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Benzothiadiazole-mediated induced resistance to fusarium oxysporum f. sp. radicis-lycopersici in tomato

Benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH), a synthetic chemical, was applied as a foliar spray to tomato (Lycopersicon esculentum) plants and evaluated for its potential to confer increased resistance against the soil-borne pathogen Fusarium oxysporum f. sp. radicis-lycopersici (FORL). In nontreated tomato plants all root tissues were massively colonized by FORL hyphae. Pathogen ingress toward the vascular stele was accompanied by severe host cell alterations, including cell wall breakdown. In BTH-treated plants striking differences in the rate and extent of fungal colonization were observed. Pathogen growth was restricted to the epidermis and the outer cortex, and fungal ingress was apparently halted by the formation of callose-enriched wall appositions at sites of fungal penetration. In addition, aggregated deposits, which frequently established close contact with the invading hyphae, accumulated in densely colonized epidermal cells and filled most intercellular spaces. Upon incubation of sections with gold-complexed laccase for localization of phenolic-like compounds, a slight deposition of gold particles was observed over both the host cell walls and the wall appositions. Labeling was also detected over the walls of fungal cells showing signs of obvious alteration ranging from cytoplasm disorganization to protoplasm retraction. We provide evidence that foliar applications of BTH sensitize susceptible tomato plants to react more rapidly and more efficiently to FORL attack through the formation of protective layers at sites of potential fungal entry.

Journal Article↗

A new approach for the recovery of precious metals from solution and from leachates derived from electronic scrap.

A new approach is described for the recovery of precious metals (PMs: Au, Pd and Ag) with >99% efficiency from aqueous solution utilising biogas produced during the aerobic growth of Klebsiella pneumoniae. Gold was recovered from electronic scrap leachate ( approximately 95%) by this method, with some selectivity against Cu. The recovered PM solids all contained metal and sulphur as determined by energy dispersive X-ray microanalysis (EDX). X-ray powder diffraction analysis (XRD) showed no crystalline metal sulphur compounds but a crystalline palladium amine was recorded. Silver was recovered as a sulphide (found by EDX), carbonate and oxide (found by XRD). EDX analysis of the Au-precipitate showed mainly gold and sulphur, with some metallic Au(0) detected by XRD. The gold compound was shock-sensitive; upon grinding it detonated to leave a sooty black deposit.

Aerobiosis↗

Variable solid state aggregations in a series of (isocyanide)gold(I) halides with the novel trimethylamine-isocyanoborane adduct.

This paper provides evidence that the degree of aurophilic character and resulting solid state arrangement observed in (isocyanide)gold(I) halides is in part dependent on the nature of halide substituent. In particular, we report here the synthesis of a series of novel (isocyanide)gold(I) halides involving trimethylamine-isocyanoborane, an unusual 'zwitterionic' isocyanide that is comparable to the more familiar methyl isocyanide, but potentially more strongly Lewis basic. The reaction of chloro(dimethyl sulfide)gold(I) and the isocyanoborane species, (RNC)(R =(H3C)3NB(H)2), gives the novel crystalline adduct [(RNC)AuCl] (1). Treatment of 1 in an organic phase with aqueous KBr effected substitution of the chloride to give the bromide analogue [(RNC)AuBr] (2). The structures of 1 and 2 were determined by X-ray crystallography to be isostructural, consisting of a zigzag topology of chains of monomers, where adjacent gold(I) centres interact aurophilically. However, similar reaction of 1 with KI solution affords the unusual and unexpected compound, [(RNC)2Au][AuI2] (3). This iodide 3, is a linear chain polymer of alternating anion, cation units that is formed via ligand redistribution. The complexes 1-3 all fluoresce in the presence of UV light; the fluorescence of 3 being most prevalent at room temperature. The free trimethylamine-isocyanoborane ligand, the dimeric structures of compounds 1,2 and the thermodynamic stabilities of the dimers in the gas phase were studied by density functional and ab initio calculations at various levels of theory. The theoretical results are compared to the corresponding experimental data.

Boron Compounds↗

Cellular interactions of auranofin and a related gold complex with RAW 264.7 macrophages.

Auranofin (AF) is an orally active chrysotherapeutic agent whose precise mechanism of action with its putative target cell, the macrophage, is not known. In a previous paper, we described a sequential thiol exchange mechanism that explained auranofin's molecular mechanism of interaction with RAW 264.7 cells. To further understand the mode of action of AF and to test the validity of the thiol exchange model, we have continued to study the interactions with macrophages of AF and a related gold complex, triethylphosphine gold chloride (TEPG). Evaluation of the effects of AF and TEPG on RAW 264.7 cells demonstrated that: more gold from TEPG than AF associated with cells over time and with a variety of concentrations; and cellular association of AF and TEPG was temperature dependent. The energy of activation for cell association, the rate-limiting step in the thiol exchange process, was lower for TEPG than AF; cellular association and uptake of both compounds did not require metabolic energy; and efflux of both AF and TEPG was time, temperature, and thiol dependent. Based on these and previous data, we conclude that sequential thiol exchange may be a generic phenomenon for cellular uptake and distribution of thiol reactive gold compounds and that the rate-limiting step is the exchange of either tetraacetylthioglucose (TATG) or chloride for a membrane-localized sulfhydryl group.

