An improved preparation of [18 F]AV-45 by simplified solid-phase extraction purification.

Amyvid (florbetapir f18, [18 F]AV-45, [18 F]5) was the first FDA-approved positron emission tomography imaging agent targeting ß-amyloid (Aß) plaques for assisting the diagnosis of Alzheimer disease. This work aimed to improve the [18 F]AV-45 ([18 F]5) preparation by using solid-phase extraction (SPE) purification. [18 F]AV-45 ([18 F]5) was synthesized by direct nucleophilic radiofluorination of O-tosylated precursor (1 mg) at 120°C in anhydrous dimethyl sulfoxide (DMSO), followed by acid hydrolysis of the N-Boc protecting group. Purification was accomplished by loading the crude reaction mixture to a cartridge (Oasis HLB 3 cc) and eluting with different combinations of solvents. This method removed the chemical impurity while leaving [18 F]AV-45 ([18 F]5) on the cartridge. The final dose was eluted by ethanol. [18 F]AV-45 ([18 F]5) was produced within 51 minutes (radiochemical yield 42.7 ± 5.9%, decay corrected, n = 3), and the radiochemical purity was greater than 95%. Total chemical impurity per batch (24.1 ± 2.7 µg per batch) was below the limit described in the package insert of Amyvid, florbetapir f18 (chemical mass: less than 50 µg/dose). In summary, [18 F]AV-45 ([18 F]5) was produced efficiently and reproducibly using a cartridge-based SPE purification. This method brings the process closer for routine preparation, similar to the commercially used [18 F]FDG.

E-cigarette liquids: Constancy of content across batches and accuracy of labeling.

AIMS: To assess whether bottles of refill liquids for e-cigarettes were filled true to label, whether their content was constant across two production batches, and whether they contained impurities. METHODS: In 2013, we purchased on the Internet 18 models from 11 brands of e-liquids. We purchased a second sample of the same models 4months later. We analyzed their content in nicotine, anabasine, propylene glycol, glycerol, ethylene glycol and diethylene glycol, and tested their pH. RESULTS: The median difference between the nicotine value on the labels and the nicotine content in the bottles was 0.3mg/mL (range -5.4 to +3.5mg/mL, i.e. -8% to +30%). For 82% of the samples, the actual nicotine content was within 10% of the value on the labels. All models contained glycerol (median 407mg/mL), and all but three models contained propylene glycol (median 650mg/mL). For all samples, levels of anabasine, ethylene glycol and diethylene glycol were below our limits of detection. The pH of all the e-liquids was alkaline (median pH=9.1; range 8.1 to 9.9). The measured content of two batches of the same model varied by a median of 0% across batches for propylene glycol, 1% for glycerol, 0% for pH, and 0.5% for nicotine (range -15% to +21%; 5th and 95th percentiles: -15% and +10%). CONCLUSIONS: The nicotine content of these e-liquids matched the labels on the bottles, and was relatively constant across production batches. The content of propylene glycol and glycerol was also stable across batches, as was the pH.

Halogenated Compounds from Directed Fermentation of Penicillium concentricum, an Endophytic Fungus of the Liverwort Trichocolea tomentella.

One new chlorinated xanthone, 6-chloro-3,8-dihydroxy-1-methylxanthone (1), a new 2-bromo-gentisyl alcohol (2), and a mixture of 6-epimers of 6-dehydroxy-6-bromogabosine C (3a and 3b), together with 19 previously identified compounds, epoxydon (4), norlichexanthone (5), 2-chlorogentisyl alcohol (6), hydroxychlorogentisyl quinone (7), 6-dehydroxy-6α-chlorogabosine C (8a), 6-dehydroxy-6ß-chlorogabosine C (8b), gentisyl alcohol (9), gentisyl quinone (10), (R,S)-1-phenyl-1,2-ethanediol (11), dehydrodechlorogriseofulvin (12), dechlorogriseofulvin (13), dehydrogriseofulvin (14), griseofulvin (15), ethylene glycol benzoate (16), alternariol (17), griseoxanthone C (18), drimiopsin H (19), griseophenone C (20), and griseophenone B (21), were isolated from cultures of Penicillium concentricum, a fungal endophyte of the liverwort Trichocolea tomentella. The structures of the new compounds (1, 2, 3a, and 3b) were elucidated by interpretation of spectroscopic data including one- and two-dimensional NMR techniques. Among these, compounds 2-4 displayed modest cytotoxicity to the MCF-7 hormone-dependent breast cancer cell line with IC50 values of 8.4, 9.7, and 5.7 µM, respectively, whereas compound 9 exhibited selective cytotoxicity against the HT-29 colon cancer cell line with an IC50 value of 6.4 µM. During this study we confirmed that the brominated gentisyl alcohol (2) was formed by chemical conversion of 4 during bromide salt addition to culture media.

