Computational study (MM and DFT) on the conformations of some aromatic crown ether rotaxane macrocycles

• An exhaustive conformational search and cluster analysis of conformations. • Comparative study with molecular mechanics and DFT. • Entropy term reorders the steric energy list of conformations. • The macrorings have the potential to allow threading of an axle molecular component. We examined the preferred conformations of several aromatic crown ether macrocycles containing dibenzo ( DB24C8 ( 1 ), BMP25C8 ( 2 ), BPP34C10 ( 3 )), dinaphtho ( 2/3DN30C10 ( 4 ), 1/5DN38C10 ( 5 )), diphenyl phenanthroline ( 6 ) or isophthalamide ( 7 ) groups in order to elucidate their preferred conformations and to test the performance of computational methods (molecular mechanics and DFT) in the description of the building blocks of some mechanically interlocked molecules. An exhaustive search for low energy conformations was carried out. The analyses of the geometries of the low-energy conformations of 1 – 7 revealed that all they have either preformed cavities for adopting substrates, or due to the high flexibility and easy deformability of the macrorings, they have the potential to allow threading of an axle-like molecular component as a slippage step in the formation of a rotaxane structure. Unexpectedly, for one of the macrorings, 4 , the geometries of the low-energy conformations differ significantly from the representative conformations of prima facie conformationally similar macrocycles. Contributions from the vibrational entropy term reorder the steric energy lists of conformations in some cases ( 1 , 2 , 4 , 6 ), compensating relative steric energies up to 0.9 kcal mol −1 . Cluster analysis of the molecular conformations was performed with examining the dependence of the results on the number of torsions for the clustering and the characteristic threshold distances, defining the clustering. All conformations with relative steric energies not exceeding 2.0 kcal mol −1 were examined also with the DFT method (M06-2X functional). In some cases ( 1 and 2 ) conformations with relative steric energies ca. 2.0 kcal mol −1 are with the lowest total energies in the corresponding DFT energy lists. These are conformations where the aromatic fragments are facing each other at short distance, ca. 5 Å. We are inclined to conclude that in such cases the DFT models used enhance the dispersion interactions at short distances.