Chelation (/kiːˈleɪʃən/) is a type of bonding ofions and their molecules to metal ions. It involves the formation or presence of two or more separatecoordinate bonds between apolydentate (multiple bonded)ligand and a single central metal atom.[1][2] These ligands are called chelants, chelators, chelating agents, or sequestering agents. They are usuallyorganic compounds, but this is not a necessity.
The wordchelation is derived fromGreek χηλή,chēlē, meaning "claw"; the ligands lie around the central atom like the claws of acrab. The termchelate (/ˈkiːleɪt/) was first applied in 1920 by SirGilbert T. Morgan andH. D. K. Drew, who stated: "The adjective chelate, derived from the great claw orchele (Greek) of the crab or other crustaceans, is suggested for the caliperlike groups which function as two associating units and fasten to the central atom so as to produceheterocyclic rings."[3]
Chelation is useful in applications such as providing nutritional supplements, inchelation therapy to remove toxic metals from the body, ascontrast agents inMRI scanning, in manufacturing usinghomogeneous catalysts, in chemicalwater treatment to assist in the removal of metals, and infertilizers.
The chelate effect is the greater affinity of chelating ligands for a metal ion than that of similar nonchelating (monodentate) ligands for the same metal.
The thermodynamic principles underpinning the chelate effect are illustrated by the contrasting affinities ofcopper(II) forethylenediamine (en) vs.methylamine.
| Cu2+ + en ⇌ [Cu(en)]2+ | 1 |
| Cu2+ + 2 MeNH2 ⇌ [Cu(MeNH2)2]2+ | 2 |
In (1) the 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 twomonodentate methylamine ligands of approximately the same donor power, indicating that the Cu–N bonds are approximately the same in the two reactions.
Thethermodynamic approach to describing the chelate effect considers theequilibrium constant for the reaction: the larger the equilibrium constant, the higher the concentration of the complex.
| [Cu(en)] =β11[Cu][en] | 3 |
| [Cu(MeNH2)2] =β12[Cu][MeNH2]2 | 4 |
Electrical charges have been omitted for simplicity of notation. The square brackets indicate concentration, and the subscripts to thestability constants,β, indicate thestoichiometry of the complex. When theanalytical 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] becauseβ11 ≫β12.
An equilibrium constant,K, is related to the standardGibbs free energy, by
whereR is thegas constant andT is the temperature inkelvins. is the standardenthalpy change of the reaction and is the standardentropy 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 lessentropy of disorder is lost when the chelate complex is formed with bidentate ligand 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.[4]
| Equilibrium | logβ | | ||
|---|---|---|---|---|
| Cu2+ + 2 MeNH2 ⇌ Cu(MeNH2)22+ | 6.55 | −37.4 | −57.3 | 19.9 |
| Cu2+ + en ⇌ Cu(en)2+ | 10.62 | −60.67 | −56.48 | −4.19 |
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 ofSchwarzenbach,[5] are discussed in Greenwood and Earnshaw (loc.cit).
Numerousbiomolecules exhibit the ability to dissolve certain metalcations. Thus,proteins,polysaccharides, and polynucleic acids are excellent polydentate ligands for many metal ions. Organic compounds such as the amino acidsglutamic acid andhistidine, organic diacids such asmalate, and polypeptides such asphytochelatin are also typical chelators. In addition to these adventitious chelators, several biomolecules are specifically produced to bind certain metals (see next section).[6][7][8][9]
Virtually all metalloenzymes feature metals that are chelated, usually to peptides or cofactors and prosthetic groups.[9] Such chelating agents include theporphyrin rings inhemoglobin andchlorophyll. Many microbial species produce water-soluble pigments that serve as chelating agents, termedsiderophores. For example, species ofPseudomonas are known to secretepyochelin andpyoverdine that bind iron.Enterobactin, produced byE. coli, is the strongest chelating agent known. The marinemussels use metal chelation, especially Fe3+ chelation with theDopa residues in mussel foot protein-1 to improve the strength of the threads that they use to secure themselves to surfaces.[10][11][12]
In earth science, chemicalweathering is attributed to organic chelating agents (e.g.,peptides andsugars) that extractmetal ions from minerals and rocks.[13] Most metal complexes in the environment and in nature are bound in some form of chelate ring (e.g., with ahumic acid or a protein). Thus, metal chelates are relevant to the mobilization ofmetals in thesoil, the uptake and the accumulation ofmetals intoplants andmicroorganisms. Selective chelation ofheavy metals is relevant tobioremediation (e.g., removal of137Cs fromradioactive waste).[14]
