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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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To read more about chelation therapy for cardiovascular disease click here.


Chelation (from Greek χηλή, chelè, meaning claw; pronounced Template:IPA) is the binding or complexation of a bi- or multidentate ligand. These ligands, which are often organic compounds, are called chelants, chelators, chelating agents, or sequestering agent. The ligand forms a chelate complex with the substrate. The term is reserved for complexes in which the metal ion is bound to two or more atoms of the chelating agent, although the bonds may be any combination of coordination or ionic bonds.

Metal-EDTA chelate


The term chelate was first applied in 1920 by Sir Gilbert T. Morgan and H. D. K. Drew, who stated: "The adjective chelate, derived from the great claw or chele (Greek) of the lobster or other crustaceans, is suggested for the caliperlike groups which function as two associating units and fasten to the central atom so as to produce heterocyclic rings."[1]


Relative to the aqua complexes, e.g. [M(H2O)6]2+, the increased stability of a chelated complex, e.g. [M(EDTA]2- is called the chelate effect. Because chelating agents bind to metals through more than one coordination site, such ligands bind more tenaciously than unidentate ligands (like water). If a chelate were replaced by several monodentate ligands (such as water or ammonia), the total number of molecules would decrease, whereas if several monodentate ligands were replaced by a chelate, the number of free molecules increases. The effect is therefore entropic in that more sites are used by fewer ligands and this leaves more unbonded molecules: a total increase in the number of molecules in solution and a corresponding increase in entropy.

Chelation in nature

Virtually all biochemicals exhibit the ability to dissolve metal cations. Thus proteins, polysaccharides, and polynucleic acids are excellent polydentate ligands for many of the metal ions. In addition to these adventitious chelators, several are produced to specifically bind certain metals. Such chelating agents include the porphyrin rings in hemoglobin or chlorophyll and the Fe3+-chelating siderophores secreted by microorganisms. Histidine, malate and phytochelatin are typical chelators used by plants to avoid having poisonous metal ions in a free form.[2][3][4]

In geology

In earth science, chemical weathering is attributed to organic chelating agents, e.g. peptides and sugars, that have the ability to solubilize the metal ions in minerals and rocks.[5] Most metal complexes in the environment and in nature are bound in some form of chelate ring, e.g. with "humic acid" or a protein. Thus, metal chelates are relevant to the mobilization of metals in the soil, the uptake and the accumulation of metals into plants and micro-organisms. Selective chelation of heavy metals is relevant to bioremediation, e.g. removal of 137Cs from radioactive waste.[6]


Chelators are used in chemical analysis, as water softeners, and are ingredients in many commercial products such as shampoos and food preservatives. A commonly used synthetic chelator is EDTA. The term is used in water treatment programs and specifically in steam engineering, to describe a boiler water treatment system: Chelant Water Treatment system.

In medicine

Antibiotic drugs of the tetracycline family are chelators of Ca2+ and Mg2+ ions. Chelation therapy describes the use of chelating agents to detoxify poisonous metal agents such as mercury, arsenic, and lead by converting them to a chemically inert form that can be excreted without further interaction with the body. Chelation is also used as a scientifically unverified treatment for autism or other conditions. There are no published peer review publications regarding the efficacy of chelation agents for the treatment of autism.[7]

In addition to its use for the treatment of metal poisoning, chelation therapy has been considered an alternative medicine for the treatment of atherosclerotic disease. Many mechanisms have been postulated, including decalcification of atherosclerotic vessels. Other potential mechanisms, more accepted in the modern era, center around metal detoxification. Opinions regarding the use of chelation therapy for cardiovascular diseases (CVD) have long been controversial, as, until recently, there was not enough high-quality evidence for or against its use. Most recently, the Trial to Assess Chelation Therapy (TACT), a randomized, double blind, placebo controlled, 2x2 factorial trial, investigated the effect of EDTA-based infusions among stable post-myocardial infarction patients more than 50 years of age and with fairly normal kidney function. TACT revealed a modest decrease in major adverse cardiovascular events among enrolled patients randomized to EDTA-based infusions. When the pre-specified subgroup of patients with diabetes was analyzed, the decrease in adverse cardiovascular outcomes was even more robust.

EDTA chelation can be a dangerous practice, especially when Na2EDTA is prescribed rather than CaEDTA. The CDC reports that use of Na2EDTA has resulted in fatalities due to hypocalcemia.[8]

EDTA is also used in root canal treatment as a way to irrigate the canal. EDTA is used as a chelating agent to either soften the dentin facilitating access to the entire canal length and to remove the smear layer formed during instrumentation.

See also

References cited

  1. J. Chem. Soc., 1920, 117, 1456
  2. U Krämer, J D Cotter-Howells, J M Charnock, A H J M Baker, J A C Smith (1996). "Free histidine as a metal chelator in plants that accumulate nickel". Nature. 379: 635-638.
  3. Jurandir Vieira Magalhaes (2006). "Aluminum tolerance genes are conserved between monocots and dicots". Proc Natl Acad Sci U S A. 103 (26): 9749-9750.
  4. Suk-Bong Ha, Aaron P. Smith, Ross Howden, Wendy M. Dietrich, Sarah Bugg, Matthew J. O'Connell, Peter B. Goldsbrough, and Christopher S. Cobbett (1999). "Phytochelatin synthase genes from arabidopsis and the yeast Schizosaccharomyces pombe". Plant Cell. 11: 1153-1164.
  5. Dr. Michael Pidwirny, University of British Columbia Okanagan,
  6. Prasad (ed). Metals in the Environment. University of Hyderabad. Dekker, New York, 2001
  7. Doja A, Roberts W (2006). "Immunizations and autism: a review of the literature". Can J Neurol Sci. 33 (4): 341–46. PMID 17168158.
  8. U.S. Centers for Disease Control, "Deaths Associated with Hypocalcemia from Chelation Therapy" (March 3, 2006),

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