Scientists Unlock Safer Carbene Synthesis for Better Medicines

New Iron-Catalyzed Method Promises Cheaper, More Potent Drugs

Chemists have pioneered a revolutionary technique to generate vital chemical compounds, utilizing metal carbenes with unprecedented ease and safety. This breakthrough offers a simpler path to creating molecules crucial for drug development and advanced materials.

A Leap in Carbene Chemistry

Carbenes, fleeting and highly reactive carbon atoms essential for synthesizing drugs and materials, have historically posed significant challenges in their laboratory creation. The methods have been limited and often involve hazardous processes. However, researchers at The Ohio State University have unveiled an innovative approach that drastically simplifies carbene production.

“Our goal all along was to determine if we could come up with new methods of accessing carbenes that others hadn’t found before,” stated David Nagib, a co-author and distinguished professor of chemistry and biochemistry at Ohio State. “Because if you could harness them in a milder catalytic way, you could reach new reactivity, which is essentially what we did.”

The team’s discovery hinges on using iron as a metal catalyst, combined with chlorine-based molecules that readily produce free radicals. This synergistic reaction successfully creates a variety of carbenes, including many previously inaccessible. These carbenes then swiftly react with strained chemical bonds to form cyclopropanes, triangular molecular fragments vital for pharmaceuticals and agrichemicals.

“Our lab is obsessed with trying to get the best methods for making cyclopropanes out there as soon as possible,” Nagib added. “We have the eye on the prize of inventing better tools to make better medicines, and along the way, we’ve solved a huge problem in the carbene world.”

The groundbreaking study, published in the prestigious journal Science, also revealed that this new method performs exceptionally well in water. This suggests a future possibility of generating metal carbenes directly within living cells to identify novel drug targets. Nagib estimates this novel approach is approximately 100 times more effective than previous tools developed by his lab over the past decade.

Impact and Future Potential

This advancement is poised to significantly impact the pharmaceutical industry by offering a safer, more efficient, and less wasteful alternative to current multi-step processes for carbene production. For consumers, this could translate into more affordable, potent, and faster-acting medications. The technique holds the potential to mitigate shortages of critical drugs, including antibiotics, antidepressants, and treatments for conditions like heart disease, COVID-19, and HIV infections.

“Our lab is very much a tool development lab,” Nagib emphasized. “And to me, the way you gauge if it’s valuable or interesting is if others use your tool.”

With the aim of ensuring broad accessibility for both large corporations and smaller research facilities, the Ohio State team is committed to refining their technique further. They plan to explore its compatibility with a wider range of catalysts and apply it to synthesize diverse and valuable molecules.

The research was supported by grants from the National Science Foundation, the National Institutes of Health, and the Brown Institute for Basic Science. Other Ohio State co-authors include Khue Nguyen, Xueling Mo, Bethany DeMuynck, Mohamed Elsayed, Jacob Garwood, Duong Ngo, and Ilias Khan Rana.