Salicylic acid (from the Latin word for the willow tree,
Salix, from whose bark it can be obtained) is a
beta hydroxy acidA beta hydroxy acid is an organic compound which contains a carboxylic acid functional group and hydroxy functional group separated by two carbon atoms...
. This colorless crystalline organic
acidAn acid is traditionally considered any chemical compound that, when dissolved in water, gives a solution with a hydrogen ion activity greater than in pure water, i.e. a pH less than 7.0...
is widely used in
organic synthesisOrganic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
and functions as a
plant hormonePlant hormones are chemicals that regulate plant growth, which, in the UK, are termed 'plant growth substances'. Plant hormones are signal molecules produced within the plant, and occur in extremely low concentrations. Hormones regulate cellular processes in targeted cells locally and when moved...
. It is derived from the metabolism of salicin. In addition to being a compound that is chemically similar to but not identical to the active component of
aspirinAspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication....
(
acetylsalicylic acid), it is probably best known for its use in anti-acne treatments. The salts and
esterEsters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
s of salicylic acid are known as
salicylates.
Chemistry
Salicylic acid has the
formulaA chemical formula or molecular formula is a way of expressing information about the atoms that constitute a particular chemical compound....
C
6H
4(OH)COOH, where the OH group is adjacent to the
carboxyl groupCarboxylic acids are organic acids characterized by the presence of a carboxyl group, which has the formula -COH, usually written -COOH or -CO2H. Carboxylic acids are Brønsted-Lowry acids — they are proton donors. Salts and anions of carboxylic acids are called...
. It is poorly soluble in water (0.2 g/100 ml H
2O at 20 °C).
AspirinAspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication....
(acetylsalicylic acid or ASA) can be prepared by the
esterificationEsterification is the general name for a chemical reaction in which two reactants form an ester as the reaction product. Esters are common in organic chemistry and biological materials, and often have a characteristic pleasant, fruity odor. This leads to their extensive use in the fragrance and...
of the
phenolPhenol, also known as carbolic acid, is a toxic, white crystalline solid. Its chemical formula is C6H5OH and its structure is that of a hydroxyl group bonded to a phenyl ring, making it an aromatic compound.-Phenols:...
ic hydroxyl group of salicylic acid.
Plant hormone
Salicylic acid (SA) is a
phenolPhenol, also known as carbolic acid, is a toxic, white crystalline solid. Its chemical formula is C6H5OH and its structure is that of a hydroxyl group bonded to a phenyl ring, making it an aromatic compound.-Phenols:...
ic phytohormone and is found in plants with roles in plant growth and development,
photosynthesisPhotosynthesis is a process that converts carbon dioxide into organic compounds, especially sugars, using the energy from sunlight. Photosynthesis occurs in plants, algae, and many species of Bacteria, but not in Archaea...
,
transpirationTranspiration is the evaporation of water from the aerial parts of plants, especially leaves but also stems, flowers and roots. Leaf surfaces are dotted with openings called stoma that are bordered by guard cells. Collectively the structures are called stomata...
,
ionAn ion is an atom or molecule where the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge...
uptake and transport. SA also induces specific changes in leaf anatomy and
chloroplastChloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.The word chloroplast is...
structure. SA is involved in
endogenousThe word endogenous means "proceeding from within", the opposite of exogenous.-Biology:Endogenous substances are those that originate from within an organism, tissue, or cell . Endogenous retrovirus are caused by ancient infections of germ cells in humans, mammals and other vertebrates...
signaling, mediating in plant defense against pathogens. It plays a role in the resistance to pathogens by inducing the production of pathogenesis-related proteins. It is involved in the
systemic acquired resistanceIn plants, systemic acquired resistance is a "whole-plant" resistance response that occurs following an earlier localized exposure to a pathogen. SAR is analogous to the innate immune system found in animals, and there is evidence that SAR in plants and innate immunity in animals may be...
