THE NATURE OF K-ETHER INTERACTIONS - A HYBRID QUANTUM MECHANICAL-MOLECULAR MECHANICAL STUDY( CROWN)

We present a hybrid quantum mechanical/molecular mechanical (QM/MM) mo lecular dynamics study of dimethyl ether (DME) and 18-crown-6 (18c6) i nteracting with K+. The QM/MM method employs the semiempirical AM1 met hod to describe the ethers, the MM parametrization of Dang for K+, and the MM SPC/e model for H2O. We parametrize the interaction Hamiltonia n to the binding energies and optimized geometries for K+/DME using ab initio HF and MP2/6-31+G results. The resulting QM/MM model describe s the polarization response of both free DME and K+-complexed DME well . The QM/MM model gives good agreement with the experimental and ab in itio structures for K+/18c6. We calculate gas-phase K+/18c6 binding en ergies of -70.2 and -72.0 kcal/mol with the QM/MM and MP2/6-31+G (CP corrected) methods, respectively. Our simulation results for K+/18c6 i n H2O show that the most probable K+/18c6 center-of-mass displacement is 0.25 Angstrom, in marked contrast to previous molecular dynamics re sults of Dang and Kollman. Our result is consistent with K+ having an optimal ''fit'' for the cavity of 18c6. Still, we find that K+ retains significant solvent accessibility coordinating two H2O molecules, on average, in the K+/18c6 simulation. The simulation average polarizatio n energy for 18c6 interacting with both K+ and the H2O solvent is -14. 9 kcal/mol, which is 17% of the total electrostatic interaction energy . This result underscores the potential importance of QM in describing the solution chemistry of ion-macrocycle interactions. Our study is t he first simulation of crown ethers that explicitly incorporates QM in the force field.