The recently discovered architecture of a copper-nitrenoid complex could revolutionize chemical synthesis

To make soap, simply insert an oxygen atom into a carbon-hydrogen bond. The recipe may seem simple. But carbon-hydrogen bonds, like gum stuck in the hair, are hard to separate. Since they are the foundation of much more than soap, finding a way to break this stubborn couple could revolutionize the way the chemical industries produce everything from pharmaceuticals to household products.

Researchers at Harvard and Cornell universities did just that: they first discovered exactly how a copper-nitrene reactive catalyst – which, like peanut butter used to loosen the gum's hair, helps to trigger a chemical reaction – could turn one of these strong carbon-hydrogen bonds into a carbon-nitrogen bond, a valuable building block for chemical synthesis.

In an article published in Science, Kurtis Carsch, Ph.D. student at the Graduate School of Arts and Sciences at Harvard University, Ted Betley, Erving Chemistry Professor at Harvard, Kyle Lancaster, Associate Professor of Chemistry at Cornell University, and their team of collaborators not only describe how a reactive copper-nitrene Reagent Catalyst achieves its magic, but also how to encapsulate the tool to break these stubborn carbon-hydrogen bonds and make products such as solvents, detergents and dyes with less waste, energy and costs.

Industries often lay the foundation for such products (amines) through a multi-step process: firstly, raw alkane raw materials are converted into reactive molecules, often with expensive, sometimes harmful catalysts. Then, the transformed substrate must exchange a chemical group, which often requires a brand new catalytic system. Avoiding this intermediate step – and instantly inserting the desired function directly into the starting material – could reduce the overall materials, energy, cost and even potentially toxicity of the process.

It is the goal of Betley and his team: to find a catalyst that can miss the chemical steps. Although researchers are looking for the exact composition of a copper-nitrene reactive catalyst for more than half a century and have even assumed that copper and nitrogen could constitute the heart of the world. chemical tool, the exact formation of electrons of the pair remained unknown. "Electrons are like real estate, dude. Location is paramount," Betley said.

"The disposition of electrons in a molecule is intimately tied to its responsiveness," said Lancaster, who, along with Ida DiMucci, a graduate student from her lab, helped establish electron inventories on copper and copper. 39; nitrogen. Using X-ray spectroscopy to find energies where the photons would be absorbed – the mark of the absence of an electron – they found two separate holes on the nitrogen.

"This nitrogen flavor – in which it lacks these two electrons – is involved in reactivity for decades, but no one has provided direct experimental evidence for such a species."

They have now. Typically, if a copper atom binds to a nitrogen, both yield a portion of their electrons to form a covalent bond, in which they share the electrons equitably. "In this case," says Betley, "it's nitrogen with two holes, so it has two free radicals and it's just linked by an isolated pair in the copper."

This bond prevents volatile nitrene from flying off and performing destructive chemistry depending on what is obstructing it. When someone cuts a leg, for example, the body sends a kind of reactive oxygen, similar to these nitrene radicals. The reactive oxygen attacks invading parasites or infectious agents, but it can also damage the DNA.

Thus, to contain the reactive nitrene, the first author, Carsch, built a massive ligand-shaped cage. The ligand, like the organic shrubs surrounding the pair of copper nitrene, keeps the catalyst intact. Cut these shrubs and introduce another substance, such as a carbon-hydrogen bond, and the burning nitrene goes into action.

Betley calls the catalyst a skeleton key, a tool that can unblock bonds that would otherwise be too powerful to use in synthesis. "Let's hope we can generate these chemical species that will now be so reactive that they make the most inert substances we have around us as something we can play with," he said. "It would be really, really powerful." Since building blocks – such as copper and amines – are plentiful and cheap, the keystone could reveal more practical ways to make pharmaceuticals or household goods.

When Carsch made the molecule for the first time, "he was literally bound to be happy," said Betley. "I said to myself, OK, calm down." "But the results have become more interesting: the nitrene reacts better than expected even if" the molecule does not have the right to be stable "and the structure of the bond seemed different from that of the models. during the last six decades of research. "If we had proposed it in the beginning, I think people would have made fun of us."

Although Betley has pursued this elusive species – what Lancaster calls "big game hunting" – since he launched his lab in 2007, he cares less about his victory and more of his collaborators. "I really appreciate seeing Kurtis and my other students marvel at what they've actually done." Carsch confronted both the critics and the chemical walls, but persisted in his hunt. "I'm glad he's stubborn, as stubborn as me," Betley said. Both could be as stubborn as the links that they can now break.

In Cornell, when Lancaster and the fifth-grad student, DiMucci, confirmed the results, he "sent a rather colorful email" to Betley's team. But he also credits his collaborators. DiMucci spent seven days at the Stanford synchrotron analyzing the electronic structure of the catalyst with his team. "Without their new experimental capabilities," said Lancaster, "we really would not have the signal at the noise and low background that made the identification of this thing quite easy."

Then, the team could be inspired by this new design to build catalysts with even more extensive applications, such as reflecting the natural way of converting dangerous methane into methanol. "A true holy grail would be to say, 'OK, this C-H bond, this one in this molecule, I want to turn it into a C-N bond or a C-O bond," Lancaster said. It may be a distant goal, but his so-called "dream team" might be the right one to look for the solution.