Background

Have you ever thought about how the shape of a molecule affects the way that it functions?

Optical isomers, or enantiomers, are molecules that are made up of identical atoms, bonded together in the same way, i.e. they have the same connectivity. And yet, the 3D arrangement of the atoms in optical isomers is different as these molecules are mirror images of each other; you cannot superimpose one onto the other without breaking and remaking bonds. Many organic compounds exist as optical isomers.

Optical isomers can be compared to our feet; each foot connects to our five toes and our ankle in the same order (ankle-foot-toes), but our left foot cannot be superimposed onto our right foot, rather they are mirror images of one another. Optical isomers are a type of chiral molecule. If you take a chiral molecule, it interacts with symmetric, and non-chiral things in the same way as its optical isomer; in just the same way, your left foot fits into symmetric socks the same as your right foot. However, chiral molecules interact quite differently with other chiral, or asymmetric species, just as your left foot fits nicely into your left shoe, but your right foot does not.

Structure and shape often determine the way in which a molecule interacts with other molecules, and we see this in nature all the time. Many of the receptors within our body that respond to drugs are chiral, or isomeric, and therefore the chirality of the drug is incredibly important. A simple example of this is in the experiment below, which looks at two optical isomers of the molecule carvone:

S-(+)-carvone (left) and R-(−)-carvone (right). The carbon highlighted in green represents the centre of chirality and is the reason why this molecule exists as optical isomers.

Both isomers, so-called S-, and R– carvone, bind to receptors in our nose which means that we can smell them. The two optical isomers smell quite different to one another; R-(−)-carvone is the main component in spearmint oil, and smells like mint, whereas S-(+)-carvone is found in caraway seeds.

Optical isomers are so-called because they rotate plane polarised light. A solution of one optical isomer (or enantiomer) will rotate the plane of polarisation in a clockwise direction, which is known as the (+) form (such as in the caraway carvone), and a solution of the other enantiomer will rotate the plane in an anticlockwise direction, the (-) form (such as in the spearmint carvone). If the solutions are equally concentrated, and light is passing through the same depth of solution, the amount of rotation is the same, but in opposite directions.

When optical isomers are made in the lab, they are often prepared as a 50:50 mixture of the two enantiomers, which is known as a racemic mixture, or a racemate. In this case, there is no rotation of the plane of polarisation as the two isomers cancel out each other’s rotation. Preparing an optical isomer as a single enantiomer is much more challenging and is an area of active research for many synthetic organic chemists, especially in the field of drug discovery.

Chemists use polarimeters, which are instruments used to measure the angle of rotation of plane polarised light, in order to characterise optical isomers. It is possible to build your own polarimeter, quite easily in the class room, or even at home, to detect the ‘optical activity. of chiral molecules:

The experiment

A pdf version of this experiment is available here. There is no safety card for this experiment. Details for teachers or technicians can be found here.

AIM

Build your own polarimeter and see how chiral compounds interact with light, and which chiral receptors in your nose

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YOU WILL NEED

• glucose syrup
• spearmint essential oil or R-(−)-carvone
• caraway essential oil or S-(+)-carvone
• 3 glass vials, 6-7 cm in height (plastic vials cannot be used, as plastic tends to polarise the light. The diameter of the vials is not important, but those used in in the images on the site were 2 cm in diameter)
• a small beaker
• a clamp
• a sheet of paper
• 2 linearly polarised filters
  

PROCEDURE

Place the beaker face down in the centre of the sheet of paper, and draw a circle around it. Make sure the “lip” of the beaker is facing towards you, and treat this as the origin of the circle. Then draw a cross intersecting the circle.

Place one of the polarised filters on top of the beaker. When you later rotate the beaker (in order to rotate the filter sat on top of it, as in the video above), rotate it within the circle, using the lip of the beaker as a marker for the rotation.

Use a clamp and retort stand to suspend the second filter above the first one, at a sufficient distance so that one of the glass vials can be stood on top of the first filter. Make sure the filters are lined up, so that you can look at the bottom one through the top one.

Once the setup is completed, try rotating the beaker and bottom filter, whilst looking down through the top filter. Depending upon the rotation, you should observe that the filters appear dark and block the cross, or light and allow the cross to be visible. Align the two filters so that they are as dark as they can be, and mark where the lip of the beaker is, on the circle, labelled ‘0’.

Fill one of the vials with glucose syrup, and place this open on top of the bottom filter. Glucose syrup is a good starting solution to use as it very strongly rotates the plane of polarisation. Glucose is a chiral molecule and the most common enantiomer that occurs in nature (and what you will buy in shops) rotates the plane strongly in the clockwise direction. Rotate the beaker as before, and see what happens as you rotate the beaker. Can you see the cross through the solution when it appears dark in the absence of the solution? Why can you see the cross through the solution, but not (or barely) through the filter?
Repeat this with the R-(−)-carvone and the S-(+)-carvone. These solutions will not rotate the polarisation plane as much as the glucose syrup, but you will be able to see that they rotate the plane in different directions. Rotate each so that the solution looks as dark as possible (obscuring the cross as much as possible), and then mark where the lip of the beaker is.

