Chemists at the University of California, Riverside have accomplished what many in the field considered impossible: they stabilized an extremely reactive molecule in water, confirming a 67-year-old theory about how vitamin B1 works inside living cells.

The breakthrough, published in Science Advances, resolves a long-standing biochemical puzzle and could transform how pharmaceuticals are manufactured — making the process safer and more environmentally friendly.

The Carbene Challenge

At the center of the discovery is a carbene, a form of carbon with just six valence electrons instead of the typical eight needed for stability. Under normal conditions, carbenes are wildly reactive, breaking down almost instantly when exposed to water or other molecules.

In 1958, Columbia University chemist Ronald Breslow proposed that vitamin B1 — also known as thiamine — might briefly form a carbene-like structure inside cells to help drive essential biochemical reactions. The idea was influential but remained unproven because no one could capture such an unstable molecule in water.

"People thought this was a crazy idea," said Vincent Lavallo, a chemistry professor at UC Riverside and corresponding author of the paper. "But it turns out, Breslow was right."

A Molecular Suit of Armor

Lavallo's team solved the problem by developing a protective molecular structure that surrounds the carbene — what he describes as "a suit of armor" designed to shield the reactive center from water and other nearby molecules.

With this protection, the carbene became stable enough not just to observe, but to isolate. The researchers sealed it in a tube and watched it remain intact for months. They confirmed its structure using nuclear magnetic resonance spectroscopy and X-ray crystallography.

"This is the first time anyone has been able to observe a stable carbene in water," Lavallo said.

First author Varun Raviprolu, who completed the research as a graduate student at UC Riverside, said the discovery was serendipitous. "We were making these reactive molecules to explore their chemistry, not chasing a historical theory. But it turns out our work ended up confirming exactly what Breslow proposed all those years ago."

Toward Greener Chemistry

The implications extend well beyond solving a scientific mystery. Carbenes are widely used as components in metal-based catalysts that help produce pharmaceuticals, fuels, and industrial materials. Currently, many of these processes depend on toxic organic solvents.

By demonstrating that carbenes can function in water, the researchers have opened a pathway to safer and more sustainable chemical production.

"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."

Closer to Nature's Playbook

The ability to maintain reactive molecules in water also brings scientists closer to replicating the chemistry that naturally occurs inside living cells, which are mostly composed of water.

"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, who has spent two decades working with carbenes, the milestone carries both scientific and personal significance. "Just 30 years ago, people thought these molecules couldn't even be made. Now we can bottle them in water. What Breslow said all those years ago — he was right."