Nobel Prize for Unprecedented Way to Create Molecules That Make Chemistry Green

Benjamin List and David Macmillan, from Germany and the US respectively, will share the 10 million Swedish kronor (£870,000) Nobel Prize in Chemistry 2021 for the development of “organocatalysis” – a precision tool for manufacturing molecules that fueled pharmaceutical research and made chemicals greener and cheaper.

His research dates back to 2000, when chemists independently developed the first step called “asymmetric organocatalysis”, which is the activation of chemical reactions by small organic molecules.

Many technologies and fields of research rely on molecules that have to be made into chemical reactions. Unfortunately, these can be very slow, which is why chemists often use catalysts – materials that speed up chemical reactions. Prior to the work of List and Macmillan, only two types of catalysts were available: metals or enzymes. In my opinion, the most important achievement of the two was discovering something that no one thought was possible: that even small organic molecules like amino acids can serve as catalysts.

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This discovery enabled the pair to create “asymmetric reactions.” In chemical reactions, many molecules are produced in two versions that are mirror images of each other (a property known as chirality). It’s annoying when you only want one of them, which is often the case in the pharmaceutical industry.

In fact, that’s exactly what went wrong with the drug thalidomide, which was developed in the 1960s to reduce morning sickness in pregnant women but caused fetal malformations. The drug was a similar mixture of both types of molecules, but it was discovered that while one was effective, its mirror image counterpart was toxic. The beauty of organocatalysis is that you can produce a specific molecule without its mirror cousin.

The possibility of avoiding the use of metals as catalysts in chemical reactions has also made it easier for pharmaceutical companies to purify the compounds. It is an important final step in the manufacture of pharmaceuticals, and involves the removal of hazardous chemicals, including some metal catalysts.

Another major improvement of organocatalysis compared to other types of catalysis is that it is easy to do: You can do it at room temperature under ordinary conditions. It is also easier to reliably predict and control outcomes than other types of catalysis.

In addition, metal catalysts such as palladium or rhodium can be expensive. An extremely beautiful example of a cheap alternative is proline, a simple amino acid often used as an organocatalyst, which is so efficient that it has completely replaced some expensive and complex metal catalysts.

Organocatalysis is not only a cheaper alternative, it is also more environmentally friendly, typically containing common and abundant elements such as oxygen, nitrogen, sulfur or phosphorus instead of iridium or palladium.

List and Macmillan soon became the leaders of this pioneering new chemistry, developing more and more reactions and catalysts, and imagining new ways to expand the field. One of the most important aspects of this work was how easily it changed the perspective of so many organic chemists who turned their attention to organocatalysis and embraced it. This meant that chemists in many different areas of research were able to synthesize complex molecules, allowing the field to develop rapidly.

I had the incredible honor of working with List at the beginning of this new field (2004–06) at the Max-Planck-Institut für Kohlenforschung in Mülheim, Germany, while I was a post-doctoral researcher. I saw with my own eyes how this field became very popular among chemists around the world. I also saw how List had a vision that set him apart from other chemists: he truly believed in his work and he pushed the limits of catalysis – fundamentally changing it forever.

I can only honor List and Macmillan for their deserving award – they have inspired the careers of many chemists, including mine.