Chelation (US: /kiːˈleɪʃən/ , UK: /tʃɪˈleɪʃən/) is a type
of bonding of ions and molecules to metal ions. It involves the
formation or presence of two or more separate coordinate bonds between
a polydentate (multiple bonded) ligand and a single central
atom. Usually these ligands are organic compounds, and are
called chelants, chelators, chelating agents, or sequestering agents.
Chelation is useful in applications such as providing nutritional
supplements, in chelation therapy to remove toxic metals from the
body, as contrast agents in
MRI scanning, in manufacturing using
homogeneous catalysts, in chemical water treatment to assist in the
removal of metals, and in fertilizers.
1 Chelate effect
2 In nature
2.1 In biochemistry and microbiology
2.2 In geology
3 Medical applications
3.1 Nutritional supplements
3.2 Dental and Oral Application
3.3 Heavy-metal detoxification
3.5 Other medical applications
3.6 Alternative medicine
4 Industrial and agricultural applications
4.2 Water softening
7 External links
Ethylenediamine ligand chelating to a metal with two bonds.
Cu2+ complexes with nonchelating methylamine (left) and chelating
ethylenediamine (right) ligands.
The chelate effect is the enhanced affinity of chelating ligands for a
metal ion compared to the affinity of a collection of similar
nonchelating (monodentate) ligands for the same metal.
Consider the two equilibria, in aqueous solution, between the
copper(II) ion, Cu2+ and ethylenediamine (en) on the one hand and
methylamine, MeNH2 on the other.
Cu2+ + en ⇌ [Cu(en)]2+
Cu2+ + 2 MeNH2 ⇌ [Cu(MeNH2)2]2+
In (1) the bidentate ligand ethylenediamine forms a chelate complex
with the copper ion.
Chelation results in the formation of a
five-membered CuC2N2 ring. In (2) the bidentate ligand is replaced by
two monodentate methylamine ligands of approximately the same donor
power, meaning that the enthalpy of formation of Cu—N bonds is
approximately the same in the two reactions.
The thermodynamic approach to describing the chelate effect considers
the equilibrium constant for the reaction: the larger the equilibrium
constant, the higher the concentration of the complex.
[Cu(en)] = β11[Cu][en]
[Cu(MeNH2)2] = β12[Cu][MeNH2]2
Electrical charges have been omitted for simplicity of notation. The
square brackets indicate concentration, and the subscripts to the
stability constants, β, indicate the stoichiometry of the complex.
When the analytical concentration of methylamine is twice that of
ethylenediamine and the concentration of copper is the same in both
reactions, the concentration [Cu(en)] is much higher than the
concentration [Cu(MeNH2)2] because β11 ≫ β12.
An equilibrium constant, K, is related to the standard Gibbs free
displaystyle Delta G^ ominus
displaystyle Delta G^ ominus =-RTln K=Delta H^ ominus -TDelta
where R is the gas constant and T is the temperature in kelvins.
displaystyle Delta H^ ominus
is the standard enthalpy change of the reaction and
displaystyle Delta S^ ominus
is the standard entropy change.
Since the enthalpy should be approximately the same for the two
reactions, the difference between the two stability constants is due
to the effects of entropy. In equation (1) there are two particles on
the left and one on the right, whereas in equation (2) there are three
particles on the left and one on the right. This difference means that
less entropy of disorder is lost when the chelate complex is formed
than when the complex with monodentate ligands is formed. This is one
of the factors contributing to the entropy difference. Other factors
include solvation changes and ring formation. Some experimental data
to illustrate the effect are shown in the following table.
displaystyle Delta G^ ominus
displaystyle Delta H^ ominus mathrm /kJ mol^ -1
displaystyle -TDelta S^ ominus mathrm /kJ mol^ -1
Cu2+ + 4 MeNH2 ⇌ Cu(MeNH2)42+
Cu2+ + 2 en ⇌ Cu(en)22+
These data confirm that the enthalpy changes are approximately equal
for the two reactions and that the main reason for the greater
stability of the chelate complex is the entropy term, which is much
less unfavorable. In general it is difficult to account precisely for
thermodynamic values in terms of changes in solution at the molecular
level, but it is clear that the chelate effect is predominantly an
effect of entropy.
