In this thesis we present the work we have done to further the understanding of neutral pion photoproduction from the proton. Our work used heavy-baryon chiral perturbation theory to fourth order, and we explicitly include the ∆(1232) resonance using the delta power-counting scheme. We also test the effects of including and excluding D-waves, partial waves with orbital angular momentum quantum number of 2. We begin our discussion in chapter 1 with a brief history of nuclear physics before showing how current algebras and the partial-conservation of the axial-vector current (PCAC) can be used to describe low-energy hadronic interactions. To improve upon PCAC results, one can make use of chiral effective field theories, taking advantage of the chiral symmetry that is present in the limit of massless quarks. We formally introduce chiral perturbation theory (χPT) in chapter 2, discussing the power-counting problem that arises once baryons are included, and present two different approaches to overcome this. We conclude chapter 2 showing how the theory can be extended to include the ∆(1232) resonance. In chapter 3 we describe the model-independent framework of pion photoproduction needed to describe both theory and experiment. We discuss the various recent efforts to describe pion photoproduction within χPT in the latter half of chapter 3. We lay out the framework we have developed in chapter 4 and present our results in chapter 5. We have compared our work to the recent experimental data released by the A2 and CB-TAPS collaborations at the Mainz Microtron. Our results show that we can accurately describe the data from threshold up to an in-coming laboratory photon energy of approximately 260 MeV, a clear improvement on previous studies. We find that including the ∆ is necessary to describe the data beyond E γ ≈ 200 MeV, but the case for D-waves is not so clear. We cannot pinpoint an energy where their inclusion is necessary but we do find evidence suggesting they are important to improve the stability of the fit. Our best results require the inclusion of both the ∆ and D-waves. Finally, in chapter 6, we present our concluding remarks from what has been achieved over the last four years of study and what forms possible extensions of our work could take.

Self-stabilizing polyacrylate nanoparticle emulsions were previously investigated in the Turos laboratory, and provided a new model for delivering antibiotics via encapsulation or covalent binding of the desired bioactive compound within the polymer nanoparticles. The method used the in water, free radical emulsion polymerization of butyl acrylate/styrene mixture to form the polymer chain stabilized with a surfactant. Current research in this dissertation further explores the versatility of related nanoparticle emulsion systems. Chapter 2 provides an overview of the loading of certain therapeutic drugs, such as 5-aminosalicylic acid and derivatives thereof, for the treatment of irritable bowel syndrome. Chapter 3 explores homo-polymer nanoparticle emulsions composed of menthyl acrylate as the monomer. Thereby obviating the need for a copolymer emulsion polymerization. The homo(menthyl acrylate) nanoparticle emulsion provided greater stability compared to the previous copolymer models. The resulting homopolymer emulsion exhibited a decrease in cytotoxicity, and a 400% increase for loading of penicillin G. Chapter 4 explores novel polyacrylamide nanoparticle emulsion using only N-acrylated ciprofloxacin to form a homo-polymer polyacrylate nanoparticle emulsion, thereby requiring no additional co-monomers. The resulting emulsion has a relatively low cytotoxicity with similar bioactivity to free ciprofloxacin.

Les effets des opérateurs liés aux anomalies axiale et de trace de QCD et de QED dans les désintégrations faibles des mésons sont analysés dans deux régimes extrêmes: tout d'abord lorsque les densités anomales de gluons et de photons sont générées à courte distance par une boucle de quark lourd, ensuite lorsqu'elles sont générées à longue distance par des corrections fortes associées aux quarks légers u, d et s. A courte distance, l'ensemble des corrections de type pingouin à une interaction effective à quatre quarks arbitraire est obtenu à partir de l'expansion en la masse inverse du propagateur d'un quark lourd plongé dans un champ de jauge classique. Une suppression des effets anomaux est ainsi mise en évidence dans le Modèle Standard. Un nouvel ensemble d'opérateurs de dimension huit décrivant les effets du quark charmé dans les désintégrations des kaons est également établi. A longue distance, les effets anomaux associés aux quarks légers dans les désintégrations faibles hadroniques et radiatives des kaons sont analysés dans le formalisme des Lagrangiens chiraux. Une contribution potentiellement importante de l'opérateur d'anomalie de trace est ainsi mise en évidence. Les implications d'une éventuelle dominance des anomalies sont également étudiées.

