Thymol
Encyclopedia
Thymol is a natural monoterpene
phenol
derivative of cymene
, C10H14O, isomeric with carvacrol
, found in oil of thyme
, and extracted
from Thymus vulgaris (common thyme)
and various other kinds of plants as a white crystalline substance of a pleasant aromatic odor
and strong antiseptic
properties. Thymol also provides the distinctive, strong flavor of the culinary herb
thyme
, also produced from T. vulgaris.
. In addition, naturally-occurring biocidal agents such as thymol can reduce bacterial resistance to common drugs such as penicillin. Numerous studies have demonstrated the antimicrobial effects of thymol, ranging from inducing antibiotic susceptibility in drug-resistant pathogens to powerful antioxidant properties. Research demonstrates that naturally occurring biocides such as thymol and carvacrol reduce bacterial resistance to antibiotics through a synergistic effect, and thymol has been shown to be an effective fungicide
, particularly against fluconazole
-resistant strains. This is especially relevant given that opportunistic Candida (fungus) infections can cause severe systemic infections in immunocompromised patients and current treatments are highly toxic, often result in drug-resistant Candida strains, and have low efficacy.
Compounds in the essential oils of one type of oregano
have demonstrated antimutagenic effects, and in particular carvacrol (isomeric with thymol) and thymol were demonstrated to have a strong antimutagenic effect. In addition, there is evidence that thymol has antitumor properties.
Though the exact mechanism is unknown, there is evidence to suggest that thymol possesses at least some of its biocidal properties via membrane disruption.
Synonyms include isopropyl-m-cresol, hydroxycymene, 1-methyl-3-hydroxy-4-isopropylbenzene, 2-hydroxy-1-isopropyl-4-methylbenzene; 3-hydroxy-p-cymene, 3-methyl-6-isopropylphenol, 5-methyl-2-(1-methylethyl)phenol, 5-methyl-2-isopropyl-1-phenol, 5-methyl-2-isopropylphenol, 6-isopropyl-3-methylphenol, 6-isopropyl-m-cresol, Apiguard, NSC 11215, NSC 47821, NSC 49142, thyme camphor, m-thymol, and p-cymen-3-ol.
Thymol has a refractive index of 1.5208 and an experimental dissociation exponent (pKa) of 10.59 ± 0.10. Thymol absorbs maximum UV radiation at 274 nm.
in the form of a preparation from the thyme
plant (a member of the mint family), because of their ability to preserve mummies. Thymol and carvacrol are now known to kill bacteria
and fungi, making thyme well suited for such purposes.
The bee balms (Monarda fistulosa
and Monarda didyma
), North American wildflowers, are natural sources of thymol. The Blackfoot
Native Americans recognized this plant's strong antiseptic
action, and used poultice
s of the plant for skin infection
s and minor wound
s. A tea made from the plant was also used to treat mouth and throat infection
s caused by dental caries
and gingivitis
.
The crystalline substance thymol was discovered by Caspar Neumann
in 1719. The chemical was synthesized in pure form in 1842 by von M. Lallemand, who used elementary chemical analysis to characterize it by determining the correct ratio
of carbon
, hydrogen
, and oxygen
that make up the thymol molecule
. Friedlieb Ferdinand Runge also studied the chemistry
of this substance. Alain Thozet and M. Perrin first published the crystal structure analysis with the exact determination of the structural atoms.
or ringworm infections, and was used in the United States to treat hookworm
infections. It is also used as a preservative
in halothane
, an anaesthetic, and as an antiseptic in mouthwash. When used to reduce plaque and gingivitis, thymol has been found to be more effective when used in combination with chlorhexidine than when used purely by itself. Thymol is also the active antiseptic ingredient in some toothpastes, such as Euthymol
.
There is evidence supporting the belief that thymol, when applied two to three times daily, can eliminate certain kinds of fungal infections that affect fingernails and toenails in humans. Regular application to the affected nail over periods of about three months has been shown to eliminate the affliction by effectively preventing further progress; by simply cutting the nail as one normally would, all infected material is eventually eliminated. The antifungal nature of thymol is caused by thymol's ability to alter in the hyphal morphology and cause hyphal aggregates, resulting in reduced hyphal diameters and lyses of hyphal wall. Additionally, thymol is lipophilic, enabling it to interact with the cell membrane of fungus cells, altering cell membrane permeability permitting the loss of macromolecules.
