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

To understand protein stability and the mechanism of protein folding, it is essential that we gain a better understanding of the ensemble of conformations that make up the denatured state of a protein. The primary goal of the research described here was to see what we might learn about the denatured state using fluorescence. To this end, tryptophan was introduced at five sites in Ribonuclease Sa (RNase Sa): D1W, Y52W, Y55W, T76W, and Y81W. The fluorescent properties of the denatured states of these five proteins were studied and compared to the fluorescent properties of eight model compounds: N-acetyl-tryptophan-amide (NATA), N-acetyl-Ala-Trp-Ala-amide (AWA), N-acetyl-Ala-Ala-Trp-Ala-Ala-amide (AAWAA), and five pentapeptides based on the sequence around the original tryptophan substitutions in RNase Sa. Regardless of the denaturant, λmax for the proteins and model compounds differed very little, 349.3 ± 1.2 nm. However, significant differences were observed in the fluorescence intensity at λmax (IF), suggesting that IF is more sensitive to the immediate environment than λmax. The differences in IF are due in part to quenching by neighboring side chains. More importantly, IF was always significantly greater in the protein than in its corresponding pentapeptide, indicating that the protein exerts an effect on the tryptophan, which cannot be mimicked by the pentapeptide models. Acrylamide and iodide quenching experiments were also performed on the model compounds and proteins. Significant differences in the Stern-Volmer quenching constant (KSV) were also observed between the proteins and between the proteins and their corresponding pentapeptides. Importantly, the KSV for the protein was always less than in its corresponding pentapeptide. These data along with the IF data show that non-local structure in the unfolded state influences tryptophan fluorescence and accessibility. In summary, these and our other studies show that fluorescence can be used to gain a better understanding of the denatured states of proteins.

En el curso de esta Tesis Doctoral, se sintetizaron librerías de (1,2)-diaminas enantiopuras y 2,2’-bifenoles pro-quirales. La transferencia de quiralidad desde la diamina al bifenol, mediante puentes de hidrógeno o coordinación a un metal (ZnII, CuII), fue demostrada por dicroísmo circular (DC). El comportamiento en disolución de los complejos supramoleculares (usando puentes de hidrógeno), así como sus constantes de asociación, fue estudiado mediante valoraciones de RMN, UV-vis y ITC. La determinación de las configuraciones absolutas de los complejos de ZnII se consiguió mediante la resolución de las estructuras de rayos-X y los estudios de DC, tanto a un nivel teórico como experimental. Un nuevo ligando fosforado, potencialmente catalítico, fue preparado a partir de 2,2’-bifenol, mostrando el camino para el desarrollo de nuevos catalizadores supramoleculares. / During the course of the thesis libraries of chiral (1,2)-diamines and prochiral 2,2’-biphenol derivatives were synthesised. The transfer of chirality from the diamine to the biphenol moiety mediated either by hydrogen bonding or coordination to a metal centre (ZnII, CuII) was demonstrated by CD (circular dicroism). The behaviour in solution of the hydrogen bonded complexes was investigated by NMR spectroscopy, UV-vis and ITC titrations (determination of association constants. The determination of absolute configurations of the ZnII complexes was achieved by X-ray structure determination and CD analyses both on the experimental and theoretical level. Last but not least, a new potentially catalytic phosphane ligand was derived from a dynamically racemic 2,2’-biphenol derivative.

No description available.

Tat1-72, is an intrinsically disordered protein at pH 4.1 as previously indicated by NMR chemical shifts and coupling constants, and confirmed by 15N-relaxation parameters. The presence of SDS elicits a conformational change to α-helicity in Tat1-72. In the presence of the non-ionic DDM detergent and zinc, Tat was found to be soluble at pH 4 when bound to TAR RNA; TAR binding also elicits a conformational shift to α-helicity in Tat1-72. The β-sheet content of Tat1-72 is increased in the presence of NaCl. In similar conditions, Tat1-72 aggregates stained with Congo Red displayed a yellow-green birefringence and a red-shift in the Congo Red absorbance that is typical of β-amyloid fibril. The web-based algorithm “WALTZ” identifies the majority of the Tat1-72 hydrophobic core region as amyloidogenic. The helical propensity of Tat1-72 in TFE was determined by two-dimensional NMR spectroscopy.

No description available.

Tat1-72, is an intrinsically disordered protein at pH 4.1 as previously indicated by NMR chemical shifts and coupling constants, and confirmed by 15N-relaxation parameters. The presence of SDS elicits a conformational change to α-helicity in Tat1-72. In the presence of the non-ionic DDM detergent and zinc, Tat was found to be soluble at pH 4 when bound to TAR RNA; TAR binding also elicits a conformational shift to α-helicity in Tat1-72. The β-sheet content of Tat1-72 is increased in the presence of NaCl. In similar conditions, Tat1-72 aggregates stained with Congo Red displayed a yellow-green birefringence and a red-shift in the Congo Red absorbance that is typical of β-amyloid fibril. The web-based algorithm “WALTZ” identifies the majority of the Tat1-72 hydrophobic core region as amyloidogenic. The helical propensity of Tat1-72 in TFE was determined by two-dimensional NMR spectroscopy.

Photocopy of typescript. / Thesis (Ph. D.)--University of Hawaii at Manoa, 1979. / Bibliography: leaves 174-182. / Microfiche. / xvi, 182 leaves ill. 29 cm

This thesis presents time-dependent density functional theory studies on electronic and vibronically resolved linear and nonlinear optical absorption and dichroism spectra of organic molecules. Special attention has been paid to the influence of solvent environment and molecular vibrations on one-, two- and three-photon absorption and one- and two-photon circular dichroism. It is found that dielectric medium as described by polarizable continuum model can enhance remarkably three-photon absorption cross section of a highly conjugated fluorene derivative, for which the simplified two-state model is shown to be largely inadequate. Origin-invariant density functional calculations on one- and two-photon circular dichroisms of a chiral molecule confirm that the recently developed CAMB3LYP functional performs better than the popular B3LYP functional for Rydberg-states. The first experimental measurement of TPCD spectra is performed on an axial chiral system in tetrahydrofunan, where the double L-scan technique is applied. Theoretical calculations well reproduce the experimental profiles when both the electron correlation and the solvent effect are taken into account. Vibronically resolved one- and two-photon absorption spectra of charge-transfer molecules have been obtained using a Linear Coupling model, where the 'borrowing mechanism' for the so-called Herzberg-Teller contribution is analyzed in detail. It is shown that Herzberg-Teller contribution can introduce a change of sign to the chiral responses of a molecule without the involvement of different electronic states, which has important consequences for the assignment of absolute configurations of chiral molecules. Adiabatic harmonic Franck-Condon model is also applied to simulate vibronically resolved one- and two-photon circular dichroism spectra of the same chiral system, where the sign-inversion and the interference between Franck-Condon and Herzberg-Teller contributions are also observed. / QC 20100727

Thesis (D. Sc.)--University of Sydney, 2003. / Title from title screen (viewed Apr. 28, 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Science to the School of Chemistry, Faculty of Science. Degree awarded 2003; thesis submitted 2002. Includes bibliographical references. Also available in print form.