Diallyl disulfide: Difference between revisions

| verifiedrevid = 414417113

| ImageFile = Diallyl_disulfide.png

| ImageFile1 = Diallyl-disulfide-3D-vdW.png

| IUPACName = 4,5-dithia-1,7-octadiene<br/>Diallyldisulfide

| OtherNames = Garlicin, DADS

| Section1 = {{Chembox Identifiers

| Section2 = {{Chembox Properties

| Formula = C₆H₁₀S₂

| Appearance = yellowish clear liquid with an intense garlic smell<ref name="gsc">[http://www.thegoodscentscompany.com/data/rw1002791.html allyl disulfide]</ref>

| MolarMass = 146.28 g/mol

| Density = 1.01 g/cm³<ref name="sa">[http://www.sigmaaldrich.com/catalog/search/ProductDetail/FLUKA/32621 Diallyl disulfide at Sigma Aldrich]</ref>

| BoilingPt = 180 °C

| Section7 = {{Chembox Hazards

| RPhrases = 22-36/37/38

| SPhrases = 22-36/37/38

'''Diallyl disulfide''' ('''DADS''' or '''4,5-dithia-1,7-octadiene''') 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]].

In 1844, [[Theodor Wertheim]] 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]].<ref Name="omar">{{cite journal|author=S. H. Omar|url=http://www.phcogrev.com/article.asp?issn=0973-7847;year=2007;volume=1;issue=1;spage=80;epage=87;aulast=Omar;type=0|title=Historical, chemical and cardiovascular perspectives on garlic: A review|journal=Pharmacognosy Reviews|volume=1|year=2007|pages=80|issue=1|author-separator=,|display-authors=1}}</ref>

== Occurrence==

Diallyl disulfide is produced by decomposition of [[allicin]], which is released upon breaking the cells of the [[Alliaceae]] 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.%.<ref>{{cite journal|doi=10.1055/s-2006-960119|title=Identification and HPLC Quantitation of the Sulfides and Dialk(en)yl Thiosulfinates in Commercial Garlic Products|year=2007|last1=Lawson|first1=Larry|last2=Wang|first2=Zhen-Yu|last3=Hughes|first3=Bronwyn|journal=Planta Medica|volume=57|pages=363–370|pmid=1775579|issue=4}}</ref><ref>{{cite journal|doi=10.1007/s00217-001-0429-2|title=Investigation of the volatile aroma components of garlic leaves essential oil. Possibility of utilization to enrich garlic bulb oil|year=2002|last1=Edris|first1=Amr|last2=Fadel|first2=Hoda|journal=European Food Research and Technology|volume=214|pages=105–107|issue=2}}</ref>

== Extraction and representation==

On 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.<ref>[http://www.wipo.int/pctdb/en/wo.jsp?wo=2006016881 WIPO Patent WO/2006/16881]</ref>

:[[Image:Diallyldisulfid formation.png|left|500px]]<br style="clear:left;"/>

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%.<ref>{{cite journal|doi=10.1007/s11771-006-0079-4|title=Synthesis, characterization and bioactivity evaluation of diallyl disulfide|year=2006|last1=Yuan|first1=Xin-ke|last2=Chen|first2=Xiao-Qing|last3=Jiang|first3=Xin-yu|last4=Nie|first4=Ya-li|journal=Journal of Central South University of Technology|volume=13|pages=515–518|issue=5}}</ref> 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.<ref>{{cite journal|doi=10.1021/jf00057a004|title=Garlic Chemistry: Stability of S-(2-Propenyl)-2-Propene-1-sulfinothioate (Allicin) in Blood, Solvents, and Simulated Physiological Fluids|year=1995|last1=Freeman|first1=Fillmore|last2=Kodera|first2=Yukihiro|journal=Journal of Agricultural and Food Chemistry|volume=43|pages=2332–2338|issue=9}}</ref>

===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 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, [[lipid]]s, and non-polar solvents such as [[hexane]] or [[toluene]].<ref Name="gsc" /><ref name="sa" />

=== Chemical reactions===

[[Image:DADS-reactions.svg|400px|right|thumb|Chemical reactions of diallyl disulfide.]]

