π holes in water: Solvation of phenol, aniline, and p-nitrophenol substituted aromatics.

Intermolecular forces are the fundamental architects of supramolecular structure. From liquid miscibility to the formation of organic crystals and biological structures, subtle interplays of charge distribution determine the outcome. Aromatic rings are a key motif in organic chemistry that provide rigid and highly directional interactions in proteins and nucleic acids. The distribution of the aromatic delocalised π electrons is strongly modulated by the substituents, giving rise to complex charge patterns across the molecule that affect reactivity and intermolecular interactions. These patterns range from axial dipoles to localised "holes" in the delocalized π network. While increasingly well-understood in the solid state, their influence on solvation and miscibility in the liquid remains unknown. We exploited neutron total scattering and experimentally constrained Monte Carlo simulations to picture the solvation of three aromatics in water: phenol, aniline, and p-nitrophenol. We observe the expected strong classical hydrogen bonds between the water and the OH, NH2, and NO2 substituents. Out of the ring plane, the solvation of phenol and aniline is centred around perpendicular, non-classical OH···π interactions. By contrast, for p-nitrophenol, the presence of the electron-withdrawing nitro group enhances the overall molecular dipole, and introduces a pronounced π hole on the nitro group that significantly disrupts the out-of-plane solvation. The latter is dominated by a close O···N contact (3.44 Å) accompanied by longer O···centroid interactions (~4.00 Å) resulting from localized charge depletion in the ring. These interactions begin to explain the complex solubility behaviour of these systems and highlight the complexity of the solvation of organic molecules.