INCORPORATION OF GAS PHASE ION/ION REACTION CHEMISTRIES AND ION PARKING INTO NATIVE MASS SPECTROMETRY

Production of multiply-charged ions, a hallmark of electrospray ionization, is advantageous for mass determination; however, for larger native complexes, closely spaced and overlapping charge states lead to congested mass spectra, hindering mass analysis. Furthermore, native ion signal can be distributed across multiple charge states, thereby reducing signal levels for the tandem mass spectrometry of any given charge state. Charge reduction via proton transfer reaction can reduce spectral overlap, and ion parking of a product ion can concentrate signal to fewer charge states. Subsequent ion-ion reactions can further reduce the charge, facilitating mass determination. Since ions have a fundamental secular frequency of motion rooted to m/z and trapping conditions, an applied auxiliary AC frequency can accelerate ions with a certain degree of selectivity. When applied during a proton transfer ion/ion reaction, ions with a distribution of charge states can be concentrated into a single charge state in a process referred to as ‘ion parking’. In this dissertation, I provide a demonstration of charge reduction strategies on proteins and protein complexes via proton transfer and multiply-charged ion attachment reactions. I also describe a general first-order forced-damped-harmonic-oscillator model for native ion parking in an electrodynamic quadrupole ion trap using a single supplementary dipolar AC frequency to inhibit the ion/ion reaction rate of a selected charge state of an analyte of interest. Lastly, I provide different applications combining proton transfer, ion parking, and then multiply-charged ion attachment to facilitate not only mass determination but also provide spectral separation of components from a mixture.