Editing Ferrocene (section)

==Applications of ferrocene and its derivatives==
Ferrocene and its numerous derivatives have no large-scale applications, but have many niche uses that exploit the unusual structure ([[ligand]] scaffolds, [[pharmaceutical drug|pharmaceutical candidate]]s), [[robustness]] ([[anti-knock|anti-knock formulation]]s, [[precursor (chemistry)|precursor]]s to materials), and redox (reagents and redox standards).

===Ligand scaffolds===
Chiral ferrocenyl [[phosphine]]s are employed as ligands for transition-metal catalyzed reactions. Some of them have found industrial applications in the synthesis of pharmaceuticals and agrochemicals. For example, the [[diphosphines|diphosphine]] [[1,1'-bis(diphenylphosphino)ferrocene|1,1′-bis(diphenylphosphino)ferrocene]] (dppf) is a valued ligand for [[palladium]]-[[coupling reaction]]s and [[Josiphos ligand]] is useful for hydrogenation catalysis.<ref name="H-U. Blaser 2002">{{cite journal | title = Solvias Josiphos ligands: From discovery to technical applications | doi = 10.1023/a:1013832630565 | volume = 19 | year = 2002 | journal = Topics in Catalysis | pages = 3–16 | vauthors = Blaser HU | s2cid = 95738043 }}</ref> They are named after the technician who made the first one, Josi Puleo.<ref>{{cite book | vauthors = Zhou QL |title=Privileged Chiral Ligands and Catalysts |date=2011 |publisher=Wiley-VCH Verlag |location=Weinheim |isbn=978-3-527-63521-4}}</ref><ref name=Stepnicka>{{cite book| vauthors = Stepnicka P |title=Ferrocenes: Ligands, Materials and Biomolecules|publisher=J. Wiley |location=Hoboken, NJ|date=2008 |isbn=978-0-470-03585-6}}</ref>

[[File:Josiphos.png|thumb|Josiphos ligand.<ref name="H-U. Blaser 2002"/>]]

===Fuel additives===
Ferrocene and its derivatives are [[antiknock agent]]s used in the fuel for [[petrol engine]]s. They are safer than previously used [[tetraethyllead]].<ref>{{cite conference | vauthors = Bennett J | conference = International Conference on Automotive Technology | location = Istanbul | date = 26 November 2004 |url=http://www.osd.org.tr/14.pdf |title=Application of fuel additives |url-status=dead |archive-url=https://web.archive.org/web/20060505193757/http://www.osd.org.tr/14.pdf |archive-date=2006-05-05 }}</ref> Petrol additive solutions containing ferrocene can be added to unleaded petrol to enable its use in vintage cars designed to run on leaded petrol.<ref>{{cite patent|country=US|number=4104036|title=Iron-containing motor fuel compositions and method for using same |inventor = Chao TS | assign1 = Atlantic Richfield Co |pubdate= 1978-08-01}}</ref> The [[iron]]-containing deposits formed from ferrocene can form a [[conductive]] coating on [[spark plug]] surfaces. Ferrocene polyglycol copolymers, prepared by effecting a polycondensation reaction between a ferrocene derivative and a substituted dihydroxy alcohol, has promise as a component of rocket propellants. These copolymers provide rocket propellants with heat stability, serving as a propellant binder and controlling propellant burn rate.<ref>{{cite patent | inventor = Dewey FM | assign1 = U.S. Air Force | title = Ferrocene Polyglycols | country = US | number = 3598850 | fdate = June 11, 1969 | gdate = Aug. 10, 1971 | url = https://patentimages.storage.googleapis.com/6f/2a/1c/dad6147ea46bcb/US3598850.pdf | postscript = .}}</ref>

Ferrocene has been found to be effective at reducing smoke and sulfur trioxide produced when burning coal. The addition by any practical means, impregnating the coal or adding ferrocene to the combustion chamber, can significantly reduce the amount of these undesirable byproducts, even with a small amount of the metal cyclopentadienyl compound.<ref>{{cite patent | inventor = Kerley RV | assign1 = Ethyl Corporation | title = Coal Combustion Process and Composition | country = US | number = 3927992 | fdate = November 23, 1971 | gdate = December 23, 1975 | url = https://patentimages.storage.googleapis.com/0d/03/57/c94e635d15e1fb/US3927992.pdf | postscript = . }}</ref>

