In Nobel-winning chemistry, simplicity is key

Prof. Morten Meldal has won the 2022 Nobel Prize in Chemistry. He shares this award with American scientists Carolyn R. Bertozzi and K. Barry Sharpless “for the development of click chemistry and bioorthogonal chemistry.” The prize of SEK 10 million (EUR 900 000) will be shared equally between the Nobel laureates.

As professor of chemistry at the University of Copenhagen, he was also a Marie Skłodowska-Curie Actions coordinator on the EU-funded ORGANOZYMES (Nanocatalytic drugs towards Alzheimer’s disease) project that increased our understanding of how catalytic molecules can be used to treat Alzheimer’s disease. The chemist received the Nobel in recognition of his important role in propelling chemistry into the era of functionalism and laying the foundations of click chemistry.

However, what is click chemistry and why is it so important? Chemists have often looked to nature – and the amazing molecular structures of plants and animals – for inspiration. To create different drugs, they have tried to construct the same molecules artificially, gradually developing such sophisticated tools that they can now create the most astonishing molecules in their labs. Nevertheless, many steps are needed to build complex molecules, with unwanted by-products being formed in the process. Removing these by-products is time consuming and often results in substantial material being lost.Then, around the year 2000, Dr Sharpless invented the concept of click chemistry “which is a form of simple and reliable chemistry,” according to a press release posted on the Nobel Prize website. Molecular building blocks snap together quickly and efficiently, rapidly causing reactions to occur and preventing the creation of unwanted by-products.

Not long after, Drs Meldal and Sharpless – working independently – discovered “the crown jewel of click chemistry.” This was the copper catalysed azide-alkyne cycloaddition. The press release states: “This is an elegant and efficient chemical reaction that is now in widespread use. Among many other uses, it is utilised in the development of pharmaceuticals, for mapping DNA and creating materials that are more fit for purpose.”

Then, Dr Bertozzi developed click reactions that can be used inside living organisms without disturbing the cell’s biochemical processes. Her bioorthogonal reactions are now used worldwide to study cell functions. Researchers are exploring ways to use these reactions to treat cancer.

“This year’s Prize in Chemistry deals with not overcomplicating matters, instead working with what is easy and simple,” remarks Nobel Committee for Chemistry Chair Johan Åqvist in the same press release. “Functional molecules can be built even by taking a straightforward route.”

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ORGANOZYMES project