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Final PhD Defense
April 18, 2019 @ 2:00 pm - 3:00 pm
Kelsey Morrison (Clowers Group) will present her final PhD defense.
INFLUENCE OF MULTIVALENT METAL CATIONS ON CARBOHYDRATE SEPARATIONS AND FRAGMENTATION PATTERNS VIA ION MOBILITY-MASS SPECTROMETRY
Carbohydrates and their polymeric form, oligosaccharides and glycans, occupy a corner of biopolymers that can be periodically overlooked in the shadow of proteins and nucleic acids, but are nonetheless essential for the survival of biological organisms. However, unlike other biological macromolecules, the array different of carbohydrate residues and glycans have largely homogeneous elemental compositions and are instead distinguished by variations in stereochemistry and branching patterns, which create more hurdles in separation and analysis of isomeric mixtures. Because this creates a scenario where complex biological samples may have a range of isomers that cannot be differentiated by mass analysis alone, incorporating ion mobility separations in front of mass spectrometry can provide another dimension of information to distinguish among glycan isomers. Yet another angle for enhancing glycan analysis withion mobility-mass spectrometry is by leveraging interactions between carbohydrate species and metal cations, which can form adducts that have altered gas-phase structures relative to bare protonated or deprotonated ions. In some situations, this can lead to exaggeration of the differences in effective size among isomers and thereby facilitate isomeric glycan separation in the drift time space.
This dissertation is focused on conveying the utility of metal-glycan interactions for improving the ion mobility-mass spectrometric analysis of carbohydrate species while also describing how some necessary complementary experiments were pursued concurrently. Of note, ultraviolet photodissociation (UVPD) with metal-enhanced fragmentation and Fourier multiplexing of ion mobility-ion trap mass spectrometry were found to contribute well to isomeric glycan mixture analysis. Divalent metal cations including select transition metals and alkaline earth metals were evaluated for their potential to enhance drift time separations, with transition metals proving particularly useful in this regard for mixture analysis. During the initial assessment of oligosaccharide analysis with divalent metal species, it was found that carbohydrate species will form both singly-charged monomeric metal-glycan adducts as well as doubly-charged dimeric metal-glycan adducts where both appear at the same m/z value. These dimeric species were subsequently scrutinized further for the potential to form heterodimeric metal-glycan dimers wherein two different isomeric glycans could form a single dimer during a mixture analysis without mobility separation and form chimeric mass spectra. Through a combination of isotopic labeling and ion mobility- mass spectrometry, it was shown that heterodimeric metal-glycan species can indeed form, and that mobility separation is vital for analysis of complex glycan mixtures.