The Chemical Concept of Stereoisomers

Introduction

Isomerism in a chemical compound is the existence of different arrangements of atoms with the same chemical formula. There are 2 kinds of isomerism:

Structural Isomerism, where isomers of different structures arise from

  • Different position of carbon chains
  • Different position of functional groups
  • Different functional groups

Stereoisomerism, where isomers have the same structure and sequence of atoms, but different spatial arrangement. There are 2 kinds of stereoisomers:

  • Geometric isomers are centered about a C=C bond. These are also known as cis-trans isomers
  • Optical Isomers are centered about chiral carbon.

Our team will focus on stereoisomerism(in particular, optical isomerism) and how it can change the effects of drugs.

Explanation

A chiral molecule is centered about a chiral carbon that has 4 different functional groups attached to it and cannot be superimposed with its mirror image. The concept is similar to how our left and right hands are mirror images of each other but not superimposable. Two mirror images of such a molecule are known as enantiomers, and a mixture containing equal amounts of both enantiomers is known as a racemic mixture.

Enantiomers are often named by R/S system. To name enantiomers by the R/S system, the viewer needs to orientate the molecule such that the functional group with the lowest priority, according to the Cahn–Ingold–Prelog priority rules, is pointed away from the viewer. The R-enantiomer is the one with the priority of the remaining 3 functional groups decrease in a clockwise direction and the S-enantiomer is the one that decreases in an anti-clockwise direction.

The +/- system of naming is also often used, in reference to the direction in which the enantiomers rotate polarised light.

To appreciate how stereoisomerism affects drugs, we have to first consider that biological molecules often react with each other via the “lock-and-key” mechanism. As a result, if a molecule is able to fit another reactant molecule, its enantiomer may not due to a different 3-D spatial arrangement. This will lead to the enantiomer being an inactive compound or a compound that reacts differently.

References

Stereochemistry in Drug Action, Jonathan McConathy, Ph.D. and Michael J. Owens, Ph.D. Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC353039/

Unit 8 Lecture Slides 48-49.