Dissertations / Theses on the topic 'Structural thermodynamics'

Calcineurin (CaN), a heterodimeric Ca2+-calmodulin-dependent Ser/Thr phosphatase, regulates diverse pathways, from stress responses in yeast to T-cell activation and cardiac hypertrophy in humans. Calmodulin (CaM), an essential mediator of calcium–dependent signaling pathways, activates CaN in the presence of calcium by binding to an intrinsically disordered region of the enzyme and altering its conformation. My hydrodynamic studies have determined that CaM participates in a 1:1 complex with the CaM-binding domain of βCaN (CaNp, residues 400–423). To explore the molecular mechanism of CaM association with CaN, I have used spectroscopic methods to determine the calcium-dependent and domain–specific interactions of CaM with CaNp. These studies revealed that the affinity of CaM1–148 for CaNp was weak in the absence of calcium, and very high (Kd in the nM to pM range) in the presence of calcium. I have demonstrated that CaNp binding to CaM increases the calcium–binding affinity of each domain of CaM1–148 to a similar degree, thereby retaining the property of sequential calcium binding to the domains, with preference for sites in the C–domain. This allows the N–domain to lag in response to an increase in cellular calcium and perhaps contribute to the regulation of CaN in a manner distinct from that of the C–domain. NMR studies of calcium–saturated CaM1–148 demonstrated that the N–domain of CaM experienced a larger structural perturbation than the C–domain upon binding CaNp. Additional NMR studies revealed that CaNp adopts an anti–parallel orientation when bound to CaM, with the sole aromatic residue of CaNp contacting the N–domain of CaM. This contrasts with many CaM-target complexes in which the sole aromatic residue contacts the C–domain of CaM. Rigorous thermodynamic studies explored how mutations in the calcium-binding sites of mammalian CaM (mCaM) and mutations known to cause disruption of CaM–mediated ion channel regulation in Paramecia (PCaM) affected the allosteric interactions of the domains of CaM in the presence of CaNp. These studies demonstrated separable roles of the domains of CaM in recognition of CaNp. The consequences of a mutation depended upon its location within the complex. Collectively, research presented in this thesis provides insight into the mechanisms whereby the two domains of CaM contribute to recognition of CaN.

Proliferating cell nuclear antigen (PCNA) is an essential protein in the cell. It is involved in transcription and many types of DNA repair and replication. Homologues of this protein are found in all orders of life. The high level of conservation and essential nature of PCNA infers that it may be a potential drug target for anti-caner drugs in humans and also a potential anti-parasitic target. X-ray structures of PCNA from Homo sapiens (Hs), Schizosaccharomyces pombe (Sp) and Leishmania major (Lm) are now available and can be used as a template for structure based drug design. In this work PCNA from these three species have been prepared in milligram quantities for biochemical and biophysical studies. The previously unknown structure of LmPCNA has been solved in an uncomplexed form and also complexed with a dodecapeptide to a resolution of 3.0Å. A comparison of PCNA structures and their peptide complexes for the three species identifies structural differences which may be relevant in analysing thermodynamic contributions of binding. All eukaryotic PCNA molecules exist as ring shaped trimers which form around DNA. In this work the oligomeric state of LmPCNA has been determined to be hexameric both in solution and in the crystal. It has also been hypothesised that HsPCNA is hexameric however these would seem to form hexamers in which the trimeric rings associate “back-to-back” while LmPCNA trimers would seem to associate “face-to-face”. The binding affinities for these three PCNAs have been determined with a selection of peptides derived from the Hs p21 protein. This work has shown, using a selection of different techniques including Surface Plasmon Resonance (SPR), Isothermal Titration Calorimetry (ITC) and Dynamic Scanning Fluorimetry (DSF); that HsPCNA and SpPCNA have similar affinities for a 12mer peptide (Kd of ~1μM) however LmPCNA shows significantly weaker interactions (Kd of ~10μM). This is most likely due to divergence in the sequence and structure of LmPCNA. A systematic investigation by SPR on the effect of peptide linker length on binding has been carried out using a series of synthesised peptides with different lengths of chemical spacer. The series of streptavidin immobilised peptides show that longer spacers are required for the recovery of the PCNA peptide binding affinity. The results presented in this work indicate that a linker length of at least 20Å is required for measurable protein binding activity. This interaction is improved with longer peptide spacers.

The main focus of the thesis is to have better understanding of the atomic and electronic structures, vibrational dynamics and thermodynamics of metallic surfaces and bi-metallic nanoparticles (NPs) via a multi-scale simulational approach. The research presented here involves the study of the physical and chemical properties of metallic surfaces and NPs that are useful to determine their functionality in building novel materials. The study follows the  bottom-up approach for which the knowledge gathered at the scale of atoms and NPs serves as a base to build, at the macroscopic scale, materials with desired physical and chemical properties. We use a variety of theoretical and computational tools with different degrees of accuracy to study problems in different time and length scales. Interactions between the atoms are derived using both Density Functional Theory (DFT) and Embedded Atom Method (EAM), depending on the scale of the problem at hand. For some cases, both methods are used for the purpose of comparison. For revealing the local contributions to the vibrational dynamics and thermodynamics for the systems possessing site-specific environments, a local approach in real-space is used, namely Real Space Green s Function method (RSGF). For simulating diffusion of atoms/clusters and growth on metal surfaces, Molecular Statics (MS) and Molecular Dynamics (MD) methods are employed.<br>Ph.D.<br>Department of Physics<br>Sciences<br>Physics PhD

Nuclear Magnetic Resonance (NMR) Spectroscopy is a crucial tool for determining the structures of biological molecules. This technique can also be used to extract thermodynamic parameters of these molecules, enhancing our understanding of their biological roles. DNA is analyzed through NMR Spectroscopy in order to identify the effect of sequence on expressivity. DNA predominantly resides in BI orientation, but a second conformation, BII, also exists. DNA can switch between BI and BII backbone conformations and the likelihood of this switching is dependent upon the energetic barrier between these two sub-states. The secondary structure of DNA, and thus its adoption of BI and BII conformation, is sequence-dependent. Therefore, the identity and neighboring base pairs of a segment of DNA have a large effect on the flexibility of the backbone. Methylation also affects backbone structure. The methyl group has been shown to promote either stabilization and/or destabilization on proximate bases. This thesis uses variable temperature NMR and Mathematica modeling to determine the backbone conformations, rate of inter-conversion between BI/BII conformations, and the energetic barrier of this fluctuation for each nucleotide step in DNA dodecamers containing the CRE binding sequence. This has been a long-term goal of the Hatcher-Skeers lab, and the data from this thesis would have been added to years of flanked CRE DNA information to reveal any patterns. In this experiment, 5’-TTTC-3’ CRE DNA dodecamers underwent NMR analyses to extract backbone flexibility parameters. Additionally, the effect of methylation was studied in scans with methylated cytosine in the central CRE sequence. The TRX scale was used to predict the BII character of these sequences. Due to technical errors, the experimental results were not able to accurately represent the specific dynamics of each backbone step. However, general trends were identified, such as adherence to and veracity of the TRX scale and the effect of methylation. It was found that the %BII of the native DNA closely resembled the TRX predictions, whilst the methylated sequence did not. The largest changes in activation energy due to methylation occurred in the central CRE sequence, suggesting methylation is a localized effect. The results reflected several trends from past CRE experiments, but the data cannot be explicitly analyzed due to the technical errors.

Shock waves create a unique environment of high pressure, high temperature and high strain-rates. It has been observed that chemical reactions that occur in this regime are exothermic and can lead to the synthesis of new materials that are not possible under other conditions. The exothermic reaction is used in the development of binary energetic materials. These materials are of significant interest to the energetic materials community because of its capability of releasing high heat content during a chemical reaction and the relative insensitivity of these types of energetic materials. Synthesis of these energetic materials, at nano grain sizes with structural reinforcements, provides an opportunity to develop a dual functional material with both strength and energetic characteristics. Shock-induced chemical reactions pose challenges in experiment and instrumentation. This thesis is addressed to the theoretical development of constitutive models of shock-induced chemical reactions in energetic composites, formulated in the framework of non-equilibrium thermodynamics and mixture theories, in a continuum scale. Transition state-based chemical reaction models are introduced and incorporated with the conservation equations that can be used to calculate and simulate the shock-induced reaction process. The energy that should be supplied to reach the transition state has been theoretically modeled by considering both the pore collapse mechanism and the plastic flow with increasing yield stress behind the shock wave. A non-equilibrium thermodynamics framework and the associated evolution equations are introduced to account for time delays that are observed in the experiments of shock-induced or assisted chemical reactions. An appropriate representation of the particle size effects is introduced by modifying the initial energy state of the reactants. Numerical results are presented for shock-induced reactions of mixtures of Al, Fe2O3 and Ni, Al with epoxy as the binder. The theoretical model, in the continuum scale, requires parameters that should be experimentally determined. The experimental characterization has many challenges in measurement and development of nano instrumentation. An alternate approach to determine these parameters is through ab-initio calculations. Thus, this thesis has initiated ab-initio molecular dynamics studies of shock-induced chemical reactions. Specifically, the case of thermal initiation of chemical reactions in aluminum and nickel is considered.

