VU Experts Help Understand: Nobel Prize-Winning Click Chemistry Simplifies Research into Cells and Biological Processes

Sukurta: 07 October 2022

shutterstock 344487542On 5 October, Wednesday, this year's chemistry Nobel laureates were announced. The Royal Swedish Academy of Sciences awarded professors Morten Meldala from Denmark, Barry Sharpless from the USA and Carolyn R. Bertozzi from the USA for the development of click chemistry and bioorthogonal chemistry. The latter is the eighth woman to win the Nobel Prize in Chemistry. Dr. Viktoras Masevičius, Professor of Organic Chemistry at Vilnius University's (VU) Institute of Chemistry, comments on what makes this an exceptional part of chemistry and how it can serve science and society.

Effective tool for chemical research

"Prof. Sharpless, who has been awarded the second Nobel Prize in Chemistry, has created the concept of click chemistry. In short, it is an effective tool for combining two molecules with the desired functional fragments into one compound," says Prof. Dr. Masevičius.

According to him, the course of all chemical reactions depends very much on the structure of the molecules, and the reaction itself takes place between two functional groups. Relatively small changes in the molecular structure can drastically change the reactivity of the reacting functional groups. Therefore, it is so important that the structural elements that do not react with each other but are present in the molecule, have as little influence as possible on the reaction rates and conditions of the functional groups that react with each other. The click chemistry reaction catalysed by the azide-alkyne monovalent copper ion takes place selectively between the azide group and the terminal triple bond, forming a heterocyclic structure and thereby joining two molecules into one.

"Furthermore, both the azide group and the triple bond are not found in living nature. This is where bioorthogonality comes from: we have a system that reacts in the living environment, including at the cellular level, thanks to which we can perform a reaction and thus connect two molecules with the desired functional fragments, without affecting the living environment and the molecules existing in that environment. These reactions are used all over the world to study cells and biological processes," explains the VU chemist.

Also applicable to medicine

According to Prof. Dr. Masevičius, the spectrum of applicability of click chemistry is wide, covering both scientific and medical research. Also, these reactions can be used both in the extracellular space and inside the cell (cytosol).

"These reactions can also be used in medicine to facilitate the monitoring and research of tissues, especially cancerous ones. The application of bioorthogonal reactions allows scientists to study the processes taking place in the cell without directly affecting them", says Prof. Dr. Masevičius.

The interviewee summarises that chemical reactions between functional groups take place under very different conditions, even if we are talking about the same functional groups. In order to carry out the reaction, it is necessary to choose various reaction conditions, which is a time-consuming task. In the case of click chemistry, we have a cross-reactive and yield-efficient pair of functional groups the mutual reaction conditions of which are almost invariant with structural changes and can be bioorthogonally applied.

This reaction is also widely used by Vilnius University scientists in their work. Among them, Prof. Dr. Masevičius of the Faculty of Chemistry and Geosciences of VU, Prof. Dr. Edvinas Orentas and members of his research group, Prof. Saulius Klimašauskas and his group of researchers should be mentioned.