Scientists finally confirm the 'crazy' hypothesis about vitamin B1 from 1958

Scientists once dismissed a 1958 hypothesis about vitamin B1, or thiamine, as unlikely. The idea was that this vitamin, vital for basic metabolic functions, might turn into a very reactive intermediate during certain biochemical processes.

Now, researchers have shown that the hunch was correct. Prof. Vincent Lavallo from the University of California, Riverside (UCR), led the investigation that confirms vitamin B1 can form a reactive species called a carbene, even in watery surroundings.

Understanding vitamin B1 and carbenes

Carbenes have only six valence electrons on the carbon atom. They are known for being so reactive that they often vanish moments after forming.

Water, which normally disrupts these molecules almost instantly, was never thought to be a friendly environment for them.

“This is the first time anyone has been able to observe a stable carbene in water. People thought this was a crazy idea. But it turns out, Breslow was right,” said Lavallo.

Thiamine is key to fundamental tasks in the body, including the breakdown of sugars for energy.

Why so much doubt for so long?

Carbenes were long considered too unstable for water because of how quickly they react. Even trace moisture in the air could destroy them before scientists had a chance to study them.

Most early attempts to observe carbenes in water ended in failure. They either disappeared or broke apart into other molecules, reinforcing the belief that they simply couldn’t last in water-based systems.

That skepticism ran deep. Researchers preferred to work with these molecules in dry, oxygen-free environments using special lab setups.

This made the idea of observing them in water, let alone storing them, sound like science fiction.

A fresh approach to working in water

A carbene in water seemed impossible because water usually attacks such electron-poor carbon centers right away.

“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 Dr. Varun Raviprolu, a postdoctoral researcher at UCLA. 

He and his colleagues developed a special chemical covering – a molecular shield – to keep the carbene from making contact with water. This shield prevented immediate breakdown.

1958 theory turned out to be true

Chemist Ronald Breslow suggested ages ago that thiamine might transform into a carbene during certain body reactions.

No one could prove it. The new findings show that under the right conditions, the carbene form of vitamin b1 is stable enough to observe with advanced tools like nuclear magnetic resonance.

Researchers say this stability helps explain how crucial transformations occur in living cells. Their protective strategy shows that the body could be forming short-lived carbene intermediates during routine metabolic tasks.

Eco-friendly B1 manufacturing

These carbenes can serve as ligands in metal-based catalysts, which are widely used to produce many substances. Carbenes in water may open a path to cleaner processes, thanks to reduced dependence on harmful solvents. 

“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,” said Raviprolu. 

These catalysts could transform how pharmaceuticals and everyday materials are produced. Some industry reactions are notorious for generating chemical waste.

By harnessing water-based techniques, the hope is to cut costs and avoid safety concerns linked to flammable liquids.

Mimicking life’s chemistry in the lab

Living cells rely on complex, water-based reactions to keep the body running. Many of those reactions involve fast, reactive intermediates that are hard to detect or replicate in a lab.

The fact that Lavallo’s team managed to stabilize a molecule that mimics this behavior could help researchers recreate cellular chemistry more accurately.

That means a better grasp of how enzymes work and possibly new ways to repair or reprogram those functions in medicine.

Carbenes are often studied for their ability to mimic parts of enzyme action. Now that scientists can make them behave in watery environments, they might start finding ways to control them for specific biological tasks.

This could eventually change how we design enzyme-inspired drugs or materials that react only under the same conditions found inside human cells.

Next steps with vitamin B1

Proving that carbene intermediates can survive in water solves a riddle about vitamin b1’s potential. It also raises new questions about other fleeting molecules that may exist in living systems.

Lavallo and his team hope that a similar method might reveal more hidden players involved in major biological reactions.

“Something that seems impossible today might be possible tomorrow, if we continue to invest in science,” said Raviprolu.

The finding suggests that nobody should dismiss theories, no matter how far-fetched, without thorough research.

The study is published in Science Advances.

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