NMR methods have been designed and employed in studying ofcomplex liquids and solids formed by surfactants. PGSE NMRexperiments are easily biased by convection; this artifact canbe avoided by changing the sample holder and by usingconvection-compensated pulse sequences. The temperaturedistribution within samples was controlled using thetemperature dependent order parameter for CBr2H2dissolved in a thermotropic nematic solvent.Electronic ringing that often spoils accurate NMR experimentsfor broad lines was removed by the using composite pulses andquadrupole echo sequences with appropriate phase cycles. Field-dependent81Br and35Cl NMR relaxation studies in micellar solutions ofC16TAX surfactants showed that the structure ordynamics of the hydration shell is more influenced by thesurfactant cation for bromide than for chloride, in agreementwith their position in the Hoffmeister series. The presence ofa small but significant frequency-dependent relaxation showedthat the lateral self diffusion of the anions may be reduced ascompared to its bulk value in diluted solutions but only with afactor of 1.0 - 2.5. The ions are clearly not "bound" to thesurface. A field-dependent2H NMR relaxation study on the CTABr-α-d2and benzene-d6showed an initial one-dimensional micellargrowth followed by the appearance of microemulsion droplets onaddition of benzene. The local mobility of the benzene wasreduced when solubilized in small amounts, consistent with aninitial average location of benzene at the micellar interface.The surfactant diffusion coefficients fromconvection-compensated PGSE NMR experiments in the C12E8-D2O system showed monotonous growth of the micellesupon increasing temperature. Emulsion droplets in the C12E5-decane-D2O system where shown to coarsen according to theOstwald ripening theory after being brought out of equilibriumby a temperature drop. X-ray scattering and2H NMR line-shape and relaxation experimentssuggested that complex solids formed by a partly-sulfatedpolysaccharide and CnTAB exhibit regular ordering at both microscopicand mesoscopic length scales. <b>Keywords</b>: CTAB, CTAC, C12E8, C12E5, decane, benzene, CBr2H2, polysaccharide, micelle, microemulsion, emulsion,Ostwald ripening, NMR,81Br,35Cl,2H, field- dependent spin relaxation, PGSE, selfdiffusion, convection, ringing, thermometer, generalized Blochequations, EXORCYCLE, quadrupole echo, SAXS, WAXS, cryo-TEM.

<p>NMR methods have been designed and employed in studying ofcomplex liquids and solids formed by surfactants. PGSE NMRexperiments are easily biased by convection; this artifact canbe avoided by changing the sample holder and by usingconvection-compensated pulse sequences. The temperaturedistribution within samples was controlled using thetemperature dependent order parameter for CBr₂H₂dissolved in a thermotropic nematic solvent.Electronic ringing that often spoils accurate NMR experimentsfor broad lines was removed by the using composite pulses andquadrupole echo sequences with appropriate phase cycles.</p><p>Field-dependent⁸¹Br and³⁵Cl NMR relaxation studies in micellar solutions ofC₁₆TAX surfactants showed that the structure ordynamics of the hydration shell is more influenced by thesurfactant cation for bromide than for chloride, in agreementwith their position in the Hoffmeister series. The presence ofa small but significant frequency-dependent relaxation showedthat the lateral self diffusion of the anions may be reduced ascompared to its bulk value in diluted solutions but only with afactor of 1.0 - 2.5. The ions are clearly not "bound" to thesurface. A field-dependent²H NMR relaxation study on the CTABr-α-<i>d</i><i>2</i>and benzene-<i>d</i><i>6</i>showed an initial one-dimensional micellargrowth followed by the appearance of microemulsion droplets onaddition of benzene. The local mobility of the benzene wasreduced when solubilized in small amounts, consistent with aninitial average location of benzene at the micellar interface.The surfactant diffusion coefficients fromconvection-compensated PGSE NMR experiments in the C₁₂E₈-D₂O system showed monotonous growth of the micellesupon increasing temperature. Emulsion droplets in the C₁₂E₅-decane-D₂O system where shown to coarsen according to theOstwald ripening theory after being brought out of equilibriumby a temperature drop. X-ray scattering and²H NMR line-shape and relaxation experimentssuggested that complex solids formed by a partly-sulfatedpolysaccharide and C_nTAB exhibit regular ordering at both microscopicand mesoscopic length scales.</p><p><b>Keywords</b>: CTAB, CTAC, C₁₂E₈, C₁₂E₅, decane, benzene, CBr₂H₂, polysaccharide, micelle, microemulsion, emulsion,Ostwald ripening, NMR,⁸¹Br,³⁵Cl,²H, field- dependent spin relaxation, PGSE, selfdiffusion, convection, ringing, thermometer, generalized Blochequations, EXORCYCLE, quadrupole echo, SAXS, WAXS, cryo-TEM.</p>

