Researcher Vincent Lavallo, a professor of chemistry at UC Riverside reported experimental confirmation of a long-standing hypothesis first proposed in 1958. Writing in Science Advances, Vincent Lavallo and colleagues described how they were able to generate and stabilise a carbene in liquid water, a feat previously considered impossible. Their achievement lends support to Ronald Breslow’s idea that vitamin B1, or thiamine, may adopt a carbene-like form during its biochemical role.
Raviprolu, V. T., Gregory, A., Banda, I., McArthur, S. G., McArthur, S. E., Goddard, W. A., Musgrave, C. B., & Lavallo, V. (2025). Confirmation of Breslow’s hypothesis: A carbene stable in liquid water. Science Advances, 11(15). https://doi.org/10.1126/sciadv.adr9681
Carbenes are unusual species in chemistry. Instead of carbon’s typical eight valence electrons, a carbene has only six, which makes it highly reactive and short-lived. In aqueous conditions, carbenes normally break down in fractions of a second, so most chemists assumed that they could never exist in biological systems. Yet in 1958, Breslow proposed that thiamine could briefly form a carbene intermediate to carry out catalytic reactions in the body. For decades, that suggestion remained untested because of the fundamental instability of carbenes in water.
Vincent Lavallo, a professor of chemistry at UC Riverside stated,
“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.”
Lavallo’s group approached the problem by designing a protective molecular framework that acts as a shield around the reactive carbon centre. This “armor” limits the carbene’s exposure to water and other molecules, allowing it to persist for months in sealed containers. The team verified the molecule’s identity and structure using nuclear magnetic resonance spectroscopy and X-ray crystallography, providing clear evidence that the carbene remained intact in aqueous conditions. According to Lavallo, this represents the first time a carbene has been observed in liquid water with such stability, showing that the long-dismissed idea may indeed have merit.
The implications of the study extend beyond confirming a historical hypothesis. Many chemical processes in industry rely on carbene chemistry, typically in conjunction with metal catalysts. These reactions usually take place in organic solvents that are hazardous and costly to handle. Demonstrating that carbene systems can be made to function in water suggests a possible path toward cleaner and more sustainable chemistry. Water, as a solvent, is safe, abundant, and inexpensive, making it highly attractive for industrial applications if the reactive intermediates involved can be controlled.
There are also consequences for basic science. Being able to stabilise reactive intermediates long enough to observe and study them provides new insights into reaction mechanisms. Until now, many of these species were inferred indirectly, leaving gaps in understanding. The protective strategies used in this work could be adapted to investigate other unstable molecules, helping chemists piece together the steps of complex reactions that occur in both laboratory and biological contexts.
Despite the excitement, limitations remain. The carbene stabilised by Lavallo’s group is a laboratory construct, and its relevance to the behaviour of vitamin B1 in cells is still uncertain. Cellular environments are highly complex, and whether thiamine generates a similar carbene during enzymatic reactions has yet to be demonstrated directly. In addition, the very strategies that make the carbene stable may also reduce its reactivity compared to the transient intermediates that occur naturally.
Nevertheless, the study illustrates how long-standing scientific questions can find answers after decades of speculation. A hypothesis dismissed as unrealistic in the mid-20th century has now been given experimental support thanks to advances in molecular design. For chemists and engineers alike, this result highlights the potential of combining creative molecular architecture with practical goals such as greener solvent use. It also underscores a broader point: in science, ideas may wait many years for the tools to catch up, but persistence can eventually bring them within reach.
Adrian graduated with a Masters Degree (1st Class Honours) in Chemical Engineering from Chester University along with Harris. His master’s research aimed to develop a standardadised clean water oxygenation transfer procedure to test bubble diffusers that are currently used in the wastewater industry commercial market. He has also undergone placments in both US and China primarely focused within the R&D department and is an associate member of the Institute of Chemical Engineers (IChemE).
