This year’s Nobel Prize in Chemistry goes to two researchers who, independently of one another, have discovered a group of completely new tools for the tailor-made production of organic molecules. The catalysts they have identified also enable the targeted production of only one of the two asymmetric molecule variants. Benjamin List from the Max Planck Institute for Coal Research in Mülheim found out that individual amino acids such as proline are suitable as catalysts for the production of such molecules. David MacMillan from Princeton University identified other catalysts based on so-called iminium ions. The asymmetric organocatalysis developed by the two researchers has since opened up completely new possibilities for producing tailor-made organic molecules for use in chemistry, drug production and other areas.
Without catalysis, many chemical reactions would not take place and a large part of our own metabolism would not be possible. Because in order to break chemical bonds and to re-establish them, an energy barrier often has to be overcome. A catalyst accomplishes this by temporarily participating in the reaction and, for example, transferring electrons from one molecule to another. Before the two award winners published their groundbreaking findings in 2000, only two types of such catalysts were known. In nature and also in the human body, enzymes serve as catalytic reaction assistants. Often whole series of such proteins are connected in series to keep the complex biochemical reactions going. However, making use of these enzymes in the laboratory for catalysis is complicated and not always possible.
The second type of catalytic converter are inorganic metal compounds, such as those used in vehicle emission control. However, they are usually not very environmentally friendly and many of them only work effectively in the absence of oxygen and in a dry environment. In addition, these inorganic catalysts usually produce mixtures of molecules, so-called racemates: In the case of chiral molecules that are asymmetrically shaped and occur in two configurations or “handedness”, these catalysts usually produce both forms in almost equal proportions. The problem, however, is that in biochemistry and medicine in particular, chirality plays a decisive role in the properties, effects and behavior of the molecule. One variant can be an effective medicine, the other ineffective. This is where the work of the two award winners begins.
List: an amino acid as a catalyst
Benjamin Lists based his research on enzymes – complex proteins made up of hundreds of amino acids. He asked himself whether the totality of all amino acids and their configuration was always necessary for the catalysis function of an enzyme: Could it be that only one or a few amino acids are sufficient for some catalysis reactions? To find an answer, List experimented with the amino acid proline, which was already known to have a catalytic effect in certain chemical reactions. In his experiments, the researcher tested whether proline can catalyze the so-called aldol reaction. During this reaction, acetone and aromatic aldehydes react with one another and form new carbon-carbon bonds.
It succeeded: As List found out, the interaction of the nitrogen atom contained in proline with a proton of the reaction partners forms an intermediate product that stabilizes and promotes the formation of the new compound. And not only that: unlike metal catalysts, one of the two asymmetric molecular shapes was preferred. In February 200, List published his results and described the concept as a completely new form of asymmetric catalysis with organic molecules.
MacMillan: Iminium ion wanted
Around the same time, David MacMillan was working on a very similar catalytic principle at the University of California at Berkeley. He was looking for simple organic molecules that could form a certain ion, the so-called iminium ion. In this charged molecular form, a nitrogen atom is bound in the hydrocarbon structure in such a way that it can accept an electron. This allows it to act as a catalyst in chemical reactions. After experiments with various molecules, MacMillan found the configuration that effectively and reliably formed the iminium ion he was looking for. Using the example of the Diels-Alder reaction, through which ring-shaped hydrocarbon compounds are formed, the researcher not only demonstrated that his organic catalysts worked, they also preferred to produce one of the two asymmetric molecular shapes. His results were also published in 2000, when MacMillan coined the term organocatalysis.
“This concept of catalysis is as simple as it is ingenious,” says Johan Åqvist, chairman of the Nobel Prize Committee for Chemistry. The work of List and MacMillan formed the starting point for a completely new area of catalysis and thus created new possibilities for the simple production of asymmetric molecules in the desired configuration. In addition to raw materials for pharmaceuticals and chemical products, this also includes, for example, new materials for organic solar cells. Because organic catalysts, unlike many metal catalysts, are non-toxic and environmentally friendly, they also help to make chemistry a little greener.
Source: Nobelprize.org