Theoretical study of the interaction of nonactin with Na+, K+, and NH

In an attempt to account for the preferential binding to nonactin of K+ relative to Na+, theoretical computations are performed using the intermolecular interaction energies of the ionophore with the two cations. Both K+ and Na+ liganding conformations are considered, and an evaluation is made of the intramolecular energy expenditure caused by the reduction of the size of the cavity. The energy balance for the complexation of the two cations computed by taking into account the cation–ionophore interactions, the interactions between the liganding groups, as well as the desolvation enthalpies of the cations in methanol, favors K+ over Na+ by 4 to 5 kcal/mol, in fair agreement with the difference in the measured enthalpies of binding. The binding of NH to nonactin is also investigated.