My Ph.D. thesis is presented in two parts. In the first part, I describe the preparation of organic-inorganic hybrid micelles formed from poly(styrene-b-4-vinylpyridine) (PS-b-P4VP) block copolymers and CdSe quantum dots (QDs). Several distinct morphologies were observed including, spheres, finite-sized wormlike networks and clusters of hollow vesicles. A series of experiments were carried out to explore whether these hybrid colloids were thermodynamically stable or formed under kinetic control. Upon addition of 2-propanol (2-PrOH) to a chloroform solution containing a mixture of PS404-b-P4VP76 plus CdSe QDs (2-PrOH is a good solvent for P4VP block and a precipitant for PS block and QDs), uniform spherical micelles formed almost instantly, with a PS core and a thin P4VP corona to which the QDs were attached. Vigorous stirring of this solution for two days led to the formation of three-dimensional wormlike networks consisted of Y-junctions and cylindrical struts, terminated by bulbous spherical end-caps. Even more profound structural changes occurred when the solution was subjected to prolonged magnetic stirring (e.g. 1 month). ii In contrast, manipulating the chemical composition of the initial block copolymer could trigger a spontaneous structural transition from sphere to network of wormlike micelles over 2 h without the need of stirring. The second part of the thesis begins by describing a modular approach for preparing polyferrocenyldimethylsilane (PFS) block copolymers via a Cu-catalyzed alkyne/azide coupling reaction to covalently combine two homopolymers synthesized separately. This strategy opens the door to a broad library of novel functional PFS block copolymers, for example, poly(ferrocenyldimethylsilane-b-N-isopropyl acrylamide) (PFS-b-PNIPAM). In an attempt to expand our understanding of PFS block copolymer self-assembly in polar solvents, I investigated the self-assembly of a new polymer (PFS26-b-PNIPAM105) in alcohol solvents. When the block polymer was dissolved in methanol, ethanol and 2-propanol, it formed long fiber-like micelles with uniform width. I also showed that micelles of this polymer underwent seeded growth in methanol, leading to cylindrical micelles that were nearly mono- dispersed in length.

My Ph.D. thesis is presented in two parts. In the first part, I describe the preparation of organic-inorganic hybrid micelles formed from poly(styrene-b-4-vinylpyridine) (PS-b-P4VP) block copolymers and CdSe quantum dots (QDs). Several distinct morphologies were observed including, spheres, finite-sized wormlike networks and clusters of hollow vesicles. A series of experiments were carried out to explore whether these hybrid colloids were thermodynamically stable or formed under kinetic control. Upon addition of 2-propanol (2-PrOH) to a chloroform solution containing a mixture of PS404-b-P4VP76 plus CdSe QDs (2-PrOH is a good solvent for P4VP block and a precipitant for PS block and QDs), uniform spherical micelles formed almost instantly, with a PS core and a thin P4VP corona to which the QDs were attached. Vigorous stirring of this solution for two days led to the formation of three-dimensional wormlike networks consisted of Y-junctions and cylindrical struts, terminated by bulbous spherical end-caps. Even more profound structural changes occurred when the solution was subjected to prolonged magnetic stirring (e.g. 1 month). ii In contrast, manipulating the chemical composition of the initial block copolymer could trigger a spontaneous structural transition from sphere to network of wormlike micelles over 2 h without the need of stirring. The second part of the thesis begins by describing a modular approach for preparing polyferrocenyldimethylsilane (PFS) block copolymers via a Cu-catalyzed alkyne/azide coupling reaction to covalently combine two homopolymers synthesized separately. This strategy opens the door to a broad library of novel functional PFS block copolymers, for example, poly(ferrocenyldimethylsilane-b-N-isopropyl acrylamide) (PFS-b-PNIPAM). In an attempt to expand our understanding of PFS block copolymer self-assembly in polar solvents, I investigated the self-assembly of a new polymer (PFS26-b-PNIPAM105) in alcohol solvents. When the block polymer was dissolved in methanol, ethanol and 2-propanol, it formed long fiber-like micelles with uniform width. I also showed that micelles of this polymer underwent seeded growth in methanol, leading to cylindrical micelles that were nearly mono- dispersed in length.

