‘Perplexanes’ achieve mind-bending molecular topology

If you like a knotty chemistry problem, this one’s a doozy. Chemists in California have woven entangled nanocarbon structures that boast some of the most fiendishly complicated shapes. Dubbed “perplexanes,” they represent an entirely new topological class of molecules (J. Am. Chem. Soc. 2025, DOI: 10.1021/jacs.5c04268).

Chemists have previously built a wide range of entangled structures, including catenanes, which contain interlocked rings, and molecular knots. These have often been constructed around metal ions that coordinate functional groups in precursor molecules. But entangled nanocarbon structures, based on carbon-rich molecules that lack these kinds of chemical handles, have been particularly difficult to make, typically requiring many steps and producing very low yields.

T. Don Tilley and his colleagues at the University of California, Berkeley, have now developed an alternative method to build entangled nanocarbons. “In our case, we’re really not relying on these directional templates to encode our structure,” says Harrison M. Bergman, who led the experimental work while he was a PhD student in Tilley’s group and who is now a postdoc at the Massachusetts Institute of Technology.

Instead, the researchers start with molecular building blocks that have three flexible arms bearing alkyne groups. They use a zirconium reagent to couple these alkynes, forging connections between several building blocks. Finally, they remove the zirconium by hydrolysis, freezing the entangled carbon structure in place. By tuning the building blocks’ core structure and the flexibility of their arms, the researchers are able to control the architecture of the final product to some extent.

The team’s first perplexane is based on a building block with a large, flat core of aromatic rings. Interactions between the rings’ π-electrons arrange the building blocks into neat stacks, guiding the arms into position. The finished structure is similar to a catenane, except that each interlocked ring also carries a smaller loop that its partner ring threads through (see picture).

The researchers applied the same method to a building block with a smaller core, which did not enable π-stacking. This unexpectedly created an entangled structure similar to a trefoil knot but with strands threading through three of the smaller loop features rather than simply crossing one another. Topologically speaking, the presence of these smaller loops means that the structure is not strictly a knot.

The syntheses produced perplexanes in overall yields of 43–55%, much higher than previous routes to entangled nanocarbons. “I think it’s an impressive piece of work,” says Nicholas Evans of Lancaster University, a supramolecular chemist who creates interlocked molecules and who was not involved in the research.

The team found that the trefoil perplexane is remarkably soluble in hexane, even though its building block is insoluble. “That suggests it’s quite a dynamic, squishy structure,” Bergman says, adding that it may be possible for the cage-like structure to bind and release guest molecules.

Evans suggests that further modifications could even introduce a catalytic site within the trefoil perplexane’s cavity, making a structure akin to an enzyme: “It could be like an artificial active site,” he says.

The perplexanes’ interlocked and interwoven architecture may also enable flexing or stretching movements that could translate into unusual mechanical properties. “There’s a fair bit of interest now in entanglement and how that might lead to new physical properties for materials,” Tilley says.

His team now plans to use the zirconium coupling method to make larger, more complex perplexanes. “One of the goals is to learn the ground rules for how the monomer structure relates to the entangled molecule that’s being created,” Tilley says.