Despite being some of the most versatile building blocks in organic chemistry, compounds called carbenes can be too hot to handle. In the lab, chemists often avoid using these highly reactive molecules because of how explosive they can be.
But in a new study, published today in the journal Science, Ohio State University researchers report on a new, safer method of changing these short-lived, high-energy molecules from much more stable molecules.
“Carbenes have an incredible amount of energy in them,” said David Nagib, study co-author and a professor of chemistry and biochemistry in the state of Ohio. “The value of that is that they can do chemistry that you just can’t do any other way.”
In fact, members of the Nagib Lab specialize in the use of reagents with such high chemical energy and have helped invent many new substances and techniques that would otherwise be chemically inaccessible.
In this study, the researchers developed catalysts made from inexpensive, earth-rich metals, such as iron, copper and cobalt, and combined them to harness their new method of harnessing carbene.
They were able to successfully use this new strategy to channel the power of reactive carbenes to fabricate valuable molecules on a larger scale and much faster than traditional methods. Nagib compared this jump to engineers figuring out how to use steel to build skyscrapers instead of brick and mortar.
For example, one molecular feature that chemists have had trouble creating is cyclopropane, a small, strained ring of twisted chemical bonds found in some drugs. More recently, cyclopropane has been used as a key ingredient in the oral antiviral pill called Paxlovíd. Used to treat COVID-19, the pill reduces the severity of the disease by preventing the virus from multiplying, rather than killing it completely.
While it has been difficult to make the cyclopropane needed to make the drug in large quantities, Nagib said he believes his lab’s new method could be applied to make the drug faster and on a larger scale. “Our new method will provide better access to dozens of types of cyclopropanes for inclusion in all kinds of drugs to treat diseases,” he said.
While the team’s research has potential applications outside of the pharmaceutical realm, such as agrochemicals, Nagib said he is most passionate about how their tool could accelerate the discovery of new, targeted drugs. “You could technically apply our methods to anything,” he said. “But in our lab, we’re more interested in accessing new species, more potent drugs.”
Nagib predicts that, using the process his team developed, a chemical reagent that currently takes 10 or 12 steps to make (with explosive intermediates) can be done in four or five, saving nearly 75% of the manufacturing time. is saved.
Overall, Nagib said he hopes this research will help other chemists do their jobs.
“There are a lot of really great scientists around the world doing this kind of chemistry, and with our tool, they could potentially have a safer lab,” Nagib said. “The taste of science that we do, the most satisfying reward is when other people use our chemical methods to make important molecules better.”
Other co-authors included Lumin Zhang, a former postdoctoral fellow, as well as Bethany M. DeMuynck, Alyson N. Paneque, and Joy E. Rutherford, all graduate students in the Department of Chemistry and Biochemistry and members of the Nagib Lab. The research was supported by the National Institutes of Health, the National Science Foundation and the Sloan Foundation.
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