Explained: The discovery that led to organocatalysis gold rush

Catalysis is a term used to describe a process in the presence of a substance (the catalyst) controls and influences the rate and/or the outcome of the reaction. The substance — the catalyst — which helps in achieving this remains intact is not consumed during the reaction and neither becomes a part of the final product.

Catalysis is a term used to describe a process in the presence of a substance (the catalyst) controls and influences the rate and/or the outcome of the reaction. The substance — the catalyst — which helps in achieving this remains intact is not consumed during the reaction and neither becomes a part of the final product. The catalyst is subsequently removed if it is not to constitute impurity in the final product.

What is catalysis?

Catalysis is Catalysis is a term used to describe a process in the presence of a substance (the catalyst) controls and influences the rate and/or the outcome of the reaction. The substance — the catalyst — which helps in achieving this remains intact is not consumed during the reaction and neither becomes a part of the final product. The catalyst is subsequently removed if it is not to constitute impurity in the final product.

Catalysis is a term used to describe a process in the presence of a substance (the catalyst) controls and influences the rate and/or the outcome of the reaction. The substance — the catalyst — which helps in achieving this remains intact is not consumed during the reaction and neither becomes a part of the final product. The catalyst is subsequently removed if it is not to constitute impurity in the final product.

Catalysts are often used to produce new and functional molecules that are used in drugs and other everyday substances. For example, catalysts in cars transform toxic substances in exhaust fumes to harmless molecules. When silver is put along with hydrogen peroxide, the latter suddenly breaks down into water and oxygen. The silver, which initiated the reaction, does not get consumed or affected by the reaction.

The Nobel release points out that in 1835, the renowned Swedish chemist Jacob Berzelius started to see a pattern. “He listed several examples in which just the presence of a substance started a chemical reaction, stating how this phenomenon appeared to be considerably more common than was previously thought. He believed that the substance had a catalytic force and called the phenomenon itself catalysis.”

What are the conventional catalysts used before the discovery of asymmetric organocatalysis?

Two very different catalysts — metals and enzymes — were routinely used by chemists before Dr. List and Dr. MacMillan developed the asymmetric organocatalysts.

What were the main challenges in using the conventional catalysts?

As the name denotes, metal catalysts often use heavy metals. This makes them not only expensive but also environmentally unfriendly as sufficient care needs to be taken to ensure the final product does not contain even traces of the catalyst. There are few other challenges when metal catalysts are used. The heavy metals used in these catalysts very often are highly sensitive to the presence of oxygen and moisture. Hence, for industrial application of this class of catalysts required equipment that ensured no contact with either oxygen and moisture, which made the process expensive.

In the case of enzyme catalysts, the problem arises from their very large sizes. They are often 10,000 times larger than the actual target medicine and can take just as long to make. Enzymes, which are proteins found in nature, are wonderful catalysts. Our bodies also contain thousands of such enzyme catalysts which help make molecules necessary for life.

Many molecules exist in mirror images — left-handed and right-handed. But the molecules of interest will be one of the two mirror images. Many enzymes engage in asymmetric catalysis, which help in producing only one mirror image.  They also work in a continuous fashion — when one enzyme is finished with a reaction, another one takes over. In this way, they can build complicated molecules with amazing precision.

What makes asymmetric organocatalysts superior to metal and enzyme catalysts?

Unlike enzyme catalysts which are very huge, asymmetric organocatalysts are made of a single amino acid. They are not only environmentally friendly but also quicken up the reaction and make the process cheap. Most importantly, asymmetric organocatalysts allow only one mirror image of the molecule to form as the catalysts are made from a single, circular amino acid. Chemists often want only one of these mirror images, particularly when producing drugs.

Organic catalysts have a stable framework of carbon atoms, to which more active chemical groups can attach. These often contain common elements such as oxygen, nitrogen, sulphur or phosphorus. This means that these catalysts are both environmentally friendly and cheap to produce.

Organocatalysts can allow several steps in the molecule production process to be performed in an unbroken sequence. This is achieved by cascade reactions in which the product of the first reaction step is the starting material for the subsequent one, thus avoiding unnecessary purification operations between each reaction step. This helps in considerably reducing waste in chemical manufacturing. Before organocatalysts could be used, it was often necessary to isolate and purify each intermediate product to prevent the accumulation of a large volume of unnecessary byproducts. This led to loss of some of the substance at every single stage of the process.

How well has asymmetric organocatalysts being utilised by chemists and industry?

Ever since the two laureates developed the novel concept of asymmetric organocatalysis, the field has witnessed rapid development. Since 2000, the asymmetric organocatalysis research area has flourished. A huge number of cheap and stable organocatalysts, which can be used to drive a huge variety of chemical reactions and applications have been developed. This period is referred to as the ‘organocatalysis gold rush’. Currently, the area is “well established in organic chemistry and has branched into several new and exciting applications”.

Besides helping the generation of novel molecules used in various industries, pharmaceutical companies have used asymmetric organocatalysis to “streamline the production of existing pharmaceuticals”. Thanks to a multitude of catalysts that can break down molecules or join them together, “they can now carve out the thousands of different substances we use in our everyday lives, such as pharmaceuticals, plastics, perfumes and food flavourings”. The fact is, according to the release, it is estimated that 35% of the world’s total GDP in some way involves chemical catalysis.

Published in The Hindu on October 10, 2021