Can Conformers Be Identified via Cyclic Ion Mobility Mass Spectrometry? Hexosamine Epimers Reveal Ultrastable Ring Structures

It was demonstrated how carbohydrate ring structures can be separated and identified using cyclic ion mobility mass spectrometry, making solid-, solution-, and gas-phase structures comparable. In addition, it was determined which collisional cross-section prediction or calculation method is the best suited for carbohydrates.

Rapid and accurate characterization of carbohydrate ring conformers in oligosaccharides, glycoproteins, foldamers, and other sugar-containing molecules remains a challenge. Here, a state-of-the-art, fine-tuned cyclic ion mobility mass spectrometry (cIM-MS) method is presented to examine and separate ring conformers of sugar moieties at the μg-ng scale without purification. We compared ring structures obtained from X-ray crystallography (solid phase), nuclear magnetic resonance spectroscopy (NMR) (solution phase), and cIM-MS (gas phase) to assign conformational motifs. We performed detailed gas-phase conformational calculations, along with experimental and theoretical collisional cross-section (CCS) measurements using various software tools, to identify the most accurate prediction method for carbohydrates. Our analysis revealed that the current CCS calculation tools require further refinement for reliable application to sugars. Thus, the combination of experimental and theoretical methods holds strong potential for confident sugar conformation assignment in the future.

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