2,4-Dinitrophenol↗

Cellular association, intracellular distribution, and efflux of auranofin via sequential ligand exchange reactions.

Auranofin (AF), an orally active, antiarthritic agent, modulates the functional activities of macrophages in vivo and in vitro. To better understand the molecular mechanism of action of auranofin with macrophages we have investigated its cellular association, intracellular distribution, and efflux with RAW 264.7 cells using auranofin radiolabeled within the triethylphosphine (Et3P) [3H], the gold [195Au] or the tetraacetylthioglucose (TATG)[14C] moieties of the molecule. Evaluation of the effects of auranofin on RAW 264.7 cells demonstrates that (1) cellular association of this compound was concentration, time and temperature dependent; (2) cellular association of AF was inhibited by N-ethylmaleimide but not by 2,4-dinitrophenol and NaF; (3) cellular association and uptake of Au and Et3P into cells was reduced when the drug was preincubated with increasing concentrations of fetal calf serum and albumin; (4) no tetraacetylthioglucose from the auranofin molecule became cell associated whereas the Au and Et3P moieties were internalized and distributed between the nuclear, cytosolic and membrane fractions of cells; and (5) efflux of Au and Et3P from RAW 264.7 cells was time and temperature dependent. Based on these data we propose a model, a sequential ligand exchange process, that describes the molecular interactions of auranofin and possibly other gold compounds with these cells.

2,4-Dinitrophenol↗

Theophylline pharmacokinetics with concomitant steroid and gold therapy.

BACKGROUND: Theophylline has been used for several decades in the treatment of asthma. In recent years, however, with the appreciation of the importance of inflammation in the pathogenesis of asthma, new therapeutic approaches have arisen, including beta2-agonists, steroid and nonsteroidal anti-inflammatory drugs, such as gold salts. OBJECTIVE: In the present work we studied the kinetic behaviour of theophylline administered concomitantly with methylprednisolone (steroid compound) and auranofin (oral gold) in six adult female patients. METHOD: Drug concentration data for patients under routine care were collected. The kinetic analysis (Bayesian Approach) was done using two different commercial software packages, PKS (Abbott Diagnostics) and CAPCIL (SIMKIN Inc., courtesy of Dade-Behring). A one-compartment open model with first-order absorption (ka for PKS=0. 5/h; ka for CAPCIL=0.3/h ) and first- order elimination. Default CL, t1/2 and Vd values were used for each program was assumed. The measured and predicted theophylline concentrations were used to calculate percentage prediction errors defined as %PE=[(predicted conc. - measured conc.)/measured conc.] x 100. A linear regression analysis was also carried out for the observed concentrations and those predicted by each method (PKS vs. CAPCIL). RESULTS: The predicted concentrations indicating persistently over-predicted the observed theophylline serum levels (results expressed as median and interquartile range; %PE for PKS=58.1 [37.1-126.0]; %PE for CAPCIL=34.0 [12.5-93.8]). The regression analysis confirmed the same tendency, showing an intercept significantly different from zero using both PKS and CAPCIL. CONCLUSION: The results suggest a possible interaction between theophylline and auranofin. Both PKS and CAPCIL failed to predict theophylline serum levels based exclusively on population pharmacokinetic parameters. The lower observed concentrations than expected have obvious implications in practice. Periodic theophylline serum determinations are advisable until further studies provide the necessary clarification about the kinetic profile of theophylline in patients taking concomitant steroids and gold salts.

Adult↗

Library design, synthesis, and screening: pyridine dicarbonitriles as potential prion disease therapeutics.

Transmissible spongiform encephalopathies (TSEs) or prion diseases are a family of invariably fatal neurodegenerative disorders, and there are no effective therapeutics currently available. In this paper, we report on the design, synthesis, and screening of a series of pyridine dicarbonitriles as potential novel prion disease therapeutics. A virtual reaction-based library of 1050 compounds was constructed. Docking and evaluation using GOLD scores assisted the initial selection of compounds for synthesis. The selection was augmented with further compounds to increase structural diversity. A total of 45 compounds were synthesized via a one-pot three-component coupling reaction. The mechanism of the three-component coupling reaction was investigated, and it was discovered that chemical oxidation is required for the last step, forming the pyridine ring (aromatization). A total of 19 compounds were identified as binders to one or more forms of prion protein by in vitro screening using surface plasmon resonance (SPR). A selection of compounds were investigated for activity in cells, resulting in the discovery of a new inhibitor of PrP(Sc) formation.