Removal of 2-butoxyethanol gaseous emissions by biotrickling filtration packed with polyurethane foam.

The removal of 2-butoxyethanol from gaseous emissions was studied using two biotrickling filters (BTF1 and BTF2) packed with polyurethane foam. Two different inoculum sources were used: a pure culture of Pseudomonas sp. BOE200 (BTF1) and activated sludge from a municipal wastewater treatment plant (BTF2). The bioreactors were operated at inlet loads (ILs) of 130 and 195 g m(-3) hour(-1) and at an empty bed residence time (EBRT) of 12.5s. Under an IL of ∼130 g m(-3) hour(-1), BTF1 presented higher elimination capacities (ECs) than BTF2, with average values of 106±7 and 68±8 g m(-3) hour(-1), respectively. However, differences in ECs between BTFs were decreased by reducing the irrigation intervals from 1 min every 12 min to 1 min every 2 hours in BTF2. Average values of EC were 111±25 and 90±7 g m(-3) hour(-1) for BTF1 and BTF2, respectively, when working at an IL of ∼195 g m(-3) hour(-1). Microbial analysis revealed a significant shift in the microbial community of BTF1 inoculated with Pseudomonas sp. BOE200. At the end of the experiment, the species Microbacterium sp., Chryseobacterium sp., Acinetobacter sp., Pseudomonas sp. and Mycobacterium sp. were detected. In BTF2 inoculated with activated sludge, the denaturing gradient gel electrophoresis (DGGE) technique showed a diverse microbial community including species that was able to use 2-butoxyethanol as its carbon source, such as Pseudomonas aeruginosa and Pseudomonas putida as representative species. Although BTF1 inoculated with Pseudomonas sp. BOE200 and higher gas velocity (probably greater gas/liquid mass transfer rate) showed a slight improvement in performance, the use of activated sludge as inoculum seems to be a more feasible option for the industrial application of this technology.

Chemical Composition and Aroma Evaluation of Essential Oils from Skunk Cabbage (Symplocarpus foetidus).

Two sample preparation methods, namely hydrodistillation (HD) and solvent-assisted flavor evaporation (SAFE), have been used to investigate the essential oils of the aerial parts (leaves and stems) of Symplocarpus foetidus, a plant with a characteristic odor, by gas chromatography mass spectrometry (GC-MS). Characteristic aroma-active compounds in the oils were detected by GC-Olfactometry (GC-O) and aroma extract dilution analysis (AEDA). From the HD method, the main compounds in the oil were found to be p-vinyl-guaiacol (15.5%), 2-pentyl-furan (13.4%), and (Z)-ligustilide (9.5%). From the SAFE method, the main compounds were 2-butoxy-ethanol (49.6%), ethyl-pentanoate (4.5%), and mesitylene (4.0%). In HD oil, the most intense aroma-active compounds were 2-pentyl-furan (flavor dilution factor (FD) = 32, odor activity value (OAV) = 57), p-vinyl-guaiacol (FD = 16, OAV = 41), and dimethyl disulfide (FD = 16, OAV = 41). In SAFE oil, the main aroma-active compounds were 2-butoxy ethanol (FD = 32, OAV = 16), and 2-methoxy thiazole (FD = 32, OAV = 25).

Planar Mn4O cluster homochiral metal-organic framework for HPLC separation of pharmaceutically important (±)-ibuprofen racemate.