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Questions

1. When you place the R-(−)-carvone in the vial, does it rotate the plane of the light’s polarisation?
2. When you place the S-(+)-carvone in the vial, does it rotate the plane of the light’s polarisation?
3. Do the two isomers behave differently to one another? If so, how?
4. Do the two isomers of carvone smell different to one another? Describe their smells. What does this tell us about the receptors that detect them in the nose?
5. Many chemical reactions can lead to the production of a racemic mixture of isomers. If a drug is made as a racemic mixture, do you think that it is important to separate the two isomers? If so, why?

Exercise 2:

A pdf version of this exercise is available here.  Details for teachers or technicians can be found here.

AIM – to appreciate what optical isomers are at the molecular level

YOU WILL NEED:

• a packet of midget gems (1 packet per group)
• cocktail sticks (~50 sticks per group)

The activity:

Start by making a tetrahedral chiral compound using cocktail sticks and the midget gems; you need to pick a central gem which will provide your centre of chirality (or stereogenic centre), and attach it to 4 differently coloured midget gems to generate a tetrahedral shape.  The outer midget gems, which form the vertices of the tetrahedron should be spaced as far apart from one another as possible:

Now make another structure that is the mirror image of your structure:

Look at the two structures – can you rotate one to make the other?

These two structures are optical isomers of one another.  Your molecule is chiral because it contains a centre of chirality (the central carbon atom). Many structures that we find in nature contain substituted carbon atoms that are attached to 4 different groups.

Now think about a molecule that contains 2 such carbon atoms, i.e. contains two stereogenic centres, starting off with the following groups that are linked together:

If we link the white midget gem to the empty stick, there are several different structures that can be formed, in which the atoms are all linked together in the same order, but which form structures that you cannot superimpose with each other, unless you break bonds. A molecule with one ‘stereogenic centre’ has two possible structures. How many possible structures are there with two stereogenic centres?

There are four possible structures, as each isomer of the first molecule has the option of being linked to each possible isomer of the second; there are 2×2 options, or 2², i.e. 4 possibilities.

A molecule that contains 3 stereogenic centres has 2×2×2 possible structures, i.e. 2³ = 8 possible structures.

This demonstrates how quickly the number of possible different structures suddenly gets more and more complicated, as the number of chiral centres within the structure increase.

Dr Liam Cox’s research group makes ‘glycolipid’ molecules.  These molecules contain a sugar group at the head, and long fatty hydrocarbon chains as the tails, such as the molecule shown below:

These glycolipids are chiral molecules, which contain 8 stereogenic centres, and therefore there are 2×2×2×2×2×2×2×2, (2⁸), i.e. 256 possible structures, possible structures which we would describe as stereoisomers!

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The importance of chirality in the development of immunotherapies at the University of Birmingham

Our immune system protects us from disease and pathogen attack by different types of cells working together like an army to generate an immune response. Researchers at the University of Birmingham, working with Dr Liam Cox, synthesise molecules called glycolipids as they are interested in understanding how these molecules are able to influence the immune system in a way that may be useful for future medicine. Glycolipids are lipid molecules, which are fatty chain molecules that dissolve well in non-polar solvents, that are attached to a carbohydrate group.

Certain glycolipids are known to bind to a protein in our body known as CD1d.  CD1d proteins are located on the surface of a range of cells in the body, known as antigen-presenting cells.  When a glycolipid is ‘loaded’ onto a CD1d molecule, the resulting CD1d–glycolipid complex can be recognised by receptor molecules (TCR) that are found on the surface of another type of cell (known as an invariant Natural Killer T-cell).  This cell–cell recognition event serves as a switch; it tells the Natural Killer T-cells to generate molecules that are released into the blood stream to provide an immune response.

Glycolipids are chiral molecules.  A glycolipid with 8 stereogenic centres has 256 possible stereoisomeric structures; however, only one of these isomers has the right structure to bind tightly with the CD1d protein molecule to generate a complex that in turn has the right shape to be recognised by the receptor molecules that are located on the surface of Natural Killer T-cells.  If we want to harness the capacity for glycolipids to activate the immune response and find potential application as immunotherapeutics, we therefore need to be able to develop selective synthetic routes to these molecules in order to generate the stereoisomer that has the therapeutic effect.

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Publications relating to this research

Abstract above reprinted with permission, Copyright (2013) American Chemical Society, under ACSAuthorChoice Agreement. http://pubs.acs.org/doi/abs/10.1021/bc300556e

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Files for download

pdf files:

Optical isomers experiment details for students

Optical isomers exercise for students

Optical isomers experiment and exercise details for technicians

Optical isomers experiment and exercise guidance for teachers

editable files:

Optical isomers experiment details for students word document

Optical isomers exercise for students word document

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This work is licensed under a Creative Commons Attribution 4.0 International License.