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  • Essay / Synthesis of cisplatin - 1135

    The synthesis of cisplatin is very well established and constitutes 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 KI to be converted to K2[PtI4]. . The product is then treated with NH3 to obtain yellow colored cis-[PtI2(NH3)2] which is collected and dried. cis-[PtI2(NH3)2] is then dissolved in AgNO3 to precipitate AgI which is eliminated. The solution containing cis-[Pt(OH2)2(NH3)2]2+ is finally treated with KCl to produce the final yellow-colored product, cisplatin. The pattern of cisplatin synthesis is deeply linked to the trans effect. Chernyaev introduced the trans effect into platinum chemistry9. The theory is based on the empirical observation that the rate of substitution of a ligand in a square planar complex depends on the group opposite it (or trans)8. The trans effect can be explained by two factors: the sigma-bonding effect and the pi-bonding effect. The sigma-bonding effect is the weakening of the bond between platinum and X, or the leaving group, by the sigma bond between platinum and sigma. -bonding ligand (T in Figure 2) trans to If the bond between Pt-T becomes stronger, less platinum dx2-y2 orbital is available for the Pt-X bond, making the bond weaker. Thus, a strong sigma-binding ligand “labilizes” the metal-trans ligand bond, which constitutes the sigma-binding effect. The pi binding effect is another factor that contributes to the trans effect. When the pi binding ligand (T in Figure 2) which is trans to X results in a strong pi-b...... middle of paper ...... c, which leads to the activation of APAF1, followed by activation of CASP9 which can also activate CASP3 and CASP711. Studies have shown that cisplatin-DNA adduct recognition signal transduction 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 article due to the limited number of pages.Reference8. Alderden, Journal of Chemical Education, 2006, 83, 728-734.9. Chernyaev, Ann, inst. Platinum USSR., 1926, 4, 261.10. Hromas, Letter on Cancer, 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 and Development, 1998, 12, 462-472.16. Vousden, Nature Review, 2002, 2, 594-604.