iron(III) citrate
{{Short description|Chemical compound}}
{{Use dmy dates|date=March 2025}}
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| ImageFile = Fe2CITdianion.svg
| ImageCaption = One of several ferric citrate complexes
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| IUPACName = iron(3+) 2-hydroxypropane-1,2,3-tricarboxylate
| OtherNames = Xoanacyl
| Section1 = {{Chembox Identifiers
| PubChem = 61300
| ChEBI = 144421
| ChemSpiderID = 55239
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| InChI = 1S/C6H8O7.Fe/c7-3(8)1-6(13,5(11)12)2-4(9)10;/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12);/q;+3/p-3
| InChIKey = NPFOYSMITVOQOS-UHFFFAOYSA-K
| SMILES = C(C(=O)[O-])C(CC(=O)[O-])(C(=O)[O-])O.[Fe+3]
| CASNo_Ref = {{cascite|correct|??}}
| CASNo = 3522-50-7
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 63G354M39Z
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| Section2 = {{Chembox Properties
| C = 6 | H = 5 | O = 7 | Fe = 1
| Appearance = dark orange-red brown solidSigma-Aldrich: [http://www.sigmaaldrich.com/Graphics/COfAInfo/SigmaSAPQM/SPEC/F6/F6129/F6129-BULK________ALDRICH__.pdf Product Specification - Iron(III) citrate, technical grade]. Accessed on 2017-03-09.
| Solubility = ~5 g/L in water
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| ATCCode_prefix = V03
| ATCCode_suffix = AE08
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| Legal_EU = Rx-only
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Ferric citrate or iron(III) citrate describes any of several complexes formed upon binding any of the several conjugate bases derived from citric acid with ferric ions. Most of these complexes are orange or red-brown. They contain two or more Fe(III) centers.
Ferric citrates contribute to the metabolism of iron by some organisms. Citrates, which are released by plant roots and by some microorganisms, can solubilize iron compounds in the soil. For example ferric hydroxide reacts with citrates to give form soluble complexes. This solubilization provides a pathway for the absorption of the ferric ions by various organisms.
Ferric citrate is used in medicine to regulate the blood levels of iron in patients with chronic kidney disease on dialysis. It acts by forming an insoluble compound with phosphate present in the diet and thus minimizing its uptake by the digestive system.{{cite journal|doi=10.1681/ASN.2014020212|title=Ferric Citrate Controls Phosphorus and Delivers Iron in Patients on Dialysis|year=2015|last1=Lewis|first1=Julia B.|last2=Sika|first2=Mohammed|last3=Koury|first3=Mark J.|last4=Chuang|first4=Peale|last5=Schulman|first5=Gerald|last6=Smith|first6=Mark T.|last7=Whittier|first7=Frederick C.|last8=Linfert|first8=Douglas R.|last9=Galphin|first9=Claude M.|last10=Athreya|first10=Balaji P.|last11=Nossuli|first11=A. Kaldun Kaldun|last12=Chang|first12=Ingrid J.|last13=Blumenthal|first13=Samuel S.|last14=Manley|first14=John|last15=Zeig|first15=Steven|last16=Kant|first16=Kotagal S.|last17=Olivero|first17=Juan Jose|last18=Greene|first18=Tom|last19=Dwyer|first19=Jamie P.|author20=Collaborative Study Group|journal=Journal of the American Society of Nephrology|volume=26|issue=2|pages=493–503|pmid=25060056|pmc=4310662}}
Structure
Citrate forms a variety of coordination complexes with ferric ions.Xiang Hao, Yongge Wei, Shiwei Zhang (2001): "Synthesis, crystal structure and magnetic property of a binuclear iron(III) citrate complex". Transition Metal Chemistry, volume 26, issue 4, pages 384–387. {{doi|10.1023/A:1011055306645}}{{cite journal |doi=10.1021/ic00101a001 |title=Syntheses, Structures, and Magnetic Properties of Two Dinuclear Iron(III) Citrate Complexes |year=1994 |last1=Shweky |first1=Itzhak |last2=Bino |first2=Avi |last3=Goldberg |first3=David P. |last4=Lippard |first4=Stephen J. |journal=Inorganic Chemistry |volume=33 |issue=23 |pages=5161–5162}} Some might be oligomers, and polymers. Thus, ferric citrate is not a single well-defined compound, but a family of compounds, many with similar formulas. These various forms can coexist in equilibrium.