Scientists have managed to synthesize molecules with a special type of molecular asymmetry.
The Metal Catalysis and Organocatalysis Research Group of the University of the Basque Country (UPV/EHU), in collaboration with the Rovira i Virgili University of Tarragona, has developed a methodology to desymmetrize some molecules and obtain a type of asymmetry molecular structure that opens the door to new structures unprecedented in nature and which could be used as therapeutic agents.
The group is led by UPV/EHU professor José Luis Vicario.
The group, which works on the asymmetric synthesis of small organic molecules, has succeeded in “synthesizing intrinsically asymmetric cyclic molecules using catalysis. “We have developed an effective and straightforward methodology, using small quantities of a catalyst derived from copper, an abundant and non-harmful metal,” says the professor of organic chemistry at the UPV/EHU.
The vast majority of organic molecules (based on a carbon structure) are not planar; They have a three-dimensional geometry. Depending on the way the atoms are arranged within each molecule, results can be obtained. In some cases a molecule and its mirror image (i.e. two symmetric molecules that have the same relationship that an object has with its image in a mirror) can have completely different properties.
Let’s use the simile of hands to explain this: our hands are mirror images of each other; It can be said that they are identical. However, when one hand is placed on top of the other (not in the position of bringing the palms together, but rather of overlapping one hand over the other), the position of the fingers is not the same. The same thing happens with some molecules, the organization of the atoms does not coincide. Each of the mirror images of a molecule that are not superimposable is called an enantiomer.
“In nature and in pharmacology there are many examples in which the two enantiomers have different properties. This is the case of thalidomide (a drug administered as a sedative and anti-nausea in the first three months of pregnancy, which has caused thousands of cases of congenital malformations), one of the enantiomers has analgesic properties and the other causes malformations – explains Efraim. Reyes, of the UPV/EHU and one of the main authors of the work. This occurs because therapeutic targets do not interact in the same way with one enantiomer or another. Therefore it is essential to control the synthesis of this type of molecule, to obtain only one of the two enantiomers.”
Pre-doctoral researcher Josebe Hurtado was able to selectively build one of two enantiomeric molecules of a group of cyclobutanes (cyclic molecules that essentially contain carbon and hydrogen atoms), “through desymmetrization; that is, breaking the planar symmetry and converting them into elementary synthetic building blocks of more complex molecules,” explains his thesis director Efraim Reyes.
Josebe Hurtado. (Photo: Laura López, Communications Office, UPV/EHU)
This result responds to a great current challenge and to a research area of growing interest. “We managed to synthesize molecules with an axial asymmetry (supported by an axis), which is unprecedented in nature and which opens the door to the study of a new type of molecules, which can also be used to develop new therapeutic avenues,” adds Vicario. Furthermore, through rigorous control of the reactions “we broke the planar symmetry to convert it into axial asymmetry and then into point asymmetry (supported at a point)”, explains the UPV/EHU professor. This shows “that there is a real possibility that even biomolecules with asymmetry could have a common origin.”
Spontaneous desymmetrization, origin of life
This finding is reminiscent of one of the theories related to the origin of life, which is based on the fact that the molecules that gave rise to life were formed through a spontaneous desymmetrization of symmetry. “One of the widely accepted theories on the origin of life says that originally only symmetrical molecules existed and that through a process of spontaneous desymmetrization asymmetrical molecules emerged, which are evidently the origin of life, because our entire organism and living systems They are based on asymmetric biomolecules that contain only one of the two enantiomers”, concludes Reyes.
This research was conducted as part of Josebe Hurtado’s doctoral thesis and in collaboration with the research group led by Rovira i Virgili University professor Elena Fernández.
The study is titled “Cu-catalyzed enantioselective borylative desymmetrization of 1-vinylcyclobutanols and axial-to-point chirality transfer in a diastereoconvergent/stereoretentive allylation scenario.” Y se published in the academic journal Angewandte Chemie. (Source: UPV/EHU)
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Interview: Time.news Editor Meets Expert in Molecular Asymmetry
Editor: Welcome, Professor José Luis Vicario, and congratulations on your groundbreaking work in molecular asymmetry! It’s a pleasure to have you here.
Professor Vicario: Thank you! It’s a pleasure to be here and share our findings.
Editor: Your research group at the University of the Basque Country has developed a new methodology for synthesizing molecules with a special type of molecular asymmetry. Can you explain what you mean by “molecular asymmetry” and why it matters?
Professor Vicario: Absolutely. Molecular asymmetry refers to the arrangement of atoms within a molecule where the mirror image – known as an enantiomer – is not superimposable on the original. This asymmetry is crucial because even slight differences between enantiomers can lead to significantly different biological properties. For example, one enantiomer can be therapeutic while its mirror image may be harmful.
Editor: That analogy of the hands you provided is quite effective. Can you elaborate on the implications of this for drug development?
Professor Vicario: Certainly! In pharmacology, the different properties of enantiomers can be profound. Take the drug thalidomide, for instance. One enantiomer is effective as a sedative, while the other caused serious birth defects. Therefore, being able to selectively synthesize a specific enantiomer can lead to safer and more effective therapeutic agents.
Editor: Your team used a copper-derived catalyst for this synthesis. How does this choice of catalyst impact the methodology and its practicality?
Professor Vicario: Copper is abundant and non-harmful, making it an excellent choice. Our method is not only effective but also straightforward, allowing us to use small quantities of the catalyst. This approach reduces costs and enhances the feasibility of scaling the process for potential industrial applications.
Editor: You mentioned “axial asymmetry” in your research. Can you explain what this entails and how it differs from previous methodologies?
Professor Vicario: Axial asymmetry refers to the specific orientation of atoms around an axis within the molecule. This is unprecedented in nature and allows us to explore new types of molecules that could have unique properties. Unlike traditional methods, our approach actively breaks the planar symmetry, which paves the way for creating complex organic structures that could lead to novel therapies.
Editor: What challenges did your team face while breaking the molecular symmetry, and how did you overcome them?
Professor Vicario: One major challenge is controlling the reaction conditions to ensure selective production of one enantiomer over the other. We invested a lot of time optimizing our reaction parameters and exploring different conditions to achieve this selectivity. Collaboration among the members of our group has been key to overcoming these hurdles.
Editor: What are the next steps for your research group? Do you foresee any immediate applications of these new asymmetrical molecules?
Professor Vicario: Yes, we are just scratching the surface. The research will continue to focus on characterizing these new asymmetric molecules and exploring their potential therapeutic applications. We hope to collaborate with pharmacologists to test these compounds and see how they interact in biological systems.
Editor: That sounds incredibly exciting! As this field evolves, what message do you have for young researchers interested in molecular chemistry?
Professor Vicario: I encourage them to keep an open mind and not shy away from challenges. Science requires creativity and perseverance. There’s so much potential in exploring the unknown, and it’s in these uncharted territories where groundbreaking discoveries often lie.
Editor: Thank you for your insights, Professor Vicario. It’s clear that your research holds significant promise for the future of medicine!
Professor Vicario: Thank you for having me! I’m excited about the future and the potential impact our findings could have.