Thesis (Ph. D.)--University of Wisconsin--Madison, 1961. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 138-143).

[No abstract submitted] / Science, Faculty of / Chemistry, Department of / Graduate

The interaction of nitrogen oxides N₂O, NO, N₂O₃, NO₂(N₂O₄) and N₂O₅ and the oxyhalides NOC1 and NO₂C1 with peroxydisulphuryldifluoride S₂O₆F₂ and bromine (1) fluorosulphate is studied under various conditions. The solid compounds NOSO₃F and NO₂SO₃F obtained were investigated via vibrational spectroscopy and solution studies. The non-spherical cations are found to cause a splitting of the E modes in S0₃F⁻ ion. Subsequently a whole range of fluoro complexes with nitrogen heterocations were studied and their vibrational spectra recorded. These include the cations NO⁺ , NO₂⁺ , N₂F₃⁺ and ONF₂⁺ and the anions AsF₆⁻ , SbF₆⁻, Sb₂F₁₁⁻ and SnF₆²⁻ . Noticeable anion-cation interaction appears to be absent for these compounds even though some minor departures from ideal behaviour are noted such as the splitting of degenerate modes for the octahedral anion (e.g. v₅F₂g). Vibrational frequencies for the N₂F₃⁺ and ONF₂⁺ cations have been assigned. The vibrational spectra of covalent fluorosulphates such as halogen fluorosulphates (where Hal = F, C1, Br), Br(0S0₂F) ₂⁻, CF₃S0₃F, NF₂SO₃F and S₂O₆F₂ are recorded. The halogen fluorosulphates have Cs symmetry, whereas C₂ symmetry is indicated for S₂O₆F₂. Finally ¹⁴N chemical shifts of some nitrogen-oxygen and halogen compounds have been measured and reported. It is found that the variation in the chemical shifts of these compounds is either due to the changes in the orbital angular momentum, or to the presence of low lying excited states or to a combination of both these effects. / Science, Faculty of / Chemistry, Department of / Graduate

Pyrolysis oil has shown potential as an environmentally-friendly petroleum replacement for the production of fuel and chemicals. Also, the use of waste materials in the production of pyrolysis oil alleviates concerns associated with waste disposal. However, there are still challenges in application of pyrolysis oil as fuel and chemicals due to its convoluted composition and properties that make it incompatible with petroleum. Although analyses have been conducted to explore the composition of pyrolysis oils, complete and in-depth characterizations are required for efficient utilization. The work presented here utilizes chromatographic separations and multiple analysis methods to explore the complexity of pyrolysis oils and the differences between samples. The composition of pyrolysis oil is highly dependent on the material used for production. Plant and food materials (biomass) result in oils that are highly oxygenated causing high acidity and viscosity. Pyrolysis of plastic material results in an oil composed of paraffinic hydrocarbons with low oxygen content. When biomass and plastics are mixed in municipal waste, the pyrolysis oil shows a composition with characteristics of both starting components; lower aromaticity than biomass pyrolysis oils and higher oxygen content than plastic pyrolysis oils. Characterization of these different pyrolysis oils requires complementary, targeted analyses for complete coverage of all compositions in each unique sample. The high resolution and mass accuracy of Fourier transform ion cyclotron resonance mass spectrometry provides elemental formulas for the thousands of components within a pyrolysis oil. This method is particularly useful for the polar and high molecular weight species that are not compatible with gas chromatography. In contrast, gas chromatography is beneficial for the analysis of volatile components and provides structural information based on retention time. Infrared spectroscopy provides bulk functional information of an oil, and is especially helpful in identifying oxygen functionalities. To further explore the complexity of pyrolysis oils, solid phase extractions reduce complexity and allow for analysis of targeted chemistries without interference. Extractions also provide functional information based on the interaction of species within the sample with the stationary phase. Combination of methods in the analysis of both biomass- and municipal waste-derived pyrolysis oils provides a molecular level understanding of their compositions and properties, illuminating efficient applications for these oils. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Spring Semester 2018. / April 11, 2018. / Includes bibliographical references. / Alan G. Marshall, Professor Directing Dissertation; Jeffery P. Chanton, University Representative; Michael Roper, Committee Member; John Dorsey, Committee Member; Geoffrey Strouse, Committee Member.

