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By Peter J. Barnard

Mitochondria play a key role in the regulation of apoptosis (cell death) and in diseases characterised by abnormal apoptotic responses such as cancer. Mitochondrial membrane permeabilisation (MMP), regulated by the mitochondrial permeability transition pore complex, is widely accepted as being central to the process of cell death. As a result there has been considerable recent interest in targeting mitochondrial cell death pathways in the development of new chemotherapeutic agents.(1) There is potential to overcome the two overriding problems in cancer chemotherapy?the common occurrence of drug-resistant tumour cells and the lack of selectivity of cancer drugs in differentiating between tumour cells and normal tissues. Significantly, carcinoma cells have an elevated mitochondrial membrane potential relative to normal cells and lipophilic cations are concentrated within mitochondria in response to mitochondrial membrane potentials. There is potential for the selective targeting to tumour cells with compounds having optimal lipophilic-hydrophilic character. Research stemming from the early 1980?s points to two distinct classes of Au(I) phosphine antitumour agents where an antimitochondrial mode of action has been implicated: (i) neutral linear two-coordinate Au(I) complexes such as triethylphosphinegold(I) chloride and the tetraacetylthioglucose gold(I) phosphine complex, Auranofin; (ii) cationic tetrahedral bis-chelated Au(I) phosphine complexes related to [Au(dppe)2]+.(2) Recently it has been reported that Auranofin, at submicromolar concentrations, induces MMP observed as mitochondrial swelling and dissipation of membrane potential.(3, 4) Both events are completely inhibited by cyclosporin-A, the specific inhibitor of MMP. The permeability changes were shown to occur at concentrations associated with the selective inhibition of mitochondrial thioredoxin reductase.(3) Auranofin is a potent and specific inhibitor of this enzyme due to Au(I) binding to the active-site selenol group.(5) The redox state of mitochondrial thiols may be critical in the control of MMP.(3) In general, swelling is stimulated by thiol blocking or oxidising agents and is prevented by thiol reducing agents.(1) Mitochondrial thioredoxin reductase may play an import role in the redox control of the permeability of mitochondrial membranes.(3) Our interest is in investigating the antitumour potential of Au(I) phosphine compounds using a number of different approaches. In recent work we have evaluated a series of hydrophilic analogs of [Au(dppe)2]+ containing pyridylphosphine ligands which have demonstrated greater tumour selectivity than the parent compound. To investigate the possible antimitochondrial mode of action we are studying the effect of [Au(dppe)2]+ and related compounds on isolated rat liver mitochondria. To assess whether the lipophiliccationic nature of the compounds determines the antitumour activity, we have synthesized a series of novel Au(I) complexes based on heterocyclic carbene rather than phosphine ligands. The similar chemistry and structural features of the two classes of complexes allow us to assess whether the phosphine ligands are essential for the antitumour properties.

Oct 1, 2003

By Ronald L. Bruening

IBC has developed a cost effective MRT process for the selective extraction and recovery of gold, copper, and a mixture of other base metals from mine leach cyanide solutions. This is a two-stage system in which the gold is first recovered selectively as a high purity salt. The copper is then recovered separately as a sulfate salt. The other base metals are then collected as a cyano anion concentrate. Three different SuperLig® materials are used. The first stage can be used alone on gold leach solutions where copper and other base metals are not a problem. The two or three stage system is used when the base metals build up in the leach solution, resulting in increased costs. The cyanide or cyanide/cyano anion concentrate can be recycled back to the leach solution until the build-up of other salts, etc. becomes too high, or this too can be controlled with a percentage bleed stream.

