Cationized Carbohydrate Gas-Phase Fragmentation Chemistry

Abstract

We investigate the fragmentation chemistry of cationized carbohydrates using a combination of tandem mass spectrometry, regioselective labeling, and computational methods. Our model system is D-lactose. Barriers to the fundamental glyosidic bond cleavage reactions, neutral loss pathways, and structurally informative cross-ring cleavages are investigated. The most energetically favorable conformations of cationized D-lactose were found to be similar. In agreement with the literature, larger group I cations result in structures with increased cation coordination number which require greater collision energy to dissociate. In contrast with earlier proposals, the B -Y fragmentation pathways of both protonated and sodium-cationized analytes proceed via protonation of the glycosidic oxygen with concerted glycosidic bond cleavage. Additionally, for the sodiated congeners our calculations support sodiated 1,6-anhydrogalactose B ion structures, unlike the preceding literature. This affects the subsequent propensity of formation and prediction of B /Y branching ratio. The nature of the anomeric center (α/β) affects the relative energies of these processes, but not the overall ranking. Low-energy cross-ring cleavages are observed for the metal-cationized analytes with a retro-aldol mechanism producing the A ion from the sodiated forms. Theory and experiment support the importance of consecutive fragmentation processes, particularly for the protonated congeners at higher collision energies. Graphical Abstract ᅟ.

MALDI‐MS Analysis of Sucrose Using a Charcoal Matrix with Different Cationization Agents

“…A CID study of fragmentation of d ‐lactose with H 0 , Li + , and Na + reported similar observations. The larger cations required higher collision energies to dissociate the d ‐lactose . Larger cations were thought to have higher fragmentation energies because they have more coordinated oxygen atoms.…”

“…The size of cation additive and degree of sucrose fragmentation were found to be inversely related, so fewer sucrose ions fragmented when larger cation additives were used. It has been reported that higher collision energies are required to dissociate carbohydrates combined with larger cations, because these cations have more coordinated oxygen atoms . Our observations agree with the previous results, showing that heavier cations cleave fewer of the glycosidic bonds in the sucrose.…”

Direct Experimental Characterization of Glycosyl Cations by Infrared Ion Spectroscopy

“…Tandem mass spectrometry (MS/MS) can be employed to generate glycosyl cations in complete isolation, and their gas-phase fragmentation has been extensively studied. 10 − 14 Recently, the use of MS in combination with infrared (IR) ion spectroscopy has emerged as a powerful method to determine the gas-phase structures of molecular ions in MS/MS 15 − 20 and to probe glycan structure. 21 − 26 …”

Linkage Memory in Underivatized Protonated Carbohydrates

“…Protonated carbohydrates present additional challenges, as they can undergo rearrangement reactions, most notably migration of fucose during collision-induced dissociation (CID) 6 . This migration process is still under investigation [7][8][9] , and a general structural understanding of the even simple protonated carbohydrate systems is only now starting to emerge 10 . For intact glycoconjugates (i.e.…”