stereoisomerism

Stereoisomers

Stereoisomers have the same molecular formula and structural formula but the atoms are arranged differently is space. There are two types of stereoisomers:

model of a polariser

Plane polarised light

The light that we see everyday objects by is unpolarised, this simply means that the waves of electromagnetic radiation (visible light) that for example a light bulb emits travel out from the bulb in every direction or plane; this is shown in the diagram below. However when this unpolarised light passes through a polariser only light waves that are vibrating in one particular plane can pass through, all the other planes of light are blocked. Think of the polariser much like a simple drain cover with slits all running parallel; if you drop an object down through this drain cover then only objects that fall parallel to the slits in the drain cover will get through!

The light that passes through the polaroid material (the same material used in sunglasses) is said to be plane polarised light, that is all the light waves are vibrating in only one single plane.

description of plane polarised light

Optical activity

If a beam of plane polarised light is passed through certain organic molecules something remarkable happens, the beam of plane polarised light is rotated, either to the left or to the right. Molecules which rotate plane polarised light are said to be optically active molecules. In the diagram below you should be able to see the unpolarised light waves travelling from the bulb, these then enter the polariser and only light waves vibrating parallel to the slits in the polariser pass through it. Next the plane polarised light enters a sample tube containing an optically active compound. In the diagram the optically active compound rotates the plane polarised light by a few degrees. The light waves now meet another polariser or analyser. The analyser is simply a piece of polaroid film, much like the polariser. However when the rotated light waves meet it they will not be able to pass through until the analyser is rotated by the same angle that the plane polarised light was rotated by the optically active sample in the tube. By simply measuring how much the analyser was rotated we can measure how much the plane polarised light was rotated by the optically active molecules in the sample tube.

diagram to show how a polariser works

As well as measuring how much plane polarised light is rotated after passing through the sample tube we can also determine whether the plane polarised light is rotated clockwise or anti-clockwise. Some optically active molecules rotate plane polarised light anti-clockwise, these molecules are said to be levorotatory. Optically active molecules which rotate plane polarised light clockwise are said to be dextorotatory. By convention anti-clockwise rotation is also give the minus sign (-) while clockwise rotation is given the positive sign (+), e.g. Glucose is an optically active molecule, (+)-glucose is dextrorotatory and will rotate plane polarised light clockwise, while (-)- glucose is laevorotatory and will rotate plane polarised light anti-clockwise.

Chiral carbon atoms

How do we know which molecules will rotate plane polarised light? Well in A-level chemistry we can say that all organic molecules with an asymmetric carbon atom will rotate plane polarised light. What this means in simple terms is that an organic molecule with a carbon atom bonded to four different groups will be optically active.

Enantiomers

Can you think of any ways in which your right and left hand are similar and also different from each other? There is the obvious fact for example that each of your hands have 5 fingers but if you are in a rush and you put a left handed glove on your right hand and the right handed glove on your left hand you would immediately know that something was not quite right! Its a similar story with your feet, if you put the wrong shoes on the wrong feet then by the end of the day you will have sore feet! So what is the relationship between your feet and your hands? Well they are mirror images of each other. It is not possible to place your right hand on top of your left hand and get all your fingers and thumbs to match up. Well its the same with optically active molecules. Mirror images forms of molecules which contain four different groups attached to a carbon atom, that is the carbon atom will be asymmetrical, will be non-superimposable onto each other. These two mirror image forms of a chiral molecule are called enantiomers.

If a molecule is unsymmetrical and contains no planes of symmetry then it will be non-superimposable on its mirror image, these molecules are chiral and will be optically active. The two mirror image forms of an optically active molecule are called enantiomers. Each of these mirror image molecules or enantiomers will be optically active and will rotate plane polarised light, but each enantiomer will rotate plane polarised light in equal but opposite directions. This is shown in the diagram below:

No matter how hard you try you cannot superimpose one enantiomer on top of another, in the examples below it is only ever possible to match-up TWO of the four groups on the central chiral carbon atom.

Racemic mixtures

Many naturally occurring molecules exist as single enantiomers. This is mainly due to the fact that many natural processes in living organism involve enzymes and since enzymes are stereospecific they can readily distinguish one enantiomer from another. It is highly likely for example that one enantiomer will fit nicely into an active site in an enzyme but the corresponding mirror image molecule, the other enantiomer is unlikely to fit into the enzyme's active site.

