Intermolecular Interactions in Molecular Complexes

The assembly and stability of molecular complexes are governed by a delicate balance of intermolecular forces. These noncovalent interactions span a spectrum from directional hydrogen bonds to the subtler yet cumulatively significant London dispersion forces. In many systems, weak CH-π interactions between aliphatic hydrogen donors and aromatic π clouds can direct molecular recognition, while π–π stacking and electrostatic contacts further modulate complex geometry. Recent advances have elucidated how orbital overlap can extend beyond covalent bonding to generate intermolecular ‘bonding’ and ‘antibonding’ states, reshaping our understanding of weakly bound assemblies. Techniques including high-resolution spectroscopy and quantum chemical calculations have converged to yield benchmark geometries and energetics, enabling predictive design of supramolecular architectures. These insights impinge on fields as diverse as drug–receptor binding, materials engineering and selective catalysis, emphasising both fundamental significance and wide-ranging applications.

Research from Nature Portfolio

Recent work has revealed that intermolecular orbital interactions can mirror intramolecular bonding phenomena. In a prototypical benzene–methane complex, sophisticated ab initio calculations uncovered significant overlap between occupied and unoccupied orbitals of the two partners. This overlap gives rise to stabilising intermolecular ‘bonding’ orbitals and destabilising ‘antibonding’ counterparts, yielding net interaction energies on the order of –1.5 kcal mol–1. These findings extend the concept of orbital hybridisation to noncovalent regimes, offering a robust framework for interpreting weak CH-π hydrogen bonding from a molecular-orbital standpoint.

Intermolecular Interactions in Molecular Complexes publication trend

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

Technical terms

Noncovalent interaction: Any stabilising force between molecules that does not involve the sharing of electron pairs, including hydrogen bonds, electrostatics and dispersion.

London dispersion forces: Weak, attractive interactions arising from instantaneous fluctuations in electron density, particularly important in large or polarisable molecules.

Hydrogen bond: A directional interaction in which a hydrogen atom covalently bound to an electronegative atom engages with a lone-pair donor, typically oxygen or nitrogen.

CH-π interaction: A specific noncovalent contact between an aliphatic C–H bond and the π cloud of an aromatic ring, contributing to molecular recognition and binding specificity.

Intermolecular orbital interaction: The overlap of molecular orbitals from separate molecules, leading to stabilising and destabilising energy contributions analogous to covalent bonding.

References

1. Strong orbital interaction in a weak CH-π hydrogen bonding system. Scientific Reports (2016).
2. Dispersion Control over Molecule Cohesion: Exploiting and Dissecting the Tipping Power of Aromatic Rings. Accounts of Chemical Research (2024).
3. Bracelet-like Complexes of Lithium Fluoride with Aromatic Tetraamides, and Their Potential for LiF-Mediated Self-Assembly: A DFT Study. Molecules (2023).
4. Rovibronic signatures of molecular aggregation in the gas phase: subtle homochirality trends in the dimer, trimer and tetramer of benzyl alcohol. Physical Chemistry Chemical Physics (2021).