Nordic Life Science 1
he Royal Swedish Academy of Sciences decided to a
ward the Nobel Prize in Chemistry 2021 to Benjamin List and David MacMillan, for “the development of asymmetric organocatalysis.” Their discoveries and developmental work have indeed had a groundbreaking effect and greatly benefited humanity. Using asymmetric organocatalysis, researchers today can more efficiently produce molecules and they also have a greener alternative for molecule production. “This concept for catalysis is as simple as it is ingenious, and the fact is that many people have wondered why we didn’t think of it earlier,” said Johan Åqvist, Chair of the Nobel Committee for Chemistry, after the announcement. The discovery of asymmetric organocatalysis began in the late 1990s. In order to construct molecules that can form elastic and durable materials, store energy in batteries, or inhibit the progression of diseases, catalysts (substances that control and accelerate chemical reactions without being part of the final product) are required. It had long been believed that there were two types of catalysts; there were metals (metal catalysis) and there were enzymes (biocatalysis). Disadvantages with these include the risk of burdening the environment and health (metals) and large and complicated molecules to work with (enzymes). Independently of each other, David MacMillan, at the time working at the University of California, Berkeley, and Benjamin List, at the time working at the Scripps Research Institute, La Jolla, started to investigate if there could be a third type. Scanning electron micrograph of methicillin-resistant Staphylococcus aureus (MRSA) and a dead human neutrophil. David MacMillan had been working with metal catalysts, but they were rarely taken up by industry due to problems fulfilling the criteria for them to work in large scale, outside controlled lab conditions. So he then began designing simple organic molecules that could work the same way as the metals, but not be destroyed when exposed to, for example, moisture conditions. For one of his first experiments, MacMillan needed an organic molecule that could catalyze a reaction that formed an iminium ion. He tested organic molecules with the right properties to see if they had the ability needed, and it worked. He chose to call his discovered method organocatalysis, so that other researchers would understand that there were more organic catalysts out there to discover. Benjamin List was during the same period in time exploring catalytic antibodies. He and his colleagues were redesigning antibodies so that they could drive chemical reactions, but List started wondering if a single amino acid could also work as a catalyst. He had read an old research reference where scientists had used the amino acid proline as a catalyst and he decided to try it. He tested if proline could catalyze an aldol reaction, in which carbon atoms from two different molecules are bonded together. Just like MacMillan’s experiment, his experiment worked. List was able to show that proline is an efficient catalyst. Both MacMillan and List’s catalysts were small organic molecules, consisting of a stable framework of carbon atoms. Active chemical groups are attached to this carbon framework, and they often contain oxygen, nitrogen, sulphur or phosphorus. Benjamin List had also shown in his proline experiment that amino acids can drive what is termed asymmetric catalysis. When building molecules, two different molecules can often form that are each other’s mirror image (they have almost identical structure but differ in the spatial arrangement of their molecular parts, like the right and the left hand). NORDICLIFESCIENCE.ORG 45