Modeling Binding Selectivity of Xylene Isomers in Resorcin[4]arene-Based Organo- and Metallo-Cavitands

Binding of xylene isomers to two resorcin[4]arene-based water-soluble cavitands, one fully organic and one with palladium bridges, is investigated by means of a combination of molecular dynamics simulations and quantum chemical calculations. Experimentally, the metallo-cavitand binds all three isomers but shows a preference for p-xylene, while the organo-cavitand prefers o-xylene and shows no affinity for p-xylene. The cavitands are first characterized and compared in aqueous solution in the absence of guests using classical molecular dynamics simulations. This is followed by a study of the dynamics of the various host-guest complexes. Finally, density functional theory is used to calculate the relative binding free energies. The molecular dynamics simulations show that both host and guest exhibit extensive motions in the complexed state, and the density functional theory calculations yield accurate results on the relative binding free energies.