The interaction between two 6 kDa proteins has been investigated. The studied complex of micromolar affinity (Kd) consists of the Z domain derived from staphylococcal protein A and the related protein ZSPA-1, belonging to a group of binding proteins denoted affibody molecules generated via combinatorial engineering of the Z domain. Affibody-target protein complexes are good model systems for structural and thermodynamic studies of protein-protein interactions. With the Z:ZSPA-1 pair as a starting point, we determined the solution structure of the complex and carried out a preliminary characterization of ZSPA-1. We found that the complex contains a rather large (ca. 1600 Å2) interaction interface with tight steric and polar/nonpolar complementarity. The structure of ZSPA-1 in the complex is well-ordered in a conformation that is very similar to that of the Z domain. However, the conformation of the free ZSPA-1 is best characterized by comparisons with protein molten globules. It shows a reduced secondary structure content, aggregation propensity, poor thermal stability, and binds the hydrophobic dye ANS. This molten globule state of ZSPA-1 is the native state in the absence of the Z domain, and the ordered state is only adopted following a stabilization that occurs upon binding. A more extensive characterization of ZSPA-1 suggested that the average topology of the Z domain is retained in the molten globule state but that it is represented by a multitude of conformations. Furthermore, the molten globule state is only marginally stable, and a significant fraction of ZSPA-1 exists in a completely unfolded state at room temperature. A complete thermodynamic characterization of the Z:ZSPA-1 pair suggests that the stabilization of the molten globule state to an ordered three helix structure in the complex is associated with a significant conformational entropy penalty that might influence the binding affinity negatively and result in an intermediate-affinity (µM) binding protein. This can be compared to a dissociation constant of 20-70 nM for the complex Z:Fc of IgG where Z uses the same binding surface as in Z:ZSPA-1. Structure analyses of Z in the free and bound state reveal an induced fit response upon complex formation with ZSPA-1 where a conformational change of several side chains in the binding surface increases the accessible surface area with almost 400 Å2 i.e. almost half of the total interaction surface in the complex. Two cysteine residues were introduced at specific positions in ZSPA-1 for five mutants in order to stabilize the conformation of ZSPA-1 by disulfide bridge formation. The mutants were thermodynamically characterized and the binding affinity of one mutant showed an improvement by more than a factor of ten. The improvement of the introduced cysteine bridge correlates with an increase in binding enthalpy rather than with entropy. Further analysis of the binding entropy suggests that the conformational entropy change in fact is reduced but its favorable contribution is opposed by a less favorable desolvation enthalpy change. These studies illustrate the structural and thermodynamic complexity of protein-protein interactions, but also that this complexity can be dissected and understood. In this study, a comprehensive characterization of the ZSPA-1 affibody has gained insight into the intricate mechanisms involved in complex formation. These theories were supported by the design of a ZSPA-1 mutant with improved binding affinity.<br>QC 20100924

This work concerns the interrelationship between thermodynamic, kinetic and structural aspects of crystal polymorphism. It is both experimental and theoretical, and limited with respect to compounds to substituted monocyclic aromatics. Two polymorphs of the compound m-aminobenzoic acid have been experimentally isolated and characterized by ATR-FTIR spectroscopy, X-ray powder diffraction and optical microscopy. In addition, two polymorphs of the compound m-hydroxybenzoic acid have been isolated and characterized by ATR-FTIR spectroscopy, high-temperature XRPD, confocal Raman, hot-stage and scanning electron microscopy. For all polymorphs, melting properties and specific heat capacity have been determined calorimetrically, and the solubility in several pure solvents measured at different temperatures with a gravimetric method. The solid-state activity (ideal solubility), and the free energy, enthalpy and entropy of fusion have been determined as functions of temperature for all solid phases through a thermodynamic analysis of multiple experimental data. It is shown that m-aminobenzoic acid is an enantiotropic system, with a stability transition point determined to be located at approximately 156°C, and that the difference in free energy at room temperature between the polymorphs is considerable. It is further shown that m-hydroxybenzoic acid is a monotropic system, with minor differences in free energy, enthalpy and entropy. 1393 primary nucleation experiments have been carried out for both compounds in different series of repeatability experiments, differing with respect to solvent, cooling rate, saturation temperature and solution preparation and pre-treatment. It is found that in the vast majority of experiments, either the stable or the metastable polymorph is obtained in the pure form, and only for a few evaluated experimental conditions does one polymorph crystallize in all experiments. The fact that the polymorphic outcome of a crystallization is the result of the interplay between relative thermodynamic stability and nucleation kinetics, and that it is vital to perform multiple experiments under identical conditions when studying nucleation of polymorphic compounds, is strongly emphasized by the results of this work. The main experimental variable which in this work has been found to affect which polymorph will preferentially crystallize is the solvent. For m-aminobenzoic acid, it is shown how a significantly metastable polymorph can be obtained by choosing a solvent in which nucleation of the stable form is sufficiently obstructed. For m-hydroxybenzoic acid, nucleation of the stable polymorph is promoted in solvents where the solubility is high. It is shown how this partly can be rationalized by analysing solubility data with respect to temperature dependence. By crystallizing solutions differing only with respect to pre-treatment and which polymorph was dissolved, it is found that the immediate thermal and structural history of a solution can have a significant effect on nucleation, affecting the predisposition for overall nucleation as well as which polymorph will preferentially crystallize. A set of polymorphic crystal structures has been compiled from the Cambridge Structural Database. It is found that statistically, about 50% crystallize in the crystallographic space group P21/c. Furthermore, it is found that crystal structures of polymorphs tend to differ significantly with respect to either hydrogen bond network or molecular conformation. Molecular mechanics based Monte Carlo simulated annealing has been used to sample different potential crystal structures corresponding to minima in potential energy with respect to structural degrees of freedom, restricted to one space group, for each of the polymorphic compounds. It is found that all simulations result in very large numbers of predicted structures. About 15% of the predicted structures have excess relative lattice energies of &lt;=10% compared to the most stable predicted structure; a limit verified to reflect maximum lattice energy differences between experimentally observed polymorphs of similar compounds. The number of predicted structures is found to correlate to molecular weight and to the number of rotatable covalent bonds. A close study of two compounds has shown that predicted structures tend to belong to different groups defined by unique hydrogen bond networks, located in well-defined regions in energy/packing space according to the close-packing principle. It is hypothesized that kinetic effects in combination with this structural segregation might affect the number of potential structures that can be realized experimentally. The experimentally determined crystal structures of several compounds have been geometry-optimized (relaxed) to the nearest potential energy minimum using ten different combinations of common potential energy functions (force fields) and techniques for assigning nucleus-centred point charges used in the electrostatic description of the energy. Changes in structural coordinates upon relaxation have been quantified, crystal lattice energies calculated and compared with experimentally determined enthalpies of sublimation, and the energy difference before and after relaxation computed and analysed. It is found that certain combinations of force fields and charge assignment techniques work reasonably well for modelling crystal structures of small aromatics, provided that proper attention is paid to electrostatic description and to how the force field was parameterized. A comparison of energy differences for randomly packed as well as experimentally determined crystal structures before and after relaxation suggests that the potential energy function for the solid state of a small organic molecule is highly undulating with many deep, narrow and steep minima.<br>QC 20110527

Grade 91 (Gr.91) is a common structural material used in boiler applications and is favored due to its high temperature creep strength and oxidation resistance. Under cyclic stresses, the material will experience creep deformation eventually causing the propagation of type IV cracks within its heat-affected-zone (HAZ) which can be a major problem under short-term and long-term applications. In this study, we aim to improve this premature failure by performing a computational thermodynamic study through the Calculation of Phase Diagram (CALPHAD) approach. Under this approach, we have provided a baseline study as well as simulations based on additional alloying elements such as manganese (Mn), nickel (Ni), and titanium (Ti). Our simulation results have concluded that high concentrations of Mn and Ni had destabilized M23C6 for short-term creep failure, while Ti had increased the beneficial MX phase, and low concentrations of nitrogen (N) had successfully destabilized Z-phase formation for long-term creep failure.

