Tmic
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Record Information
Version2.0
Creation Date2009-07-30 17:56:41 UTC
Update Date2014-12-24 20:26:01 UTC
Accession NumberT3D3241
Identification
Common NameDiacetyl
ClassSmall Molecule
DescriptionDiacetyl is a natural by-product of secondary or malolactic fermentation. It is a vicinal diketone (two C=O groups, side-by-side) with the molecular formula C4H6O2. Carrier of aroma of butter, vinegar, coffee, and other foods. Beer sometimes undergoes a diacetyl rest, which entails waiting two or three days after fermentation is complete, to allow the yeast to absorb the diacetyl it produced earlier in the fermentation cycle. The makers of some wines, such as chardonnay, deliberately promote the production of diacetyl because of the feel and flavors it imparts.
Compound Type
  • Animal Toxin
  • Food Toxin
  • Fragrance Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Ketone
  • Lachrymator
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
Synonyms
Synonym
2,3-Butadione
2,3-Butandione
2,3-Butanedione
2,3-Diketobutane
2,3-Dioxobutane
Acetoacetaldehyde
Biacetyl
Butadione
Butan-2,3-dione
Butane-2,3-dione
Butanedione
Dimethyl diketone
Dimethyl glyoxal
Dimethylglyoxal
Chemical FormulaC4H6O2
Average Molecular Mass86.089 g/mol
Monoisotopic Mass86.037 g/mol
CAS Registry Number431-03-8
IUPAC Namebutane-2,3-dione
Traditional Namediacetyl
SMILESCC(=O)C(C)=O
InChI IdentifierInChI=1S/C4H6O2/c1-3(5)4(2)6/h1-2H3
InChI KeyInChIKey=QSJXEFYPDANLFS-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as alpha-diketones. These are organic compounds containing two ketone groups on two adjacent carbon atoms.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassCarbonyl compounds
Direct ParentAlpha-diketones
Alternative Parents
Substituents
  • Alpha-diketone
  • Organic oxide
  • Hydrocarbon derivative
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Gonads
  • Neuron
  • Skeletal Muscle
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceYellow to green liquid (14).
Experimental Properties
PropertyValue
Melting Point-2.4°C
Boiling Point88°C
Solubility200 mg/mL at 15°C
LogP-1.34
Predicted Properties
PropertyValueSource
Water Solubility129 g/LALOGPS
logP0.07ALOGPS
logP0.4ChemAxon
logS0.18ALOGPS
pKa (Strongest Acidic)15.98ChemAxon
pKa (Strongest Basic)-8.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area34.14 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity21.54 m³·mol⁻¹ChemAxon
Polarizability8.41 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0006-9000000000-eeaaf8aa838a1d6a7ddeView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0006-9000000000-622030119adee3079d84View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0006-9000000000-eeaaf8aa838a1d6a7ddeView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0006-9000000000-622030119adee3079d84View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-9000000000-58f4b3973bdf0094a5e3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000i-9000000000-4e7132ef8eb6971544b1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-00r5-9000000000-0cc5c90a4394d550268fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-06dj-9000000000-a74bfecfcdb93a5c3e07View in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-80B) , Positivesplash10-0006-9000000000-eeaaf8aa838a1d6a7ddeView in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI RMU-7M) , Positivesplash10-0006-9000000000-171c3774c90fd50b6d6bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-9000000000-e8c63126caa0f371f336View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00kr-9000000000-82affa84acc0579c193bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-9000000000-f63598734c0af05eb392View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-9000000000-e8c63126caa0f371f336View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00kr-9000000000-82affa84acc0579c193bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-9000000000-f63598734c0af05eb392View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-9000000000-2599bbcd002f75cefa1dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-9000000000-1171c0cf98959e7315c6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014i-9000000000-7dcc0fc66bb1e551b332View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-9000000000-2599bbcd002f75cefa1dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-9000000000-1171c0cf98959e7315c6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014i-9000000000-7dcc0fc66bb1e551b332View in MoNA
MSMass Spectrum (Electron Ionization)splash10-0006-9000000000-8d1a3988261033033e03View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureOral (14) ; inhalation (14) ; dermal (14) ; eye contact (14)
Mechanism of ToxicityDiacetyl is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
MetabolismDiacetyl is reduced to 2,3-butanediol (1).
