The Nature of K+/Crown Ether Interactions: A Hybrid Quantum Mechanical-Molecular Mechanical Study

We present a hybrid quantum mechanical/molecular mechanical (QM/MM) molecular dynamics study of dimethyl ether (DME) and 18-crown-6 (18c6) interacting with K[sup +]. The QM/MM method employs the semiempirical AM1 method to describe the ethers, the MM parametrization of Dang for K[sup +], and the MM SPC/e model for H[sub 2]O. We parametrize the interaction Hamiltonian to the binding energies and optimized geometries for K[sup +]/DME using ab initio HF and MP2/6-31+G* results. The resulting QM/MM model describes the polarization response of both free DME and K[sup +]-complexed DME well. The QM/MM model gives good agreement with the experimental and ab initio structures for K[sup +]/18c6. We calculate gas-phase K[sup +]/18c6 binding energies of [minus]70.2 and [minus]72.0 kcal/mol with the QM/MM and MP2/6-31+G* (CP corrected) methods, respectively. Our simulation results for K[sup +]/18c6 in H[sub 2]O show that the most probable K[sup +]/18c6 center-of-mass displacement is 0.25 [angstrom], in marked contrast to previous molecular dynamics results of Dang and Kollman. Our result is consistent with K[sup +] having an optimal [open quotes]fit[close quotes] for the cavity of 18c6. Still, we find that K[sup +] retains significant solvent accessibility coordinating two H[sub 2]O molecules, on average, in the K[sup +]/18c6 simulation. 81 refs., 13 figs., 4 tabs.