How handedness shapes the world

Dr PAUL Elliott, lecturer in chemistry, University of Huddersfield

When you get to the puzzle page of this newspaper and pick up your pen, what do you do?

The chances are that you will pick up the pen in your right hand whilst a few of you will use your left hand. This is because, unless you are ambidextrous, we are wired into being of one handedness, left or right.

On a chemical level, nature also exhibits handedness. Many of the molecules that our bodies use are of one handedness or the other. To illustrate the point lets go back to real hands.

Look at your hands, are they identical? You might think so but your two hands are very different from one another in a very fundamental way; they are mirror images of each, and more importantly, are non-superimposable.

This means that if you try and line up your hands, it is impossible to make them look exactly the same.

You might now be trying and place your palms together to prove me wrong, saying “look, they overlap perfectly”.

However, the palms of your hands are facing in opposite directions. Turn one hand around so that they point in the same direction and now one thumb is on the right, the other thumb is on the left.

No matter what way you put your hands, you would not be able to arrange them so that they could superimpose upon one another.

Many molecules are similarly non-superimposable just like the human hand.

The molecules of nature are based on frameworks constructed from atoms of the element carbon. Carbon atoms like to form four chemical bonds that bind them to other atoms.

A carbon atom will often arrange itself so that it sits at the top of a tripod formed using three of the atoms it binds to as legs with a fourth atom sitting above it.

In this arrangement, if the four other atoms that the central carbon atom is connected to are all different from one another (by virtue of being a different element or from what atoms are in turn attached to them) then the molecule similarly can not be superimposed on its mirror image.

These molecules are said to be chiral and the chirality of molecules is of the upmost importance to nature and medicine.

The two mirror images forms of a chiral chemical compound will under ordinary circumstances react in exactly the same way as each other, interact with light and heat in the same way and melt at the same temperature. While they are physically and chemically the same, biologically they will be very different.

The molecules of the sugars our bodies use, the amino acids that make up the chains of protein in our cells are all of one specific handedness. Because our body’s sugars and proteins etc are of only one handedness, any chiral molecule introduced into the body will interact differently depending on whether it itself is “left-handed” or “right-handed”.

With medicinal molecules, one handedness of molecule may therefore have the desired beneficial therapeutic effects whilst the other handedness might at best be useless but at worst could be deadly.

Those left-handed readers will have commonly come across problems analogous to this chiral selectivity in their daily lives.

The handles of the many of scissors are ergonomically designed to fit comfortably into a right hand.

Try using them in a left hand and they are cumbersome and difficult to use. This is because the chiral scissor handle interacts differently with the shape of your chiral hands.

The interactions of drugs with the body on a molecular level are very similar to this. Drugs often act by fitting into binding sites in biomolecules which then affects their functions.

Since the biomolecules are of one-handedness, a chiral drug molecule will interact in different ways with them depending on their own handedness.

The most famous (or infamous) example of the importance of the chiral handedness of drug molecules is thalidomide.

Thalidomide is a very effective drug for alleviating vomiting but crucially comes in two molecular mirror image forms.

One-handedness is the useful drug with useful properties, the other handedness was tragically found to cause severe birth defects when the drug was used (as a mixture of the two forms) to relieve morning sickness in pregnant women.

Today, when new medicines are developed which have two chiral forms, drugs companies must produce their pharmaceuticals purely in the correct mirror image form.

This can be very difficult to achieve. The chemical reactions that form these molecules will ordinarily result in a 50:50 mixture of the two which then have to be exhaustively separated. A less wasteful approach is to try and make the drug molecules selectively in only one form in the first place.

Great efforts have been made in conquering these challenges in academia, including work by scientists in Huddersfield, and in industry to develop such efficient catalysts for this very purpose.

So you may not have thought of being right handed or left handed as being of any particular importance. But to nature and medicine, it is a vitally important issue.