Combinatorial Chemistry Techniques↗

Classification of perioperative histamine-related reactions.

OBJECTIVE: Histamine release may cause anaphylactoid reactions. However, during anaesthesia and surgery especially cardiovascular effects may not be regarded as histamine-related. Therefore, we adapted the classical concept of histamine release reactions to the perioperative situation and validated the new paradigm. METHODS: Elevated plasma histamine (diagnostic gold standard) was correlated to potentially related intraoperative signs and symptoms. The validity, repeatability and sensitivity of the 'gold standard' was tested by ROC analysis in volunteers, who also received H1-/H2-histamine antagonists. Additionally, a dose-response relationship was determined in dogs using the histamine releaser compound 48/80. RESULTS: The 'gold standard' had a sensitivity of 96% (90%-100%) and a specificity of 93% (85%-100%). The reproducibility was proven by repeated injections of histamine. Skin reactions, tachycardia and hypertension were identified as histamine-related diagnostic variables. A dose-response curve of plasma histamine release was created. CONCLUSIONS: The defined 'gold standard' is valid for the diagnosis of histamine-related reactions during anaesthesia and surgery. It may help to identify patients, who could benefit from pre-anaesthetic antihistamine prophylaxis.

Animals↗

Carboranethiol-modified gold surfaces. A study and comparison of modified cluster and flat surfaces.

Four different carboranethiol derivatives were used to modify the surfaces of gold nanoparticles and flat gold films. The novel materials engendered from these modifications are extraordinarily stable species with surfaces that support self-assembled monolayers of 1-(HS)-1,2-C2B10H11, 1,2-(HS)2-1,2-C2B10H10, 1,12-(HS)2-1,12-C2B10H10, and 9,12-(HS)2-1,2-C2B10H10, respectively. Surprisingly, characterization of these materials revealed that a number of molecules of the carboranethiol derivatives are incorporated inside the nanoparticles. This structural feature was studied using a number of techniques, including X-ray photoelectron spectroscopy (XPS), UV-vis, and IR spectroscopies. Thermal desorption experiments show that carborane molecules detach and leave the nanoparticle surface mostly as 1,2-C2B10H10 isotopic clusters, leaving sulfur atoms bound to the gold surface. The surfaces of both the gold nanoparticles and the flat gold films are densely packed with carboranethiolate units. One carborane cluster molecule occupies an area of six to seven surface gold atoms of the nanoparticle and eight surface gold atoms of the flat film. XPS data showed that molecules of 1,12-(HS)2-1,12-C2B10H10 bind to the flat gold surface with only half of the thiol groups due to the steric demands of the icosahedral carborane skeleton. Electrochemical measurements indicate complete coverage of the modified gold surfaces with the carboranethiol molecules.

Boron Compounds↗

Ultrastructural autometallography: a method for silver amplification of catalytic metals.

The autometallographic technique involves application of a silver bromide-containing emulsion on the surface of ultrathin sections placed on grids that are subsequently exposed to a photographic developer. In tissue sections from animals treated intravitally with gold, silver, or mercury compounds, accumulations of the metals are visualized by autometallography and can be used for quantitative studies. After amplification, sections can be stained with lead citrate and uranyl acetate. Using autometallography, particles of colloidal gold dispersed in a film of gelatin showed a time-dependent growth and were gradually amplified up to 3.5-fold after 15 min of development. Hence the method may prove useful tracing colloidal gold particles in sections with low particle density, and be a powerful tool for revealing metals in biological tissues.

Animals↗

Synthesis, structure, and reactions of binuclear gold(I) complexes containing two different bridging ligands.

