The saying that ‘nature is wise’ is fulfilled in the scientific discovery awarded this year with the Nobel Prize in Chemistry. Because award-winning Barry Sharpless y Morten Meldal they laid the foundations of the so-called ‘click chemistry’, which, explained in a very simple way’, allows simple molecular blocks to be ‘glued’ to create more complex ones. A basic technique for creating materials with desired properties (such as conducting electricity or having antibacterial properties) and for laboratory research. Share the prize with Carolyn Bertozziwho took the technique to a new level: he began using it on living cells to map them, although his discoveries have gone further and his team has created a drug that could prevent the spread of cancer.
In general, molecules have a structure of bonded carbon atoms. Nature has developed methods to create them, but it has been much more complex for chemists. The reason is that the carbon atoms of different molecules often lack a chemical drive to form bonds with each other, so they must be activated artificially. Give them a ‘push’. This momentum often creates unwanted side reactions, creating ‘leftover’ material that must be removed before the next step, often leading to costly material loss.
Instead of trying to get reluctant carbon atoms to react with each other, Barry Sharpless devised an alternative way: imitating nature, use smaller molecules that already had a complete carbon structure, and then link them together by bridging nitrogen atoms. or oxygen atoms, easier to control. “It’s a Lego molecular -explained at the award announcement press conference Olof Ramström, Professor of Chemistry and member of the Committee- The great thing is that this discovery can be used for almost anything, from drugs, polymers, gels… You can even build complicated structures that transport drugs to the human body. You can do almost anything », he stressed.
Sharples dubbed this method ‘click chemistry’ because, just like in building games, you can easily fit small blocks together to create more complex elements. In his study, published in 2001 – the same year in which, precisely, he received his first Nobel Prize in Chemistry – he listed several criteria that must be met for a chemical reaction to be within this method and to be stable. In addition, the reaction should not use solvents or, if it does, use a benign or easily removable one (preferably water). This was only the beginning.
an unexpected discovery
The next step was in the hands of the Danish chemist Morten Meldalthough he didn’t know it. In his laboratory at the University of Copenhagen he was developing methods to find potential pharmaceutical substances when, performing a routine reaction of an alkyne with an acyl halide, he found something unexpected. It turned out that the alkyne had reacted with the wrong end of the acyl halide molecule. At the opposite extreme was a chemical group called they hate it. Together with the alkyne, the azide created a ring-shaped structure, a triazole.
Triazoles are very useful chemical structures, as they are very stable. In fact, they are found in many pharmaceuticals, dyes, or agricultural products. Due to their reliability, they are products that chemists tried to create in their laboratories; however, until the advent of click chemistry this process created many unwanted by-products. Meldal realized that the copper ions had controlled the reaction so that initially only one substance was formed. Even the acyl halide, which really should have been attached to the alkyne, remained more or less intact in the container. Therefore, it was obvious to Meldal that the reaction between the azide and the alkyne was something exceptional. Although he had much of the technique described by Sharpless, he did not relate to it until later.
Independently, Sharpless also published an article on the copper-catalyzed reaction between azides and alkynes, which shows that the reaction works in water and is reliable. He described it as an ‘ideal’ click reaction, “the jewel in the crown”, as explained by the Academy. The azide is like a loaded spring, where the force is released by the copper ion, in a safe process with “enormous potential”, as described by Sharpless. That reaction would be like a ‘glue’ to join different molecules: if chemists want to join two different molecules, they can now, with relative ease, introduce an azide into one molecule and an alkyne into the other, then joining them with the help of some ions. coppermade.
Applications also in living cells
This technique was a revolution that allowed not only to use it in research and new drugs, but also to create materials with specific properties, such as being conductors of electricity, being antibacterial or protecting against ultraviolet radiation. However, there was something that Sharpless did not predict: this technique could also be used in living beings. She was the third awardee, Carolyn Bertozziwho discovered this app.
With great ingenuity, he modified a known reaction, the Staudinger’s reactionand used it to attach a fluorescent molecule to the azide that he introduced into the glycans cells – polysaccharides found naturally in the structure of cells. Because azide does not affect cells, it can even be introduced into living things (thanks to what are known as ‘bioorthogonal reactions‘), so he used his invention to map cells.
Later, he refined his technique: as copper is toxic to living beings, he found a method to eliminate this substance from the equation (thanks to the azide-alkyne cycloaddition reaction promoted by ring strain), which has given a huge boost to exploring how these reactions interact with biomolecules in cells and to studying disease processes. In fact, Bertozzi has created a biological drug to prevent cancerous tumors they expand. This treatment is currently being tested in human clinical trials.
«This year’s Chemistry Prize tries not to complicate things too much, but to work with what is easy and simple. Functional molecules can be built even by following a direct route,” he noted. Johan Åqvistchairman of the Nobel Committee for Chemistry. A direct route that is still on its way.