The yttria-stabilized zirconia (YSZ) system has been extensively studied because of its critical applications, like solid oxide fuel cells (SOFCs), oxygen sensors, and jet engines. However, there are still important questions that need to be answered and significant thermodynamic information that needs to be provided for this system. There is no predictive tool for the ionic conductivity of the cubic-YSZ (c-YSZ), as an electrolyte in SOFCs. In addition, no quantitative diagram is available regarding the oxygen ion mobility in c-YSZ, which is highly effective on its ionic conductivity. Moreover, there is no applicable phase stability diagram for the nano-YSZ, which is applied in oxygen sensors. Phase diagrams are critical tools to design new applications of materials. Furthermore, even after extensive studies on the thermodynamic database of the YSZ system, the zirconia-rich side of the system shows considerable uncertainties regarding the phase equilibria, which can make the application designs unreliable. During this dissertation, the CALPHAD (CALculation of PHase Diagrams) approach was applied to provide a predictive diagram for the ionic conductivity of the c-YSZ system. The oxygen ion mobility, activation energy, and pre-exponential factor were also predicted. In addition, the CALPHAD approach was utilized to predict the Gibbs energy of bulk YSZ at different temperatures. The surface energy of each polymorph was then added to the predicted Gibbs energy of bulk YSZ to obtain the total Gibbs energy of nano-YSZ. Therefore, a 3-D phase stability diagram for the nano-YSZ system was provided, by which the stability range of each polymorph versus temperature and particle size are presented. Re-assessment of the thermodynamic database of the YSZ system was done by applying the CALPHAD approach. All of the available thermochemical and phase equilibria data were evaluated carefully and the most reliable ones were selected for the Gibbs energy optimization process. The results calculated by the optimized thermodynamic database showed good agreement with the selected experimental data, particularly on the zirconia-rich side of the system.

Kohlenhydrate stellen aufgrund der strukturellen Vielfalt und ihrer oft exponierten Lage auf Zelloberflächen wichtige Erkennungsstrukturen dar. Die Wechselwirkungen von Proteinen mit diesen Kohlenhydraten vermitteln einen spezifischen Informationsaustausch. Protein-Kohlenhydrat-Interaktionen und ihre Triebkräfte sind bislang nur teilweise verstanden, da nur wenig strukturelle Daten von Proteinen im Komplex mit vorwiegend kleinen Kohlenhydraten erhältlich sind. Mit der vorliegenden Promotionsarbeit soll ein Beitrag zum Verständnis von Protein-Kohlenhydrat-Wechselwirkungen durch Analysen struktureller Thermodynamik geleistet werden, um zukünftig Vorhersagen mit zuverlässigen Algorithmen zu erlauben. Als Modellsystem zur Erkennung komplexer Kohlenhydrate diente dabei das Tailspike Protein (TSP) aus dem Bakteriophagen HK620. Dieser Phage erkennt spezifisch seinen E. coli-Wirt anhand der Oberflächenzucker, der sogenannten O-Antigene. Dabei binden die TSP des Phagen das O-Antigen des Lipopolysaccharids (LPS) und weisen zudem eine hydrolytische Aktivität gegenüber dem Polysaccharid (PS) auf. Anhand von isolierten Oligosacchariden des Antigens (Typ O18A1) wurde die Bindung an HK620TSP und verschiedener Varianten davon systematisch analysiert. Die Bindung der komplexen Kohlenhydrate durch HK620TSP zeichnet sich durch große Interaktionsflächen aus. Durch einzelne Aminosäureaustausche im aktiven Zentrum wurden Varianten generiert, die eine tausendfach erhöhte Affinität (KD ~ 100 nM) im Vergleich zum Wildtyp-Protein (KD ~ 130 μM) aufweisen. Dabei zeichnet sich das System dadurch aus, dass die Bindung bei Raumtemperatur nicht nur enthalpisch, sondern auch entropisch getrieben wird. Ursache für den günstigen Entropiebeitrag ist die große Anzahl an Wassermolekülen, die bei der Bindung des Hexasaccharids verdrängt werden. Röntgenstrukturanalysen zeigten für alle TSP-Komplexe außer für Variante D339N unabhängig von der Hexasaccharid-Affinität analoge Protein- und Kohlenhydrat-Konformationen. Dabei kann die Bindestelle in zwei Regionen unterteilt werden: Zum einen befindet sich am reduzierenden Ende eine hydrophobe Tasche mit geringen Beiträgen zur Affinitätsgenerierung. Der Zugang zu dieser Tasche kann ohne große Affinitätseinbuße durch einen einzelnen Aminosäureaustausch (D339N) blockiert werden. In der zweiten Region kann durch den Austausch eines Glutamats durch ein Glutamin (E372Q) eine Bindestelle für ein zusätzliches Wassermolekül generiert werden. Die Rotation einiger Aminosäuren bei Kohlenhydratbindung führt zur Desolvatisierung und zur Ausbildung von zusätzlichen Wasserstoffbrücken, wodurch ein starker Affinitätsgewinn erzielt wird. HK620TSP ist nicht nur spezifisch für das O18A1-Antigen, sondern erkennt zudem das um eine Glucose verkürzte Oligosaccharid des Typs O18A und hydrolysiert polymere Strukturen davon. Studien zur Bindung von O18A-Pentasaccharid zeigten, dass sich die Triebkräfte der Bindung im Vergleich zu dem zuvor beschriebenen O18A1-Hexasaccharid verschoben haben. Durch Fehlen der Seitenkettenglucose ist die Bindung im Vergleich zu dem O18A1-Hexasaccharid weniger stark entropisch getrieben (Δ(-TΔS) ~ 10 kJ/mol), während der Enthalpiebeitrag zu der Bindung günstiger ist (ΔΔH ~ -10 kJ/mol). Insgesamt gleichen sich diese Effekte aus, wodurch sehr ähnliche Affinitäten der TSP-Varianten zu O18A1-Hexasaccharid und O18A-Pentasaccharid gemessen wurden. Durch die Bindung der Glucose werden aus einer hydrophoben Tasche vier Wassermoleküle verdrängt, was entropisch stark begünstigt ist. Unter enthalpischen Aspekten ist dies ebenso wie einige Kontakte zwischen der Glucose und einigen Resten in der Tasche eher ungünstig. Die Bindung der Glucose in die hydrophobe Tasche an HK620TSP trägt somit nicht zur Affinitätsgenerierung bei und es bleibt zu vermuten, dass sich das O18A1-Antigen-bindende HK620TSP aus einem O18A-Antigen-bindenden TSP evolutionär herleitet. In dem dritten Teilprojekt der Dissertation wurde der Infektionsmechanismus des Phagen HK620 untersucht. Es konnte gezeigt werden, dass analog zu dem verwandten Phagen P22 die Ejektion der DNA aus HK620 allein durch das Lipopolysaccharid (LPS) des Wirts in vitro induziert werden kann. Die Morphologie und Kettenlänge des LPS sowie die Aktivität von HK620TSP gegenüber dem LPS erwiesen sich dabei als essentiell. So konnte die DNA-Ejektion in vitro auch durch LPS aus Bakterien der Serogruppe O18A induziert werden, welches ebenfalls von dem TSP des Phagen gebunden und hydrolysiert wird. Diese Ergebnisse betonen die Rolle von TSP für die Erkennung der LPS-Rezeptoren als wichtigen Schritt für die Infektion durch die Podoviren HK620 und P22.<br>Carbohydrates are important for recognition events because of their diverse structure and their exposition on cell surfaces. Interactions between proteins and carbohydrates mediate a specific exchange of information crucial for manifold biological functions. The energetics of protein-carbohydrate-interactions are not very well understood so far due to the lack of structural data of proteins in complex with extensive oligosaccharides consisting of more than two building blocks. This dissertation improves the understanding of how proteins recognize complex carbohydrates by analysis of structural thermodynamics, which might lead to reliable algorithms for predictions of protein-carbohydrate-interactions. As model system for this work the tailspike protein (TSP) from coliphage HK620 was used. This phage recognizes specifically the surface O-antigen of its E. coli host by its TSP. HK620TSP does not only bind the O-antigen of host lipopolysaccharide (LPS), but also cleaves the polysaccharide (PS) by its endo-N-acetylglusaminidase activity. HK620TSP binds hexasaccharide fragments of this PS with low affinity (KD ~ 130 μM). However, single amino acid exchanges generated a set of high-affinity mutants with submicromolar dissociation constants (KD ~ 100 nM). Strikingly, at room temperature association is driven by enthalpic and entropic contributions emphasizing major solvent rearrangements upon complex formation. Regardless of their affinity towards hexasaccharide the TSP complexes showed only minor conformational differences in crystal structure analysis accept of mutant D339N. The extended sugar binding site can be subdivided into two regions: Firstly, there is a hydrophobic pocket at the reducing end with minor affinity contributions. Surprisingly, access to this site is blocked by a single exchange of aspartate to asparagine (D339N) without major loss in hexasaccharide affinity. Secondly, there is a region where specific exchange of glutamate for glutamine (E372Q) creates a site for an additional water molecule. Upon sugar binding side chain rearrangements lead to displacement of this water molecule and additional hydrogen bonding. Thereby this region of the binding site is defined as the high affinity scaffold. HK620TSP is not only specific for the O18A1-antigen, but also the lacking of the branching glucose in the O18A1-antigen can be tolerated so that the accordant O18A PS can be bound and cleaved by HK620TSP as well. Surprisingly, in binding studies with the smallest O-antigen units of these PS the O18A pentasaccharide was bound by TSP variants with nearly the same affinity or even a slightly increased one compared to the O18A1 hexasaccharide. However, there is a change in thermodynamic contributions to binding: the lack of the glucose moiety leads to a less entropically favored binding compared to binding of O18A1-hexasaccharide (Δ (-TΔS) ~ 10 kJ/mol). In contrast the enthalpic contribution to the binding is more favorable (ΔΔH ~ -10 kJ/mol) for the binding of O18A pentasaccharide. The side-chain glucose contributes to entropy by the release of four water molecules out of a hydrophobic pocket. The binding of this branching glucose is paid by an enthalpic penalty because of the breakup of hydrogen bonding of displaced water molecules and destabilizing contacts between sugar and protein in this hydrophobic pocket. Therefore the binding of the glucose in this pocket does not account for generating affinity and an evolutionary relation of HK620TSP to an O18A-antigen binding protein is presumed. Finally, the infection mechanism of phage HK620 was studied as well. In analogy to the related phage P22 the DNA-ejection could be triggered by incubation of HK620 with the host LPS in vitro. The morphology and chain length of the LPS as well as the activity of HK620TSP towards the LPS are crucial for this in vitro DNA-ejection. Thus, the DNA-ejection could also be induced by LPS from bacteria of serogroup O18A which can be bound and hydrolyzed by HK620TSP. These results stress the role of TSP for the recognition of host LPS-receptors as a crucial step of infection by podoviruses P22 and HK620.