Synthetic chelates such asethylenediaminetetraacetic acid (EDTA) proved 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 other minerals from the body.[15] 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 metal ions from a soluble metal salt with amino acids, with amole ratio in the range of 1–3 (preferably 2) moles of amino acids for one mole of metal.[citation needed] 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.[citation needed] 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.[16]
Dentin adhesives were first designed and produced in the 1950s based on a co-monomer chelate with calcium on the surface of the tooth and generated very weak water-resistant chemical bonding (2–3 MPa).[17]
Chelation therapy is an antidote for poisoning bymercury,arsenic, andlead. Chelating agents convert these metal ions into a chemically and biochemically inert form that can be excreted. Chelation usingsodium calcium edetate has been approved by theU.S. Food and Drug Administration (FDA) for serious cases oflead poisoning. It is not approved for treating "heavy metal toxicity".[18] Although beneficial in cases of serious lead poisoning, use of disodium EDTA (edetate disodium) instead of calcium disodium EDTA has resulted in fatalities due tohypocalcemia.[19] Disodium EDTA is not approved by the FDA for any use,[18] and all FDA-approved chelation therapy products require a prescription.[20]
Chelate complexes ofgadolinium are often used ascontrast agents inMRI scans, althoughiron particle andmanganese chelate complexes have also been explored.[21][22] Bifunctional chelate complexes ofzirconium,gallium,fluorine,copper,yttrium,bromine, oriodine are often used for conjugation tomonoclonal antibodies for use in antibody-basedPET imaging.[23] These chelate complexes often employ the usage ofhexadentate ligands such asdesferrioxamine B (DFO), according to Meijset al.,[24] and the gadolinium complexes often employ the usage of octadentate ligands such as DTPA, according to Desreuxet al.[25]Auranofin, a chelate complex ofgold, is used in the treatment of rheumatoid arthritis, andpenicillamine, which forms chelate complexes ofcopper, is used in the treatment ofWilson's disease andcystinuria, as well as refractory rheumatoid arthritis.[26][27]
Chelation in the intestinal tract is a cause of numerous interactions between drugs and metal ions (also known as "minerals" in nutrition). As examples,antibioticdrugs of thetetracycline andquinolone families are chelators ofFe2+,Ca2+, andMg2+ ions.[28][29]
EDTA, which binds to calcium, is used to alleviate thehypercalcemia that often results fromband keratopathy. The calcium may then be removed from thecornea, allowing for some increase in clarity of vision for the patient.[30][31]
Homogeneous catalysts are often chelated complexes. A representative example is the use ofBINAP (a bidentatephosphine) inNoyori asymmetric hydrogenation and asymmetric isomerization. The latter has the practical use of manufacture of synthetic(–)-menthol.
A chelating agent is the main component of some rust removal formulations.Citric acid is used tosoften water insoaps and laundrydetergents. A common synthetic chelator isEDTA.Phosphonates are also well-known chelating agents. Chelators are used in water treatment programs and specifically insteam engineering.[citation needed] 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 and lower the water'spH level.
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.[32]
Because of their wide needs, the overall chelating agents growth was 4% annually during 2009–2014[33] and the trend is likely to increase.Aminopolycarboxylic acids chelators are the most widely consumed chelating agents; however, the percentage of the greener alternative chelators in this category continues to grow.[34] The consumption of traditional aminopolycarboxylates chelators, in particular the EDTA (ethylenediaminetetraacetic acid) and NTA (nitrilotriacetic acid), is declining (−6% annually), because of the persisting concerns over their toxicity and negative environmental impact.[33] In 2013, these greener alternative chelants represented approximately 15% of the total aminopolycarboxylic acids demand. This is expected to rise to around 21% by 2018, replacing and aminophosphonic acids used in cleaning applications.[35][34][33] Examples of some Greener alternative chelating agents includeethylenediamine disuccinic acid (EDDS),polyaspartic acid (PASA),methylglycinediacetic acid (MGDA),glutamic diacetic acid (L-GLDA),citrate,gluconic acid, amino acids, plant extracts etc.[34][36]
Dechelation (or de-chelation) is a reverse process of the chelation in which the chelating agent is recovered by acidifying solution with a mineral acid to form a precipitate.[37]: 7
This article incorporatestext by Kaana Asemave available under theCC BY 4.0 license.
The dictionary definition ofchelate at Wiktionary