Oct 1, 2003

By K. Wongpreedee

Recovery and recrystallization of Au wire can degrade strength and alter conductivity properties during exposure to elevated temperature. Au Deformation Processed Metal Metal Composites (Au DMMC's) are being developed for electronic applications requiring high conductivity and high strength. This paper discusses the relationships between microstructure, strength, and resistivity of Au DMMC's. It also presents the results of a recent study on the elevated temperature stability of Au DMMC's of several compositions. Au-7 vol %Ag, Au-14 vol %Ag, and Au-vol 7%Pt DMMC samples were prepared by a powder metallurgy technique. All specimens were processed into wire by extrusion, swaging, and drawing. The smallest final diameter of these wires was 120 ?m. Thermal stability was analyzed by electrical resistivity measurements to determine the relation between transformation rates and time at elevated temperature. The extensive deformation used to produce these composites reshaped the initially equi-axed powder into filaments that are 30 to 100 nm in diameter and 16 to 180 mm in length. The small filament diameter confers high strength on the composite. The high conductivity can be explained by electrons flowing parallel to the filamentary microstructure aligned with the wire axis. Using the Avrami and Arrhenius equation relationships, it is possible to predict the times and temperatures needed to achieve various degrees of homogenization. The Au DMMC's were found to have good thermal stability compared to conventional coldworked Au interconnection wires. Although these composites will revert to solid solutions if exposed to high temperatures for prolonged time periods, their relative stability is sufficient to allow them to maintain their twophase microstructure during the anticipated lifetime temperature profiles of many products.

Oct 1, 2003

By Chih-Huey Lin

The Au/?-Al2O3 catalyst prepared by AuCl3 impregnation is subjected to the influence of residual chlorine after an oven drying. A post-impregnation NH4OH treatment was able to eliminate chlorine, and to reduce the cluster size of Au moiety. However, the CO oxidation activity was not increased by this post-impregnation NH4OH treatment. This suggests that certain metal-support interaction (MSI) is the determining factor for the activity of Au catalysts. Thermal treatment under H2, O2 or He was attempted to increase MSI of the prepared catalyst with or without the post-impregnation NH4OH treatment. No significant activity enhancement was found but the TPD analysis suggests that a H2 treatment has a higher chance to induce MSI.

Oct 1, 2003

By Simon P. Fricker

Gold drugs have been used for the treatment of rheumatoid arthritis since the mid 20th century as disease-modifying antirheumatic drugs (DMARD) class. Methotrexate is often the preferred DMARD, and with the advent of new therapies gold drugs are now used infrequently. Since the introduction of auranofin in 1985 there has been no new clinically approved gold drug. In spite of this apparent lack of progress there has been a great deal of interest in the use of gold compounds for cancer therapy and early promising indications were achieved with a gold phosphine complex [Au(dppe)2]Cl. This compound was not entered for clinical trials, however, due to problems with cardiotoxicity highlighted during pre-clinical toxicology studies. Gold(III) is isoelectronic (d8) with platinum(II) and likewise forms square planar complexes. It is therefore tempting to speculate that such complexes would have similar antitumor activity to cisplatin. In order to stabilise the gold(III) oxidation cycloaurated complexes were synthesised with a single mononegative bidentate ligand, damp, (2-[(dimethylamino)methyl]phenyl), and two monodentate anionic ligands e.g. Cl or acetate. The damp ligand forms part of a five-membered chelate ring. The monodentate ligands are readily hydrolysed and are available for substitution. These compounds had limited anti-tumor activity in in vivo against human tumor xenografts. Mechanistic studies indicated that these compounds had a different mechanism of action to cisplatin. An alternative molecular target for these compounds is biologically important thiol-containing molecules such as the cysteine protease cathepsin B. Modifications were made to the Au(III) damp structure to give compounds with a six-membered chelate ring. These compounds were shown to be inhibitors of cathepsin B. Compounds were also tested for cytotoxicity against a panel of human tumor cell lines. Three compounds were selected for further evaluation against a human colon tumor xenograft. The compounds showed modest anti-tumor activity but with no marked improvement over the parent Au(III)damp complexes. Initial indications are that Au(III) compounds targeted against disease-specific thiol-containing biological molecules have potential as drugs, particularly for cancer. However, further work is required to produce a target-specific drug with a suitable pharmacological activity and toxicity profile.

