Diallyl disulfide
Encyclopedia
Diallyl disulfide is an organosulfur compound found in plants of the genus Allium
. Along with diallyl trisulfide and diallyl tetrasulfide, it is one of the principal components of the distilled oil
of garlic
. It is a yellowish liquid which is insoluble in water and has a strong garlic odor. It is produced during the decomposition of allicin, which is released during incision of garlic
and other plants of the Alliaceae
family. Diallyl disulfide has many health benefits of garlic, but it also an allergen
causing the garlic allergy
. Highly diluted, it is used as a flavoring in the food
.
separated by steam distillation
a pungent-smelling substance from garlic and named it "allyl
", however only in 1892 Friedrich Wilhelm Semmler
could identify diallyl disulfide as one of the components of the product. Its precursor, allicin, was discovered in 1944 by Chester J. Cavallito and John Hays Bailey. In 1947, A. Stoll and E. Seebeck found that DADS and allicin can be produced from derivatives of cysteine
(such as alliin
) using the enzyme alliinase
.
plants, especially garlic
, onion
and leek
. The DADS yield is the highest for the steam distillation
of garlic bulbs which contain about 2 wt.% of DADS-rich oil. DADS can also be extracted from garlic leaves, but their oil content is significantly lower at 0.06 wt.%.
or allyl chloride
at temperatures of 40–60 °C in an inert gas
atmosphere; sodium disulfide is generated in situ by reacting sodium sulfide
with sulfur
. The reaction is exothermic
and its theoretical efficiency of 88% has been achieved in practice.
Smaller quantities can be synthesized from the same starting materials, but in air and using tetrabutylammonium as a catalyst. The corresponding yield is below 82%. The major problem, both in the industrial synthesis and in the extraction from plants, is separation of diallyl disulfide from higher sulfides (diallyl trisulfide, etc.). They have very similar physical properties and therefore, a typical commercial product contains only 80% of diallyl disulfide. The reduction of allicin to diallyl disulfide takes place particularly rapidly above 37 °C.
at 50 °C, a density
of about 1.0 g/mL and a vapor pressure
of 1 mmHg at 20 °C. It is non-polar; therefore, DADS is insoluble in water and is soluble in fats, oils, lipid
s, and non-polar solvents such as hexane
or toluene
.
-based catalyst, DADS can produce sulfur-containing hetero-polycycles.
or copper chloride
catalyst, DADS can be used as a precursor for the synthesis of higher diallyl polysulfides. It is also a starting material for the synthesis of allicin. In food industry, DADS is used to improve the taste of meat, vegetables and fruits.
had long been present not only in humans and animals, but even in fungi. Thus, Alliaceae
plants have likely developed the DADS-TRPA1 protection mechanism against predators at the early stages of the evolution.
(GST), which binds electrophilic toxins in the cell. Garlic therefore supports, for example, the detoxification function of liver cells in vitro and protects nerve cells from oxidative stress, also in vitro. The detoxification effect may prevent symptoms of inflammation. This was confirmed a study on rats where prolonged administration of DADS protected poisoning of their intestinal cells. This study also showed that certain side effects of high doses of garlic oil are not attributable to the diallyl disulfide. By supporting the detoxification activity in the liver, diallyl disulfide might offer liver protection during the chemotherapy
, e.g. against cyanide
detoxification.
and larvicidal
properties of those compounds. In particular, DADS is the main reason for inhibiting the growth of mold
s and bacteria by garlic oil. It is also acts against the stomach ulcer germ Helicobacter pylori
, however not as efficiently as allicin. Because of its antimicrobial effects, diallyl disulfide, together with tobramycin, is included to preparations which are used for selective decontamination of the organs (e.g. gut) before surgical operations. A clinical study showed that such preparations prevent endotoxemia in heart valve operations.
, and several studies revealed that diallyl disulfide is a major component responsible for this action. The effect is dose dependent as demonstrated on mice. DADS affects cancer cells much stronger than normal cells. It also results in a strong and dose-dependent accumulation of several agents, such as reactive oxygen species, which activate enzyme and lead to destruction of cancer cells.
or coronary heart disease
is oxidative stress
. The latter is reduced by diallyl disulfide by assisting in the detoxification of the cell, as well as some other mechanisms. By activating the TRPA1 ion channel, DADS leads to a short-term lowering of blood pressure.
