Diallyl disulfide (DADS or4,5-dithia-1,7-octadiene) is anorganosulfur compound derived fromgarlic and a few other plants in the genusAllium.[3] Along withdiallyl trisulfide and diallyl tetrasulfide, it is one of the principal components of thedistilledoil ofgarlic. It is a yellowish liquid which is insoluble in water and has a strong garlic odor. It is produced during the decomposition ofallicin, which is released upon crushinggarlic and other plants of the familyAlliaceae. Diallyl disulfide has many of the health benefits of garlic, but it is also anallergen causinggarlic allergy. Highly diluted, it is used as a flavoring infood. It decomposes in the human body into other compounds such asallyl methyl sulfide.
Diallyl disulfide and the related trisulfide are produced by decomposition ofallicin, which is released upon breaking the cells of theAlliaceae plants, especiallygarlic. The diallyl disulfide yield is the highest for thesteam distillation of garlic bulbs which contain about 2 wt.% of diallyl disulfide-rich oil. Diallyl disulfide can also be extracted from garlic leaves, but their oil content is significantly lower at 0.06 wt.%.[5][6]
On an industrial scale, diallyl disulfide is produced from sodium disulfide andallyl bromide orallyl chloride at temperatures of 40–60 °C in aninert gas atmosphere; sodium disulfide is generatedin situ by reactingsodium sulfide withsulfur. The reaction isexothermic and its theoretical efficiency of 88% has been achieved in practice.[7]
Smaller quantities can be synthesized from the same starting materials, but in air and usingtetrabutylammonium bromide as a catalyst. The corresponding yield is below 82%.[8] The major problem, both in the industrial synthesis and in the extraction from plants, is separation of diallyl disulfide from higher sulfides (diallyl trisulfide (DATS), etc.). They have very similar physical properties and therefore, a typical commercial product contains only 80% of diallyl disulfide. The conversion of allicin to diallyl disulfide and trisulfide takes place particularly rapidly above 37 °C.[9]
Diallyl disulfide has a strong garlic smell. It is a clear, yellowish liquid which boils at 138–139 °C (for the typical 80% purity) and has itsflash point at 50 °C, adensity of about 1.0 g/mL and avapor pressure of 1 mmHg at 20 °C. It is non-polar; therefore, diallyl disulfide is insoluble in water and is soluble in fats, oils,lipids, and non-polar solvents such ashexane ortoluene.[1][2]
Diallyl disulfide can be readily oxidized toallicin withhydrogen peroxide orperacetic acid.Allicin in turn can hydrolyze giving diallyl disulfide and trisulfide. Reaction of diallyl disulfide with liquidsulfur gives a mixture containing diallylpolysulfides with as many as 22sulfur atoms in a continuous chain identified.[3][10] When diallyl disulfide is heated it decomposes giving a complex mixture. The carbon-sulfur bond of diallyl disulfide is 16 kcal mol−1 weaker than the sulfur-sulfur bond (46 kcal mol−1 versus 62 kcal mol−1, respectively), with the consequence that on heating diallyl disulfide gives the allyldithio radical (AllSS•), which through addition to the double bonds in diallyl disulfide followed by fragmentation and subsequent reactions generates numerous organosulfur compounds, many of which are found in trace amounts in distilled garlic oil.[3][11] In the presence of a catalyst, diallyl disulfide can combine withalkyl halides forming 1-alkylthio-3-allylthio-1-propene and 1,3-di(alkylthio)propene.[12]
In the presence ofiron chloride orcopper chloride catalyst, or of liquidsulfur at 120 °C[3][13] Diallyl disulfide can be used as a precursor for the synthesis of higher diallylpolysulfides (polysulfanes). In agriculture, diallyl disulfide and related diallyl polysulfides show useful activity as environmentally-benignnematicides.[3] Diallyl disulfide is also a starting material for the synthesis ofallicin. In the food industry, diallyl disulfide is used to improve the taste of meat, vegetables and fruits.[1][14]
The unpleasant smell of diallyl disulfide is perceived through thetransient receptor potential cation channel, member A1 (TRPA1). Thision channel had long been present not only in humans and animals, but even in fungi. Thus,Alliaceae plants have likely developed the diallyl disulfide-TRPA1 protection mechanism against predators at the early stages of the evolution.[15][16]