The binuclear cycloaurated compounds [Au(2)(mu-C(6)H(3)-2-PPh(2)-n-Me)(2)] (n = 5, 1a; n = 6, 1b) react with the digold(I) complexes [Au(2)(mu-S(2)CN(n)()Bu(2))(2)] and [Au(2)(mu-dppm)(2)](PF(6))(2) to give heterobridged dinuclear complexes [Au(2)(mu-C(6)H(3)-2-PPh(2)-n-Me)(mu-S(2)CN(n)Bu(2))] (n = 5, 5a; n = 6, 5b) and [Au(2)(mu-C(6)H(3)-2-PPh(2)-n-Me)(mu-dppm)]PF(6), (n = 5, 9a; n = 6, 9b), respectively. Complex 5a exists in the solid state as an infinite zigzag chain of dimeric units with intramolecular Au-Au separations of 2.8331(3) and 2.8243(3) A for independent molecules and intermolecular Au-Au separations of 3.0653(3) and 3.1304(3) A. Both 5a and 5b undergo oxidative addition with halogens to give the heterovalent, gold(I)-gold(III) compounds [XAu(I)(mu-2-Ph(2)PC(6)H(3)-n-Me)Au(III)X(eta(2)-S(2)CN(n)Bu(2))] [n = 5, X = Cl (6a), I (8a); n = 6, X = Cl (6b), Br (7b), I (8b)]. Compound 8a has been shown by X-ray crystallography to contain a gold(III) atom coordinated in a planar array by bidentate, chelating di-n-butyldithiocarbamate, iodide, and the sigma-aryl carbon atom, together with a gold(I) atom that is linearly coordinated by the phosphorus atom of the arylphosphine and by iodide. The intramolecular gold-gold distance of 3.2201(3) A indicates little or no interaction between the metal atoms. In contrast to the behavior of the homobridged complexes 1a and 1b, the heterobridged dithiocarbamate complexes 5a and 5b give structurally similar products on reaction with halogens, irrespective of the position of the ring methyl substituent. Crystal data for [Au(2)(mu-C(6)H(3)-2-PPh(2)-5-Me)(mu-S(2)CN(n)Bu(2))] (5a): triclinic, space group P1 (No. 2), with a = 11.3398(1), b = 15.9750(2), c = 16.4400(3) A, alpha = 91.0735(9), beta = 109.3130(7), gamma = 90.7666(8) degrees, V = 2809.47(6) A(3), and Z = 4. Crystal data for [IAu(I)(mu-2-Ph(2)PC(6)H(3)-5-Me)Au(III)I(eta(2)- S(2)CN(n)Bu(2))] (8a): triclinic, space group P1 (No. 2), with a = 8.6136(2), b = 9.3273, c = 21.1518(4) A, alpha = 84.008(1), beta = 84.945(1), gamma = 75.181(1) degrees, V = 1630.54(6) A(3), and Z = 2.

Journal Article↗

An approach for fabricating self-assembled monolayer of Ag nanoparticles on gold as the SERS-active substrate.

In this paper, an approach for fabricating an active surface-enhanced Raman scattering (SERS) substrate is adopted. This approach is based on the assembling of silver nanoparticles film on gold substrate. Rhodamine 6G (R6G) and p-aminothiophenol (p-ATP) were used as probe molecules for SERS experiments, showing that this new active substrate has sensitivity to SERS response. Tapping-mode atomic force microscopy (AFM) was also used to investigate the surface morphology following the fabricating process of the active SERS substrate, which showed that large quantities of silver nanoparticles were uniformly coated on the substrate.

Aniline Compounds↗

Contact allergy to gold after systemic administration of gold for rheumatoid arthritis.

A patient with seropositive, nodular rheumatoid arthritis (RA) developed contact allergy to gold jewellery following a severe skin rash which occurred after 13 weeks of treatment with sodium aurothiomalate. Patch testing confirmed that the contact allergy was due to gold. This is the first proved case of contact allergy to gold or any other compound initiated by systemic administration of the allergen.

Arthritis, Rheumatoid↗

Acquired resistance against gold(III)-chloride in cultured human cells.

Acquired resistance against gold(III)-chloride was developed in cultures of human epithelial cells derived from normal skin, by growing them with stepwise increased concentrations of the compound in the medium. Resistance to 350 mumol gold-chloride/l, about twice the commonly tolerated concentration and an otherwise lethal concentration to the cells, was attained after an adaptation period of 2-3 months. These cells had preserved their normal appearance except from small inclusion bodies in the cytoplasm. The effect of 350 mumol gold-chloride/l culture medium on cell growth of the sensitive (HE) and resistant (HEAu350) cell strain, was tested over a period of 9 days. On day 9, 2% of the HE cells and 80% of the HEAu350 cells remained adherent to the flasks compared with their nontreated control cells. The doubling time of the HE cells grown without gold was 24 h, that of the HEAu350 cells grown continuously on 350 mumol/l was 36 h. The HE cells died on prolonged exposure to this concentration. Measurement of the cellular content of Au, Cu and Zn by atomic absorption spectrophotometry revealed that the HEAu350 cells contained 1.8 times as much cellular and cytosolic Au per mg cell protein as the HE cells. Sixty per cent of the cytosolic gold in the HEAu350 cells was bound to high molecular weight proteins; no metallothionein was detected. Both strains contained minor amounts of zinc and copper compared with gold. The HEAu350 cells contained twice as much cellular Cu/mg cell protein as the HE cells, whereas the zinc content remained unchanged. The mechanism of acquired resistance against gold-chloride in these cells remains unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