A planar tetracoordinated oxygen containing a homochiral metal-organic framework (MOF) has been synthesized and characterized that can be used as a new chiral stationary phase in high-performance liquid chromatography to efficiently separate racemates such as pharmaceutically important (±)-ibuprofen and (±)-1-phenyl-1,2-ethanediol.

Investigation of nonylphenol and nonylphenol ethoxylates in sewage sludge samples from a metropolitan wastewater treatment plant in Turkey.

Nonylphenol ethoxylates (NPEOs) have drawn significant attention within the last decade for both scientific and legislative reasons. In Turkey, the Regulation Regarding the Use of Domestic and Urban Sludges on Land states a limit value for the sum of nonylphenol (NP), nonylphenol monoethoxylate (NP1EO) and nonylphenol diethoxylate (NP2EO) as NPE (NPE=NP+NP1EO+NP2EO). Unfortunately a standard method for the determination of these chemicals has not been yet set by the authorities and no data exists about the concentrations of NP and NPEOs in sewage sludge in Turkey. The aim of this study is to propose simple and easily applicable extraction and measurement techniques for 4-n-nonylphenol (4-n-NP), NP, NP1EO and NP2EO in sewage sludge samples and investigate the year round concentrations in a Metropolitan Wastewater Treatment Plant (WWTP) in Turkey. Different extraction techniques and GC/MS methods for sewage sludge were tested. The best extraction method for these compounds was found to be ultrasonication (5 min) using acetone as the solvent with acceptable recovery of analytes suggested by USEPA and other studies. The optimized extraction method showed good repeatability with relative standard deviations (RSDs) less than 6%. The recovery of analytes were within acceptable limits suggested by USEPA and other studies. The limits of detection (LODs) were 6 µg kg(-1) for NP and NP1EO, 12 µg kg(-1) for NP2EO and 0.03 µg kg(-1) for 4-n-NP. The developed method was applied to sewage sludge samples obtained from the Central WWTP in Ankara, Turkey. The sum NPE (NP+NP1EO+NP2EO) was found to be in between 5.5 µg kg(-1) and 19.5 µg kg(-1), values which are in compliance with Turkish and European regulations.

Escherichia coli ß-galactosidase-catalyzed synthesis of 2-phenoxyethanol galactoside and its characterization.

We synthesized 2-phenoxyethanol galactoside (PE-Gal) from 2-phenoxyethanol (PE), in which Escherichia coli ß-gal (as E. coli cells) and lactose were added in the reaction mixture for galactosylation. About 40 mM PE-Gal was maximally synthesized from about 80 mM PE at 24 h as about 50% conversion yield. After purifying PE-Gal, the structure of PE-Gal was identified using LC-MS, (1)H NMR, and (13)C NMR analyses. In addition, it was observed that the water solubility of PE-Gal was increased by galactosylation of PE. The MICs of PE and PE-Gal against Gram-negative and Gram-positive bacteria were fairly similar with each other (23.3-61.3 mM as the average value). PE-Gal was noticeably less cytotoxic against HACAT cells, in particular a remarkable difference in cell viability was observed at concentrations of 20-60 mM PE or PE-Gal. Finally, we accomplished the synthesis of less toxic PE-Gal, compared with PE, using ß-gal-containing E. coli cells without changing in the MICs against microorganisms. In the future, PE-Gal will be applicable as a substitute for PE as a less toxic preservative for the cosmetic, pharmaceutical, and food industries.

Direct analysis in real time-mass spectrometry (DART-MS) for rapid qualitative screening of toxic glycols in glycerin-containing products.

