What happens when molecules won’t stay still? UCLA researchers have just demonstrated that the rigidest rules in chemistry are not unbending. The results of their experiment look as if they were taken straight out of science-fiction.
Neil Garg and his team from UCLA have broken Bredt’s rule in 2024. This said that double bonds could not form on the bridgehead of a molecule. They’ve now gone one step further and created cage-like molecules cubene, quadricyclene that twist double bond into 3D shapes.
The key group in organic chemistry is alkenes. Alkenes are characterized by flat trigonal planar shapes on each end and strong sigma-pi bonding, giving them an order of bonding close to two.
In this study, scientists considered unusual alkenes, which exhibit intense geometric distortion called hyperpyramidalization. Hyperpyramidalized atoms do not maintain their flat shapes. The double bond, instead, is bent, distorted and weakens the p bond. These unusual molecules include cubene and the 1,7-quadricyclene.
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Researchers began synthesizing stable compounds as precursors to cubene and Quadricyclene. They contained silicon-bonded silyl groups and leaving groups. The reaction inside the vessel produced quadricyclene or cubene when treated with salts of fluoride.
These molecules reacting so rapidly, other chemicals were able to trap them instantly. The result was a complex and unusual product that is normally difficult to produce using conventional methods.
Cubane is very unstable and strained, and therefore it cannot be observed or separated. Nevertheless, computer simulations and experiments show that they are present briefly in reactions.
The chemists of the past believed that alkenes like this should be possible, but due to our reliance on textbooks, we have avoided molecules such as cubene or quadricyclene. said UCLA chemist Neil Garg. It turns out that almost all these rules are more suitable as guidelines.
The drug industry is increasingly looking for complex 3D molecules capable of locking onto targets biologically with precision. Flat molecules have run out of tricks.
Garg believes that cubene and quadricyclene are part of this shift. Making cubene and Quadricyclene in the early 20th Century was probably considered a niche activity. He said. But today, we’re starting to run out of options for the more regular and flattened structures. It is more important to create unusual rigid 3-D molecules.”
Garg’s discovery was not just about breaking the rules, but about teaching future chemical researchers to question them. Garg believes that these findings could be used to help researchers create the next generation medicines.
The way we teach and think about bond orders is very different now. He said. Scientists need to challenge the rules. We can’t create new ideas if we don’t stretch our imagination or knowledge.
Journal Reference
- Ding, J., French, S.A., Rivera, C.A. et. al. As synthetic building blocks, hyperpyramidalized ethenes have bond orders close to 1.5. Nat. Chem. (2026). DOI: 10.1038/s41557-025-02055-9