Diallyl disulfide is an efficient agent for detoxication of the cells. It significantly increases the production of the enzymeglutathione S-transferase (GST), which bindselectrophilic toxins in the cell. Garlic therefore supports, for example, the detoxification function of liver cellsin vitro and protects nerve cells from oxidative stress, alsoin vitro.[17][18][19][20][21][22][23][24] The detoxification effect may prevent symptoms of inflammation. This was confirmed in a study on rats where prolonged administration of diallyl disulfide 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.[25] By supporting the detoxification activity in the liver, diallyl disulfide might offer liver protection during thechemotherapy, e.g. againstcyanide detoxification.[26][27]
The release oforganosulfur compounds upon destruction of Alliaceae plant cells has great importance, because of the antimicrobial,insecticidal andlarvicidal properties of those compounds.[28] In particular, diallyl disulfide is the main reason for inhibiting the growth ofmolds and bacteria by garlic oil. It is also acts against thestomach ulcer germHelicobacter pylori, however not as efficiently as allicin.[29][30] Because of its antimicrobial effects, diallyl disulfide, together withtobramycin, is included in preparations which are used for selective decontamination of the organs (e.g. gut) before surgical operations. A clinical study showed that such preparations preventendotoxemia in heart valve operations.[31]
Garlic can preventcolorectal cancer,[32] and several studies revealed that diallyl disulfide is a major component responsible for this action. The effect is dose dependent as demonstrated on mice.[33][34] Diallyl disulfide affects cancer cells much more strongly than normal cells.[35] 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.[36]
There is evidence that garlic may prevent the development of cardiovascular diseases. A possible reason for some of these diseases, such asatherosclerosis orcoronary heart disease isoxidative stress. The latter is reduced by diallyl disulfide by assisting in the detoxification of the cell, as well as some other mechanisms.[4] By activating the TRPA1 ion channel, diallyl disulfide leads to a short-term lowering of blood pressure.[15]
Diallyl disulfide is a skin irritant and anallergen. In particular, it is the main cause ofgarlic allergy (allergic contact dermatitis to garlic). The allergy usually starts at the fingertips and cannot be prevented by wearing gloves because diallyl disulfide penetrates through most commercial glove types.[37][38][39][40]
The medianlethal dose (LD50) for oral intake inrats 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 throughhemolytic anemia.[1][41]
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^Edris, A; Fadel, H (2002). "Investigation of the volatile aroma components of garlic leaves essential oil. Possibility of utilization to enrich garlic bulb oil".European Food Research and Technology.214 (2):105–107.doi:10.1007/s00217-001-0429-2.S2CID95448926.
^WO 2006016881, "PROCESS FOR PRODUCING DIALLYL DISULFIDE", published 16-02-2006
^Yuan, X; Chen, X; Jiang, X; Nie, Y (2006). "Synthesis, characterization and bioactivity evaluation of diallyl disulfide".Journal of Central South University of Technology.13 (5):515–518.doi:10.1007/s11771-006-0079-4.S2CID97570822.
^Freeman, F; Kodera, Y (1995). "Garlic Chemistry: Stability of S-(2-Propenyl)-2-Propene-1-sulfinothioate (Allicin) in Blood, Solvents, and Simulated Physiological Fluids".Journal of Agricultural and Food Chemistry.43 (9):2332–2338.Bibcode:1995JAFC...43.2332F.doi:10.1021/jf00057a004.
^Wang, Kai; Groom, Murree; Sheridan, Robert; Zhang, Shaozhong; Block, Eric (2013). "Liquid sulfur as a reagent: Synthesis of polysulfanes with 20 or more sulfur atoms with characterization by UPLC-(Ag+)-coordination ion spray-MS".Journal of Sulfur Chemistry.34 (1–2):55–66.doi:10.1080/17415993.2012.721368.S2CID95562164.
^Block, Eric; Iyer, Rajeshwari; Grisoni, Serge; Saha, Chantu; Belman, Sidney; Lossing, Fred P (1988). "Lipoxygenase inhibitors from the essential oil of garlic. Markovnikov addition of the allyldithio radical to olefins".Journal of the American Chemical Society.110 (23):7813–7827.Bibcode:1988JAChS.110.7813B.doi:10.1021/ja00231a037.
