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

To make soap, just insert an oxygen atom into a carbon-hydrogen bond. The recipe may sound simple. But carbon-hydrogen bonds, like gum stuck in hair, are difficult to pull apart. Since they provide the foundation for far more than just soap, finding a way to break that stubborn pair could revolutionize how chemical industries produce everything from pharmaceuticals to household goods.

Now, researchers at Harvard University and Cornell University have done just that: For the first time, they discovered exactly how a reactive copper-nitrene catalyst—which like the peanut butter used to loosen gum's grip on hair, helps nudge a chemical reaction to occur—could transform one of those strong carbon-hydrogen bonds into a carbon-nitrogen bond, a valuable building block for chemical synthesis.

In a paper published in Science, Kurtis Carsch, a Ph.D. student in the Graduate School of Arts and Sciences at Harvard University, Ted Betley, the Erving Professor of Chemistry at Harvard, Kyle Lancaster, Associate Professor of Chemistry at Cornell University, and their team of collaborators, not only describe how a reactive copper-nitrene catalyst performs its magic, but also how to bottle the tool to break those stubborn carbon-hydrogen bonds and make products like solvents, detergents, and dyes with less waste, energy, and cost.

Industries often forge the foundation of such products (amines) through a multi-step process: First, raw alkane materials are converted to reactive molecules, often with high-cost, sometimes noxious catalysts. Then, the transformed substrate needs to exchange a chemical group, which often requires a whole new catalytic system. Avoiding that intermediate step—and instead instantly inserting the desired function directly into the starting material—could reduce the overall materials, energy, cost, and potentially even the toxicity of the process.

That's what Betley and his team aimed to do: Find a catalyst that could skip chemical steps. Even though researchers have hunted for the exact make-up of a reactive copper-nitrene catalyst for over a half century and even speculated that copper and nitrogen might be the core of the chemical tool, the exact formation of the pair's electrons remained unknown. "Electrons are like real estate, man. Location is everything," Betley said.

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

"This flavor of nitrogen—in which you have these two electrons missing—has been implicated in reactivity for decades, but nobody has provided direct experimental evidence for such a species."

They have now. Typically, if a copper atom binds to a nitrogen, both give up some of their electrons to form a covalent bond, in which they share the electrons equitably. "In this case," Betley said, "it's the nitrogen with two holes on it, so it has two free radicals and it's just bound by a lone pair into the copper."

That binding prevents the volatile nitrene from whizzing off and performing destructive chemistry with whatever gets in its way. When someone gets a cut on their leg, for example, the body sends out a reactive oxygen species, similar to these nitrene radicals. The reactive oxygen species attacks invading parasites or infectious agents, but they can damage DNA, too.