A new class of oxazolidinone chiral auxiliary has been synthesized from various α-amino acids, incorporating a perfluoroalkyl functional chain as a soluble support. This feature allows the chiral auxiliaries to be employed under standard solution-phase reaction conditions, and rapidly purified from crude mixtures using fluorous solid phase extraction (FSPE). Our investigation of these new materials has been divided into two main sections. To obtain the chiral auxiliaries in multi-gram quantities a synthetic protocol was designed, where efficiency and reproducibility were the primary objectives. Meeting these goals required an extensive study of the reactivity of perfluoroalkyl nucleophiles. This study identified a versatile and scalable protocol for the perfluoroalkylation of the required amino acid starting materials. These results have allowed us to design a general, five-step synthetic pathway to create the fluorous chiral auxiliaries quickly and effectively. The new auxiliaries were then applied in several model reactions, specifically chosen to examine the reactivity and behavior of these compounds. In particular, the auxiliaries were tested for their stereoselectivity, recyclability, and ease of purification, in a series of Aldol reactions, 1,3 dipolar cycloadditions, and radical conjugate additions. This set of model reactions, combined with the facile and efficient synthesis clearly demonstrates that these new chiral auxiliaries are useful alternatives to the non-fluorous oxazolidinone chiral auxiliaries currently employed in stoichiometric asymmetric syntheses. / February 2006

S’han sintetitzat quatre alquil i aril (9 anthry1) carbinol (metil, fenil isopropil, terc-butil, i) que van revelar la rotació restringida al voltant de l'enllaç C9-C11. La seva energia lliure d'activació per a la rotació s'ha determinat, sent 11.0, 14.0, 21.7, i 9.8 kcal / mol, respectivament. Es descriuen l’aplicació mètodes de mesura del NOE i del temps de relaxació per a la determinació de l'energia d'activació per a la rotació de bons. El bon acord amb els valors obtinguts amb el mètode de la temperatura de coalescència confirma que l'enfocament basat NOE és una bona alternativa per a la determinació de les elevades barreres de rotació. Els càlculs de Mecànica Molecular (MM2) donen valors propers als experimentals. S’han preparat els carbamats homoquirals del 9-anthryl-terc-butylcarbinol i s’ha estudiat el seu equilibri conformacional. La configuració absoluta es va determinar mitjançant la comparació de les dades de RMN amb càlculs de MM. Els enantiòmers de l'alcohol es van obtenir després de la separació cromatogràfica dels derivats de carbamat i la seva hidròlisi. Els alcohols homoquirals van ser preparats per columna de cromatografia quiral directa. S’han detectat i o separat a temperatura ambient els confòrmers cisoid i transoid del 9,10 dipivaloylantracè i del 9,10-bis(1-imino-2,2-dimetilpropil)antracè. La transformació entre dues atropisómers va ser estudiada per RMN i modelat pels mètodes de MM. La difracció de raigs X es va realitzar per als derivats imino. El 9-antril-terc-butilcarbinol es va provar com a agent de solvatació quiral (CSA) en presència de formes racèmica de p-toluenesulfinate de mentil, 9-(1-amino-2,2- dimetilpropil)-9,19-dihydroantracè, àcid R-methoxyfenylacetic i 1-phenyl-1,2- ethanediol. Es formaren els complexes diastereòmers entre el reactiu quiral i cada enantiòmer d'aquests últims compostos. Un dels enantiòmers de 9-antril-tertbutylcarbinol va ser estudiat mitjançant NOE intermolecular i càlculs de dinàmica molecular. Es trobaren les principals diferencies termodinàmiques i estructurals. / Se han preparado Cuatro alquil- y aril- (9-antril)carbinols (metil, isopropil, tert-butil, y fenil) y mostraron la rotación restringida del enlace de C9-Cll. Su energía libre de activación para la rotación ha sido determinada, siendo 11.0, 14.0, 21.7, y 9.8 kcal/mol, respectivamente. Hemos determinado la energía de activación para la rotación de enlace C9-C11 por la aplicación de medidas de NOE y de tiempo de relajación. El buen acuerdo con los valores obtenidos con el método de temperatura coalescencia confirma que el método basado en el NOE es una buena alternativa para la determinación de barreras de rotatorión altas. La Mecánica Molecular (MM2) da valores cercanos a los experimentales. Se ha preparado el carbamato homochiral de 9-antril-tert-butilcarbinol y se ha estudiado su equilibrio conformacional. La configuración absoluta fue determinada por la comparación de los datos NMR con cálculos de MM. Los enantiomers del alcohol fueron obtenidos después de la separación cromatográfica de los carbamatos y tres su hidrólisis. Los mismos alcoholes se obtuvieron a través de una columna HPLC quiral Se han detectado o separado, a temperatura ambiente, los confórmeros cisoide y transoide del 9,10 dipivaloylantraceno y del 9,10-bis(1-imino-2,2- dimetilpropil)antraceno. La transformación entre los dos atropoisómeros se estudió por RMN i se modeló por métodes de MM. La difracción de rayos X se realitzó con los derivados imino. Se ha probado el 9-anthryl-tert-butylcarbinol como agente solvatación chiral (CSA) en presencia de las formas de racemicas de p-toluenesulfinato de mentilo, 9-(1-amino-2,2- dimetilpropil) - 9,19-dihydroanthracene, ácido de R-methoxyphenylacetic y 1-phenyl- 1,2-ethanediol. Se formaron los complejos diastereoisómericos el reactivo quiral y cada enantiomer de estos últimos compuestos. Uno de los enantiomers de 9-anthryltertbutylcarbinol fue estudiado por medio de NOE intermolecular y cálculos de dinámica moleculares. Las diferencias termodinámicas y estructurales principales fueron encontradas. / Four alkyl- and aryl-(9-anthry1)carbinols (methyl, isopropyl, tert-butyl, and phenyl) were synthesized and revealed restricted rotation about the C9-Cll bond. Their free energy of activation for rotation has been determined, being 11.0, 14.0, 21.7, and 9.8 kcal/mol, respectively. The application of NOE enhancement and relaxation time measurements for the determination of the activation energy for bond rotation is described. The good agreement with the values obtained with the coalescence temperature method bears out that the NOE based approach is a good alternative for the determination of high rotational barriers. Molecular Mechanics (MM2) calculations give values close to the experimental ones. The homochiral carbamates of 9-anthryl-tert-butylcarbinol were prepared and their conformational equilibrium was studied. The absolute configuration was determined by comparison of the NMR data with MM calculations. The enantiomers of the alcohol were obtained after chromatographic separation of carbamate derivatives and their hydrolysis. The same homochiral alcohols were prepared by direct chiral column chromatography Cisoid and transoid conformations of 9,10-dipivaloylanthracene and 9,10-bis(1-imino- 2,2-dimethylpropyl) anthracene were separated and detected for the former and isolated for the latter at room temperature. The transformation between two atropisomers was studied by NMR and modeled by MM methods. X-ray diffraction was performed for the imino derivatives. The 9-anthryl-tert-butylcarbinol was tested as a chiral solvating agent (CSA) in the presence of racemic forms of mentil-p-toluenesulfinate, 9-(1-amino-2,2- dimethylpropyl)-9,19-dihydroanthracene, R-methoxyphenylacetic acid and 1-phenyl- 1,2-ethanediol. Diastereomeric complexes were found to form between each enantiomer of these last two compounds. One of the enantiomers of 9-anthryltert-butylcarbinol was studied by means of intermolecular NOE and molecular dynamics calculations. Major thermodynamic and structural differences were found.

