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dc.contributor.advisorWilson, Derek J.
dc.creatorLiuni, Peter Paul
dc.description.abstractThe analytical power and versatility of mass spectrometry can be enhanced by adding front-end devices, which provide additional functionality before, during or immediately after ElectroSpray Ionization (ESI). Such devices can include Ion mobility spectrometry (IMS) and Time-Resolved ElectroSpray Ionization (TRESI) which provide enhanced analysis of illicit compounds, protein folding, enzyme kinetics, and catalysis-linked dynamics. With respect to IMS, this work describes implementation of a hybrid Trace Compound Detector (TCD) system that combines IMS and MS to allow for rapid front-end mobility separation, followed by characterization and identification of analytical markers of seized opium by mass spectrometry. Ultimately, this device provides an avenue for rapid prosecution based on simultaneous detection and unambiguous identification of illicit drugs. TRESI is used to extend Mass Spectrometry (MS) to millisecond-timescale reaction studies. In the first instance, we combine TRESI with Travelling Wave Ion Mobility Spectrometry (TWIMS) to compare equilibrium and kinetic unfolding intermediates of cytochrome c, showing a high degree of correlation between all species populated under these substantially different regimes. We then combine TRESI with Hydrogen Deuterium Exchange (TRESI-HDX) to elucidate the relationship between structural fluctuations (conformational dynamics) of enzymes and their catalytic activity. The results of this work include a new model for catalysis-linked dynamics, in which the nature of the conformational landscape explored by an enzyme is independent of catalysis, but the rate at which the landscape is explored is enhanced for catalytically active species.
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.titleFront-End Methods For Enhancing the Analytical Power of Mass Spectrometry
dc.typeElectronic Thesis or Dissertation - Doctor of Philosophy
dc.subject.keywordsMass Spectrometry
dc.subject.keywordsElectrospray Ionization
dc.subject.keywordsIon Mobility
dc.subject.keywordsTrace Compound Detector
dc.subject.keywordsProtein Unfolding
dc.subject.keywordsKinetic Unfolding
dc.subject.keywordsEquilibrium Unfolding
dc.subject.keywordsCytochrome C
dc.subject.keywordsTraveling-Wave Ion Mobility Spectrometry
dc.subject.keywordsHydrogen/Deuterium Exchange
dc.subject.keywordsEnzyme Catalysis
dc.subject.keywordsKinetic Isotope Effect
dc.subject.keywordsDeuterium Isotope Effect
dc.subject.keywordsHeavy-Atom Isotope Effect
dc.subject.keywordsInternal Competition
dc.subject.keywordsYeast Alcohol Dehydrogenase
dc.subject.keywordsCatalysis-linked Dynamics
dc.subject.keywordsProtein Dynamics
dc.subject.keywordsConformer Selection
dc.subject.keywordsInduced Fit
dc.subject.keywordsGlobal Hydrogen/Deuterium Exchange.

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