We performed FEP and MD simulations on enantiomeric complexes of seven 18-c
rown-6 ether compounds and a chiral protonated amine to obtain the free ene
rgy differences, and to elucidate the mechanism responsible for enantiosele
ctivity. The FEP calculation reproduced the experimental enantioselectivity
quite well. We partitioned the binding free energy in solution into the bi
nding free energy in the gas phase and the solvation energy, and discussed
the results. In the MD simulations, the detailed motion of host-guest compl
exes was monitored.