Date of Award

12-2017

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Committee Member 1

R. Graham Cooks

Committee Member 2

Mary Wirth

Committee Member 3

Philip Low

Committee Member 4

David Thompson

Abstract

Chemical derivatization is the act of taking an analyte and transforming it into something with more desirable properties, typically for analytical purposes. In the cases presented here, the desirable properties are those which increase the ionization efficiency of the species of interest or those which facilitate the discrimination of isomers. Nanoparticles are often utilized in biological assays, but unless they are made of metal such that they can be ionized directly by inductively coupled plasma (ICP) ionization, they are undetectable by mass spectrometry. Surface functionalization of silica nanoparticles (SiNPs) facilitates the reversible binding of highly ionizable molecules which can serve as reporters for the presence of the particle. This constitutes chemical derivatization. In this dissertation, the synthesis of imidazolium salts for use as chemical derivatization reagents (mass labels) is reported. They were designed to be synthesized quickly and cheaply and bind reversibly to amine and diol functionalized nanoparticles. The “pre-charged” (imidazolium) nature of the labels facilitates excellent limits of detection (1 nM). Binding and release of the mass labels from nanoparticles is demonstrated and analysis of the loading and release efficiency is conducted. Isobaric amino acids in the backbone of a peptide are difficult to determine. The prime example of a problematic isobaric pair of amino acids is the coding aspartic acid (Asp) and the product of its post-translational modification, isoaspartic acid (isoAsp). Reported here is the use of a common reagent which binds carboxylic acids, substituted carbodiimide, to determine the

percentage of isoAsp in a sample of peptide. The carbodiimide is added to a solution of the peptide and it binds the carboxylate of the Asp or isoAsp residue. The resulting acylisourea (AiU) is ionzed and, in the gas phase, it rearranges via a 1-3 acyl shift to yield an N-acylurea (NAU). The AiU and NAU yield different fragment ions and so even though they are isobaric, they can be differentiated via collision induced dissociation (CID) product ion mass spectrometry. Importantly, the AiU derived from isoAsp rearranges more slowly to NAU than the AiU from derived from Asp. The rearrangement occurs on the timescale of the MS experiment (milliseconds) and so can be affected by the residence time of ions in the ion trap, the bandwidth of the isolation waveform, the potential offset applied to the transfer optics in the high-pressure region of the atmospheric pressure interface and the amplitude of the activation waveform. Saturated alkanes are a third example of analytes which pose a problem to mass spectrometry. They are completely inaccessible to spray-based ionization methods and often require specialized equipment or niche methods for ionization. Field ionization persists as the gold-standard in hydrocarbon ionization and atmospheric pressure chemical ionization (APCI) continues to develop in the field. Typical products of APCI of saturated hydrocarbons are hydride abstraction ([M-H]+), nitric oxide addition ([M+NO]+) or electron abstraction (M+.). This dissertation reports the chemical derivatization of saturated hydrocarbons by selective fixation of nitrogen (to generate ions of the formula [M+N]+) or oxygen (to generate ions of the formula [M+O-H]+). The standard Waters APCI-Gas Chromatography (APGC) ion source was used to affect this chemistry. The oxidation process was shown to be regioselective and energetic enough to induce C-C bond cleavage. The off-line collection of ketones and aldehyde fragments of those ketones is reported. Subsequent analysis of the collected species shows that even outside of the mass spectrometry experiment, the chemistry is regioselective. The ion chemistry leading to

oxidation is elucidated as an ion/molecule reaction between charged hydrocarbons and neutral ozone. Spray-based mass spectrometry has yielded interesting insights into the acceleration of reaction rates at the interface between small charged droplets and air. Other developments have included accelerated reactions in thin films. The phase of the reaction at the point of acceleration is explored in this dissertation by utilizing the Fischer Indole Synthesis under conditions which produce different products depending on the phase in which the reaction takes place. Reaction acceleration has typically been conducted on the small-scale. Production of milligrams of material per hour has been demonstrated with spray-based ionization sources but this scale still does not represent synthetically useful quantities. Discussed herein is the scale-up of the accelerated Claisen-Schmidt and Katritzky reactions as well as the acceleration of ester hydrolysis and imine formation in a rotary evaporator. The Suziki reaction is also demonstrated to undergo reaction acceleration at the interface of chloroform and water; a biphasic system commonly encountered in a separating funnel during the normal workflow of the synthetic organic chemist.

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