Determining the structural preferences of dimannosides through the linkage constraint and hydrogen-bonded network

The fully random conformational search and the structural optimization of the dimannosides with α(1,2)-, α(1,3)- and α(1,6)-linkages have been investigated using the Monte–Carlo Multiple Minimum method with the MMFFs force fields and the high-level quantum mechanical calculations. During the two-level optimization, the regeneration of inter-ring hydrogen bonds can be achieved by the changes of glycosidic dihedral angles, which increasingly contributes to the conformational stability. Moreover, the formation of cooperative intra-ring hydrogen bonds could further lower the energies and produce the amalgamation of some categories. The results of lowest-energy structure demonstrated that cooperative intra- and inter-ring hydrogen bonds provide the key to gaining the structural stability. Particularly, the linkage site of dimannosides leads to the species diversity in inter-ring hydrogen bonds, which significantly restricts the favorable selection of glycosidic dihedral angles. Taken together, a three-step procedure based on understanding the linkage constraint, the driving force of inter-ring hydrogen bonds and the cooperative intra-ring hydrogen bonds is proposed to simply build up the favorable geometries for oligosaccharides, and its combination with density functional theory calculation has been successfully employed to predict the preferred conformations of β(1,4)-linked lactoside.