He tames explosive molecules

Certain groups of atoms are extremely useful. One of these is the nitro group. On its own, nitrogen dioxide (NO₂) is a poisonous, pungent gas; but as an additional group of atoms, it lends practical, sometimes even explosive properties to previously innocuous molecules. Explosives such as picric acid and TNT belong to the nitroaromatic compounds, a class of substances that play an important role in many other products, such as dyes, plastic polymers, pesticides and medicines. That is why such nitroaromatics are produced in large quantities on an industrial scale. Doing so involves introducing a nitro group to a starting set of molecules. However, “the conventional processes have major disadvantages,” says Dmitry Katayev, chemist and group head at ETH Zurich. He and his team have now found a simpler and more resource-efficient method of incorporating nitro groups into organic molecules.

Today’s industrial processes require strong acids such as a mixture of nitric and sulphuric acid or metalliferous compounds – substances that endanger health and the environment and which then have to be treated and disposed of at great expense. Moreover, these procedures do not appear to be very precise: they essentially sprinkle NO₂ groups over the original substance out of a watering can. Thus, instead of only one nitro group at the desired position, two or more are sometimes incorporated into one molecule. This results in a mixture that contains numerous undesirable by-products, which have to be removed in a time-consuming and expensive process.

Precise control

Katayev’s team has come up with a more elegant approach. The chemists have developed a set of reagents and a corresponding methodology that allows them to precisely introduce either one or several NO₂ groups into various original molecules as required, and in just a single step. “To do this, the reaction must be very precise,” Katayev says. “It must not alter anything else on the original molecule, regardless of what that looks like or what atom groups it already contains.”

This is relatively easy when the original molecules consist exclusively of carbon and hydrogen, because the electron distribution of such hydrocarbons make them inert. In other words, they need a pretty strong push to produce a chemical reaction. The situation is different for molecules that contain, for example, oxygen or a halogen atom such as fluorine or chlorine. In these groups of atoms – chemists call them “functional groups” – the electron distribution makes them willing to react with a newcomer and enter into a new “partnership” with it. It is therefore much more difficult to leave such atom groups unchanged.

Katayev’s new method manages this by closely controlling the reaction. He found a mild, controllable source for the NO₂ group: a form of the oldest synthetic sweetener, saccharin, known as N-nitrosaccharin. The molecule can be controlled via a catalyst, a kind of activation molecule that first has to be triggered – for example, through irradiation with visible light – to set off the reaction and transfer the nitro group to the target molecule. This makes it possible to precisely set conditions for the reaction, such as temperature or number of original molecules, before the reaction begins. Similarly, the chemists can adjust the amount of nitrosaccharin they add to determine how many nitro groups are integrated into the original molecule at which points. And because the reaction takes place under very mild conditions – no addition of acids, a maximum temperature of 50° Celsius – no other functional groups of the original molecules are affected or destroyed. After the reaction is complete, the saccharin can be recovered and used again for the preparation of reagent.

Work during the lockdown

Two patent applications are currently pending for this new methodology and Katayev’s miracle N-nitrosaccharide powder is already in use at several chemical companies. For his achievement, the 34-year-old group head was awarded the renowned Ružička Prize (see box) last year.

Like all members of the ETH community, he and his team have been working from home during the coronavirus lockdown. Katayev reports that he quickly got used to it, and stays in touch with his group members and colleagues. “Sometimes I have up to five video meetings in one day,” he says as he grins into the computer camera. His team members are using their working hours at home to write articles or work on their doctoral theses. They speak with Katayev at least twice a week to discuss their recent chapters, and the regular group meeting takes place once a week, just as before the lockdown.

What Katayev is really missing these days are his hobbies: skiing, fishing and especially table tennis. He is just as adept at making table tennis balls behave the way he wants as he is at manipulating chemical bonds. As one of the top players at D. I. Mendeleev University of Technology , he competed successfully for years, even earning the title of “Master of Table Tennis”. At Russian universities, he explains, the table tennis rankings are given academic titles: Bachelor, Master, Doctor, Professor. It may be some time since he played competitively, but the pride is clear in his voice when he talks about it.

Taming radical atoms

A native of Kaluga, Russia, Katayev came to Switzerland to do his doctorate at the University of Geneva. He moved to ETH in 2015, where since 2017 he has led his own team in the research group headed by Professor of Chemistry Antonio Togni. For some years now, Katayev has specialised in finding new ways to incorporate useful atom groups into molecules – ways that are efficient, controllable and sparing of resources.

One of its pet projects in this regard is research into radicals, atoms or groups of atoms that have just one electron where they should have an electron pair. This makes them highly reactive, which means they are excellent drivers of chemical reactions. However, they must be properly controlled if they are not to wreak havoc. For example, a reaction involving radicals often involves a mix of two combinations: the desired molecule and its mirror image. Katayev is researching how chemical processes with radicals can be steered so that only one of the two versions is produced.

He accomplished this recently with a process known as trifluoromethylation. This reaction is frequently needed when incorporating a certain functional group containing fluorine (CF₃) into pesticides and medications to enhance their biological effect. Katayev’s newly developed mechanism is much more efficient: after just one round, 99 percent of the resultant product consists of only the desired form of the molecule.

Katayev will not remain at ETH for long. Thanks to his outstanding research, he recently obtained an „SNSF Eccellenza Professorial Fellowship“ from the Swiss National Science Foundation, enabling him to accept a position next year as an assistant professor at the University of Fribourg.