Dichloroacetic acid

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Dichloroacetic acid
Dichloroacetic-acid-2D-skeletal.png Dichloroacetic-acid-3D-vdW.png
Identifiers
CAS number 79-43-6 YesY
PubChem 6597
ChemSpider 10771217 YesY
UNII 9LSH52S3LQ YesY
DrugBank DB08809
KEGG C11149 YesY
MeSH Dichloroacetate
ChEBI CHEBI:36386 YesY
ChEMBL CHEMBL13960 YesY
RTECS number AG6125000
Jmol-3D images Image 1
Properties
Molecular formula C2H2Cl2O2
Molar mass 128.94 g mol−1
Appearance Colorless liquid
Density 1.5634 g/cm3 (20 °C)
Melting point 9 to 11 °C (48 to 52 °F; 282 to 284 K)
Boiling point 194 °C (381 °F; 467 K)
Solubility in water miscible
Solubility miscible with ethanol, diethyl ether[1]
Acidity (pKa) 1.35[1]
Thermochemistry
Std enthalpy of
formation
ΔfHo298
-496.3 kJ·mol-1[1]
Hazards
MSDS MSDS (jtbaker)
R-phrases R35 R50
S-phrases (S1/2) S26 S45 S61
NFPA 704
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g., canola oil Health code 3: Short exposure could cause serious temporary or residual injury. E.g., chlorine gas Reactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogen Special hazards (white): no codeNFPA 704 four-colored diamond
Related compounds
Related chloroacetic acids Chloroacetic acid
Trichloroacetic acid
Related compounds Acetic acid
Difluoroacetic acid
Dibromoacetic acid
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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Infobox references

Dichloroacetic acid, often abbreviated DCA, is the chemical compound with formula CHCl
2
COOH
. It is an acid, an analogue of acetic acid, in which two of the three hydrogen atoms of the methyl group have been replaced by chlorine atoms.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 have been studied as potential drugs because they inhibit the enzyme pyruvate dehydrogenase kinase.[2]

Although preliminary studies have shown DCA can slow the growth of certain tumors in animal studies and in vitro studies, "Available evidence does not support the use of DCA for cancer treatment at this time."[3]

Chemistry and occurrence

The chemistry of dichloroacetic acid is typical for halogenated organic acids. It is a member of the chloroacetic acids family. The dichloroacetate ion is produced when the acid is mixed with water. As an acid with a pKa of 1.35,[1] pure dichloroacetic acid is very corrosive and extremely destructive to tissues of the mucous membranes and upper respiratory tract via inhalation.[4]

DCA has been shown to occur in nature in at least one seaweed, Asparagopsis taxiformis.[5] It is a trace product of the chlorination of drinking water and is produced by the metabolism of various chlorine-containing drugs or chemicals.[6] DCA is typically prepared by the reduction of trichloroacetic acid. DCA is prepared from chloral hydrate also by the reaction with calcium carbonate and sodium cyanide in water followed by acidifying with hydrochloric acid.

Research

Lactic acidosis

A randomized controlled trial in children with congenital lactic acidosis found that while DCA was well tolerated, it was ineffective in improving clinical outcomes.[7] A separate trial of DCA in children with MELAS (a syndrome of inadequate mitochondrial function, leading to lactic acidosis) was halted early, as all 15 of the children receiving DCA experienced significant nerve toxicity without any evidence of benefit from the medication.[8] A randomized controlled trial of DCA in adults with lactic acidosis found that while DCA lowered blood lactate levels, it had no clinical benefit and did not improve hemodynamics or survival.[9]

Thus, while early case reports and pre-clinical data suggested that DCA might be effective for lactic acidosis, subsequent controlled trials have found no clinical benefit of DCA in this setting. In addition, clinical trial subjects were incapable of continuing on DCA as a study medication owing to progressive toxicities.

Cancer

Although preliminary studies have shown DCA can slow the growth of certain tumors in animal studies and in vitro studies, "Available evidence does not support the use of DCA for cancer treatment at this time."[10] Physicians warned of potential problems if people attempt to try DCA outside a controlled clinical trial. "If it starts going badly, who is following you before it gets out of control? By the time you realize your liver is failing, you're in big trouble", said Laura Shanner, Associate Professor of Health Ethics at the University of Alberta.[11]

References

  1. ^ a b c d Haynes, William M., ed. (2011). CRC Handbook of Chemistry and Physics (92nd ed.). Boca Raton, FL: CRC Press. ISBN 1439855110. 
  2. ^ Kato, M.; Li, J.; Chuang, J. L.; Chuang, D. T. (2007). "Distinct Structural Mechanisms for Inhibition of Pyruvate Dehydrogenase Kinase Isoforms by AZD7545, Dichloroacetate, and Radicicol". Structure 15 (8): 992–1004. doi:10.1016/j.str.2007.07.001. PMC 2871385. PMID 17683942.  edit
  3. ^ "Dichloracetate (DCA)". American Cancer Society. Retrieved 1 December 2012. 
  4. ^ J.T. Baker MSDS
  5. ^ http://paradigmslip.ca/references/uhm_phd_7810263_r.pdf
  6. ^ Stacpoole P, Henderson G, Yan Z, James M (1998). "Clinical pharmacology and toxicology of dichloroacetate". Environ Health Perspect. 106 Suppl 4: 989–994. doi:10.2307/3434142. JSTOR 3434142. PMC 1533324. PMID 9703483. 
  7. ^ Stacpoole P, Kerr D, Barnes C, Bunch S, Carney P, Fennell E, Felitsyn N, Gilmore R, Greer M, Henderson G, Hutson A, Neiberger R, O'Brien R, Perkins L, Quisling R, Shroads A, Shuster J, Silverstein J, Theriaque D, Valenstein E (2006). "Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children". Pediatrics 117 (5): 1519–1531. doi:10.1542/peds.2005-1226. PMID 16651305. 
  8. ^ Kaufmann P, Engelstad K, Wei Y, Jhung S, Sano M, Shungu D, Millar W, Hong X, Gooch C, Mao X, Pascual J, Hirano M, Stacpoole P, DiMauro S, De Vivo D (2006). "Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial". Neurology 66 (3): 324–330. doi:10.1212/01.wnl.0000196641.05913.27. PMID 16476929. 
  9. ^ Stacpoole P, Wright E, Baumgartner T, Bersin R, Buchalter S, Curry S, Duncan C, Harman E, Henderson G, Jenkinson S (1992). "A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group". N Engl J Med 327 (22): 1564–1569. doi:10.1056/NEJM199211263272204. PMID 1435883. 
  10. ^ "Dichloracetate (DCA)". American Cancer Society. Retrieved 1 December 2012. 
  11. ^ Andrea Sands (March 18, 2007). "Experts caution against patients compiling own data on unapproved cancer drug". Edmonton Journal. 

External links