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.