Mass spectrometry (MS) has become an important analytical method for proteomic research due to its high mass accuracy, resolution, and selectivity. Even though the traditional bottom-up MS-based method is still a widespread routine for proteomic analysis, middle- and top-down approaches should provide more comprehensive characterization of proteins isoforms and post-translational modifications (PTMs) due to their capabilities of maintaining the connectivity between modifications. The Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer equipped with multiple efficient fragmentation techniques offers the ultrahigh mass accuracy and resolution to enable separation and assignment of overlapped precursor and fragment spectral peaks from extremely complex spectra without ambiguity, which gives us great advantages in middle- and top-down MS-based proteomic analysis. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Fall Semester 2017. / November 6, 2017. / FT-ICR, LC-MS, Mass spectrometry, Middle-down, Proteomics, Top-down / Includes bibliographical references. / Alan G. Marshall, Professor Directing Dissertation; Hengli Tang, University Representative; John G. Dorsey, Committee Member; Wei Yang, Committee Member.

The work in this dissertation presents a chiral separation method for the quantitative measurement of primary amines secreted from murine islets of Langerhans along with whole brain tissue and astrocytes. Primary amines, including amino acids, can have a chiral center which leads to nomenclature of the resulting enantiomers, L- or D-. Most alpha amino acids exist in either form, however, prior to the 1980’s D-amino acids (DAAs) were thought to not be utilized by cells.1 Of the alpha amino acids, D-serine (D-Ser)2, D-alanine (D-Ala)3,4, and D-aspartate (D-Asp)5,6, to name a few, have been identified throughout the body in considerably lower concentrations to the corresponding enantiomer. Even at low concentrations, DAAs are important to the overall homeostasis of the mammalian body. For example, D-Ser can activate the Gly binding site on N-methyl-D-aspartate receptors (NMDARs). D-Ser appears throughout the brain in varying concentrations depending on the region.7,8 Unfortunately, detection of the D-enantiomers is difficult when the sheer abundance of the L-enantiomer is considered. Several methods have monitored primary amines from numerous biological systems, including murine islets of Langerhans, whether directly or indirectly.9-14 In recent years, direct methods for monitoring cellular content have gained some ground in effort to have quantitative methods to measure chiral amines. Direct measurements of chiral amines would elucidate the roles of DAAs better compared to the indirect methods that require assumptions about pathways or signaling mechanisms. In this work, the optimized separation conditions utilized four internal standards to quantify 17 primary amines, of which were 5 D-amino acids, with limits of detection (LOD) ranging from 0.3 nM to 8 nM. The normalized migration times had relative standard deviations (RSD) less than 0.6% and the majority of the normalized peak areas were less than 10% RSD. The effects of glucose were tested on small batches of islets and a small shoulder corresponding to the same migration time as D-Ser standard was observed under high glucose. While the islet samples did not yield any D-amino acid peak, other tissues are known to contain numerous D-amino acids such as whole brain tissue. Utilizing the optimized chiral separation method, changes in D-Ser secretion and content from three different brain regions under two conditions were investigated. D-Ser is proposed to be in lower concentrations, secreted or content, in murine brains after identified with the status condition compared to the non-status brains. Samples were treated in the same manner as the islet samples with one caveat, β-Ala was no longer considered an internal standard due to its presence in the samples. The chiral separation method was capable of observing D-Ser in most of the samples, which was identified through the use of D-Ser standard spikes and D-amino acid oxidase (DAAO) to eliminate of the peak in question. The role of pure populations of astrocytes has yet to be fully examined in relation to the effects of drug abuse, specifically the direct effect of D-Ser concentration in cellular content. Due to differences in astrocytic populations based on brain region, a different set of three brain regions were selected for the next experiment. Content from whole brain regions from the hippocampus, cortex, and olfactory bulb were examined utilizing the optimized chiral separation method for the presence of D-Ser. To elucidate if astrocytes contained D-Ser in the absence of neurons, cultures of only astrocytes and co-cultures of astrocytes with neurons from the previously mentioned regions were stimulated with high potassium to induce release of cellular content. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / 2019 / September 10, 2019. / capillary electrophoresis, Chiral, D-amino acids, separation / Includes bibliographical references. / Michael G. Roper, Professor Directing Dissertation; Paul Trombley, University Representative; Yan-Yan Hu, Committee Member; Geoffrey Strouse, Committee Member.

