Cation-pi interactions play important roles in the stabilization of protein structures and protein ligand complexes. They contribute to the binding of quaternary ammonium ligands (mainly RNH3+ and RN(CH3)(3)(+)) to various protein receptors and are likely involved in the blockage of potassium channels by tetramethylammonium (TMA(+)) and tetraethylammonium (TEA(+)). Polarizable molecular models are calibrated for NH4+, TMA(+), and TEA(+) interacting with benzene, toluene, 4-methylphenol, and 3-methylindole (representing aromatic amino acid side chains) based on the ab initio MP2(full)/6-311++G(d,p) properties of the complexes. Whereas the gas-phase affinity of the ions with a given aromatic follows the trend NH4+ > TMA(+) > TEA(+), molecular dynamics simulations using the polarizable models show a reverse trend in water, likely due to a contribution from the hydrophobic effect. This reversed trend follows the solubility of aromatic hydrocarbons in quaternary ammonium salt solutions, which suggests a role for cation-pi interactions in the salting-in of aromatic compounds in solution. Simulations in water show that the complexes possess binding free energies ranging from -1.3 to -3.3 kcal/mol (compared to gas-phase binding energies between -8.5 and -25.0 kcal/mol). Interestingly, whereas the most stable complexes involve TEA(+) (the largest ion), the most stable solvent-separated complexes involve TMA+ (the intermediate-size ion).