Editing Chelation (section)

== Applications ==
=== Animal feed additives ===
Synthetic chelates such as [[ethylenediaminetetraacetic 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.<ref>{{cite book |last=Ashmead |first=H. DeWayne |name-list-style=vanc |title=The Roles of Amino Acid Chelates in Animal Nutrition |year=1993 |publisher=Noyes Publications |location=Westwood|isbn=0815513127}}{{page needed|date=December 2015}}</ref> 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 a [[mole ratio]] in the range of 1–3 (preferably 2) moles of amino acids for one mole of metal.{{Citation needed|date=October 2018}} The average weight of the hydrolyzed amino acids must be approximately 150 and the resulting molecular weight of the chelate must not exceed 800&nbsp;[[Dalton (unit)|Da]].{{citation needed|date=December 2015}} 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. [[Iron supplement|Ferrous bis-glycinate]] is an example of one of these compounds that has been developed for human nutrition.<ref>{{cite web |publisher=Albion Laboratories, Inc. |title=Albion Ferrochel Website |url=http://www.albionferrochel.com/ |access-date=July 12, 2011 |archive-date=September 3, 2011 |archive-url=https://web.archive.org/web/20110903054502/http://www.albionferrochel.com/ |url-status=dead}}</ref>

=== Dental use ===
[[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).<ref>{{cite book |last1=Anusavice |first1=Kenneth J. |name-list-style=vanc |title=Phillips' Science of Dental Materials |publisher=Elsevier Health |isbn=978-1-4377-2418-9 |chapter=Chapter 12: Bonding and Bonding Agents |pages=257–268 |edition=12th |oclc=785080357 |date=September 27, 2012}}</ref>

=== Chelation therapy ===
[[Chelation therapy]] is an antidote for poisoning by [[mercury poisoning|mercury]], [[arsenic]], and [[lead]].  Chelating agents convert these metal ions into a chemically and biochemically inert form that can be excreted. Chelation using [[sodium calcium edetate]] has been approved by the [[U.S. Food and Drug Administration]] (FDA) for serious cases of [[lead poisoning]]. It is not approved for treating "[[heavy metal toxicity]]".<ref name="warning">{{cite web |url=http://www.chelationwatch.org/reg/fda_warning.shtml |title=FDA Issues Chelation Therapy Warning |date=September 26, 2008 |access-date=May 14, 2016}}</ref> Although beneficial in cases of serious lead poisoning, use of disodium EDTA (edetate disodium) instead of calcium disodium EDTA has resulted in fatalities due to [[hypocalcemia]].<ref>{{cite journal |author=Centers for Disease Control Prevention (CDC) |title=Deaths associated with hypocalcemia from chelation therapy--Texas, Pennsylvania, and Oregon, 2003–2005 |journal=MMWR. Morbidity and Mortality Weekly Report |volume=55 |issue=8 |pages=204–7 |date=March 2006 |pmid=16511441 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5508a3.htm}}</ref> Disodium EDTA is not approved by the FDA for any use,<ref name="warning" /> and all FDA-approved chelation therapy products require a prescription.<ref>{{cite web |url=https://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/MedicationHealthFraud/ucm229313.htm |archive-url=https://web.archive.org/web/20101017040749/http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/MedicationHealthFraud/ucm229313.htm |url-status=dead |archive-date=October 17, 2010 |title=Questions and Answers on Unapproved Chelation Products |publisher=[[U.S. Food and Drug Administration|FDA]] |date=February 2, 2016 |access-date=May 14, 2016}}</ref>