(SAR) in which a pathogenic attack on one part of the plant induces resistance in other parts. The signal can also move to nearby plants by salicyclic acid being converted to the volatile ester,
methyl salicylateMethyl salicylate is a natural product of many species of plants. Some of the plants producing it are called wintergreens, hence the common name.-Botanical background:...
.
Production
Salicylic acid is an organic acid
biosynthesizeBiosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
d from the amino acid
phenylalaninePhenylalanine is an α-amino acid with the formula HO
2CCHCH
2C
6H
5. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. The codons for
L-phenylalanine are UUU and UUC...
.
Sodium salicylateSodium salicylate is a sodium salt of salicylic acid. It can be prepared from sodium phenolate and carbon dioxide under higher temperature and pressure...
is commercially prepared by treating sodium phenolate (the sodium salt of
phenolPhenol, also known as carbolic acid, is a toxic, white crystalline solid. Its chemical formula is C6H5OH and its structure is that of a hydroxyl group bonded to a phenyl ring, making it an aromatic compound.-Phenols:...
) with
carbon dioxideCarbon dioxide is a chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom. It is a gas at standard temperature and pressure and exists in Earth's atmosphere in this state...
at high pressure (100 atm) and high temperature (390K) -a method known as the
Kolbe-Schmitt reactionThe Kolbe-Schmitt reaction/Kolbe process is a carboxylation chemical reaction that proceeds by heating sodium phenolate with carbon dioxide under pressure , then treating the product with sulfuric acid...
. Acidification of the product with
sulfuric acidSulfuric acid, , is a strong mineral acid. It is soluble in water at all concentrations. Sulfuric acid has many applications, and is one of the top products of the chemical industry. World production in 2001 was 165 million tonnes, with an approximate value of US$8 billion...
gives salicylic acid:
It can also be prepared by the
hydrolysisHydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions, which may go on to participate in further reactions. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization...
of
AspirinAspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication....
(acetylsalicylic acid) or
methyl salicylateMethyl salicylate is a natural product of many species of plants. Some of the plants producing it are called wintergreens, hence the common name.-Botanical background:...
(Oil of Wintergreen) with a strong acid or base.
History
The Greek physician
HippocratesHippocrates of Cos or Hippokrates of Kos - Greek: ; Hippokrátēs was an ancient Greek physician of the Age of Pericles, and was considered one of the most outstanding figures in the history of medicine...
wrote in the 5th century BC about a bitter powder extracted from
willowWillows, sallows, and osiers form the genus Salix, around 400 species of deciduous trees and shrubs, found primarily on moist soils in cold and temperate regions of the Northern Hemisphere...
bark that could ease aches and pains and reduce fevers. This remedy was also mentioned in texts from ancient
SumerSumer was a civilization and historical region in southern Iraq . It is the earliest known civilization in the world and is known as the Cradle of Civilization...
,
LebanonLebanon , officially the Republic of Lebanon
[Republic of Lebanon is the most common term used by Lebanese government agencies...]
, and
AssyriaAssyria was a civilization centered on the Upper Tigris river, in Mesopotamia , that came to rule regional empires a number of times in history. It was named for its original capital, the ancient city of Assur...
. The
CherokeeThe Cherokee are a Native American people from the Southeastern United States...
and other Native Americans used an infusion of the bark for fever and other medicinal purposes for centuries. The medicinal part of the plant is the inner bark and was used as a pain reliever for a variety of ailments. The Reverend Edward (Edmund) Stone, a vicar from
Chipping Norton, OxfordshireChipping Norton is a town in the Cotswold Hills in Oxfordshire, England, about southwest of Banbury. It is the highest town above sea level in Oxfordshire.-History until the 17th century:...
,
EnglandEngland is a country that is part of the United Kingdom. It shares land borders with Scotland to the north and Wales to the west; the Irish Sea is to the north west, the Celtic Sea to the south west and the North Sea to the east, with the English Channel to the south separating it from continental...
, noted in 1763 that the bark of the willow was effective in reducing a fever.
