Thymol

Thymol (also known as 2-isopropyl-5-methylphenol, IPMP) is a natural monoterpene phenol derivative of cymene, C10H 14O, 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.

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 carvacrol. 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.

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.

History
The Ancient Egyptians used thymol and carvacrol 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 poultices of the plant for skin infections and minor wounds. A tea made from the plant was also used to treat mouth and throat infections 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.

Uses
Thymol has microbial activity because of its phenolic structure, and has shown antibacterial activity against bacterial strains including Aeromoans hydrophila and Staphylococcus aureus. Thymol has been used in alcohol solutions and in dusting powders for the treatment of tinea 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.

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 spores. However, this practice is not currently recommended due to apparent accelerated degradation suffered by these objects.

List of plants that contain thymol

 * Monarda didyma
 * Monarda fistulosa
 * Origanum compactum
 * Origanum dictamnus
 * Origanum onites
 * Origanum vulgare
 * Thymus glandulosus
 * Thymus hyemalis
 * Thymus vulgaris
 * Thymus zygis

Toxicology and environmental impacts
The U.S. Environmental Protection Agency (EPA) 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 coli
 * Antimicrobial activities against
 * Listeria monocytogenes
 * Bacillus subtilis

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.

Compendial status

 * British Pharmacopoeia
 * Japanese Pharmacopoeia