In this blog post, we’ll explore the concept and importance of optical isomers, as well as their significance in pharmaceuticals and biological processes.
The world we live in is made up of various small particles. Among them, the most functional and readily accessible particles are molecules. Molecules are composed of various types of atoms, and each molecule has its own unique molecular formula. While there are several ways to name molecules, the most basic method is to use a molecular formula that indicates the types and numbers of atoms that make up the molecule.
C₄H₈
A molecule with this molecular formula is composed of 4 carbon (C) atoms and 8 hydrogen (H) atoms. However, there is one limitation to these molecular formulas. This is because even molecules with the same molecular formula can differ in the way their atoms are bonded together. In other words, even molecules composed of four carbon atoms and eight hydrogen atoms can have different structures. Molecules that share the same molecular formula but have different structures are called isomers.
The two isomers described above differ not only in structure but also in their actual properties. Therefore, in chemistry, various methods of representation—such as structural formulas—are used alongside molecular formulas to indicate the actual structure, which cannot be determined by the molecular formula alone.
These isomers are classified into several types based on their structure and properties, and among them, the most interesting are optical isomers.
Imagine a doughnut with cream spread on only one half. If you hold this doughnut up to a mirror, you’ll see a doughnut that is an exact mirror image of the original. If you think of these two doughnuts as different, you’ll realize that they are actually completely identical—they just face different directions.
On the other hand, consider our right and left hands. If you hold your right hand up to a mirror, you’ll see an exact mirror image of your left hand. Just as with the donuts, if you treat the right hand and the left hand in the mirror as two different hands, you’ll notice that this time, the two hands do not completely overlap.
The same phenomenon occurs in the world of molecules. Some molecules have a mirror image that perfectly matches the original molecule, while for others, the mirror image and the original molecule do not overlap. A pair of molecules that are mirror images of each other but cannot overlap—as in the latter case—is called optical isomers.
Optical isomers differ only in the orientation of their atomic arrangement; their composition is identical. Because of this minor difference, most of their physicochemical properties—such as molecular weight, melting point, and boiling point—are nearly identical. Optical isomers are generally distinguished using notations such as R, S, D, or L, and in some cases, the symbols (+) and (-) are used to indicate the direction of optical rotation. So why is it necessary to distinguish between two molecules with nearly identical physicochemical properties?
There are various reasons, but the most easily understood one is that the two optical isomers may interact with living organisms in different ways.
The most famous example is thalidomide, which was once used as a medication. This drug was sold in several countries starting in the late 1950s as a treatment for morning sickness in pregnant women. Thalidomide has two optical isomers; while one form exhibits sedative and anti-nausea effects, the other interferes with normal fetal development and can cause severe congenital malformations. After it was revealed that thalidomide had caused widespread congenital malformations in pregnant women, more than 10,000 people were affected worldwide.
However, it has since been discovered—a fact unknown at the time—that the two optical isomers can interconvert within the human body. For this reason, simply isolating one form does not completely resolve the problem. This incident remains a prime example illustrating how crucial it is to accurately understand and manage optical isomers in drug development.
As this example illustrates, seemingly minor differences between optical isomers often lead to significant differences in actual outcomes. Since substances obtained through standard chemical synthesis in the laboratory are often produced in nearly equal proportions of both optical isomers, active research has been conducted to selectively obtain only the desired optical isomer. However, separating two optical isomers with very similar properties is by no means an easy task. In recognition of these research achievements, three scientists who developed selective synthesis methods using asymmetric catalysts were awarded the Nobel Prize in Chemistry in 2001.
Research aimed at selectively obtaining optical isomers is now expanding its focus to nature. Proteins, which constitute all living organisms, are composed of amino acids; interestingly, in all living organisms worldwide—including those in South Korea—nearly all the amino acids that make up proteins are L-amino acids. Not only amino acids but also many biomolecules produced in nature exist with one specific optical isomer overwhelmingly dominant. Scientists are investigating the possibility that while both types of optical isomers existed on the primordial Earth, one became selectively dominant through some process. Although the cause has not yet been clearly identified, it is expected that uncovering this secret of nature will lead to the development of technologies for more efficient synthesis or separation of desired optical isomers, which will have a significant ripple effect on the fields of pharmaceutical science and chemistry.
