Thesis (M.S.)--West Virginia University, 2004. / Title from document title page. Document formatted into pages; contains xi, 94 p. : ill. (some col.). Includes abstract. Includes bibliographical references and index.

Honors Project--Smith College, Northampton, Mass., 2010.

<p> An experimental study of the steric stabilizing ability of a water soluble polyvinyl alcohol (PVA) polymer is presented.</p> <p> The free film thickness of a lamella formed between a drop of n-butylchloride and bulk n-butylchloride stabilized by PVA was measured by the Hodgson and Woods technique in order to evaluate the stabilizing ability of the polymer. A maximum in the stability was observed as the concentration of the polymer was increased. This maximum trend can be explained by the HVO theory.</p> / Thesis / Master of Engineering (MEngr)

<p> Studies examining the characteristics of membranes that facilitate and affect fusion are central to understanding the intricacies of inter- and intra-cellular fusion processes and expanding the existing knowledge of other roles membranes may have. In this thesis a model membrane system, using Sendai Virus and Egg phosphatidylcholine (EggPC) liposomes containing the receptor glycophorin A (proteoliposomes), was used in examining different fusion with proteoliposomes prepared by different methods. For the first time glycophorin A was incorporated into EggPC liposomes vectorially. This was accomplished separately with two detergents: octylglucoside and CHAPS. Fusion of Sendai Virus with the reconstituted proteoliposomes revealed that octylglucoside reconstituted proteoliposomes exhibited lower fusion compared with CHAPS reconstituted proteoliposomes. Efforts to determine the basis for this difference, using either proteinase K or O-glycosidase digestion and subsequent fragment analysis using SDS-PAGE and silver-staining, were inconclusive. A separate study examined the ability of large membrane-anchored biopolymers (chosen in virtue of their large hydrophilic domains) to sterically stabilize Egg PC liposomes. Glycophorin A, the lipophosphoglycan (LPG) from Leishmania donovani, and a polyethyleneglycol-conjugated phospholipid (PEG5000-PE) were incorporated into Egg PC liposomes. In each case, binding of a soluble fluorescent probe, NeutrAvidin Oregon Green, to liposomes containing biotin-conjugated lipid was restricted. This supports the idea that large membrane-anchored biopolymers are able to sterically stabilize liposomes.</p> / Thesis / Master of Science (MSc)

Poly(dimethylsiloxane) (PDMS) fluids containing magnetite nanoparticles stabilized with carboxylic acid-functionalized PDMS were prepared. PDMS-magnetite complexes were characterized using transmission electron microscopy, elemental analysis, and vibrating sample magnetometry. PDMS-magnetite complexes containing up to 67 wt% magnetite with magnetizations of ~52 emu gram-1 were prepared. The magnetite particles were 7.4 ± 1.7 nm in diameter. Calculations suggested that the complexes prepared using mercaptosuccinic acid-functionalized PDMS (PDMS-6COOH) complexes contained unbound acid groups whereas the mercaptoacetic acid-functionalized PDMS (PDMS-3COOH) complexes did not. Calculations showed that the PDMS-3COOH and PDMS-6COOH covered the same surface area on magnetite. Calculations were supported by molecular models and FTIR analyses. The complexes were dispersed into PDMS carrier fluids by ultrasonication, resulting in magnetic PDMS fluids with potential biomedical applications. Magnetite particles (100 nm to 1 mm in diameter) were prepared by crystallization from goethite/glycol/water solutions under pressure. Two methods for particle growth were investigated in which the crystallization medium was varied by adjusting the amount of water or by adding itaconic acid. Particle surfaces were analyzed by x-ray photoelectron spectroscopy (XPS). Particles with clean surfaces were coated with carboxylic acid-functionalized poly(e-caprolactone) stabilizers. Adding itaconic acid to the reactions afforded particles ~100 nm in diameter. The magnetite particles displayed magnetic hysteresis. The particles were dispersed into vinyl ester resins by ultrasonication and it was demonstrated that the ~100 nm particles remained dispersed for three days without agitation. These dispersions have applications in magnetic induction heating for composite repair. Living polymerizations of hexamethylcyclotrisiloxane were terminated with dimethylchlorosilane, phenylmethylchlorosilane, or diisopropylchlorosilane (DIPCS). Platinum-catalyzed hydrosilation of the hydrosilane-terminated PDMS with allyloxyethanol afforded a systematic series of hydroxyalkyl-terminated PDMS. The reactions were successful except for the hydrosilation of the sterically-hindered DIPCS-functionalized PDMS where no reaction was observed. Hydroxyalkyl-terminated PDMS oligomers were successful in initiating the stannous octoate-catalyzed copolymerization of e-caprolactone, which afforded PDMS-b-PCL diblock copolymers of controlled composition. / Ph. D.

