Chemists have achieved what many once thought impossible by stabilizing a highly reactive molecule in water, confirming a 67-year-old theory about vitamin B1. This breakthrough not only solves a long-standing biochemical mystery, but also points toward cleaner and more efficient ways to make medicines.
The discovery centers on carbenes, a type of carbon with only six valence electrons. Under normal conditions, carbon atoms are most stable when they have eight electrons. With only six carbenes, it is highly unstable and reacts almost instantly with its surroundings. It usually breaks down quickly in water.
For decades, scientists have suspected that vitamin B1, also known as thiamine, temporarily forms carbene-like structures within cells that help facilitate essential biochemical reactions. But this molecule is so unstable that no one has been able to observe it directly under such conditions.
Stable carbene observed for the first time in water
Researchers have now succeeded in producing carbenes that are stable in water. They not only produced it, but separated it, sealed it in a tube, and observed that it remained intact for months. The findings are detailed in a study published in Science Advances.
“This is the first time we’ve been able to observe stable carbenes in water,” said Vincent Lavallo, a professor of chemistry at the University of California, Riverside, and corresponding author of the paper. “People thought this was a crazy idea. But as it turned out, Breslow was right.”
1958 hypothesis finally confirmed
Ravallo is referring to Columbia University chemist Ronald Breslow, who in 1958 proposed that vitamin B1 could be converted to carbenes, enabling important biochemical reactions. Although the idea was influential, it remained unproven because carbenes were known to be too unstable, especially in water, to be captured or studied.
To overcome this challenge, Lavallo’s team developed a protective molecular structure surrounding the carbene. He describes it as “like an armor,” designed to protect the reaction center from water and other nearby molecules. This protection makes the carbene stable enough for detailed analysis using nuclear magnetic resonance spectroscopy and X-ray crystallography, providing clear evidence that such molecules can exist in water.
“We were creating these reactive molecules not to follow historical theory, but to explore their chemistry,” said lead author Varun Raviprole. He completed his research as a graduate student at UCR and is currently a postdoctoral fellow at UCLA. “But our study turned out to confirm exactly what Breslow had proposed many years ago.”
Aiming for more environmentally friendly chemistry and pharmaceutical production
Its meaning is more than solving a scientific puzzle. Carbenes are widely used as “ligands,” or supporting components of metal-based catalysts that help accelerate chemical reactions. These catalysts play an important role in the production of pharmaceuticals, fuels, and other materials. However, many of these processes rely on toxic organic solvents.
By stabilizing carbenes in water, researchers may have opened the door to safer and more environmentally friendly chemical production.
“Water is an ideal solvent: it’s abundant, non-toxic and environmentally friendly,” Raviprole said. “Being able to make these powerful catalysts work in water would be a big step toward greener chemistry.”
Getting closer to mimicking the chemistry of living cells
The ability to create and maintain reactive intermediate molecules in water also brings scientists closer to replicating the chemical reactions that naturally occur inside living cells, which are made up mostly of water.
“There are other reactive intermediates that we haven’t been able to separate so far,” Ravallo said. “With a defensive strategy like ours, we might finally be able to watch them and learn from them.”
Milestones over the years
For Ravallo, who has spent 20 years researching carbene, this result has both scientific and personal significance.
“Just 30 years ago, people thought you couldn’t even make these molecules,” he says. “Now you can soak it and bottle it. What Breslow said all those years ago, he was right.”
Raviprole sees this milestone as a broader lesson about tenacity in science.
“If we continue to invest in science, what seems impossible today may be possible tomorrow,” he said.