^Amosova, S.V.; Nosyreva, V.V.; Musorin, G.K.; Sigalov, M.V.; Sinegovskaya, L.M.; Trofimov, B.A. (1986). "Synthesis of 1-alkylthio-3-allylthio-1-propenes by the reaction of dialllyl disulfide with allyl halides in the alkali-metal hydroxide-DMSO superbasic system".Journal of Organic Chemistry of the USSR.22 (5):856–61.OCLC4434235280.OSTI6388212.
^Hile, Arla G; Shan, Zhixing; Zhang, Shao-Zhong; Block, Eric (2004). "Aversion of European Starlings (Sturnus vulgaris) to Garlic Oil Treated Granules: Garlic Oil as an Avian Repellent. Garlic Oil Analysis by Nuclear Magnetic Resonance Spectroscopy".Journal of Agricultural and Food Chemistry.52 (8):2192–2196.Bibcode:2004JAFC...52.2192H.doi:10.1021/jf035181d.PMID15080619.
^Fukao, T; Hosono, T; Misawa, S; Seki, T; Ariga, T (2004). "The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachloride".Food and Chemical Toxicology.42 (5):743–749.doi:10.1016/j.fct.2003.12.010.PMID15046820.
^Koh, Seong-Ho; Kwon, Hyugsung; Park, Kee Hyung; Ko, Jin Kyung; Kim, Joo Hwan; Hwang, Myung Sil; Yum, Young Na; Kim, Ok-Hee; Kim, Juhan; Kim, Hee-Tae; Do, Byung-Rok; Kim, Kyung Suk; Kim, Haekwon; Roh, Hakjae; Yu, Hyun-Jeung; Jung, Hai Kwan; Kim, Seung Hyun (2005). "Protective effect of diallyl disulfide on oxidative stress-injured neuronally differentiated PC12 cells".Molecular Brain Research.133 (2):176–186.doi:10.1016/j.molbrainres.2004.10.006.PMID15710234.
^Kim, Jun-Gyou; Koh, Seong-Ho; Lee, Young Joo; Lee, Kyu-Young; Kim, Youngchul; Kim, Sunyoun; Lee, Myung-Koo; Kim, Seung Hyun (2005). "Differential effects of diallyl disulfide on neuronal cells depend on its concentration".Toxicology.211 (1–2):86–96.Bibcode:2005Toxgy.211...86K.doi:10.1016/j.tox.2005.02.011.PMID15863251.
^Chiang, Yi-Hsuan; Jen, Lin-Ni; Su, Hsiau-Yuan; Lii, Chong-Kuei; Sheen, Lee-Yan; Liu, Cheng-Tzu (2006). "Effects of garlic oil and two of its major organosulfur compounds, diallyl disulfide and diallyl trisulfide, on intestinal damage in rats injected with endotoxin".Toxicology and Applied Pharmacology.213 (1):46–54.Bibcode:2006ToxAP.213...46C.doi:10.1016/j.taap.2005.08.008.PMID16274720.
^Yu, J; Xiao, YB; Wang, XY (2007). "Effects of preoperatively selected gut decontamination on cardiopulmonary bypass-induced endotoxemia".Chinese Journal of Traumatology.10 (3):131–7.PMID17535634.
^World Cancer Research Fund/American Institute for Cancer Research: Food, Nutrition, Physical Activity and the Prevention of Cancer. 2nd Edition, 2007 (ISBN0-97225222-3) S.pp.93–94Archived 2009-03-25 at theWayback Machine (PDF, 12 MB)
^Huang, Z; Lei, X; Zhong, M; Zhu, B; Tang, S; Liao, D (2007). "Bcl-2 small interfering RNA sensitizes cisplatin-resistant human lung adenocarcinoma A549/DDP cell to cisplatin and diallyl disulfide".Acta Biochimica et Biophysica Sinica.39 (11):835–43.doi:10.1111/j.1745-7270.2007.00356.x.PMID17989874.
^Sun, X; Guo, T; He, J; Zhao, M; Yan, M; Cui, F; Deng, Y (2006). "Simultaneous determination of diallyl trisulfide and diallyl disulfide in rat blood by gas chromatography with electron-capture detection".Die Pharmazie.61 (12):985–8.PMID17283653.
