is a type of bonding of ions
and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bond
s between a polydentate
(multiple bonded) ligand
and a single central atom. IUPAC definition of chelation.
, from Greek, denotes a claw. Usually these ligands are organic compound
s, 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 catalyst
s, in chemical water treatment
to assist in the removal of metals, and in fertilizer
chelating to a metal with two bonds.]]
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.
In () the bidentate
ligand ethylenediamine forms a chelate complex with the copper ion. Chelation results in the formation of a five-membered CuC2N2 ring. In () 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.
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.
11 Cu en
12 Cu MeNH2
Electrical charges have been omitted for simplicity of notation. The square brackets indicate concentration, and the subscripts to the stability constant
s, 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 energy
\Delta G^\ominus = - RT \ln K = \Delta H^\ominus - T \Delta S^\ominus
is the gas constant
is the temperature in kelvin
s. is the standard enthalpy
change of the reaction and is the standard entropy
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 () there are two particles on the left and one on the right, whereas in equation () 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.
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
exhibit the ability to dissolve certain metal cation
s. Thus, protein
s, and polynucleic acids are excellent polydentate ligands for many metal ions. Organic compounds such as the amino acids glutamic acid
, 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.S. J. Lippard, J. M. Berg "Principles of Bioinorganic Chemistry" University Science Books: Mill Valley, CA; 1994. . Such chelating agents include the porphyrin
rings in hemoglobin
. Many microbial species produce water-soluble pigments that serve as chelating agents, termed siderophores
. For example, species of Pseudomonas
are known to secrete pyochelin
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 surfaces.
In earth science, hot chemical weathering
is attributed to organic chelating agents (e.g., peptide
s and sugar
s) that extract metal ions
from minerals and rocks.Dr. Michael Pidwirny, University of British Columbia Okanagan, http://www.physicalgeography.net/fundamentals/10r.html 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
s. Selective chelation of heavy metals
is relevant to bioremediation
(e.g., removal of 137Cs
from radioactive waste).Prasad (ed). Metals in the Environment. University of Hyderabad. Dekker, New York, 2001
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.
Chelation therapy is the use of chelating agents to detoxify
a patient's body of poison
ous metal agents, such as mercury
, and lead
, by converting them to a chemically inert form that can be excreted without further interaction with the body. Chelation using calcium disodium 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 agent
s in MRI scan
, 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 drug
s of the tetracycline
families are chelators of Fe
2+ and Mg
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
. 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
s 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
and asymmetric isomerization. The latter has the practical use of manufacture of synthetic (–)-menthol
is used to soften water
s and laundry detergent
s. A common synthetic chelator is EDTA
s 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 complex
es composed of monodentate ligands
, which form only one bond with the central atom. The word chelation is derived from Greek
, 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
) 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