Glycosidic linkage, N-acetyl side-chain, and other structural properties of methyl 2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→4)-β-D-mannopyranoside monohydrate and related compounds

Abstract

The crystal structure of methyl 2-acetamido-2-deoxy-β-D-glycopyranosyl-(1→4)-β-D-mannopyranoside monohydrate, C15H27NO11·H2O, was determined and its structural properties compared to those in a set of mono- and disaccharides bearing N-acetyl side-chains in βGlcNAc aldohexopyranosyl rings. Valence bond angles and torsion angles in these side chains are relatively uniform, but C—N (amide) and C—O (carbonyl) bond lengths depend on the state of hydrogen bonding to the carbonyl O atom and N—H hydrogen. Relative to N-acetyl side chains devoid of hydrogen bonding, those in which the carbonyl O atom serves as a hydrogen-bond acceptor display elongated C—O and shortened C—N bonds. This behavior is reproduced by density functional theory (DFT) calculations, indicating that the relative contributions of amide resonance forms to experimental C—N and C—O bond lengths depend on the solvation state, leading to expectations that activation barriers to amide cis–trans isomerization will depend on the polarity of the environment. DFT calculations also revealed useful predictive information on the dependencies of inter-residue hydrogen bonding and some bond angles in or proximal to β-(1→4) O-glycosidic linkages on linkage torsion angles ϕ and ψ. Hypersurfaces correlating ϕ and ψ with the linkage C—O—C bond angle and total energy are sufficiently similar to render the former a proxy of the latter.