Thesis (M.Sc.)--Memorial University of Newfoundland, 2000. / Restricted until November 2001. Bibliography: leaves 100-105.

The binding between the survival protein Bcl-xL and the death-promoting region of the Bcl-2-related protein Bak is one of the key protein-protein interactions in the regulation of programmed cell death (apoptosis). Since it is well recognized that the BH3 domain of Bak adopts an amphipathic α-helix to interact with Bcl-xL through hydrophobic and electrostatic effects, conformational studies and possible applications of the α-aminoxy acid-containing peptides as mimics of the α-helix of Bak BH3 domain have been carried out. The main results are summarized below. Four short peptides ZT1?ZT4 containing alternating α-aminoxy acids/α-amino acids as the mimics of the α-helix of Bak protein were designed and synthesized. However, none of these four peptides, at the concentration of 25 μM, exhibited a significant inhibitory effect on the Bcl-xL inhibition test. Circular dichroism spectroscopic studies on ZT1?ZT4 as well as short model peptides N-minus, N-plus, C-minus and C-plus suggest that the proposed secondary structure, the 7/8 helix, is not stable in aqueous solutions. 1H NMR, 2D NMR and circular dichroism spectroscopic studies on the disulfide bond-constrained short peptides 4.7?4.9 with alternating α-aminoxy acids and α-amino acids suggest that a disulfide linker with three methylene units between adjacent α-amino acid residues could dramatically increase the stability of the 7/8 helix even in a mixed buffer/methanol solution. 1H NMR, 2D NMR and circular dichroism spectroscopic studies have also revealed that the hybrid soluble peptides C-free, N-free and Both-free containing α-amino acids and β-2,2-cyclopropyl-amino acids adopted a stable 8/8 helix in aqueous solution. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

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Mass-selected cluster anions are employed as model micro-solutions to study solvent effects on the structural motifs and electronic structure of anionic solutes, including the roles of the solvent in controlling the outcomes of photochemical processes. Interaction of light with cluster anions can potentially lead to cluster photodissociation in addition to photodetachment. We investigate these competing processes by means of photoelectron imaging spectroscopy combined with tandem time-of-flight (TOF) mass spectrometry. Photoelectron images are reported for members of the [(CO2)n(H2O)m]- cluster series. For homogeneous solvation, the photodetachment bands show evidence of cluster core switching between a CO2- monomer anion and a covalent (CO2)2- dimer anionic core, confirming previous observations. The Photoelectron Angular Distributions (PADs) of the monomer- and dimer-based clusters reveal an interference effect that result in similar PADs. Stabilization of the metastable CO2- anion by water solvent molecules is highlighted because its ability to "trap" the excess electron on CO2. Most surprising is the effect of the water solvent in quenching the autodetachment channel in excited states normally embedded in the electron detachment continuum, allowing excited CO2-(H2O)m clusters to follow reaction paths that lead to cluster fragmentation. Observed O- based photoproducts are attributed to photodissociation of the CO2- cluster core and are dominant for small parent clusters, whereas a water evaporation channel dominates for larger clusters. Addition of a second CO2 to these clusters is shown to preferentially form monomer based clusters, whose photodissociation exhibit an additional CO3- based channel, characteristic of a photoinitiated intracluster ion-molecule reaction between nascent O- and the additional CO2 solvent molecule. Changes in the PADs of NO- are monitored as a function of electron kinetic energy for the NO-(N2O)n and NO-(H2O)n cluster anions. In contrast with hydration, angular distributions become progressively more isotropic for the N2O case, particularly when the photoelectron kinetic energies are in the vicinity of the 2Pi shape resonance of the N2O solvent molecules. First time observation of the CH3SOCH- anion of dimethylsulfoxide is reported along with the photoelectron images of this organic anion and of the monohydrated cluster. Observed photodissociation products are HCSO- and SO-.

