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Record Information
Version2.0
Creation Date2014-09-11 02:05:05 UTC
Update Date2014-12-24 20:26:55 UTC
Accession NumberT3D4690
Identification
Common NameDichloroacetic Acid
ClassSmall Molecule
DescriptionDichloroacetic acid, often abbreviated DCA, is an acid analogue of acetic acid in which two of the three hydrogen atoms of the methyl group have been replaced by chlorine atoms. The salts and esters of dichloroacetic acid are called dichloroacetates. Salts of DCA are used as drugs since they inhibit the enzyme pyruvate dehydrogenase kinase. Early reports of its activity against brain cancer cells led patients to treat themselves with DCA, which is commercially available in non-pharmaceutical grade. A phase 1 study in 5 patients concluded that DCA was safe, but wasn't designed to establish effectiveness.
Compound Type
  • Drug
  • Household Toxin
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
DCA
Dichloroacetate
dichloroacetate
Dichloroacetic acid
Chemical FormulaC2H2Cl2O2
Average Molecular Mass128.942 g/mol
Monoisotopic Mass127.943 g/mol
CAS Registry Number79-43-6
IUPAC Name2,2-dichloroacetic acid
Traditional Namedichloroacetic acid
SMILESOC(=O)C(Cl)Cl
InChI IdentifierInChI=1S/C2H2Cl2O2/c3-1(4)2(5)6/h1H,(H,5,6)
InChI KeyInChIKey=JXTHNDFMNIQAHM-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as alpha-halocarboxylic acids. These are carboxylic acids containing a halogen atom bonded to the alpha carbon atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAlpha-halocarboxylic acids and derivatives
Direct ParentAlpha-halocarboxylic acids
Alternative Parents
Substituents
  • Alpha-halocarboxylic acid
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Alkyl halide
  • Alkyl chloride
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceNot Available
Experimental Properties
PropertyValue
Melting Point13.5°C
Boiling Point194°C
Solubility1E+006 mg/L (at 20°C)
LogP0.92
Predicted Properties
PropertyValueSource
Water Solubility72.3 g/LALOGPS
logP0.99ALOGPS
logP1.06ChemAxon
logS-0.25ALOGPS
pKa (Strongest Acidic)2.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity22.62 m³·mol⁻¹ChemAxon
Polarizability9.32 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0059-6900000000-9d33b2f109bd8208b818JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-001i-9000000000-cdde3faa793ecb51af1bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-001i-9000000000-c1ded91474fde2787d95JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0019-9000000000-cea4fe3c3f1653aa150dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-000i-9000000000-68d75216c4534c61a4b4JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0059-6900000000-55338ed4fe8335b6f8baJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-001i-9000000000-d0c2081f59cf4a1d9bb9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-001i-9000000000-aa8cfce9c157e8ce5c26JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0019-9000000000-d0fd266005ba1e11af9fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-000i-9000000000-67e8e2a12579c484a9d1JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0900000000-2c591b536e9b1cdd5103JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-0900000000-e235e740081767bebeb0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03ec-7900000000-19ec9f5725beb405a85fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0900000000-9824d7737d8edd5c640cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-1900000000-047b42b607987ffb5cbaJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-1900000000-d56ccde35fe241d821f6JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0002-9000000000-5cc2c87638085fad9afcJSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureIngestion
Mechanism of ToxicityThe dichloroacetate ion stimulates the activity of the enzyme pyruvate dehydrogenase by inhibiting the enzyme pyruvate dehydrogenase kinase. Thus, it decreases lactate production by shifting the metabolism of pyruvate from fermentation towards oxidation in the mitochondria. (Wikipedia)
MetabolismDichloroacetic acid is metabolized in the liver by oxidative dechlorination to yield glyoxylate, which can enter intermediary metabolism and either be oxidized to oxalate and excreted, converted to carbon dioxide, and/or incorporated into amino acids or other cellular molecules. (3)
Toxicity ValuesORAL (LD50): Acute: 2820 mg/kg [Rat]; DERMAL (LD50): Acute: 510 mg/kg [Rabbit]
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (4)
Uses/SourcesDichloroacetic acid has shown promise as a potentially new class of anti-cancer medication, but has yet to complete clinical trials. Early reports of its activity against brain cancer cells led patients to treat themselves with DCA, which is commercially available in non-pharmaceutical grade. As of October 2014, dichloroacetic acid was undergoing phase III clinical trials for cancer treatment (1) (Wikipedia). Dichloroacetic acid has undergone clinical trials for the treatment of lactic acidosis in humans, but the trials found no clinical benefit (Wikipedia). In 2014 Thomas E. Mallouk and colleagues published a new technique for the production of graphene by intercalation of graphite with non-oxidizing Brønsted acids including dichloroacetic acid, raising the prospect that dichloroacetic acid might be used in industrial graphene production in the future (2).
Minimum Risk LevelNot Available
Health EffectsMultiple independent studies demonstrate that DCA has the ability to alter normal carbohydrate metabolism. Dichloroacetic acid treatment results in a significant reduction in plasma levels of glucose, pyruvate, and lactate. Another consistent finding in DCA ingestion studies is a dose-related increase in liver size, generally accompanied (or caused) by an increase in glycogen deposition in the liver. There is an extensive and consistent data base demonstrating the reproductive toxicity of DCA in males and females. Neurologic symptoms and morphologic changes in the nervous system have been reported in humans, dogs, and rats. (3)
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB08809
HMDB IDNot Available
PubChem Compound ID6597
ChEMBL IDCHEMBL13960
ChemSpider ID10771217
KEGG IDC11149
UniProt IDNot Available
OMIM ID
ChEBI ID36386
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkDichloroacetic_acid
References
Synthesis Reference

Joanne D. Burger, William L. Howard, “Method for preparing pentachloroacetone and dichloroacetic acid from isopropyl ethers.” U.S. Patent US3996272, issued August, 1968.

MSDST3D4690.pdf
General References
  1. American Cancer Society - Dichloroacetate (DCA) [Link]
  2. Nina I. Kovtyukhova, Yuanxi Wang, Ayse Berkdemir, Rodolfo Cruz-Silva, Mauricio Terrones, Vincent H. Crespi & Thomas E. Mallouk. Non-oxidative intercalation and exfoliation of graphite by Brønsted acids. Nature Chemistry (2014), published online 07 September 2014. doi:10.1038/nchem.2054. [Link]
  3. US EPA - Toxicological Review of Dichloroacetic Acid (August 2003) [Link]
  4. 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:
Pyruvate dehydrogenase (acetyl-transferring) kinase activity
Specific Function:
Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress.
Gene Name:
PDK1
Uniprot ID:
Q15118
Molecular Weight:
49243.765 Da
References
  1. Stacpoole PW: The pharmacology of dichloroacetate. Metabolism. 1989 Nov;38(11):1124-44. [2554095 ]