Zugl.: Kaiserslautern, Techn. Universiẗat, Diss., 2008.

Hohenheim, Univ., Diss., 2006.

Regensburg, Univ., Diss., 2003. / Erscheinungsjahr an der Haupttitelstelle: 2003.

Oximas têm sido extensivamente usadas como antídoto para envenenamento por organofosforados e como desontaminante. Micelas e vesículas, utilizadas como catalisadores e transportadores de drogas, constituem agentes potenciais para tratamento e descontaminação. Neste trabalho descrevemos a reação de p-Nitrofenildifenilfosfato (PNPDPP), um substrato modelo para organofosforado, com: acetofenoxima (I); ácido 10- fenil-10-hidroxiiminodecanóico (II); 4-(9-carboxinonanil)-1-(9-carboxi-1-hidroiimino nonanil) benzeno (III); cloreto de N-dodecilpiridina (IV); cloreto N-metilpiridina 2-aldoxima (V), na presença de micelas catiônicas e zwitteriônicas de cloreto de hexadeciltrimetilamônio, CTAC e N-Hexadecil-N,N-dimetil-1-propano sulfonato, HPS, respectivamente, e vesículas catiônicas de dioctadecildimetilamônio, DODAC. O pKa aparente, pKap, das oximas em agregados de anfifilicos, a constante de velocidade de segunda ordem de oximólise em micelas ou vesículas, km, e as constantes de velocidade observadas para a oximólise de PNPDPP, kobs, foram determinadas espectrofotometricamente, a pH constante, variando-se a concentração dos anfifílicos. Os resultados foram analisados usando as teorias: modelo de pseudofase (PP) e modelo de pseudofase com considerações de troca iônica (PIE), descrita na literatura pelo nosso grupo. As constantes de segunda ordem para oximólise de PNPDPP em água, kox, determinadas foram 6,5 M^-1 min^-1 (I, II e III) e 2,8 M^-1 min^-1 (IV e V). O kobs máximo em micelas e vesículas, kobsmax, e o kobs em água, kw, no mesmo pH, foram utilizadas para calcular o fator de aceleração máxima, AF, para cada anfifílico (AF = kobsmax/kw). Os agregados catalisam a decomposição de PNPDPP e os valores de AF (e km) foram da ordem de 10^4 (32 min^-1), 10^4 (125 min^-1) e 10^6 (80 min^-1) para a reação da oxima IV com CTAC, HPS e DODAC, respectivamente. A análise quantitativa da dependência da concentração de agregados anfifílicos na oximólise mostrou um considerável aumento da constante de velocidade da reação produzido por micelas e vesículas (maior que 8 x 10^6 vezes). Esse efeito é parcialmente devido a: concentração local dos reagentes, efeitos nos pKas dos nucleófilos e, mais importante, mudança na reatividade intrínseca das oximas. / Oximes have been extensively used as antidotes and decontaminants of organophosphates. Micelles and vesicles, catalysts and drug transport agents, constitute potential vehicles for Oxime treatment. Here we describe the reaction of p-nitrophenyldiphenylphosphate (PNPDPP) with: acetophenoxime (I); 10-phenyl-10-hydroxyiminodecanoic acid (II); 4-(9-carboxynonanyl)-1-(9-carboxy-1-hydroyiminononanyl) benzene (III); N-dodecylpyridinium chloride (IV); N-methylpyridinium 2-aldoxime chloride (V), in the presence of cationic and zwitterionic micelles, hexadecyltrimethylammonium chloride, CTAC and N-Hexadecyl-N,N-dimethyl-1-propanesulfate, HPS, respectively, and cationic vesicles of dioctadecyldimethylammonium, DODAC. The apparent pKa, pKap, of the oximes in the amphiphile aggregates, the second order rate constants of oximolysis in micelles and vesicles, km, and the observed rate constants for PNPDPP oximolysis, kobs, were determined spectrophotometrically at constant varying amphiphilic concentrations. The results were analyzed using the pseudo-phase theory (PP) and pseudo-phase / ion exchange (PIE). The second order rate constant for (uncatalyzed) oximolysis of PNPDPP were 6.5 M^-1 min^-1 (I, II and III) and 2.77 M^-1 min^-1 (IV and V). From the maximum value of kobs in micelles and vesicles, kobsmax, and the value of kobs in water, kox, at the same pH, the maximum acceleration factor, AF, were calculated (AF = kobsmax / kw). The amphiphiles catalyzed the oximolysis of PNPDPP and the values of AF (and km) were ca 10^4 (32 min^-1), 10^4 (125 min^-1) and 10^6 (80 min^-1) for the reactions of Oxime IV in CTAC, HPS and DODAC, respectively. Quantitative analysis of the amphiphile concentration-dependence of rates demonstrated that the considerable rate increase produced by micelles and vesicles on the rate of oximolysis (up to 8 x 10^6 fold) is partly due to reagent concentration in the aggregate, effects on the pKas of the nucleophiles and, more importantly, catalysis.

