CONFORMATIONAL-ANALYSIS OF CROWN-ETHERS .1. 12-CROWN-4

An exhaustive conformational search of 12-crown-4 was performed with t he MM3 program. The results of this search are discussed with respect to available experimental data. Conformers that have been observed in crystal structures are (i) found to be among the lowest energy conform ers (within 2 kcal mol(-1) of the global minimum) and (ii) the structu ral features are well reproduced by the model. After correction for sy mmetry and mixing, relative free energies indicate that, in non-polar solvents, 12-crown-4 consists of a mixture of conformers with four con formers that account for over 90% of the total. The most highly popula ted conformer has not previously been reported. Comparison of MM3 resu lts with those of ab initio SCF calculations show a good agreement wit h the relative order of conformer stability for the six lowest energy conformers. Comparison of MM3 results with those of other force field models (MM2, AMBER, and WBFF) reveals that conformational search resul ts on 12-crown-4 are highly force field dependent and indicates that c are is required both in the choice of a force field model and in the i nterpretation of the calculation results.