Browsing by Subject "Crystallography"
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Item Crystalline Metal-Organic Frameworks Based on Conformationally Flexible Phosphonic Acids(2013-07-19) Gagnon, Kevin JamesThe goal of the work described in this dissertation was to investigate the structure of metal phosphonate frameworks which were composed of conforma-tionally flexible ligands. This goal was achieved through investigating new syn-thetic techniques, systematically changing structural aspects (i.e. chain length), and conducting in situ X-ray diffraction experiments under non-ambient condi-tions. First, the use of ionic liquids in the synthesis of metal phosphonates was in-vestigated. Reaction systems which had previously been studied in purely aqueous synthetic media were reinvestigated with the addition of a hydrophobic ionic liq-uid to the reaction. Second, the structural diversity of zinc alkylbisphosphonates was investigated through systematically varying the chain length and reaction conditions. Last, the structural changes associated with externally applied stimuli (namely temperature and pressure) on conformationally flexible metal phospho-nates were investigated. Elevated temperature was used to investigate the structur-al changes of a 1-D cobalt chain compound through three stages of dehydration and also applied pressures of up to 10 GPa were used to probe the structural resili-ence of two zinc alkylbisphosphonate materials under. The iminobis(methylphosphonic acid) type ligands are a good example of a small, simple, conformationally flexible ligand. There are three distinct different structural types, utilizing this ligand with cobalt metal, described in the literature, all of which contain bound or solvated water molecules. The addition of a hydrophobic ionic liquid to an aqueous synthesis medium resulted in new anhydrous compounds with unique structural features. Systematic investigations of zinc alkylbisphosphonate materials, construct-ed with three to six carbon linker ligands, resulted in four new families of com-pounds. Each of these families has unique structural features which may prove in-teresting in future applications developments. Importantly, it is shown that wheth-er the chain length is odd or even plays a role in structural type although it is not necessarily a requirement for a given structural type; furthermore, chain length itself is not strictly determinative of structural type. Dehydration in a cobalt phosphonate was followed via in situ single crystal X-ray diffraction. The compound goes through a two-stage dehydration mecha-nism in which the compound changes from a 1-D chain to a 2-D sheet. This pro-cess is reversible and shows unique switchable magnetic properties. The high pressure studies of an alkyl chain built zinc metal phosphonate showed that the chains provide a spring-like cushion to stabilize the compression of the system allowing for large distortions in the metal coordination environment, without destruction of the material. This intriguing observation raises questions as to whether or not these types of materials may play a role as a new class of piezo-functional solid-state materials.Item Descriptive geometry in the geosciences(Texas Tech University, 1952-06) Huzarski, Richard GeorgeNot availableItem Electronic structure of dimetal bonded systems: ditungsten, dimolybdenum and diruthenium systems(Texas A&M University, 2007-04-25) Villagran Martinez, DinoThis dissertation investigates three topics in the field of multiple-bonded metal chemistry. The first topic concerns the synthetic and theoretical considerations of ditungsten formamidinates and guanidinates compounds. This work presents an enhanced synthetic path to the W2(hpp)4 molecule (Hhpp = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine). The reflux of W(CO)6 with Hhpp in o-dichlorobenzene at 200 oC produces W2(hpp)4Cl2 in a one-pot reaction in 92% yield. This compound is stable and easily stored for further use, and it can be efficiently reduced in a one-step reaction to the most easily ionized compound W2(hpp)4. This work also examines the electronic structure and geometry of the intermediates W2(????-CO)2(????- hpp)2(????2-hpp)2 and W2(hpp)4Cl2. The second topic concerns the theoretical investigation by DFT of the electronic structure of [Mo2] units bridged by oxamidate ligands or bridging hydride ions ([Mo2] = (Mo2(DArF)3, where DArF is the anion of a diarylformamidine). It is shown that the effect of the gauche conformation of the ???? oxamidate isomers is due to steric interactions, and that the planar ???? oxamidate isomers have an electronic structure similar to that of naphthalene when it is doubly oxidized. The [Mo2](????-H)2[Mo2] compound shows interdimetal unit interactions between the ???? orbitals of the two [Mo2] units. These interactions are theoretically predicted and experimentally observed by a decrease in the [Mo2]---[Mo2] distance with a one-electron oxidation of [Mo2](????- H)2[Mo2]. The final topic concerns the magnetic and structural properties of two Ru2(DArF)4Cl compounds. The compounds with Ar = p-anisyl (para) and m-anisyl (meta) both show different temperature dependence of their molar magnetic susceptibility, ????. For the para compound, there is a Boltzmann distribution between a ????*3 ground state and a ????*2????