Charge Inversion Ion/Ion Reactions for Separations of Isomers by Ion Mobility/Mass Spectrometry: Oligosaccharides

Various ion mobility-based separation techniques and instruments have been recently developed to increase the operational resolution of ion mobility separations, especially of isomers and isobars. In addition to developments in instrumentation, different covalent and noncovalent derivatization techniques have helped achieve effective separations by magnifying minor differences in collision cross section. Among these methodologies is host-guest complex formation and, a new development presented herein, charge inversion ion-ion reactions coupled to ion mobility separations. We used these methods to enable formation of complexes between isomeric deprotonated oligosaccharides and alkaline earth metals (in solution) and alkaline earth metal-tris-phenanthroline complexes (in vacuo), observing shifts in ion mobility arrival times for the charge inversion reaction products as well as unique mobility fingerprints indicative of high resolution separations of anomers of disaccharides. For example, we have demonstrated separations between reducing disaccharides such as lactose and lactulose and nonreducing disaccharides. We also observed separations based on the hexose/pentose configurations of the isomers. These results suggest the potential for ion/ion reactions to enable isomer separation of biomolecules from various compound classes using IM-MS.