Other explanations, including that of Schwarzenbach, are discussed
in Greenwood and Earnshaw (loc.cit).
Numerous biomolecules exhibit the ability to dissolve certain metal
cations. Thus, proteins, polysaccharides, and polynucleic acids are
excellent polydentate ligands for many metal ions. Organic compounds
such as the amino acids glutamic acid and histidine, organic diacids
such as malate, and polypeptides such as phytochelatin are also
typical chelators. In addition to these adventitious chelators,
several biomolecules are specifically produced to bind certain metals
(see next section).
In biochemistry and microbiology
Virtually all metalloenzymes feature metals that are chelated, usually
to peptides or cofactors and prosthetic groups. Such chelating
agents include the porphyrin rings in hemoglobin and chlorophyll. Many
microbial species produce water-soluble pigments that serve as
chelating agents, termed siderophores. For example, species of
Pseudomonas are known to secrete pyochelin and pyoverdine that bind
iron. Enterobactin, produced by E. coli, is the strongest chelating
agent known. The marine mussels use metal chelation esp. Fe3+
chelation with the Dopa residues in mussel foot protein-1 to improve
the strength of the threads that it uses to secure itself to
In earth science, hot chemical weathering is attributed to organic
chelating agents (e.g., peptides and sugars) that extract metal ions
from minerals and rocks. Some metal complexes in the environment
and in nature are not found in some form of chelate ring (e.g., with a
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 microorganisms. Selective chelation of heavy
metals is relevant to bioremediation (e.g., removal of 137Cs from
In the 1960s, scientists developed the concept of chelating a metal
ion prior to feeding the element to the animal. They believed that
this would create a neutral compound, protecting the mineral from
being complexed with insoluble salts within the stomach, which would
render the metal unavailable for absorption. Amino acids, being
effective metal binders, were chosen as the prospective ligands, and
research was conducted on the metal-amino acid combinations. The
research supported that the metal-amino acid chelates were able to
enhance mineral absorption.
During this period, synthetic chelates such as
ethylenediaminetetraacetic acid (EDTA) were being developed. These
applied the same concept of chelation and did create chelated
compounds; but these synthetics were too stable and not nutritionally
viable. If the mineral was taken from the
EDTA ligand, the ligand
could not be used by the body and would be expelled. During the
expulsion process the
EDTA ligand randomly chelated and stripped
another mineral from the body.
According to the Association of American Feed Control Officials
(AAFCO), a metal amino acid chelate is defined as the product
resulting from the reaction of a metal ion from a soluble metal salt
with a mole ratio of one to three (preferably two) moles of amino
acids. The average weight of the hydrolyzed amino acids must be
approximately 150 and the resulting molecular weight of the chelate
must not exceed 800 Da.
Since the early development of these compounds, much more research has
been conducted, and has been applied to human nutrition products in a
similar manner to the animal nutrition experiments that pioneered the
technology. Ferrous bis-glycinate is an example of one of these
compounds that has been developed for human nutrition.
Dental and Oral Application
First-Generation Dentin Adhesives were first designed and produced in
the 1950s. These systems were based on a co-monomer chelate with
calcium on the surface of the tooth and generated very weak water
resistance chemical bonding (2-3 MPa).
Chelation therapy is the use of chelating agents to detoxify a
patient's body of 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.
EDTA has been approved by the U.S. Food and Drug
Administration (FDA), but only for serious cases of lead poisoning. It
is not approved for treating "heavy metal toxicity".
Although they can be beneficial in cases of serious lead poisoning,
use of unapproved chelating agents is dangerous. Use of disodium EDTA
(edetate disodium) instead of calcium disodium
EDTA has resulted in
fatalities due to hypocalcemia. Disodium
EDTA is not approved by
the FDA for any use, and all FDA-approved chelation therapy
products require a prescription.
