You have before the year 2000, and after 2000. In that key year, two chemists, independently of each other, carried out a series of reactions in their laboratory that would very quickly make a then still limited chemical subdiscipline very large. The production of pharmaceuticals in particular has greatly improved since then and has become more efficient.
The two chemists, Benjamin List and David MacMillan, got Wednesday the Nobel Prize in Chemistry, ‘for the development of asymmetric organocatalysis’. Small organic molecules (which are made up of atoms that are important in living organisms, such as carbon, hydrogen and nitrogen) are used as a catalyst. A catalyst is a molecule that speeds up a chemical reaction without itself being changed or consumed. Catalysis was already a large field in 2000 – it has already been awarded a Nobel Prize in Chemistry seven times before this year. It accompanying background document at the price mentions that 35 percent of the world’s GDP comes from catalysis.
List and MacMillan have translated the working principle of enzymes into small molecules
Paul Alsters chemist
But until the year 2000, the acceleration of chemical reactions was mainly done with metals or enzymes. That it could also be done with organic molecules had already been demonstrated several times in the past century – for the first time in 1912. “But List and MacMillan have brought this option back on the table, and it has moved quickly after that,” says Bert Weckhuysen, professor inorganic chemistry and catalysis at Utrecht University. This is confirmed by Paul Alsters, chemist at Innosyn in Geleen, a spin-off of DSM. “List and MacMillan have translated the working principle of enzymes into small molecules that are cheap and easy to produce. That worked pretty well.”
Weckhuysen calls the fact that List and MacMillan both carried out their groundbreaking experiments in 2000 – and that they are both the same age – coincidence. “It might as well have happened in 1998 or 2003.”
An advantage of using organic molecules is that they have a specific shape. Organic molecules can come in two forms. Written out as a formula, they are exactly the same, but in 3D they are mirror images of each other – often represented as the left and right hands that, when placed on top of each other, do not overlap. In living organisms usually only one of the two forms is present as an active molecule.
This is especially important for the production of medicines. This production often creates both mirror images, but only one is effective. That makes production inefficient. And sometimes even harmful, as was shown in the 1960s with thalidomide (brand name Softenon), a drug taken by pregnant women for nausea. The molecule was administered in both forms, and one of them was found to be harmful to the unborn child – babies were born with severe limb abnormalities.
Not for bulk chemicals
In their experiments List and MacMillan used one particular shape of an organic molecule as a catalyst, and showed that it transfers its specific shape to the end product, as it were. So only one of the two mirror images is created. After their publications, the sub-discipline quickly flourished, becoming the ‘third pillar’ of catalysis. The technology certainly offers advantages for the pharmaceutical industry, says Alsters. It is used, among other things, in the production of the antiviral drug Tamiflu, of the drug Renin against high blood pressure, and of vitamin E. Alsters: “But it is less suitable for bulk chemistry because it produces by-products that are not so easy to get rid of. ”
Bert Meijer, professor of organic chemistry at Eindhoven University of Technology, says he is “very surprised” by the choice of the Nobel Committee. “I expected that the price would go to mRNA and the production of corona vaccines.” Moreover, he says, the name of the Dutchman Hans Wijnberg would not have been out of place next to List and MacMillan. Wijnberg is regarded as one of the founders of asymmetric organocatalysis – he died in 2011. He was a professor in Groningen for a long time, where he supervised PhD student Ben Feringa, who was awarded a Nobel Prize in 2016.
MacMillan could not be reached immediately after the announcement. “I started getting text messages from people from Sweden very early on, but I thought they were kidding me and went back to sleep. Then my phone went on tilt,” he said later in the day. List was reached by telephone shortly after the announcement. He was in Amsterdam, near the Concertgebouw.
With the scientific honor of the prize also comes a cash prize of ten million Swedish kronor (about 955,000 euros), which List and MacMillan have to divide.