Conformational Study of α‐ N ‐Acetyl‐D‐Neuraminic Acid by Density Functional Theory

The stable structures of alpha-N-acetyl-D-neuraminic acid (Neu5Ac alpha) in the gas phase were studied at the B3LYP level of theory using 6-31G(d,p) and 6-31++G(d,p) basis sets. They are classified into five types according to the patterns of the intramolecular hydrogen bond formations. One of the stable structures had intramolecular hydrogen bond network of O9HO9 (...) O8H O-8 ... O=C-1 -O-1 H-O1 and O-7 HO7 ...O=CHN-C-5 similar to the crystal structure of Neu5Ac-alpha-methyl glycoside methyl ester. The stable structures of Neu5Ac alpha are reasonable for the following sialooligosaccharide ligand studies with respect to the relationship between OH group orientations and intramolecular hydrogen bond formations. The barrier heights for isomerizations between the stable structures were computed to be 2.8 to 6.7 kcal/mol at the B3LYP/6-31++G(d,p)//B3LYP/6-31G(d,p) level, which are basic factors for the conformational behavior of Neu5Ac alpha before its interactions with receptors. We also calculated Neu5Ac alpha-4 or 5-water complexes to take account of the solvent effect on the intramolecular hydrogen bonds in the stable structures. Consequently, the structures of Neu5Ac alpha in the complexes are similar to each other, which is consistent with the known NMR data. Thus, the optimum Neu5Ac alpha-water complexes are some of the reasonable pseudohydrous Neu5Ac alpha.