The active extract of the bark, called
salicin, after the
LatinLatin is an Italic language originally spoken in Latium and Ancient Rome. Through the Roman conquest, Latin spread throughout the Mediterranean and a large part of Europe...
name for the white willow (
Salix alba), was isolated in crystalline form in 1828 by Henri Leroux, a
FrenchFrance , officially the French Republic , is a country located in Western Europe, with several overseas islands and territories located on other continents. Metropolitan France extends from the Mediterranean Sea to the English Channel and the North Sea, and from the Rhine to the Atlantic Ocean...
pharmacist, and Raffaele Piria, an
ItalianItaly , officially the Italian Republic , is a country located on the Italian Peninsula in Southern Europe and on the two largest islands in the Mediterranean Sea, Sicily and Sardinia. Italy shares its northern, Alpine boundary with France, Switzerland, Austria and Slovenia...
chemist. Piria was able to convert the substance into a sugar and a second component, which on oxidation becomes salicylic acid.
Salicylic acid was also isolated from the herb
meadowsweetFilipendula ulmaria, commonly known as Meadowsweet, is a perennial herb in the family Rosaceae, which grows in damp meadows. It is native throughout most of Europe and western Asia though it has been successfully introduced and naturalized in North America.Meadowsweet has also been referred to as...
(
Filipendula ulmariaFilipendula is a genus of 12 species of perennial herbaceous flowering plants in the family Rosaceae, native to the temperate regions of the Northern Hemisphere. Well-known species include Meadowsweet and Dropwort , both native to Europe, and Queen-of-the-forest and Queen-of-the-prairie...
, formerly classified as
Spiraea ulmariaSpiraea , or meadowsweet, is a genus of about 80-100 species of shrubs in the family Rosaceae, subfamily Spiraeoideae. They are native to the temperate Northern Hemisphere, with the greatest diversity in eastern Asia....
) by German researchers in 1839. While their extract was somewhat effective, it also caused digestive problems such as gastric irritation, bleeding,
diarrheaIn medicine, diarrhea , also spelled diarrhoea , is the condition of having frequent loose or liquid bowel movements. Acute diarrhea is a common cause of death in developing countries and the second most common cause of infant deaths worldwide...
, and even death when consumed in high doses.
Medicinal and cosmetic uses
Salicylic acid is known for its ability to ease aches and pains and reduce
feverFever is a frequent medical sign that describes an increase in internal body temperature to levels above normal...
s. These medicinal properties, particularly fever relief, have been known since ancient times, and it was used as an anti-inflammatory drug.
In modern medicine, salicylic acid and its derivatives are used as constituents of some
rubefacientA rubefacient is a substance for external application that produces redness of the skin e.g. by causing dilation of the capillaries and an increase in blood circulation....
products. For example,
methyl salicylateMethyl salicylate is a natural product of many species of plants. Some of the plants producing it are called wintergreens, hence the common name.-Botanical background:...
is used as a
linimentLiniment, from the Latin linere, to anoint, is a medicated topical preparation for application to the skin. Preparations of this type are also called balm...
to soothe joint and muscle pain, and choline salicylate is used topically to relieve the pain of
aphthous ulcerAn aphthous ulcer, also known as a canker sore, is a type of oral ulcer, which presents as a painful open sore inside the mouth or upper throat caused by a break in the mucous membrane...
s.
As with other
beta hydroxy acidA beta hydroxy acid is an organic compound which contains a carboxylic acid functional group and hydroxy functional group separated by two carbon atoms...
s, salicylic acid is a key ingredient in many skin-care products for the treatment of
acneAcne vulgaris is a common skin condition, caused by changes in pilosebaceous units, skin structures consisting of a hair follicle and its associated sebaceous gland, via androgen stimulation. It is characterized by noninflammatory follicular papules or comedones and by inflammatory papules,...
,
psoriasisPsoriasis is a chronic, non-contagious autoimmune disease that affects the skin and joints. It commonly causes red, scaly patches to appear on the skin. The scaly patches caused by psoriasis, called psoriatic plaques, are areas of inflammation and excessive skin production. Skin rapidly...
