Cation−π and π–π Interactions in Aqueous Solution Studied Using Polarizable Potential Models

Polarizable potential models for the interaction of Li+, Na+, K+, and NH4+ions with benzene are parametrized based on ab initio quantum mechanical calculations. The models reproduce the ab initio complexation energies and potential energy surfaces of the cation−π dimers. They also reproduce the cooperative behavior of “stacked”, cation−π–π trimers and the anticooperative behavior of “sandwiched”, π–cation−π trimers. The NH4+model is calibrated to reproduce the energy of the NH4+–H2O dimer and yields correct free energy of hydration and hydration structure without further adjustments. The models are used to investigate cation−π interactions in aqueous solution by calculating the potential of mean force between each of the four cations and a benzene molecule and by analyzing the organization of the solvent as a function of the cation–benzene separation. The results show that Li+and Na+ions are preferentially solvated by water and do not associate with benzene, while K+and NH4+ions bind benzene with 1.2 and 1.4 kcal/mol affinities, respectively. Molecular dynamics simulations of NH4+and of K+in presence of two benzene molecules in water show that cation−π and π–π affinities are mutually enhanced compared to the pairwise affinities, confirming that the cooperativity of cation−π and π–π interactions persists in aqueous solution.