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When it clicks: The 2022 Nobel Prize in Chemistry

Humans have an extensive history of copying mother nature’s creations, from inventions like velcro (inspired by burs) to needles (inspired by mosquitos). The advantage of natural systems is that they have had the time and patience to evolve in a direction that maximizes efficiency. 

But sometimes nature is too complex to mimic, like the various alkaloids found in plants traditionally used in folk medicine. Chemists spend years trying to synthesize compounds that nature seems to make effortlessly, but many have yet to be replicated. But in the instances where they have succeeded, we have ended up with some of the most useful remedies available to us today. The importance of studying the natural processes occurring around us can not be stressed enough; the discoveries made have the potential to change the world.

In October of this year, Barry Sharpless, Carolyn Bertozzi, and Morten Meldal received the Nobel Prize for their collective work in click chemistry. As described by Dr. Sharpless in 2001, click chemistry is a term used to define reactions that seemingly snap together like a sort of molecular seatbelt. Dr. Sharpless drew inspiration from the aqueous chemistry of nature and sought to mimic the speed and single-product outcome of these reactions. 

With this goal in mind, he decided to recreate these reactions using highly reactive molecules he described as “spring-loaded”. The first of these molecules was azides, which are known to be rich in energy and highly reactive, much like a spring. 

Sharpless and Meldal discovered independently that these azides could react with copper catalysts to lock molecules together. The reactions were both high-yield and incredibly fast, making them a valuable tool for chemists everywhere.

Inspired by their work, Dr. Bertozzi questioned how this new science could be used to invent reactions that can occur in biological settings as complex as the human body. Her contribution was bioorthogonal reactions, which emphasize the importance of finding molecules that can ‘click’ with the right partners in a biological system.

This proved to be a complex task because elaborate reactions constantly occur within biological settings and choosing the right elements to come together in this sea of complex materials is difficult. 

Furthermore, the copper catalysts in the previous model could cause damage to cells. To remedy this, Bertozzi came up with the idea of using strained alkynes. As the name implies, these molecules are under a lot of stress, or ring strain, making them highly reactive and seemingly ready to pop. Eventually, her team came across cyclooctyne, which can conduct click chemistry without a copper catalyst due to the immense strain on its rings. Much like a student rushing out of their last class before Thanksgiving break, when this tremendous stress is released, the reaction takes place very quickly. 

The possible uses for click chemistry are seemingly endless. Advancements in this field could mean anything from imaging probes in biological molecules that could help us spot cancers to the manufacturing of new medicinal molecules.

~ Victoria Melehov `25

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