No description available.

Steroid sulfatase (STS) catalyzes the desulfation of sulfated steroids such as estrone sulfate to the corresponding steroid such as estrone. Inhibitors of STS are believed to have potential for treating estrogen-dependent breast cancer. A new class of potential irreversible suicide inhibitors of STS, based on aryl sulfates bearing a monofluoromethyl or difluoromethyl group ortho to the sulfate group, was synthesized. Key to the success of these syntheses was the use of new sulfation methodology recently developed in the Taylor group. A new and efficient route to 4-formyl estrone, a time-dependent, irreversible STS inhibitor, is also reported. Several new classes of potential, reversible STS inhibitors were synthesized. These compounds are analogs of known STS substrates in which the sulfate group is replaced with an ,-difluoromethylenesulfonamide group, a boronic acid group or a sulfinic acid group. We also report the synthesis of estrone sulfate analogs that bear a carboxylate moiety at the 17-position and a sulfate surrogate at the 3-position. It is anticipated that these compounds will inhibit STS by interacting with Arg98 which lies at the periphery of the active site. Key to the success of this synthesis was the use of the t-butyl group as a protecting group for the 2-position of estrone. Finally, our preliminary investigations into the synthesis of a new class of chiral electrophilic fluorinating agents are presented. These reagents are based on a chiral binaphthyl sulfonimide scaffold and are expected to be capable of performing enantioselective electrophilic fluorinations. Such reagents may be useful in synthesizing organofluorines of biological significance including STS inhibitors.