Oct 1, 2003

By Rodolfo Zanella

Au/TiO2 catalysts were prepared by deposition-precipitation using NaOH (DPN) (~3 wt % Au) and urea (DPU) (~8 wt % Au), and calcined at various temperatures between 100 and 400 °C. They were characterized by UV-Visible, XANES, EXAFS and TEM. Their activity were tested in the reaction of CO oxidation at 5°C. After preparation, the gold species are in the oxidic state III. They begin to transform into metallic gold under air at ~100 °C for DPN and ~150 °C for DPU. At 200 °C, all the gold is metallic for the two preparation methods. The particle size increases from 1.5 to 3.5 nm with the calcination temperature. The catalytic activity for CO oxidation increases with the percentage of metallic gold, and it is maximum at 200°C for both types of samples. The activities (per mole of Au) are the same for the two types of catalysts. At higher temperatures, the catalytic activity drops. The decrease of activity is mainly due to a change of particle shape with the calcination temperature rather than to the increase of the particle size. At a calcination temperature of 200°C, the particles present small facets with rounded parts, and their outer surface contains a large proportion of low coordinated sites (steps and corners) while at high temperature of calcination, they are truncated octahedra with smooth facets.

Oct 1, 2003

By Mari Yamamoto

Controlled thermolysis of gold(I) complex, [Au(C13H27COO)(PPh3)], at 180 °C for 5 h under an N2 atmosphere affords the new type of monodispersed spherical gold nanoparticles capped by myristate and a small amount of PPh3 ligands (average diameter 23±1.5 nm), in spite of no use of solvent, reducing agent and stabilizer. Much attention has been paid to the preparation and structure determination of transition metal nanoparticles, because of their widespread use in technological applications.1 In general, the chemical reduction of metal salts and organometallic complexes2 by the use of reducing agent is carried out to prepare gold nanoparticles. In some cases, a large amount of solvent and stabilizers such as surfactants,3 polymers4 and ligands5 are used to prevent agglomeration of particles and control the particle size. For instance, Brust et al. reported a two-phase reduction of AuCl4 - by NaBH4 in the presence of dodecanethiol as stabilizer to prepare gold nanoparticles.6 On the other hand, O?Brien et al. recently reported an one-phase preparation of gold nanoparticles by the reduction of AuCl4 - by NaBH4 in the mixture of tri-n-octylphosphine oxide and octadecylamine which act as both solvent and stabilizer, but this procedure also needs reducing agent.7

Oct 1, 2003

By Hua-Zhong Yu

Gold is one of the most widely used substrate materials for self-assembly. Self-assembled monolayers (SAMs) prepared from alkanethiols and their derivatives on gold are the most reliable and well-studied systems to date, which have attracted much attention because of interest in two-dimensional molecular assemblies, and of their potential applications in molecular devices, sensors, and functionalized interfaces. Gold electrodes are also very important in microelectronics and electroanalytical chemistry. This work reports the characterization of a new type of gold substrates for self-assembly. The gold substrates are constructed from recordable compact disks (R-CDs) with simple and straightforward wet-chemical treatment, and can be made at desired sizes and shapes that satisfy different experimental needs. In particular, an easy, inexpensive, and reproducible method to prepare self-assembled monolayers (SAMs) on CD-R gold substrates after removing the protective polymer films with concentrated nitric acid was described.

Oct 1, 2003

By Renaud Cousin

Supported gold catalysts were prepared by Direct Anionic Exchange on an alumina support and tested during the reaction of CO oxidation and of saturated and unsaturated hydrocarbons (C1 to C3). The catalysts showed high activies over a range of concentrations and temperatures compatible with an application to automotive exhaust cleaning. Furthermore, a complete resistance to thermal ageing at 600°C in the absence or presence of water was observed due to the obtention of strongly anchored nanosized gold particles during the preparation step.

Oct 1, 2003

By Kenji Koga

In order to derive the population distribution of gold nanoparticle morphologies as a function of size, highresolution electron microscopic (HREM) observations and structural analyses were done for over 4000 particles (3-18 nm) grown by an inert gas aggregation (IGA) source using helium. To obtain structural features threedimensionally and not to skip high-contrast images, twenty photos were taken for each particle by changing tilting angle of a specimen holder in combination with the through-focus procedure. For the reliable structural determinations, HREM images and their tilting sequences were directly compared with multislice-simulation results for icosahedral, decahedral and face-centered cubic morphologies, and finally the population distribution of each morphology was obtained as a function of size. In the present sample, icosahedral particles were dominantly populated over the whole observed size range and decahedral particles with non-spherical truncated bi-pyramid shape were secondly dominant. Even though a large number of sampling has been done, few crystalline particles were observed.

