Host‐guest preorganization and complementarity: A molecular mechanics and molecular dynamics study of cation complexes of a cyclic urea‐anisole spherand

Abstract

AbstractMolecular mechanics and molecular dynamics calculations were carried out in vacuo for 1 and for the complexes of 1 with alkali metal cations and t‐BuNH. The calculations identify perching and nesting conformations of the complexes not available from X‐ray data. For the Li+ −1 complex, the MD simulations identify a new global minimum not found by the molecular mechanics calculation. In general, the net favorable ion‐spherand complexation energy is due to the offset of the unfavorable reorganization energy of the spherand by the overwhelmingly favorable electrostatic component of the ion‐spherand interaction energy. The host is least preorganized for the binding of Li+ and, even in its complexed conformation, presents the least steric complementarity to this ion. The complexation energy becomes significantly more favorable due to a large increase in the electrostatic complementarity of the ion binding site when the spherand adopts its complexed conformation. Correction of the calculated complexation energy by the experimental free energy of ion aqueous desolvation leads to results in line with the findings of Cram and co‐workers that K+ is the most, and Li+ the least, favorably bound by 1.