Cisplatin Synthesis

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The synthesis of cisplatin is very well established and is one of the most classic examples of synthesis in inorganic chemistry (figure 1). Dhara reported in 1970 “A rapid method for the synthesis of cis-[PtCl2(NH3)2].”8 The starting material, K2[PtCl4], is treated with excess of KI to be converted into K2[PtI4]. The product is subsequently treated with NH3 to obtain yellow colored cis-[PtI2(NH3)2] that is collected and dried. cis-[PtI2(NH3)2] is then dissolved in AgNO3 to precipitate out AgI that is removed. The solution containing cis-[Pt(OH2)2(NH3)2]2+ is lastly treated with KCl to produce the final, yellow-colored product, cisplatin.
The synthesis scheme of cisplatin is deeply related to the trans effect. Chernyaev introduced the trans effect in platinum chemistry9. The theory is based on empirical observation that the rate of substitution of a ligand in a square planar complex is dependent on the group opposite (or trans) to it8. The trans effect can be explained by two factors: sigma-bonding effect and pi-bonding effect.
The sigma-bonding effect is the weakening of the bonding between platinum and X, or the leaving group, by the sigma bonding between platinum and the sigma-bonding ligand (T in figure 2) trans to X. The Pt-X bond is affected by Pt-T bond because both bondings make use of platinum Px and dx2-y2 orbitals. If the bonding between Pt-T becomes stronger, less of platinum dx2-y2 orbital is available for Pt-X bond, making the bond weaker as a result. Thus a strong sigma-bonding ligand “labilizes” the metal-ligand bond trans to it, which is sigma-bonding effect.
The pi-bonding effect is another factor that contributes to trans effect. When pi-bonding ligand (T in figure 2) that is trans to X result in strong pi-b...

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... c, which leads to APAF1 activation, followed by CASP9 activation that can also activate CASP3 and CASP711.
Studies have shown that the transduction of cisplatin-DNA adduct recognition signal occurs through pathways other than p53, including the following: AKT pathway, c-ABL, MAPK/JNK/ERK, and MKP1/CL10011. These other pathways are not covered in this paper due to page limits.

Reference
8. Alderden, Journal of Chemical Education, 2006, 83, 728-734.
9. Chernyaev, Ann, inst. Platine USSR., 1926, 4, 261.
10. Hromas, Cancer Letter, 1987, 36, 197-201.
11. Wang, Nature Reviews, 2005, 4, 307-320.
12. Takahara, Nature, 1995, 377, 649-652.
13. Imamura, The journal of Biological Chemistry, 2001, 276, 7534-7540.
14. Ohndorf, Nature, 1999, 399, 708-712.
15. Jayaraman, Genes & Development, 1998, 12, 462-472.
16. Vousden, Nature Reviews, 2002, 2, 594-604.

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