ß-Secretase (BACE1) inhibitory and neuroprotective effects of p-terphenyls from Polyozellus multiplex.

Alzheimer's disease (AD), a major neurodegenerative disorder, is associated with the enzymatic reaction of ß-secretase (BACE1) on the amyloid precursor protein (APP) for the generation of neurotoxic amyloid-ß (Aß). Therefore, Aß accumulation and oxidative stress-induced neuronal cell death are the pathogenic hallmarks of AD. In this study, we tried to identify BACE1 inhibitors and neuroprotectants from natural products, in particular, from the Korean mushroom Polyozellus multiplex. Four p-terphenyls were identified from the ethanolic extract of P. multiplex; polyozellin (1), thelephoric acid (2), polyozellic acid (3), and kynapcin-12 (4). Compounds 1-4 effectively inhibited BACE1 activity with a half-maximal inhibitory concentration (IC50) of 3.08, 3.50, 4.78, and 15.79 µM, respectively. Compounds 1-3 reduced the production of neurotoxic Aß1-42 production in APPswe-N2a cells in a concentration-dependent manner. When HT22 cells were stressed with 5 mM glutamate, compounds 2 and 3 significantly recovered cell viability. It was correlated with their inhibitory properties against glutamate-mediated Ca(2+) influx, intracellular reactive oxygen species (ROS) generation, lipid peroxidation, reduction in Bcl-2 and Bid levels, and enhanced phosphorylation of mitogen-activated protein kinase (MAPK). Thus, P. multiplex and the isolated p-terphenyls might be useful in the development of lead compounds for the prevention of neurodegenerative diseases, especially AD.

Tuning preparation conditions towards optimized separation performance of thermally polymerized organo-silica monolithic columns in capillary liquid chromatography.

Tuning of preparation conditions, such as variations in the amount of a porogen, concentration of an aqueous acid catalyst, and adjustment in polymerization temperature and time, towards optimized chromatographic performance of thermally polymerized monolithic capillaries prepared from 3-(methacryloyloxy)propyltrimethoxysilane has been carried out. Performance of capillary columns in reversed-phase liquid chromatography was assessed utilizing various sets of solutes. Results describing hydrophobicity, steric selectivity, and extent of hydrogen bonding enabled comparison of performance of hybrid monolithic columns prepared under thermal (TSG) and photopolymerized (PSG) conditions. Reduced amounts of porogen in the polymerization mixture, and prolonged reaction times were necessary for the preparation of monolithic columns with enhanced retention and column efficiency that reached to 111,000 plates/m for alkylbenzenes with shorter alkyl chains. Both increased concentration of catalyst and higher temperature resulted in faster polymerization but inevitably in insufficient time for pore formation. Thermally polymerized monoliths produced surfaces, which were slightly more hydrophobic (a methylene selectivity of 1.28±0.002 TSG vs 1.20±0.002 PSG), with reduced number of residual silanols (a caffeine/phenol selectivity of 0.13±0.001 TSG vs 0.17±0.003 PSG). However, steric selectivity of 1.70±0.01 was the same for both types of columns. The batch-to-batch repeatability was better using thermal initiation compared to monolithic columns prepared under photopolymerized conditions. RSD for retention factor of benzene was 3.7% for TSG capillaries (n=42) vs. 6.6% for PSG capillaries (n=18). A similar trend was observed for columns prepared within the same batch.

A calculation mode for the correct GC/ECNI-MS-SIM determination of polychlorinated terphenyls in the presence of high excesses of polychlorinated biphenyls.

Polychlorinated terphenyls (PCTs) are a class of persistent organic pollutants difficult to analyze by gas chromatography with mass spectrometry operated in the selected ion monitoring mode (GC/MS-SIM) in environmental samples due to the retention time and mass range overlap with polychlorinated biphenyls (PCBs). To overcome these drawbacks, we developed and evaluated a mathematical calculation algorithm which allows to detail the interference of PCT congeners in GC/electron capture negative ion (ECNI)-MS-SIM chromatograms by PCBs. The calculation takes advantage of the abundance and ratio of two suitable isotope peaks of the molecular ion of PCTs. With the help of this method, we detected at least 63 tetra- to nonachlorinated terphenyls in the blubber of a harbour porpoise (Phocoena phocoena) from the North Sea. The interference of these peaks by PCBs ranged from >100 to 0 %. The novel calculation method used in combination with GC/ECNI-MS-SIM is suitable to analyze PCTs in environmental and food samples. However, it can also be applied to GC/EI-MS measurements.