. In particular, it is the main cause of garlic allergy
(allergic contact dermatitis
to garlic), which especially affects chef
s and housewives. The allergy usually starts at the fingertips and can not be prevented by wearing gloves because DADS penetrates through most commercial glove types.
The median lethal dose
(LD50) for oral intake in rat
s is 260 mg per kg of body weight and it is 3.6 g/kg for dermal intake. High doses of 5 g/kg placed on the skin of cats cause death through hemolytic anemia
.
DADS can be easily detected in the air or in the blood with gas chromatography.
Allium
Allium is a monocot genus of flowering plants, informally referred to as the onion genus. The generic name Allium is the Latin word for garlic....
. Along with diallyl trisulfide and diallyl tetrasulfide, it is one of the principal components of the distilled oil
Oil
An oil is any substance that is liquid at ambient temperatures and does not mix with water but may mix with other oils and organic solvents. This general definition includes vegetable oils, volatile essential oils, petrochemical oils, and synthetic oils....
of garlic
Garlic
Allium sativum, commonly known as garlic, is a species in the onion genus, Allium. Its close relatives include the onion, shallot, leek, chive, and rakkyo. Dating back over 6,000 years, garlic is native to central Asia, and has long been a staple in the Mediterranean region, as well as a frequent...
. It is a yellowish liquid which is insoluble in water and has a strong garlic odor. It is produced during the decomposition of allicin, which is released during incision of garlic
Garlic
Allium sativum, commonly known as garlic, is a species in the onion genus, Allium. Its close relatives include the onion, shallot, leek, chive, and rakkyo. Dating back over 6,000 years, garlic is native to central Asia, and has long been a staple in the Mediterranean region, as well as a frequent...
and other plants of the Alliaceae
Alliaceae
Allioideae is the botanical name of a monocot subfamily of flowering plants in the family Amaryllidaceae, order Asparagales. It was formerly treated as a separate family, Alliaceae...
family. Diallyl disulfide has many health benefits of garlic, but it also an allergen
Allergen
An allergen is any substance that can cause an allergy. In technical terms, an allergen is a non-parasitic antigen capable of stimulating a type-I hypersensitivity reaction in atopic individuals....
causing the garlic allergy
Garlic allergy
Garlic allergy or allergic contact dermatitis to garlic is a common inflammatory skin condition caused by contact with garlic oil or dust. It mostly affects people who cut and handle fresh garlic, such as chefs, and presents on the tips of the thumb, index and middle fingers of the non-dominant hand...
. Highly diluted, it is used as a flavoring in the food
Food
Food is any substance consumed to provide nutritional support for the body. It is usually of plant or animal origin, and contains essential nutrients, such as carbohydrates, fats, proteins, vitamins, or minerals...
.
History
In 1844, Theodor WertheimTheodor Wertheim
Theodor Wertheim was an Austrian chemist born in Vienna.He was privatdozent in Vienna, and a professor at the University of Pest from 1853 to 1860. Afterwards he returned to Vienna, and beginning in 1861 worked at the University of Graz. In May, 1864 he moved back to Vienna, where he died soon...
separated by steam distillation
Steam distillation
Steam distillation is a special type of distillation for temperature sensitive materials like natural aromatic compounds....
a pungent-smelling substance from garlic and named it "allyl
Allyl
An allyl group is a substituent with the structural formula H2C=CH-CH2R, where R is the connection to the rest of the molecule. It is made up of a methylene , attached to a vinyl group . The name is derived from the Latin word for garlic, Allium sativum. Theodor Wertheim isolated an allyl...
