Intermolecular Interactions in Inclusion Complexes

Inclusion complexes are assemblies in which a host molecule with a defined cavity encapsulates a guest species through non-covalent interactions. These interactions include hydrogen bonding, van der Waals forces, ion–dipole attractions, dispersion interactions and hydrophobic effects, often acting synergistically to stabilise the host–guest pair. Precise control of cavity size, shape complementarity and functional group placement governs selectivity and binding strength. Characterisation of these complexes employs techniques such as X-ray crystallography, nuclear magnetic resonance spectroscopy, isothermal titration calorimetry and advanced computational methods. Insights into intermolecular forces in these systems underpin advances in drug delivery vehicles, molecular sensing platforms, catalysis and separation technologies. The ability to tailor host frameworks, from cyclodextrins and cucurbiturils to cryptands and pillararenes, has global significance for the design of responsive materials and therapeutics.

Research from Nature Portfolio

A combined experimental and theoretical study investigated a glucose-derived diazacrown cryptand as a carrier for busulfan and lomustine. Synthesis and 1H NMR confirmed formation of stable complexes, while water-solubility assays demonstrated substantially enhanced aqueous compatibility of both drug–cryptand assemblies. Density functional theory calculations in implicit and explicit solvent models revealed the coexistence of inclusion and non-inclusion geometries, with binding energies indicating highly favourable encapsulation. Cellular assays showed that the cryptand itself was non-toxic and that its complexes exhibited increased selectivity towards cancer cells, with divergent effects on the potency of busulfan versus lomustine. These findings highlight the dual importance of cavity architecture and solvation effects in modulating host–guest interactions and therapeutic performance.

Intermolecular Interactions in Inclusion Complexes publication trend

The graph below shows the total number of articles in intermolecular interactions in inclusion complexes across all publications each year (not limited to Nature Index journals).

Technical terms

Inclusion complex: A non-covalent assembly in which a host’s cavity partially or fully encloses a guest molecule.

Host–guest chemistry: The study of molecular recognition processes between a cavity-bearing host and a complementary guest.

Van der Waals forces: Weak, distance-dependent interactions arising from transient electric dipoles.

Ion–dipole interaction: An attraction between a charged ion and the partial charges of a polar molecule.

Hydrogen bond: A directional interaction between an electronegative atom and a hydrogen atom bound to another electronegative atom.

References

1. Experimental and computational studies on possibility of using glucose diazacrown cryptand as a carrier for anticancer drugs busulfan and lomustine. Scientific Reports (2024).
2. DFT-D4 Insight into the Inclusion of Amphetamine and Methamphetamine in Cucurbit[7]uril: Energetic, Structural and Biosensing Properties. Molecules (2021).
3. In Search of Preferential Macrocyclic Hosts for Sulfur Mustard Sensing and Recognition: A Computational Investigation through the New Composite Method r2SCAN-3c of the Key Factors Influencing the Host-Guest Interactions. Nanomaterials (2022).