Functionalizing metal nanostructured film with graphene oxide for ultrasensitive detection of aromatic molecules by surface-enhanced Raman spectroscopy.

Surface-enhanced Raman spectroscopy (SERS) as a powerful analytical tool has gained extensive attention. Despite of many efforts in the design of SERS substrates, it remains a grand challenge for creating a general substrate that can detect diverse target analytes. Herein, we report our attempt to address this issue by constructing a novel metal-graphene oxide nanostructured film as SERS substrate. Taking advantages of the high affinity of graphene oxide (GO) toward aromatic molecules and the SERS property of nanostructured metal, this structure exhibits great potential for diverse aromatic molecules sensing, which is demonstrated by using crystal violet (CV) with positive charge, amaranth with negative charge, and neutral phosphorus triphenyl (PPh(3)) as model molecules.

A novel hybrid mode of sample injection to enhance CZE sensitivity for simultaneous determination of a pyridine-triphenylborane anti-fouling agent and its degradation products.

We developed a novel hybrid sample injection mode (HSIM) that presents the combination of electrokinetic injection and vacuum injection to enhance detection sensitivity in CZE. Samples were introduced using both vacuum and electrokinetic injections simultaneously, with a water plug injected into the capillary prior to sample introduction (i.e. similarly to field-amplified sample injection, FASI). Using a sample mixture containing an anti-fouling agent applied to ship hulls, pyridine-triphenylborane and its degradation products (diphenylborinic acid, phenylboronic acid, and phenol) dissolved in ACN, the length of water plug, time, and voltage for sample introduction were optimized. The signal intensity (peak height) was found to be up to a 30-fold increased using HSIM by applying 4 kV for 4 s at the inlet end of the capillary as the cathode with supplementary vacuum in comparison with only vacuum injection for 4 s. The LODs (at a S/N of 3) for pyridine-triphenylborane, diphenylborinic acid, phenylboronic acid, and phenol were 0.88, 1.0, 21, and 23 µg/L, respectively. At the level of 0.04 mg/L, the RSDs (n=4, intra-day) for the above analytes were in the ranges of 1.9-11, 4.3-9.2, and 0.34-0.66% for peak area, peak height, and migration time, respectively. The HSIM is a simple and promising procedure useful for enhancing the sensitivity for both low-and high-mobility ions in CZE.

Congener specific analysis of polychlorinated terphenyls.

In order to identify and to quantify polychlorinated terphenyls (PCT) in environmental matrices, the chromatographic behavior of coplanar and non-coplanar congeners was evaluated. A mixture of 16 single PCT congeners was used for method development. Four of these compounds were synthesized for the first time by SUZUKI-coupling reaction. These were p-PCT (2,2'',6,6''-tetrachloro-, 2',3,3'',4,4'',5',-hexachloro-, 2',3,3'',5,5',5''-hexachloro-) and m-PCT (2,2'',3,3'',5,5''-hexachloro-). They were characterized by NMR ((1)H,(13)C) spectroscopy. By means of the new column chromatographic clean-up reported here, a good matrix removal and the separation of the coplanar PCT congeners from the non-coplanar ones was obtained. The recovery rates for all congeners were good for the PCT in different test matrices like fat, charcoal, and soil. The quality of the clean-up, the separation and the recovery rates were determined by GC/MS analysis. The method was applied for the first time to a real sample from a fire accident, where different PCT, obviously formed during the combustion process, were found. The conclusion is drawn that this method is suitable for the analysis of PCT in different environmental samples.

[Study of sample collection and analysis methods for the hydrogenated terphenyl in workplace air].

OBJECTIVE: To establish solvent desorption gas chromatographic method for determination of hydrogenated terphenyl in workplace air. METHODS: According to standards of methods for determination of toxic substances in workplace air, hydrogenated terphenyl in the air was first adsorbed by activated carbon, desorbed by carbon disulfide, and determined by gas chromatography, then quality was used with retention time and quantitation was used by the sums of peaks area. RESULTS: The method presented linear relationship within the ranges of 6-60 microg/ml. The relative standard deviations (RSD) were 1.3%-2.0% and the detection limits were 1.2 microg/ml. The desorption efficiencies were 89.3%-95.4%. Sampling efficiencies were 100% and the breakthrough volumes were beyond 6.7 mg in a 100 mg active carbon with glass wool. The samples in active carbon tubes could be stored for 7 days at room temperature and its repetition was good. Other solvents in the air such as coexisting diphenyl, ortho-, meta-, para-terphenyls had no interferences in this method. CONCLUSION: The method could meet with the requirements of Standards of methods for determination of toxic substances in workplace air and be feasible for determination of hydrogenated terphenyl in workplace air.

