Salicylic acid is an organic compound with the formula HOC6H4COOH.[ A colorless (or white), bitter-tasting solid, it is a precursor to and a metabolite of acetylsalicylic acid (aspirin).][ It is a plant hormone,][
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Uses
Medicine
Salicylic acid as a medication is commonly used to remove the outermost layer of the skin. As such, it is used to treat , psoriasis, acne vulgaris, ringworm, dandruff, and ichthyosis.
Similar to other hydroxy acids, salicylic acid is an ingredient in many skincare products for the treatment of seborrhoeic dermatitis, acne, psoriasis, , corns, keratosis pilaris, acanthosis nigricans, ichthyosis, and warts.
Uses in manufacturing
Salicylic acid is used as a food preservative, a bactericide, and an antiseptic.
Salicylic acid is used in the production of other pharmaceuticals, including 4-aminosalicylic acid, sulpiride, and landetimide (via salethamide).
Salicylic acid has long been a key starting material for making acetylsalicylic acid (ASA or aspirin).[ ASA is prepared by the acetylation of salicylic acid with the acetyl group from acetic anhydride or acetyl chloride.]
Bismuth subsalicylate, a salt of bismuth and salicylic acid, "displays anti-inflammatory action (due to salicylic acid) and also acts as an antacid and mild antibiotic".
Other derivatives include methyl salicylate, used as a liniment to soothe joint and muscle pain, and choline salicylate, which is used topically to relieve the pain of aphthous ulcer.
Sodium salicylate is a useful phosphor in the vacuum ultraviolet spectral range, with nearly flat quantum efficiency for wavelengths between 10 and 100 nm.[Samson, James (1976). Techniques of Vacuum Ultraviolet Spectroscopy. Wiley, .] It fluoresces in the blue at 420 nm. It is easily prepared on a clean surface by spraying a saturated solution of the salt in methanol followed by evaporation.
Mechanism of action
Salicylic acid modulates COX-1 enzymatic activity to decrease the formation of pro-inflammatory Prostaglandin. Salicylate may competitively inhibit prostaglandin formation.
Salicylic acid, when applied to the skin surface, works by causing the cells of the epidermis to slough off more readily, preventing pores from clogging up, and allowing room for new cell growth. Salicylic acid inhibits the oxidation of uridine-5-diphosphoglucose (UDPG) competitively with NADH and noncompetitively with UDPG. It also competitively inhibits the transferring of glucuronyl group of uridine-5-phosphoglucuronic acid to the phenolic acceptor.
The wound-healing retardation action of salicylates is probably due mainly to its inhibitory action on mucopolysaccharide synthesis.
Safety
If high concentrations of salicylic ointment are used topically, high levels of salicylic acid can enter the blood. In such cases , hemodialysis would be required to avoid further complications.
Cosmetic applications of the drug pose no significant risk.[ Since oral aspirin (which produces much higher salicylic acid plasma concentrations than dermal salicylic acid applications) poses no significant adverse pregnancy outcomes in terms of frequency of stillbirth, birth defects or developmental delay, use of salicylic acid containing cosmetics is safe for pregnant women.][ Salicylic acid is present in most fruits and vegetables as for example in greatest quantities in Berry and in beverages like tea.
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Production and chemical reactions
Biosynthesis
Salicylic acid is biosynthesis from the amino acid phenylalanine. In Arabidopsis thaliana, it can be synthesized via a phenylalanine-independent pathway.
Chemical synthesis
Commercial vendors prepare sodium salicylate by treating sodium phenolate (the sodium salt of phenol) with carbon dioxide at high pressure (100atm) and high temperature (115°C) – a method known as the Kolbe-Schmitt reaction. Acidifying the product with sulfuric acid gives salicylic acid:
At the laboratory scale, it can also be prepared by the hydrolysis of aspirin (acetylsalicylic acid)
Reactions
Upon heating, salicylic acid converts to phenyl salicylate:[
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Further heating gives xanthone.[
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Salicylic acid as its conjugate base is a chelating agent, with an affinity for iron(III).
Salicylic acid slowly degrades to phenol and carbon dioxide at 200–230 °C:
All isomers of chlorosalicylic acid and of dichlorosalicylic acid are known. 5-Chlorosalicylic acid is produced by direct chlorination of salicylic acid.[
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History
Willow has long been used for medicinal purposes. Dioscorides, whose writings were highly influential for more than 1,500 years,
Hippocrates, Galen, Pliny the Elder, and others knew that decoctions containing salicylate could ease pain and reduce fevers.
It was used in Europe and China to treat these conditions.
The Cherokee and other Native Americans use an infusion of the bark for fever and other medicinal purposes.[ Cited in A search of this database for "salix AND medicine" finds 63 entries.] In 2014, archaeologists identified traces of salicylic acid on seventh-century pottery fragments found in east-central Colorado.
Edward Stone, a vicar from Chipping Norton, Oxfordshire, England, reported in 1763 that the bark of the willow was effective in reducing a fever.
An extract of willow bark, called salicin, after the Latin name for the white willow ( Salix alba), was isolated and named by Germans chemist Johann Andreas Buchner in 1828.[
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A report on Leroux's presentation to the French Academy of Sciences also appeared in:
Raffaele Piria, an Italy chemist, was able to convert the substance into a sugar and a second component, which on oxidation becomes salicylic acid.[ Piria mentions "Hydrure de salicyle" (hydrogen salicylate, i.e., salicylic acid).][ Löwig and Weidman called salicylic acid Spiräasäure (spiraea acid).] Their extract caused digestive problems such as gastric irritation, bleeding, diarrhea, and even death when consumed in high doses.
In 1874 the Scottish physician Thomas MacLagan experimented with salicin as a treatment for acute rheumatism, with considerable success, as he reported in The Lancet in 1876.
In 1979, salicylates were found to be involved in induced defenses of tobacco against tobacco mosaic virus.
Dietary sources
Salicylic acid occurs in plants as free salicylic acid and its carboxylated esters and phenolic glycosides. Several studies suggest that humans metabolize salicylic acid in measurable quantities from these plants.
Some people with sensitivity to dietary salicylates may have symptoms of allergic reaction, such as bronchial asthma, rhinitis, gastrointestinal disorders, or diarrhea, so may need to adopt a low-salicylate diet.[
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Plant hormone
Salicylic acid is a natural phenol phytohormone, and is found in plants with roles in plant growth and development, photosynthesis, transpiration, and ion uptake and transport.
Exogeny, salicylic acid can aid plant development via enhanced seed germination, bud flowering, and fruit ripening, though too high of a concentration of salicylic acid can negatively regulate these developmental processes.
The volatile methyl ester of salicylic acid, methyl salicylate, can also diffuse through the air, facilitating plant-plant communication.
Signal transduction
A number of proteins have been identified that interact with SA in plants, especially salicylic acid binding proteins (SABPs) and the NPR genes (nonexpressor of pathogenesis-related genes), which are putative receptors.[Kumar, D. 2014. Salicylic acid signaling in disease resistance. Plant Science 228:127–134.]
Further reading
External links