=== Contrast agents ===
Chelate complexes of [[gadolinium]] are often used as [[contrast medium|contrast agent]]s in [[MRI|MRI scan]]s, although [[iron]] particle and [[manganese]] chelate complexes have also been explored.<ref name=":0">{{cite journal |vauthors=Caravan P, Ellison JJ, McMurry TJ, Lauffer RB |title=Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications |journal=Chemical Reviews |volume=99 |issue=9 |pages=2293–352 |date=September 1999 |pmid=11749483 |doi=10.1021/cr980440x}}</ref><ref>{{cite journal |vauthors=Pan D, Schmieder AH, Wickline SA, Lanza GM |title=Manganese-based MRI contrast agents: past, present and future |journal=Tetrahedron |volume=67 |issue=44 |pages=8431–8444 |date=November 2011 |pmid=22043109 |pmc=3203535 |doi=10.1016/j.tet.2011.07.076}}</ref> Bifunctional chelate complexes of [[zirconium]], [[gallium]], [[fluorine]], [[copper]], [[yttrium]], [[bromine]], or [[iodine]] are often used for conjugation to [[monoclonal antibodies]] for use in antibody-based [[PET imaging]].<ref>{{cite journal |vauthors=Vosjan MJ, Perk LR, Visser GW, Budde M, Jurek P, Kiefer GE, van Dongen GA |title=Conjugation and radiolabeling of monoclonal antibodies with zirconium-89 for PET imaging using the bifunctional chelate p-isothiocyanatobenzyl-desferrioxamine |journal=Nature Protocols |volume=5 |issue=4 |pages=739–43 |date=April 2010 |pmid=20360768 |doi=10.1038/nprot.2010.13 |s2cid=5087493}}</ref> These chelate complexes often employ the usage of [[hexadentate ligand]]s such as [[desferrioxamine B]] (DFO), according to Meijs ''et al.'',<ref>{{Cite journal|last1=Price|first1=Eric W.|last2=Orvig|first2=Chris |date=January 7, 2014|title=Matching chelators to radiometals for radiopharmaceuticals|journal=Chemical Society Reviews|volume=43|issue=1|pages=260–290|doi=10.1039/c3cs60304k|issn=1460-4744|pmid=24173525}}</ref> and the gadolinium complexes often employ the usage of octadentate ligands such as DTPA, according to Desreux ''et al''.<ref>{{Cite journal|last1=Parac-Vogt|first1=Tatjana N.|last2=Kimpe|first2=Kristof|last3=Laurent |first3=Sophie|last4=Vander Elst|first4=Luce|last5=Burtea|first5=Carmen|last6=Chen|first6=Feng|last7=Muller |first7=Robert N.|last8=Ni |first8=Yicheng|last9=Verbruggen|first9=Alfons|date=May 6, 2005|title=Synthesis, characterization, and pharmacokinetic evaluation of a potential MRI contrast agent containing two paramagnetic centers with albumin binding affinity |journal=Chemistry: A European Journal|volume=11 |issue=10|pages=3077–3086|doi=10.1002/chem.200401207|issn=0947-6539|pmid=15776492 |url=https://lirias.kuleuven.be/handle/123456789/20303|url-access=subscription}}</ref> [[Auranofin]], a chelate complex of [[gold]], is used in the treatment of rheumatoid arthritis, and [[penicillamine]], which forms chelate complexes of [[copper]], is used in the treatment of [[Wilson's disease]] and [[cystinuria]], as well as refractory rheumatoid arthritis.<ref>{{cite journal |vauthors=Kean WF, Hart L, Buchanan WW |title=Auranofin |journal=British Journal of Rheumatology |volume=36 |issue=5 |pages=560–72 |date=May 1997 |pmid=9189058 |doi=10.1093/rheumatology/36.5.560 |doi-access=free}}</ref><ref>{{cite journal |vauthors=Wax PM |title=Current use of chelation in American health care |journal=Journal of Medical Toxicology |volume=9 |issue=4 |pages=303–307 |date=December 2013 |pmid=24113860 |pmc=3846961 |doi=10.1007/s13181-013-0347-2}}</ref>

=== Nutritional advantages and issues ===
Chelation in the intestinal tract is a cause of numerous interactions between drugs and metal ions (also known as "[[Dietary mineral|minerals]]" in nutrition). As examples, [[antibiotic]] [[medication|drug]]s of the [[tetracycline]] and [[Quinolone antibiotic|quinolone]] families are chelators of [[iron|Fe]]<sup>2+</sup>, [[Calcium|Ca]]<sup>2+</sup>, and [[Magnesium|Mg]]<sup>2+</sup> ions.<ref>{{cite journal |vauthors=Campbell NR, Hasinoff BB |title=Iron supplements: a common cause of drug interactions |journal=British Journal of Clinical Pharmacology |volume=31 |issue=3 |pages=251–5 |date=March 1991 |pmid=2054263 |pmc=1368348 |doi=10.1111/j.1365-2125.1991.tb05525.x}}</ref><ref>{{cite journal |vauthors=Lomaestro BM, Bailie GR |title=Absorption interactions with fluoroquinolones. 1995 update |journal=Drug Safety |volume=12 |issue=5 |pages=314–33 |date=May 1995 |pmid=7669261 |doi=10.2165/00002018-199512050-00004 |s2cid=2006138}}</ref>