One of the grand challenges in the field of human health is to understand the structure-function relationship of biological molecules. To date, there exist many types of low and high resolution methods for interrogating the structure of biological monomeric and assembly systems. No one structural technique is up to the challenge in elucidating the detailed three dimensional structure of every analyte of interest. A culmination of structural data collected by an assortment of methods is the only approach in overcoming the diverse limitations that inevitably plague each technique. Ion mobility mass spectrometry (IMS-MS) certainly occupies an area in the spectrum of structural elucidation platforms. IMS-MS has certain advantages other techniques that make it a powerful tool for studying the structure of biological complexes. Trapped ion mobility spectrometry (TIMS) is a recently developed and commercialized high resolution ion mobility technique. TIMS as a new method must be validated in its ability to probe the biologically relevant structures of biological molecules and their assemblies. My work in the Bleiholder lab began with working on a project that showed for the first time that native like conformers of the protein ubiquitin could be retained during the course of a TIMS analysis. The remainder of this document seeks to continue to develop TIMS as a useful tool for structural biology. Chapter one gives a brief and general overview of some of the structural methods available to date, and presents some of the details related to ion mobility and TIMS. Chapter two shift from preserving monomeric to multimeric systems in TIMS. We show there that inadvertent fragmentation leading to structural artefacts can be overcome. Chapter three shows as a proof of concept that tandem-TIMS can perform CID of proteins up to ~18 kDa. We show that TIMS-CID-TIMS can not only provide sequence coverage similar to other mass spectrometry platforms, but that it also can sample conformational differences between fragments of the same m/z ratio. Chapter four exhibits the ability of tandem-TIMS to thermally unfold the protein ubiquitin in the electrospray source. Chapter 5 seeks to characterize the trapping efficiency of the TIMS analyzer and shows ions can be retained for upwards of 15 seconds. Finally chapter six provides a conclusion and future direction. Additional details in the aforementioned chapters are found in the appendices. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Summer Semester 2018. / July 19, 2018. / analytical chemistry, Ion mobility, mass spectrometry, structural biology, trapped ion mobility / Includes bibliographical references. / Christian Bleiholder, Professor Directing Dissertation; William Landing, University Representative; Alan Marshall, Committee Member; Michael Shatruk, Committee Member.

Metal complexes of meso-dimercaptosuccinic (DMSA) acid were studied by potentiometric and infrared methods. The coordination sites were found to be metal dependent. In the cases of Pb²⁺ and Cd²⁺, one oxygen and one sulfur act as donors; in the case of Hg²⁺, two sulfur atoms act as donors. The solubilities of the chelates were found to be pH dependent. When the uncoordinated sulfhydryl and carboxylic acid groups dissociate, the chelates dissolve and remain in aqueous solution. In the case of racemic-DMSA, two types of Pb²⁺ chelates were isolated: one in which rac-DMSA is coordinated to Pb²⁺ via one oxygen and one sulfur atom and the other in which the Pb²⁺ is coordinated via two sulfur atoms. The monomethyl ester and the dimethyl ester of meso-DMSA (MoMeDMSA and DiMeDMSA, respectively) were synthesized and their metal chelates with Pb²⁺, Cd²⁺, and Hg²⁺ studied. Esterification of meso-DMSA was found to change its biological properties. Both compounds, MoMeDMSA and DiMeDMSA, increased the biliary excretion of cadmium, which strongly suggests that the two derivatives of meso-DMSA enter the hepatocyte. The acid dissociation constants of the chelating agents and the uncoordinated groups in its metal chelates were determined. The results suggested that these acid-base properties in addition to the polarity of the chelating agent contribute to the effectiveness in the mobilization of intracellular deposits of cadmium. The dimethyl ester of DMSA was found to compete effectively with metallothionein for Cd²⁺ and Zn²⁺ ions by ¹H NMR spectroscopy. The structures of the metal chelates formed upon interaction of DiMeDMSA and Cd²⁺, or Zn²⁺ in solution at physiological pH were determined by multinuclear magnetic resonance spectroscopy. Mononuclear complexes were found to be formed. In these complexes, the metal ions are tetrahedrally coordinated by four thiolate groups from two DiMeDMSA molecules.

