Do bonds need a name?: New classification of Non-Covalent Interactions

Non-covalent interactions (NCIs) span a wide range of electronic behaviours, yet traditional names such as hydrogen bond or halogen bond group are used for interactions with very different energetic origins. We propose that a more robust classification should rely on electronic characteristics in analogy with the long-standing covalent/ionic distinction for strong interactions. In the case of non-covalent interactions, the extent of directionality versus non-directionality determines the structural organisation and dynamic behaviour of interactions, being the source of information used for selectivity or drug design. From an energetic viewpoint, it can be understood as the ratio between electrostatic and dispersive contributions. However, this characterisation is cumbersome from a computational viewpoint. We show that these characteristics can be captured by a simple density-based descriptor, q_NCI/V_vdW , which distinguishes directional, electrostatically driven interactions from more diffuse dispersion-dominated contacts. Application to model systems and benchmark datasets (S66, X40, NCIAtlas - 2421 complexes) shows that this descriptor reveals substantial variation hidden by atom-centred nomenclature and provides a unified, transferable framework for analysing weak interactions in big systems such as macrocyclic host-guest structures or ligand-protein complexes.