The voltage-gated sodium ion channel regulates the transport of Na+ across the plasma membrane of electrically-excitable cells in a voltage-dependent manner. Its activity mediates the rising phase of action potentials. The sodium channel's essential role in the function of the nervous system has made it a target for a diverse array of toxins and insecticides during evolution. It is also the receptor for local anesthetics and drugs used in the treatment of disorders such as epilepsy and cardiovascular disease. Recently-solved crystal structures of bacterial potassium channels have revealed the structural basis of ion selectivity and channel gating that underlie their controlled, ionspecific conductance. These potassium channel structures were used to generate homology models for the sodium channel. Docking studies of an homology model with an insecticide, deltamethrin, were undertaken to identify potential binding contacts. Channel modeling studies were also undertaken of a simpler structure, antiamoebin, an antibiotic peptide that polymerizes in lipid bilayers to form channels. Comparisons of this channel model with bacterial potassium channel structures demonstrated common functionally-related structural features. The mam goals of this project were to structurally and functionally characterize purified voltage-gated sodium channels and to prepare homogeneous preparations suitable for crystallization. Sodium channels were purified from electric eel electroplax membranes, which are a rich natural source of this protein. Purification of channels from detergentsolubilized membranes was achieved using immunoaffinity chromatography or alternatively using a succession of chromatography steps, including ion exchange, lectin affinity and gel filtration chromatographies. Sodium channels are heavily glycosylated molecules and purified channels were enzymatically deglycosylated for some structural studies. The function of purified sodium channels was assessed using electrical studies in planar lipid bilayers. Channels displayed toxin-sensitivity and a single-channel conductance, 17.5 picoSiemens, that corresponds well with values reported in the literature for electric eel sodium channels (20-25 picoSiemens). Circular dichroism spectroscopy was used to determine the effect of a toxin, batrachotoxin, and a drug, lamotrigine, on the secondary structure of sodium channels. The channels' helicity increased in the presence of either ligand. This suggests that the ligands stabilize conformations associated with specific functional states, thus shifting the equilibrium between the mixture of functional states present in the ligand-free channels. The ability to detect sodium channels' toxin-sensitivity using circular dichroism spectroscopy was used as an assay for determining the effectiveness of different purification methods to yield functional protein for 2D crystallization trials. 2D crystallization is a technique of special application for membrane proteins as their structures are stabilised in a lipid bilayer. Electron crystallography and 3D reconstruction o can yield structures with resolutions that extend to 7-8 A, at which point elements of secondary structure can become distinguishable. A structure of the sodium channel at this resolution would enable more accurate modeling of this pharmacologically-important protein. 2D crystallization of sodium channels was attempted using a dialysis method and the lipid layer strategy. The latter technique sought to facilitate 2D crystallization by exploiting properties of the sodium channel, namely the significant amount of negative charges localized to the extracellular domain and the asymmetry in the sizes of the intra- and extra-cellular domains.

Two simulated (non-radioactive) borosilicate high-level waste (HLW) glasses were supplied by Nexia Solutions; Blend glass and Oxide glass. This work is primarily concerned with identifying the crystal phases present in both as-cast and heat treated (simulating the retarded cooling experienced by 'real ' (radioactive) borosilicate HLW glasses after pouring) samples of these two glasses; as well as determining the aqueous durability of these samples. An as-cast Oxide glass sample contained a 'yellow phase' inclusion which was also investigated. Combined direct current plasma atomic emission spectroscopy (DCP-AES) and X-ray fluorescence spectroscopy (XRF) determined the chemical composition of both glasses. Differential thermal analysis (DTA) identified their glass transition temperatures, whilst Archimedes' principle yielded their densities. X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) identified crystal phases and, in the case of microscopy, determined microstructural homogeneity. As-cast Blend glass samples were compositionally homogeneous and contained RU02 crystals. Heat treated Blend glass samples contained Cel- (x+y)ZrxGdy0 2- (y/2), (Sr,Nd,La) molybdate and lanthanide (Nd,Gd,La,Ce) silicate crystals. As-cast Oxide glass samples were either compositionally homogeneous (Type I microstructure) or compositionally inhomogeneous (Type II microstructure). RU02, metallic Pd-Te and (Cr,Fe,Ni)304 crystals were observed in both Type I and Type II microstructures, with Na3Li(Mo04)2 . 6H20 crystals occasionally detected. Zrl- (x+y)CexGdy0 2- (y/2) and lanthanide (Nd,Gd,La,Ce) silicate crystals were only detected in Type II microstructures. Heat treated Oxide glass samples displayed either: extensive crystallisation and matrix cracking (Type A microstructure) or 'banded' crystallisation (Type B microstructure), depending on their parent (as-cast) microstructure (Type I or Type II respectively). (Na,Sr,Nd,La)Mo04, Cel- (x+y)ZrxGdy0 2- (y!2) and aNi-rich crystal phase were detected in both Type A and Type B microstructures. a-cristobalite crystals were found exclusively in Type A microstructures, whilst lanthanide (Nd,Gd,La,Ce) silicate and zektzerite crystals were only detected in Type B microstructures. A modified product consistency test (modified PCT-B) determined the aqueous durability of as-cast and heat treated samples of both glasses. Heat treatment of Blend glass improved its aqueous durability marginally. Heat treatment of Oxide glass decreased its aqueous durability significantly (as-cast and heat treated Oxide glass samples had Type I and Type A microstructures respectively). Combined DCP-AES and XRF revealed the chemical composition of the 'yellow phase' inclusion, showing it to be enriched in Mo, Cs, Na, Li, Cr, Ba, Sr and Te compared to Oxide glass. XRD identified the 'yellow phase' inclusion as crystalline, containing CsLiMo04, Na3Li(Mo04)2 . 6H20, (Na,Sr,Nd)Mo04 and BalxSrxMo04 (where 0 <x < 0.5) crystals.

