On the path to glycan conformer identification: Gas-phase study of the anomers of methyl glycosides of N-acetyl-d-glucosamine and N-acetyl-d-galactosamine

The methyl glycosides of N-acetyl-d-glucosamine (d-GlcNAc) and N-acetyl-d-galactosamine (d-GalNAc) have been used as model glycan analogs to study the effects of lithium cation binding on glycan structure in gas-phase experiments. Infrared multiple photon dissociation (IRMPD) spectra for the two Li+-complexed anomers of methyl-d-GlcNAc revealed a difference of 10 cm−1 between their respective carbonyl stretching band positions. A corresponding 11 cm−1 shift was observed for the two Li+-complexed anomers of methyl-d-GalNAc. Theoretical calculations indicate that the position of the methyl group (α and β, or axial and equatorial, respectively) on carbon 1 of the sugar and its close proximity to the carbonyl of the acetamido group on carbon 2 cause the average orientation of the carbonyl to change in order to minimize steric hindrance. This change in orientation is postulated to be the cause of the observed CO stretching band shift. The calculations also predict competitive binding of the lithium cation between two or more regions of d-GlcNAc and d-GalNAc. This is primarily due to differences in the spatial arrangement and orientation of lone pairs of electrons among the isomers, and stereochemical differences in hydrogen bonding. From an application point of view, differences in the infrared spectra of lithium adducts of acetamido sugars establish the value of variable-wavelength IRMPD as an alternative to fragmentation patterns in discriminating between these isomers.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (146 K)Download as PowerPoint slideHighlights► Wavelength shifts were seen in IRMPD spectra of anomers of Li+-N-acetyl-d-hexosamines. ► Similar shifts were predicted using the B3LYP/6-311++G(d,p) level of theory. ► Wavelength shifts can be used for anomeric differentiation of monosaccharide epimers. ► Significant, wavelength-dependent differences in IRMPD fragment ions were also seen for the isomers. ► Variable wavelength IRMPD provides another dimension for isomeric differentiation.