Lecture 24


The word chiral comes from the Greek word for "hands". Look at your hands. They are mirror images of each other. Now try to superimpose your two hands. It can't be done. They are non-superimposable mirror images, or chiral. This is a good test for chirality since everything, except vampires, has a mirror image. Another way of determining chirality is to look for a plane of symmetry in an object or molecule. If an object has a plane of symmetry, it is achiral (not chiral).

In our study of alkanes, you were presented with the concept of chiral carbons, those being carbons with four different substituents. Shown below is a representation of a substituted methane and its mirror image.

In this type of representation, a Fischer projection, the atoms on the vertical axis go into the paper, and the atoms on the horizontal axis come out of the paper. These two molecules, mirror images of each other, can not be superimposed. A pair of molecules that are non-superimposable on their mirror images are called enantiomers. Alternatively, I could have looked for a plane of symmetry in the molecule. There isn't one, so this molecules is chiral and exists as a pair of enantiomers.

A pair of chemical enantiomers are identical in most of their physical and chemical properties, like density, boiling point, and melting point. They differ from each other in two important ways. The first difference is the way they interact with polarized light.

[This explanation may be of interest but is not material you need to know]

Ordinary light can be thought of as a wave phenomenon in which the vibrations of its electrical and magnetic fields occur at right angles to the direction is which the light is traveling. There are an infinite number of planes through the line of propagation, and ordinary light is vibrating in all of these planes. Plane-polarized light is light whose vibrations take place in only one of these planes. This is achieved by passing the light through a polarizing filter, which blocks out all but one plane of light. This light can only be detected by aligning a second filter to allow the passage of this plane of light. When polarized light is passes through some substances, the plane of the light is rotated away from the plane of the light entering the sample. Why does this happen?

When a beam of polarized light passes through a molecule, the plane of the light is rotated by its interaction with the charged particles of the molecule. Remember that light has magnetic and electronic fields perpendicular to its line of transmission, that will interact with the magnetic and electric fields in molecules. The direction and extent of orientation depends on the orientation of the particular molecule in the light beam. For most compounds, because of the large number of molecules that make up the sample, for every molecule that the beam encounters, it will, statistically, encounter another , identical molecule, oriented as the mirror image of the first, which will exactly cancel the effect of the first molecule. The result is no net rotation of the polarized light, or no optical activity. In order to be optically inactive (no net rotation), each molecule in a sample must have a second molecule positioned as its mirror image.

[End of interesting but non-testable material]

If the sample we are looking at is a 50-50 mixture of the enantiomers shown above, it will be optically inactive, because for each enantiomer present, its mirror image, the other enantiomer, will also be present. The rotation of the plane polarized light will always be reversed. This is called a racemic mixture.

However, in a pure sample containing only one of the enantiomers, no molecule can serve as the mirror image of any other, there is no canceling out of the rotations of the polarized light and the net result is optical activity.

One enantiomer will rotate light in a clockwise direction and is designated as the (+) isomer. It is also called the dextrorotatory (dexter = right) isomer. The enantiomer that rotated light in a counterclockwise direction is the (-) isomer, or levorotatory (laevus = left). This has to be determined experimentally.

The second way in which enantiomers differ is their interaction with chiral environments. The easiest analogy to this relationship is the relationship between your hands and gloves or mittens. We've already determined that hands are chiral. What about mittens? There is usually a plane of symmetry in mittens, the top and bottom are superimposable mirror images. This achiral environment, the mittens, can accommodate either hand. An achiral environments can accommodate either of the enantiomers

Gloves are chiral. They have no plane of symmetry between the top and bottom. Each glove can accommodate only one hand. A chiral environment can discriminate between chiral molecules. This is analogous to what happens in biological systems. Very often, the site at which biomolecules interact can accommodate only one of the two enantiomers, they are stereospecific.

We did an experiment in which you tasted a caraway seed and some spearmint gum. They had distinctly different tastes, and yet , chemically, they are simply stereoisomers of the same compound, carvone, a ketone:

The chiral carbon is marked (*). Because of this chirogenic center, this compound can exist as a pair of optical isomers, enantiomers. Since there is no plane of symmetry, this compound is optically active. Spearmint, (-) carvone, rotates light to the left and caraway, (+) carvone, rotates plane polarized light to the right. Both enantiomers will be reduced by NaBH4 to secondary alcohols. They have the same boiling and melting points, yet your olfactory system can tell them apart. That is because your smell receptors are chiral.

Our next task is to learn to represent large, three dimensional molecules in two dimensions. Let's use glyceraldehyde as an example:

The rules for making Fischer projections are :

1. Put the C=O group as close to the top as possible
2. Groups on the vertical axis curve into the paper
3. Groups on the horizontal axis come out of the paper
4. If the -OH group on the C* furthest away from the C=O is on the left, it's the L enantiomer. If this -OH is on the right, it's the D enantiomer.
5. (+) and (-) must be determined experimentally with a polarimeter, and have no relationship to D or L.

Let's look at a compound with more than one chiral carbon:

How many chiral carbons does it have? It has 2, marked in the Fischer projection below:

The aldehyde function is at the top. The chiral carbons(*) are located where the lines cross. We have put both OH groups on the left. The OH on the C* furthest from the C=O is on the left, so this is the L enantiomer. Let's also draw the D enantiomer.

Enantiomers are mirror image stereoisomers.

We put both OH on the same side. We could have put them on opposite sides:

This pair of enantiomers are diastereomers of the Erythrose compounds. Diastereomers are non-mirror image stereoisomers.

The rule for calculating the maximum possible number of stereoisomers is 2n, where n is the number of chiral carbons. Since n=2 in this case, there can be up to 4 stereoisomers.

I and II are enantiomers of each other, L and D Erythrose.

III and IV are enantiomers of each other, L and D Threose.

I and III are diastereomers of each other.

Let's look at a di-carboxylic acid:

For this molecule, n=2, so there can be a maximum of 4 stereoisomers.

I and II are the same compound.

There is a plane of symmetry along the middle of the compound. This is called a meso-compound, it has multiple chiral centers but it is not optically active. Because of the plane of symmetry, the C* are equivalent so there are fewer than 22 stereoisomers, there are only 3.

How are optically active molecules made? Reactions occurring in living systems are usually catalyzed by chiral enzymes. Under these conditions, even if the starting material is not optically active, the product will be optically active, if a chiral center is created in the process, since only one of the two enantiomers will be produced at a chiral enzymatic site. This is illustrated by the following examples:

An optically inactive reactant (no stereocenters) is hydrated (H2O added across a C=C) by a chiral enzyme, creating an optically active product, since only one of the enantiomers is formed.

In the lab, starting with optically active reactants, a reaction is carried out in which no bonds are broken to the C*, then the products will be optically active.

If, however, formation of a product with a C* begins with an optically inactive reactant, a racemic mixture will be formed (50% of each enantiomer) which will also be optically inactive.