Submitted by Alison Vanceto (alison-vanceto@hotmail.com) on 2017-03-20T12:19:29Z No. of bitstreams: 1 TeseCBB.pdf: 8155829 bytes, checksum: 9a5289c818bd72bed1bf08cb0aecbd14 (MD5)<br>Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-04-20T12:57:24Z (GMT) No. of bitstreams: 1 TeseCBB.pdf: 8155829 bytes, checksum: 9a5289c818bd72bed1bf08cb0aecbd14 (MD5)<br>Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-04-20T12:57:31Z (GMT) No. of bitstreams: 1 TeseCBB.pdf: 8155829 bytes, checksum: 9a5289c818bd72bed1bf08cb0aecbd14 (MD5)<br>Made available in DSpace on 2017-04-20T13:11:43Z (GMT). No. of bitstreams: 1 TeseCBB.pdf: 8155829 bytes, checksum: 9a5289c818bd72bed1bf08cb0aecbd14 (MD5) Previous issue date: 2016-09-12<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)<br>Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)<br>Ionic conductivity in glasses was first discovered and demonstrated by Warburg in 1884, but although it has been studied for over a century, the mechanisms underlying ionic conduction in glasses are not yet entirely clear. Glasses are commonly known to be electrical insulators, but some of them may present high conductivity and be candidates for different applications. The more conductive glasses result from the dissolution of halogenated salts in the glassy matrix, causing its ionic conductivity to increase by several orders of magnitude. Our approach proposes that glass can be compared to a solution in which a dissolved halogenated salt (solute) is weakly dissociated in the glassy matrix (solvent). This approach, called the weak electrolyte model, was initially proposed in the 70s to explain the almost exponential increase in the ionic conductivity of glasses in response to increasing concentrations of network modifiers (alkaline oxides). Our work proposes to expand this approach, correlating the increase in ionic conductivity with the increase in the thermodynamic activity of AgI. In addition, experiments were carried out at different temperatures in various glass compositions to confirm this correlation, using electromotive force (EMF) measurements to determine the thermodynamic activity and electrochemical impedance spectroscopy (EIS) measurements to determine the ionic conductivity of these glasses. Ionic transport was also used to examine the structural relaxation of AgPO3 glass. The glass was heated to another fictive temperature in the glass transition range and its ionic conductivity measured in situ by EIS. The kinetic parameters of the structural relaxation process, i.e., structural relaxation time ( ) and stretching parameter (β), were determined as a function of time by fitting the experimental data to KWW equations.<br>A condutividade iônica em vidros foi observada e demonstrada pela primeira vez por Warburg em 1884, mas apesar de mais de um século dessa descoberta, os mecanismos pelos quais se dá essa condutividade iônica não são totalmente claros. Vidros, em geral, são conhecidos como isolantes elétricos, mas alguns deles podem apresentar uma alta condutividade e portanto bons candidatos para diferentes aplicações. Os vidros com os valores mais elevados de condutividade iônica resultam da dissolução de sais halogenados em uma matriz vítrea, resultando em um aumento de várias ordens de grandeza na propriedade. Nossa proposta é a de que vidros podem ser comparados com uma solução em que um sal halogenado dissolvido (soluto) está fracamente dissociado em uma matriz vítrea (solvente). Essa aproximação, chamada de modelo do eletrólito fraco, foi inicialmente proposta nos anos 70 para explicar o aumento quase exponencial da condutividade iônica em vidros em resposta ao aumento da concentração de modificadores de rede (óxidos alcalinos). Nosso trabalho propõe expandir essa aproximação, correlacionando o aumento da condutividade iônica com a atividade termodinâmica de AgI. Além disso, experimentos foram feitos em diferentes temperaturas com várias composições de vidro para confirmar essa correlação, usando medidas de força eletromotriz (FEM) para determinar a atividade termodinâmica e medidas de espectroscopia de impedância (IES) para determinar a condutividade iônica desses vidros. O transporte iônico também foi utilizado para estudar a relaxação estrutural de vidros AgPO3. O vidro, previamente equilibrado a uma temperatura fictícia inicial, foi tratado termicamente a uma outra temperatura fictícia próxima da temperatura de transição vítrea e a sua condutividade iônica medida in situ por EIS. Os parâmetros cinéticos do processo de relaxação estrutural, i.e., tempo de relaxação estrutural ( ) e o parâmetro exponencial (β), foram determinados em função do tempo pelo ajuste da equação KWW.

The nucleic acids, RNA in particular, are conformationally complex biomolecules. The structures that they can form and the subtle sequence dependent modifications of conformation are of pivotal importance to their function <I>in vivo</I>. The advent of solid phase chemical synthesis methodologies for DNA and, more recently RNA, has fuelled the rapid growth in our knowledge of nucleic acid structure. The work described here is concerned with the development of rapid and reliable synthesis and purification protocols for the automated chemical synthesis of RNA. The use of RNA phosphoramidite monomers incorporating two different 2'-hydroxyl protecting groups is described, along with ion-exchange and reversed phase HPLC protocols for the purification of oligoribonucleotides. The quality of the material obtained by these methods has allowed detailed biophysical investigations by UV melting, high field NMR and X-ray crystallography.

This thesis reports progress in two domains, namely causal structures and microscopic thermodynamics, both of which are highly pertinent in the development of quantum technologies. Causal structures fundamentally influence the development of protocols for quantum cryptography and microscopic thermodynamics is crucial for the design of quantum computers. The first part is dedicated to the analysis of causal structure, which encodes the relationship between observed variables, in general restricting the set of possible correlations between them. Our considerations rely on a recent entropy vector method, which we first review. We then develop new techniques for deriving entropic constraints to differentiate between causal structures. We provide sufficient conditions for entropy vectors to be realisable within a causal structure and derive new, improved necessary conditions in terms of so-called non-Shannon inequalities. We also report that for a family of causal structures, including the bipartite Bell scenario and the bilocal causal structure, entropy vectors are unable to distinguish between classical and quantum causes, in spite of the existence of quantum correlations that are not classically reproducible. Hence, further development is needed in order to understand cause from a quantum perspective. In the second part we explore an axiomatic framework for modelling error-tolerant processes in microscopic thermodynamics. Our axiomatisation allows for the accommodation of finite precision levels, which is crucial for describing experiments in the microscopic regime. Moreover, it is general enough to permit the consideration of different error types. The framework leads to the emergence of manageable quantities that give insights into the feasibility and expenditure of processes, which for adiabatic processes are shown to be smooth entropy measures. Our framework also leads to thermodynamic behaviour at the macroscopic scale, meaning that for thermodynamic equilibrium states a unique function provides necessary and sufficient conditions for state transformations, like in the traditional second law.

Non-equilibrium physical systems, be they biological or otherwise, are powered by differences in intensive thermodynamic variables, which result in flows of matter and energy through the system. This thesis is concerned with the response of physical systems and ecosystems to complex types of boundary conditions, where the flows and intensive variables are constrained to be functions of one another. I concentrate on what I call negative feedback boundary conditions, where the potential difference is a decreasing function of the flow. Evidence from climate science suggests that, in at least some cases, systems under these conditions obey a principle of maximum entropy production. Similar extremum principles have been suggested for ecosystems. Building on recent work in theoretical physics, I present a statisticalmechanical argument in favour of this principle, which makes its range of application clearer. Negative feedback boundary conditions can arise naturally in ecological scenarios, where the difference in potential is the free-energy density of the environment and the negative feedback applies to the ecosystem as a whole. I present examples of this, and develop a simple but general model of a biological population evolving under such conditions. The evolution of faster and more efficient metabolisms results in a lower environmental energy density, supporting an argument that simpler metabolisms could have persisted more easily in early environments. Negative feedback conditions may also have played a role in the origins of life, and specifically in the origins of individuation, the splitting up of living matter into distinct organisms, a notion related to the theory of autopoiesis. I present simulation models to clarify the concept of individuation and to back up this hypothesis. Finally I propose and model a mechanism whereby systems can grow adaptively under positive reinforcement boundary conditions by the canalisation of fluctuations in their structure.