* upper state, and this is confirmed by a temperature dependence of the Ru-Ru bond length: 2.4471(5) ???? at 23 K and 2.3968(5) ???? at 300 K. For the meta compound, a ????*2????*configuration persists over the range of 23-300 K as shown by an invariant Ru-Ru bond length and its molar magnetic susceptibility.Item Inside the microbial weapons factory: structural studies of polyketide biosynthetic machinery(2015-08) Gay, Darren Christian; Keatinge-Clay, Adrian Tristan; Robertus, Jon; Hoffman, Dave; Barrick, Jeff; Ekerdt, JohnPolyketides are a class of small molecules synthesized by a broad spectrum of bacteria, plants, and fungi, and many exhibit powerful bioactive properties. The number of clinically-relevant compounds adapted from polyketide scaffolds is growing, eliciting attempts from synthetic organic chemists to construct polyketide-related compounds in the laboratory from simple chemical building blocks. Unfortunately, the current efficiency by which a skilled artisan can synthesize even small quantities of a polyketide is severely limited by the functional and stereochemical complexity of these compounds. Conceptually, it would be much simpler to genetically reprogram the enzymes responsible for polyketide biosynthesis to produce designer molecules; however, the massive size of polyketide synthase enzymes has hindered efforts towards understanding critical features of their structures and mechanisms. Only very recently has structural information become available for enzymes involved in polyketide biosynthesis, providing an initial glimpse into the inner workings of these subcellular pharmaceutical factories. It will not be possible for mankind to fully realize the potential of engineered polyketide synthases without understanding how their architectures govern the molecules they have evolved to produce. In this work, the structure and mechanism of several enzymes involved in polyketide biosynthesis is investigated. An unprecedented architecture for the ketoreductase-enoylreductase didomain from the second module of the spinosyn polyketide synthase reveals structural divergence from the related mammalian fatty acid synthase, and reconstituted in vitro activity of the enoylreductase domain indicates the isolated enzyme retains activity apart from its parent polyketide synthase module. The dehydratase domain isolated from the tenth module of the rifamycin polyketide synthase, previously hypothesized to only form double bonds with (Z) geometry, was found to have altered stereoselectivity dependent on the carrier handle bound to the substrate. The enoyl-isomerase domain, isolated from the fourteenth module of the bacillaene polyketide synthase, utilizes a catalytic mechanism that relies only on a single active site histidine. A series of ketosynthase domains from trans-acyltransferase polyketide synthases reveal how polyketides bind covalently to the active site of the ketosynthase, and how the flanking subdomain of the ketosynthase is used as an anchor point for the assembly of the polyketide synthase megacomplex.Item Max Weber at work 1910-1912 : 'primitive' experiments beyond the known dimensions(2015-08) Plunger, Brady James; Henderson, Linda Dalrymple, 1948-; Rather, SusanThis thesis seeks to build on earlier interpretations of Weber's writings and paintings in the years between 1910 and 1912 by illustrating how the contemporary discourses of primitivism inflected Weber's assimilation of these and other areas of knowledge into his understanding of the intellectual, affective, and sensorial processes involved in the making and viewing of art. Of particular interest here are the intersections that Weber created in his two 1910 essays, "The Fourth Dimension from a Plastic Point of View" and "Chinese Dolls and Modern Colorists," between certain key primitivist tropes, his interest in "plastic" formal values and aspects of popular science and mathematics, and the wider cultural fascination with the spiritual. This thesis explores this web of associations to reveal that Weber's transformative engagement with primitivism alongside these other key concerns that governed his theorizing on the function and value of works of art. Central to this thesis are Weber's two 1910 texts along with his paintings of 1910-1912, including his "Crystal Figures," which stand as Weber's most substantive theoretical and aesthetic statements at this early moment of his career. These various productions are analyzed simultaneously to illustrate the ways in which Weber's writings and visual experimenting complement each other and reveal the novel ways in which he integrated diverse areas of knowledge into his arguments for the importance of art in the new world of the twentieth century.Item The molecular basis of nucleotide recognition for T7 DNA polymerase(2008-08) Jin, Zhinan, 1972-; Johnson, Kenneth AllenDNA replication demands extraordinary specificity and efficiency of catalysis from a DNA polymerase. Previous studies on several DNA polymerases suggested that a rate-limiting conformational change preceding chemistry accounts for the high specificity following the induced fit mechanism. However, the identity of this rate-limiting conformational change and how it contributes to the fidelity is still under debate. An important study of T7 DNA polymerase performed by Tsai and Johnson using a conformationally