Conformational analysis of crown ethers. Part 1. 12-Crown-4

Abstract

An exhaustive conformational search of 12-crown-4 was performed with the MM3 program. The results of this search are discussed with respect to available experimental data. Conformers that have been observed in crystal structures are 1. (i) found to be among the lowest energy conformers (within 2 kcal mol −1 of the global minimum) and 2. (ii) the structural features are well reproduced by the model. After correction for symmetry and mixing, relative free energies indicate that, in non-polar solvents, 12-crown-4 consists of a mixture of conformers with four conformers that account for over 90% of the total. The most highly populated conformer has not previously been reported. Comparison of MM3 results with those of ab initio SCF calculations show a good agreement with 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 results on 12-crown-4 are highly force field dependent and indicates that care is required both in the choice of a force field model and in the interpretation of the calculation results.