Chirality and Enantiomers

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Enantiomers

Stereoisomers are molecules that have the same molecular formula and the same connectivity of atoms, but differ only in the three-dimensional arrangement of those atoms in space. Two general forms of stereoisomerism are geometric isomers, and optical isomers or enantiomers.

Enantiomers are pairs of stereoisomers that are chiral. A chiral molecule is non-superimposable on its mirror image, so that the mirror image is actually a different molecule.* The two non-identical mirror images are a pair of enantiomers. Unlike other sorts of isomers, enantiomers have identical physical and chemical properties (except those involving interaction with other chiral objects).

* A common macroscopic example of chirality is your hands. Your hands have the same connectivity of fingers and thumbs, but they are mirror images of each other, and so you cannot superimpose them. The word chiral comes from the Greek ceiros, meaning hand.

One common origin of chirality (and that found almost exclusively in organic chemistry) is a tetrahedral coordination of four different groups about a central atom. The central atom is referred to as a chiral centre or stereocentre. If any two of the groups bound to a tetrahedral centre are the same, then the molecule has a plane of symmetry, and the mirror image is an identical and superimposable molecule. This is shown below at left. However, if all four groups are different, the molecule does not have a plane of symmetry, such that the mirror image is non-superimposable, and so is a different molecule. The result is two enantiomers, as shown below at right. (Note that this four-different-groups rule has limited application. There are other, more rigorous ways to spot a chiral compound.

These molecules are mirror images, but can be superimposed, demonstrating that they are not isomers but are in fact the same molecule. Push the button to see that this is so. These mirror image molecules are non-superimposable, and so they are enantiomers. Each is a different chiral molecule.

The two enantiomers of 2-butanol are shown at right. The mirror image of the first molecule can be rotated such that the -H and -CH3 groups are in the same positions as in the original molecule. The -OH and -CH2CH3 groups are in the reverse positions, so the mirror image is a different molecule: 2-butanol contains a chiral centre and exists as two enantiomers.

 

Optical Activity of Enantiomers

Plane-polarized light is also chiral, due to the relative orientations of the electrical and magnetic field oscillations. As a result, a solution of a chiral molecule can interact with such light, rotating the plane of polarization, a property called optical activity. Chiral molecules are usually optically active, and two enantiomers will exhibit equal and opposite light rotation; thus, enantiomers are also called optical isomers. A 50:50 mixture of both enantiomers is called a racemate or racemic mixture, and does not rotate the light plane. A useful method of differentiating enantiomers, or analyzing the purity of enantiomers, is based on this difference:

There are other systems for naming enantiomers, based instead on the structure of the molecules. See some examples from both organic and inorganic chemistry.

 

Importance of Enantiomers

For the most part, enantiomers have identical physical and chemical properties. Nevertheless, the difference between two enantiomers can have enormous impact, particularly in biological systems, because many important biological molecules are chiral.

Amino acids are the building blocks of proteins and enzymes in all terrestrial life, and have the formula +H3NCH(R)CO2. Note that the central C atom is surrounded by four different groups (except in the case of glycine, where R = H), so that amino acids are chiral. All naturally-occurring amino acids exist as only one of the two possible enantiomers, and so by extension, all proteins and enzymes are also chiral.

  This enantiomer of the amino acid alanine is found in nature. This enantiomer of alanine is not naturally occurring.

The chemistry of your body is therefore controlled by chiral molecules. Your body is effectively a chiral environment, and so different enantiomers of a molecule will react with it in different ways. This includes pharmaceuticals: different enantiomers of a chiral drug can often exhibit different bioavailabilities, metabolism rate, potency, or toxicity. For example, the S-enantiomer of citalopram, used to treat depression, is 30 times as potent as the R-enantiomer. A commonly cited classic example is the drug thalidomide, shown at right, which was sold worldwide to pregnant women as a treatment for morning sickness from 1957-1962, and was responsible for the birth of over 10000 deformed babies. Thalidomide is chiral: the carbon with four different groups is shown in yellow. There is evidence to suggest that only one of the two isomers is teratogenic in mice,* and it is commonly believed that the birth defects could have been avoided if thalidomide had been marketed as an enantiomerically pure substance rather than a racemic mixture. However, even enantiomerically pure thalidomide racemizes in vivo, so that it is effectively impossible to administer just one form.

* A teratogenic substance can cause developmental malformities, affecting how genetic material is expressed, but not causing permanent genetic damage. This effect is distinct from that of mutagenic substances, which permanently alter the genetic material. Mutagenic abnormalities are potentially hereditary; teratogenic abnormalities are not.

Another classic example of the different physiological behaviour of enantiomers is the carvone molecule. One isomer interacts with your body to provide the scent of spearmint, while the other is the scent of caraway seeds.

R-thalidomide: suggested non-teratogen

S-thalidomide: potent teratogen

R-carvone, scent of spearmint oil

S-carvone, scent of caraway


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