Optical isomerism is a type of stereoisomerism in which the optical isomer has a chiral centre and does not possess a plane of symmetry.
The ⍺-carbon in ⍺-amino acids (except for glycine) is an example of a chiral centre with four different groups bonded to it.
Molecules with a chiral centre are non-identical with their mirror image – the two isomers are said to be non-superimposable. Your hands are a classic example of chiral objects …
More complex molecules may have several chiral carbon atoms, often denoted with an *.
Pairs of optical isomers that are mirror images of each other are called enantiomers …
Enantiomers interact with plane-polarised light in different ways. If we pass a beam of plane-polarised light with a single wavelength through a solution of one enantiomer, the beam of light will be rotated either clockwise or anticlockwise when it emerges.
The enantiomer of a chiral molecule which rotates plane-polarised light in a clockwise direction is labelled the (+) isomer or D-isomer. The enantiomer which rotates plane-polarised light in an anti-clockwise direction is labelled the (-) isomer or L-isomer.
If we have a solution of enantiomers in a 1:1 ratio (an equal mixture), half the molecules will rotate plane-polarised light clockwise and half anti-clockwise. Overall the mixture will not be optically active. This mixture is called a racemic mixture.
Enantiomers behave identically in test-tube chemical reactions, and they have identical melting points, density and solubility. However, enantiomers behave differently in the presence of other chiral molecules which has significant implications in terms of any biological activity.
For example, proteins are built from chiral amino acids, which means that enzymes and many hormones are also chiral. One enantiomer of a biological substrate molecule or pharmacological drug will interact differently with a protein receptor / enzyme to the other enantiomer because the enantiomers have different 3D shapes (in the same way that you need a right handed glove for your right hand).
For example, enantiomers interact differently with our chiral taste-buds with D-amino acids tasting sweet and L-amino acids tasting bitter. Similarly, enantiomers may smell different (see the example of carvone above).
Epinephrine, better known as adrenaline, is a hormone that is integral to our ‘fight or flight’ response. It is made in the adrenal glands and the medulla part of the brain from the amino acids L-tyrosine and L-phenylalanine.
Since enantiomers have identical physical and chemical properties, the production of chiral pharmaceutical drug molecules in the laboratory will always produce a racemic mixture of enantiomers which are very difficult to separate (currently this is a major area for research). In many instances pharmaceutical drugs are taken as a racemic mixture as one enantiomer has little or no pharmacological activity / side-effect. However, the thalidomide story is a cautionary tale …
Practice questions
- Butan-2-ol has a chiral centre and two enantiomers. Draw two molecules of butane-2-ol to illustrate the meaning of these terms.
- Salbutamol is a chiral molecule. Identify the chiral centre and suggest why one enantiomer is seventy times more effective for treating asthma than the other.
- Given that the general formula of an amino acid is RCH(NH2)COOH, draw 3D diagrams to show the optical isomers of lysine (R= (CH2)4NH2.
- The amino acid glycine exists as a zwitterion in solution. Explain the effect, if any, of an aqueous solution of glycine on a single wavelength of plane-polarised light.
- A single enantiomer of nicotine is found naturally in tobacco leaves.
(a) Draw 3D structures of both enantiomers showing that they are non-superimposable.
(b) Explain how you could distinguish between separate samples of the two enantiomers.
Answers
2.
Each enantiomer has a different configuration of groups around the chiral carbon atom and the enantiomers are non-superimposable. The active site of the receptor for salbutamol is also chiral so only one enantiomer has the correct 3D orientation to bind effectively with it.
3.
4. The glycine zwitterion has no chiral carbon / centre as the ⍺-carbon is not bonded to four different groups. The mirror image of the zwitterion is superimposable, so it will have no effect on plane-polarised light.
5. (a)
(b) Shine plane polarised light through each sample and they will rotate it in different directions / clockwise and anticlockwise.