===Pharmaceuticals===
[[File:Ferroceron.svg|thumb|Ferrocerone]]
Ferrocene derivatives have been investigated as drugs,<ref>{{cite journal | vauthors = van Staveren DR, Metzler-Nolte N | title = Bioorganometallic chemistry of ferrocene | journal = Chemical Reviews | volume = 104 | issue = 12 | pages = 5931–5985 | date = December 2004 | pmid = 15584693 | doi = 10.1021/cr0101510 }}</ref> with one compound {{ill|ferrocerone|ru|Ферроцерон}} approved for use in the USSR in the 1970s as an [[iron supplement]], though it is no longer marketed today.<ref>{{cite journal | vauthors = Ong YC, Gasser G | title = Organometallic compounds in drug discovery: Past, present and future | journal = Drug Discovery Today: Technologies | volume = 37 | pages = 117–124 | date = December 2020 | pmid = 34895650 | doi = 10.1016/j.ddtec.2019.06.001 | s2cid = 198268304 | url = https://hal.archives-ouvertes.fr/hal-02169801/file/Organometallic%20Compounds%20in%20Drug%20Discovery%20Past%2C%20Present%20and%20futur.pdf }}</ref> Only one drug has entered clinical trials in recent years, [[Ferroquine]] (7-chloro-N-(2-((dimethylamino)methyl)ferrocenyl)quinolin-4-amine), an [[antimalarial]],<ref name="BiotNosten2011">{{cite journal | vauthors = Biot C, Nosten F, Fraisse L, Ter-Minassian D, Khalife J, Dive D | title = The antimalarial ferroquine: from bench to clinic | journal = Parasite | volume = 18 | issue = 3 | pages = 207–214 | date = August 2011 | pmid = 21894260 | pmc = 3671469 | doi = 10.1051/parasite/2011183207 }} {{open access}}</ref><ref>{{cite journal | vauthors = Roux C, Biot C | title = Ferrocene-based antimalarials | journal = Future Medicinal Chemistry | volume = 4 | issue = 6 | pages = 783–797 | date = April 2012 | pmid = 22530641 | doi = 10.4155/fmc.12.26 }}</ref><ref>{{cite journal | vauthors = Wani WA, Jameel E, Baig U, Mumtazuddin S, Hun LT | title = Ferroquine and its derivatives: new generation of antimalarial agents | journal = European Journal of Medicinal Chemistry | volume = 101 | pages = 534–551 | date = August 2015 | pmid = 26188909 | doi = 10.1016/j.ejmech.2015.07.009 | pmc = 7115395 }}</ref> which has reached Phase IIb trials.<ref>{{cite journal | vauthors = Adoke Y, Zoleko-Manego R, Ouoba S, Tiono AB, Kaguthi G, Bonzela JE, Duong TT, Nahum A, Bouyou-Akotet M, Ogutu B, Ouedraogo A, Macintyre F, Jessel A, Laurijssens B, Cherkaoui-Rbati MH, Cantalloube C, Marrast AC, Bejuit R, White D, Wells TN, Wartha F, Leroy D, Kibuuka A, Mombo-Ngoma G, Ouattara D, Mugenya I, Phuc BQ, Bohissou F, Mawili-Mboumba DP, Olewe F, Soulama I, Tinto H | display-authors = 6 | title = A randomized, double-blind, phase 2b study to investigate the efficacy, safety, tolerability and pharmacokinetics of a single-dose regimen of ferroquine with artefenomel in adults and children with uncomplicated Plasmodium falciparum malaria | journal = Malaria Journal | volume = 20 | issue = 1 | pages = 222 | date = May 2021 | pmid = 34011358 | doi = 10.1186/s12936-021-03749-4 | pmc = 8135182 | doi-access = free }}</ref> Ferrocene-containing polymer-based drug delivery systems have been investigated.<ref>{{Cite journal| vauthors = Gu H, Mu S, Qiu G, Liu X, Zhang L, Yuan Y, Astruc D |date=June 2018|title=Redox-stimuli-responsive drug delivery systems with supramolecular ferrocenyl-containing polymers for controlled release|journal=Coordination Chemistry Reviews|volume=364|pages=51–85|doi=10.1016/j.ccr.2018.03.013|s2cid=103022297 |issn=0010-8545}}</ref>