In 2007, the United States Food and Drug Administration released guidance recommending testing of glycerin used in regulated consumer products, such as cough syrup preparations, toothpaste, and other pharmaceutical and food products, for the toxic compounds ethylene glycol and diethylene glycol. Regulatory laboratories routinely test glycerin, and products containing glycerin or related compounds for these toxic glycols, using an official gas chromatographic method, to ensure the safety of these products. The current work describes a companion technique to compliment this GC-FID method utilizing Orbitrap mass spectrometry with direct analysis in real time ionization to rapidly screen these samples qualitatively, with results in as little as five seconds, with no sample preparation required. This allows the more time and resource intensive method to be reserved for those rare cases when these compounds are detected, potentially greatly improving laboratory efficiency. The technique was evaluated for qualitative sensitivity and repeatability, and compared against the GC-FID method. The method appears to perform well against these metrics.

Three new phenyl-ethanediols from the fruiting bodies of the mushroom Fomes fomentarius.

Three new phenyl-ethanediols, (1R)-(3-ethenylphenyl)-1,2-ethanediol (1), (1R)-(3-formylphenyl)-1,2-ethanediol (2), and (1R)-(3-acetophenyl)-1,2-ethanediol (3), were isolated from the fruiting bodies of the mushroom Fomes fomentarius, together with two related known compounds, (3-ethylphenyl)-1,2-ethanediol (4) and (4-acetophenyl)-1,2-ethanediol (5). Their structures were elucidated by spectroscopic methods including extensive 2D NMR techniques. Compounds 1-3 showed weak antimicrobial activity.

Two new compounds from the roots of Rhodiola crenulata.

Two new compounds, named (3R,5R,8R)-3-O-[α-l-arabinopyranosyl (1 â†’ 6)-ß-d-glucopyranosyl]-5-hydroxymegastigma-6,7-dien-9-one (1) and (1R)-1-O-(ß-d-glucopyranosyl)-phenylethylene glycol (2), were isolated from the extract of Rhodiola crenulata. Their structures were determined on the basis of various spectroscopic methods, including IR, HR-ESI-MS, 1D and 2D NMR, and chemical evidences. The cytotoxicity of these two compounds was evaluated by using MTT method.

The hydroxyl radical scavenging effect of textile preparation auxiliaries on the photochemical treatment of nonylphenol ethoxylate.

The present paper deals with the effects of frequently used textile preparation chemicals and common ions on the H2O2/UV-C treatment of a commercially important and slowly biodegradable nonionic surfactant, namely a nonylphenol bearing 10 ethoxylated chains. For this purpose, the effect of soda ash carbonate (0-5.0 g L(-1)), two phosphonic acid-based organic sequestering agents (0-2.5 g L(-1)) and chloride (0-3.0 g L(-1)) at two different pH values (3.5 and 10.5) as hydroxyl radical scavengers was experimentally investigated. Among the studied textile preparation chemicals and hydroxyl radical scavengers, the decreasing order of hydroxyl radical scavenging capacity was established as diethylene triamine pentamethylene phosphonic acid > 1-hydroxy ethylidene-1,1-diphosphonic acid > soda ash carbonate at pH 10.5 > chloride at pH 3.5 > chloride at pH 10.5.

The effectiveness of anaerobic digestion in removing estrogens and nonylphenol ethoxylates.

The fate and behaviour of two groups of endocrine disrupting chemicals, steroid estrogens and nonylphenol ethoxylates, have been evaluated during the anaerobic digestion of primary and mixed sewage sludge under mesophilic and thermophilic conditions. Digestion occurred over six retention times, in laboratory scale reactors, treating sludges collected from a sewage treatment works in the United Kingdom. It has been established that sludge concentrations of both groups of compounds demonstrated temporal variations and that concentrations in mixed sludge were influenced by the presence of waste activated sludge as a result of transformations during aerobic treatment. The biodegradation of total steroid estrogens was >50% during primary sludge digestion with lower removals observed for mixed sludge, which reflected bulk organic solids removal efficiencies. The removal of nonylphenol ethoxylates was greater in mixed sludge digestion (>58%) compared with primary sludge digestion and did not reflect bulk organic removal efficiencies. It is apparent that anaerobic digestion reduces the concentrations of these compounds, and would therefore be expected to confer a degree of protection against exposure and transfer of both groups of compounds to the receiving/re-use environment.

Diethylene glycol removal by Echinodorus cordifolius (L.): the role of plant-microbe interactions.

