Researchers at UC Riverside have successfully synthesized a carbene that remains stable in water, overturning the long-held chemical assumption that water destroys these highly reactive carbon species instantly. This breakthrough provides the first direct experimental evidence supporting a hypothesis proposed nearly 70 years ago regarding the mechanistic function of Vitamin B1 (thiamine).
Validating Breslow’s Hypothesis
In 1958, chemist Ronald Breslow theorized that Vitamin B1 performs key metabolic functions by forming a carbene-like intermediate. This idea was difficult to prove because carbenes are typically unstable in aqueous environments like the human body. The new study confirms that carbenes can exist in water if they are sufficiently protected, suggesting that enzymes function by creating specific microenvironments that exclude bulk water to stabilize high-energy intermediates.
Engineering a Molecular "Suit of Armor"
To achieve water stability, the research team utilized steric shielding and electronic tuning. They wrapped the reactive carbene center in a bulky, highly chlorinated carborane-based framework. This structure acts as a physical barrier, preventing water from attacking the reactive orbitals. Using nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography, the team verified that the carbene remained stable in water for months without decomposing.
Implications for Green Chemistry
Beyond biological insights, this discovery has significant industrial potential. Carbenes are widely used as ligands in metal catalysts for pharmaceutical and material synthesis, processes that currently rely on toxic organic solvents. Proving that powerful catalysts can be stabilized in water could allow manufacturers to switch to water—a non-toxic, abundant solvent—leading to cleaner and more sustainable chemical production methods.
Mentoring question
How might the ability to stabilize highly reactive intermediates in water influence your approach to designing more sustainable, environmentally friendly chemical processes?