On the molecular level as in macroscopic life, one should never underestimate the importance of the right support system to weather a potentially reactive situation.
Alkyl oxonium cations are notoriously strong electrophiles; they eagerly react with almost anything that has a lone pair of electrons. “You can’t use them anywhere near water or alcohols or halides . . . they’ll be gone in an instant,” says Mark Mascal of the University of California, Davis. Putting an oxonium and an alcohol group in the same molecule would seem impossible.
Mascal and his team decided to do it anyway.
After a decade of work, they managed to combine an oxonium and three alcohols into a stable molecule using a clever 3D geometry (Angew. Chem., Int. Ed. 2026, DOI: 10.1002/anie.2727232).
It’s “basically got the seeds of its own destruction,” Mascal says, and yet the compound is “perfectly stable. We can chromatograph it, we can do whatever we want with it.” The researchers even took things a step further by deprotonating one of the alcohol groups—and the molecule was still stable enough to study spectroscopically, albeit at cryogenic temperatures.
The secret to getting the oxonium to play nicely with nucleophiles was to stick it in the middle of a bowl-shaped scaffold, with the alcohols sticking out from the edges of the bowl. This arrangement enables the OH groups to form tight, stabilizing hydrogen bonds with each other.
“They can talk to each other and they can mutually stabilize each other,” Mascal says. The molecule’s nuclear magnetic resonance shifts didn’t change significantly when the researchers deprotonated it, indicating that the hydrogen-bonding network was distributing the negative charge. The researchers tracked the deprotonation using NMR signals from the base.
When the researchers turned two of the hydroxy groups into methyl esters and then attempted deprotonation, the molecule quickly decomposed, offering further proof that the three-alcohol arrangement is key to the molecule’s stability.
Mascal says that projects like this are like a tree: they’re rooted in fundamental physical organic chemistry and branch out into lots of new questions about the molecular world. That’s what he loves most about basic research, he says. “Learning more about bonding and electrons, and how far you can push molecules . . . that has been my big raison d’être, so to speak.”
CORRECTION
This story was updated on May 26, 2026, to correct the DOI citation. The correct DOI is 10.1002/anie.2727232, not 1002/anie.2727232.
