Hydrogen-bonded organic cages (HOCs) exhibit considerable potential in the fields of molecular recognition, catalysis, and separation due to their reversible, dynamic, and multifunctional structural features. However, rational design of giant HOCs composed of many components and possessing large cavities has remained a challenge, constrained by the weak and directional nature of hydrogen-bond interactions.

In a study published in J. Am. Chem. Soc., Profs. YUAN Daqiang and SU Kongzhao and their colleagues from Fujian Institute of Research on the Structure of Matter of the Chinese Academy of Sciences proposed an assembly strategy synergizing covalent and hydrogen‑bond interactions. They constructed an extra‑large hydrogen‑bonded snub cube (HSC), one of the 13 Archimedean solids, composed of 30 components, demonstrating selective recognition and separation of fullerenes.

Although progress has been made in HOC research based on building blocks such as calix[4]resorcinarene (C4RA), most structures are limited by the directionality and strength of hydrogen bonds, making it difficult to form giant architectures incorporating a larger number of components and larger cavities. Combining the dynamic covalent chemistry of a C4RA derivative with the triple-hydrogen-bond assembly capability of pyrazole molecules, a novel assembly strategy was developed.

Researchers selected tetraformyl‑C4RA (C4RACHO) and 3,5‑dimethyl‑1H‑pyrazol‑4‑amine as building blocks. In a one-pot reaction, phenolic hydroxyl groups of C4RACHO and pyrazole amine first formed imine bonds which then underwent keto-enol tautomerization to yield thermodynamically more stable β‑ketoenamine bonds. Meanwhile, pyrazole units self‑assembled through intermolecular N-H···N hydrogen bonds to form trimers which acted as connecting nodes enclosing six C4RA units.

Single-crystal X-ray diffraction confirmed the structure to be a hydrogen‑bonded snub cube, stabilized collectively by 24 intramolecular hydrogen bonds, 24 intramolecular hydrogen bonds, and 24 intermolecular hydrogen bonds, totaling 72 hydrogen bonds, making it one of the HOCs with the highest reported number of hydrogen bonds to date.

The HSC possesses an exceptionally large internal cavity with a volume of 5391 ų and an internal height of about 2.9  nm, far exceeding the reported analogues. Diffusion-ordered spectroscopy nuclear magnetic resonance measurements yielded a hydrodynamic diameter of 3.7 nm, consistent with the crystallographic data. The HSC can simultaneously accommodate two fullerene molecules (C₆₀ or C₇₀), forming a rare 1:2 host-guest complex.

Host-guest titration experiments and Density Functional based Tight Binding calculations revealed that the binding affinity of HSC for C₇₀ is significantly higher than that for C₆₀. This selectivity originates from tighter π···π interactions between C₇₀ and the pyrazole units of the host. Leveraging this property, the HSC can preferentially extract C₇₀ from C₆₀/C₇₀ mixtures, demonstrating its potential application as a separation material for fullerenes.

This study provides a novel approach for designing giant supramolecular cages with ultra-large cavities and specific recognition functions. It also offers a new type of adsorbent material for the efficient separation of fullerenes.

Schematic representation illustrating the constructing of HSC via synergistic covalent and hydrogen-bonding interactions. (Image by Prof. YUAN's team)