Stephan Walter
Chemistry can be a messy, sluggish business, frequently involving cocktails of chemicals in round-bottomed flasks that must later be painstakingly separated. But in 2001, K. Barry Sharpless and his colleagues that broke the聽mould. The snappy name, which was聽Sharpless鈥檚 wife聽Janet Dueser鈥檚 idea, summed it up well: a new set of reactions that worked quickly,聽cleanly聽and consistently.
If it seems like a simple idea, it is 鈥 and therein lies its brilliance. Sharpless and his colleagues Hartmuth C. Kolb and M. G. Finn described their new reactions as 鈥渟pring-loaded鈥. The idea was that you could apply them to a plethora of different starting chemicals, snapping them together almost like Lego bricks, and so quickly build a huge range of new and useful molecules 鈥 it was medicines that Sharpless mostly had in mind.
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The unifying thought behind these reactions was that they shied away from forming carbon-carbon bonds, as was the orthodoxy among chemists at the time, and instead formed bonds between carbon and what chemists call 鈥渉eteroatoms鈥,聽principally oxygen and nitrogen. The best-known click reaction snaps together two reactants to form a triazole, a ring of carbon and nitrogen atoms. This chemical motif tends to be聽 like proteins, making it useful in creating drug molecules. Sharpless unveiled this particular reaction independently, but at the same time as chemist at the University of Copenhagen, and it has since been used to make, among other things, the anticonvulsant drug .
This reaction, says chemist聽聽at the University of Oxford, was easy, highly specific and worked in almost any solvent. 鈥淚 think you can say this was just a great idea,鈥 he says.
A few years later, chemist 聽at Stanford University聽in California聽developed a click-style reaction that works without any toxic catalysts, meaning it could be used inside cells without disrupting them.
For chemist聽聽at聽the聽University聽of聽Edinburgh,聽UK,聽it was this work that elevated click chemistry from聽a good idea聽to聽a聽truly聽great聽one. It enabled biologists to peg together proteins and other bits of biological machinery at will, and to label them with fluorescent tags to investigate what happened. 鈥淚t鈥檚 just so simple and straightforward,鈥 says Hulme. 鈥淚t brought small molecule chemistry to biologists in a way that doesn鈥檛 require a chemistry degree.鈥
Bertozzi, Meldal and Sharpless shared the 2022 Nobel prize in chemistry for their work 鈥 to the surprise of no one.
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