Brendan J. Kennedy

Copper complexes of non-steroidal anti-inflammatory drugs: an opportunity yet to be realized

The proposed curative properties of Cu-based non-steroidal anti-inflammatory drugs (NSAIDs) have led to the development of numerous Cu(II) complexes of NSAIDs with enhanced anti-inflammatory activity and reduced gastrointestinal (GI) toxicity compared with their uncomplexed parent drug. These low toxicity Cu drugs have yet to reach an extended human market, but are of enormous interest, because many of todays anti-inflammatory drug therapies, including those based on the NSAIDs, remain either largely inadequate and/or are associated with problematic renal, GI and cardiovascular side effects. The origins of the anti-inflammatory and gastric-sparing actions of Cu-NSAIDs, however, remain uncertain. Their ability to influence copper metabolism has been a matter of debate and, apart from their frequently reported superoxide dismutase (SOD)-like activity in vitro, relatively little is known about how they ultimately regulate the inflammatory process and/or immune system. Furthermore, little is known of their pharmacokinetic and biodistribution profile in both humans and animals, stability in biological media and pharmaceutical formulations, or the relative potency/efficacy of the Cu(II) monomeric versus Cu(II) dimeric complexes. The following review will not only discuss the etiology of inflammation, factors influencing the metabolism of copper and historical overview of the development of the Cu-NSAIDs, but also outline the structural characteristics, medicinal and veterinary properties, and proposed modes of action of the Cu-NSAIDs. It will also compare the SOD, anti-inflammatory and ulcerogenic effects of various Cu-NSAIDs. If the potential opportunities of the Cu-NSAIDs are to be completely realized, a mechanistic understanding and delineation of their in vivo and in vitro pharmacological activity is fundamental, along with further characterization of their pharmacokinetic/pharmacodynamic disposition.

Structural Studies of Rutile‐Type Metal Dioxides

The structures of the four metal dioxides GeO2, SnO2, RuO2 and IrO2 (germanium, tin, ruthenium and iridium dioxides, respectively) have been redetermined by Rietveld refinement from neutron diffraction powder data. The four dioxides all adopt the rutile-type structure, space group P42/mnm (no. 136), with a = 4.4066 (1), 4.7374 (1), 4.4968 (2) and 4.5051 (3), c = 2.8619 (1), 3.1864 (1), 3.1049 (1) and 3.1586 (2) A, and x = 0.3060 (1), 0.3056 (1), 0.3053 (1) and 0.3077 (3), respectively. These results are compared with those for other metal dioxides that adopt the rutile structure and trends in structural and thermal vibrations for a series of 11 metal dioxides which adopt the rutile-type structure are described.

Phase transitions in perovskite at elevated temperatures - a powder neutron diffraction study

The structure of CaTiO3 has been studied at high temperatures by powder neutron diffraction methods. From inspection of the diffraction data two phase transitions are evident, with an intermediate tetragonal (I/mcm) structure forming near 1500 K and a primitive cubic structure above 1580 K. Detailed Rietveld analyses of the data suggest there may also be a phase transition from the room temperature Pbnm structure to an orthorhombic Cmcm structure around 1380 K. A remarkable feature of the results is the regular variation in the out-of-phase octahedral tilt angle over the entire temperature range.

Neutron powder diffraction study of rhombohedral rare-earth aluminates and the rhombohedral to cubic phase transition

Neutron powder diffraction has been used to examine the structural changes of the rare-earth aluminates LaAlO3 , PrAlO3 and NdAlO3 over a wide range of temperatures. At room temperature, all three aluminates adopt the rhombohedral perovskite structure in space group R c (a = 5.3647(1) A, c = 13.1114(3) A for LaAlO3 , a = 5.3337(2) A, c = 12.9842(4) A for PrAlO3 , a = 5.3223(2) A, c = 12.9292(5) A for NdAlO3 ). The rhombohedral structure is characterized by rotation of the oxygen atom octahedra about the threefold axis, and compression of these octahedra parallel to the same axis. As the temperature is increased, the rotation angle and the compression decrease, indicative of an approach to the cubic symmetry of the ideal perovskite. Only for LaAlO3 , however, was the transition at a low enough temperature to unequivocally obtain the cubic phase. For PrAlO3 the transition was closely approached before the sample can failed, but for NdAlO3 the transition appeared to be inaccessible within the available temperature range. The rotation angle is taken to represent the order parameter, and its temperature variation is well described by a generalized mean field approach. Such a description suggests the transitions are continuous, being at 820 K and second order for the transition in LaAlO3 , and at 1768 K and tricritical for the transition in PrAlO3 . In the proximity of the phase transition, the octahedral compression varies with the square of the rotation angle, though this description is inadequate remote from the transition, and the constant of proportionality is different for the different compounds.

