Chemical compounds can have a "handedness", with their atoms aligning themselves in a left-handed or right-handed way making them mirror images. Their chemical actions can be radically different as a result, with one form being, for example, a useful drug and the other a deadly toxin.
The handedness or "chirality" of chemicals was the subject for the winning entry in the Royal Irish Academy/Irish Times chemistry science writing competition. Open to both secondary and third-level students, the object was to write a 2,000 word essay on some aspect of chemistry, using non-technical language.
The overall winner was Alison Squire, a secondary school student from Killiney, Co Dublin, who in clear and understandable prose wrote about chirality and its impact on the pharmaceutical industry. Her efforts have won her £250 and a John Coen bronze sculpture, both sponsored by AGB Scientific Ltd.
The following is the essay prepared by Ms Squire:
YOUR hands are chiral, they are exactly the same, but they are mirror images of each other. If you put one hand on top of the other, your little finger will end up on top of your thumb, therefore they are non-super-imposable. In 1848, Louis Pasteur found that the principle of chirality applied to chemistry. Some molecules are chiral, they have exactly the same elements, in the same ratios, but they have different arrangements of their atoms in space.
So how does this affect us? Our body works by using chemicals acting as "keys" to release other chemicals. Some of these chemicals come from our food, some we have naturally, and some we take as medicine to either stimulate a reaction or to stop another reaction occurring. These keys are not just two-dimensional, they are three-dimensional. Just as your left hand will not fit into a right-handed glove, the "left hand" of these molecules may fit into one of these "locks" to initiate one response, while the "right hand" may initiate another.
So how do you tell the difference between the left hand and the right hand? These compounds are optically active. This means that when you shine plane-polarised light on them, they will make the light rotate. One of the formations will rotate the light in one direction and the other will rotate it by the same amount, but in the opposite direction.
Sometimes you will get a mixture of the two to form an optically inactive compound, and this is known as a racemic mixture. Until quite recently, many medicines were developed as racemic mixtures. Some investigation into the properties of "enantiomers", or different chiral forms of some drugs, has yielded benefits for many companies and patients alike.
The advantages of drugs that are developed as just one of the two possible forms are huge. For the patient, single enantiomer drugs are in many cases far more effective than racemic or mixed form drugs. If a single enantiomer is given instead of a racemic drug, you may be able to reduce the dosage. The patient may also escape many of the unwanted side effects caused by the less desirable enantiomer in the drug.
There are also benefits for the manufacturer. The US Food and Drug Administration (FDA) strongly advises that when a racemic drug is developed, the mixed form and both the enantiomers undergo clinical trials. If only one enantiomer is produced, then the company can save valuable time and money by doing only one set of clinical trials. They also save in production. If 10 doses of a mixed-drug form drug take up a certain amount of space on the production line, producing only one enantiomer will reduce the manufacturing volume. This allows 20 doses to fit in the same space.
The application of chirality to drug development has seen many people benefit. This has included both asthma and Parkinson's disease sufferers.
L-Dopa
IT had been known that one of the causes of Parkinson's disease was a lack of a chemical in the brain called dopamine. So, the solution seemed simple, make dopamine and give it to the patients to top up their supplies. But there was a problem. Our brain is delicate, so to protect it we have a layer between our blood vessels and the brain itself. This is known as the blood brain barrier. It prevents many unwanted chemicals in our bloodstream from entering and damaging our brain. However, it also prevented any dopamine that the Parkinson's patients were given from entering the brain and taking effect.
Through further research it was discovered that in the brain the drug L-Dopa was converted to dopamine. (L-Dopa is an enantiomer, the "left" hand of a pair.) Only 1 per cent of L-Dopa reached the central nervous system, the other 99 per cent being converted into dopamine in the gastro-intestinal tract.
However, when a second substance was added the results were so much better that L-Dopa is now used as one of the main drugs used to alleviate the symptoms of Parkinson's.
L-albuterol
ALBUTEROL has been used for many years for the treatment of asthma. It is a bronchodialator or "reliever", sold by Glaxo Wellcome PLC under the name Ventolin and by Schering-Plough Corp as Proventil. Albuterol, despite its effectiveness, has problems associated with it. Besides producing jitteriness and irregular heartbeat, repeated use worsens the asthma (W.O. Spitzer et al., New England Journal of Medicine, 326:501-6, 1992).
Another company, Sepracor, tried to improve albuterol by separating the active enantiomer. In 1994, it patented L-albuterol. This produces the same results at one eighth of the dose, and the side effects are reduced by half. It also does not worsen asthma with repeated use.
This is an example of why the separation of the two "hands" is so important. The research into separation of these isomers can be expensive and time consuming, but when you get it right, the results are so good that many companies are now being set up to research into chiral science alone.
L-Dopa and L-albuterol are two of the many successes that can be attributed to the application of a basic principle of chemistry to the production of medicines. Of course giving the body a single enantiomer does not always have the desired effect. The body can convert it naturally to the two forms, giving you the enantiomer that produces unwanted effects as well, with one example being Thalidomide. A racemic mixture can also produce results that cannot be matched by giving the individual enantiomers.
There is a potentially huge market to be exploited by further research into chiral drugs. More methods are being developed for the separation and production of enantiomers, making the process increasingly efficient, and hence productive.
Alison Squire is a student at St Joseph of Cluny Secondary School, Killiney. She is interested in science, and although she is studying physics and chemistry, has not decided which area of science she would like to go into as a career