Chemistry can often be a complex and slow process, typically involving intricate mixtures in round-bottomed flasks that require meticulous separation afterward. However, in 2001, K. Barry Sharpless and his team introduced a transformative concept known as click chemistry. This innovative approach revolutionizes the field, with a name coined by Sharpless’s wife, Janet Dueser, perfectly encapsulating its essence: a new set of rapid, clean, and reliable reactions.
Though the idea appears straightforward, its elegance lies in its simplicity. Sharpless, along with colleagues Hartmas C. Kolb and MG Finn, described their creation as “spring-loaded.” This concept hinges on applying these reactions to various starting materials, assembling them akin to Lego blocks, thereby enabling the swift construction of a vast array of novel and beneficial molecules. Sharpless’s primary focus? Pharmaceuticals.
The overarching principle guiding these reactions was to steer clear of forming carbon-carbon bonds, which was the norm among chemists at the time, and instead to create bonds between carbon and what are known as “heteroatoms,” primarily oxygen and nitrogen. The most recognized click reaction involves the fusion of two reactants to create a triazole, a cyclic structure of carbon and nitrogen atoms. This motif proves to be highly effective at binding to large biomolecules such as proteins, making it invaluable in drug development. Sharpless independently published this specific reaction concurrently with chemist Morten Meldal, who researched it at the University of Copenhagen. This reaction has since been instrumental, notably in the production of the anticonvulsant drug Rufinamide.
Chemists like Tom Brown from the University of Oxford describe this reaction as simple, highly specific, and versatile enough to work in almost any solvent. “I would say this was just a great idea,” he asserts.
Years later, chemist Carolyn Bertozzi and her team at Stanford University developed a click-type reaction that operates without toxic catalysts, enabling its application within living cells without risking cellular damage.
For chemist Alison Hulme at the University of Edinburgh, this research was pivotal in elevating click chemistry from a promising idea to a revolutionary advancement. It granted biologists the ability to assemble proteins and other biological components while labeling them with fluorescent tags for investigation. “It’s very straightforward and user-friendly,” Hulme explains. “We bridged small molecule chemistry to biologists without necessitating a chemistry degree.”
For their groundbreaking contributions, Bertozzi, Meldal, and Sharpless were awarded the 2022 Nobel Prize in Chemistry—an outcome that surprised no one.
Topics:
Source: www.newscientist.com
