|
| | Ascorbic Acid Basic information |
| | Ascorbic Acid Chemical Properties |
| Melting point | 190-194 °C (dec.) | | alpha | 20.5 º (c=10,H2O) | | Boiling point | 227.71°C (rough estimate) | | density | 1,65 g/cm3 | | FEMA | 2109 | ASCORBIC ACID | | refractive index | 21 ° (C=10, H2O) | | storage temp. | Store at +5°C to +30°C. | | solubility | H2O: 50 mg/mL at 20 °C, clear, nearly colorless | | pka | 4.04, 11.7(at 25℃) | | form | powder | | color | white to slightly yellow | | Odor | Odorless | | PH | 3.59(1 mM solution);3.04(10 mM solution);2.53(100 mM solution); | | PH Range | 1 - 2.5 | | Odor Type | green | | optical activity | [α]25/D 19.0 to 23.0°, c = 10% in H2O | | Water Solubility | 333 g/L (20 ºC) | | Merck | 14,830 | | BRN | 84272 | | BCS Class | 1 | | Stability: | Stable. May be weakly light or air sensitive. Incompatible with oxidizing agents, alkalies, iron, copper. | | InChIKey | CIWBSHSKHKDKBQ-JLAZNSOCSA-N | | LogP | -1.85 | | CAS DataBase Reference | 50-81-7(CAS DataBase Reference) | | NIST Chemistry Reference | L-Ascorbic acid(50-81-7) | | EPA Substance Registry System | Ascorbic acid (50-81-7) |
| | Ascorbic Acid Usage And Synthesis |
| Description | Ascorbic acid, a water-soluble dietary supplement, is consumed by humans more than any other supplement. The name ascorbic means antiscurvy and denotes the ability of ascorbic to combat this disease. Vitamin C is the l-enantiomer of ascorbic acid. Ascorbic acid deficiency in humans results in the body’s inability to synthesize collagen, which is the most abundant protein in vertebrates. | | Description | L-Ascorbic acid is a naturally occurring electron donor and therefore serves as a reducing agent. It is synthesized from glucose in the liver of most mammalian species, excluding humans, non-human primates, or guinea pigs who must obtain it through dietary consumption. In humans, L-Ascorbic acid acts as an electron donor for eight different enzymes, including those related to collagen hydroxylation, carnitine synthesis (which aids in the generation of adenosine triphosphate), norepinephrine synthesis, tyrosine metabolism, and amidating peptides. L-Ascorbic acid demonstrates antioxidant activity that may be of some benefit for reducing the risk of developing chronic diseases such as cancer, cardiovascular disease, and cataracts. | | Chemical Properties | White crystals (plates or needles). Soluble in water; slightly soluble in alcohol;
insoluble in ether, chloroform, benzene, petroleum
ether, oils and fats. Stable to air when dry. One
international unit is equivalent to 0.05 milligram of
l-ascorbic acid. | | Chemical Properties | Ascorbic acid occurs as a white to light-yellow-colored, nonhygroscopic,
odorless, crystalline powder or colorless crystals with a
sharp, acidic taste. It gradually darkens in color upon exposure to
light. | | Physical properties | Appearance: white crystal or crystalline powder, and it is odorless and flavors sour. The color changes yellowish when exposed in the air for a long time. Its aqueous solution is acidic reaction. Solubility: vitamin C is soluble in water, slightly soluble in ethanol, and insoluble in chloroform or ether. Melting point: 190–192? °C.? It would decompose when it melts. Specific optical rotation: +20.5 to +21.5°. Ascorbic acid is two-base acid (the pKa is 4.1 and 11.8). It occurs mainly in the form of sodium salt and calcium salt, and its aqueous solution is strongly acidic reaction. Ascorbic acid is a strong reducing agent. | | Originator | Ascorbic aci,Natur Product,France | | History | Vitamin C is a general term for compounds having ascorbic acid activity, including ascorbic acid, dehydroascorbic acid, and its isomers.