This work presents the use of the plant Echinodorus cordifolius for remediating diethylene glycol (DEG) contaminated waters. The potential of this plant for treating DEG wastewater in a remediation system was observed. We found that E. cordifolius was able to remove DEG from wastewater, decrease the pH to neutral and remove approximately 95% of the chemical oxygen demand within 12 days. The plants can grow well in DEG wastewater, as indicated by their root and leaf biomass, which was found to be statistically similar to control. Wilting, chlorosis and necrosis were observed in DEG-treated plants, but the relative water content was not significantly different between control and treated plants, suggesting that the plants were able to take up and tolerate DEG present in the wastewater. Plant roots changed to black colour during experimental period. The fluorescence in situ hybridisation and bacterial enrichment confirmed that 4.30 × 10(5) cells/g of sulphate reducing bacteria and 9.30 × 10(8) cells/g of acid-producing bacteria were found associated with the plant roots. Furthermore, volatile fatty acids were found in non-sterile soil treatments, indicating that soil microorganisms are associated with DEG remediation. These results demonstrated that plants and bacteria have the ability to form a relationship to remove the organic contaminant DEG.

Highly enantioselective reduction of 2-hydroxy-1-phenylethanone to enantiopure (R)-phenyl-1,2-ethanediol using Saccharomyces cerevisiae of remarkable reaction stability.

Saccharomyces cerevisiae JUC15 was successfully obtained by target reaction-oriented screening, which reduced 2-hydroxy-1-phenylethanone (HPE) to (R)-phenyl-1,2-ethanediol ((R)-PED) of excellent enantiomeric excess (e.e. >99.9%). There was no significant decrease in the yield and optical purity of (R)-PED when the free cells were reused for 40 repeated cycles at 2gL(-1) substrate concentration. The strain used cheap sucrose for cofactor regeneration and worked over a considerably wider range of pH (4-9). The optimum substrate concentration was 8gL(-1), which was higher than any other biocatalysts reported so far. Interesting, when HPE concentration reached 20gL(-1) in reaction system, where 43.2% of the substrate was present in suspended solid form, the reaction still gave enantiopure (R)-PED in 71% yield. Last but not least, the product e.e. kept above 99.9% in all examined conditions. These results suggest the potential of this strain for the industrial production of optically active (R)-PED.

Extraction of nonylphenol and nonylphenol ethoxylates from sewage sludge using the pressurized fluid extraction method and the supercritical fluid extraction method.

To establish endocrine disruptor (ED) monitoring and control methods for wastewater treatment plants, it is necessary to clarify the fate of EDs in each process of a sludge treatment system. However, the ED analysis method for sewage sludge containing large quantities of organic matters has not been established. So, a highly reliable analytical method that accurately measures EDs in sewage sludge must be developed. This paper reports on the results of applying the Pressurized Fluid Extraction (PFE) method and the Supercritical Fluid Extraction (SFE) method to the extraction of nonylphenol (NP) and nonylphenol ethoxylate (NPnEO) existence of which has often been confirmed in past surveys. To clarify the quantity of EDs in sludge specimens and the fate of EDs in the sludge treatment process, appropriate analytical methods should be developed. In this study, the PFE method and the SFE method were tested to extract NP and NPnEO from sewage sludge specimens. The findings indicate that the extraction from dried sludge by the PFE method can extract a larger quantity of NP and NPnEO in a shorter time than the widely used heating reflux method. Regarding the extraction by the SFE method, conditions for extraction of NP and NPnEO at a higher rate than the heating reflux method were not found.

Molecularly imprinted polymer for selective extraction of endocrine disrupters nonylphenol and its ethoxylated derivates from environmental solids.