", however only in 1892 Friedrich Wilhelm Semmler
Friedrich Wilhelm Semmler
Friedrich Wilhelm Semmler was a German chemist.-Life:Semmler studied chemistry at the University of Straßburg and at the University of Breslau. He received is PhD in Breslau in 1887 and his habilitation at the University of Greifswald in 1890...
could identify diallyl disulfide as one of the components of the product. Its precursor, allicin, was discovered in 1944 by Chester J. Cavallito and John Hays Bailey. In 1947, A. Stoll and E. Seebeck found that DADS and allicin can be produced from derivatives of cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
(such as alliin
Alliin
Alliin is a sulfoxide that is a natural constituent of fresh garlic. It is a derivative of the amino acid cysteine. When fresh garlic is chopped or crushed, the enzyme alliinase converts alliin into allicin, which is responsible for the aroma of fresh garlic...
) using the enzyme alliinase
Alliinase
In enzymology, an alliin lyase is an enzyme that catalyzes the chemical reactionHence, this enzyme has one substrate, S-alkyl-L-cysteine S-oxide, and two products, alkyl sulfenate and 2-aminoacrylate....
.
Occurrence
Diallyl disulfide is produced by decomposition of allicin, which is released upon breaking the cells of the AlliaceaeAlliaceae
Allioideae is the botanical name of a monocot subfamily of flowering plants in the family Amaryllidaceae, order Asparagales. It was formerly treated as a separate family, Alliaceae...
plants, especially garlic
Garlic
Allium sativum, commonly known as garlic, is a species in the onion genus, Allium. Its close relatives include the onion, shallot, leek, chive, and rakkyo. Dating back over 6,000 years, garlic is native to central Asia, and has long been a staple in the Mediterranean region, as well as a frequent...
, onion
Onion
The onion , also known as the bulb onion, common onion and garden onion, is the most widely cultivated species of the genus Allium. The genus Allium also contains a number of other species variously referred to as onions and cultivated for food, such as the Japanese bunching onion The onion...
and leek
Leek
The leek, Allium ampeloprasum var. porrum , also sometimes known as Allium porrum, is a vegetable which belongs, along with the onion and garlic, to family Amaryllidaceae, subfamily Allioideae...
. The DADS yield is the highest for the steam distillation
Steam distillation
Steam distillation is a special type of distillation for temperature sensitive materials like natural aromatic compounds....
of garlic bulbs which contain about 2 wt.% of DADS-rich oil. DADS can also be extracted from garlic leaves, but their oil content is significantly lower at 0.06 wt.%.
Extraction and representation
On industrial scale, diallyl disulfide is produced from sodium disulfide and allyl bromideAllyl bromide
Allyl bromide is an organic halide. Its refractive index is 1.4697 . Allyl bromide is an alkylating agent used in synthesis of polymers, pharmaceuticals, allyls and other organic compounds. Physically, allyl bromide is a clear liquid with an intense, acrid, and persistent smell...
or allyl chloride
Allyl chloride
Allyl chloride is the organic compound with the formula CH2=CHCH2Cl. This colorless liquid is insoluble in water but soluble in common organic solvents. It is mainly converted to epichlorohydrin, used in the production of plastics. It is a chlorinated derivative of propylene.-Production:Allyl...
at temperatures of 40–60 °C in an inert gas
Inert gas
An inert gas is a non-reactive gas used during chemical synthesis, chemical analysis, or preservation of reactive materials. Inert gases are selected for specific settings for which they are functionally inert since the cost of the gas and the cost of purifying the gas are usually a consideration...
atmosphere; sodium disulfide is generated in situ by reacting sodium sulfide
Sodium sulfide
Sodium sulfide is the name used to refer to the chemical compound Na2S, but more commonly it refers to the hydrate Na2S·9H2O. Both are colorless water-soluble salts that give strongly alkaline solutions...
with sulfur
Sulfur
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...
. The reaction is exothermic
Exothermic
In thermodynamics, the term exothermic describes a process or reaction that releases energy from the system, usually in the form of heat, but also in the form of light , electricity , or sound...
and its theoretical efficiency of 88% has been achieved in practice.
Smaller quantities can be synthesized from the same starting materials, but in air and using tetrabutylammonium as a catalyst. The corresponding yield is below 82%. The major problem, both in the industrial synthesis and in the extraction from plants, is separation of diallyl disulfide from higher sulfides (diallyl trisulfide, etc.). They have very similar physical properties and therefore, a typical commercial product contains only 80% of diallyl disulfide. The reduction of allicin to diallyl disulfide takes place particularly rapidly above 37 °C.
