In a discovery that’s sending ripples through the chemistry world, UCLA scientists have proven that a fundamental rule of organic chemistry – one that has held back researchers for 100 years – isn’t as unbreakable as everyone thought. The breakthrough could open new paths for drug development and pharmaceutical research.
The rule in question, known as Bredt’s rule, has been chemistry gospel since 1924. It’s like telling architects they can never build a certain type of bridge because the laws of physics won’t allow it. But now, UCLA researchers have not only built that “impossible” bridge – they’ve shown others how to do it too.
“People aren’t exploring anti-Bredt olefins because they think they can’t,” says Neil Garg, UCLA’s Kenneth N. Trueblood Distinguished Professor of Chemistry and Biochemistry, who led the research, in a media release. “We shouldn’t have rules like this — or if we have them, they should only exist with the constant reminder that they’re guidelines, not rules. It destroys creativity when we have rules that supposedly can’t be overcome.”
To understand why this matters, imagine organic molecules as tiny 3D structures, like molecular Lego builds. These structures often contain what chemists call “double bonds” between carbon atoms. According to the traditional rules, these double bonds must lie flat – like a tabletop – and can’t exist in certain twisted positions within the molecule. Bredt’s rule specifically said you couldn’t put these double bonds at certain junction points in more complex molecular structures.
However, Garg’s team found a way around this limitation. Using a clever chemical strategy, they created these supposedly impossible structures by treating specific molecules (called silyl pseudohalides) with fluoride. Because these “forbidden” structures are highly unstable – think of a house of cards in a windstorm – the team also developed a way to “trap” them, making them useful for further chemical reactions. The implications could be significant for drug development.
“There’s a big push in the pharmaceutical industry to develop chemical reactions that give three-dimensional structures like ours because they can be used to discover new medicines,” Garg explains.
The research, published in the prestigious journal Science, was a team effort involving UCLA graduate students and postdoctoral scholars Luca McDermott, Zachary Walters, Sarah French, Allison Clark, Jiaming Ding, and Andrew Kelleghan, along with computational chemistry expert Ken Houk.
This discovery serves as a powerful reminder that in science, even our most trusted rules sometimes need revisiting. After all, as the UCLA team has shown, sometimes breaking the rules can lead to breakthrough discoveries.
Source : https://studyfinds.org/chemists-break-100-year-old-rule