Toxicity ValuesLD50: 1580 mg/kg (Oral, Rat) (14) LD50: >5 gm/kg (Dermal, Rabbit) (14)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity (not listed by IARC). (15)
Uses/SourcesCarrier of aroma of butter, vinegar, coffee and other foods (3).
Minimum Risk LevelNot Available
Health EffectsAcute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
SymptomsCauses eye irritation, redness and pain. Causes moderate skin irritation. Harmful if swallowed. May cause gastrointestinal irritation with nausea, vomiting and diarrhea. Causes respiratory tract irritation. Vapors may cause dizziness or suffocation. Harmful if inhaled. High exposure to butanedione may cause headache, drowsiness, lack of coordination and seizures (14).
TreatmentIf the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB03407
PubChem Compound ID650
ChEMBL IDCHEMBL365809
ChemSpider ID630
KEGG IDC00741
UniProt IDNot Available
OMIM ID
ChEBI ID16583
BioCyc IDNN-DIACETYLCHITOBIOSYLDIPHOSPHODOLICHO
CTD IDNot Available
Stitch IDDiacetyl
PDB IDNot Available
ACToR ID1588
Wikipedia LinkDiacetyl
References
Synthesis ReferenceXu, Ping; Chen, Hong; Du, Yi; Chen, Wanqiu; Xiao, Zijun. Method of preparation diacetyl by oxidization. Faming Zhuanli Shenqing Gongkai Shuomingshu (2005), 6 pp.
MSDSLink
General References
  1. Otsuka M, Mine T, Ohuchi K, Ohmori S: A detoxication route for acetaldehyde: metabolism of diacetyl, acetoin, and 2,3-butanediol in liver homogenate and perfused liver of rats. J Biochem. 1996 Feb;119(2):246-51. [8882713 ]
  2. Bryant GM, Argus MF, Arcos JC: Mitochondrial membrane-linked reactions in carcinogenesis: change in steroselective uncoupling of oxidative phosphorylation by aliphatic dicarbonyls and in the Arrhenius plot of NADH-indophenol reductase. Gann. 1977 Feb;68(1):89-98. [405268 ]
  3. McAlister ED, Van Vugt DA: Effect of leptin administration versus re-feeding on hypothalamic neuropeptide gene expression in fasted male rats. Can J Physiol Pharmacol. 2004 Dec;82(12):1128-34. [15644956 ]
  4. Mehta RC, Hogan TF, Mardmomen S, Ma JK: Chromatographic studies of mitomycin C degradation in albumin microspheres. J Chromatogr. 1988 Sep 9;430(2):341-9. [3148622 ]
  5. Hayes BK, Varki A: O-acetylation and de-O-acetylation of sialic acids. Sialic acid esterases of diverse evolutionary origins have serine active sites and essential arginine residues. J Biol Chem. 1989 Nov 15;264(32):19443-8. [2509478 ]
  6. Lombardo D, Campese D, Multigner L, Lafont H, De Caro A: On the probable involvement of arginine residues in the bile-salt-binding site of human pancreatic carboxylic ester hydrolase. Eur J Biochem. 1983 Jun 15;133(2):327-33. [6852044 ]
  7. Espinosa-Mansilla A, Duran-Meras I, Salinas F: High-performance liquid chromatographic-fluorometric determination of glyoxal, methylglyoxal, and diacetyl in urine by prederivatization to pteridinic rings. Anal Biochem. 1998 Jan 15;255(2):263-73. [9451513 ]
  8. Ostap EM: 2,3-Butanedione monoxime (BDM) as a myosin inhibitor. J Muscle Res Cell Motil. 2002;23(4):305-8. [12630704 ]
  9. Sokolchik I, Tanabe T, Baldi PF, Sze JY: Polymodal sensory function of the Caenorhabditis elegans OCR-2 channel arises from distinct intrinsic determinants within the protein and is selectively conserved in mammalian TRPV proteins. J Neurosci. 2005 Jan 26;25(4):1015-23. [15673683 ]
  10. Sohaskey CD, Barbour AG: Esterases in serum-containing growth media counteract chloramphenicol acetyltransferase activity in vitro. Antimicrob Agents Chemother. 1999 Mar;43(3):655-60. [10049283 ]
  11. Peretti E, Karlaganis G, Lauterburg BH: Acetylation of acetylhydrazine, the toxic metabolite of isoniazid, in humans. Inhibition by concomitant administration of isoniazid. J Pharmacol Exp Ther. 1987 Nov;243(2):686-9. [3681700 ]
  12. O'Neil MJ (ed) (2006). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th ed. Whitehouse Station, NJ: Merck and Co., Inc.