Recent medical research on rats concludes that "Thyme extract had relaxing effects on organs possessing β2-receptors (uterus
and trachea
)."
In a 1994 report released by five major cigarette
companies, thymol was listed as one of 599 additives to cigarettes.
Thymol has been used to successfully control varroa mites and prevent fermentation and the growth of mold
in bee colonies, methods developed by beekeeper R.O.B. Manley
.
Thymol is also used as a rapidly degrading, non-persisting pesticide
.
A minor use of thymol is in book and paper conservation: Paper with mold damage can be sealed in bags with thymol crystals to kill fungal spore
s. However, this practice is not currently recommended due to apparent accelerated degradation suffered by these objects.
reviewed the literature and published research on the toxicology and environmental impact of thymol in 2009 and concluded that “Thymol has minimal potential toxicity and poses minimal risk”
Studies have shown that hydrocarbon monoterpenes and thymol in particular degrade rapidly (DT50 16 days in water, 5 days in soil) in the environment and are, thus, low risks because of rapid dissipation and low bound residues, supporting the use of thymol as a pesticide agent that offers a safe alternative to other more persistent chemical pesticides that can be dispersed in runoff and produce subsequent contamination.
Monoterpene
Monoterpenes are a class of terpenes that consist of two isoprene units and have the molecular formula C10H16. Monoterpenes may be linear or contain rings...
phenol
Phenols
In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of a hydroxyl group bonded directly to an aromatic hydrocarbon group...
derivative of cymene
Cymene
Cymene, or p-cymene, is a naturally occurring aromatic organic compound. It is classified as a hydrocarbon related to a monoterpene. Its structure consists of a benzene ring para-substituted with a methyl group and an isopropyl group...
, C10H14O, isomeric with carvacrol
Carvacrol
Carvacrol, or cymophenol, C6H3CH3, is a monoterpenoid phenol. It has a characteristic pungent, warm odor of oregano and a pizza-like taste.- Natural occurrence :...
, found in oil of thyme
Thyme
Thyme is a culinary and medicinal herb of the genus Thymus.-History:Ancient Egyptians used thyme for embalming. The ancient Greeks used it in their baths and burnt it as incense in their temples, believing it was a source of courage...
, and extracted
Liquid-liquid extraction
Liquid–liquid extraction, also known as solvent extraction and partitioning, is a method to separate compounds based on their relative solubilities in two different immiscible liquids, usually water and an organic solvent. It is an extraction of a substance from one liquid phase into another liquid...
from Thymus vulgaris (common thyme)
Thymus vulgaris
Thymus vulgaris or common thyme is a low growing herbaceous plant, sometimes becoming somewhat woody. It is native to southern Europe, where it is often cultivated as a culinary herb....
and various other kinds of plants as a white crystalline substance of a pleasant aromatic odor
Odor
An odor or odour is caused by one or more volatilized chemical compounds, generally at a very low concentration, that humans or other animals perceive by the sense of olfaction. Odors are also commonly called scents, which can refer to both pleasant and unpleasant odors...
and strong antiseptic
Antiseptic
Antiseptics are antimicrobial substances that are applied to living tissue/skin to reduce the possibility of infection, sepsis, or putrefaction...
properties. Thymol also provides the distinctive, strong flavor of the culinary herb
Herb
Except in botanical usage, an herb is "any plant with leaves, seeds, or flowers used for flavoring, food, medicine, or perfume" or "a part of such a plant as used in cooking"...
thyme
Thyme
Thyme is a culinary and medicinal herb of the genus Thymus.-History:Ancient Egyptians used thyme for embalming. The ancient Greeks used it in their baths and burnt it as incense in their temples, believing it was a source of courage...
, also produced from T. vulgaris.
Biological activity
Thymol is part of a naturally occurring class of compounds known as biocides, with strong antimicrobial attributes when used alone or with other biocides such as carvacrolCarvacrol
Carvacrol, or cymophenol, C6H3CH3, is a monoterpenoid phenol. It has a characteristic pungent, warm odor of oregano and a pizza-like taste.- Natural occurrence :...
