Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 111-120). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 101-107). Also available on the Internet.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 71-79).

Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 112-113). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 114-126). Also available on the Internet.

Thesis (Ph. D.)--Institute of Paper Chemistry, 1940. / Includes bibliographical references (p. 74-75).

Thesis (Ph. D.)--University of Missouri-Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 101-107). Also available on the Internet.

Abstract Fluorescent molecules used as detection probes and sensors provide vital information about the chemical events in living cells. Despite the large variety of available fluorescent dyes, new improved fluorogenic systems are of continued interest. The Diaryl-substituted Maleimides (DMs) exhibit excellent photophysical properties but have remained unexplored in bioscience applications. Herein we present the identification and full spectroscopic characterization of 3,4-bis(2,4-difluorophenyl)-maleimide and its first reported use as a donor component in Forster resonance energy transfer (FRET) systems. The FRET technique is often used to visualize proteins and to investigate protein-protein interactions in vitro as well as in vivo. The analysis of the photophysical properties of 3,4-bis(2,4-difluorophenyl)-maleimide revealed a large Stokes shift of 140 nm in MeOH, a very good fluorescence quantum yield in DCM (Ffl 0.61), and a high extinction coefficient ε(340) 48,400 M-1cm-1, thus ranking this molecule as superior over other reported moieties from this class. In addition, 3,4-bis(2,4-difluorophenyl)-maleimide was utilized as a donor component in two FRET systems wherein different molecules were chosen as suitable acceptor components - a fluorescent quencher (DABCYL) and another compatible fluorophore, tetraphenylporphyrin (TPP). It has been demonstrated that by designing a FRET peptide which contains the DM donor moiety and the acceptor (quencher) motif, a depopulation of the donor excited state occurred via intermolecular FRET mechanism, provided that the pairs were in close proximity. The Forster-Radius (R0) calculated for this FRET system was 36 % and a Forster-Radius (R0) of 26 % was determined for the second FRET system which contained TPP as an acceptor. The excellent photophysical properties of this fluorophore reveal a great potential for further bioscience applications. The 3,4-bis(2,4-difluorophenyl)-maleimide fluorescent moiety was also implemented in an alternative application targeting the enzyme carbonic anhydrase (CAs) are metalloenzymes that regulate essential physiologic and physio-pathological processes in different tissues and cells, and modulation of their activities is an efficient path to treating a wide range of human diseases. Developing more selective CA fluorescent probes as imaging tools is of significant importance for the diagnosis and treatment of cancer related disorders. The kinetic TGS approach is an efficient and reliable lead discovery strategy in which the biological target of interest is directly involved in the selection and assembly of the fragments together to generate its own inhibitors. Herein, we investigated whether the in situ click chemistry approach can be implemented in the design of novel CA inhibitors from a library of non-sulfonamide containing scaffolds, which has not been reported in the literature. In addition, we exploit the incorporation of the (recently reported by us) fluorescent moiety 3,4-bis(2,4-difluorophenyl)-maleimide) as a potential biomarker with affinity to CA, as well as two coumaine derivatives representing a newly discovered class of inhibitors. The screening of a set of library with eight structurally diverse azides AZ1-AZ8 and fifteen functionalized alkynes AK1-AK12 led to the identification of 8 hit combinations among which the most prominent ones were those containing the coumarine and fluorescent maleimide scaffolds. The syn- and anti-tirazole hit combinations, AK1AZ2, AK1AZ3, AK4AZ2, and AK4AZ3 were synthesized, and in a regioisomer-assignment co-injection test it was determined that the enzyme favored the formation of the anti-triazoles for all identified combinations. The mechanism of inhibition of these triazoles was validated by incubating the alkyne/azide scaffolds in the presence of Apo-CA (non-Zn containing) enzyme. It was demonstrated that the Zn-bound water/hydroxide was needed in order to hydrolyze the coumarins which generated the actual inhibitor, the corresponding hydroxycinnamic acid. The time dependent nature of the inhibition activity typical for all coumarine-based inhibitors was also observed for the triazole compounds whose inhibition constants (Ki) were determined in two independent experiments with pre-incubation times of 3 and 25 minutes, respectively. It was observed that the lower Ki values were determined, the longer the pre-incubations lasted. Thus, a novel type of coumarin-containing triazoles were presented as in situ generated hits which have the potential to be used as fluorescent bio-markers or other drug discovery applications. The proteins from the Bcl-2 family proteins play a central role in the regualtion of normal cellular homeostasis and have been validated as a target for the development of anticancer agents. Herein, in a proof-of-concept study based on a previous kinetic TGS study targeting Bcl-XL, it was demonstrated that a multi-fragment kinetic TGS approach coupled with TQMS technology was successfully implemented in the identification of known protein-protein modulators. Optimized screening conditions utilizing a triple quadruple mass spectrometer in the Multiple Reaction Monitoring (MRM) mode was demonstrated to be very efficient in kinetic TGS hit identification increasing both the throughput and sensitivity of this approach. The multi-fragment incubation approach was studied in detail and it was concluded that 200 fragment combinations in one well is an optimal and practical number permitting good acylsulfonamide detectability. Subsequently, a structurally diverse liberty of forty five thio acids and thirty eight sulfonyl azides was screened in parallel against Mcl-1 and Bcl-XL, and several potential hit combinations were identified. A control testing was carried out by substituting Bcl-XL with a mutant R139ABcl-XL, used to confirm that the potential kinetic TGS hit combinations were actually forming at the protein's hot spot and not elsewhere on the protein surface. Although, the synthesis of all these kinetic TGS hit compounds is currently ongoing, preliminary testing of several acylsulfonamides indicate that they disrupt the Bcl-XL/Bim or Mcl-1/Bim interaction.

