Understanding the Interplay of Dispersion, Charge Transfer, and Electrostatics in Noncovalent Interactions: The Case of Bromine–Carbonyl Short Contacts

We have performed a combined structural and computational analysis of short contacts between bromine and the carbon atom of a carbonyl group. Surprisingly, 9% of such contacts are arranged in such a way that the positively charged regions of the two atoms involved, i.e., Br and C, are in close contact, so the interaction geometry cannot be predicted in terms of molecular electrostatic potential maps. Remarkably, despite this like-like electrostatic configuration, the interaction energies associated with these contacts are attractive and considerably large (ca. 1 kcal/mol). Comprehensive energy decomposition analysis and natural bond orbital analysis have allowed us to unveil the physical origin of these interactions, which arise from a precise balance between steric factors (Pauli and electrostatics), dispersion, and charge transfer. These results reinforce the idea of noncovalent interactions as a more or less subtle combination of attractive and repulsive forces rather than a “purely electrostatic” or a “purely orbital” process and open the way to explore new types of interactions beyond the electron density holes model.