  13. Wikipedia. Diacetyl. Last Updated 30 June 2009. [Link]
  14. Fisher Scientific (2007). Material Safety Data Sheet for 2,3-Butanedione (Diacetyl). [Link]
  15. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Serine hydrolase activity
Specific Function:
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:
ACHE
Uniprot ID:
P22303
Molecular Weight:
67795.525 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>100 uMNot AvailableBindingDB 22725
References
  1. Wadkins RM, Hyatt JL, Wei X, Yoon KJ, Wierdl M, Edwards CC, Morton CL, Obenauer JC, Damodaran K, Beroza P, Danks MK, Potter PM: Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases. J Med Chem. 2005 Apr 21;48(8):2906-15. [15828829 ]
  2. Parkinson EI, Jason Hatfield M, Tsurkan L, Hyatt JL, Edwards CC, Hicks LD, Yan B, Potter PM: Requirements for mammalian carboxylesterase inhibition by substituted ethane-1,2-diones. Bioorg Med Chem. 2011 Aug 1;19(15):4635-43. doi: 10.1016/j.bmc.2011.06.012. Epub 2011 Jul 4. [21733699 ]
General Function:
Methylumbelliferyl-acetate deacetylase activity
Specific Function:
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Shows high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and 6-monoacetylmorphine.
Gene Name:
CES2
Uniprot ID:
O00748
Molecular Weight:
61806.41 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>100 uMNot AvailableBindingDB 22725
References
  1. Wadkins RM, Hyatt JL, Wei X, Yoon KJ, Wierdl M, Edwards CC, Morton CL, Obenauer JC, Damodaran K, Beroza P, Danks MK, Potter PM: Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases. J Med Chem. 2005 Apr 21;48(8):2906-15. [15828829 ]
  2. Parkinson EI, Jason Hatfield M, Tsurkan L, Hyatt JL, Edwards CC, Hicks LD, Yan B, Potter PM: Requirements for mammalian carboxylesterase inhibition by substituted ethane-1,2-diones. Bioorg Med Chem. 2011 Aug 1;19(15):4635-43. doi: 10.1016/j.bmc.2011.06.012. Epub 2011 Jul 4. [21733699 ]
General Function:
Triglyceride lipase activity
Specific Function:
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate.
Gene Name:
CES1
Uniprot ID:
P23141
Molecular Weight:
62520.62 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>100 uMNot AvailableBindingDB 22725
References
  1. Wadkins RM, Hyatt JL, Wei X, Yoon KJ, Wierdl M, Edwards CC, Morton CL, Obenauer JC, Damodaran K, Beroza P, Danks MK, Potter PM: Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases. J Med Chem. 2005 Apr 21;48(8):2906-15. [15828829 ]
  2. Parkinson EI, Jason Hatfield M, Tsurkan L, Hyatt JL, Edwards CC, Hicks LD, Yan B, Potter PM: Requirements for mammalian carboxylesterase inhibition by substituted ethane-1,2-diones. Bioorg Med Chem. 2011 Aug 1;19(15):4635-43. doi: 10.1016/j.bmc.2011.06.012. Epub 2011 Jul 4. [21733699 ]
General Function:
Temperature-gated cation channel activity
Specific Function:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
Gene Name:
TRPA1
Uniprot ID:
O75762
Molecular Weight:
127499.88 Da
References
  1. Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]