Chelate complexes of gadolinium are often used as contrast agents in
MRI scans. Auranofin, a chelate complex of gold, is used in the
treatment of rheumatoid arthritis.
Other medical applications
Chelation in the intestinal tract is a cause of numerous interactions
between drugs and metal ions (also known as "minerals" in nutrition).
As examples, antibiotic drugs of the tetracycline and quinolone
families are chelators of Fe2+, Ca2+ and Mg2+ ions.
EDTA, which binds to and sequesters calcium, is used to alleviate the
hypercalcimia that often results from band keratopathy. The calcium
may then be scraped from the cornea with a spatula-shaped instrument,
allowing for some increase in clarity of vision for the patient. This
procedure requires the use of numbing drops, as the acid, though weak
from a pH standpoint, would cause acute ocular discomfiture. Patients
normally wear an eye shield following such procedures and are advised
against swimming for some weeks afterwards. This is normally an
outpatient procedure, requiring no general anesthetics to be employed
prior to performing the procedure.
Although the practice has been discredited  and even condemned
by organizations such as the U.S. National Institutes of Health, the
Journal of the American Medical Association, and The New England
Journal of Medicine, chelation was used as a treatment for autism.
This practice has largely ended due to the absence of scientific
plausibility, its potentially deadly side-effects, and the lack of
approval by the U.S. Food and Drug Administration
Industrial and agricultural applications
Homogeneous catalysts are often chelated complexes. A typical example
is the ruthenium(II) chloride chelated with
BINAP (a bidentate
phosphine) used in e.g.
Noyori asymmetric hydrogenation
Noyori asymmetric hydrogenation and asymmetric
isomerization. The latter has the practical use of manufacture of
Citric acid is used to soften water in soaps and laundry detergents. A
common synthetic chelator is EDTA. Phosphonates are also well-known
chelating agents. Chelators are used in water treatment programs and
specifically in steam engineering, e.g., boiler water treatment
system: Chelant Water Treatment system. Although the treatment is
often referred to as "softening," chelation has little effect on the
water's mineral content, other than to make it soluble. What does
change is the water's pH level, which is lowered.
Metal chelate compounds are common components of fertilizers to
provide micronutrients. These micronutrients (manganese, iron, zinc,
copper) are required for the health of the plants. Most fertilizers
contain phosphate salts that, in the absence of chelating agents,
typically convert these metal ions into insoluble solids that are of
no nutritional value to the plants.
EDTA is the typical chelating
agent that keeps these metal ions in a soluble form.
The ligand forms a chelate complex with the substrate. Chelate
complexes are contrasted with coordination complexes composed of
monodentate ligands, which form only one bond with the central atom.
The word chelation is derived from Greek χηλή, chēlē, meaning
"claw"; the ligands lie around the central atom like the claws of a
lobster. 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
^ IUPAC definition of chelation.
^ Latin chela, from Greek, denotes a claw.
^ Greenwood, Norman N.; Earnshaw, Alan (1997). Chemistry of the
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^ Schwarzenbach, G. (1952). "Der Chelateffekt". Helvetica Chimica
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^ Krämer, Ute; Cotter-Howells, Janet D.; Charnock, John M.; Baker,
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Bugg, Sarah; O'Connell, Matthew J.; Goldsbrough, Peter B.; Cobbett,
Christopher S. (1999). "
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^ Das, Saurabh; Rodriguez, Nadine R. Martinez; Wei, Wei; Waite, J.
Herbert; Israelachvili, Jacob N. (2015). "
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^ a b "FDA Issues
Chelation Therapy Warning". September 26, 2008.
Retrieved May 14, 2016.
^ Centers for Disease Control Prevention (CDC) (2006). "Deaths
associated with hypocalcemia from chelation therapy--Texas,
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^ "Questions and Answers on Unapproved
Chelation Products". FDA.
February 2, 2016. Retrieved May 14, 2016.
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^ Morgan, Gilbert T.; Drew, Harry Dugald Keith (1920).
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The dictionary definition of chelate at Wiktionary
Chelating agents / chelation therapy (V03AC, others)
‡Withdrawn from market