No description available.

The overwhelming increase in antibiotic resistant bacterial strains poses a serious public health problem, with multiply-resistant strains becoming an important cause of mortality in hospitals. The predominant mechanism of resistance to aminoglycoside antibiotics involves enzymatic modification of the drug, rendering it ineffective. The crystal structure of the aminoglycoside-modifying enzyme aminoglycoside acetyltransferase(6')-Ii (AAC(6')-Ii) in complex with its cofactor, acetyl coenzyme A (AcCoA), was determined at 2.7 Å resolution by the multiwavelength anomalous diffraction technique. The resolution of this structure was subsequently extended to 2.15 Å by molecular replacement, with no significant changes in the topology of the complex. The enzyme was found to exhibit a novel CoA-binding fold, with the cofactor bound in a cleft between the N-and C-terminal arms of the protein molecule. Although the enzyme packs as a monomer in the I4₁32 crystal form, the most probable physiological dimer of the complex was determined through analysis of a number of symmetry-related molecules. The crystal structure of the AAC(6')-Ii•AcCoA complex was compared to the structures of three members of a large superfamily of GCN5-related 𝘕-acetyltransferases (GNATs), namely yeast histone acetyltransferase HAT1, 𝘕-myristoyltransferase, and aminoglycoside acetyltransferase(3)-Ia. Despite negligible sequence similarity between these GNAT superfamily members, a distinct folding pattern is conserved in all four structures. This establishes AAC(6')-Ii as a structural homolog of enzymes with protein acetylating activity, supporting the hypothesis that the enzyme may possess another physiological function in 𝘌𝘯𝘵𝘦𝘳𝘰𝘤𝘰𝘤𝘤𝘶𝘴 𝘧𝘢𝘦𝘤𝘪𝘶𝘮. / Thesis / Master of Science (MS)

No / The predicted stability differences of the conformational polymorphs of oxalyl dihydrazide and ortho-acetamidobenzamide are unrealistically large when the modeling of intermolecular energies is solely based on the isolated-molecule charge density, neglecting charge density polarization. Ab initio calculated crystal electron densities showed qualitative differences depending on the spatial arrangement of molecules in the lattice with the greatest variations observed for polymorphs that differ in the extent of inter- and intramolecular hydrogen bonding. We show that accounting for induction dramatically alters the calculated stability order of the polymorphs and reduces their predicted stability differences to be in better agreement with experiment. Given the challenges in modeling conformational polymorphs with marked differences in hydrogen bonding geometries, we performed an extensive periodic density functional study with a range of exchange-correlation functionals using both atomic and plane wave basis sets. Although such electronic structure methods model the electrostatic and polarization contributions well, the underestimation of dispersion interactions by current exchange-correlation functionals limits their applicability. The use of an empirical dispersion-corrected density functional method consistently reduces the structural deviations between the experimental and energy minimized crystal structures and achieves plausible stability differences. Thus, we have established which types of models may give worthwhile relative energies for crystal structures and other condensed phases of flexible molecules with intra- and intermolecular hydrogen bonding capabilities, advancing the possibility of simulation studies on polymorphic pharmaceuticals.

No / No Abstract

No / Crystallisation is a widely used technique for purification and manipulation of the final crystal form of therapeutic agents. In particular, potential exists to control the mechanical properties of ibuprofen through control of crystal habit. The aim of this study was therefore to understand the influence of crystallisation conditions on the morphology of ibuprofen to enable production of crystals with different habits.

Yes / The creation of salts is a frequently used approach for the modification of physicochemical properties of an active pharmaceutical ingredient. Despite the frequency of application, there has been little research into the structural-property relationships of the final material and the nature of the counterion present. This work reports on five new salts of sulfathiazole and compares the energetics of the intermolecular interactions with variation in the crystal packing motifs.

No description available.

The preparation of bicrystal specimens of high interfacial purity and accurately controlled mismatch of orientation between grains with a specific boundary orientation are critical for fundamental studies of the structure and properties of grain boundaries. A method was developed for routinely producing high-purity aluminum bicrystals of desired mismatch and boundary orientation. A strain annealing technique was used for making large single crystals. The orientation, structural perfection, and chemical purity of the seeds were characterized, then the seeds were joined by using an electron beam welder. The welder was designed and built as a major portion of this work.

In this thesis, the nonlinear properties of dye-doped liquid crystal films measured via Z-scan technique are presented, and we¡¦ve also compared the features of nonlinear effect between nematic and cholesteric liquid crystals, because the purpose was to obtain a strong nonlinear effect which is polarization independent. The nonlinear refraction of the samples would induce self-focusing/self-defocusing effect, therefore the Z-scan technique was utilized for the measurements in this study. The degrees of self-focusing/self-defocusing effect can be used to calculate the optical Kerr constants n2 related to the variation of refractive indices. Moreover, this technique is uncomplicated and powerful for nonlinear effect observations, because it only requires a single laser beam and a simple setup to measure both nonlinear refractive indices and nonlinear absorption coefficients. In the first section of the study, we had investigated the nonlinear effect of azo-dye-doped liquid crystal (ADDLC) films by Z-scan technique. Owing to the birefringence provided by homogeneous-alignment liquid crystal films and the absorption difference between the long axis and the short axis of the azo dye, the self-defocusing effect in nematic phase was larger than that in isotropic state as the polarization of incident light was parallel to the long axis of aligned liquid crystals. While we set the incident polarization perpendicular to the long axis of liquid crystals, a self-focusing effect was observed and the in nematic phase was found smaller than that in isotropic state. As a result, it can be analyzed that the nonlinear effect of homogeneous aligned ADDLC films is intensely polarization-dependent. In the second section, in order to acquire a polarization-independent nonlinear effect, we fabricated the azo-dye-doped cholesteric liquid crystal (ADDCLC) films which were arranged in planar texture with the reflection bands managed to avoid the III wavelength of incident light. We had studied the nonlinear effects in different concentrations of the azo dye and also measured the influence of incident polarizations. We discover that when the concentration of dyes was raised, the n2 increased as well; the nonlinear indices were almost the same in various polarized light. The incident light suffered an average refractive index in an ADDCLC film, and azo dye arranged in helices resulted in identical absorption to different polarized light. In summary, employing ADDCLCs with planar texture in nonlinear optical applications, we could achieve not only strong nonlinear effects but also high polarization independence in liquid crystals.

In this study, we study three kinds of surface treatments in the blue phase lasers. Three kinds of surface treatments include no surface treatment, homogeneous alignment ,HA, and vertical alignment ,VA. Blue Phase liquid crystal is a three-dimensional photonic crystal, and it can be used to be a laser cavity. When the blue phase doped with a laser dye, a laser emission can be observed under appropriate pumping energy. In the first part, we fabricate the blue phase lasers with three kinds of surface, there are different surface treatments to study the surface effect of the optoelectronic properties. It is found that the threshold pumping power is significantly decreased under a surface treatment on glass substrate. In the second part, we change cooling rate in the formation of the blue phase liquid crystals, and study the optoelectronic properties of blue phase lasers. The experiment results reveal that the slower cooling rate leads to a order blue phase substrate, resulting in a lower threshold pumping energy of the blue phase laser.