Pharmaceuticals: The importance of stereoisomerism.
Stereoisomerism is the term applied to isomers that have the same structural formula but different arrangements of atoms in space. The level of priority groups refers to the molecular mass of a group attached to the parent chain or central atom/ion; highest priority groups have the highest molecular mass. An isomer will be deemed as ‘Cis’ if the highest priority groups are on the same side of the molecule, an isomer would be deemed as ‘Trans’ if the highest priority groups are on different sides of the molecule. An example of cis – trans isomerism is shown above. The structure and position of the groups is highly important to chemistry and the manufacture of pharmaceuticals.
An example of cis-trans isomerism used in the pharmaceutical industry is cisplatin and transplatin. The complex consists of a central platinum ion (2+) with two ammonia (NH^3) ligands (groups that are able to donate a lone pair of electrons to form a dative covalent bond) and two Chloride (Cl-) ligands. Both compounds are a square planar shape with bond angles of 90 degrees, the only difference between these two compounds is the position of the Cl- ligand and NH^3 ligand. Cisplatin is used in chemotherapy whereas transplatin is completely inactive. Cisplatin works firstly by ligand substitution; the chloride ligand is replaced with a water ligand and the complex becomes activated. The water ligand is then substituted by nitrogen atoms on nitrogenous bases of DNA; it is specifically displaced by the guanine nitrogenous base. Once attached the other chloride ligand is replaced by another guanine base, this forms a cross link in the DNA double helix. This cross link inhibits transcription and DNA replication thus effectively inhibiting over stimulation of mitosis which leads to cancerous tumours.
Moreover a compound called carboplatin is more commonly used as it is cheaper and the side effects are more tolerable. Cisplatin can have a range of side effects such as nausea, hearing loss, nerve damage, dizziness and even kidney damage. This is because platinum is a heavy transition metal that is extremely rare, this means we haven’t evolved to used this metal ion as a defence mechanism or to aid biochemical processes meaning our body is likely to reject the complex and a range of side effects occur.