Contamination of dry foods with trimethyldiphenylmethanes by migration from recycled paper and board packaging.

Contamination of foods with trimethyldiphenylmethanes is reported and the origin is shown to be migration from food packaging materials of which the use of recycled carbonless copy paper was found to be the major source. This chemical is one of the solvents used in the carbonless copy paper and its presence in food and the environment has not been previously identified. In this paper we have pursued previous studies on diisopropylnaphthalenes and hydrogenated terphenyls contamination from packaging and now report the identification of this new food contaminant and present evidence of its source. Solid foods such as egg pasta, barley coffee and rice were analysed by GC/MS and a mean concentration of 18 microg/kg of trimethyldiphenylmethanes was found. Extracts from carbonless copy paper were analysed by proton NMR to characterize the trimethyldiphenylmethanes. Since trimethyldiphenylmethanes are found in solid food together with diisopropylnaphthalenes, and considering their similar chemical character, they may follow the same migration pathway as one another.

Orientational anisotropic studies by field rotation technique: near zero-field pulsed EPR experiments of pentacene doped in p-terphenyl.

We report a new technique to map the orientational anisotropy of paramagnetic systems without physically changing the crystal orientations in near zero-field (NZF) pulsed EPR experiments. By implementing three sets of orthogonal coils around the sample, we are ble to create a magnetic vector up to 2 mT in any three-dimensional orientation in space. In NZF region, the hyperfine tensor elements are comparable to the electronic Zeeman interaction energy, thus very rich spectral patterns can be obtained by "dialing" in a magnetic field vector without moving the sample. The technique further allows us to examine the site symmetry of organic crystals and powdered solids doped with chromophores which can be photo-excited to the triplet state by laser light. The technique is exemplified in the study of pentacene in p-terphenyl crystals.

[Determination of hydrogenated terphenyls by ultraviolet spectrophotometer in the air of work place].

OBJECTIVE: To determine Hydrogenated terphenyls in the air of work place. METHODS: Hydrogenated terphenyls in the air was collected with 40% alcohol solution and determined by ultraviolet spectrophotometer. RESULTS: The detectable limit was 0.87mg/m3. When the concentration of standard solution was 0 - 20mg/L, the relative standard deviation (RSD) was 4.6% - 2.3%. The sampling efficiency was 97.3%. The samples were stable for 7 days. CONCLUSION: It was proved that the method was fast, simple and accurate. It was suitable for the determination of hydrogenated terphenyls in the air of work place.

Triphenylphosphane complex formation with hexyn-1-yl silver.

Hexyn-1-yl silver shows broad signals in 1H, 13C and 109Ag NMR. In the presence of 1 equiv. of triphenylphosphane, the signals are much sharper and at low temperature 109Ag,31P and 107Ag,31P coupling can be observed. On 109Ag decoupling, the 31P spectrum still shows the 107Ag,31P coupling indicating the formation of a coordination complex.

Quantitative analysis of triphenylboron in environmental water samples by liquid chromatography/mass spectrometry.

Liquid chromatography/mass spectrometry (LC/MS) has been applied to the analysis of triphenylboron, which has been produced as a substitute for organotin compounds, in water. Although commercial triphenylboron compounds are produced as pyridinyl complexes, the chemical form in water is supposed to be mainly triphenylboron after liberating pyridine. The triphenylborons were extracted from water with an Empore C18 extraction disk under acidic condition, and the extracts were introduced directly into a liquid chromatograph-mass spectrometer equipped with a negative ion electrospray ionization interface. Identification of the compounds was performed with specific ions produced from the triphenylboron, and a quantitative analysis was carried out using the peak areas. The average recoveries from distilled water, seawater and river water at 0.30 ng/ml were 92.3, 100 and 85.3%, respectively. A detection limit of 0.023 ng/ml for triphenylboron was achieved.

Isolation and characterization of antioxidant compounds from Aspergillus candidus broth filtrate.