sensitive fluorophore (CSF) characterized a conformational change directly and presented a new paradigm for nucleotide selectivity. This thesis describes work to further characterize the underlying molecular basis regulating the conformational change by a combination of site-directed mutagenesis, transient kinetics and crystallography. One flexible segment (gly-ala-gly) within the fingers domain was mutated to (ala-alaala). The kinetic analysis on this mutant showed that the mutations decreased the forward rate of the conformational change reported by the fluorophore about 1200-fold but there was no significant change on the reverse rate. The data suggested that the movement of the fingers domain is not a rigid body motion but may be complex due to the movements of various helices within the fingers domain. Quantification of the kinetics of incorporation of correct and incorrect base pairs showed the decrease of fidelity mainly was from the decreased forward rate during correct nucleotide incorporation. The roles of three active site residues, K522, H506, and R518, which form polar interactions with [alpha]-,[beat]- and [gamma]-phosphates of the incoming nucleotide respectively, in conformational change and catalysis were also characterized. All the mutants showed a slower conformational change than the wild type enzyme. After this conformational change, there was a rate limiting step with a rate comparable to kpol measured by quench-flow experiments. Correct nucleotide binding caused an increase in fluorescence, suggesting that the conformational change of the fingers domain delivers incoming nucleotide to a misaligned status even for a correct nucleotide with each of the mutants. The data suggested that active site residues play important roles in maintaining a fast conformational change and an accurate alignment of the active site during correct nucleotide incorporation. Yellow crystals of CSF-labeled T7 DNA polymerase with DNA and correct nucleotide (closed complex), incorrect nucleotide (misaligned complex) or no nucleotide (open complex) were grown to good size and diffracted to 3 Å during X-ray data collection. The structures of these complexes are still under refinement.Item NMR structure and preliminary crystallographic studies of small protein B (SmpB) from Aquifex aeolicus(2002) Dong, Gang; Hoffman, David W., Ph. D.The tmRNA-SmpB system is a highly conserved quality control system in all prokaryotes. It has the dual function of rescuing ribosomes stalled on defective mRNA templates and tagging proteins resulting from problematic messages for degradation. Small protein B (SmpB) is an essential component of this system, lacking significant homology with any known proteins other than the same proteins from different species. The structure of the SmpB from Aquifex aeolicus was determined by multidimensional NMR techniques. It consists of an antiparallel b-barrel, with three helices packed outside the core of the barrel. While the overall structure of SmpB appears to be unique, the protein does contain an embedded oligonucleotide binding (OB) fold; in this respect SmpB has similarity to several other RNA-binding proteins that are known to be associated with translation, including initiation factor 1 (IF1), ribosomal protein S17 and the N-terminal domain of aspartyltRNA synthetase (DRS). Conserved amino acids on the protein surface that are likely candidates for direct interactions with the tmRNA and other components of the translational apparatus were identified. The presence of the two widely separated clusters of conserved surface amino acids suggests that SmpB could function either by stabilizing two distal regions of the tmRNA, or by facilitating an interaction between the tmRNA and another component of the translational apparatus. While the C-terminal ~20 amino acids appear to be unstructured, their presence may be essential for the function of SmpB in the trans-translation process. The structural model reported in this dissertation will be essential in ultimately determining the detailed mechanism by which the tmRNASmpB system performs its functions. Results of preliminary NMR perturbation studies on the complexes between SmpB and several RNA molecules are described. In addition, single crystals of the core fragment of the SmpB were obtained by the vapor diffusion method in sitting-drops at room temperature. Preliminary crystallographic analysis reveals that the crystal belongs to a tetragonal lattice, with unit cell parameters a = b = 55.0 Å, c = 65.9 Å, a = b = g = 90°. Further structural determinations by molecular rep.Item Structural studies of ribosomal RNA based on cross-analysis of comparative models and three-dimensional crystal structures(2003) Lee, Jung Chull; Whitman, Christian P.; Gutell, RobinBasepair mapping of the rRNAs in the high-resolution crystal structures of the Thermus thermophilus 30S and Haloarcula marismortui 50S ribosomal subunits not only proved the authenticity of covariation analysis in predicting RNA secondary structures with high accuracy, but also provided a great wealth of information on RNA structure, ranging from diverse basepair conformations to structure motifs. Based on cross-analysis of comparative structure models and crystal structures of rRNAs, a systematic and unambiguous classification for basepair conformations