Same But Different: A Story in Chirality

                For many of you making your way through your autumn chemistry syllabuses, you would have likely encountered the topic of chirality by now. Chirality is a property of individual molecules, properly characterized as a molecule having two enantiomeric forms which is a molecule of identical composition but arranged in a non-super imposable mirror image configuration. The most commonly used example are our hands; the two “molecules” have the same composition (one thumb, four fingers etc.) but while identical, they are mirror images of one another and are non-super imposable.

                For such a tiny difference, surely there is no difference in how different enantiomers behave chemically? In fact, the opposite is quite true and for today’s blog, I would like to illustrate this example with the fascinating example of thalidomide.

               Thalidomide has two enantiomers, the R and S forms seen above and was first marketed in 1957 in West Germany under the trade-name Contergan. Primarily prescribed as a sedative or hypnotic, thalidomide gained popularity as a treatment for nausea and to alleviate morning sickness in pregnant women. However, for those pregnant women who used thalidomide, their infants ran a very high risk of being born with phocomelia (malformation of the limbs) and less than half of these children survived. Throughout the world, about 10,000 cases were reported of infants with phocomelia due to thalidomide; only 50% of the 10,000 survived. Those subjected to thalidomide while in the womb experienced limb deficiencies in a way that the long limbs either were not developed or presented themselves as stumps.

                This horrible occurrence occurred because while one of the enantiomers of thalidomide had a soothing effect and quelled nausea, the other enantiomer binds to and inactivates the protein cereblon, which is important in limb formation. During development, the different enantiomers were not tested separately and it was assumed that their clinical effects would be similar. Fortunately, since this time all products being developed for use clinically must ensure that all enantiomeric forms are properly tested to avoid the tragedy seen with thalidomide. Interesting, while the drug was then pulled from the market and production ceased, research into the molecule continued and more recently it was re-launched as Thalomid, a treatment for the hematological cancer multiple myeloma. Today you can see that on the product’s website a substantial warning regarding the embryo-fetal toxicity of the program and oncologists must now perform a rigorous safety assessment when preparing to prescribe Thalomid to ensure that the patient is not pregnant, nor trying to conceive.

While thalidomide is one striking and famous example of chirality in action, there are many other examples which I urge you to go find and research as good examples to discuss in your Oxbridge interviews. As a clue, if you don’t sweeten you tea with sugar, what chiral molecule might you add?