Several surfaces chemically modified with a variety of surface modifiers have been studied using chromatographic, nuclear magnetic resonance, and computational techniques. The goal was to determine the effect of modifier structure on the solvation, selectivity, and efficiency of chemical interactions occurring at chemically modified surfaces. Oleyldimethylchlorosilane has been synthesized and bonded to silica to determine the effect of a conformational change at the center of the chain on the behavior of the entire surface. It has been shown with these studies that the configuration of the modifier plays an important role in determining the selectivity of chemical interactions at modified surfaces. By comparison with phospholipid bilayers, of the structure, solvation and dynamics of alkylmodified silicas has been achieved. Octyldimethylsilyl- and octadecyldimethylsilyl-modified silicas have been further reacted with t-butyltrichlorosilane, t-butyldimethylchlorosilane and trimethylchlorosilane to determine both the utility of t-butyltrichlorosilane as an end-capping reagent and the extent to which solvation of the near-surface region affects the performance of these surfaces. It was shown that the orientation and solvation of modifiers at the near surface has a profound effect on the selectivity and efficiency of chemical interactions at the surface. Sepharose gels modified with iminodiacetic acid have been studied by titrimetric and spectroscopic means. A model compound has been synthesized and characterized in solution. The results have led to a better understanding of the behavior of chelating agents at sepharose surfaces and the effects of immobilization on the behavior of ligands at a surface. Finally, quartz crystalline microbalances modified with physisorbed polymer layers have been studied by correspondence analysis. In this case, it has been shown that the polymer backbone of the modifying agent plays an important role in determining the selectivity of the modified surfaces. Together these studies have led to a more complete understanding of the effects of the structure and solvation of modified surfaces on the selectivity and efficiency of chemical interactions occurring at those surfaces. These observations apply to interactions occurring at chromatographic stationary phases and to interactions at chemically modified surfaces in general.

The metallacyclopentadiene (DIPp)₂CITa(CCMe₃=CHCH=CCMe₃) (α, α') (DIPP=2,6-diisopropylphenoxide) is isolated from the 2 electron reduction of Ta(DIPP)₂CI₃(OEt₂) in the presence of excess Me₃CC=CH. The α, α' isomer represents the kinetic product of this reaction since it can be thermolyzed to produce (DIPP)₂CITa(CCMe₃=CHCCMe₃=CH) (α, β’). The reactivity of these two isomers toward the addition of ethylene and alkynes has been investigated and found to be driven primarily by steric effects with the less hindered α, β’ isomer showing a more comprehensive chemistry. The rearrangement of α, α' to α, β’ was followed through several kinetic and mechanistic studies. This data support a mechanism involving dissociation of the a,a' isomer to the metallacyclopropene, (DIPP)₂CITa(HC=CCMe₃), and free Me₃CC=CH. These intermediates then recouple to form the thermodynamic product, the α, β’ isomer. The reaction of TA(DIPP)₃Cl₂(OEt₂) with quinoline or 6-methylquinoline (HC) produces the ligand exchange product (η¹-HC)Ta(DIPP)₃CI₂, the 2 electron reduction of either of these products yields [η²-(N,C)-HC]Ta(DIPP)₃ which can be isolated as the phosphine complex [η²-(N,C)-HC]Ta(DIPP)₃(PMe₃) upon reaction with trimethylphosphine. The reaction of either [η²-(N,C)-quinoline]Ta(DIPP)₃ or [η²-(N,C)quinoline] Ta(DIPP)₃(PMe₃) with hydrogen both in the presence and absence of Pd/C produces 1,2,3,4-tetrahydroquinoline and 2,2'-bisquinoline. The production of these compounds implicates the η²-(N,C) bonding mode in selective hydrogenation of heterocycles and ortho functionalization. The reaction of Nb(NEt₂)₂CI₃ with two equivalents of LiNHMes (Mes=2,4,6- C₆H₂Me₃) followed by addition of pyridine produces Nb(NMes)₂CI(py)₂. The reaction of Nb(NEt₂)₂CI₃ with 6 equivalents of LiNHMes produces the first tris imido complex of group 5, [(THF)₂Li][Nb(NMes)₃(NHMes)]. Comparable chemistry is seen with Ta. [(THF)₂Li][Nb(NMes)₃(NHMes)] reacts with lithium alkyls under kinetic conditions to produce [(THF)2Li][Nb(NMes)₃(R)] (R=Me, ⁿSu, ᵗSu, Me₃SiCH₂). Under thermodynamic conditions, however, the reaction of [(THF)₂Li][Nb(NMes)₃(NHMes)] with ᵗBuLi yields the first tetrakis imido complex of group 5, [(THF)₄Li₃][Nb(NMes)₄]