Diallyl disulfide

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Diallyl disulfide
Diallyl disulfide
Diallyl-disulfide-3D-vdW.png
Identifiers
CAS number 2179-57-9 YesY
PubChem 16590
ChemSpider 15730 YesY
KEGG C08369 YesY
ChEBI CHEBI:4488 YesY
ChEMBL CHEMBL366603 YesY
Jmol-3D images Image 1
Properties
Molecular formula C6H10S2
Molar mass 146.28 g/mol
Appearance yellowish clear liquid with an intense garlic smell[1]
Density 1.01 g/cm3[2]
Boiling point 180 °C
Solubility in water soluble in ethanol and oils[1]
Hazards
R-phrases 22-36/37/38
S-phrases 22-36/37/38
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 YesY (verify) (what is: YesY/N?)
Infobox references

Diallyl disulfide (DADS or 4,5-dithia-1,7-octadiene) is an organosulfur compound derived from garlic and a few other genus Allium plants.[3] 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 upon crushing garlic and other plants of the Alliaceae family. Diallyl disulfide has many of the health benefits of garlic, but it is also an allergen causing garlic allergy. Highly diluted, it is used as a flavoring in food.

History[edit]

In 1844, Theodor Wertheim separated by steam distillation a pungent-smelling substance from garlic and named it "allyl sulfur." However, only in 1892 could Friedrich Wilhelm Semmler identify diallyl disulfide as one of the components of distilled garlic oil. The natural precursor of DADS, allicin, was discovered in 1944 by Chester J. Cavallito and John Hays Bailey. In 1947, A. Stoll and E. Seebeck found that allicin in turn can be produced from the cysteine derivative alliin using the enzyme alliinase.[3][4]

Occurrence[edit]

Diallyl disulfide and trisulfide are produced by decomposition of allicin, which is released upon breaking the cells of the Alliaceae plants, especially garlic. 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.%.[5][6]

Extraction and representation[edit]

On an industrial scale, diallyl disulfide is produced from sodium disulfide and allyl bromide 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.[7]

Diallyldisulfid formation.png

Smaller quantities can be synthesized from the same starting materials, but in air and using tetrabutylammonium 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]

Properties[edit]

Physical characteristics[edit]

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 point 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, lipids, and non-polar solvents such as hexane or toluene.[1][2]

Chemical reactions[edit]

Diallyl disulfide can be readily oxidized to allicin with hydrogen peroxide or peracetic acid. Allicin in turn can hydrolyze giving diallyl disulfide and trisulfide. Reaction of DADS with liquid sulfur gives a mixture containing diallyl polysulfides with as many as 22 sulfur atoms in a continuous chain.[3][10] When DADS is heated it decomposes giving a complex mixture. The carbon-sulfur bond of DADS 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 DADS gives the allyldithio radical (AllSS•), which through addition to the double bonds in DADS 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, DADS can combine with alkyl halides forming 1-alkylthio-3-allylthio-1-propene and 1,3-di(alkylthio)propene.[12]

Applications[edit]

In the presence of iron chloride or copper chloride catalyst, or of liquid sulfur at 120 °C[3][13] DADS can be used as a precursor for the synthesis of higher diallyl polysulfides (polysulfanes). In agriculture, DADS and related diallyl polysulfides show useful activity as environmentally-benign nematicides.[3] DADS is also a starting material for the synthesis of allicin. In the food industry, DADS is used to improve the taste of meat, vegetables and fruits.[1][14]

Biological importance[edit]

Smell and taste[edit]

The unpleasant smell of DADS is perceived through the transient receptor potential cation channel, member A1 (TRPA1). This ion channel 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.[15][16]

Poisoning and detoxification[edit]

Diallyl disulfide is an efficient agent for detoxication of the cells. It significantly increases the production of the enzyme glutathione S-transferase (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.[17][18][19][20][21][22][23][24] 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.[25] By supporting the detoxification activity in the liver, diallyl disulfide might offer liver protection during the chemotherapy, e.g. against cyanide detoxification.[26][27]

Antimicrobial effect[edit]

The release of organosulfur compounds upon destruction of Alliaceae plant cells has great importance, because of the antimicrobial, insecticidal and larvicidal properties of those compounds.[28] In particular, DADS is the main reason for inhibiting the growth of molds and bacteria by garlic oil. It is also acts against the stomach ulcer germ Helicobacter pylori, however not as efficiently as allicin.[29][30] Because of its antimicrobial effects, diallyl disulfide, together with tobramycin, 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 prevent endotoxemia in heart valve operations.[31]

Protection against colon cancer[edit]

Garlic can prevent the colorectal 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] DADS affects cancer cells much stronger 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]

Protection against cardiovascular disease[edit]