EDTA, which binds to calcium, is used to alleviate the [[hypercalcemia]] that often results from [[band keratopathy]].  The calcium may then be removed from the [[cornea]], allowing for some increase in clarity of vision for the patient.<ref>{{Cite journal |last=Najjar |first=Dany M. |last2=Cohen |first2=Elisabeth J. |last3=Rapuano |first3=Christopher J. |last4=Laibson |first4=Peter R. |date=June 2004 |title=EDTA chelation for calcific band keratopathy: results and long-term follow-up |url=https://pubmed.ncbi.nlm.nih.gov/15183790/ |journal=American Journal of Ophthalmology |volume=137 |issue=6 |pages=1056–1064 |doi=10.1016/j.ajo.2004.01.036 |issn=0002-9394 |pmid=15183790}}</ref><ref>{{Cite journal |last=Al-Hity |first=A |last2=Ramaesh |first2=K |last3=Lockington |first3=D |date=December 1, 2017 |title=EDTA chelation for symptomatic band keratopathy: results and recurrence |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC5770724/ |journal=Eye |language=en |volume=32 |issue=1 |pages=26–31 |doi=10.1038/eye.2017.264 |issn=0950-222X |archive-url=http://web.archive.org/web/20250202182230/https://pmc.ncbi.nlm.nih.gov/articles/PMC5770724/ |archive-date=February 2, 2025|pmc=5770724}}</ref>

[[Homogeneous catalyst]]s are often chelated complexes. A representative example is the use of [[BINAP]] (a bidentate [[phosphine]]) in [[Noyori asymmetric hydrogenation]] and asymmetric isomerization. The latter has the practical use of manufacture of synthetic [[Menthol|(–)-menthol]].

=== Cleaning and water softening ===
A chelating agent is the main component of some rust removal formulations.
[[Citric acid#Cleaning and chelating agent|Citric acid]] is used to [[water softening|soften water]] in [[soap]]s and laundry [[detergent]]s. A common synthetic chelator is [[EDTA]]. [[Phosphonate]]s are also well-known chelating agents. Chelators are used in water treatment programs and specifically in [[steam engineering]].{{cn|date=September 2023}}  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's [[pH]] level.

=== Fertilizers ===
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.<ref name="Ullmann">{{cite book |last1=Hart |first1=J. Roger |name-list-style=vanc |chapter=Ethylenediaminetetraacetic Acid and Related Chelating Agents |title=Ullmann's Encyclopedia of Industrial Chemistry |year=2011 |doi=10.1002/14356007.a10_095.pub2 |isbn=978-3527306732}}</ref>

=== Economic situation ===
Because of their wide needs, the overall chelating agents growth was 4% annually during 2009–2014<ref name=":1">(2013) IHS Chemical, Chemical Insight and Forecasting: Chelating Agents.</ref> and the trend is likely to increase. [[Aminopolycarboxylic acid|Aminopolycarboxylic acids]] chelators are the most widely consumed chelating agents; however, the percentage of the greener alternative chelators in this category continues to grow.<ref name=":2">{{cite book |author=Dixon NJ |year=2012 |chapter=Greener chelating agents |title=Handbook of green chemistry: Designing safer chemicals. |publisher=Wiley |pages=281–307}}</ref> 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.<ref name=":1" /> 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.<ref>{{cite book |author=Kołodyńska D |year=2011 |chapter=Chelating agents of a new generation as an alternative to conventional chelators for heavy metal ions removal from different waste waters |title=Expanding Issues in Desalination |pages=339–370.}}</ref><ref name=":2" /><ref name=":1" /> Examples of some Greener alternative chelating agents include [[Ethylenediaminedisuccinic acid|ethylenediamine disuccinic acid]] (EDDS), [[polyaspartic acid]] (PASA), [[methylglycinediacetic acid]] (MGDA), [[glutamic diacetic acid]] (L-GLDA), [[Citric acid|citrate]], [[gluconic acid]], amino acids, plant extracts etc.<ref name=":2" /><ref>{{cite journal |author=Kolodynska D |title=Application of a new generation of complexing agents in removal of heavy metal ions from different wastes  |date=March 6, 2013 |journal=Environmental Science and Pollution Research |volume=20 |issue=9 |pages=5939-5949 |pmid=23463276 |doi=10.1007/s11356-013-1576-2|pmc=3720993 }}</ref>