This thesis describes the effect of placing a phosphorus atom in a sterically strained environment with particular emphasis on the geminal disubstitution of two 2,4,6-tri-tert-butylphenyl (Mes*) groups on a single phosphorus centre and intramolecular sub-van der Waals interactions between peri-substituted atoms on naphthalene and acenaphthene. Chapter 2 outlines the reactive chemistry of a sterically encumbered phosphinic chloride (Mes*)₂P(=O)Cl, which was shown to have extremely low reactivity at the phosphorus centre. It has however, been demonstrated that synthetically significant transformations are possible. The phosphine oxide (Mes*)₂P(=O)H and a secondary phosphine Mes*(2,4-tBu₂C₆H₃)PH were obtained from the reduction of (Mes*)₂P(=O)Cl with hydridic reagents under forcing conditions. The corresponding phosphinite was acquired from the deprotonation of (Mes*)₂P(=O)H, which furnished very crowded tertiary phosphine oxides (Mes*)₂P(=O)R (R = Me and Et) on reactions with electrophiles. We have been unable to chlorinate or deprotonate Mes*(2,4-tBu₂C₆H₃)PH, however the reaction with elemental sulfur afforded the affiliated phosphine sulfide Mes*(2,4-[supercript(t)]Bu₂C₆H₃)P(=S)H, albeit under forcing conditions. Our computations (B3LYP and M06-2X level) show that strain energies of geminally substituted compounds are extremely high (180 to 250 kJ mol⁻¹), the majority of the strain is stored as boat distortions to the phenyl rings in Mes* substituents. Chapter 3 describes the strain inherent with non-bonding atomic distances shorter than the sum of their van der Waals radii, specifically heteroatom substitution of the peri-positions of naphthalene and acenaphthene. It also documents the importance of amine protecting groups in chlorophosphine chemistry. The preparation of Ace[P(Ph)N(ⁱPr)₂]Br (Ace = acenaphthene-5,6-diyl) and Ace[P(Ph)N(ⁱPr)₂]₂, plus the elucidation of the molecular structures of Mes*P[N(CH₃)₂]₂, Ace[P(Mes)N(ⁱPr)₂]Br (Mes = 2,4,6-tri-methylphenyl) and Ace[P([supercript(t)]Bu)N(Et)₂]Br sufficiently demonstrate the ring distorting characteristics of structurally encumbered molecules. The reaction of Ace[P(Ph)N(ⁱPr)₂]Br and Ace[P(Ph)N(ⁱPr)₂]₂ with a methylating agent was also investigated.

Thesis (M.Sc.)--Memorial University of Newfoundland, 1997. / Bibliography: leaves 142-143.

