(a) The coordination complex cis- [Pt(NH_3)_2 Cl_2] is an important anti-tumour
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Question
(a) The coordination complex cis- [Pt(NH_3)_2 Cl_2] is an important anti-tumour agent used for the treatment of testicular and ovarian cancers. Describe the currently accepted mechanism of action of cis - [Pt(NH_3)_2 Cl_2]. Focus on changes in coordination sphere as the drug moves through plasma to intracellular binding sites Mention the likely mechanisms of any substitution processes you identify. (b) Would you expect cis- [Pt(NH_3)_2 Cl_2] or cis- [Pd(NH_3)_2 Cl_2] to react faster with water? Explain your answer.Explanation / Answer
Initially, one of the two chloride ligands of cis-platin is slowly displaced by water to give the aqua complex cis-[PtCl(NH3)2(H2O)]+ and this process is known as aquation. This process is favored inside the cell because the intracellular chloride concentration is less than that of extracellular fluid.
Further, water in cis-[PtCl(NH3)2(H2O)]+ easily displaced by the nuclear bases of DNA. Especially, guanine and results in the formation of [PtCl (guanine-DNA)(NH3)2]+, further the crosslinking of this complex can occur through the displacement of the other chloride ligand and follow by another guanine. In effect, these processes interfere cell division process by mitosis.
b). Trans –complexes are generally stable. Thus their reactivity will be less. The higher energy of cis complexes can be attributed to the repulsion of the bigger groups on the same side of the double bond. This will make the cis complex more reactive towards aqua substitution reactions.
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