The synthesis of cisplatin is 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 KI to be converted to K2[PtI4]. The product is subsequently treated with NH3 to obtain yellow cis-[PtI2(NH3)2] which is collected and dried. cis-[PtI2(NH3)2] is then dissolved in AgNO3 to precipitate AgI which is removed. The solution containing cis-[Pt(OH2)2(NH3)2]2+ is finally treated with KCl to produce the final yellow product, cisplatin. The synthesis scheme of cisplatin is profoundly related 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 (or trans) to it8. The trans effect can be explained by two factors: sigma binding effect and pi binding effect. The sigma bonding effect is the weakening of the bond between platinum and X, or the leaving group, due to the sigma bond between platinum and the sigma-bonding ligand (T in figure 2) trans to is affected by the Pt-T bond because both bonds make use of platinum Px and dx2-y2 orbitals. If the Pt-T bond becomes stronger, less platinum dx2-y2 orbital is available for the Pt-X bond, consequently making the bond weaker. Therefore, a strong sigma binding ligand "labilizes" the trans metal-ligand bond to it, which is a sigma binding effect. The pi binding effect is another factor that contributes to the trans effect. When the binding ligand pi (T in figure 2) which is trans to 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 paths are not covered in this document due to page limitations. Reference 8. 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 Reviews, 2002, 2, 594-604.