Two decades after discovering a new way to construct molecules, David MacMillan and Benjamin List win Nobel Prize
Catalysts play a vital role in drug development, driving complex sequences of chemical reactions to break down molecules or join them together. But until just a couple of decades ago, only two types of catalysts were known to scientists: metals and enzymes.
Metal catalysts are easily destroyed by moisture, so while it’s simple enough to deploy them in a lab, large-scale manufacturing becomes a challenge. Enzymes, on the other hand, consist of hundreds of amino acids, though frequently enough, only a few of those 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 a simpler way. Their work led to the discovery of a third catalysis that builds upon small organic molecules — coined asymmetric organocatalysis — that promises to make molecular construction faster, more efficient, and “greener.”
Now, more than 20 years later, it won them a Nobel Prize.
This year’s Nobel Prize in Chemistry went to Benjamin List, director at the Max-Planck-Institut für Kohlenforschung, and David MacMillan, a Princeton University professor, for the development of asymmetric organocatalysis. MacMillan almost didn’t believe the win at first, convinced it was an elaborate prank pulled off by his students, according to a Twitter post by Princeton. The scientists will share a prize of 10 million Swedish kronor, or about $1.35 million.
Professor MacMillan starts the day with interviews, telling the story of being notified that he won the #NobelPrize – and not believing it!
— Princeton University (@Princeton) October 6, 2021
HN Cheng, president of the American Chemical Society, told Endpoints News that the discovery is like giving chemists a “new magic wand.”
Enzymes are specialists in something called asymmetric catalysis. During chemical construction, a situation often arises in which two molecules form, which are mirror images of each other. When making drugs, chemists often want just one of those mirror images, and enzymes almost always form just one out of the two. However, they tend to be slower, and are more expensive to make than List and MacMillan’s organocatalysts, 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 the molecule to be a “dream tool.”
Meanwhile, over 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 drive 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 proven not only to be faster – speeding up the synthesis of one complicated toxin called strychnine by 7,000 times — but also sustainable, Cheng noted.
“Organocatalysts tend to be smaller molecules, and they are relatively less toxic, and they can be run under mild conditions in most cases,” he said. “So these reactions are greener.”
A raft of prominent scientists took to Twitter to congratulate List and MacMillan, including top geneticist and White House scientific advisor Eric Lander: “It’s an outstanding example of how basic research can lead to new tools that drive the green revolution, create more efficient industries, and make drugs more efficiently,” he wrote.
Today’s #NobelPrize in Chemistry recognizes a brilliant idea for creating the “asymmetric” molecules needed to make medicines, build better batteries, and clean toxic emissions from cars. The trick: Add a tiny pinch of asymmetry (small organic molecules) as a catalyst. (1/6) https://t.co/Wu0JNf4z5b
— Eric Lander (@EricLander46) October 6, 2021
Others in the industry, though, expressed disappointment that mRNA pioneer Katalin Kariko — the Hungarian biochemist whose research contributed to the swift development of Covid-19 vaccines — didn’t take home a Nobel Prize. Only seven women in history have won the Nobel Prize in Chemistry, out of 188 total recipients.
Really disappointed, again, in the @NobelPrize committee. No women, no people of color, and as this thread captures so nicely, a dereliction of duty in public health to not give it for COVID vaccines *this* year. 😠 https://t.co/XQlJkkECha
— Dr. Nicole Paulk (Vaccines work) (@Nicole_Paulk) October 6, 2021