La question générale traitée dans cette thèse est de déterminer si, à l’heure actuelle, nous disposons d’outils théoriques efficaces pour décrire la structure, la liaison et les propriétés thermodynamiques de système comprenant un actinide. Cette large question va être abordée à l’aide de trois études différentes. Les deux premières sont directement liées à l’industrie plastique et à la sureté nucléaire. La dernière, plus fondamentale concerne une analyse comparative d’une approche théorique nouvellement développée sur des systèmes comprenant des éléments f. Tout d’abord, les cations alkyles contenant un actinide (Th, U) ou un métal de transition (Zr) coordonné à un arène se sont révélés efficaces pour la catalyse de la synthèse du polyéthylène. Étonnamment, les activités catalytiques des cations alkyles dépendent du solvant. Pour comprendre cela et confirmer la tendance qu’ont ces complexes à se lier à l’arène, une étude en DFT dans un contexte relativiste combinée à une caractérisation de liaison avec la méthode ETS-NOCV fut faite. La deuxième étude vise à étoffer les bases de données thermodynamiques qui servent à explorer numériquement les scénarios d’accidents. Notre étude in silico porte sur la détermination des enthalpies de formation des deux espèces pour lesquelles des incertitudes expérimentales subsistent (PuO3 ou PuO2(OH)2 …), en utilisant une méthode quantique multiconfigurationnelle et relativiste. La dernière partie de la théorie se concentre sur l’estimation de la précision de la fonctionnelle B2-PLYP pour les éléments f, qui s'avère assez précise en comparaison aux données expérimentales et à la méthode de référence CCSD(T)<br>The main question of this thesis is: do we have today the tools to efficiently describe the structure, the bonding and the thermodynamics of actinide systems? This broad question is answered thanks to three studies. The first two are directly applied to the plastic industry and the nuclear plant safety. The last one, more fundamental, concerns the benchmarking of newly developed theoretical approach on f-element systems.First, actinides and transition metal arene-coordinated alkyl cations have been recently proven to be efficient catalysts for ethylene polymerizations. Interestingly, thorium, uranium and zirconium alkyl cations’ catalytic activity depends on the solvent. To understand these behaviors and to confirm the tendency of these complexes to engage in unusual-arene coordination, relativistic DFT calculations combined with a characterization of the interaction thanks to the ETS-NOCV method are used. Second, in accident scenario along the reprocessing of spent nuclear fuel, plutonium can be released in various volatile forms (PuO2, PuO3 or PuO2(OH)2, …). The exploration of these scenarios by the use of simulations requires, among the various parameters, the knowledge of the thermodynamic properties of the possibly formed elements. Our in-silico study focusses on the determination of the enthalpies of formation of the former two species for which experimental uncertainties remain, using multi-configurational relativistic wavefunction method. The last part of the thesis focusses on the benchmark of the B2-PLYP functional for f-element systems, which turns out quite accurate with respect to the experimental data and the gold-standard CCSD(T) method

Inclusion properties of the following seven diol host compounds were investigated: Host 1 9,9'-bis(9,91-dihydroxy-fluorene) Host 2 1, 1'-binaphthyl-2,2'-bis( diphenylhydroxymethyl) Host 3 2,2'-bis(9-hydroxy-9-fluorenyl)biphenyl Host 4 trans-9, 10-dihydroxy-9,10-diphenyl-9, 10-dihydroanthracene Host 5 trans-9, 10-dihydroxy-9,10-di-p-tolyl-9,10-dihydroanthracene Host 6 trans-9, 10-dihydroxy-9, 10-di-p-tert-butylphenyl-9, 10-dihydroanthracene Host 7 trans-9, 10-dihydroxy-9, 10-di-a-naphthyl-9, 10-dihydroanthracene These compounds all possess molecular planes with bulky substituents and opposing hydroxyl moieties as probes for possible coordination to guest molecules by means of hydrogen bonding. Sixteen different inclusion compounds were formed with common organic solvents as the guests. Various characterisation techniques were used and the crystal structures of the inclusion compounds and of the a-phases of Hosts 2 and 5 were elucidated using single crystal X-ray diffraction methods. Thermal decomposition studies using thermogravimetry and differential scanning calorimetry (DSC) were carried out in order to relate the strength of the host-guest interactions to the structures of the inclusion compounds. Owing to practical limitations, the DSC technique is not suitable for the measurement of '1H for the decomposition of an inclusion compound where the guest is relatively volatile. Therefore an apparatus was devised to yield accurate '1H0 values for this process.

Includes bibliographical references.<br>This work is predominantly concerned with the structural analysis of the coordinatoclathrates formed by the host compound trans-9,10-dihydroxy-9,10-diphenyl- 9,10-dihydroanthracene (1) with compounds containing neutral nitrogen atoms (Lewis bases). The structures of inclusion compounds with two nitriles (acetonitrile and 3- hydroxypropionitrile), with pyridine and with three substituted pyridines (3- methylpyridine, 2,4-dimethylpyridine and 2,6-dimethylpyridine) have been solved by single crystal X-ray diffraction methods. The crystal packing modes and hydrogen bonding schemes have been elucidated, while the guest cavities have been investigated. The thermal stability of the complexes was analysed by thermogravimetric analyses and differential scanning calorimetry. These techniques were employed in determining the guest content, in investigating the thermal properties of the compounds and in establishing the activation energies for the desorption processes. Desorption studies, utilising X-ray powder diffraction, were used to investigate the structures resulting from the desorption of guest from the complexes. The selectivity of the host for either of the isomers 2,4- and 2,6-dimethylpyridine was investigated.

The preparation of layered double hydroxides via titration with sodium hydroxide was thoroughly investigated for a number of M(II)/M(III) combinations. These titration curves were examined and used to calculate nominal solubility product constants and other thermodynamic quantities for the various LDH chloride systems.

En cas d’accidents nucléaires (Tchernobyl, Fukushima) ou d’exposition à de l'uranium appauvri dans des zones de conflit, la décontamination est nécessaire pour réduire au mieux les conséquences de l’ingestion de radionucléides. Après une contamination externe ou interne, les actinides solubilisées sont distribués dans les organes cibles (squelette, foie, tissus, reins, etc.) via la circulation sanguine. Compte tenu de cette dispersion, la chélation de ces radionucléides par des ligands biologiques est une méthode efficace de décorporation pour favoriser l'excrétion de ces métaux déposés et ainsi réduire les risques pour la santé. En raison du faible taux de distribution dans les organes cibles (os, foie, reins) de l'acide diéthylènetriaminepentaacétique (DTPA), des agents de chélation ont été synthétisés et testés in vitro ou in vivo. Dans ce projet, plusieurs ligands polyaminophosphonates, (conçus à l'origine pour être des agents de contraste), ont été synthétisés selon leurs propriétés de bio-distribution, de leurs groupes fonctionnels, de leur potentiel site de coordination et de leur lipophilie. Des études structurales et thermodynamiques ont ensuite été effectuées sur les complexes entre l'uranium (VI) et l’europium (III) (comme analogue de l’américium (III) et curium (III)) et les ligands polyaminophosphonates. La sphère de coordination de ces cations a été observée par spectroscopie UV-visible, TRLFS, FT-IR et la spectroscopie d’absorption X (EXAFS). L'étude de l’affinité a été réalisée par spectroscopie UV-visible. Enfin, les spectroscopies UV-visible et TRLFS ont été utilisées d’une part pour tester la stabilité du complexe ligand/uranyle en présence d’un ion métallique et d’autre part pour étudier le système ternaire : ion uranyle/ligand/calmoduline. Ces résultats ont permis de mieux comprendre les mécanismes de chélation et d’évaluer l'affinité chimique de ces ligands polyaminophosphonates pour l'uranium (VI) et l’europium (III). Cela devrait ainsi aider à la conception de nouveaux agents de chélation de plus en plus efficaces du point de vue de la décorporation<br>For exposed person who suffers from contamination from nuclear accidents (Chernobyl, Fukushima) or depleted uranium in war zones, decontamination is required to reduce the sequence damage of radionuclide intake. After an external or internal contamination, the solubilized actinides could be distributed to the target organs (skeletal, liver, kidneys tissues, etc.) via the bloodstream. Considering the dispersion, fate and health effect of the actinides, chelation therapy is an effective decorporation method to promote the excretion of deposited actinides to reduce the health risk. Due to the defect on weak distribution rate to the target organs (bone, liver, kidneys) of diethylenetriaminepentaacetic acid (DTPA) which currently used in clinics, plenty chelation agents were synthesized and tested in vitro or in vivo. In this project, several polyaminophosphonates ligands, a series ligand originally designed for MRI contrast and SPECT agents, were synthesized according to the properties of ligand bio-distribution, functional groups, coordination site and lipophilic. Then the structural and thermodynamic studies were done with the complexes between metal ion such as uranium(VI) and europium(III) (as americium/curium(III) analogue), and polyaminophosphonates ligands. The sphere of coordination of these cations was observed by UV-visible spectroscopy, TRLFS, FT-IR and Extended X-Ray Absorption Fine Structure (EXAFS). The affinity study was done with UV-visible spectroscopy. Finally, the UV-visible spectroscopy and TRLFS were used to test the stability of uranyl ligand complex with competition metal ion in biological conditions and to reveal the interactions between the ternary system, uranyl ion/ligand/calmodulin. These results allow to better understand the chemical affinity and possible chelation mechanism of the polyaminophosphonates ligands for the above actinides and therefore to promote the design of new chelation agents