The understanding of vitamin C has gone through a long and painful process. Although the relationship between scurvy and stored food is obvious, but the
treatments of this disease have been misguided. By 1601, British armed Captain
James Lancaster discovered the disease on the ship of the East India Company and
regarded the scurvy as “rot,” which could be made tissue alkaline.
At the early stage of the nineteenth century, the understanding and treatment of scurvy had developed to a right approach. The exposition of
scurvy etiology and metabolic theory took more than a century.
By the early stage of the twentieth century, inspired by the animal model of beriberi, researchers in the Christchurch Oslo University discovered one animal that
could suffer scurvy accidentally and then established a valuable scurvy animal
model. This experiment demonstrated that the extract isolated from lemon had antiscurvy activity. Until 1932, many research groups obtained the anti-scurvy crystal
from different plants and identified the crystal as ascorbic acid vitamin C. Next year,
the chemical structure of ascorbic acid was elucidated, and then its artificial synthesis was accomplished.
| | Uses | The starting point for synthesis of vitamin C is the selective of oxidation
of the sugar compound D-sorbit to L-sorbose using Acetobacter suboxidans
bacteria. L-sorbose is then converted to L-ascorbic acid, better
known as vitamin C. | | Uses | Sodium, potassium, and calcium salts of ascorbic acids are called ascorbates and are used as food preservatives. To make ascorbic acid fat-soluble, it can be esterified. Esters of ascorbic acid and acids, such as palmitic acid to form ascorbyl palmitate and stearic acid to form ascorbic stearate, are used as antioxidants in food, pharmaceuticals, and cosmetics. Ascorbic acid is also essential in the metabolism of some amino acids. It helps protect cells from free radical damage, helps iron absorption, and is essential for many metabolic processes. | | Uses | vitamin C is a well-known anti-oxidant. Its effect on free-radical formation when topically applied to the skin by means of a cream has not been clearly established. The effectiveness of topical applications has been questioned due to vitamin C’s instability (it reacts with water and degrades). Some forms are said to have better stability in water systems. Synthetic analogues such as magnesium ascorbyl phosphate are among those considered more effective, as they tend to be more stable. When evaluating its ability to fight free-radical damage in light of its synergistic effect with vitamin e, vitamin C shines. As vitamin e reacts with a free radical, it, in turn, is damaged by the free radical it is fighting. Vitamin C comes in to repair the free-radical damage in vitamin e, allowing e to continue with its free-radical scavenging duties. Past research has indicated that high concentrations of topically applied vitamin C are photoprotective, and apparently the vitamin preparation used in these studies resisted soap and water, washing, or rubbing for three days. More current research has indicated that vitamin C does add protection against uVB damage when combined with uVB sunscreen chemicals. This would lead one to conclude that in combination with conventional sunscreen agents, vitamin C may allow for longer-lasting, broader sun protection. Again, the synergy between vitamins C and e can yield even better results, as apparently a combination of both provides very good protection from uVB damage. However, vitamin C appears to be significantly better than e at protecting against uVA damage. A further conclusion is that the combination of vitamins C, e, and sunscreen offers greater protection than the sum of the protection offered by any of the three ingredients acting alone. Vitamin C also acts as a collagen biosynthesis regulator. It is known to control intercellular colloidal substances such as collagen, and when formulated into the proper vehicles, can have a skin-lightening effect. Vitamin C is said to be able to help the body fortify against infectious conditions by strengthening the immune system. There is some evidence (although debated) that vitamin C can pass through the layers of the skin and promote healing in tissue damaged by burns or injury. It is found, therefore, in burn ointments and creams used for abrasions. Vitamin C is also popular in anti-aging products. Current studies indicate possible anti-inflammatory properties as well. | | Uses | antiscorbutic, antiviral | | Uses | analgesic, antipyretic | | Uses | Physiological antioxidant. Coenzyme for a number of hydroxylation reactions; required for collagen synthesis. Widely distributed in plants and animals. Inadequate intake results in deficiency syndrome
