[MUSIC] So far in this course we have worked with one dimensional and two dimensional symmetry. We've also looked at patents and tiling. These types of symmetry require mirror lines, and they also require rotation points. For tiling, we also use translation. And when we combine translation with mirrors, then we created glide planes. In this part of the course, we need to introduce one final concept, the idea of chirality. What we would like to do is have you understand the difference between a chiral and an achiral object. And also to be able to describe and explain the function of chirality. The definiton of chirality is very straightforward. If you have two objects, one of which is a mirror of the other, and they are not super imposable, then you have a chiral object. A good example are your hands. Clearly, they are mirror images of each other. But you cannot superimpose one upon the other. A simple example of an achiral object would be a wine glass. In the case of wine glasses clearly we have a mirror relationship between them, but in this case one can be superimposed upon the other. So the definition of chirality is very straightforward, but it also turns out to be very, very important. Chirality is also described in textbooks on chemistry. Methane is composed of carbon surrounded by four hydrogens. It's in the shape of a tetrahedron. And we'll talk about tetrahedra later in this course. But it is possible to draw multiple mirror planes that intersect that molecule. Therefore, the molecule is said to be achiral. Because its mirror image can superimpose upon the original object. There are a series of molecules which can be used to illustrate chirality. These are the so-called halogenated methanes. In the halogenated methanes we progressively take away one hydrogen and introduce a halogen. The halogens are fluorine, chlorine, bromine, and iodine. [BLANK AUDIO] If we replace just one of the hydrogens by a halogen, so for example, as in fluoromethane, we still have mirrors therefore the molecule is still achiral. If we were able to make a molecule contain two halogens, say fluorochloromethane, we still have a mirror. But when we introduce three different halogens, for example fluorochlorobromomethane, then we destroy all the mirrors, and this is known as a chiral molecule. This idea of having a carbon where each of the four species, or entities around it are different, extends to very complicated molecules. And this is where the biological significance of chirality becomes especially important. We're very fortunate today to have Professor Subbu Venkatraman from the School of Materials Science and Engineering at NTU to speak to us about this topic. So we welcome you, Subbu, to talk to us today, and in particular to tell us about the troubles that turned about with thalidomide when it was introduced many years ago. >> Yeah, Tim, the story of thalidomide in my opinion is a very instructive one. Less fating the importance of chirality in nature, and how very specific nature is in dealing with molecules. So if you remember the story dates back to the 1950s when it was first touted as a cure for many things from headaches to insomnia to morning sickness. Unfortunately, not a lot of studies were done to look at the safety of this drug molecule. But it was prescribed very readily for pregnant women. And sometimes it was allowed to be prescribed or given without a prescription. Over the counter, as they call it. It was considered to be that safe. Unfortunately, almost half of the women who took this drug during pregnancy ended up with deformed babies. And this was widespread. Throughout the western world, this was happening. And then, a series of studies were done to associate this deformity with the drug, with the thalidomide drug, and it was found that one of the two chiral forms, one of the two enantiomers, is the responsible culprit for the bad effects of thalidomide. While the other enantiomer's responsible for the good effects. So it turns out that the so-called S enantiomer is the one that has the sedative and the tranquilizing effects associated with morning sickness. Whereas the other enantiomer is the one that stops blood vessels from growing. And that leads to deformed limbs, and sometimes deaths of the fetuses. So [COUGH] hindsight is 20/20 of course, but it turned out that introspectively the study’s should have been done to prove that this was safe in pregnant women by using animal models. And that, in fact, is now mandated for all drugs with not only just animal studies but also clinical trials. >> So let's just maybe take a quick look at the thalidomide molecule. And we have the two molecular forms in front of us here. And we can see that they're clearly chiral objects. The molecules themselves have an aromatic part. They also have some oxygens and some nitrogens involved. But there is clearly a mirror between these two forms, the R and the S form. If we dissect the molecule, then you can see quite clearly, that there are four discrete entities bonded to that central chiral atom. It's because of that relationship, that geometric relationship between these entities, that all the problems with thalidomide began. What really needed to happen, however, was that these drugs would be separated. But it was not so easy to do that. And I think you have some ideas about what went wrong in terms of separation and also how this might be improved or solved for future drugs. >> Yeah. Typically the synthesis of this molecule results in a racemic mixture. The technology was there, and is still around to separate the two enantiomers, or to do a stereospecific synthesis. Unfortunately, in this particular case, it's not very helpful to use one of the enantiomers. Because in the body [COUGH] there is a racemization that happens. So it defeats the purpose. But there are many other examples where stereospecific isomer can be synthesized. And is shown to be the bioactive form. For example, penicillin is a good example, where the levorotatory form is the one that is bioactive, and is in fact the one that is synthesized and prescribed. >> Right, very good. I think that we should also say that what we're talking about here is the chemistry of the molecule as a stand-alone entity. And something that I would like to say is if we look in the textbooks and we observe the molecules thalidomide, it's always shown as a plane. But in fact it's not really a planar molecule. The two parts have to rotate away from each other. Otherwise, we find that two of the oxygen atoms are too close to each other. So the story in the textbooks is correct. But it is somewhat simplified to the real case. And later on, in this course, when we come to look at crystals and we look at molecular crystals, we'll find the story is in fact even a little more complicated. When thalidomide crystallizes, it can do so in different ways. These are the alpha and beta polymers of thalidomide. And this is something which we'll discuss in part three of this course. So thank you very much, professor Subbu >> You're welcome. >> We really appreciate your insight today, and I hope that you have learned something more about the importance of chirality in medicine. So now you know what chirality is. A chiral object is one which cannot be superimposed upon its mirror image. In addition, chirality turns out to be tremendously important in a lot of biological functions, and therefore an understanding of chirality is critical in biomedicine. Shortly, we will start to introduce how we represent chirality mathematically, and in particular, in symmetry diagrams.
