What happens when molecules refuse to sit still? A team at UCLA has just shown that even the most rigid rules of chemistry can bend, and the results look like something out of science fiction.
In 2024, Neil Garg’s team at UCLA broke Bredt’s rule, which said double bonds couldn’t form at a molecule’s bridgehead. Now they’ve gone further, creating cage-like molecules, cubene and quadricyclene, that twist double bonds into unusual 3D shapes.
Alkenes are key groups in organic chemistry. They usually have flat, trigonal planar shapes at each end, with strong sigma and pi bonding that gives them a bond order close to 2.
In this study, scientists considered unusual alkenes, which exhibit intense geometric distortion called hyperpyramidalization. In a hyperpyramidalized alkene, the atoms don’t stay in their usual flat shape. Instead, the double bond is bent and distorted, which makes the π-bond weaker and lowers the bond strength to about 1.5 instead of 2. Examples of these unusual molecules are cubene and 1,7‑quadricyclene.
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To generate cubene and quadricyclene, the researchers began by synthesizing stable precursor compounds. These contained silyl groups (atoms bonded to silicon) and leaving groups. When treated with fluoride salts, the reaction produced cubene or quadricyclene inside the vessel.
Because these molecules react so quickly, they were instantly trapped by other chemicals. This produced complex, unusual products that are normally very hard to make using standard methods.
Cubane and quadricyclane are very strained and unstable, so they can’t be separated or directly observed. Still, experiments and computer models show they exist briefly during reactions.
“Decades ago, chemists found strong support that we should be able to make alkene molecules like these, but because we’re still very used to thinking about textbook rules of structure, bonding, and reactivity in organic chemistry, molecules like cubene and quadricyclene have been avoided,” said UCLA chemist Neil Garg. “But it turns out almost all of these rules should be treated more like guidelines.”
Drug designers are increasingly seeking complex 3D molecules that can lock onto biological targets with precision. Flat molecules are running out of tricks.
Garg sees cubene and quadricyclene as part of that shift: “Making cubene and quadricyclene was likely considered pretty niche in the 20th century,” he said. “But nowadays we are beginning to exhaust the possibilities of the regular, more flat structures, and there’s more of a need to make unusual, rigid 3D molecules.”
For Garg, the discovery is not only about breaking rules but also about teaching future chemists to challenge them. He thinks these results could help drug researchers design the next generation of medicines.
“Having bond orders that are not one, two, or three is pretty different from how we think and teach right now,” he said. “Time will tell how important this is, but scientists need to question the rules. If we don’t push the limits of our knowledge or imaginations, we can’t develop new things.”
Journal Reference:
- Ding, J., French, S.A., Rivera, C.A. et al. Hyperpyramidalized alkenes with bond orders near 1.5 as synthetic building blocks. Nat. Chem. (2026). DOI: 10.1038/s41557-025-02055-9
