For decades, scientists have thought that the human body briefly forms a highly unstable molecule, a carbene, from a form of vitamin B1, also known as thiamine. These molecules are unique in that their carbon atoms have only six electrons, rather than the average eight, making them incredibly reactive and fleeting. This is especially true in aqueous media, where carbenes can have half-lives as short as nanoseconds to picoseconds.
The idea was proposed in 1958 by chemist Ronald Breslow. That idea seemed close to unimaginable at the time. Because carbenes were too unstable to observe directly, researchers struggled to determine whether they existed, particularly in a water-rich environment like the human body.
Now, more than 60 years later, that mystery has at long last been solved.
This is a revolutionary finding, made possible only through creative thinking, the new application of advanced techniques, and a great deal of patience, say chemists who have now proved a theory about vitamin B1 that has stood for decades. In the process, they may have laid the groundwork for a more sustainable method of making drugs.
A team of researchers at the University of California, Riverside, led by Vincent Lavallo, has done the seemingly impossible: it synthesized a stable carbene in water, isolated it from the solution, sealed it in a glass tube, and found it remained intact for months.
“This is the first time anyone has been able to observe a stable carbene in water,” said Lavallo. “People thought this was a crazy idea. But it turns out, Breslow was right.”
Their findings were published in the journal Science Advances.
So how did they achieve this?
The team devised a protective molecule, what Lavallo calls a “suit of armor,” that wraps around the carbene to prevent it from reacting with water or other substances. This design strategy allowed the normally unstable molecule to remain long enough to be studied in detail.
Using techniques such as nuclear magnetic resonance and X-ray crystallography, scientists demonstrated that the carbene was stable, providing strong evidence that such molecules exist in water.
“We were making these reactive molecules to explore their chemistry, not chasing a historical theory,” said Varun Raviprolu, the study’s first author. “But it turns out our work ended up confirming exactly what Breslow proposed all those years ago.”
This discovery is not just the thrill of solving an old puzzle; It could revolutionize how we make key chemicals. In catalysis, carbenes act as catalysts, enabling chemical reactions used in industries producing medicines, fuels, and materials. These processes typically depend on toxic compounds. The new technique could allow those reactions to take place in water instead.
“Water is the ideal solvent; it’s abundant, non-toxic, and environmentally friendly,” Raviprolu said. “If we can get these powerful catalysts to work in water, that’s a big step toward greener chemistry.”
The finding also improves scientists’ understanding of the chemistry occurring inside living cells, which are largely water. By stabilizing such ephemeral molecules, the researchers may, in turn, have the chance to study other transitory chemical intermediates that had been out of reach.
“There are other reactive intermediates we’ve never been able to isolate, just like this one,” Lavallo said. “Using protective strategies like ours, we may finally be able to see them, and learn from them.”
For Lavallo, the achievement marks a major milestone in a career spent studying these tricky molecules.
“Just 30 years ago, people thought these molecules couldn’t even be made,” he said. “Now we can bottle them in water. What Breslow said all those years ago was right.”
For Raviprolu, the discovery carries a broader message:
“Something that seems impossible today might be possible tomorrow, if we continue to invest in science.”
Journal Reference:
- Varun Tej Raviprolu, Aaron Gregory, Isaac Banda, Scott G. McArthur, Sarah E. McArthur, William A. Goddard, Charles B. Musgrave, Vincent Lavallo. Confirmation of Breslow’s hypothesis: A carbene stable in liquid water. Science Advances, 2025; 11 (15) DOI: 10.1126/sciadv.adr9681