Monte Carlo Investigations of Selective Anion Complexation by a Bis(phenylurea) <i>p</i>-<i>tert</i>-Butylcalix[4]arene

Monte Carlo statistical mechanics simulations have been employed to elucidate the complexation of halide ions in chloroform by the bis(phenylurea) p-tert-butylcalix[4]arene of Scheerder et al. The calculations employed OPLS potential functions including new parameters for iodide ion. Gas-phase optimizations for the host−guest systems, as well as for halide−water and halide−urea complexes, were performed to characterize the structures of the complexes and to quantify the intrinsic binding affinities. The computations reveal that the gas-phase optimized structures of the complexes are largely maintained in chloroform solution, though there is a ca. 20 kcal/mol reorganization penalty for the host to achieve the binding geometry. Statistical perturbation theory was used to compute the relative free energies of binding for the halide ions with the calixarene in chloroform. The observed affinity order, Cl- > Br- > I-, was quantitatively well reproduced; however, in contrast to the experimental report of no complexation for F-, the simulations find that F- should bind with by far the greatest affinity among the halides. The possibility that interference by water in the experiments led to the observed lack of fluoride binding was explored through simulations of the halides with water molecules in chloroform. The results indicate that complexation of F- by two water molecules would be sufficient to overcome complexation by the bis-urea host.