Current affairs

Put your hands together for the Nobel Prize in Chemistry 2021

How fundamental research can lead to new opportunities in innovation

This year the Nobel Prize in Chemistry goes to Benjamin List and David MacMillan for ‘the development of asymmetric organocatalysis’. This is a fine example of a fundamental scientific discovery that has quickly found a practical application. It concerns chemical ‘equipment’ that helps to build better and useful molecules. Inventions are then naturally lying in the offing.

We find ourselves in the specialization of organic chemical synthesis. Simply put, this means putting together new molecules that consist of skeletons and/or rings. These molecules are primarily made based on carbon and hydrogen. A limited number of other elements — such as oxygen, nitrogen, fluorine, chlorine and sulfur — are also part of this. Organic chemical molecules can be found all around us, such as in coatings, cosmetics, and coloring agents. Many new, often complex, organic chemical molecules are continuously being developed for medicines. But organic molecules are also constructed for applications in modern electronics. Just think of the organic luminous diodes used in monitors or organic memory storage in smart cards.

Synthesis is creating

The synthesis of organic molecules is a creative profession. You have to devise a smart sequence of chemical reaction steps (often five to ten or more). This allows you to create parts of a molecule, join them together, and tweak the side groups. Various chemical tools, such as reagents, solvents and — very important — catalysts, are used to do this. Catalysts are substances that are not molecule building blocks in and of themselves, but they do accelerate a reaction step and/or influence how the components are joined.

Molecules in mirror image

In many complex organic molecules there is at least one chiral carbon atom that is asymmetric — there is another atom or another series of atoms on all four sides. Due to the presence of an asymmetric carbon atom, these molecules have two shapes. Both have exactly the same components and in exactly the same relative sequence, but one variant is the mirror image of the other. This can best be compared with the difference between the left and right hands. Both normally have the same palm and, in the same relative sequence, the same fingers. The left hand and the right hand do not fit over each other but they do fit against each other, in mirror image. In chemistry, this is termed chirality, after the Ancient Greek word for hand (χείρ). A famous example of this is the mirror images (enantiomers) of lactic acid in “levorotatory (L)” or “dextrorotatory (D)” yogurt.


Creating the correct variant can be essential, especially with medicines. Usually one enantiomer has the desired healing properties and the other does not. Or the other shape specifically provides the side effects. An infamous example of this is the sedative Thalidomide, which was prescribed for pregnant women in the 1960s. Children of these women were born with stunted extremities. This would not have happened if the sedative consisted only of the ‘good’ enantiomer.

Organic molecules accelerate reactions

Partly due to these types of incidents, people increasingly proceeded to separate the enantiomers or to synthesize selectively. This is usually a difficult process. With selective synthesis, chemists already recognized that catalysts could influence which enantiomer is formed. In 2001, the Nobel Prize in Chemistry was awarded for work on chiral catalyzed reactions.


Traditionally, there were two large groups of catalysts in organic synthesis: inorganic (based on metals) and biochemical (involves enzymes). From the point of view of sustainable chemistry, it is better to avoid metals. Enzymes are more suitable in this respect, but they are very complex molecules that are often difficult to isolate or to produce.

With selective synthesis, chemists already recognized that catalysts could influence which enantiomer is formed.

At the turn of the current century, List and MacMillan independently found a solution to this problem. They discovered that simple organic molecules that have a suitable form of nitrogen in a useful location could also accelerate certain chemical reactions. This opened up the new field of organocatalysis, which has since become very popular.


Various things aligned in organocatalysis. Because the catalyst itself is an organic chemical molecule, variants of it could be created more easily than could be done with traditional catalysts. Therefore, many more possibilities for asymmetric catalysis arose. This made it possible to synthesize the correct enantiomers from many more different molecules. Without metals, it also became much more possible to conduct the chemistry of asymmetric catalysis as green, sustainable chemistry.

Benjamin List and David W.C. MacMillan

Candy store for chemists

For synthetic chemists, organocatalysis is a candy store for creating new molecules. Because of the specialization, new catalysts have been developed and new substances have been created, such as medicines. These types of innovations have ensured that this 21st-century specialization also has a place in patent law. Here, it’s not only about the catalysts and the medicines. Often, even the chemical synthesis itself is a new and inventive process. 


That Nobel Prize winners List and MacMillan discovered the asymmetric organocatalysts doesn’t mean that the creation of a pure enantiomer with an organic catalyst can no longer be an invention. On the contrary: Certainly in an ‘unpredictable art’ such as chemistry, predicting how pure enantiomers can be obtained in the case of a complicated molecule containing chirality cannot be done. For good synthetic chemists, there are still many more useful inventions to be garnered/harvested. 

If you have any questions about this subject, please contact Hajo Kraak.

Share