Making supramolecular snub cubes

Chemists have unveiled new supramolecular snub cubes—2,712-atom polyhedral assemblies made up of 12 identical helical macrocycles that are held together by 144 weak hydrogen bonds. Snub cubes are Archimedean solids with 60 edges, 38 faces, and 24 vertices. Snub cubes can be right- or left-handed, and these snub cube supramolecules can also be right- or left-handed, depending on the stereochemistry of the macrocyles used to make them. Each supramolecular snub cube has distinct compartments within its framework and can host two different guest components simultaneously. The new snub cube supramolecules’ creators say they could be used for chiral separations or asymmetric catalysis (Nature 2025, DOI: 10.1038/s41586-024-08266-3).

Huang Wu and the late J. Fraser Stoddart of the University of Hong Kong along with Wenping Hu and Yu Wang of Tianjin University led the effort to make and characterize the snub cube supramolecules. The chemists say they were inspired by biological encapsulants like virus capsids and the iron-storing protein ferritin.

These aren’t the first supramolecular snub cubes. That was made in 1997 by Leonard R. MacGillivray and Jerry L. Atwood, who were both then at the University of Missouri–Columbia. That complex was held together by just 60 hydrogen bonds. The new snub cube supramolecules are the first to be made stereoselectively. The chemists were able to selectively make only right- or left-handed snub cubes using the stereochemistry of the starting helical macrocycles.

Shiki Yagai, who studies supramolecular materials at Chiba University and was not involved in the research, says the discovery that small chiral components can noncovalently assemble into chiral nanostructures without the help of proteins is “truly astonishing.” He says in an email that “this groundbreaking material exemplifies an extraordinary level of hierarchical self-organization, rivaling the complexity and sophistication of biological systems.”

Peter J. Stang, an expert in supramolecular assembly at the University of Utah who was also not involved in the work, says in an email that “this is bold, imaginative chemical science that moves the area of supramolecular chemistry forward and has the potential of providing a better understanding and insight of this exciting, broad field.”

Wu tells C&EN that the discovery of the snub cubes was serendipitous. He synthesized many macrocycles with the hopes that one of them would assemble into a complex polyhedron, but he hadn’t planned to form a snub cube. Once he made the key helical macrocycle and found that it assembled into more complex architecture, it took some time for him to figure out that it had taken on the snub cube shape. Wu also says that the day after he showed Stoddart the crystal structure of the snub cube, Stoddart confessed he couldn’t sleep all night because he was so excited about the complex.

Next, Wu says, he’d like to try using artificial intelligence to design supramolecular snub cubes of different sizes and mechanically interlocked snub cubes.