There is evidence that garlic may prevent the development of cardiovascular diseases. A possible reason for some of these diseases, such as atherosclerosis 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.[4] By activating the TRPA1 ion channel, DADS leads to a short-term lowering of blood pressure.[15]

Safety[edit]

DADS is a skin irritant and an allergen. In particular, it is the main cause of garlic allergy (allergic contact dermatitis to garlic). The allergy usually starts at the fingertips and can not be prevented by wearing gloves because DADS penetrates through most commercial glove types.[37][38][39][40]

The median lethal dose (LD50) for oral intake in rats 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.[1][41]

DADS can be easily detected in the air or in the blood with gas chromatography.[42][43]

See also[edit]

References[edit]

  1. ^ a b c d e allyl disulfide
  2. ^ a b Diallyl disulfide at Sigma Aldrich
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  7. ^ WIPO Patent WO/2006/16881
  8. ^ 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. 
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  10. ^ Wang, K; Groom, M; Sheridan, R; Zhang, S; Block, E (2013). “Liquid Sulfur as a Reagent: Synthesis of Families of Polysulfanes with Twenty or More Sulfur Atoms with Characterization by Ultra Performance Liquid Chromatography–(Ag+)Coordination Ion Spray–Mass Spectrometry” J. Sulfur Chem. 34:55-66. doi: 10.1080/17415993.2012.721368
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  12. ^ Amosova SV et al. (1986) "Synthesis of 1-alkylthio-3-allylthio-1-propene by the reaction of allyl halides with dialllyl disulfide in the alkali-metal hydroxide-DMSO superbasic system" J. Org. Chem USSR (Engl Transl.) 22(5): 957–963. Abstract
  13. ^ U.S. Patent 8,101,802
  14. ^ U.S. Patent 5,231,114
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  19. ^ Wu, CC; Sheen, LY; Chen, HW; Kuo, WW; Tsai, SJ; Lii, CK (2002). "Differential effects of garlic oil and its three major organosulfur components on the hepatic detoxification system in rats". Journal of Agricultural and Food Chemistry 50 (2): 378–83. doi:10.1021/jf010937z. PMID 11782211. 
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  23. ^ Koh, SH; Kwon, H; Park, KH; Ko, JK; Kim, JH; Hwang, MS; Yum, YN; Kim, OH et al. (2005). "Protective effect of diallyl disulfide on oxidative stress-injured neuronally differentiated PC12 cells". Brain Research. Molecular Brain Research 133 (2): 176–86. doi:10.1016/j.molbrainres.2004.10.006. PMID 15710234. 
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  26. ^ Iciek, M; Marcinek, J; Mleczko, U; Włodek, L (2007). "Selective effects of diallyl disulfide, a sulfane sulfur precursor, in the liver and Ehrlich ascites tumor cells". European Journal of Pharmacology 569 (1–2): 1–7. doi:10.1016/j.ejphar.2007.04.055. PMID 17560567. 
  27. ^ Iciek, M; Bilska, A; Ksiazek, L; Srebro, Z; Włodek, L (2005). "Allyl disulfide as donor and cyanide as acceptor of sulfane sulfur in the mouse tissues". Pharmacological Reports 57 (2): 212–8. PMID 15886420. 
  28. ^ Amonkar, SV; Banerji, A (1971). "Isolation and characterization of larvicidal principle of garlic". Science 174 (16): 1343–4. doi:10.1126/science.174.4016.1343. PMID 5135721. 
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  30. ^ O'Gara, EA; Hill, DJ; Maslin, DJ (2000). "Activities of garlic oil, garlic powder, and their diallyl constituents against Helicobacter pylori". Applied and Environmental Microbiology 66 (5): 2269–73. doi:10.1128/AEM.66.5.2269-2273.2000. PMC 101489. PMID 10788416. 
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  36. ^ Jo, HJ; Song, JD; Kim, KM; Cho, YH; Kim, KH; Park, YC (2008). "Diallyl disulfide induces reversible G2/M phase arrest on a p53-independent mechanism in human colon cancer HCT-116 cells". Oncology Reports 19 (1): 275–80. PMID 18097607. 
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  38. ^ Horn, TD (2003). Dermatology, Volume 2. Elsevier Health Sciences. p. 305. ISBN 0-323-02578-1. 
  39. ^ Garlic
  40. ^ Moyle, M; Frowen, K; Nixon, R (2004). "Use of gloves in protection from diallyl disulphide allergy". The Australasian Journal of Dermatology 45 (4): 223–5. doi:10.1111/j.1440-0960.2004.00102.x. PMID 15527433. 
  41. ^ EPA documents
  42. ^ documents of the U.S. Department of Labor Occupational Safety & Health
  43. ^ 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. PMID 17283653.