The objectives of this study were to isolate the antioxidative components in the broth filtrate of Aspergillus candidus (CCRC 31543), to characterize their antioxidative properties, and to evaluate their safety. Three major compounds were isolated and identified as 3,3' '-dihydroxyterphenyllin, 3-hydroxyterphenyllin, and candidusin B. In the linoleic acid peroxidation system, the inhibition of peroxidation in these three compounds was greater than 95% and was significantly higher than that of alpha-tocopherol but equal to that of BHA at 12.5-200 microg/mL. As measured using the Rancimat method in lard, 3,3' '-di-OH-terphenyllin exhibited a protection factor value of 7.82, which was substantially higher than those of BHA (5.58) and alpha-tocopherol (4.29) at 200 microg/mL. 3,3' '-di-OH-terphenyllin and 3-OH-terphenyllin also exhibited marked scavenging effects on the alpha,alpha-diphenyl-beta-picrylhydrazyl radicals (94.7 and 96.0%, respectively), which were similar to those of BHA and alpha-tocopherol. Safety studies showed that these three compounds were neither cyto- nor geno-toxic toward human intestine 407 (INT 407) cells, nor mutagenic toward Salmonella typhimurium TA98 and TA100.

Terferol, an inhibitor of cyclic adenosine 3',5'-monophosphate phosphodiesterase. II. Structural elucidation.

Streptomyces showdoensis SANK 65080 produced terferol, an inhibitor of cyclic adenosine 3',5'-monophosphate phosphodiesterase (cAMP-PDE). NMR spectrometry and X-ray analysis were used to determine the structure of the compound, a new member of the terphenyl family.

Polychlorinated terphenyls (PCTs) use, levels and biological effects.

Polychlorinated terphenyls (PCTs) have almost identical characteristics to high chlorinated PCBs: extremely stable, bioaccumulable and biomagnification through food webs might take place. PCT is especially used in investment casting waxes and as a substitute for PCB. In spite of the limited use until now, PCT has been detected in a great variety of environmental samples such as soil, water, shellfish, fish, seals, birds and terrestrial animals. Furthermore, it has been found in paper products and foodstuffs. PCT residues in human tissues--blood, liver, fat and milk--have been detected in some countries. Animal experiments have shown that long-term toxic effects of PCT are of most importance. PCT has a marked inductive effect on the microsomal enzymes in the liver in vertebrates and may cause liver-damage--including tumours. Disturbance of the hormonal--and immunological--systems have also been reported. The most important ecological hazard of PCT--as well as PCB--is the possible disturbance of the reproduction system of the organisms. Many countries do not regulate the use of PCT. In some countries the use of PCT is regulated to closed systems, but the expansion of usage is under consideration in the EEC.

An evaluation of chromatographic methods for the analysis of polychlorinated terphenyls in environmental samples.

Gas chromatography (GC) with packed and capillary columns, high-performance liquid chromatography (HPLC) and thin-layer chromatography have been used to characterize various commercially available mixtures of polychlorinated terphenyls (PCTs). Besides, UV absorption and mass spectrometry data have been collected, and the behaviour of PCTs upon perchlorination to the tetradecachloroterphenyls has been studied. Using GC, the PCT content of a number of paper and sewage sludge samples has been determined. The application of perchlorination/GC as method of analysis often yields unreliable, i.e., too high, results compared with the direct GC pattern-comparison method. In the case of paper samples, hydrogenated terphenyls appear to be the principal interfering compounds.

Polychlorinated terphenyls as an environmental pollutant in Japan.

This paper summarizes the results of the studies made by our group and other investigators in Japan on the residue levels of polychlorinated terphenyls (PCTs) in a variety of items in the environment including the human body. In contrast to widespread distribution of PCBs in the environment, PCT residues were seldom found in samples from aquatic environments such as water and sludge and waterfowl and fish, and, if found, the levels of PCTs were so low as to be practically negligible. Similarly, no significant levels of PCTs were detectable in foodstuffs such as edible oils, vegetables, dairy products and meat and in prepared diets. These findings may be explained by the fact that PCTs are much less volatile and soluble than PCBs and the total industrial output of PCTs was as small as 2700 tonnes which is 1/20 of PCBs produced in Japan. However, the levels of PCTs in human fat and blood were shown to be almost equivalent to PCBs, despite a negligible amount of PCTs being found in food. No clear explanation of human contamination by PCTs has been proposed so far.