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Chemists at The Ohio State University have developed a new approach for generating reactive carbon-based intermediates known as metal carbenes, according to a study published in Science. These intermediates serve as essential building blocks in the synthesis of pharmaceuticals and materials.
Carbenes are short-lived, highly reactive species that contain a divalent carbon atom. While valuable in chemical transformations, they are often challenging to produce due to their instability and the hazardous conditions typically required for their formation.
The Ohio State team reports a method that uses iron as a catalyst along with chlorine-containing molecules that release radicals. Together, these components generate carbenes under milder conditions. The resulting carbenes can then undergo a reaction to form cyclopropanes – three-membered ring structures commonly found in medicines and agrochemicals.
“Our goal all along was to determine if we could come up with new methods of accessing carbenes that others hadn’t found before,” said David Nagib, co-author of the study, a distinguished professor in arts and sciences and a professor of chemistry and biochemistry at The Ohio State University. “Because if you could harness them in a milder catalytic way, you could reach new reactivity, which is essentially what we did.”
Cyclopropanes are valued for their compact size and high ring strain, which can influence the biological activity of compounds. Although many synthetic routes to these structures exist, the new method provides an alternative path by accessing carbenes that were previously difficult or impossible to create.
Enabling faster and safer transformations
The researchers also found that their new method can also be carried out effectively in water, raising the possibility that carbenes could one day be generated inside of living cells. Such an approach could be transformative in discovering new drug targets, according to the researchers.
Having access to a new way of creating carbenes that can replace the current, more wasteful approaches, could also help to bring down the cost of drugs by making their production safer and easier.
Similarly, the researchers hope that this method could help to prevent shortages of important medicines, including antibiotics, antidepressants and treatments for conditions such as heart disease, COVID and HIV.
Looking ahead, the team plans to continue refining the approach and exploring how the reaction might be extended to other catalysts and molecular targets.
“Our team at Ohio State came together in the coolest, most collaborative way to develop this tool,” Nagib said. “So we’re going to continue racing to show how many different types of catalysts it could work on and make all kinds of challenging and valuable molecules.”
Reference: Nguyen KNM, Mo X, DeMuynck BM, et al. Harnessing carbene polarity: Unified catalytic access to donor, neutral, and acceptor carbenes. Science. 2025;389(6756):183-189. doi: 10.1126/science.adw4177
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