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).<ref>Amosova SV ''et al.'' :''Synthesis of 1-alkylthio-3-allylthio-1-propene by the reaction of allyl halides with dialllyl disulfide in the alkali-metal hydroxide-DMSO system super basic'' J. Org. Chem USSR (Engl Transl.) Vol. 22 No. 5, 1986, pp. 957–963. [http://www.osti.gov/energycitations/product.biblio.jsp?osti_id=6388212 Abstract]</ref> With a [[ruthenium]]-based catalyst, DADS can produce sulfur-containing hetero-polycycles.<ref>Kondo T. et al.''Cyclization Ruthenium Complex-Catalyzed Novel Addition Reaction of Allylic Disulfide with 2 -norbornene.''Nippon Kagakkai Koen Yokoshu. 76/2'''1999''', p. 922 [http://sciencelinks.jp/j-east/article/200003/000020000300A0104528.php Abstract]</ref>

In presence of [[iron chloride]] 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.<ref Name="gsc"/><ref>{{US Patent|5231114}}</ref>

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.<ref Name="stink">{{cite journal|doi=10.1073/pnas.0505356102|pmc=1189336|pmid=16103371|title=Pungent products from garlic activate the sensory ion channel TRPA1|first9=PM|last9=Zygmunt|first8=SE|last8=Jordt|first7=D|last7=Julius|first6=ED|last6=Högestätt|first5=O|last5=Sterner|first4=HE|last4=Axelsson|first3=A|last3=Hinman|first2=P|year=2005|last2=Movahed|last1=Bautista|first1=D. M.|journal=Proceedings of the National Academy of Sciences|volume=102|issue=34|pages=12248–12252}}</ref><ref>{{cite journal|pmid=15080619|year=2004|last1=Hile|first1=AG|last2=Shan|first2=Z|last3=Zhang|first3=SZ|last4=Block|first4=E|title=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|volume=52|issue=8|pages=2192–6|doi=10.1021/jf035181d|journal=Journal of agricultural and food chemistry}}</ref>

===Poisoning and detoxification ===

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 [[electrophilicity|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''.<ref Name="germ">{{cite journal|pmid=14742141|year=2003|last1=Germain|first1=E|last2=Chevalier|first2=J|last3=Siess|first3=MH|last4=Teyssier|first4=C|title=Hepatic metabolism of diallyl disulphide in rat and man|volume=33|issue=12|pages=1185–99|doi=10.1080/00498250310001636840|journal=Xenobiotica}}</ref><ref>{{cite journal|pmid=16251611|year=2005|last1=Tsai|first1=CW|last2=Yang|first2=JJ|last3=Chen|first3=HW|last4=Sheen|first4=LY|last5=Lii|first5=CK|title=Garlic organosulfur compounds upregulate the expression of the pi class of glutathione S-transferase in rat primary hepatocytes|volume=135|issue=11|pages=2560–5|journal=The Journal of nutrition}}</ref><ref>{{cite journal|doi=10.1021/jf010937z|pmid=11782211|year=2002|last1=Wu|first1=CC|last2=Sheen|first2=LY|last3=Chen|first3=HW|last4=Kuo|first4=WW|last5=Tsai|first5=SJ|last6=Lii|first6=CK|title=Differential effects of garlic oil and its three major organosulfur components on the hepatic detoxification system in rats|volume=50|issue=2|pages=378–83|journal=Journal of agricultural and food chemistry}}</ref><ref>{{cite journal|pmid=15046820|year=2004|last1=Fukao|first1=T|last2=Hosono|first2=T|last3=Misawa|first3=S|last4=Seki|first4=T|last5=Ariga|first5=T|title=The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachloride|volume=42|issue=5|pages=743–9|doi=10.1016/j.fct.2003.12.010|journal=Food and chemical toxicology }}</ref><ref name="lemar">{{cite journal|pmid=17534841|year=2007|last1=Lemar|first1=KM|last2=Aon|first2=MA|last3=Cortassa|first3=S|last4=O'Rourke|first4=B|last5=Müller|first5=CT|last6=Lloyd|first6=D|title=Diallyl disulphide depletes glutathione in Candida albicans: oxidative stress-mediated cell death studied by two-photon microscopy|volume=24|issue=8|pages=695–706|doi=10.1002/yea.1503|pmc=2292485|journal=Yeast (Chichester, England)}}</ref><ref>{{cite journal|pmid=17937621|year=2007|last1=Hu|first1=Y|last2=Urig|first2=S|last3=Koncarevic|first3=S|last4=Wu|first4=X|last5=Fischer|first5=M|last6=Rahlfs|first6=S|last7=Mersch-Sundermann|first7=V|last8=Becker|first8=K|title=Glutathione- and thioredoxin-related enzymes are modulated by sulfur-containing chemopreventive agents|volume=388|issue=10|pages=1069–81|doi=10.1515/BC.2007.135|journal=Biological chemistry}}</ref><ref>{{cite journal|pmid=15710234|year=2005|last1=Koh|first1=SH|last2=Kwon|first2=H|last3=Park|first3=KH|last4=Ko|first4=JK|last5=Kim|first5=JH|last6=Hwang|first6=MS|last7=Yum|first7=YN|last8=Kim|first8=OH|last9=Kim|first9=J|title=Protective effect of diallyl disulfide on oxidative stress-injured neuronally differentiated PC12 cells|volume=133|issue=2|pages=176–86|doi=10.1016/j.molbrainres.2004.10.006|journal=Brain research. Molecular brain research}}</ref><ref>{{cite journal|pmid=15863251|year=2005|last1=Kim|first1=JG|last2=Koh|first2=SH|last3=Lee|first3=YJ|last4=Lee|first4=KY|last5=Kim|first5=Y|last6=Kim|first6=S|last7=Lee|first7=MK|last8=Kim|first8=SH|title=Differential effects of diallyl disulfide on neuronal cells depend on its concentration|volume=211|issue=1–2|pages=86–96|doi=10.1016/j.tox.2005.02.011|journal=Toxicology}}</ref> 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.<ref>{{cite journal|pmid=16274720|year=2006|last1=Chiang|first1=YH|last2=Jen|first2=LN|last3=Su|first3=HY|last4=Lii|first4=CK|last5=Sheen|first5=LY|last6=Liu|first6=CT|title=Effects of garlic oil and two of its major organosulfur compounds, diallyl disulfide and diallyl trisulfide, on intestinal damage in rats injected with endotoxin|volume=213|issue=1|pages=46–54|doi=10.1016/j.taap.2005.08.008|journal=Toxicology and applied pharmacology}}</ref> By supporting the detoxification activity in the liver, diallyl disulfide might offers liver protection during the [[chemotherapy]], e.g. against [[cyanide]] detoxification.<ref>{{cite journal|pmid=17560567|year=2007|last1=Iciek|first1=M|last2=Marcinek|first2=J|last3=Mleczko|first3=U|last4=Włodek|first4=L|title=Selective effects of diallyl disulfide, a sulfane sulfur precursor, in the liver and Ehrlich ascites tumor cells|volume=569|issue=1–2|pages=1–7|doi=10.1016/j.ejphar.2007.04.055|journal=European journal of pharmacology}}</ref><ref>{{cite journal|pmid=15886420|year=2005|last1=Iciek|first1=M|last2=Bilska|first2=A|last3=Ksiazek|first3=L|last4=Srebro|first4=Z|last5=Włodek|first5=L|title=Allyl disulfide as donor and cyanide as acceptor of sulfane sulfur in the mouse tissues|volume=57|issue=2|pages=212–8|journal=Pharmacological reports : PR}}</ref>