. In addition, naturally-occurring biocidal agents such as thymol can reduce bacterial resistance to common drugs such as penicillin. Numerous studies have demonstrated the antimicrobial effects of thymol, ranging from inducing antibiotic susceptibility in drug-resistant pathogens to powerful antioxidant properties. Research demonstrates that naturally occurring biocides such as thymol and carvacrol reduce bacterial resistance to antibiotics through a synergistic effect, and thymol has been shown to be an effective fungicide
Fungicide
Fungicides are chemical compounds or biological organisms used to kill or inhibit fungi or fungal spores. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality and profit. Fungicides are used both in agriculture and to fight fungal infections in animals...
, particularly against fluconazole
Fluconazole
Fluconazole is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections. In a bulk powder form, it appears as a white crystalline powder, and it is very slightly soluble in water and soluble in alcohol. It is commonly marketed under the trade...
-resistant strains. This is especially relevant given that opportunistic Candida (fungus) infections can cause severe systemic infections in immunocompromised patients and current treatments are highly toxic, often result in drug-resistant Candida strains, and have low efficacy.
Compounds in the essential oils of one type of oregano
Oregano
Oregano – scientifically named Origanum vulgare by Carolus Linnaeus – is a common species of Origanum, a genus of the mint family . It is native to warm-temperate western and southwestern Eurasia and the Mediterranean region.Oregano is a perennial herb, growing from 20–80 cm tall,...
have demonstrated antimutagenic effects, and in particular carvacrol (isomeric with thymol) and thymol were demonstrated to have a strong antimutagenic effect. In addition, there is evidence that thymol has antitumor properties.
Though the exact mechanism is unknown, there is evidence to suggest that thymol possesses at least some of its biocidal properties via membrane disruption.
Chemistry
Thymol is only slightly soluble in water at neutral pH, but it is extremely soluble in alcohols and other organic solvents. It is also soluble in strongly alkaline aqueous solutions due to deprotonation of the phenol.Synonyms include isopropyl-m-cresol, hydroxycymene, 1-methyl-3-hydroxy-4-isopropylbenzene, 2-hydroxy-1-isopropyl-4-methylbenzene; 3-hydroxy-p-cymene, 3-methyl-6-isopropylphenol, 5-methyl-2-(1-methylethyl)phenol, 5-methyl-2-isopropyl-1-phenol, 5-methyl-2-isopropylphenol, 6-isopropyl-3-methylphenol, 6-isopropyl-m-cresol, Apiguard, NSC 11215, NSC 47821, NSC 49142, thyme camphor, m-thymol, and p-cymen-3-ol.
Thymol has a refractive index of 1.5208 and an experimental dissociation exponent (pKa) of 10.59 ± 0.10. Thymol absorbs maximum UV radiation at 274 nm.
History
The Ancient Egyptians used thymol and carvacrolCarvacrol
Carvacrol, or cymophenol, C6H3CH3, is a monoterpenoid phenol. It has a characteristic pungent, warm odor of oregano and a pizza-like taste.- Natural occurrence :...
in the form of a preparation from the thyme
Thyme
Thyme is a culinary and medicinal herb of the genus Thymus.-History:Ancient Egyptians used thyme for embalming. The ancient Greeks used it in their baths and burnt it as incense in their temples, believing it was a source of courage...
plant (a member of the mint family), because of their ability to preserve mummies. Thymol and carvacrol are now known to kill bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
and fungi, making thyme well suited for such purposes.
The bee balms (Monarda fistulosa
Monarda fistulosa
Wild bergamot or Bee Balm is a wildflower in the mint family widespread and abundant as a native plant in much of North America. This plant, with showy summer-blooming white flowers, is often used as a honey plant, medicinal plant, and garden ornamental...
and Monarda didyma
Monarda didyma
Monarda didyma is an aromatic herb in the family Lamiaceae, native to eastern North America from Maine west to Ohio and south to northern Georgia. Its name is derived from its odor, which is considered similar to that of the bergamot orange...
), North American wildflowers, are natural sources of thymol. The Blackfoot
Blackfoot
The Blackfoot Confederacy or Niitsítapi is the collective name of three First Nations in Alberta and one Native American tribe in Montana....
