Do more chemistry functional
In pharmaceutical research, the production of complicated molecules can be an expensive and time-consuming process. Building molecules in a lab can take many steps, produce unnecessary byproducts, and waste valuable materials. Conventional methods may work on a small scale for clinical trials or trials, but become inefficient in large-scale production.
To solve this problem, Karl Barry Sharpless, an American chemist at Scripps Research, developed a minimalist form of chemistry in which molecular blocks can fit together quickly and efficiently: he called it “click chemistry.”
Sharpless, who also won the award in 2001 and is the fifth person to win twice, found that instead of forcing carbon atoms – the building blocks of organic matter – to bond together in the process of building molecules, it’s more easy to connect molecules with complete carbon structures. The central idea is to choose simple reactions between molecules that have a “stronger intrinsic drive” to bind together, resulting in a faster and less expensive process. While click chemistry cannot perfectly mimic naturally occurring molecules, it can still build modular molecules that serve the same purpose.
Around the same time, in the early 2000s, Danish chemist Morten Meldal and Sharpless developed a technique that is now the “crown jewel” of click chemistry: copper-catalyzed azidealkine cycloaddition. While studying new pharmaceutical materials, Meldal found that adding copper ions to a reaction between an alkyne and an acyl halide unexpectedly created a triazole, a stable ring-shaped chemical structure that is a common building block in pharmaceuticals, dyes and agricultural chemicals. The alkyne ended up reacting with the wrong end of the acyl halide molecule, creating a chemical group known as azide at the other end. Together, the alkyne and azide joined together to form a triazole.
Until then, researchers had not been able to produce triazoles without creating unwanted by-products. But Meldal found that adding copper ions helped control the reaction and create a single substance. Sharpless called it the “ideal” click reaction.
Now, when chemists want to combine two different molecules to create a new one, they just have to attach an azide molecule to one and an alkyne molecule to the other, which then join in the presence of copper ions. The applications of click chemistry go far beyond research labs – its industrial potential is immense. Click chemistry is already being used to produce new, purpose-built materials.
For example, adding a clickable azide to a plastic or fiber could allow manufacturers to “click” on substances that can conduct electricity or fight bacteria.
The chemistry of clicks can help fight cancer
While researching glycans, an elusive type of carbohydrate found on the surface of cells and critical to the immune system, Stanford University’s Carolyn Bertozzi, the eighth woman to win the award, found she didn’t have the right tools. to study them. Lei bertozzi wanted to attach fluorescent molecules to the glycans so that they could be easily detected. You have found a way to attach “chemical handles” to the glycans that the fluorescent molecules attach to. But she needed a “bioorthogonal reaction” in which the handle would not react with any other part of the cell. Bertozzi turned to the same azide used by Sharpless and Meldal to act as a handle. Not only does azide avoid interacting with other parts of the cell, it is also safe to introduce into living things.
As the importance of azides grew with the importance of click chemistry, Bertozzi realized that his bioorthogonal reaction had more potential. In 2004, he developed an alternative click chemical reaction that worked without toxic copper, making it safe for living cells.
Bertozzi’s work is already being used to identify glycans on the surface of cancer cells and block their protective mechanisms that can disable immune cells. This method is currently in clinical trials for people with advanced cancer. Researchers have also started developing “clickable antibodies” that can help track tumors and accurately deliver radiation doses to cancer cells.
