Use of ¹³C chemical shift surfaces in the study of carbohydrate conformation. Application to cyclomaltooligosaccharides (cyclodextrins) in the solid state and in solution

The anomeric carbon chemical shifts of free cyclomaltohexaose, -heptaose, -octaose, -decaose, and -tetradecaose (α-, β-, γ-, ε-, and η-cyclodextrin, respectively), and of α-cyclodextrin inclusion complexes, both in the solid state and in solution, were computed using ab initio ¹³C chemical shift surfaces for the D-Glcp-α-(1→4)- D-Glcp linkage as a function of the glycosidic bond 〈Φ,Ψ〉 dihedral angles. Chemical shift calculations in the solid state used 〈Φ,Ψ〉 angle pairs measured from cyclodextrin X-ray structures as input. For estimations in the liquid state two different approaches were employed to account for dynamic averaging. In one, the computed solid-state anomeric carbon chemical shifts for each cyclodextrin D-Glcp monomer were simply averaged to obtain an estimate of the ¹³C shifts in solution. In the other, chemical shifts for the anomeric carbons were determined by averaging back-calculated ¹³C shift trajectories derived from a series of 5ns molecular dynamic simulations for the oligosaccharides with explicit representation of water. Good agreement between calculated and experimental ¹³C shifts was found in all cases. Furthermore, our results show that the ab initio ¹³C chemical shift surfaces are sufficiently sensitive to reproduce the small variations observed for the anomeric ¹³C shifts of the different cyclodextrin D-Glcp units in the solid state with excellent accuracy. The use of chemical shift surfaces as tools in conformational studies of oligosaccharides is discussed.