D.8.2 Discuss the importance of chirality in drug action
Chiral carbon atoms in molecules form two optically active isomers. Because of the different stereochemistry, the two enantiomers act differently on the body. Different isomers can also interact differently with disease organisms.

In synthetic drugs, both enantiomers are created, making a racemic mixture (50% of both isomers). Currently, there is no effective way to seperate the two enantiomers from each other within a sythetic drug because the two are identical is almost every way. Therefore, many drugs may posses harmful side effects. For example, Thalidomide has two enantiomers. One alleviates morning sickness while the other causes deformities in the limbs of fetuses. Unlike when thalidomide was first released, scientsits now study the effects of both enantiomers when new drugs are synthesized.

Not all racemic mixtures may have harmful effects on the body and, in some cases, one enantiomer will provide the desired pharmacological properties while the other will have no effect on the body. For example, the amino acid DOPA's L- isomer is an intermediate in dopamine biosynthesis and is given to patients to help manage Parkinson's Disease. The D-isomer has no biological effects on the body.


Enantiomers (Optical Isomers)

In three-dimensional (3D) space, the four covalent bonds of carbon atoms point toward the corners of a regular tetrahedron. The molecule represented to the right is methane (CH4).



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Whenever a carbon atom has four different structures bonded to it, two different molecules can be formed.
external image Ala.gif
EXAMPLE: the amino acid alanine. Bonded to its alpha carbon atom are:
  • a carboxyl group (COO−)
  • an amino group (NH3+)
  • a methyl group (CH3)(its R group)
  • a hydrogen atom
If you orient the molecule so that you look along it from the COO− group to the NH3+ group, the methyl (R) group can extend out
  • to the left, forming L-alanine(shown below on the left) or
  • to the right, forming D-alanine (on the right).
external image DL-alanine.gif
Although they share the same chemical formula, they are not interchangeable any more than a left-hand glove is interchangeable with right-hand glove.











Use of chiral auxilliaries to produce only one enantiomer rather than a racemic mixture
Effect of enantiomers on plane polarizes light
Drawing enantiomers using wedge/dash line diagrams