Simple idea that catalyzed revolutionary reactions

“Simple ideas are often the hardest to imagine,” the Nobel Prize committee said in honoring Benjamin List and David MacMillan with this year’s Nobel Prize in Chemistry.

The simple idea that List and MacMillan came up with, working independently, was to research new catalysts, the substances used to speed up chemical reactions, when most believed they were stuck with an existing, somewhat ineffective package.

The new catalysts, derived from natural chemicals, were more environmentally friendly and cheaper, and ensured that the end product of the chemical reaction was of a specific variety and did not need to go through a purification process to produce the type. of desired compound.

“The 2021 Nobel Prize-winning discovery in chemistry took molecular construction to a whole new level,” the Nobel committee said. “Its uses include research into new pharmaceuticals and it has also helped make chemistry greener. “


When two or more compounds react to form new compounds, the process is often aided by other chemicals that do not change but help speed up the reaction. These catalysts have been known at least since the mid-19th century and are now used in virtually all chemical processes.

Until around 2000, only two types of chemicals were known to act as effective catalysts: metals, mainly heavier metals; and enzymes, heavy molecules of natural origin that facilitate all the biochemical processes essential to life. These two sets of catalysts had limitations.

Heavier metals are expensive, difficult to extract, and toxic to humans and the environment. Despite the best processes, traces remained in the final product; this posed problems in situations where very high purity compounds were required, such as in the manufacture of medicaments. In addition, metals required an environment free of water and oxygen, which was difficult to guarantee on an industrial scale.

In contrast, enzymes work best when water is used as the medium for the chemical reaction. But it’s not an environment for all kinds of chemical reactions.


List and MacMillan, both 53, began experimenting with simple organic compounds. Organic compounds are mostly naturally occurring substances, built around a framework of carbon atoms and usually containing hydrogen, oxygen, nitrogen, sulfur or phosphorus. Chemicals essential to life like proteins, which are long chains of amino acids (carbon compounds containing nitrogen and oxygen) are organic. Enzymes are also proteins, and therefore organic compounds.

List and MacMillan were aware of earlier research from the 1970s in which an amino acid called proline was used as a catalyst in some specific reactions. But its role has not been fully explored. They started working with individual amino acids in enzymes – and found gold.

Asymmetric catalysis

The individual amino acids had an added advantage: they ensured that only one variety of the final product was produced in the reaction.

Substances can have exactly the same chemical composition and molecular formula; yet differ widely in their properties. They are known as isomers. One type of isomers are those which differ in how individual atoms are oriented in three-dimensional space. Two molecules could be exactly the same, except that they are mirror images of each other, like our hands. For the sake of simplicity, scientists often refer to these molecules as being left-handed or right-handed. This simple difference can sometimes have huge consequences, as it allows molecules to bind in different places when interacting with other molecules.

The end product of a chemical reaction is usually a mixture of left-handed and right-handed molecules. Normal chemical reactions performed in laboratories are not selective in this regard. But nature is. Because mirror images can have very different properties, natural processes are extremely selective and precise. They produce a left or right molecule.

List and MacMillan found that by using a naturally occurring compound like an amino acid as a catalyst, they only got a specific mirror image of the end product. This was later named asymmetric catalysis.

List and MacMillan came up with an absolute game changer. The field of organo-catalysts, a name MacMillan later used to describe these new sets of catalysts, has exploded over the past two decades. They’ve discovered a simple tool. and ingenious but its impact has been enormous, mainly in the pharmaceutical industry, but also in several other places, ”said Professor RG Bhat of the Indian Institute of Science Education and Research in Pune, who works with organo-catalysts itself.

Dr S Chandrashekhar, director of the Indian Institute of Chemical Technology based in Hyderabad, said the great importance of the work was that it made the processes much safer and more sustainable than before.

“I am also very happy to note that the Nobel committee selected this time a breakthrough in pure chemistry. In the past, the Nobel laureate in chemistry has often recognized work that essentially belonged to the field of biology, ”he said.

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