Scientists Accidentally Prove 'Crazy' 70-Year-Old Vitamin B1 Theory Right

In 1958, when chemist Ronald Breslow proposed a theory about vitamin B1, people found it impossible to believe. It turns out that the idea wasn't that crazy after all. Chemists have pulled off an experiment, proving a bizarre theory right, as per the study published in Science Advances. Breslow believed that vitamin B1 (thiamine) could carry out metabolic chemistry by briefly forming carbene-like structures. However, the carbenes are highly reactive to their atmosphere and could be instantly destroyed after contact with water. Although Breslow's proposal was impressive, it didn't seem practical at the time. Scientists couldn't see how a fragile molecule could exist long enough inside cells to conduct metabolic chemistry. Now, almost 70 years later, a team led by UC Riverside chemist Vincent Lavallo managed to bottle the ultra-reactive carbene in water.

The newly designed carbene is not just water-tolerant but also water-stable. Nuclear magnetic resonance (NMR) spectroscopy and single-crystal X-ray crystallography helped the team confirm the nature of the carbene molecule. “This is the first time anyone has been able to observe a stable carbene in water,” Vincent Lavallo, a professor of chemistry at UC Riverside and corresponding author of the paper, said in a statement. “People thought this was a crazy idea. But it turns out, Breslow was right," he added. But how did the carbene lose its reactive nature? Lavallo’s team curated a protective "suit of armor,” wrapped around the molecule. The 3D structure protects the reactive orbitals of the carbene molecule and prevents water from reaching it.

The electron-withdrawing substituents pull electrons away from the highly reactive carbene, making it more stable. According to the study, the team of scientists created a protective hydrophobic pocket around the reactive carbon. The chlorinated carborane-based framework was wrapped around the thick center of the molecule, preventing water from causing any harm. “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,” said first author Varun Raviprolu. This research goes beyond a biochemical breakthrough because carbenes also have practical implications in real-world industries.

Carbenes are often used as support structures in metal-based catalysts, which are essential for making medicines, fuels, and many everyday materials. The production of these materials involves toxic and dangerous organic solvents. The researchers' successful attempt at stabilizing carbene molecules could prove useful in medicine or fuel production in the future, making the workspace less expensive and safer. “Water is the ideal solvent — it’s abundant, non-toxic, and environmentally friendly. If we can get these powerful catalysts to work in water, that’s a big step toward greener chemistry," Raviprolu said. Lavallo hopes that the same process could help stabilize other such substances. “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,” Lavallo said.