further developed in the 1990s, bypassing acetone-protecting groups. A secondgenetically modifiedmicrobe species, such as mutantErwinia, 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.Researchers are exploring means for one-step fermentation.
The traditional way to analyze the ascorbic acid content is bytitrationwith anoxidizing agent, and several procedures have been developed.
The populariodometryapproach usesiodinein the presence of astarch 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.
This iodometric method has been revised to exploit the reaction of ascorbic acid withiodateandiodideinacidsolution. Electrolyzing the potassium iodide solution produces iodine, which reacts with ascorbic acid. The end of the process is determined bypotentiometric titrationlikeKarl Fischer titration. The amount of ascorbic acid can be calculated byFaraday's law.
Another alternative usesN-bromosuccinimide(NBS) as the oxidizing agent in the presence ofpotassium iodideand 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.