,
callusA callus is an especially toughened area of skin which has become relatively thick and hard in response to repeated friction, pressure, or other irritation. Rubbing that is too frequent or forceful will cause blisters rather than allow calluses to form. Since repeated contact is required,...
es,
cornsA callus is an especially toughened area of skin which has become relatively thick and hard in response to repeated friction, pressure, or other irritation. Rubbing that is too frequent or forceful will cause blisters rather than allow calluses to form. Since repeated contact is required,...
,
keratosis pilarisKeratosis pilaris is a very common genetic follicular condition that is manifested by the appearance of rough bumps on the skin, hence referred to as chicken skin...
, and
wartA wart is generally a small, rough tumor, typically on hands and feet but often other locations, that can resemble a cauliflower or a solid blister. Warts are common, and are caused by a viral infection, specifically by the human papillomavirus and are contagious when in contact with the skin of...
s. It works as a
keratolyticKeratolytic therapy is treatment to remove warts and other lesions in which the epidermis produces excess skin. In this therapy, acid medicine, such as salicylic acid is put on the lesion. Keratolytic therapy thins the skin on and around the lesion...
by causing the cells of the
epidermisThe epidermis is the outer layer of the skin, composed of terminally differentiated stratified squamous epithelium, acting as the body's major barrier against an inhospitable environment...
to shed more readily, preventing
poresThe sebaceous glands are microscopic glands in the skin which secrete an oily/waxy matter, called sebum, to lubricate the skin and hair of animals. In humans, they are found in greatest abundance on the face and scalp, though they are distributed throughout all skin sites except the palms and...
from clogging up, and allowing room for new cell growth. Because of its effect on skin cells, salicylic acid is used in several
shampooShampoo is a hair care product used for the removal of oils, dirt, skin particles, dandruff, environmental pollutants and other contaminant particles that gradually build up in hair...
s used to treat
dandruffDandruff is the excessive shedding of dead skin cells from the scalp. Dandruff can also be caused by frequent exposure to extreme heat and cold. As it is normal for skin cells to die and flake off, a small amount of flaking is normal and in fact quite common...
. Use of concentrated solutions of salicylic acid may cause
hyperpigmentationIn dermatology, hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin.-Causes:Hyperpigmentation may be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris...
on unpretreated skin for those with darker skin types (
FitzpatrickThe Fitzpatrick Scale is a numerical classification schema for the color of skin. It was developed in 1975 by T.B. Fitzpatrick, a Harvard dermatologist, as a way to classify the response of different types of skin to UV light...
phototypes IV, V, VI), as well as with the lack of use of a broad spectrum sunblock.
Bismuth subsalicylateBismuth subsalicylate, with a chemical formula C7H5BiO4, is a drug used to treat nausea, heartburn, indigestion, diarrhea, and other temporary discomforts of the stomach and gastrointestinal tract...
, a salt of
bismuthBismuth is a chemical element that has the symbol Bi and atomic number 83. This trivalent poor metal chemically resembles arsenic and antimony. Bismuth is heavy and brittle; it has a silvery white color with a pink tinge owing to the surface oxide. Bismuth is the most naturally diamagnetic of all...
and salicyclic acid, is the active ingredient in stomach relief aids such as
Pepto-BismolPepto-Bismol is an over-the-counter drug currently produced by the Procter and Gamble company in the United States of America and in Canada to treat minor digestive system upset. Its active ingredient is bismuth subsalicylate, which is also responsible for its distinctive pink color...
. Bismuth subsalicylate helps control
diarrheaIn medicine, diarrhea , also spelled diarrhoea , is the condition of having frequent loose or liquid bowel movements. Acute diarrhea is a common cause of death in developing countries and the second most common cause of infant deaths worldwide...
, nausea, heartburn, and gas. It is also a very mild
antibioticIn common usage, an antibiotic is a substance or compound that kills or inhibits the growth of bacteria...
.
Other uses
- Although toxic in large quantities, salicylic acid is used as a food preservative. For some people with salicylate sensitivity
Salicylate sensitivity, also known as salicylate intolerance, is any adverse effect that occurs when a normal amount of salicylate is introduced into a person's body...
even these small doses can be harmful.