Oct 1, 2003

By Heidi Fauser

The aim of the project was the development of an electroforming process for the production of medical implants out of gold. To prove the applicability of this technology, tympanostomy tubes were chosen as demonstrators. These barbell-shaped tubes are usually produced mechanically; of silicone or, for higher therapeutic demands, of metal ? gilded silver or gilded stainless steel. Gold electroforming of the tubes as an alternative manufacturing process would reduce the expenditures for the mechanical preparation and lower the corrosion susceptibility significantly. To obtain electroformed gold tubes of the desired shape, the following steps are necessary: fabrication of a negative template by drilling holes with countersinks in an insulated aluminium sheet, electroforming process, removal of the aluminium by using a sodiumhydroxide solution. For the optimisation of the shape and surface quality of the tubes respectively the simplification of the manufacturing process, various parameters were tested, e.g. aluminium quality and sheet thickness, type of insulation layer, substrate processing, hydrodynamic conditions, type of electroforming electrolyte, electrodes position, etc. The manufactured tubes were characterised in view of thickness distribution, hardness, surface roughness and purity in comparison to mechanically produced reference tubes. From the results obtained during the project it can be concluded that electroforming processes can be easily adopted for the manufacture of medical implants. The time-consuming electroforming process is by far compensated by the simultaneous production of an arbitrary number of implants.

Oct 1, 2003

By Matthew S. Hall

Gold/iron oxide catalysts have been prepared and their catalytic performance evaluated for low temperature CO oxidation. The method and temperature used to dry the sample has a significant effect on their catalytic activity. Analysis by TEM revealed the catalysts contained Au particles, although catalysts with high and low activity did not always differ in their microstructure as evidenced by TEM. Catalysts were characterised using XPS and the difference between the Au(4d) and C(1s) binding energies measured; in general the greater the difference, the higher the catalytic activity of the material.

Oct 1, 2003

By Anna Maria Venezia

Bimetallic Au-Pd catalysts supported on amorphous silica-alumina (ASA) with vary amount of alumina (0, 8, 14, 28 and 100%) were prepared by the simultaneous reduction of palladium and gold precursors by ethanol in the presence of the polyvinylpyrrolidone (PVP). X-ray diffraction and X-ray photoelectron spectroscopy analyses indicated formation of alloyed Au-Pd particles. Ammonia temperature programmed desorption measurements were performed to monitor the acid strength and the amount of acid sites on the catalysts after their reduction with 10%H2/Ar at 573 K for 1h. The effect of the support acidity on the catalytic activity was investigated in the simultaneous hydrogenation (HYD) of toluene (T) and naphthalene (NP) in the presence of dibenzothiophene (DBT). Coke formation was also determined. Under the selected conditions (P = 5.0 MPa, T = 523 K, WHSV = 41.2 h-1), all the catalysts were resistant to poisoning with 113 ppm of S (as DBT). The hydrogenation activity of toluene and the HDS activity of DBT were found to correlate with the concentration of the medium strength acid sites. The enhancement of the HYD activity and the S- tolerance was related to modifications of the electronic properties of the metal atom upon interaction with the Brönsted acid sites and upon intermetallic interaction.

Oct 1, 2003

By Gary Pattrick

A new class of spongy Au catalysts is studied for the selective catalytic reduction of NOx by propene under leanburn conditions. The spongy catalyst is an unsupported powdered Au that consists of micrometer particles (~5 microns) that have nanometer scale (~10 nm) internal skeletal structures. The effects of alloying 1 ? 50 atom % platinum group metals (M= Pt, Pd, Rh) and 5 wt% first row transition metals (M = Ti, Mn, Fe, Co) were studied. Even low additions of PGMs (1 at.%) cause significant shifts to lower temperature regions of activity and the largest shift is obtained for Rh. For Rh this is interpreted as a strong synergistic interaction between Rh and Au. Possibly related to the Rh effect, Co is the only other metal studied that lowers the temperature of NOx reduction. The other first row transition metals inhibit the reduction reaction.

