Cisplatin kills cancer cells by binding to their DNA and stopping it from being copied.Blood plasma has a high chloride ion concentration, so cisplatin stays as [Pt(NH3)2Cl2] while it is carried round the body. Inside cells the chloride concentration is much lower, so a chloride ligand can be replaced by a water molecule, making the complex more reactive.The platinum then bonds to DNA in a ligand substitution reaction. A nitrogen atom on a guanine base has a lone pair and acts as a ligand: it forms a co-ordinate bond to Pt, displacing a chloride (or water) ligand. The second leaving ligand is then replaced by a nitrogen atom on a second guanine, usually the neighbouring guanine on the same strand. The two NH3 ligands stay bonded to the platinum.
This works only for the cis isomer, because the two replaceable ligands must be next to each other (at 90°) to reach two adjacent bases.Binding to two bases bends and distorts the double helix. The DNA strands can no longer separate and be copied properly, so DNA replication is prevented. The cell cannot divide and eventually dies.Cancer cells divide rapidly and uncontrollably, so they replicate their DNA much more often than most normal cells. This makes them especially sensitive to cisplatin.Worked example. Classify the reaction between cisplatin and guanine, and state what happens to the oxidation state of platinum. Chloride ligands are replaced by nitrogen donor atoms, so it is a ligand substitution reaction. The co-ordination number stays 4 and platinum stays in the +2 oxidation state, so it is not a redox reaction.
This works only for the cis isomer, because the two replaceable ligands must be next to each other (at 90°) to reach two adjacent bases.Binding to two bases bends and distorts the double helix. The DNA strands can no longer separate and be copied properly, so DNA replication is prevented. The cell cannot divide and eventually dies.Cancer cells divide rapidly and uncontrollably, so they replicate their DNA much more often than most normal cells. This makes them especially sensitive to cisplatin.Worked example. Classify the reaction between cisplatin and guanine, and state what happens to the oxidation state of platinum. Chloride ligands are replaced by nitrogen donor atoms, so it is a ligand substitution reaction. The co-ordination number stays 4 and platinum stays in the +2 oxidation state, so it is not a redox reaction.