Cisplatin
Cisplatin, historically called Peyrone's salt,[1] is a drug used in chemotherapy to treat many types of cancer.[2]
Chemistry
[change | change source]Cisplatin is a coordination complex of platinum with amine and chloride ligands. It has the chemical name cis-diamminodichloridoplatinum(II) and chemical formula Pt(NH3)2Cl2. It is specifically the cis isomer of this compound: the trans isomer, transplatin, does not have any effect on cancer. There is also a polymeric isomer called Magnus's green salt.
Preparation
[change | change source]Since its discovery in 1845,[3] cisplatin has been made from potassium tetrachloroplatinate. Three different routes have been used since the 20th century.[4] The first modern preparation was published by George B. Kauffman, and reacted potassium tetrachloroplatinate directly with aqueous ammonia:[1]
- K2PtCl4 + 2 NH3 → KCl2 + P2(NH3)2Cl2
A more advanced preparation uses ammonium acetate instead:[5][better source needed]
- K2PtCl4 + 2 NH4CO2CH3 → Pt(NH3)2Cl2 + 2 CH3COOH + 2 KCl
These methods also make Magnus's green salt as an impurity. To avoid this impurity, a more complicated synthesis developed by S.C. Dhara first makes potassium tetraiodoplatinate in situ:[5][better source needed]
- K2PtCl4 + 4 KI → K2PtI4 + 4 KCl
- K2PtI4 + 2 NH3 → Pt(NH3)2I2 + 2 KCl
The stronger cis effect of the iodide ligand means that the iodide relative of Magnus's green salt is not made. To change the iodido complex back to cisplatin, aqueous silver nitrate is used to precipitate silver iodide, making the cationic complex [Pt(NH3)2(H2O)2]2+:[6]
- Pt(NH3)2I2 + 2 AgNO3 + 2 H2O → [Pt(NH3)2(H2O)2](NO3)2 + 2 AgI
This complex is then treated with a chloride source to make cisplatin.
- [Pt(NH3)2(H2O)2]2+ + 2 Cl− → Pt(NH3)2Cl2 + 2 H2O
The Dhara process is the main route used to make cisplatin today.[4]
Sources
[change | change source]- 1 2 Kauffman, George B.; Cowan, Dwaine O.; Slusarczuk, George; Kirschner, Stanley (1963). "cis - and trans -Dichlorodiammineplatinum(II)". Inorganic Syntheses. Vol. 7. pp. 239–245. doi:10.1002/9780470132388.ch63.
- ↑ Ghosh, Sumit (2019). "Cisplatin: The first metal based anticancer drug". Bioorganic Chemistry. 88 102925. doi:10.1016/j.bioorg.2019.102925. PMID 31003078.
- ↑ Kauffman, George B.; Pentimalli, Raffaele; Doldi (1908–2001), Sandro; Hall, Matthew D. (2010). "Michele Peyrone (1813–1883), Discoverer of Cisplatin". Platinum Metals Review. 54 (4): 250–256. doi:10.1595/147106710X534326.
{{cite journal}}: CS1 maint: numeric names: authors list (link) - 1 2 Petruzzella, Emanuele; Chirosca, Cristian V.; Heidenga, Cameron S.; Hoeschele, James D. (2015). "Microwave-assisted synthesis of the anticancer drug cisplatin, cis-[Pt(NH3)2Cl2]". Dalton Transactions. 44 (7): 3384–3392. doi:10.1039/C4DT03617D. PMID 25600831.
- 1 2 Kukushikin, Vadim Yu.; Oskarsson, Åke; Elding, Lars I.; Farrell, Nicholas; Dunham, Stephen; Lippard, Stephen J. (1998). "Facile Synthesis of Isomerically Pure cis -Dichlorodiammineplatinum(II), Cisplatin". Inorganic Syntheses. Vol. 32. pp. 141–144. doi:10.1002/9780470132630.ch23. ISBN 978-0-471-24921-4.
- ↑ Wilson, Justin J.; Lippard, Stephen J. (2014). "Synthetic Methods for the Preparation of Platinum Anticancer Complexes". Chemical Reviews. 114 (8): 4470–4495. doi:10.1021/cr4004314. PMC 3999256. PMID 24283498.