Oct 1, 2003

By Jolanta Olkowska-Oetzel

Reactions of gold?phosphino complexes [(AuX)(PR3)] (X= Cl, Br, I; R = organic rest) with Se(SiMe3)2 lead to the formation of gold complexes with chalcogenide bridges. The reaction of the complex Ph3PAuCl and tBuSe(SiMe3) gives the cluster [Au5Se2(PPh3)4]Cl 1. The in situ preparation of the complex [(AuCl)2dpph] (dpph = Ph2P(CH2)6PPh2) by reaction of dpph with Me2SAuCl, and subsequent reaction with Se(SiMe3)2 leads to the formation of [(Au3Se)2(dpph)3]Cl2 2. Reactions of the gold(I) complex [(AuCl)2dpppe], (dpppe = Ph2P(CH2)5PPh2) with Se(SiMe3)2 and InCl3 in different molar ratios lead to the formation of [Au10Se4(dpppe)4]InCl5 3 and [Au4(SeInCl3)2(dpppe)2] 4. The reaction of [(AuCl)2dpph] with Te(SiMe3)2 and GaCl3 produces the isostructural cluster compound [Au4(TeGaCl3)2(dpph)2] 5. From the reaction of Se(SiMe3)2 with [(AuCl)2dppe] (dppe = Ph2P(CH2)2PPh2) and InCl3 [Au8Se4In(dppe)4](InCl4)3 6 can be isolated. The structures of 1 - 6 were determined by X?ray diffraction.

Oct 1, 2003

By Emile D. L. Rienks

We have studied the interaction of NO with the quasi-hexagonally reconstructed Au(100) surface. Using variable temperature scanning tunneling microscopy we have observed formation of the unreconstructed phase of Au(100) after NO exposure. This NO adsorption induced phase transition is observed in a window of temperatures around 170 K. Under the same conditions, CO and O2 cannot drive the phase transition, suggesting weaker interaction. Thermal desorption spectroscopy experiments provide an estimate for the strength of NO chemisorption on Au(100) of 57 ± 4 kJ mol-1.

Oct 1, 2003

By Ayako Iwakoshi

Highly concentrated pastes of gold nanoparticles were successfully produced by use of a special kind of protective polymer and a mild reductant. Solid part of the pastes consists of up to 85wt% of gold nanoparticles, 10~30 nm in diameter, and residual protective polymer. This component can be diluted by any kinds of solvent at arbitrary rates. Electronics, optics, catalysts, colorants and surface metal coatings are possible application fields. 1. Introduction Noble metal nanoparticles are of interest in a variety of fields ? such as colorants, metal coatings, electronics(1), optics(2), and chemical catalysis(3). Especially, in the color field, the gold nanoparticle has been known as an aesthetic red colorant for stained glass and fine glassware, such as Venetian glass. The mechanism of coloring is attributed to surface plasmon absorption of gold nanoparticles(4,5). The gold nanoparticle in stained glass shows very clear red color, which is very durable for hundreds years. On the other hand, the red color of organic pigment in paint films often fades away within several years. We intended to reproduce the elegant and stable coloring of stained glass in paint films. In order to color a very thin, 20~50?m, paint film like stained glass, production of highly concentrated dispersion of gold nanoparticle is necessary. To achieve this, there were two issues to be overcome. One is how to prevent the coagulation of gold nanoparticles in highly concentrated solution. So far, several methods to prepare gold nanoparticles(6,7) were reported. But only a few methods succeeded to stabilize the gold nanoparticle dispersion at higher concentration than ppm order. The other is controlling of the particle size, this is because the color of gold nanoparticles is very sensitive to the particle size. Only when the particle size lies around 10 nm, the suspension exhibits red color like stained glass.