<p> So far to our knowledge, the bromine-xenon double clathrate hydrate has not yet been completely studied. In recent research in Janda lab at UC Irvine, we obtained the thermodynamic properties and structure of bromine-xenon double clathrate by applying UV-Vis spectroscopy and determining the total vapor pressure of the clathrate. In both of the TS-I and CS-II structures, bromine could only stay in the bigger size cages, while introducing xenon as a helper gas to occupy the smaller cages. Based on this concept, we hypothesize that the bromine-xenon double clathrate has the TS-I structure type below 273K, and the CS-II structure type above this temperature. Also we calculated the enthalpy of dissociation of the TS-I bromine-xenon double clathrate as 12.305&plusmn;0.170kJ/mol/K, and the CS-II clathrate as 16.574&plusmn;0.143 kJ/mol/K.</p>

A considerable amount of mineral particles are found to have a plate-like shape. The work in this thesis concerns theoretical investigations, using a Monte Carlo method, of the properties of such particles in aqueous solutions. The objectives were first to create a model that could capture the essential physics of clay suspensions and also to understand the role of thermodynamics in certain chemical processes. For all investigations, the results are related to experimental studies. The acid-base behavior of clays have been studied, using the primitive model, and an excellent agreement between simulated and experimental results was found. The formation of gel phases as a function of the charge anisotropy have also been investigated. Liquid-gel and sol-gel transitions are found to occur for high and moderate charge anisotropy, respectively. These transitions were also found to be size and salt dependent. In absence of charge anisotropy, a liquid-glass transition is reported. The formation of smectic and columnar liquid crystals phases with plate-like particles has been found to be favored by a strong charge anisotropy, in opposition to what was observed for nematic phases. New liquid-crystal phases were also reported. The stability and growth of nanoplatelets is discussed. It was found that the internal Coulombic repulsion could be the cause of the limited growth of C-S-H platelets. The influence of thermodynamics on the agregation mode of such platelets was also investigated

<p> Understanding structured information and computation in thermodynamics systems is crucial to progress in diverse fields -- from biology at a molecular level to designed nano-scale information processors. Landauer's principle puts a bound on the energy cost of erasing a bit of information. This suggests that devices which exchange energy and information with the environment, which we call information engines, can use information as a thermodynamic fuel to extract work from a heat reservoir, or dissipate work to erase information. However, Landauer's Principle on its own neglects the detailed dynamics of physical information processing -- the mechanics and structure between the start and end of a computation. Our work deepens our understanding of these nonequilibrium dynamics, leading to new principles of efficient thermodynamic control. We explore a particular type of information engine called an information ratchet, which processes a symbol string sequentially, transducing its input string to an output string. We derive a general energetic framework for these ratchets as they operate out of equilibrium, allowing us to exactly calculate work and heat production. We show that this very general form of computation must obey a Landauer-like bound, the Information Processing Second Law (IPSL), which shows that any form of temporal correlations are a potential thermodynamic fuel. We show that in order to leverage that fuel, the autonomous information ratchet must have internal states which match the predictive states of the information reservoir. This leads to a thermodynamic principle of requisite complexity, much like Ashby's law of requisite variety in cybernetics. This is a result of the modularity of information transducers. We derive the <i> modularity dissipation,</i> which is an energetic cost beyond Landauer's bound that predicts the structural energy costs of different implementations of the same computation. Applying the modularity dissipation to information ratchets establishes design principles for thermodynamically efficient autonomous information processors. They prescribe the ratchet's structure such that the computation saturates the bound set by the IPSL and, thus, achieves maximum thermodynamic efficiency.</p><p>

In the potential event of a clad breach in a Sodium-cooled Fast Reactor (SFR), the sodium metallic coolant could come into contact with the (U,Pu,Np)$O_2$ nuclear fuel. The reaction products are numerous, but there is little knowledge of their structural and thermodynamic properties. Under the oxygen potential conditions of the reactor, pentavalent $Na_3AnO_4$ (An=U,Pu,Np) is expected to form, but its structure was the subject of controversy until now. We showed that $\alpha-Na_3UO_4$ adopts a monoclinic symmetry in space group $\textit{P2/c}$. Neutron diffraction combined with X-ray Absorption Near Edge Structure (XANES) spectroscopy at the U-M$_4$ edge also revealed that this phase could accommodate excess sodium on the uranium site, with subsequent charge compensation of the uranium cation from U(V) to U(VI), which was not previously foreseen. The corresponding mixed valence state composition is written $Na_3(U_{1-x},Na_x)O_4$ with 0<$\textit{x}$<0.16(2). To complete the data on the Na-U-O system, the thermodynamic functions of $Na_2U_2O_7$ and $Na_4UO_5$ were evaluated using Knudsen effusion mass spectrometry (KEMS) and thermal-relaxation calorimetry. In addition, the oxygen content required at 900 K within liquid sodium to form pentavalent $Na_3UO_4$ and hexavalent $Na_4UO_5$ were calculated to be 0.7 and 1.5 wppm, respectively, which are levels typically encountered in SFRs. A thermodynamic model for the Np-O system was then developed using the CALPHAD method. This is particularly relevant since it is envisaged to incorporate minor actinides into the fuel to minimize the nuclear waste inventory. The poorly known structures of the Na- Np-O and Na-Pu-O phases diagrams, i.e., tetravalent $Na_2AnO_3$ (An=Np,Pu), pentavalent $Na_3AnO_4$, hexavalent $Na_4AnO_5$ and $\alpha-Na_2NpO_4$, and heptavalent $Na_5AnO_6$, were also re-fined by the Rietveld method. The structures of $Na_3NpO_4$ and $Na_3PuO_4$ were determined ab initio from powder X-ray diffraction data, and found to be orthorhombic in the space group $\textit{Fmmm}$. The valence states of the neptunium cations were confirmed from the isomer shift values of their Mössbauer spectra. Having established the charge states without ambiguity, XANES spectra were collected at the $Np-L_3$ and $Pu-L_3$ edges to serve as reference data for An(V), An(VI), and An(VII) oxide phases in the solid state. Finally, KEMS studies of $\alpha-Na_2NpO_4$ showed very promising results for the determination of the enthalpies of formation of the sodium neptunates and plutonates, for which there is almost no data available. The heat capacities and entropies at 298.15 K of $\alpha-Na_2NpO_4$, $Na_4NpO_5$, $Na_5NpO_6$, and $Na_5PuO_6$ were also determined. Comparing their Gibbs energy values, the sodium neptunates were found to be slightly more stable than their isostructural uranium analogues.

A molecule can crystallise in more than one crystal structure, a common phenomenon in organic compounds known as polymorphism. Different polymorphic forms may have significantly different physical properties, and a reliable prediction would be beneficial to the pharmaceutical industry. However, crystal structure prediction (CSP) based on the knowledge of the chemical structure had long been considered impossible. Previous failures of some CSP attempts led to speculation that the thermodynamic calculations in CSP methodologies failed to predict the kinetically favoured structures. Similarly, regarding the stabilities of co-crystals relative to their pure components, the results from lattice energy calculations and full CSP studies were inconclusive. In this thesis, these problems are addressed using the state-of-the-art CSP methodology implemented in the GRACE software. Firstly, it is shown that the low-energy predicted structures of four organic molecules, which have previously been considered difficult for CSP, correspond to their experimental structures. The possible outcomes of crystallisation can be reliably predicted by sufficiently accurate thermodynamic calculations. Then, the polymorphism of 5- chloroaspirin is investigated theoretically. The order of polymorph stability is predicted correctly and the isostructural relationships between a number of predicted structures and the experimental structures of other aspirin derivatives are established. Regarding the stabilities of co-crystals, 99 out of 102 co-crystals and salts of nicotinamide, isonicotinamide and picolinamide reported in the Cambridge Structural Database (CSD) are found to be more stable than their corresponding co-formers. Finally, full CSP studies of two co-crystal systems are conducted to explain why the co-crystals are not easily obtained experimentally.