- Sodium salicylate
Sodium salicylate is a sodium salt of salicylic acid. It can be prepared from sodium phenolate and carbon dioxide under higher temperature and pressure...
is a useful phosphorA phosphor is a substance that exhibits the phenomenon of phosphorescence ....
in the vacuum ultraviolet with nearly flat quantum efficiency for wavelengths between 10 to 100 nm. 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 methanolMethanol, also known as methyl alcohol, wood alcohol, wood naphtha or wood spirits, is a chemical with formula CH3OH . It is toxic: drinking 10 ml will cause blindness, and as little as 100 ml will cause death...
followed by evaporation.
Safety
Salicylic acid has an ototoxic effect by inhibiting
prestinPrestin is the motor protein of the outer hair cells of the inner ear of the mammalian cochlea. It is highly expressed in the outer hair cells, and is not expressed in the nonmotile inner hair cells. Immunolocalization shows prestin is expressed in the lateral plasma membrane of the outer hair...
. It can induce transient hearing loss in
zincZinc , also known as spelter, is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
-deficient individuals.
This finding is based on clinical studies with
ratRats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...
s. An injection of salicylic acid induced hearing loss in zinc-deficient rats, while a simultaneous injection of zinc reversed the hearing loss. An injection of
magnesiumMagnesium is a chemical element with the symbol Mg, atomic number 12 and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the earth's crust by mass, although ninth in the Universe as a whole...
in the zinc-deficient rats did not reverse the salicylic acid-induced hearing loss.
Salicylic acid is used to treat acne, warts and other dermatological problems. There are no studies specifically looking at topical salicylic acid in pregnancy. Oral salicylic acid has not been associated with an increase in malformations if used during the first trimester, but use in late pregnancy has been associated with bleeding, especially intracranial bleeding. The risks of aspirin late in pregnancy are probably not relevant for a topical exposure to salicylic acid, even late in the pregnancy, because of its low systemic levels. Topical salicylic acid is common in many over-the-counter dermatological agents, and the lack of adverse reports suggests a low teratogenic potential.
Salicylic acid overdose can lead to salicylate intoxication, which often presents clinically in a state of
metabolic acidosisIn medicine, metabolic acidosis is a process which if unchecked leads to acidemia, i.e. blood pH is low due to increased production of H+ by the body or the inability of the body to form bicarbonate in the kidney. Its causes are diverse, and its consequences can be serious, including...
with compensatory
respiratory alkalosisRespiratory alkalosis is a medical condition in which increased respiration elevates the blood pH . It is one of four basic categories of disruption of acid-base homeostasis.-Types:...
. In patients presenting with an acute overdose, a 16% morbidity rate and a 1% mortality rate are observed.
Some people are
hypersensitive to salicylic acidSalicylate sensitivity, also known as salicylate intolerance, is any adverse effect that occurs when a normal amount of salicylate is introduced into a person's body...
and related compounds.
The United States
Food and Drug AdministrationThe Food and Drug Administration is a Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, tobacco products, dietary supplements, Medication drugs, vaccines, Biopharmaceutical, blood transfusion,...
recommends the use of sun protection when using skincare products containing salicylic acid (or any other BHA) on sun-exposed skin areas.
There is data to support an association between exposure to salicylic acid and
Reye's SyndromeReye's syndrome is a potentially fatal disease that causes numerous detrimental effects to many organs, especially the brain and liver, as well as causing hypoglycemia...
, the National Reye's Syndrome Foundation cautions against the usage of these substances, and other substances similar to aspirin on children and adolescents.
Epidemiological research has shown an association between the development of Reye's Syndrome and the use of aspirin (a salicylate compound) for treating the symptoms of influenza-like illnesses, chicken pox, colds, etc.
The U.S. Surgeon General, the Food and Drug Administration, the Centers for Disease Control and Prevention, and the American Academy of Pediatrics recommend that aspirin and combination products containing aspirin not be given to children under 19 years of age during episodes of fever-causing illnesses.
Footnotes