Click here! Explaining the science that won the Nobel Prize in Chemistry

Click chemistry and bioorthoganal chemistry have won this year’s Nobel Prize in Chemistry…but what are they?

The Nobel Prize has been awarded to three researchers – Carolyn Bertozzi, Morten Meldal, and Barry Sharpless. Between them and their groups, the researchers developed an elegant series of reactions that get used everywhere in chemical manufacture, and have been particularly helpful in making pharmaceuticals, mapping DNA and developing cancer treatments.

So what, exactly, did they do?

A resumé of reactions

Assembling new molecules, sometimes atom by atom, is the driver behind a lot of chemistry. It’s at the heart of all pharmaceutical development, and also crucial to materials science, recycling, and agricultural chemistry – among other things.

Over the past century, chemists have developed tens of thousands of different reactions to make these substances.

At this stage, it’s possible to make just about any molecule you can imagine – but you might need, for instance, six years, diamond anvils, and some very strong lasers.

If you’re trying to make a lot of something, you need to be able to do it cheaply, precisely, and with as few toxic ingredients as possible.

This is where US chemist Karl Barry Sharpless comes in. During the 1990s and early 2000s, he and his research group refined a list of chemical reactions around a series of requirements, including:

• They be applicable to a wide range of reactants
• They operate under simple reaction conditions – no ridiculous temperatures or pressures
• They should require inoffensive solvents and generate inoffensive by-products
• They should be efficient, with high yields of the thing you want to make

They summarised these reactions in a 2001 paper as ‘Click chemistry’. These reactions have become simple, effective tools for every chemist’s arsenal.

Sharpless, who had already won the 2001 Nobel Prize in Chemistry for other work, becomes the fifth person ever to win two Nobel Prizes, and the second to win two Chemistry prizes.

Copper catalyst kills at click chemistry

Among Sharpless et al.’s clicks, there was one reaction that carried particularly high potential: a reaction called 1,3-dipolar cycloaddition.

This reaction was fast and efficient, but at the advent of click chemistry, it lacked precision and often needed strict requirements to work.

The next leap was made by Sharpless and Danish chemist Morten Meldal independently.

Both researchers’ groups developed a copper catalyst that, like a pair of hands fastening a seatbelt, joins the two reagents together neatly and effectively. It works in a few hours, in a variety of environments, at room temperature.

The potential of the copper catalyst was so exciting, that manufacturers quickly started stocking up on reagents that they knew would be useful for it. It’s become a tremendously common reaction in chemistry.

First celebration! @ChemKUniversity @UCPH_Research @NobelPrize pic.twitter.com/pQAytyP3U2

— Jiwoong Lee (@TheLeeLab_Chem) October 5, 2022

Becoming bioorthoganal

The copper click catalyst is very good at its job, but it doesn’t work in every environment.

Biological applications were particularly limited, because the copper ions are too toxic to cells.

But US chemist Carolyn R. Bertozzi, along with her research group, found an alternative to copper. They realised that a class of large, carbon-based molecules, called cycloalkynes, could take the place of copper.

This adapted reaction could then work in lab-based human cells.

This discovery led to Bertozzi’s development of ‘bioorthoganal’ chemistry, or reactions that happen on the surface of a cell without disrupting the cell’s behaviour. The reactions have even been shown to work in living mice.

Bioorthoganal chemistry has now become a valuable tool for studying cells of all types. It’s also been critical to the development of several different cancer pharmaceuticals which are currently in clinical trials.

Bertozzi is the eighth woman to win the Nobel Prize in Chemistry, and among the first openly LGBT Nobel laureates in science.