===Antimicrobial effect ===

The release of [[organosulfur compound]]s upon destruction of Alliaceae plant cells has great importance, because of the antimicrobial, [[Insecticide|insecticidal]] and [[Larvicide|larvicidal]] properties of those compounds.<ref>{{cite journal|pmid=5135721|year=1971|last1=Amonkar|first1=SV|last2=Banerji|first2=A|title=Isolation and characterization of larvicidal principle of garlic|volume=174|issue=16|pages=1343–4|journal=Science|doi=10.1126/science.174.4016.1343}}</ref> 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.<ref>{{cite journal|pmid=11185736|year=2000|last1=Avato|first1=P|last2=Tursil|first2=E|last3=Vitali|first3=C|last4=Miccolis|first4=V|last5=Candido|first5=V|title=Allylsulfide constituents of garlic volatile oil as antimicrobial agents|volume=7|issue=3|pages=239–43|journal=Phytomedicine : international journal of phytotherapy and phytopharmacology}}</ref><ref>{{cite journal|doi=10.1128/AEM.66.5.2269-2273.2000|pmid=10788416|year=2000|last1=O'Gara|first1=EA|last2=Hill|first2=DJ|last3=Maslin|first3=DJ|title=Activities of garlic oil, garlic powder, and their diallyl constituents against Helicobacter pylori|volume=66|issue=5|pages=2269–73|pmc=101489|journal=Applied and environmental microbiology}}</ref> 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.<ref>{{cite journal|pmid=17535634|year=2007|last1=Yu|first1=J|last2=Xiao|first2=YB|last3=Wang|first3=XY|title=Effects of preoperatively selected gut decontamination on cardiopulmonary bypass-induced endotoxemia|volume=10|issue=3|pages=131–7|journal=Chinese journal of traumatology = Zhonghua chuang shang za zhi / Chinese Medical Association}}</ref>