京都大学 / 0048 / 新制・課程博士 / 博士(人間・環境学) / 甲第21873号 / 人博第902号 / 新制||人||215(附属図書館) / 2018||人博||902(吉田南総合図書館) / 京都大学大学院人間・環境学研究科相関環境学専攻 / (主査)教授 小松 直樹, 教授 加藤 立久, 准教授 廣戸 聡 / 学位規則第4条第1項該当 / Doctor of Human and Environmental Studies / Kyoto University / DFAM

Knowledge of how intermolecular interactions of amyloidogenic proteins cause protein aggregation and how those interactions are affected by sequence and solution conditions is essential to our understanding of the onset of many degenerative diseases. Of particular interest is the aggregation of the amyloid-β (Aβ) peptide, linked to Alzheimer's disease, and the aggregation of the Sup35 yeast prion peptide, which resembles the mammalian prion protein (PrP) linked to spongiform encephalothopies. To facilitate the study of these important peptides, experimentalists have identified small peptide congeners of the full-length proteins that exhibit amyloidogenic behavior, including the KLVFFAE sequence of the Aβ protein, and the GNNQQNY sequence of Sup35. Reverse micelles provide an important environment for the study of protein folding and aggregation. In a reverse micelle, it is possible to observe the effects that confinement and water activity, believed to play a critical role in an in vivo cellular environment, have on protein folding, misfolding, and aggregation. We employed molecular dynamics simulations of reverse micelles as well as peptides encapsulated in reverse micelles in order to characterize the reverse micelle environment and identify fundamental principles that inform how sequence and solution environment influence protein aggregation. The peptides studied include the alanine-rich peptide AKA2 as well as the amyloidogenic KLVFFAE and GNNQQNY peptide fragments. The results of these studies suggest that substantial fluctuations in reverse micelle shape away from an idealized spherical geometry enables significant interaction between peptides and the surfactant interface. Analysis these results, including evaluation of water dynamics and calculated IR spectra of the amide I vibration of the peptides, indicate that our model of the reverse micelle is a robust one which captures essential features of this complex system. Moreover, our studies provide critical insight into the complex role played by a heterogeneous cellular environment in the earliest stages of protein aggregation and amyloid formation.