Supramolecular Chemistry of Host-Guest Systems

Supramolecular chemistry of host-guest systems centres on the design and study of reversible, non-covalent assemblies in which a defined host molecule selectively binds a complementary guest. This discipline exploits hydrogen bonding, π–π stacking, cation–π interactions, hydrophobic effects and metal-coordination to drive the formation and modulation of discrete complexes and extended networks. Macrocyclic hosts such as crown ethers, cyclodextrins, calixarenes, cucurbiturils and pillararenes provide well-defined cavities that can encapsulate a wide range of guests, from small organic molecules to charged ions and functional nanoparticles. By tuning cavity size, functionality and binding motifs, researchers have created systems capable of energy transfer, selective separations, sensing, controlled release and catalysis. Recent advances include the integration of dynamic host-guest interactions into light-harvesting assemblies, stimuli-responsive drug carriers and adaptive porous frameworks. Together, these developments underscore the global significance of host-guest chemistry in sustainable energy technologies, environmental remediation and precision medicine.

Research from Nature Portfolio

Recent studies have reported the metal-coordination driven self-assembly of double helicates based on [2,2] paracyclophane scaffolds bearing terpyridine ligands. In aqueous tetrahydrofuran/water mixtures, these helicates exhibit pronounced aggregation-induced emission and exceptional energy-transfer efficiencies, enabling one-step and sequential artificial light-harvesting systems and white-light-emitting devices in solid films.
Another investigation described the generation of a homogeneous supramolecular metal-organic framework in water at room temperature via a hexa-armed ruthenium polypyridyl precursor and a macrocyclic host. The resulting cubic network retains its periodicity upon solvent removal, encapsulates polyoxometalate anions in a one-cage–one-guest manner and, under visible-light irradiation, facilitates rapid multi-electron transfer to drive efficient hydrogen evolution.
A foundational report demonstrated the construction of a three-dimensional periodic organic framework in water using aromatic dimerisation within a macrocyclic host. The porous microcrystals formed act as an ‘ion sponge’ capable of selective uptake and release of anionic guests, including drug molecules, while maintaining framework periodicity in both solution and solid phases.

Supramolecular Chemistry of Host-Guest Systems publication trend

The graph below shows the total number of articles in supramolecular chemistry of host-guest systems across all publications each year (not limited to Nature Index journals).

Technical terms

Supramolecular chemistry: The branch of chemistry concerned with the study of organised entities of higher complexity formed through non-covalent interactions.

Host-guest interaction: A reversible non-covalent binding event in which a host molecule selectively recognises and encapsulates a guest species within its cavity.

Macrocycle: A large cyclic molecule, typically comprising repeating units, that provides a defined internal cavity for guest binding.

Inclusion complex: A supramolecular assembly in which a guest molecule is fully or partially enclosed within the cavity of a host.

Cucurbituril: A family of rigid macrocyclic hosts composed of glycoluril units linked by methylene bridges, known for high binding affinities towards cationic and neutral guests.

Pillar[n]arene: A class of macrocyclic hosts formed by hydroquinone units linked through methylene bridges in a pillar-shaped architecture, notable for their tunable cavity size and functionalisation.

References

1. [2,2] Paracyclophanes-based double helicates for constructing artificial light-harvesting systems and white LED device. Nature Communications (2023).
2. Supramolecular metal-organic frameworks that display high homogeneous and heterogeneous photocatalytic activity for H2 production. Nature Communications (2016).
3. Three-dimensional periodic supramolecular organic framework ion sponge in water and microcrystals. Nature Communications (2014).
4. A novel strategy of constructing 2D supramolecular organic framework sensor for the identification of toxic metal ions. Nano Materials Science (2023).
5. Near-Ideal Xylene Selectivity in Adaptive Molecular Pillar[n]arene Crystals. Journal of the American Chemical Society (2018).
6. Host-Guest Chemistry in Supramolecular Theranostics. Theranostics (2019).