The High Resolution Powder Diffraction Beamline for the Australian Synchrotron

A beamline for high resolution powder diffraction studies will be installed as one of the first operational beamlines at the Australian Synchrotron and will be located on a bending magnet source. The beamline will be cable of using energies of 4–30 keV and comprise two end stations. The optical and end station design and performance specifications are presented.

Methanol oxidation on unsupported and carbon supported Pt + Ru anodes

A novel Pt + Ru electrode material is shown to be highly active for the direct electro-oxidation of methanol in H2SO4 solutions and to show very little tendency to poison. X-ray photoelectron spectroscopy of this material before use as an anode showed that the ruthenium is oxidised and that there is an important surface concentration of oxidised platinum. After prolonged use as a methanol-oxidation anode, the concentration of oxidised platinum is somewhat increased and there is no evidence for any Pt-CO or Pt2 = CO species; rather adsorbed formate is present. These data are consistent with Ru acting as a promoter of active surface oxygen. Dispersion of the Pt and Ru on a pure carbon support gives a much greater performance per gram of precious metal; however, the initial increase in overpotential is greater by over 100 mV. The differences in the catalytic behaviour of these two materials is discussed, and the importance of competing reactions is considered.

Powder neutron diffraction study of the high temperature phase transitions in NaTaO3

Neutron powder diffraction has been used to examine the structural phase transitions in the perovskite-like NaTaO3, from room temperature to 933 K. The room temperature orthorhombic structure (Pbnm, a = 5.4768(1), b = 5.5212(1), c = 7.7890(2)) transforms to orthorhombic Cmcm at around 700 K, then to tetragonal P4/mbm at 835 K, and finally to cubic Pmm above 890 K. The structure in orthorhombic Cmcm is characterized by simultaneous tilting of the oxygen atom octahedron about two of its tetrad axes, the tilting of successive octahedra being out of phase along the b-axis, and in phase along the c-axis. The two tilt angles are comparable just above 700 K, but the out-of-phase tilt angle falls smoothly to zero as the transition to tetragonal is approached, in the manner suggestive of a tricritical transition. This results in an unusual variation of lattice parameters with temperature in the orthorhombic Cmcm phase. In the tetragonal phase the lattice parameters vary smoothly; however near the transition to cubic the in-phase tilt angle changes more rapidly with temperature than might be expected in a continuous phase transition.

Porous carbon anodes for the direct methanol fuel cell—I. The role of the reduction method for carbon supported platinum electrodes

The efficiency of platinised porous-carbon electrodes for the electrooxidation of methanol in H2SO4 is found to vary quite markedly with the method used to deposit the platinum. This is shown to be a consequence of both the size and the electronic nature of the platinum crystallites. The most efficient electrodes are those that possess both small crystallite sizes, ∼ 20 A diameter, and a minimum amount of ionic platinum species as identified by XPS studies. A comparison is drawn with optimised platinised carbon electrodes for oxygen reduction, and an explanation for the different requirements of these two types of electrode suggested.

Effect of temperature on cation disorder in ABi2Nb2O9 (A=Sr, Ba)

The influence of thermal annealing on cation disorder in ABi 2 Nb 2 O 9 (A=Sr, Ba) has been studied using synchrotron powder X-ray diffraction methods. BaBi 2 Nb 2 O 9 adopts a tetragonal (I4 1 /mmm) structure, whilst SrBi 2 Nb 2 O 9 is orthorhombic, space group A2 1 am, irrespective of the annealing conditions. In both complexes the A-type cations, Sr and Ba, are disordered over the perovskite and Bi 2 O 2 layers. Quenching the samples from high temperature results in a slight increase in both the cell volume and the degree of disorder, the extent of disorder being greater in the Ba complex. Variable temperature diffraction studies are also reported.

Structural studies of the distorted perovskite Ca0.25Cu0.75TiO3

The crystal structure of Ca0.25Cu0.75TiO3 has been studied between 25 and 1000°C using powder neutron diffraction methods. The diffraction data is well described in space group Im3, and there is no indication of any crystallographic phase transition. The preference of the Jahn-Teller active Cu ion for square planar geometry is believed to be a significant factor in the stabilization of the observed structure.