MOLECULAR DYNAMICS STUDY OF A NEW RIGIDIFIED 18-CROWN-6 DERIVATIVE USING A QM/MM METHOD

摘要

We present results of the first molecular dynamics study of a new rigidified 18-crown-6 derivative, recently synthesized by Li and Still. We refer to this new crown as s18c6, which contains a central 18-crown-6 core locked into a D-3d configuration by the addition of six exocyclic saturated hydrocarbon rings, two of which also contain a single exocyclic heteroatom (X), peripheral to the central cation binding ring. X can be either a hemiacetal (X = oxygen) or hemithioacetal (X = sulfur). The enhanced rigidity and the exocyclic heteroatoms are thought to be involved in the novel cation binding properties of s18c6 in aqueous solutions; it is more ionophoric than 18c6, and it is selective for Na+ over K+ when X = oxygen but is selective for K+ over Na+ when X = sulfur. In the present communication, we report results for the X = oxygen isomer of s18c6. We use a hybrid quantum mechanical/molecular mechanical (QM/MM) approach to study the solvation properties of the uncomplexed crown in H2O. The QM/MM method described here is based on our previous QM/MM study of K+/18c6 which employs the semiempirical AM1 method for s18c6 and the SPC/E model for H2O. Both AM1 and HF/6-31+G* optimized geometries give similar results for the gas-phase structure of s18c6. The ab initio results show that s18c6 has a slightly smaller cavity than 18c6 (5.681 vs. 5.802 Angstrom, respectively) based on the average transannular oxygen-oxygen distances. A 100-ps equilibrium molecular dynamics simulation shows that the s18c6 core remains in a rigid D-3d configuration. S18c6 avidly binds two solvent waters, one on either side of the macrocycle plane. The simulation average binding energy per bound water is -14.8 kcal/mol, which is greater than our previously reported result of -12.3 kcal/mol for H2O bound by 18c6. Both of the s18c6-bound waters maintain multiple hydrogen bonds to the oxygens of the macrocycle, and there is evidence for involvement of the exocyclic oxygens in this binding. (C) 1996 John Wiley & Sons, Inc. [References: 65]