Almost all the chemical reactions that you are likely to carry out are not stereospecific and it is almost certain that any synthesis will produce equal amounts of the two enantiomers. If a mixture of the two enantiomers are present in equal amounts then this mixture will be optically inactive and will not rotate plane polarised light. This is simply because if equal amounts of the laevorotatory and dextrorotatory enantiomers are present then the effects of the equal and opposite amount of rotation of any plane polarised light will simply cancel each other out. Solutions which contain equal amounts of both enantiomers are called racemic mixtures or a racemate and are optically inactive.

As an example consider the synthesis of the optically active compound 2-hydroxypropanoic acid. This compound can be prepared by the nucleophilic attack of a cyanide ion (:CN-) on a molecule of ethanal. Ethanal is a flat planar molecule and the cyanide ion (:CN-) can attack the ╬┤+ carbon atom in the carbonyl group in a molecule of ethanal. Since the nucleophilic cyanide ion can attack the carbonyl group with equal probability from either side of the carbonyl group an equal mixture of the two possible enantiomers is produced, that is a racemic mixture of the (-) and (+) enantiomers of 2-hydroxypropanoic acid are formed. This is outlined in the diagram below:

nucleophilic attack of a cyanide ion on ethanal to 
form a racemic mixture of enantiomers of 2-hydroxypropanoic acid

Drugs and racemic mixtures

ibuprofen is sold as a racemic mixture

In the lab it is unlikely that you will get the opportunity to use just one particular enantiomer of an optical active compound. The reasons for this are fairly simple:

However most naturally produced compounds, that is one produced by living organisms will only produce one enantiomer. This is because the natural processes that take place in living organisms are likely to be controlled in some way by an enzyme and since enzymes use active sites this means that only one enantiomer will fit the active site.

Drugs work by changing or interfering with a chemical reaction inside the body. Most drugs do this by binding to an active site on a particular enzyme or receptor molecule. This means that the drug must be the exact shape to fit into the active site in the enzyme. If one enantiomer fits into the active site it is highly unlikely that the mirror image molecule or other enantiomer will fit. Indeed it maybe that this unwanted enantiomer could bind to another active site elsewhere which could result in harmful side-effects, these side-effects could be minor or may even result in the death of a patient. Two examples of this are:

Thalidomide

Thalidomide was a drug developed by the German pharmaceutical company Chemie Gr├╝nenthal GmbH. Thalidomide was prescribed by a doctor to treat conditions such as colds and flu and for relieving the symptom of nausea and morning sickness often experienced in the early stages of pregnancy. Thalidomide is an optically active substance with chiral centres present. While one of the enantiomers had the desired therapeutic effects the other enantiomer caused serious birth defects in babies. The drug only affected the unborn embryo if the mother took thalidomide between 20 and 37 days after conception. Thalidomide resulted in the death of over 2000 unborn babies and caused approximately 10 000 babies to be born with serious limb defects and defective organs.

Seldane is another drug where one enantiomer is an effective antihistamine used to treat the symptoms of hay fever and congestion while the mirror image enantiomer can cause serious and fatal heart defect in some patients.

Considering the two drug examples mentioned above most new drugs prescribed now are likely to consist of one enantiomer. This has a number of benefits:

However to separate out a mixture of enantiomers, which will have similar if not identical physical properties such as melting and boiling points and solubility’s is not easy and is expensive. To get round this scientists have developed a number of other methods to produce only one enantiomer of any particular drug molecule. Processes which occur in living organisms such as bacteria and moulds are controlled by enzymes and these enzymes only produce one enantiomer of an optically active compound. If these same organisms can be used as part of the method used in manufacturing the drug it is likely to be stereospecific and produce only one enantiomer. Alternatively if chemists can use naturally occurring compounds such as amino-acids or sugars as the starting materials as these will consist of only one enantiomer, then this can help in ensuring the production of only single enantiomeric products. Finally the use of transition metal complexes can produce catalysts which are stereospecific and will enable the production of only single enantiomeric products.

structure of ibuprofen

Not all drugs consist of single enantiomers. Ibuprofen is an analgesic which is taken to relieve the symptoms of muscle pain, migraines, period pains and to treat the symptoms of colds and flu. The ibuprofen molecule has a single chiral carbon atom so it consists of a pair of optical isomers. The (+)-enantiomer acts much more quickly to relieve pain than its mirror image enantiomer. Luckily once inside the body the less active (-)-enantiomer is converted into the more active (+)-enantiomer, this means that the whole dose taken is active and it is not necessary to take a double dose to achieve the desired therapeutic effect.

Key Points


Practice questions

Check your understanding - Questions on optical activity.

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