Nonylphenol isomers (NP), linear nonylphenol (4-n-NP) and NP short chain ethoxylated derivates (NPEO1 and NPEO2) are degradation products of nonylphenol polyethoxylates, a worldwide used group of surfactants. All of them are considered endocrine disrupters due to their ability to mimic natural estrogens. In this paper, the preparation and evaluation of several 4-n-NP molecularly imprinted polymers (MIPs) for the selective extraction and clean-up of 4-n-NP, NP, NPEO1 and NPEO2 from complex environmental solid samples is described. Among the different combinations tested, a methacrylic acid-based imprinted polymer prepared in toluene provided the better performance for molecularly imprinted SPE (MISPE). Under optimum MISPE conditions, the polymer was able to selectively retain not only linear NP but also the endocrine disruptors NPEO1, NPEO2 and NP with recoveries ranging from 60 to 100%, depending upon the analyte. The developed MISPE procedure was successfully used for the determination of 4-n-NP, NP, NPEO1 and NPEO2 in sediments and sludge samples at concentration levels according to data reported in the literature for incurred samples. Finally, various sludge samples collected at five different sewage treatment plants from Madrid and commercial sludge for agriculture purposes were analysed. The measured concentrations of the different compounds varied from 3.7 to 107.5 mg/kg depending upon the analyte and the sample.

Impact of sewage sludge treatment processes on the removal of the endocrine disrupters nonylphenol ethoxylates.

Several treatment processes of mixed sludge naturally contaminated with nonylphenol ethoxylates (NPE) were compared in order to evaluate their efficiency for the removal of these endocrine disrupters. Anaerobic and aerobic treatments were carried out in continuous stirred tank reactors, operated separately or combined together, at mesophilic and thermophilic temperatures and with or without ozone post-treatment. Anaerobic mesophilic removal of NPE consisted of complete removal of nonylphenol diethoxylate, incomplete removal of nonylphenol monoethoxylate and non stoechiometric production of nonylphenol, with consequently a NPE removal of 25%. At thermophilic temperature, anaerobic digestion led to an increase of the total solids removal efficiency, while improving NPE degradation (30%). Under thermophilic aerobic condition, the three compounds were removed simultaneously with a NPE removal efficiency higher than under anaerobic condition (39%). This removal is always well correlated to the total solids removal meaning that bioavailability remains the main limiting factor. Combination of either thermophilic aerobic-mesophilic anaerobic or mesophilic anaerobic-ozonation treatments enhanced the NPE removal by comparison to single systems (45% and 48%, respectively). These results confirm the high potential of existing and up-grading sewage sludge treatments to degrade such refractory and aged compounds.

A new ethylene glycol triterpenoid from the leaves of Psidium guajava.

One new pentacyclic triterpenoid psidiumoic acid (5) along with four known compounds beta-sitosterol (1), obtusol (2), oleanolic acid (3), and ursolic acid (4) have been isolated from the leaves of Psidium guajava. The new constituent 5 has been characterized as 2 alpha-glycolyl-3beta-hydroxyolean-12-en-28-oic acid through 2D NMR techniques. This is the first report of isolation of compound 2 from the genus Psidium.

Column temperature as an active variable in the isocratic, normal-phase high-performance liquid chromatography separation of lipophilic metabolites of nonylphenol ethoxylates.

Normal-phase separation of technical grade nonylphenol (t-NP, about 90% 4-nonylphenol), 4-nonylphenol mono-ethoxylate (4-NP1EO) and 4-nonylphenol di-ethoxylate (4-NP2EO) was assessed, with the inclusion of column temperature as an active variable. The compound 2,4,6-trimethylphenol was evaluated for use as internal standard. Isocratic elution with 2-propanol/hexanes mixtures from an amino-silica column and spectrometric UV detection at 277 nm were employed. Technical nonylphenol presented a significant contribution from unknown substances that eluted with retention times similar to that of 4-NP1EO. GC-MS analysis of the unknowns allowed to identify them as isomers of 2-NP. The response of the system to joint variations in flow rate, eluent composition and column temperature was investigated by means of Doehlert statistical experimental design. A model for retention of the analytes as a function of the experimental variables was proposed, and separation selectivity was studied. Selection of the optimal working zone was made through desirability function (D) calculations. Potential co-elution of 2-NP isomers with 4-NP1EO was considered when optimizing the separation. The occurrence of a restricted region of the experimental space where baseline resolution of analytes, associated impurities and internal standard results feasible (D not equal to 0) is apparent.