Heavy ions are collided at the Relativistic Heavy Ion Collider (RHIC) at Brookhaven National Laboratory (BNL) in an effort to create a unique state of nuclear matter, where quarks and gluons can freely move over volumes larger than the typical size of a nucleon (typical scale of Quantum Chromodynamics, QCD). In this state, called a "Quark Gluon Plasma" (QGP), it is proposed Chiral symmetry is restored. The fact that Chiral symmetry is a symmetry of the Standard model and is broken at low energy (current energy scale of universe) makes the study of its possible very interesting. The analysis in this dissertation searches for signatures of chiral symmetry restoration at the phase transition between the QGP and the hadronic gas phase by using resonance particles as probes. Resonances may decay inside of hot dense matter due to their short lifetimes, and therefore their decay daughters carry away dynamical information such as the mass and decay width. Mass shift and width broadening are predicted signatures of chiral symmetry restoration. The [phi](1020) resonances reconstructed from the dielectron decay channel are investigated in this dissertation. This decay channel does not suffer scattering from the late hadronic medium due to the relatively small interaction cross section of leptons with hadrons. The disadvantage of this channel comes from the small branching ratio. Therefore, large statistics and clean Particle IDentification (PID) are necessary for this analysis. Those requirements were fulfilled with high luminosity beams at RHIC and the newly developed and installed Time Of Flight (TOF) detectors, which provide clear particle identification up to momentum of 2-3 GeV/c, as well as the large acceptance of the Solenoidal Tracker At RHIC (STAR) detector. In this dissertation, measurements of mass, width, transverse momentum spectrum, and yields of [phi][right arrow] e⁺e⁻ at mid-rapidity [mathematical symbols] from the STAR experiment in Au+Au collisions at [mathematical symbols]=200 GeV are presented and compared to a previously measured [phi] meson result from a hadronic decay channel. The possibility of medium modification which implies Chiral symmetry restoration is discussed. / text

In chapter 1 the principles behind circular dichroism spectroscopy and exciton coupled circular dichroism spectroscopy are outlined, and examples are cited that illustrate the utility of these methods in the determination of absolute configuration and ee of chiral amines. This provides background and context for this thesis, which mostly pertains to the sensing of chirality in amines. An exciton coupled circular dichroism method based on the induction of helical chirality in an organometallic host for sensing chiral amines is presented in chapter 2. The method can be used to determine absolute configuration by relating the sign of the first Cotton effect of the host-amine complex to the handedness of the amine. Analysis of the primary circular dichroism optical data is by principal component analysis allows for differentiation of the analytes based on their idendity and handedness. A novel circular dichroism method for detecting chiral amines is discussed in chapter 3. The method uses a highly efficient derivatization method to convert the primary amine into a bidentate imine. Three equivalents of the imine are then assembled together by coordination to Fe(II). The proximity and chiral orientation of the imines leads to exciton coupled circular dichroism, which is of utility in the determination of absolute configuration. Additionally, there is a metal-to-ligand charge transfer band in the visible region that can be used to develop calibration curves, which allow for the determination of the enantiomeric excess of unknown samples with an absolute error of ±5%. Chapter 4 details another imine based circular dichroism method for chiral amines. The method uses a commercially available aldehyde, Fe(II), and circular dichroism spectrometry to sense chirality in amines. It is shown that the circular dichroism signals in the ultraviolet spectrum vary predictably with the handedness of the chiral amine, which has potential applications in the determination of absolute configuration. By developing calibraton curves, signals in the visible spectrum can be used to determine enantiomeric excess with an absolute error of ±6%. Analyzing the primary circular dichroism optical data with linear discriminant analysis allows for differentiation between amines based on their identity and handedness. Finally, chapter 5 illustrates the potential of using the thermodynamic parameters of partitioning between water and octanol as a predictive tool for estimating the contributions of hydrophobicity to host-guest binding events. This is done by showing a relationship between the thermodynamics of partitioning and thermodynamics of hydrophobic binding events for a series of guests and cyclodextrin. A plot of the thermodynamic parameters of binding of a variety of guests to cyclodextrin as a function of the thermodynamic parameters of partitioning between water and octanol shows a linear relationship for a series of alcohols. / text

Pseudoephedrine is well established as a chiral auxiliary in the alkylation of amide enolates to form tertiary and quaternary carbon stereocenters. However, due to its facile transformation into the illegal narcotic methamphetamine, pseudoephedrine is either illegal or highly regulated in many countries, which limits its use in academic and industrial settings. To address this issue, pseudoephenamine has been developed as a replacement for pseudoephedrine in organic synthesis. This new auxiliary suffers no regulatory issues and exhibits several practical advantages over pseudoephedrine, including the high diastereoselectivities observed in alkylation reactions forming quaternary carbon stereocenters, the propensity for pseudoephenamine amides to be free-flowing crystalline solids, and the sharp, well-defined peaks that typically compose the 1H NMR spectra of these amides. / Chemistry and Chemical Biology