The objectives of this project were to determine the reaction schemes of formanilide and substituted formanilides in acidic and alkaline solutions, to quantiate the kinetics of hydrolysis, to propose reaction mechanisms, and to assess the role of ortho words substitution in formanilide hydrolysis kinetics. A set of thirty substituted formanilides were synthesized and characterized. Hydrolysis of the formanilides was carried out under first order conditions in hydrochloric acid (0.01-8 M, 40°C) and in hydroxide solutions (0.01-3 M, 25°C and 40°C). Hydrolysis kinetics were evaluated in terms of temperature (20°C- 60°C), solvent composition (0-50 % dimethyl sulfoxide, dioxane, ethanol and acetone) and ionic strength (0.1-1) effects. The degradation products were separated and identified using RP-HPLC, and the alkaline and acidic reaction schemes were proposed. For acidic hydrolysis of formanilides, the observed rate constants were proportional to the hydronium concentrations. Modified Hammett plots constructed using the second order rate constants for specific acid catalysis were linear. The ortho effect was analyzed using the Fujita-Nishioka method. In alkaline solutions the observed rate constants showed mixed first and second order dependences with respect to hydroxide concentration. A complex degradation scheme was used to estimate individual rate constants and to construct Hammett plots. Ortho effects were examined for the first order hydroxide concentration dependent pathway. Arrhenius plots for substituted formanilides were linear in both acidic and alkaline media. Ionic strength did not show any effect on the acidic and alkaline hydrolysis rates. In both acidic and alkaline media the rate of hydrolysis decreased with increase in organic solvent content. Formanilide hydrolyzes in acidic solutions by specific acid catalysis and the kinetic study results were consistent with AAC2 mechanism. Ortho substitution led to reduction in rates. The orthoeffect could be split in steric inhibition of resonance, retardation due to steric bulk and through space interactions. In alkaline solutions a complicated kinetic scheme was used to describe the multiple pathways of degradation. The results from the kinetic studies could be explained using a modified BAC2 mechanism. The hydrolysis of meta and parasubstituted formanilides in alkaline conditions did not show substituent effects however ortho substitution led to an decrease in rate constants proportional to the steric bulk of the substituent.

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第20935号 / 理博第4387号 / 新制||理||1630(附属図書館) / 京都大学大学院理学研究科化学専攻 / (主査)教授 時任 宣博, 教授 大須賀 篤弘, 教授 依光 英樹 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

Post-translational modifications (PTMs) diversify the functions and control the stability of proteins by the covalent addition of chemical groups or proteins. These modifications include phosphorylation, acetylation, glycosylation, methylation, ubiquitination, etc. and affect all aspects of cellular activities. Dysregulation of PTMs is often linked to aging, oncogenesis, and various autoimmune diseases. Proteins involved in the PTM writing, removing, and reading process are very important biomarkers and hot therapeutic targets. Yet, current chemical methodologies to globally profiling PTM substrates rely on coppercatalyzed azide-alkyne cycloaddition (CuAAC) reaction in which bulky alkyne or azide groups in length and size are used. The intrinsic steric hinderance limits the general application of chemical reporters to metabolic incorporation by PTM writers possessing spacious active pockets.This dissertation will start with the demonstration that the alpha fluorine to amide bond was a steric free chemical reporter in protein acetylation. Fluorinated cofactors or precursors could be utilized by acetyltransferases to modify peptides and proteins both in vitro and in live cells. A novel bioorthogonal reaction named as fluorine thiol displacement reaction (FTDR) using thiophenol as the warhead was developed for converting a fluorine label in biomolecules to a fluorophore or biotin tag. This whole platform showed great potential to label, image, and enrich acetylation substrates. Another goal of this dissertation was the evolution of FTDR to fluorine selenol displacement reaction (FSeDR). Aliphatic selenol, aromatic selenol and thiol derivatives were compared in parallel in the labelling of fluorinated small molecules and proteins. Aliphatic selenol displayed the best reactivity under the mild physiological condition and exhibited a high degree of chemical stability. The updated platform was then used in the SILAC-based quantitative proteomics study of acetylation in the prostate cancer cell PC-3. The final goal of this dissertation focuses on the study of steric-free bioorthogonal labeling of glycosylation substrates based on FSeDR. The fluorine-tag labelled unnatural monosaccharides could be utilized by glycotransferases in live cells to modify sialylated glycoproteins, N-glycoproteins, and O-GlcNAcylated proteins. With the help of FSeDR, the fluorine reporter was further functionalized to fluorescent probes or affinity tags for imaging or enrichment studies. The steric-free fluorine reporter has the potential to become a powerful chemical reporter for glycan labelling. / Chemistry