This thesis reflects two main aims. Firstly, the synthesis and characterisation of a number of potential anion receptors was undertaken and their anion binding properties were assessed. In so doing, a second aim was fulfilled, namely a comparison of the various methods of detecting the bound anion, and quantifying the binding strength. Four techniques appear in this thesis; ¹H nuclear magnetic resonance, UV-visible spectroscopy, electrochemistry and luminescent emission. Quantitative titrations were performed and, where possible, stability constants estimated. Chapter One provides an introduction to some of the themes of molecular recognition and provides a brief overview of the literature associated with anion recognition. A Prologue describes the design of the receptors studied; they all incorporate a metal centre and appended amide groups which provide sources of hydrogen bonding. The molecules are mostly cationic and a combination of positive charge and hydrogen bonding constitutes the binding interaction. Chapter Two is concerned with receptors based on cobalticinium, [Cp₂Co]⁺ . A number of receptors are presented and are found to bind anions with stability constants typically in the range of 500-1000 dm³mol^-1 . Receptors involving more than one cobalticinium centre are found to bind much more strongly and, furthermore, variations in functional groups appended close to the proposed coordination site impart selectivity; dihydrogen phosphate is bound more strongly than chloride. It is also found that different techniques give different stability constants and comment is made on this phenomenon. Chapter Three examines the role of positive charge in anion binding and describes the synthesis and coordination properties of several neutral receptors. These molecules retain hydrogen bonding sites, and it is found that this is sufficient to bind anions, but the strength of the interaction is greatly reduced. Chapter Four introduces another system, based on RuL(bpy)₂²⁺ , where L is a 4,4'-amide disubstituted bpy. The strength of binding is an order of magnitude greater than the cobalticinium systems as detected by several methods including emission studies, which are very sensitive. Comparison with a neutral, rhenium-based receptor is made. A dihydrogen phosphate-selective luminescent sensor is also presented. The Epilogue identifies areas for future research. Specialised introductions and summaries are found at the beginning and end of each chapter.

Experiments were conducted to investigate the effect of reducing dietary anion-cation balance (AC-balance), defined as meq $ sp circ$(Sodium + Potassium)-(Chloride + Sulfur) S, on calcium (Ca) metabolism. Reducing the dietary AC-balance from +314 to $-22$ (meq kg$ sp{-1}$ dry matter (DM)) did not affect plasma Ca level but reduced Ca retention mainly due to a 10-fold increase in urinary Ca excretion with similar rate of apparent absorption. It also decreased urine pH and titratable acidity. The response to induced hypocalcemia created by the infusion of 4.6% EDTA solution revealed that reducing dietary AC-balance from +354 to +37 (meq kg$ sp{-1}$DM) did not affect the volume of the compartment, within which there was rapid equilibration of free Ca but tended to increase the rate of Ca mobilization from it during the infusion. The Ca kinetic study with a four-compartment model indicated that reducing dietary AC-balance from +338 to $-127$ (meq kg$ sp{-1}$DM) during the eucalcemic period and from +429 to $-147$ (meq kg$ sp{-1}$DM) during an EGTA-infusion period (simulated lactational Ca loss) caused hypercalciuria and increased ionized form of plasma Ca. Increased true intestinal Ca absorption and reduced bone accretion were observed in the lowest AC-balance diet only during the EGTA-infusion period. There were no differences in the size of total exchangeable Ca pool but the amount of Ca movement between them tended to increase in reduced AC-balance diets during both periods. Results indicated that feeding reduced AC-balanced diet may have a beneficial role in preventing parturient paresis (milk fever) by increasing Ca flux through the exchangeable Ca pool and Ca mobilization capability.

Copies of author's previously published articles inserted. / Includes bibliographical references (leaves 193-215) / xiv, 216 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Studies the structure and reactivity of organic, organosilicon and organophosphorus anions in the gas phase. Theoretical ab initio calculations and collisional activation in a reverse geometry mass spectrometer revealed structural information and reactivity was probed using the flowing afterglow reactor. / Thesis (Ph.D.)--University of Adelaide, Dept. of Organic Chemistry, 1991

Thesis (M.Sc. (Organic Chemistry)) -- Mahidol University, 1978. / Supported by the University Development Commission.

Thesis (Ph. D.)--University of Texas at Austin, 2004. / Supervisor: Jonathan L. Sessler. Vita. Includes bibliographical references. Available also from UMI company.