Oct 1, 2003

By Fabian Mohr

The methyl substituted binuclear cyclometallated gold(I) complexes [Au2(?-n-MeC6H3PPh2)2] [n = 4, 5 and 6] all undergo oxidative addition reactions with halogens and, in the case of the 4- and 5-methyl substituted analogues, with dibenzoyl peroxide to give metal-metal bonded digold(II) complexes [Au2X2(?-C6H3-n-MePPh2)2]. The 4- and 5-methyl substituted digold(II) compounds on warming or exposure to light undergo carbon-carbon coupling reactions to give gold(I) complexes containing the corresponding 2,2'-n,n'-biphenylyldiphenylphosphines. The 6- methyl substituted digold(II) complexes rapidly isomerise above ca. -20° C to binuclear heterovalent gold(I)/gold(III) compounds [XAu(?-2-Ph2PC6H3-6-Me)AuX{?2-(6-MeC6H3-2-PPh2)}], containing a fourmembered cyclometallated ring on a gold(III) centre. Surprisingly, no carbon-carbon coupling could be induced for any of the 6-methyl substituted compounds, even under forcing conditions. This difference in reactivity of the 6- methyl derivative, compared to that of the 5-methyl and unsubstituted analogues was studied by ab initio calculations using a series of model compounds. The results are in excellent agreement with the experimental findings and suggest that the key-step in the C-C coupling reaction is the partial opening of the Au(III)-P bond in one of the transition states. In the 6-methyl system this transition state is energetically inaccessible and hence no C-C coupling occurs.

Oct 1, 2003

By Gaby Steinbach

A novel synthesis is described for the preparation of supported gold catalysts for low-temperature CO oxidation. The novel route is a variation of the inverse co-precipitation method and requires amphoteric metal hydroxides, with zinc and aluminium hydroxides chosen. Catalysts were prepared by inverse co-precipitation (ICPa) and by the novel route (ICPb) and tested for CO oxidation at 60ºC. Preliminary results showed the novel route to be superior to ICPa; the catalysts prepared by ICPb showed higher catalytic activities. The effect on catalytic activity of parameters such as pH, calcination temperature, washing of precursor and calcined catalysts and ageing was investigated. A preparation pH of 9 and a Zn to Al mass ratio of 3 proved to be optimal. It was possible to remove residual chloride by washing thereby enhancing catalyst performance. Ageing and Mg citrate addition were also shown to improve catalyst performance. Characterization of the catalysts revealed that better activities were obtained when the support was more crystalline and had a higher surface area. The presence of carbonate-containing species in the support decreased catalytic activity. 197Au Mössbauer Spectroscopy revealed the presence of Au3+ when catalysts were heat-treated at temperatures of 200ºC and below. Catalysts calcined at 400º had 75% of the gold present as Au0, with the remaining gold present as Au3+.

Oct 1, 2003

By József L. Margitfalvi

Different Au/MgO catalysts modified with Mn, and Fe were prepared by precipitation-deposition. The catalysts were characterized by XRD, FTIR, Temperature Programmed Reduction (TPR) and CO chemisorption and were tested in CO oxidation in the temperature range of 243-523 K. The catalytic tests using both Temperature Programmed Oxidation (TPO) technique and time on stream (TOS) experiments revealed the high activity of catalysts prepared. In TPO experiments the modification by Mn significantly increased the activity above 300 K, however in the subambient temperature range the activity decreased considerably. Catalysts modified by iron did not show any decrease in the activity below 300 K, while the activity at high temperature increased significantly. Catalysts modified by Mn, Fe showed higher activity, selectivity and stability in preferential CO oxidation, carried out in the presence of hydrogen than the unmodified Au/MgO catalysts. Results of in situ FTIR spectroscopy on both the base Au/MgO and the iron modified catalyst unambiguously revealed the formation of ionic gold in the presence of CO/O2 mixture. The formation of this species was strongly hindered in catalyst modified by manganese. Results obtained strongly support the need for the formation of "metal ion - metal nanocluster" ensemble sites. These sites are involved in the activation of the CO molecule prior to its reaction with atomic oxygen. It is suggested that at subambient temperature these ensemble sites contain mainly ionic forms of gold, while at higher temperature iron or manganese ions are involved in CO activation.

Oct 1, 2003