is established, and the structural features and biological implications for a wide variety of RNA sequence and structure motifs, including the AA.AG@helix.ends motif, the sticky motif consisting of AGUA/GAA, GUA/GAA, and GGA/GAA motifs, and the lonepair triloop motif, are discussed.Item Structure, function, and inhibition of enoyl reductases(2009-05-15) Kuo, Mack RyanMalaria and tuberculosis constitute two of the world?s deadliest infectious diseases. Together, they afflict over one third of the world?s population. Once thought of as one of a group of nearly vanquished diseases only 50 years ago, malaria and tuberculosis have experienced renewed prominence due to issues such as multi-drug resistance and a lack of responsiveness by the global community. Fatty acid biosynthesis has been shown to be an essential pathway to the causative organisms of malaria and tuberculosis. One integral component of the fatty acid biosynthesis pathway, enoyl acyl-carrier-protein (ACP) reductase, has repeatedly been validated as an appropriate drug target in other organisms. The 2.4 ? crystal structure of the enoyl-ACP reductase from the human parasite Plasmodium falciparum (PfENR) reveals a nucleotide-binding Rossmann fold, as well as the identity of several active site residues important for catalysis. The 2.43 ? crystal structure of PfENR bound with triclosan, a widely utilized anti-bacterial compound, provides new information concerning key elements of inhibitor binding. Applying knowledge attained from these initial crystal structures, several triclosan derivatives were synthesized, and subsequently PfENR:inhibitor co-crystal structures were determined to extend our knowledge of protein:inhibitor interactions within the active site. Additionally, the crystal structures of the enoyl-ACP reductase from the mouse parasite Plasmodium berghei (PbENR), in apo-form and in complex with triclosan, were refined to 2.9 ? and 2.5 ? resolution, respectively. These structures confirm the structural and active site conservation between the human and mouse parasite enoyl-ACP reductases, suggesting that utilizing a murine model for in vivo testing of promising inhibitors is viable. The 2.6 ? crystal structure of the enoyl-ACP reductase from Mycobacterium tuberculosis (InhA) in complex with triclosan reveals a novel configuration of triclosan binding, where two molecules of triclosan are accommodated within the InhA active site. Finally, high-throughput screening approaches using enoyl acyl-carrier-protein reductases as the targets were utilized to identify new lead compounds for future generations of drugs. The 2.7 ? crystal structure of InhA bound with Genz-10850 confirms the value of this technique.Item Symmetry-Guided Design of Advanced Porous Materials with Anticipated Porosities and Functionalities(2014-10-08) Zhang, MuweiFor the past few decades, advanced porous materials (APMs) have attracted a tremendous amount of attention due to their fascinating structures and diverse applications. Metal-organic frameworks (MOFs), metal-organic polyhedra (MOPs) and porous polymer networks (PPNs) are important categories of APMs. By unravelling their structure-property relationships and employing the principles of group theory and topochemistry, this dissertation will focus on the rational design of these APMs with anticipated structures, porosities and properties. The vast majority of this dissertation will rely on the utilization of the tetrahedral building blocks in the construction of MOFs and PPNs. A few representative examples of MOMs with biomimetic features will also be presented. The first part of this dissertation introduces background knowledge for the chemistry of APMs. In addition to their definition and potential applications, it provides a systematic overview of different methods for the rational design of APMs. The second part illustrates the structures and gas storage applications of a series of MOFs constructed from a synthetically-accessible tetrahedral ligand. The study of symmetry-guided design of MOFs includes further exploration of tetrahedral ligands. The third part elucidates how the employment of topochemistry can lead to the discovery of a MOF with the largest porosity among all MOFs made from tetrahedral linkers. The symmetry-guided strategy can also be applied to the synthesis of PPNs. The fourth part describes the rational design, preparation and characterization of a commercially affordable PPN for highly efficient CO2 capture. Tetrahedral building units are also highly attractive for constructing mixed-ligand MOFs. In the next part is a close examination of the symmetry elements in Bravais lattices seen in MOFs, which has led to the discovery of a series of highly porous mixed-ligand MOFs. The sixth part discusses the design and synthesis two nucleobase-incorporated MOMs. It also briefly covers the rational design of MOMs with biomimetic features. In summary, a wide variety of APMs with anticipated structures and properties are rationally designed, based on a close examination of the symmetry elements of their basic building blocks. This work also offers a general perspective on the rational design of APMs with desired porosities and functionalities.Item The x-ray crystal structure of wheat translation initiation factor eIF4E(2002) Sadow, Jennifer Beth Hurley; Robertus, Jon D.