s such as scurvy. Used as antimicrobial and antioxidant in foodstuffs. | | Definition | ChEBI: The L-enantiomer of ascorbic acid and conjugate acid of L-ascorbate. | | Production Methods | Ascorbic acid is prepared synthetically or extracted from various
vegetable sources in which it occurs naturally, such as rose hips,
blackcurrants, the juice of citrus fruits, and the ripe fruit of
Capsicum annuum L. A common synthetic procedure involves the
hydrogenation of D-glucose to D-sorbitol, followed by oxidation
using Acetobacter suboxydans to form L-sorbose. A carboxyl group
is then added at C1 by air oxidation of the diacetone derivative of Lsorbose
and the resulting diacetone-2-keto-L-gulonic acid is
converted to L-ascorbic acid by heating with hydrochloric acid. | | Production Methods | Ascorbic acid is produced synthetically using the Reichstein process, which has been the standard method of production since the 1930s. The process starts with fermentation followed by chemical synthesis. The first step involves reduction of D-glucose at high temperature into D-sorbitol. D-sorbitol undergoes bacterial fermentation, converting it into L-sorbose. L-sorbose is then reacted with acetone in the presence of concentrated sulfuric acid to produce diacetone-L-sorbose, which is then oxidized with chlorine and sodium hydroxide to produce di-acetone-ketogulonic acid (DAKS). DAKS is then esterified with an acid catalyst and organics to give a gulonic acid methylester. The latter is heated and reacted with alcohol to produce crude ascorbic acid, which is then recrystallized to increase its purity. Since the development of the Reichstein process more than 70 years ago, it has undergone many modifications. In the 1960s, a method developed in China referred to as the two-stage fermentation process used a second fermentation stage of L-sorbose to produce a different intermediate than DAKS called KGA (2-keto-L-gulonic acid), which was then converted into ascorbic acid. The two stage process relies less on hazardous chemicals and requires less energy to convert glucose to ascorbic acid. | | Indications | Vitamin C (ascorbic acid) is essential for the maintenance
of the ground substance that binds cells together
and for the formation and maintenance of collagen.The
exact biochemical role it plays in these functions is not
known, but it may be related to its ability to act as an
oxidation–reduction system. | | Manufacturing Process | D-Glucose was reduced to the D-sorbitol with a hydrogen over Ni Raney, then
it was turned into the L-sorbose with the acetobacter suboxydans and the
hydroxyl groups of L-sorbose were protected with acetone treatment yielded
the diaceton-L-sorbose. Subsequent treatment with NaOCl/Raney Ni produced
di-O-isopropylidene-2-oxo-L-gulonic acid. Partial hydrolysis with aqueous HCl
gave deprotected 2-oxo-L-gulonic acid, which yielded ascorbinic acid by
heating with HCl. | | Brand name | Ascorbin (Marion Merrell Dow). | | Therapeutic Function | Vitamin | | General Description | Scurvy (from the French word scorbutus) has been recognized as a disease afflicting mankind for thousands of years. Citrus fruits such as oranges, lemons, and limes were later identified as equally effective treatments. Only within the last 100 years has a deficiency in vitamin C been definitively identified as the cause of scurvy. In 1932, Waugh and King isolated crystalline vitamin C from lemon juice and showed it to be the antiscorbutic factor present in each of these treatments.
The structure and chemical formula of vitamin C was identified in 1933 by Hirst et al.Because humans are one of the few animal species that cannot synthesize vitamin C, it has to be available as a dietary component. Dietary sources of ascorbic acid include fruits (especially citrus fruits), vegetables (especially peppers), and potatoes. Although the sources of some commercial products are rose hips and citrus fruits, most ascorbic acid is prepared synthetically.
