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How a very simple idea that had been forgotten in a drawer for more than 20 years took us out of the “stone age” of molecular engineering and just won the Nobel

At the beginning of the 19th century, when the first modern chemists began to take the steps that would take them away from medieval alchemy, to their amazement they discovered that the world of reactions was much weirder than they had ever thought. For example, if you put some silver in a glass filled with hydrogen peroxide, it would start to break down into water and oxygen, but the silver remained exactly the same as it was.

It is no longer that the elements were combined with others, no: it is that there were certain substances that, without combining with each other and only with their mere presence, were capable of initiating reactions without being affected in appearance. But there is still more. It is that they realized that this “force” capable of “initiating reactions” was more common than it seemed. They just discovered the catalysts: a very powerful idea that has allowed us to manufacture all kinds of medicines, materials and food. Precisely about them (and how the world has changed in the last 20 years) goes the 2021 Nobel Prize in Chemistry.

Leaving the “Stone Age” of Chemical Engineering

“I could be enclosed in a nutshell and feel like the king of infinite space,” Shakespeare wrote 400 years ago in a dialogue of his famous ‘Hamlet’. And, if I have to be honest, I am convinced that there is no better description of contemporary chemistry than that: We are “kings of an infinite space” capable of creating molecules of all kindsMedicines for almost any disease, materials for almost any utility we can think of, systems capable of doing things that just a handful of years ago would seem like magic or science fiction.

However, if we look at nature, at its awe-inspiring ability to create incredibly specific tools, we realize that despite all our advances we are still locked in the same nutshell. But, and in this “but” is the wonderful thing about science, we do not give up in the effort to have better tools, to be able to make better molecules.

Historically, catalysts have been one of our best assets to get out of what the Nobel Commission has called the “Stone Age” of molecular engineering. Until the turn of the millennium, all the catalysts we encountered were metals or enzymes. Metals, on the other hand, are fantastic catalysts because they have a special ability to temporarily accommodate or ‘lend’ electrons. Their big “but” is that they are usually very sensitive to oxygen and water, which makes it difficult to work with them.

Enzymes, for their part, are very precise tools that make it possible to make complex molecules with astonishing precision. The drawback with them is that we have what we have: those that nature needs for its normal functioning. There are many, but usually we do not have at our disposal the enzyme we need for the problem we want to solve. Why do we want a very powerful drill if what we need is a pasta strainer?

Eureka!

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For this reason, in the 90s, many teams They tried to advance the creation of synthetic enzymes that would solve many of our problems. On one of those teams (the one at the Scripps Institute in California) was Benjamin List. List, in particular, is trying to use the antibodies to act as catalysts. It was then that he realized that looking for a complete macromolecule was absurd: in most cases, it is enough to find the specific chain of amino acids that produces the reaction.

However, when he began to investigate the matter discovered that 20 years earlier something similar had already been tried and no one had continued with the line of work. That probably meant it was a dead end. Luckily for everyone, List decided to try to see what happened and what happened is that it was an immediate success. He had found a quick and easy way to cause “asymmetric catalysis.”

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In February 2000, List published his findings and, unlike others who had worked on the same idea, he understood the potential of what he had in hand. Unlike others, yes; but not unlike everyone. Because at that very moment, David MacMillan was discovering the exact same thing while designing organic molecules capable of doing like metals and accommodating electrons very easily. He submitted his scientific paper for publication in January 2020, a few weeks before List published his work. He called it “organocatalysis”

The organocatalysis revolution

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The result of all this is a boom in our ability to create molecules. To get an idea, the synthesis of strychnine (one of the most complex molecules that we know of) is now 7,000 times more efficient than before the development of Liste and MacMillan saw the light. And all thanks to an idea so damn simple that it had been in front of scientists for decades without anyone seeing it. As they say in Sweden, “sometimes the simple ideas are the hardest to imagine.”

Imagen | Chromatograph