For nearly 100 years, a basic rule in organic chemistry has shaped the way scientists create molecules, especially in pharmaceuticals.
Known as “Bredt’s rule,” this guideline was laid down in 1924 and claimed that certain molecules couldn’t exist in a stable form.
But researchers from UCLA have just shown that this rule isn’t quite right, paving the way for new approaches to molecule design and even drug discovery.
In simple terms, Bredt’s rule states that a double bond (a type of strong link between two carbon atoms) cannot be placed at the “bridgehead” position of certain ring-shaped molecules.
Imagine a molecule with a carbon “bridge” that connects two parts of a ring structure.
According to Bredt’s rule, having a double bond at this bridge point would twist and stress the molecule, making it too unstable to exist.
This rule has been accepted for decades and has limited how chemists think about building molecules, particularly those known as olefins, which are useful in many chemical reactions.
The UCLA team, led by Professor Neil Garg, questioned whether this rule was as absolute as it seemed. They decided to experiment with anti-Bredt olefins (ABOs), which are molecules that defy Bredt’s rule by placing double bonds at the bridgehead.
To test their idea, the team created a special reaction. They treated molecules called silyl halides with fluoride, which caused a reaction that produced these rare anti-Bredt olefins.
Since ABOs are highly unstable, they quickly added a second substance to “trap” and stabilize them so they could analyze the results.
Their work shows that not only can anti-Bredt olefins exist, but they also hold great potential for practical use, particularly in pharmaceutical research.
By breaking Bredt’s rule, chemists now have more freedom to create complex molecules that could be beneficial in drug development.
Professor Garg believes that chemists shouldn’t treat rules like Bredt’s as unbreakable barriers. Instead, they should think of them as guidelines that can evolve as new discoveries emerge. His team’s work proves that even long-standing scientific ideas can be challenged, leading to breakthroughs that may improve our ability to design and create new medicines.
This study, published in the journal Science, marks an exciting step forward, inviting chemists everywhere to rethink what’s possible in molecule design and open new paths for innovation.
Source: UCLA.