Vitamin C is now commonly referred to as ascorbic acid because of its acidic character and its effectiveness in the treatment and prevention of scorbutus (scurvy). The acidic character is because of the two enolic hydroxyls; the C3 hydroxyl has a pKa value of 4.1, and the C2 hydroxyl has a pKa of 11.6. All biological activities reside in L-ascorbic acid; therefore, all references to vitamin C, ascorbic acid, ascorbate, and their derivatives refer to this form. The monobasic sodium salt is the usual salt form. | | General Description | White to very pale yellow crystalline powder with a pleasant sharp acidic taste. Almost odorless. | | Air & Water Reactions | May be sensitive to prolonged exposure to air and light. Sensitive to moisture. Soluble in water. Aqueous solutions are oxidized by air in a reaction that is accelerated by alkalis, iron and copper. The rate depends on the pH and on oxygen concentration. Also subject to degradation under anaerobic conditions. | | Reactivity Profile | L(+)-Ascorbic acid is a lactone. Reacts as a relatively strong reducing agent and decolorizes many dyes. Forms stable metal salts. Incompatible with oxidizers, dyes, alkalis, iron and copper. Also incompatible with ferric salts and salts of heavy metals, particularly copper, zinc and manganese . | | Fire Hazard | Flash point data for L(+)-Ascorbic acid are not available; however, L(+)-Ascorbic acid is probably combustible. | | Pharmaceutical Applications | Ascorbic acid is used as an antioxidant in aqueous pharmaceutical
formulations at a concentration of 0.01–0.1% w/v. Ascorbic acid
has been used to adjust the pH of solutions for injection, and as an
adjunct for oral liquids. It is also widely used in foods as an
antioxidant. Ascorbic acid has also proven useful as a stabilizing
agent in mixed micelles containing tetrazepam. | | Biochem/physiol Actions | L-ascorbic acid mainly exhibits antioxidant properties. It protects plants from oxidative stress and mammals from diseases associated with oxidative stress. L-ascorbic acid mainly protects from hydroxyl radicals, superoxide and singlet oxygen. In addition, it also reduces the membrane-linked antioxidant α-tocopherol (oxidised form). L-Ascorbic acid enhances endothelium-dependent vasodilation in various disorders, including diabetes, coronary artery disease, hypertension and chronic heart failure. | | Pharmacology | Vitamin C is considered as a classical enzyme cofactor or antioxidant but also as a transition material in metal ion reaction. And all of these functions of vitamin C are related to the property of antioxidation. | | Clinical Use | Vitamin C is indicated for the treatment and prevention of known or suspect deficiency. Although scurvy occurs infrequently, it is seen in the elderly, infants, alcoholics, and drug users.Ascorbate can also be used to enhance absorption of dietary nonheme iron or iron supplements. Ascorbic acid (but not the sodium salt) was historically used to acidify the urine as a result of excretion of unchanged ascorbic acid, although this use has fallen into disfavor. Ascorbate also increases iron chelation by deferoxamine, explaining its use in the treatment of iron toxicity. | | Clinical Use | Vitamin C is found in fresh fruit and vegetables. It is
very water soluble, is readily destroyed by heat, especially
in an alkaline medium, and is rapidly oxidized in
air. Fruit and vegetables that have been stored in air, cut
or bruised, washed, or cooked may have lost much of
their vitamin C content.
The deficiency disease associated with a lack of
ascorbic acid is called scurvy. Early symptoms include
malaise and follicular hyperkeratosis. Capillary fragility
results in hemorrhages, particularly of the gums.
Abnormal bone and tooth development can occur in
growing children.The body’s requirement for vitamin C
increases during periods of stress, such as pregnancy
and lactation. | | Side effects | Megavitamin intake of vitamin C may result in diarrhea
due to intestinal irritation. Since ascorbic acid is
partially metabolized and excreted as oxalate, renal oxalate
stones may form in some patients. | | Toxicology | L-Ascorbic acid, or vitamin C, is widely present in plants. The structures of ascorbic acid and dehydroascorbic acid are shown in Figure 10.5. Vitamin C is not only an important nutrient but is also used as an antioxidant in various foods. However, it is not soluble in fat and is unstable under basic conditions. Vitamin C reduces cadmium toxicity and excess doses prolong the retention time of an organic mercury compound in a biological system. Overdoses of vitamin C (106 g) induce perspiration, nervous tension, and lowered pulse rate. WHO recommends that daily intake be less than 0.15 mg/kg. Toxicity due to ascorbic acid has not been reported. Although repeated intravenous injections of 80 mg dehydroascorbic acid was reported to be diabetogenic in rats, oral consumption of 1.5 g/day of ascorbic acid for six weeks had no effect on glucose tolerance or glycosuria in 12 normal adult males and produced no change in blood glucose concentrations in 80 diabetics after five days. The same report noted that a 100-mg intravenous dose of dehydroascorbic acid given daily for prolonged periods produced no signs of diabetes. Ascorbic acid is readily oxidized to dehydroascorbic acid, which is reduced by glutathione in blood. | | Safety Profile | Moderately toxic by
ingestion and intravenous routes. Human
systemic effects by intravenous route: blood,
changes in tubules (including acute renal
failure, acute tubular necrosis). An
experimental teratogen. Other experimental
reproductive effects. Mutation data
reported. When heated to decomposition it
emits acrid smoke and irritating fumes. | | Safety | Ascorbic acid is an essential part of the human diet, with 40 mg
being the recommended daily dose in the UK and 60 mg in the
USA. However, these figures are controversial, with some
advocating doses of 150 or 250mg daily. Megadoses of 10 g daily
have also been suggested to prevent illness although such large
doses are now generally considered to be potentially harmful.