===Protection against colon cancer ===

Garlic can prevent the [[colorectal cancer]],<ref>World Cancer Research Fund/American Institute for Cancer Research: Food, Nutrition, Physical Activity and the Prevention of Cancer. 2nd Edition, 2007 (ISBN 0-97225222-3) S. [http://www.dietandcancerreport.org/downloads/Second_Expert_Report.pdf pp.93–94] (PDF, 12 MB)</ref> and several studies revealed that diallyl disulfide is a major component responsible for this action. The effect is dose dependent as demonstrated on mice.<ref>{{cite journal|pmid=16484574|year=2006|last1=Milner|first1=JA|title=Preclinical perspectives on garlic and cancer|volume=136|issue=3 Suppl|pages=827S–831S|journal=The Journal of nutrition}}</ref><ref>{{cite journal|pmid=16475702|year=2006|last1=Yang|first1=JS|last2=Kok|first2=LF|last3=Lin|first3=YH|last4=Kuo|first4=TC|last5=Yang|first5=JL|last6=Lin|first6=CC|last7=Chen|first7=GW|last8=Huang|first8=WW|last9=Ho|first9=HC|title=Diallyl disulfide inhibits WEHI-3 leukemia cells in vivo|volume=26|issue=1A|pages=219–25|journal=Anticancer research}}</ref> DADS affects cancer cells much stronger than normal cells.<ref>{{cite journal|doi=10.1111/j.1745-7270.2007.00356.x|pmid=17989874|year=2007|last1=Huang|first1=Z|last2=Lei|first2=X|last3=Zhong|first3=M|last4=Zhu|first4=B|last5=Tang|first5=S|last6=Liao|first6=D|title=Bcl-2 small interfering RNA sensitizes cisplatin-resistant human lung adenocarcinoma A549/DDP cell to cisplatin and diallyl disulfide|volume=39|issue=11|pages=835–43|journal=[[Acta Biochimica et Biophysica Sinica]]}}</ref> 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.<ref>{{cite journal|pmid=18097607|year=2008|last1=Jo|first1=HJ|last2=Song|first2=JD|last3=Kim|first3=KM|last4=Cho|first4=YH|last5=Kim|first5=KH|last6=Park|first6=YC|title=Diallyl disulfide induces reversible G2/M phase arrest on a p53-independent mechanism in human colon cancer HCT-116 cells|volume=19|issue=1|pages=275–80|journal=Oncology reports}}</ref>

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.<ref Name="omar" /> By activating the TRPA1 ion channel, DADS leads to a short-term lowering of blood pressure.<ref Name="stink" />

DADS is a skin irritant and an [[allergen]]. 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.<ref>{{cite book|url=http://books.google.com/?id=6AB89RHV9ucC&pg=PA288|page=228|title=Garlic and other alliums: the lore and the science|author=Eric Block|publisher=Royal Society of Chemistry|year=2009|isbn=0854041907}}</ref><ref>{{cite book|url=http://books.google.com/?id=f2IwYiyh3YUC&pg=PT305|page=305|title=Dermatology, Volume 2|author=Thomas D. Horn|publisher=Elsevier Health Sciences|year=2003|isbn=0323025781}}</ref><ref>[http://www.allallergy.net/fapaidfind.cfm?cdeoc=684 Garlic]</ref><ref>{{cite journal|pmid=15527433|year=2004|last1=Moyle|first1=M|last2=Frowen|first2=K|last3=Nixon|first3=R|title=Use of gloves in protection from diallyl disulphide allergy|volume=45|issue=4|pages=223–5|doi=10.1111/j.1440-0960.2004.00102.x|journal=The Australasian journal of dermatology}}</ref>

DADS can be easily detected in the air or in the blood with [[gas chromatography]].<ref>[http://www.osha.gov/dts/chemicalsampling/data/CH_231730.html documents of the U.S. Department of Labor Occupational Safety & Health]</ref><ref>{{cite journal|pmid=17283653|year=2006|last1=Sun|first1=X|last2=Guo|first2=T|last3=He|first3=J|last4=Zhao|first4=M|last5=Yan|first5=M|last6=Cui|first6=F|last7=Deng|first7=Y|title=Simultaneous determination of diallyl trisulfide and diallyl disulfide in rat blood by gas chromatography with electron-capture detection|volume=61|issue=12|pages=985–8|journal=Die Pharmazie}}</ref>

*[[Allyl propyl disulfide]]

{{reflist|2}}

== External links ==

*[http://www.herbalchem.net/GarlicAdvanced.htm Organosulfur Compounds From Garlic]

*[http://www.old.uni-bayreuth.de/departments/didaktikchemie/umat/knoblauch/knoblauch.htm garlic - Chemical aspects]

[[Category:Alkenes]]

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