The 2023 Nobel Prize in Chemistry, awarded toHenri Kagan,from the University of Paris-Sud, in France, and toKenso Soai,from the University of Tokyo, in Japan, recognizes fundamental work related to the control and amplification of chirality in chemical reactions. But what is chirality?
In simple terms, some molecules can exist in two mirror-image forms, such as our left and right hands. They have the same atoms, but a different spatial arrangement – in the context of molecules, we call this phenomenon enantiomers.
And this is very important because our body is also chiral. Our proteins, enzymes, and receptors have very specific three-dimensional structures and can interact differently with each of these forms.
This leads us to one of the most well-known examples in the history of medicine: thalidomide.
In the 1950s, it was used as a sedative and also to treat nausea during pregnancy. Its use caused a major tragedy, with thousands of children being born withsevere deformitiesincluding fetal malformations, such as polydactyly.
Thalidomide is a chiral molecule: one of its forms is actually sedative and has therapeutic effects. The other is teratogenic and causes fetal malformations during pregnancy – but until then, this was not known. This case helped to show, in a very dramatic way, that the three-dimensional structure of a molecule can be as important as its chemical composition.
Today, this is a fundamental issue in the development of APIs (Active Pharmaceutical Ingredients).
Depending on the drug, different chiral forms can exhibitsignificant differencesof activity, metabolism, and safety. Therefore, one of the strategies of pharmaceutical chemistry is to develop asymmetric syntheses, which are capable of preferentially producing the desired form, avoiding or reducing the need to subsequently separate a mixture of enantiomers.
And it is precisely in this context that the Nobel Prize-winning work is so important: Kagan and Soai helped to show how small differences in chirality can be controlled and even amplified during a chemical reaction.
There is also a fascinating connection with the very origin of life. The amino acids present in proteins are predominantly of the L configuration, while many biologically important sugars belong to the D family. These configurations are correlated with the three-dimensional arrangement of these molecules, as if they were our hands, a left and a right. In the case of molecules, we use an L and D convention to distinguish the two forms. We have been studying how this preference emerged, including because chiral organic molecules are found in meteorites.
At Sirius, a look at the behavior of molecules
But, after synthesizing a chiral molecule, we also need to know what we actually produce.
And then there are characterization techniques, such as circular dichroism, one of the techniques that we can use at Sirius, the particle accelerator at the CNPEM (National Research Centre for Energy and Materials), one of the four 4th generation accelerators in operation worldwide, located in the city of Campinas (SP). CEDRO is one of the Sirius light beams and uses synchrotron light to study the structure and behavior of molecules, especially proteins.
Understanding the structure of a protein is fundamental, because a change in its three-dimensional structure can completely change the way it functions.
A recent example that has become quite well known in Brazil is thecase of influencer Lito Sousafrom the Aviões e Músicas channel, who was diagnosed with Creutzfeldt-Jakob disease, a prion disease. In this type of disease, a protein can adopt an abnormal conformation and favor the change of conformation of other proteins, triggering a process that leads to the degeneration of nerve tissue. It is a very interesting example of how the structure of a protein is directly related to its function and, in certain situations, to the disease itself.
And that is precisely why techniques like circular dichroism are important: they help us understand how these molecules are structured and how this structure can change under different conditions.
At CEDRO, we use synchrotron radiation to perform circular dichroism experiments. This technique allows us to study how chiral molecules interact differently with circularly polarized light and obtain important information about their structure and organization. This is an interesting connection in light of this year's Nobel announcement.
In this interaction process, a small chemical asymmetry can be amplified during a reaction, favoring the production of one form of a molecule. This is important in the development of pharmaceutical molecules, which then need to be characterized in order to understand their structure and organization.
This is an example of how a fundamental question in chemistry can connect research on the origin of life, the pharmaceutical industry, and a major scientific infrastructure like Sirius.
Lindomar José Calumby Albuquerque does not provide consulting services, works, owns shares, or receives funding from any company or organization that could benefit from the publication of this article, and has not revealed any relevant connections other than his academic position.