[[Image:Ferroquine.png|thumb|220 px|Ferroquine]]
The anticancer activity of ferrocene derivatives was first investigated in the late 1970s, when derivatives bearing [[amine]] or [[amide]] groups were tested against lymphocytic [[leukemia]].<ref name=":0">{{Cite journal| vauthors = Ornelas C |s2cid=56521492|title=Application of ferrocene and its derivatives in cancer research|journal=New Journal of Chemistry|volume=35|issue=10|pages=1973|doi=10.1039/c1nj20172g|year=2011}}</ref> Some ferrocenium salts exhibit anticancer activity, but no compound has seen evaluation in the clinic.<ref name=Babin>{{cite journal | vauthors = Babin VN, Belousov YA, Borisov VI, Gumenyuk VV, Nekrasov YS, Ostrovskaya LA, Sviridova IK, Sergeeva NS, Simenel AA, Snegur LV | display-authors = 6 | year = 2014 | title = Ferrocenes as potential anticancer drugs. Facts and hypotheses | journal = Russ. Chem. Bull. | volume = 63 | issue = 11| pages = 2405–2422 | doi = 10.1007/s11172-014-0756-7 | s2cid = 94618726 }}</ref> Ferrocene derivatives have strong inhibitory activity against human lung cancer cell line A549, colorectal cancer cell line HCT116, and breast cancer cell line MCF-7.<ref>{{cite patent | inventor = Yong J, Lu C | assign1 = Xiamen Institute of Rare Earth Materials | title = Ferrocene Derivative, Preparation Method and Use Thereof. | country = US | number = 9738673 | fdate = November 29, 2016 | gdate = August 22, 2017 | url = https://patentimages.storage.googleapis.com/dd/6e/d6/9fd8e3c5c96b67/US9738673.pdf | postscript = . }}</ref> An experimental drug was reported which is a ferrocenyl version of [[tamoxifen]].<ref name = top2003 /> The idea is that the tamoxifen will bind to the [[estrogen]] binding sites, resulting in cytotoxicity.<ref name=top2003>{{cite journal | vauthors = Top S, Vessières A, Leclercq G, Quivy J, Tang J, Vaissermann J, Huché M, Jaouen G | display-authors = 6 | title = Synthesis, biochemical properties and molecular modelling studies of organometallic specific estrogen receptor modulators (SERMs), the ferrocifens and hydroxyferrocifens: evidence for an antiproliferative effect of hydroxyferrocifens on both hormone-dependent and hormone-independent breast cancer cell lines | journal = Chemistry: A European Journal | volume = 9 | issue = 21 | pages = 5223–5236 | date = November 2003 | pmid = 14613131 | doi = 10.1002/chem.200305024 }}</ref><ref>{{cite journal|journal=[[Chemical and Engineering News]]|date=16 September 2002| title= The Bio Side of Organometallics| vauthors = Dagani R | volume = 80| issue= 37| pages = 23–29| url=http://pubs.acs.org/cen/science/8037/8037sci1.html|doi=10.1021/cen-v080n037.p023}}</ref>

Ferrocifens are exploited for cancer applications by a French biotech, Feroscan, founded by Pr. Gerard Jaouen.

=== Solid rocket propellant ===
Ferrocene and related derivatives are used as powerful burn rate catalysts in [[ammonium perchlorate composite propellant]].<ref>{{Cite web|url=https://www.rocketmotorparts.com/index.aspx?pageid=1577809&prodid=15759228|title=Ferrocene Burn Rate Catalyst|website=www.rocketmotorparts.com|access-date=2020-01-13}}</ref>