A synthetic click: On 2022 Chemistry Nobel

The chemistry awards show that it pays to rethink the fundamentals

October 08, 2022 12:15 am | Updated 12:05 pm IST

The Nobel Prize for Chemistry has been awarded to Carolyn Bertozzi, Morten Meldal and Barry Sharpless, the last of whom features in a group of only five to have won the Prize twice. The three chemists have been awarded for pioneering ‘click chemistry’ or getting molecules that wouldn’t normally bond together to do so in an efficient and uncomplicated manner. The ‘click’ comes from an analogy Sharpless drew of molecules snapping together, like airline seatbelts fitting into their buckles. Historically, chemistry has sought to imitate nature. From medicine to fertilizer, the chemist has sought to make synthetic products that mimic natural molecules. The artificial synthesis of indigo, instead of extraction from plants, had disastrous consequences for colonial India’s economy. On the other hand, several molecules have been synthesised in ingenious ways to create drugs and medicines to kill bacteria and relieve pain. The flip side is that these processes are likely laborious, can create unwanted by-products, many toxic. Often, the number of intermediary steps is so great and complicated that the desired result is usually too expensive to be useful.

Sharpless began the conversation, almost immediately after winning his first Nobel Prize, of creating molecular building blocks — like Lego blocks — that could snap together quickly and efficiently. The first breakthrough came when Meldal and Sharpless, independently of each other, discovered what has become the foundational stone of click chemistry, namely the copper catalysed azide-alkyne cycloaddition. Two kinds of chemicals — azides and alkynes — react very efficiently when copper ions are added, Meldal discovered in his Copenhagen laboratory, and form a very stable structure called a triazole. Previous attempts to join azides and alkynes were cumbersome, but the trick this time was copper. From then on, if chemists wanted to link two different molecules, all that was required was to introduce an azide in one molecule and an alkyne in the other. They then snapped the molecules together with the help of some copper ions. This has now become an industry standard. However, Bertozzi took click chemistry to a new dimension and showed that it could be used in living organisms. Copper is toxic to living cells, but she figured out a way to produce a copper-free click reaction, called the strain-promoted azide-alkyne cycloaddition, and showed it could be used to treat tumours. The awards demonstrate that it pays to rethink the fundamentals of a field and persevere at it for long enough to spark a revolution.

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