In this thesis, two different experimental approaches to capacitive deionization (CDI) process are presented. In the first approach, transient system characteristics were analyzed to find three different operating points, first based on minimum outlet concentration, second based on maximum average adsorption rate and third based on maximum adsorption efficiency. These three operating points were compared in long term desalination tests. In addition, the effects of inlet stream salinity and CDI system size have been characterized to assess the feasibility of a commercial CDI system operating at brackish water salinity levels. In the second approach, the physical phenomena occurring inside a capacitive deionization system were studied by laser-induced fluorescence visualization of a “pseudo-porous” CDI microstructure. A model CDI cell was fabricated on a silicon-on-insulator (SOI) substrate and charged fluorophores were used to visualize the simultaneous electro migration of oppositely charged ions and to obtain in situ concentration measurements. / text

A new diagnostic technique for studying the turbulent mixing characteristics of supersonic mixing flowfields is developed and implemented in two Mach 3 mixing flowfields. The diagnostic utilizes simultaneous particle image velocimetry and quantitative planar laser-induced fluorescence of krypton gas to study the interaction between turbulent scalar and velocity fields. The fluorescence properties of krypton gas are determined; measurements of the pressure and temperature dependence of the collisional quenching rates and cross-sections are made for various mixtures with krypton. The gases tested in this fashion include helium, nitrogen, air, oxygen, and ethylene. Additional measurements are performed to measure the relative two-photon absorption cross-section for krypton gas. The non-dimensional quenching rates are found to follow a power-law dependence for temperature, while the pressure dependence of the total quenching rate is found to be linear. Two injection flowfields are studied for their general topology and kinematic characteristcs. The first injector model is a basic injector meant to serve as a baseline case; there are no hypermixing elements present in this model. The second model is an asymmetric, unswept hypermixing injector featuring 15 degree expansive ramps flanking a central block. These studies utilize particle image velocimetry in planar and stereoscopic configurations in various planes. Results for the mean flowfield show distinct differences between the two flowfields; the planar injector flowfield is shown to be highly two-dimensional and exhibits minimal coherent unsteady behavior. The hypermixing injector flowfield exhibits a highly three-dimensional wake, with a pair of stream-wise vortices driving both mean deviations in the flowfield and considerable vortical coupling in the span-wise direction. Simultaneous krypton PLIF and PIV are employed in the two mixing flowfields. An assay of the dependence of the krypton mole fraction calculations on the fluorescence signal is performed. The overall sensitivity and the resulting dynamic range of the calibration is dictated largely by the reference mole fraction. Additionally, several different theoretical models of the temperature dependence of the fluorescence signal are studied to assess their validity and influence over the PLIF calibration procedure. Finally, the technique is employed in the two mixing flowfields, and a brief analysis of the mean and unsteady behavior of the two is conducted. / text