Intermolecular Interactions in Molecular Systems

Intermolecular interactions govern the association and aggregation of molecules, underpinning phenomena from protein folding to material assembly. These forces may be broadly classified as electrostatic, dispersion, induction and exchange–repulsion components. Electrostatic interactions arise from permanent charges or multipoles; dispersion forces reflect instantaneous correlated fluctuations in electron density; induction describes polarisation of one partner by the field of another; and exchange–repulsion counters attractive interactions at close contact. The balance of these contributions dictates the strength, selectivity and dynamics of molecular recognition, self-assembly and macroscopic properties such as solubility and phase behaviour. Recent advances in experimental measurement and high-level computation have elucidated subtle context-dependent effects, for example how solvent environment, conformational constraints and cooperative networks modify both the magnitude and directionality of individual contacts. Such insights underpin the rational design of catalysts, pharmaceuticals and functional materials, enabling precise control of binding affinities and assembly pathways. The global significance of this research extends to energy storage, biomolecular engineering and sustainable chemical processes, where targeted modulation of weak forces can yield transformative performance.

Research from Nature Portfolio

Investigations have revealed unconventional modes of attraction, notably the demonstration of π-hole bonding in nitrate anions. In the solid state, comprehensively analysed structures show that resonance-delocalised nitrate ions can adopt a Lewis-acidic π-hole on nitrogen, engaging oxygen- and sulfur-containing partners. Quantum mechanical studies confirm donor–acceptor orbital overlap stabilises these assemblies despite overall negative electrostatic potential. This finding expands the classical view of ionic interactions and suggests new strategies for crystal engineering and biological recognition by exploiting polarisation and anisotropic charge distribution in seemingly simple ions.

Intermolecular Interactions in Molecular Systems publication trend

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

Technical terms

Hydrogen bond: A directed interaction between a hydrogen atom covalently bound to an electronegative donor and an electronegative acceptor, combining electrostatic, covalent and dispersion components.

London dispersion: An attractive van der Waals force arising from correlated instantaneous fluctuations of electron density between neighbouring atoms or molecules.

π-hole bonding: A noncovalent interaction in which an electron-deficient region above a π-system or atom accepts electron density from a donor, leading to stabilising donor–acceptor overlap.

Cooperativity: A phenomenon in which the formation of one noncovalent interaction alters the strength of neighbouring interactions, often enhancing overall network stability.

Functional group interaction profile (FGIP): A solvent-dependent free energy map that quantifies the contribution of a single point interaction between two functional groups in diverse solvent environments.

References

1. NO3− anions can act as Lewis acid in the solid state. Nature Communications (2017).
2. Context-Dependent Significance of London Dispersion. Accounts of Chemical Research (2023).
3. Functional group interaction profiles: a general treatment of solvent effects on non-covalent interactions. Chemical Science (2020).
4. Strong Short‐Range Cooperativity in Hydrogen‐Bond Chains. Angewandte Chemie International Edition (2017).