Native Americans recognized this plant's strong antiseptic
Antiseptic
Antiseptics are antimicrobial substances that are applied to living tissue/skin to reduce the possibility of infection, sepsis, or putrefaction...
action, and used poultice
Poultice
A poultice, also called cataplasm, is a soft moist mass, often heated and medicated, that is spread on cloth over the skin to treat an aching, inflamed, or painful part of the body. It can be used on wounds such as cuts...
s of the plant for skin infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s and minor wound
Wound
A wound is a type of injury in which skin is torn, cut or punctured , or where blunt force trauma causes a contusion . In pathology, it specifically refers to a sharp injury which damages the dermis of the skin.-Open:...
s. A tea made from the plant was also used to treat mouth and throat infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s caused by dental caries
Caries
Caries is a progressive destruction of any kind of bone structure, including the skull, ribs and other bones, or the teeth. Caries can be caused by osteomyelitis, which is a microorganism disease. A disease that involves caries is mastoiditis, an inflammation of the mastoid process, in which the...
and gingivitis
Gingivitis
Gingivitis is a term used to describe non-destructive periodontal disease. The most common form of gingivitis is in response to bacterial biofilms adherent to tooth surfaces, termed plaque-induced gingivitis, and is the most common form of periodontal disease...
.
The crystalline substance thymol was discovered by Caspar Neumann
Caspar Neumann
Caspar Neumann was a German professor and clergyman from Breslau with a special interest in mortality rates.-Biography:...
in 1719. The chemical was synthesized in pure form in 1842 by von M. Lallemand, who used elementary chemical analysis to characterize it by determining the correct ratio
Ratio
In mathematics, a ratio is a relationship between two numbers of the same kind , usually expressed as "a to b" or a:b, sometimes expressed arithmetically as a dimensionless quotient of the two which explicitly indicates how many times the first number contains the second In mathematics, a ratio is...
of carbon
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
, hydrogen
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...
, and oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
that make up the thymol molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
. Friedlieb Ferdinand Runge also studied the chemistry
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....
of this substance. Alain Thozet and M. Perrin first published the crystal structure analysis with the exact determination of the structural atoms.
Uses
Thymol has microbial activity because of its phenolic structure, and has shown antibacterial activity against bacterial strains including Aeromoans hydrophila and Staphylococcus aureus. This antibacterial activity is caused by inhibiting growth and lactate production, and by decreasing cellular glucose uptake. Thymol has been used in alcohol solutions and in dusting powders for the treatment of tineaTinea
Tinea is a general term used to describe skin mycoses. The term ringworm is even less precise, but is usually considered a synonym.It is sometimes equated with dermatophytosis, and it is true that most conditions identified as "tinea" are members of the imperfect fungi that make up the dermatophytes...
or ringworm infections, and was used in the United States to treat hookworm
Hookworm
The hookworm is a parasitic nematode that lives in the small intestine of its host, which may be a mammal such as a dog, cat, or human. Two species of hookworms commonly infect humans, Ancylostoma duodenale and Necator americanus. A. duodenale predominates in the Middle East, North Africa, India...
infections. It is also used as a preservative
Preservative
A preservative is a naturally occurring or synthetically produced substance that is added to products such as foods, pharmaceuticals, paints, biological samples, wood, etc. to prevent decomposition by microbial growth or by undesirable chemical changes....
in halothane
Halothane
Halothane is an inhalational general anesthetic. Its IUPAC name is 2-bromo-2-chloro-1,1,1-trifluoroethane. It is the only inhalational anesthetic agent containing a bromine atom; there are several other halogenated anesthesia agents which lack the bromine atom and do contain the fluorine and...
, an anaesthetic, and as an antiseptic in mouthwash. When used to reduce plaque and gingivitis, thymol has been found to be more effective when used in combination with chlorhexidine than when used purely by itself. Thymol is also the active antiseptic ingredient in some toothpastes, such as Euthymol
Euthymol
Euthymol is a brand of antiseptic, fluoride-free toothpaste distributed by Johnson & Johnson that is characterised by its bright pink colour and medicinal taste. It is also notable for its packaging, which is old fashioned, having merely a pattern and the product name. The antiseptic ingredient in...
.
There is evidence supporting the belief that thymol, when applied two to three times daily, can eliminate certain kinds of fungal infections that affect fingernails and toenails in humans. Regular application to the affected nail over periods of about three months has been shown to eliminate the affliction by effectively preventing further progress; by simply cutting the nail as one normally would, all infected material is eventually eliminated. The antifungal nature of thymol is caused by thymol's ability to alter in the hyphal morphology and cause hyphal aggregates, resulting in reduced hyphal diameters and lyses of hyphal wall. Additionally, thymol is lipophilic, enabling it to interact with the cell membrane of fungus cells, altering cell membrane permeability permitting the loss of macromolecules.