Understanding of the interrelationship between structure, thermodynamic properties and phase diagrams is very useful for rationalizing the behavior of materials and development of predictive models, which can be used to optimize the composition of materials and their fabrication processes. The properties of materials are governed by its electronic and crystallographic structure. Chemical bonding determines the electronic structure of materials. Furthermore, the electronic structure plays a predominant role in determining the physical, electrical, magnetic, thermal and optical properties of materials. Crystal structure also influences most properties of materials. Since changes in thermodynamic variables such as temperature, pressure, and composition dramatically alter the physical properties of materials and its structure, it is desirable to study the thermodynamic stability of materials in conjunction with phase relations. Phase diagrams can indicate the ranges of pressure, temperature and chemical composition where specific phases and mixtures of phases are stable. If the Gibbs energies of all the phases involved are known, phase diagram can be computed using Gibbs energy minimization algorithms. In recent times, one of the important uses of thermodynamics in materials science has been in the computation of phase diagrams. To materials scientists phase diagrams are like maps to travelers. They guide the path through the composition space to find phases, fulfilling specific materials performance requirements. As phase diagrams are the graphic representations of minimizations of Gibbs energy under given constraints, computational thermodynamics significantly expands our capability to walk in the multi-component space of engineering materials. High-temperature phase-equilibrium studies, thermodynamics and materials processing have had a close relationship over a number of decades. Successful utilization of ceramic materials under different environmental conditions at high temperatures requires accurate thermodynamic data. Focus of the present investigation is to obtain correct phase relations and accurate thermodynamic data in selected technologically important ceramic oxide systems in which the data are either not available or are inconsistent. Based on the experimental data, different types of phase diagrams are computed for the systems of contemporary relevance. After a brief introduction, Chapter 1 discusses the brief overview of the experimental techniques available for determining the phase relations and thermodynamic properties at high temperatures and the methods used in this study. The chapter reviews the possible sources of errors in experimental techniques and tests for correct functioning. In Chapter 2, systematic studies on high-temperature phase equilibria and thermodynamic properties of compounds in the ternary systems Ln-Pd-O (Ln = La, Pr, Eu, Gd, Tb, Dy, Ho and Er) are presented. Some of the ternary oxides on the Ln-Pd-O systems have potential application in catalysis and electrochemistry. To optimize the parameters for the synthesis and to understand the behavior of the catalysts, it is useful to have information on the thermodynamic stability domain of each compound. Quantitative information on the stability of the ternary oxides is also useful for assessing the interaction of metal Pd with ceramic compounds containing rare-earth elements under different environments. Furthermore, the thermodynamic data are beneficial for the design of processes for the recovery of rare earth and precious metals from scrap. There is very little thermodynamic and phase diagram information on the Ln-Pd-O systems. Isothermal sections of phase diagram for the ternary system La-Pd-O at 1200 K and for the systems Ln-Pd-O (Ln = Pr, Eu, Gd, Tb, Dy, Ho and Er) at 1223 K, were established by the isothermal equilibration technique at high temperatures. Phases were identified after quenching by optical and scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectroscopy (EDS). Based on the phase relations, the thermodynamic properties of ternary interoxide compounds were determined by the solid-state galvanic cell technique over a range of temperature between 925 - 1400 K. An advanced version of the solid-state cell incorporating a buffer electrode was used for high temperature thermodynamic measurements. The function of the buffer electrode, placed between reference and working electrodes, was to absorb the electrochemical flux of the mobile species through the solid electrolyte caused by trace electronic conductivity. The buffer electrode prevented polarization of the measuring electrode and ensured accurate data. Yttria-stabilized zirconia was used as the solid electrolyte and pure oxygen gas at a pressure of 0.1 MPa as the reference electrode. These novel features enhanced the accuracy of thermodynamic data. From electrochemical measurements, the standard enthalpies of formation of these oxides from elements and their standard entropies at 298.15 K were also evaluated. The variation of the lattice parameters and unit cell volume as a function of rare earth atomic number for the three ternary compounds Ln4PdO7, Ln2PdO4 (Ln = La, Pr, Nd, Sm, Eu, Gd) and Ln2Pd2O5 (Ln = La to Er) are discussed. The systematic variations of thermodynamic properties of all the ternary compounds as a function of rare earth atomic number are presented and correlated with structural features. Thermodynamic and structural parameters of uninvestigated Ln-Pd-O systems (Ln = Ce, Pm) can be obtained by interpolation. Based on the thermodynamic information obtained in this study and auxiliary data on binary compounds available in the literature, different types of phase diagrams, isothermal oxygen potential diagrams, isobaric phase diagrams, isothermal two dimensional and three-dimensional chemical potential diagrams for the systems Ln-Pd-O (Ln = La, Pr, Eu, Gd, Tb, Dy, Ho and Er) are constructed. Chapter 3 contains the studies on partial phase diagrams of the systems M-Ru-O (M = Ca and Sr) at 1300 K and determination of Gibbs energies of formation of calcium and stronsium ruthenates in the temperature range from 925 to 1350 K using solid-state cells with yttria-stabilized zirconia as the electrolyte and Ru + RuO2 as the reference electrode. Gibbs energies, enthalpies and entropies of formation of calcium and strontium ruthenates from their component binary oxides were deduced. The standard enthalpies of formation of these oxides from elements and their standard entropies at 298.15 K were also evaluated. Based on the thermodynamic data obtained in this study and auxiliary information from the literature, the three dimensional representation of oxygen potential diagram for the M-Ru-O systems (M = Ca and Sr) as a function of composition and temperature are computed. The purpose of this chapter is to determine the thermodynamic stability of alkaline earth metal ruthenates in the perovskite related layered system Mn+1RunO3n+1 (n = 1, 2, and ¥ for Ca-Ru-O system and n = 1, 2, 3 and µ for Sr-Ru-O system) since these calcium and stronsium ruthenates have interesting magnetic and electronic device applications. Moreover, there is no literature available for thermodynamic properties on first and second members of the Ruddelsdon-Popper (R-P) series in Ca-Ru-O system, Ca2RuO4, Ca3Ru2O7 and third member of R-P series in Sr-Ru-O system, Sr4Ru3O10. Some of the available literature information on thermodynamic properties for other compounds of R-P series in Mn+1RunO3n+1 (M = Ca, Sr) are found to be based on incorrect assumptions and erroneous calculation. Thus, this chapter provides the complete thermodynamic information for all the electronically and magnetically applicable alkaline earth metal ruthenates for optimizing the deposition condition in device fabrications. Chapter 4 gives the structure-properties correlations of 2-3 spinel compounds and spinel-corundum equilibria for the system NiO-Al2O3-Cr2O3 at 1373 K. Nickel, aluminum and chromium are important base-constituent elements of high-temperature oxidation-resistant alloys. A spinel phase is usually found in the protective scale formed on the surface of the alloys. There is no thermodynamic data on spinel solid solution NiAl2O4-NiCr2O4. Thus, the phase relations and mixing properties of the spinel solid solution have been determined in this chapter. The inter-crystalline ion-exchange equilibrium between NiAl2+2xO4+3x-NiCr2O4 spinel solid solution and Al2O3-Cr2O3 solid solution with corundum structure in pseudo-ternary system NiO-Al2O3-Cr2O3 have been determined by the conventional tie-line rotation method at 1373 K. The nonstoichiometry of NiAl2+2xO4+3x has been taken into consideration. Lattice parameters were used to obtain the compositions of the corundum and spinel solid solutions at equilibrium. Formation of homogeneous solid solutions and attainment of equilibrium were confirmed by X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDS). From the experimental tie-line information and thermodynamic data on Al2O3-Cr2O3 solid solution available in the literature, the activities in the spinel solid solution were derived by using a modified Gibbs-Duhem integration technique. Gibbs energy of mixing of the spinel solid solution has been calculated from the derived activity data. Since high temperature data generation is expensive and time consuming, it is useful to develop models, which relate thermodynamic properties to electronic and crystallographic structure, leading to predictive modeling of mixing properties. By comparing the results from models with experimental information, one can evolve methodologies for the prediction of the properties of uninvestigated system. A model can be used to discriminate among conflicting experimental data and extrapolate the data into regions where direct measurements are lacking or difficult to perform. In this chapter, a model approach has also been considered to analyze the activity-composition relationship in the NiAl2O4-NiCr2O4 spinel solid solution in terms of the intra-crystalline exchange of cations between the tetrahedral and octahedral sites of the spinel structure governed by site preference energies of the cations. Since Ni2+ and Cr3+ ion in tetrahedral coordination exhibits Jahn-Teller distortion, an entropy corresponding to randomization of the distortion in the cubic phase has been incorporated in the cation distribution model. The thermodynamic mixing properties of stoichiometric spinel solid solution NiAl2O4-NiCr2O4 in terms of one mole of mixing species were computed at 1373 K. The strain energy caused by size mismatch was added as a separate term to the Gibbs energy of mixing using empirical relationship between enthalpy of mixing for a pair of ions and the difference in their ionic volumes. Madelung constant and electrostatic contribution of energy of mixing of the spinel solid solution have also been computed. Comparison of Gibbs energy of mixing calculated using the cation mixing model for the stoichiometric spinel solid solution NiAl2O4-NiCr2O4 with that of the experimental tie-line data for nonstoichiometric spinel solid solution NiAl2+2xO4+3x-NiCr2O4 were included in this chapter. The thermodynamic mixing properties obtained in this study would be helpful in understanding the formation of complex spinel protective layers on alloys containing nickel, aluminium and chromium in high-temperature applications. The summary of the important finding and the conclusions arrived at on the basis of results obtained from the present investigations are presented in Chapter 5.