{{cite journal|doi=10.1039/B910970F|title=Iron(III) citrate speciation in aqueous solution|year=2009|last1=Silva|first1=Andre M. N.|last2=Kong|first2=Xiaole|last3=Parkin|first3=Mark C.|last4=Cammack|first4=Richard|last5=Hider|first5=Robert C.|journal=Dalton Transactions|issue=40|pages=8616–25|pmid=19809738}} At physiological pH, ferric citrate forms an insoluble red polymer. In other conditions, it forms anionic complexes like [{{chem|Fe||C|6|H|4|O|7}}]2({{chem|H|2|O}})2]2−. In the presence of excess citrate anions, the iron forms negatively charged complexes like [{{chem|Fe}}({{chem|C|6|H|4|O|7}})2]5− and [{{chem|Fe|9|O}}({{chem|C|6|H|4|O|7}})8({{chem|H|2|O}})3]7−.{{cite journal|doi=10.1021/ic9715658|title=A Novel Nonairon(III) Citrate Complex: A "Ferric Triple-Decker"|year=1998|last1=Bino|first1=Avi|last2=Shweky|first2=Itzhak|last3= Cohen|first3=Shmuel|last4=Bauminger|first4=Erika R.|last5=Lippard|first5=Stephen J.|journal=Inorganic Chemistry|volume=37|issue=20|pages=5168–5172}}{{cite journal|doi=10.1023/A:1009225701332|year=2000|last1=Pierre|first1=J. L.|journal=Biometals|title=Iron and Citric Acid: A Fuzzy Chemistry of Ubiquitous Biological Relevance|volume=13|pages=91–96|last2=Gautier-Luneau|first2=I.|issue=1|pmid=10831230|s2cid=2301450}}
Photoreduction
The {{chem|Fe|3+}} ion in ferric citrate (as in many iron(III) carboxylates) is reduced by exposure to light,Wu Feng and Deng Nansheng (2000): "Photochemistry of hydrolytic iron (III) species and photoinduced degradation of organic compounds: A minireview". Chemosphere, volume 41, issue 8, pages 1137–1147. {{doi|10.1016/S0045-6535(00)00024-2}} especially blue and ultraviolet, to {{chem|Fe|2+}} (ferrous) ion with concomitant oxidation of the carboxyl group adjacent to the hydroxyl, yielding carbon dioxide and acetonedicarboxylate:
: 2{{chem|Fe|3+}} + R2-C(OH)-{{chem|CO|2|−}} → 2{{chem|Fe|2+}} + R2-C=O + {{chem|H|+}} + {{chem|CO|2}}
where -R represents the group -{{chem|C|H|2|C|O|2|−}}.
This reaction plays an important role in plant metabolism: iron is carried up from the roots as ferric citrate dissolved in the sap,{{cite journal|doi=10.1093/pcp/pcp170|title=Identification of a Tri-Iron(III), Tri-Citrate Complex in the Xylem Sap of Iron-Deficient Tomato Resupplied with Iron: New Insights into Plant Iron Long-Distance Transport|year=2010|last1=Rellán-Álvarez|first1=Rubén|last2=Giner-Martínez-Sierra|first2=Justo|last3=Orduna|first3=Jesús|last4=Orera|first4=Irene|last5=Rodríguez-Castrillón|first5=José Ángel|last6=García-Alonso|first6=José Ignacio|last7=Abadía|first7=Javier|last8=Álvarez-Fernández|first8=Ana|journal=Plant and Cell Physiology|volume=51|issue=1|pages=91–102|pmid=19942594|doi-access=free|hdl=10651/6671|hdl-access=free}}
and photoreduced in the leaves to iron(II) that can be transported into the cells.
Society and culture
= Legal status =
In March 2025, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Xoanacyl, intended for the treatment of concomitant hyperphosphatemia and iron deficiency in adults with chronic kidney disease. The active substance of is ferric citrate coordination complex. The applicant for this medicinal product is Averoa SAS.{{cite web | title=Xoanacyl EPAR | website=European Medicines Agency (EMA) | date=27 March 2025 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/xoanacyl | access-date=29 March 2025}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Xoanacyl was authorized for medical use in the European Union in June 2025.{{cite web | title=Xoanacyl PI | website=Union Register of medicinal products | date=12 June 2025 | url=https://ec.europa.eu/health/documents/community-register/html/h1923.htm | access-date=14 June 2025}}
Additional reading
{{cite journal |doi=10.1016/0020-1693(94)04077-X |title=Photochemical and Spectroscopic Studies of Complexes, of Iron(III) with Citric Acid and Other Carboxylic Acids |year=1994 |last1=Abrahamson |first1=Harmon B. |last2=Rezvani |first2=Ahmad B. |last3=Brushmiller |first3=J.George |journal=Inorganica Chimica Acta |volume=226 |issue=1–2 |pages=117–127}}
References
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