Recent medical research on rats concludes that "Thyme extract had relaxing effects on organs possessing β2-receptors (uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
and trachea
Vertebrate trachea
In tetrapod anatomy the trachea, or windpipe, is a tube that connects the pharynx or larynx to the lungs, allowing the passage of air. It is lined with pseudostratified ciliated columnar epithelium cells with goblet cells that produce mucus...
)."
In a 1994 report released by five major cigarette
Cigarette
A cigarette is a small roll of finely cut tobacco leaves wrapped in a cylinder of thin paper for smoking. The cigarette is ignited at one end and allowed to smoulder; its smoke is inhaled from the other end, which is held in or to the mouth and in some cases a cigarette holder may be used as well...
companies, thymol was listed as one of 599 additives to cigarettes.
Thymol has been used to successfully control varroa mites and prevent fermentation and the growth of mold
Mold
Molds are fungi that grow in the form of multicellular filaments called hyphae. Molds are not considered to be microbes but microscopic fungi that grow as single cells called yeasts...
in bee colonies, methods developed by beekeeper R.O.B. Manley
R.O.B. Manley
Robert "Bert" Orlando Beater Manley was a British Beekeeper, an authority on commercial honey farming and developer of the popular Manley moveable frame hives and frame systems.-Achievements:...
.
Thymol is also used as a rapidly degrading, non-persisting pesticide
Pesticide
Pesticides are substances or mixture of substances intended for preventing, destroying, repelling or mitigating any pest.A pesticide may be a chemical unicycle, biological agent , antimicrobial, disinfectant or device used against any pest...
.
A minor use of thymol is in book and paper conservation: Paper with mold damage can be sealed in bags with thymol crystals to kill fungal spore
Spore
In biology, a spore is a reproductive structure that is adapted for dispersal and surviving for extended periods of time in unfavorable conditions. Spores form part of the life cycles of many bacteria, plants, algae, fungi and some protozoa. According to scientist Dr...
s. However, this practice is not currently recommended due to apparent accelerated degradation suffered by these objects.
List of plants that contain thymol
- Monarda didymaMonarda didymaMonarda didyma is an aromatic herb in the family Lamiaceae, native to eastern North America from Maine west to Ohio and south to northern Georgia. Its name is derived from its odor, which is considered similar to that of the bergamot orange...
- Monarda fistulosaMonarda fistulosaWild bergamot or Bee Balm is a wildflower in the mint family widespread and abundant as a native plant in much of North America. This plant, with showy summer-blooming white flowers, is often used as a honey plant, medicinal plant, and garden ornamental...
- Trachyspermum ammi
- Origanum compactum
- Origanum dictamnusOriganum dictamnusOriganum dictamnus , known in Greek as Δίκταμο or in Cretan dialect Έρωντας , is a tender perennial plant that grows 20–30 cm high...
- Origanum onites
- Origanum vulgare
- Thymus glandulosus
- Thymus hyemalis
- Thymus vulgarisThymus vulgarisThymus vulgaris or common thyme is a low growing herbaceous plant, sometimes becoming somewhat woody. It is native to southern Europe, where it is often cultivated as a culinary herb....
- Thymus zygis
Toxicology and environmental impacts
The U.S. Environmental Protection Agency (EPA)United States Environmental Protection Agency
The U.S. Environmental Protection Agency is an agency of the federal government of the United States charged with protecting human health and the environment, by writing and enforcing regulations based on laws passed by Congress...
reviewed the literature and published research on the toxicology and environmental impact of thymol in 2009 and concluded that “Thymol has minimal potential toxicity and poses minimal risk”
- Antibacterial potent of Escherichia coliEscherichia coliEscherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
- Antimicrobial activities against
- Listeria monocytogenes
- Bacillus subtilisBacillus subtilisBacillus subtilis, known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium commonly found in soil. A member of the genus Bacillus, B. subtilis is rod-shaped, and has the ability to form a tough, protective endospore, allowing the organism to tolerate...
Studies have shown that hydrocarbon monoterpenes and thymol in particular degrade rapidly (DT50 16 days in water, 5 days in soil) in the environment and are, thus, low risks because of rapid dissipation and low bound residues, supporting the use of thymol as a pesticide agent that offers a safe alternative to other more persistent chemical pesticides that can be dispersed in runoff and produce subsequent contamination.