Thesis (Ph.D.)--University of Missouri-Columbia, 2006.<br>The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file viewed on (February 27, 2007). Vita. Includes bibliographical references.

Among three basic states of matter (solid, liquid, gas), liquids are least understood from the theoretical point of view. The perceived diffculty is that interactions in a liquid are both strong and system-specific, implying that the energy strongly depends on the liquid type and that, therefore, liquid energy can not be calculated in general form. In this thesis, a phonon theory of liquids is developed where this problem is avoided. Central to the thesis is a development an alternative to calculating liquid energy and heat capacity. The proposed phonon theory of liquids covers both classical and quantum regimes and accounts for the contribution of anharmonicity and thermal expansion to liquid energy and heat capacity. Within the framework of the phonon theory of liquids a good agreement of calculated and experimental heat capacity of liquids, including helium, noble, metallic, molecular and hydrogen-bonded network liquids in a wide range of temperature and pressure is demonstrated. It was also found that in the very wide pressure range 5 MPa-500 MPa liquid helium near melting temperature is both solid-like and quantum. The thermodynamic properties of the supercritical state are studied, which lead to discovery that specific heat shows a crossover between two different dynamic regimes of the low-temperature rigid liquid and high-temperature non-rigid supercritical fluid. A theory of heat capacity above the crossover is formulated, and good agreement between calculated and experimental data for rare-gas supercritical liquids is obtained. The relationship between power exponents of heat capacity and viscosity in the supercritical region is derived. The thermodynamic properties are explained by the temperature behaviour of the maximal length of the longitudinal phonons that can exist in the supercritical system and that is not sensitive to system details. We also introduce a new idea that enables a unified description of all three states of matter. A generic form of an interacting phonon Hamiltonian with ground state configurations minimising the potential is introduced. Symmetry breaking leads to emergence of energy gaps of shear excitations as a consequence of the Goldstone theorem, and readily results in the emergence of energy spectra of solid, liquid and gas phases.

Calmodulin (CaM) is an essential protein found in all eukaryotes ranging from vertebrates to unicellular organisms such as Paramecia. CaM is a calcium sensor protein composed of two domains (N and C) responsible for the regulation of numerous calcium-mediated signaling pathways. Four calcium ions bind to CaM, changing its conformation and determining how it recognizes and regulates its cellular targets. Since the discovery of CaM, most studies have focused on the role of its calcium-saturated form. However, an increasing number of target proteins have been discovered that preferentially bind apo (calcium-depleted) CaM. My study focused on understanding how apo CaM recognizes drugs and protein sequences, and how those interactions differ from those of calcium-saturated CaM. I have used spectroscopic methods to explore CaM binding the drug Trifluoperazine (TFP) and the IQ-motif of the type 2 Voltage-Dependent Sodium Channel (Nav1.2IQp). These studies have shown that both TFP and Nav1.2IQp preferentially bind to the "semi-open" conformation of apo CaM. TFP was shown to be an unusual allosteric effector of calcium binding to CaM. Using 15N-HSQC NMR spectroscopy, I determined the stoichiometry of TFP binding to apo Cam to be 2:1 and to (Ca2+)4-CaM to be 4:1 TFP:CaM. That difference in stoichiometry determined whether TFP decreased or increased the affinity of CaM for calcium. Analysis of residue-specific chemical shift differences indicated that TFP binding to apo and (Ca2+)4-CaM perturbed the C-domain more than the N-domain, prompting high-resolution structural studies of the isolated C-domain of CaM. Crystallographic studies of TFP bound to a calcium-saturated C-domain fragment of CaM (CaM76-148) revealed that CaM adopted an "open" tertiary conformation. The unit cell contained two protein and 4 drug molecules. The orientation of TFP revealed that its trifluoromethyl group was found in two alternative positions (one in each protein in the unit cell), and that Met 144 acted as a gatekeeper to select the orientation of TFP. In contrast to TFP binding to the "open" conformation of calcium-saturated CaM76-148, my NMR studies showed that TFP bound the "semi-open" conformation of apo CaM76-148. TFP interacted with CaM residues near the perimeter of the hydrophobic pocket, but did not contact residues that are solvent-accessible only in the "open" form. Allosteric effects due to TFP binding were observed in the calcium-binding loops of apo CaM76-148. These properties suggest that TFP may antagonize interactions between apo CaM and target proteins such as ion channels that preferentially bind apo CaM. Nav1.2, is responsible for the passage of Na+ ion across cellular membranes. Apo binding of CaM to Nav1.2 poises it for action upon calcium release in the cell. My NMR studies of CaM binding to the Nav1.2 IQ-motif sequence (Nav1.2IQp) showed that the C-domain of apo CaM was necessary and sufficient for binding. My high-resolution structure of the isolated C-domain of CaM bound to Nav1.2IQp revealed that the domain adopted a "semi-open" conformation. At the interface between the IQ-motif and CaM, the highly conserved I and two Y residues of Nav1.2IQp interacted with hydrophobic residues of CaM, while the invariant Q residue interacted with residues in the loop between helices F and G of CaM. This is the first CaM-IQ complex to be determined by NMR; the only other available structure of apo CaM bound to an IQ-motif was determined crystallographically. To accomplish its regulatory roles in response to cellular Ca2+ fluxes, CaM has evolved multiple binding interfaces that are allosterically linked to its Ca2+-ligation state. My studies of CaM binding to TFP and NaV1.2 demonstrate the versatility of CaM functioning as a regulatory protein comprised of domains having separable functions.

The research presented in this dissertation presents a methodology to experimentally predict and simulate the mechanical behavior of polymers under high strain rate deformation. Specifically, the interplay between the effects of temperature and strain rate on polymer behavior is examined and then used as a tool to help recreate the high rate mechanical response of several different polymers: ranging from rubbers to amorphous polymers to composites. Multiple literature reviews are conducted and presented in this thesis, e.g. experimental mechanics test methods, high rate behavior, time-temperature equivalence, constitutive modeling, and temperature measurement methods. In accordance with mechanical theory, an experimental and analytical protocol in rate- and temperature- dependence was applied to a range of PVC materials ranging in plasticizer contents. Further to this, these PVC materials were modeled with a rubbery model describing the network stress seen in polymer behavior, and an amorphous polymer model to describe PVC low to high rate responses to deformation. This modeling develops insights in the adiabatic nature of high rate response. Time-temperature equivalence, and the temperature rise during adiabatic deformation, are studied and exploited in order to implement a proposed experimental method which simulates the high rate deformation of polymeric materials. The development of an experimental methodology to simulate and predict high rate behavior is presented, applied, and expanded to a range of materials: amorphous polymers (e.g. PVC 20wt% plasticizer, PMMA, PC) and composites (e.g. polymer bonded explosive simulant). The work also presents and highlights the fact that micro to nano-scale imaging may be used in parallel with the simulation method in order to better understand high rate behavior. Furthermore, in result of the studies conducted in this body of work, several novel techniques were developed, or improved upon, and applied to the current research (e.g. additions to time-temperature equivalence, temperature measurement methods at high, moderate, and low strain rates, and a method for measuring the high rate behavior of soft materials).

Thesis (Ph.D.)--University of Delaware, 2009.<br>Principal faculty advisors: Norman J. Wagner, Dept. of Chemical Engineerin; and Eric W. Kaler, College of Engineering. Includes bibliographical references.

Thesis (Ph.D.) --University of Montana, 2009.<br>Title from author supplied metadata. Description based on contents viewed on June 11, 2009. ETD number: etd-03252009-151239. Author supplied keywords: Protein Folding ; Denatured State ; Random Coil ; Aggregation ; TR-FRET. Includes bibliographical references.

The generalized Langevin equation (GLE) has been used to describe the dynamics of particles in a stationary environment. To better understand the dynamics of polymerization, the GLE has been generalized to the irreversible generalized Langevin equation (iGLE) so as to incorporate the non-stationary response of the solvent. This non-stationary response is manifested in the friction kernel and the behavior of the projected (stochastic) force. A particular polymerizing system, such as living polymerization, is specified both through the parameters of the friction kernel and the potential of mean force (PMF). Equilibrium properties such as extent of polymerization have been obtained and are consistent with Flory-Huggin¡¯s theory. In addition, time-dependent non-equilibrium observables such as polymer length, the polymer length distribution, and polydispersity index (PDI) of living polymerization have been obtained. These have been compared to several experiments so as to validate the models, and to provide additional insight into the thermodynamic and kinetic properties of these systems. In addition to the iGLE, a stochastic model has been used to study the effect of nonequilibrium reactivity on living polymerization. This model can be used to determine whether the reaction is controlled by kinetics or diffusion. A combination of the iGLE and stochastic models may help us obtain more information about living polymerization.