Whether drugs, plastics or other complex molecules: many of the chemical compounds required for this are now produced using modular synthesis methods. The 2022 Nobel Prize in Chemistry will go to three scientists who invented and advanced this so-called "click chemistry" - a modular synthesis in which standardized reactions can produce almost any organic molecule from simple starting materials. US chemist Barry Sharpless was the first to introduce click chemistry, Danish chemist Morten Meldal developed one of the nuclear reactions for it, and US chemist Carolyn Bertozzi further developed the methods for use in living cells.
The chemical elements in the periodic table can be combined into a wide variety of molecules through reactions and chemical bonds. However, especially for complex molecules and active substances, chemical synthesis often requires numerous reaction steps to be completed one after the other, which also have to take place under specific conditions. For a long time, this made the production of many substances extremely complex and inefficient. The 2022 Nobel Prize in Chemistry goes to three organic chemists who have made significant contributions to simplifying chemical synthesis.
Molecules build according to the Ikea principle
The first to do so was the US chemist Barry Sharpless, who was awarded the Nobel Prize in Chemistry in 2001. At the time he was looking for a way to simplify the often complicated syntheses. His idea: if you use a set of simple, widely applicable reactions as tools, then you could use them to create a wide variety of products from simple starting materials through modular syntheses. This approach can be compared to the principle used by the furniture manufacturer Ikea: a series of standardized components that have not yet been assembled are supplied with simple tools and can then be assembled into different shelves or cupboards.
In their specialist article published in 2001, Sharpless and his colleagues also describe the principle as modules that are simply “clicked together”. With this, Sharpless laid the foundation for “click chemistry”. Sharpless and his team also set out the criteria that the reactions and starting materials of their modular synthesis method had to meet: the chemical reactions had to be efficient and also take place in the presence of oxygen and water and without special solvents in order to make them as universally applicable as possible. In addition, the starting materials should be readily available and the by-products should be easily separable. The chemists have already suggested the first reactions that could be used as tools for Click. chemistry – but only theoretically at first.
The most important reaction tool for the "click"
Among the reactions proposed by Sharpless and his colleagues was one presented at a symposium that same year by Danish chemist Morten Meldal – the second prize winner. He had discovered that a certain synthetic reaction in organic chemistry, the so-called azide-alkyne cycloaddition, can be made much more efficient by adding a copper catalyst: high temperatures are no longer required and the reaction runs more or less on its own and with high yields . In this copper-catalyzed azide-alkyne cycloaddition, the azine and alkyne groups, like their two counterparts, work in a click-cap and combine with each other. By attaching them to any organic molecule, you can "click" together increasingly complex constructs. Today, this reaction forms the basis for chemical syntheses, which are used in the manufacture of drugs, plastics and countless other materials in technology, medicine and chemistry.
Click chemistry also for living cells
The third prizewinner, the US chemist Carolyn Bertozzi, has extended this basic click chemistry reaction so that it can also be used in living cells – for example to attach fluorescent marker proteins to cell-specific substances. However, because copper is toxic to cells, she had to develop a version of the azide-alkyne cycloaddition that works without this catalyst but still requires no energy input and runs efficiently. The chemist succeeded in doing this by using a ring-shaped variant of the alkyne. In addition, Bertozzi further developed a previously known synthesis reaction, the Staudinger reaction, so that it could also be used to “click together” molecules in the cell environment. The chemist coined the term bioorthogonal reactions for this click chemistry that can be used in cells. They are defined as the reactions of functional groups that are so selective for each other that they can link molecules together even in a highly dynamic and complex biological milieu.
"Together, the achievements and discoveries of Carolyn Bertozzi, Morten Meldal and K. Barry Sharpless have had a tremendous impact on our society," according to the Nobel Prize Foundation. "Through their new concepts and highly efficient methods, the award winners have expanded our possibilities to improve our world and our lives - for the benefit of mankind."
Source: Nobel Prize Foundation