Fragmentation mechanisms of protonated cyclodextrins in tandem mass spectrometry

Tandem mass spectrometry has found widespread application as a powerful tool for the characterization of linear and branched oligosaccharides. Though the technique has been applied to the analysis of cyclic oligosaccharides as well, the underlying fragmentation mechanisms have hardly been investigated. This study focuses on the mechanistic aspects of the gas-phase dissociation of protonated β-cyclodextrins. Elucidation of the dissociation mechanisms is supported by tandem mass spectrometric experiments and by experiments on di- and trimethylated cyclodextrin derivatives. The fragmentation pathway comprises the linearization of the macrocyclic structure as the initial step of the decomposition, followed by the elimination of glucose subunits and the subsequent release of water and formaldehyde moieties from the glucose monomer and dimer fragment ions. Linearization of the macrocycle occurs due to proton-driven scission of the glycosidic bond adjacent to carbon atom C1 in conjunction with the formation of a new hydroxy group. The resulting ring-opened structure further decomposes in charge-independent processes forming either zwitterionic fragments, a 1,4-anhydroglucose moiety, or a new macrocyclic structure, that is lost as a neutral, and an oxonium ion. Since the hydroxy group formed at the ring-opening site can be regarded as the non-reducing end of the linearized structure, the fragment ion nomenclature commonly used for linear and branched oligosaccharides, which relies on the designation of a reducing and a non-reducing end, can also be applied to the description of fragment ions derived from cyclic structures.