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The thesis describes the results of studies on the morphology, growth kinetics and defect structure of sodium chlorate crystals grown from aqueous solutions at temperatures near the ambient. For the investigation of the growth morphology and habit modification of the crystals as a function of supersaturation and concentration of Na₂S₂0₆·2H₂0 impurity, experimental data on the morphological importance of different faces were supplemented by examination of the surface topography, the dislocation structure land changes in the lattice parameter of the crystals. The results showed that the habit of the crystals grown from pure solutions is cubic at high supersaturations, while it is cuboid with relatively small {110} and {111} faces at low supersaturations. Optical examination of the as-grown surfaces did not reveal the presence of growth spirals or hillocks, but screw, edge and mixed dislocations were identified by Lang topography at both low and high values of supersaturations (undercooling). Addition of the impurity to the growth solution led to the development of tetrahedral faces with randomly situated hillocks of different sizes at the expense of cubic faces, and to an increase in the lattice parameter of the grown crystals. The influence of the impurity was also studied on the nucleation kinetics of the compound. Effects of applied supersaturation on the regeneration process at the seed and the dislocation structure at the seed-crystal interface, and of the strain, applied externally on large crystals and inherently present in small crystals of dimensions 50 - 150 µm, on growth rates were investigated by using X-ray diffraction topography. It was found that the strain generated at the newly-grown interface and the numerical density of dislocations formed therefrom increase with the value of the supersaturation used for the refacetting process. It was unequivocally established that the growth rates of crystals decrease with an increase in the strain applied externally on large crystals and inherently present in small crystals.

This thesis investigates the structural properties of the AM2O7 family of materials, many of which show interesting thermal expansion properties and remarkably complex structures. It also develops Parametric Rietveld refinement, a method of extracting more information from multi-condition powder diffraction data. Chapter 1 reviews the relevant literature. Chapter 2 describes the equipment and analytic techniques used in the work. Chapter 3 describes Parametric Rietveld refinement, which aims to fit a single, evolving structural model to a series of diffraction data collected as a function of time, temperature, pressure or other external variable. This can lead to a number of benefits over conventional, sequential Rietveld refinement: it can increase the precision of refined parameters; allow physically realistic models to be applied during data analysis; and allow 'non-crystallographic’ quantities, such as temperature or rate constants, to be refined directly from diffraction data. Chapter 4 presents a full structure solution of ZrP(_2)O(_7) at room temperature from powder diffraction data. This involved developing a method for combining Rietveld refinement, restraints and simulated annealing. Despite 136 unique atoms and close-to metrically cubic symmetry, the true structure of this orthorhombic material can be refined to a high degree of precision. Chapter 5 is an investigation into the structures and thermal expansion of two AM(_2)O(_7) species, pseudo-cubic SnP(_2)O(_7) and GeP(_2)o(_7). A full structure solution of the room temperature phase of SnP(_2)O(_7) is presented. Two higher temperature phases of SnP(_2)O(_7) and the low temperature phase of GeP(_2)o(_7) are also analysed. Variable temperature data for both materials are presented. Chapter 6 describes the synthesis and characterisation via powder diffraction of solid-state solutions of the general formula Zr(_x)Sn(_1-x)P(_2)o(_7). The variation of properties across the series is investigated both at room temperature and upon heating.

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