The body can absorb about 500 mg of ascorbic acid daily with
any excess immediately excreted by the kidneys. Large doses may
cause diarrhea or other gastrointestinal disturbances. Damage to
the teeth has also been reported. However, no adverse effects
have been reported at the levels employed as an antioxidant in
foods, beverages, and pharmaceuticals. The WHO has set an
acceptable daily intake of ascorbic acid, potassium ascorbate, and
sodium ascorbate, as antioxidants in food, at up to 15 mg/kg bodyweight
in addition to that naturally present in food.
LD50 (mouse, IV): 0.52 g/kg
LD50 (mouse, oral): 3.37 g/kg
LD50 (rat, oral): 11.9 g/kg | | target | p53 | DNA/RNA Synthesis | Mdm2 | | Metabolism | Ascorbic acid is reversibly oxidised to dehydroascorbic
acid; some is metabolised to ascorbate-2-sulfate, which is
inactive, and oxalic acid which are excreted in the urine.
Ascorbic acid in excess of the body's needs is also rapidly
eliminated unchanged in the urine; this generally occurs
with intakes exceeding 100 mg daily. | | storage | In powder form, ascorbic acid is relatively stable in air. In the
absence of oxygen and other oxidizing agents it is also heat stable.
Ascorbic acid is unstable in solution, especially alkaline solution,
readily undergoing oxidation on exposure to the air.The
oxidation process is accelerated by light and heat and is catalyzed by
traces of copper and iron. Ascorbic acid solutions exhibit maximum
stability at about pH 5.4. Solutions may be sterilized by filtration.
The bulk material should be stored in a well-closed nonmetallic
container, protected from light, in a cool, dry place. | | Purification Methods | Crystallise it from MeOH/Et2O/pet ether [Herbert et al. J Chem Soc 1270 1933]. [Beilstein 18/5 V 26.] | | Toxicity evaluation | Metabolism of ascorbic acid can lead to deposition of oxalate
crystals in kidney tissue. Reduction of carcinogenic Cr(VI) by
ascorbic acid generates ascorbate–Cr(III)–DNA cross-links that
have been linked to mutagenicity and the formation of DNA
lesions. Uranyl acetate–ascorbate has also been shown to nick
plasmid DNA. | | Incompatibilities | Incompatible with alkalis, heavy metal ions, especially copper and
iron, oxidizing materials, methenamine, phenylephrine hydrochloride,
pyrilamine maleate, salicylamide, sodium nitrite, sodium
salicylate, theobromine salicylate, and picotamide. Additionally,
ascorbic acid has been found to interfere with certain colorimetric
assays by reducing the intensity of the color produced. | | Regulatory Status | GRAS listed. Accepted for use as a food additive in Europe.
Included in the FDA Inactive Ingredients Database (inhalations,
injections, oral capsules, suspensions, tablets, topical preparations,
and suppositories). Included in medicines licensed in the UK.
Included in the Canadian List of Acceptable Non-medicinal
Ingredients. |
| | Ascorbic Acid Preparation Products And Raw materials |
|