Physical characteristics
DADS has a strong garlic smell. It is a clear, yellowish liquid which boils at 138–139 °C (for the typical 80% purity) and has its flash pointFlash point
The flash point of a volatile material is the lowest temperature at which it can vaporize to form an ignitable mixture in air. Measuring a flash point requires an ignition source...
at 50 °C, a density
Density
The mass density or density of a material is defined as its mass per unit volume. The symbol most often used for density is ρ . In some cases , density is also defined as its weight per unit volume; although, this quantity is more properly called specific weight...
of about 1.0 g/mL and a vapor pressure
Vapor pressure
Vapor pressure or equilibrium vapor pressure is the pressure of a vapor in thermodynamic equilibrium with its condensed phases in a closed system. All liquids have a tendency to evaporate, and some solids can sublimate into a gaseous form...
of 1 mmHg at 20 °C. It is non-polar; therefore, DADS is insoluble in water and is soluble in fats, oils, lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s, and non-polar solvents such as hexane
Hexane
Hexane is a hydrocarbon with the chemical formula C6H14; that is, an alkane with six carbon atoms.The term may refer to any of four other structural isomers with that formula, or to a mixture of them. In the IUPAC nomenclature, however, hexane is the unbranched isomer ; the other four structures...
or toluene
Toluene
Toluene, formerly known as toluol, is a clear, water-insoluble liquid with the typical smell of paint thinners. It is a mono-substituted benzene derivative, i.e., one in which a single hydrogen atom from the benzene molecule has been replaced by a univalent group, in this case CH3.It is an aromatic...
.
Chemical reactions
Diallyl disulfide can oxidize to allicin, which can dissociate back to the diallyl disulfide (top right in the figure). In presence of a catalyst, it can combine with alkyl halide forming 1-alkylthio-3-1-propene and 1,3-di(alkylthio)propene (left). With a rutheniumRuthenium
Ruthenium is a chemical element with symbol Ru and atomic number 44. It is a rare transition metal belonging to the platinum group of the periodic table. Like the other metals of the platinum group, ruthenium is inert to most chemicals. The Russian scientist Karl Ernst Claus discovered the element...
-based catalyst, DADS can produce sulfur-containing hetero-polycycles.
Applications
In presence of iron chlorideIron chloride
Iron chloride can refer to* Iron chloride , FeCl2* Iron chloride , FeCl3...
or copper chloride
Copper chloride
Copper forms two stable chlorides:*Copper chloride , CuCl, mineral name nantokite.*Copper chloride , CuCl2, mineral name eriochalcite....
catalyst, DADS can be used as a precursor for the synthesis of higher diallyl polysulfides. It is also a starting material for the synthesis of allicin. In food industry, DADS is used to improve the taste of meat, vegetables and fruits.
Smell and taste
The unpleasant smell of DADS is perceived through the transient receptor potential cation channel, member A1 (TRPA1). This ion channelIon channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
had long been present not only in humans and animals, but even in fungi. Thus, Alliaceae
Alliaceae
Allioideae is the botanical name of a monocot subfamily of flowering plants in the family Amaryllidaceae, order Asparagales. It was formerly treated as a separate family, Alliaceae...
plants have likely developed the DADS-TRPA1 protection mechanism against predators at the early stages of the evolution.
Poisoning and detoxification
Diallyl disulfide is an efficient agent for detoxication of the cells. It significantly increases the production of the enzyme glutathione S-transferaseGlutathione S-transferase
Enzymes of the glutathione S-transferase family are composed of many cytosolic, mitochondrial, and microsomal proteins. GSTs are present in eukaryotes and in prokaryotes, where they catalyze a variety of reactions and accept endogenous and xenobiotic substrates.GSTs can constitute up to 10% of...
