Two decades after discovering a new way to build molecules, David MacMillan and Benjamin List win the Nobel Prize – Endpoints News

Catalysts play a vital role in drug development, causing complex sequences of chemical reactions to break down molecules or join them. But until twenty years ago, only two types of catalysts were known to scientists: metals and enzymes.

Metal catalysts are easily destroyed by moisture, so while deploying them in a lab is fairly straightforward, large-scale manufacturing becomes a challenge. Enzymes, on the other hand, are made up of hundreds of amino acids, although quite frequently only a few of them are actually involved in a chemical reaction.

In the 1990s, two researchers in separate corners of California came to the same conclusion: There must be an easier way. Their work led to the discovery of a third catalysis that relies on small organic molecules – called asymmetric organocatalysis – that promises to make molecular construction faster, more efficient and “greener”.

Today, more than 20 years later, it has won them a Nobel Prize.

This year’s Nobel Prize in Chemistry was awarded to Benjamin List, director of the Max-Planck-Institut für Kohlenforschung, and David MacMillan, professor at Princeton University, for the development of asymmetric organocatalysis. MacMillan hardly believed in the victory at first, convinced it was an elaborate prank by his students, according to a Twitter post from Princeton. Scientists will share a prize of SEK 10 million, or roughly $ 1.35 million.

HN Cheng, President of the American Chemical Society, said Terminal news that the discovery amounts to giving chemists a “new magic wand”.

HN Cheng

Enzymes are specialists in what is called asymmetric catalysis. In the course of chemical construction, a situation often arises where two molecules are formed, which are mirror images of each other. When making drugs, chemists often want only one of these mirror images, and enzymes almost always form only one in two. However, they tend to be slower and more expensive to manufacture than organocatalysts from List and MacMillan, Cheng said.

In Carlos Barbas III’s lab at the Scripps Research Institute in Southern California, List wondered if a single amino acid – as opposed to hundreds – or other simple molecules could do the same job as an enzyme. . He tested the hypothesis with an amino acid called proline, which had already been used as a catalyst in the early 1970s, and found that the molecule was a “dream tool”.

Meanwhile, at UC Berkeley, List abandoned his work on improving asymmetric catalysis using metals and was working on designing simple organic molecules to do the trick instead. He selected several organic molecules with the right properties, then tested their ability to conduct a Diels-Alder reaction, which chemists use to build rings of carbon atoms. The rest is history.

MacMillan published his work just before List in 2000, coining the term organocatalysis. It’s a process that’s been shown to not only be faster – by speeding up the synthesis of a complicated toxin called strychnine by 7,000 times – but also long-lasting, Cheng noted.

“Organocatalysts tend to be smaller molecules, and they’re relatively less toxic, and they can be used under mild conditions in most cases,” he said. “So these reactions are greener.”

A group of eminent scientists took to Twitter to congratulate List and MacMillan, including top White House geneticist and science adviser Eric Lander: and making drugs more efficiently, ”he wrote.

Others in the industry, however, have expressed disappointment that mRNA pioneer Katalin Kariko – the Hungarian biochemist whose research has contributed to the rapid development of Covid-19 vaccines – did not win a Nobel Prize. Only seven women in history have won the Nobel Prize in chemistry, out of a total of 188 recipients.


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