(GST), which binds electrophilic toxins in the cell. Garlic therefore supports, for example, the detoxification function of liver cells in vitro and protects nerve cells from oxidative stress, also in vitro. The detoxification effect may prevent symptoms of inflammation. This was confirmed a study on rats where prolonged administration of DADS protected poisoning of their intestinal cells. This study also showed that certain side effects of high doses of garlic oil are not attributable to the diallyl disulfide. By supporting the detoxification activity in the liver, diallyl disulfide might offer liver protection during the chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, e.g. against cyanide
Cyanide
A cyanide is a chemical compound that contains the cyano group, -C≡N, which consists of a carbon atom triple-bonded to a nitrogen atom. Cyanides most commonly refer to salts of the anion CN−. Most cyanides are highly toxic....
detoxification.
Antimicrobial effect
The release of organosulfur compounds upon destruction of Alliaceae plant cells has great importance, because of the antimicrobial, insecticidalInsecticide
An insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...
and larvicidal
Larvicide
A larvicide is an insecticide that is specifically targeted against the larval life stage of an insect. Their most common use is against mosquitoes...
properties of those compounds. In particular, DADS is the main reason for inhibiting 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...
s and bacteria by garlic oil. It is also acts against the stomach ulcer germ Helicobacter pylori
Helicobacter pylori
Helicobacter pylori , previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were...
, however not as efficiently as allicin. Because of its antimicrobial effects, diallyl disulfide, together with tobramycin, is included to preparations which are used for selective decontamination of the organs (e.g. gut) before surgical operations. A clinical study showed that such preparations prevent endotoxemia in heart valve operations.
Protection against colon cancer
Garlic can prevent the colorectal cancerColorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
, and several studies revealed that diallyl disulfide is a major component responsible for this action. The effect is dose dependent as demonstrated on mice. DADS affects cancer cells much stronger than normal cells. It also results in a strong and dose-dependent accumulation of several agents, such as reactive oxygen species, which activate enzyme and lead to destruction of cancer cells.
Protection against cardiovascular disease
There is evidence that garlic may prevent the development of cardiovascular diseases. A possible reason for some of these diseases, such as atherosclerosisAtherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
or coronary heart disease
Coronary heart disease
Coronary artery disease is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the myocardium with oxygen and nutrients. It is sometimes also called coronary heart disease...
is oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
. The latter is reduced by diallyl disulfide by assisting in the detoxification of the cell, as well as some other mechanisms. By activating the TRPA1 ion channel, DADS leads to a short-term lowering of blood pressure.
Safety
DADS is a skin irritant and an allergenAllergen
An allergen is any substance that can cause an allergy. In technical terms, an allergen is a non-parasitic antigen capable of stimulating a type-I hypersensitivity reaction in atopic individuals....
. In particular, it is the main cause of garlic allergy
Garlic allergy
Garlic allergy or allergic contact dermatitis to garlic is a common inflammatory skin condition caused by contact with garlic oil or dust. It mostly affects people who cut and handle fresh garlic, such as chefs, and presents on the tips of the thumb, index and middle fingers of the non-dominant hand...
(allergic contact dermatitis
Allergic contact dermatitis
Allergic contact dermatitis is a form of contact dermatitis that is the manifestation of an allergic response caused by contact with a substance....
to garlic), which especially affects chef
Chef
A chef is a person who cooks professionally for other people. Although over time the term has come to describe any person who cooks for a living, traditionally it refers to a highly skilled professional who is proficient in all aspects of food preparation.-Etymology:The word "chef" is borrowed ...
s and housewives. The allergy usually starts at the fingertips and can not be prevented by wearing gloves because DADS penetrates through most commercial glove types.
The median lethal dose
Lethal dose
A lethal dose is an indication of the lethality of a given substance or type of radiation. Because resistance varies from one individual to another, the 'lethal dose' represents a dose at which a given percentage of subjects will die...
(LD50) for oral intake in rat
Rat
Rats 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 is 260 mg per kg of body weight and it is 3.6 g/kg for dermal intake. High doses of 5 g/kg placed on the skin of cats cause death through hemolytic anemia
Hemolytic anemia
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
.
DADS can be easily detected in the air or in the blood with gas chromatography.