Batch Versus Flow Lithiation-Substitution of 1,3,4-Oxadiazoles: Exploitation of Unstable Intermediates Using Flow Chemistry.

1,3,4-Oxadiazoles are a common motif in pharmaceutical chemistry, but few convenient methods for their modification exist. A fast, convenient, high yielding and general α-substitution of 1,3,4-oxadiazoles has been developed using a metalation-electrophilic trapping protocol both in batch and under continuous flow conditions in contradiction to previous reports which suggest that α-metalation of this ring system results in ring fragmentation. In batch, lithiation is accomplished at an industrially convenient temperature, -30 °C, with subsequent trapping giving isolated yields of up to 91 %. Under continuous flow conditions, metalation is carried out at room temperature, and subsequent in flow electrophilic trapping gave up to quantitative isolated yields. Notably, lithiation in batch at room temperature results only in ring fragmentation and we propose that the superior mixing in flow allows interception and exploitation of an unstable intermediate before decomposition can occur.

Auto-Tandem Catalysis: PdII -Catalysed Dehydrogenation/Oxidative Heck Reaction of Cyclopentane-1,3-diones.

A PdII catalyst system has been used to successfully catalyse two mechanistically distinct reactions in a one-pot procedure: dehydrogenation of 2,2-disubstituted cyclopentane-1,3-diones and the subsequent oxidative Heck coupling. This auto-tandem catalytic reaction is applicable to both batch and continuous flow processes, with the latter being the first example of a tandem aerobic dehydrogenation/oxidative Heck in flow. In addition, a telescoped reaction involving enantioselective desymmetrisation of the all-C quaternary centre was successfully achieved.

The influence of scenario-based training and real-time audiovisual feedback on out-of-hospital cardiopulmonary resuscitation quality and survival from out-of-hospital cardiac arrest.

STUDY OBJECTIVE: We assess whether an initiative to optimize out-of-hospital provider cardiopulmonary resuscitation (CPR) quality is associated with improved CPR quality and increased survival from out-of-hospital cardiac arrest. METHODS: This was a before-after study of consecutive adult out-of-hospital cardiac arrest. Data were obtained from out-of-hospital forms and defibrillators. Phase 1 included 18 months with real-time audiovisual feedback disabled (October 2008 to March 2010). Phase 2 included 16 months (May 2010 to September 2011) after scenario-based training of 373 professional rescuers and real-time audiovisual feedback enabled. The effect of interventions on survival to hospital discharge was assessed with multivariable logistic regression. Multiple imputation of missing data was used to analyze the effect of interventions on CPR quality. RESULTS: Analysis included 484 out-of-hospital cardiac arrest patients (phase 1 232; phase 2 252). Median age was 68 years (interquartile range 56-79); 66.5% were men. CPR quality measures improved significantly from phase 1 to phase 2: Mean chest compression rate decreased from 128 to 106 chest compressions per minute (difference -23 chest compressions; 95% confidence interval [CI] -26 to -19 chest compressions); mean chest compression depth increased from 1.78 to 2.15 inches (difference 0.38 inches; 95% CI 0.28 to 0.47 inches); median chest compression fraction increased from 66.2% to 83.7% (difference 17.6%; 95% CI 15.0% to 20.1%); median preshock pause decreased from 26.9 to 15.5 seconds (difference -11.4 seconds; 95% CI -15.7 to -7.2 seconds), and mean ventilation rate decreased from 11.7 to 9.5/minute (difference -2.2/minute; 95% CI -3.9 to -0.5/minute). All-rhythms survival increased from phase 1 to phase 2 (20/231, 8.7% versus 35/252, 13.9%; difference 5.2%; 95% CI -0.4% to 10.8%), with an adjusted odds ratio of 2.72 (95% CI 1.15 to 6.41), controlling for initial rhythm, witnessed arrest, age, minimally interrupted cardiac resuscitation protocol compliance, and provision of therapeutic hypothermia. Witnessed arrests/shockable rhythms survival was 26.3% (15/57) for phase 1 and 55.6% (20/36) for phase 2 (difference 29.2%; 95% CI 9.4% to 49.1%). CONCLUSION: Implementation of resuscitation training combined with real-time audiovisual feedback was independently associated with improved CPR quality, an increase in survival, and favorable functional outcomes after out-of-hospital cardiac arrest.

Occurrence of pharmaceutical compounds in wastewater process streams in Dublin, Ireland.

The aim of this work is to establish baseline levels of pharmaceuticals in three wastewater treatment plant (WWTP) streams in the greater Dublin region to assess the removal efficiency of the selected WWTPs and to investigate the existence of any seasonal variability. Twenty compounds including several classes of antibiotics, acidic and basic pharmaceuticals, and prescribed medications were selected for investigation using a combination of membrane filtration, solid phase extraction (SPE) cleanup, and liquid chromatography-electrospray ionization tandem mass spectrometry. Fourteen of the selected compounds were found in the samples. Increased effluent concentrations, compared to influent concentrations, for a number of compounds (carbamazepine, clotrimazole, propranolol, nimesulide, furosemide, mefenamic acid, diclofenac, metoprolol, and gemfibrozil) were observed. The detected concentrations were generally below toxicity levels and based on current knowledge are unlikely to pose any threat to aquatic species. Mefenamic acid concentrations detected in both Leixlip and Swords effluents may potentially exert ecotoxicological effects with maximum risk quotients (i.e., ratio of predicted exposure concentration to predicted no effect concentration) of 4.04 and 1.33, respectively.

Superprotonic conduction of intrinsically zwitterionic microporous polymers based on easy-to-make squaraine, croconaine and rhodizaine dyes.

Porous organic polymers (POPs) have been prepared via a novel metal free polycondensation between a tritopic indole-based monomer and squaric, croconic and rhodizonic acids. Each of the three POPs exhibited high BET surface areas (331-667 m2 g-1) and zwitterionic structures. Impedance measurements revealed that the intrinsic POPs were relatively weak proton conductors, with a positive correlation between the density of oxo-groups and the proton conduction. Doping the materials with LiCl vastly improved the proton conductivity up to a value of 0.54 S cm-1 at 90 °C and 90% relative humidity.

On the adsorption/photodegradation of amoxicillin in aqueous solutions by an integrated photocatalytic adsorbent (IPCA): experimental studies and kinetics analysis.

Activated carbon-supported TiO(2) nanoparticles, termed integrated photocatalytic adsorbents (IPCAs), were prepared using an ultrasonic impregnation technique and investigated for the photocatalytic degradation of amoxicillin (AMO), a ß-lactam antibiotic. The IPCAs had high adsorption affinity for AMO with the amount adsorbed proportional to the TiO(2) loading and the highest adsorption was at 10 wt% TiO(2) loading. A pseudo-second-order model was found to fit the experimental data and consistently predicted the amount of AMO adsorbed over the adsorption period. Equilibrium isotherm studies showed that the adsorption followed the Redlich-Peterson model with maximum adsorption capacity of 441.3 mg g(-1) for 10% IPCA, 23% higher than the pure activated carbon (AC). Kinetic studies on the photocatalytic degradation of AMO using non-linear regression analysis suggest that the degradation followed Langmuir-Hinshelwood (L-H) kinetics. The adsorption rate constant (K(ad)) was considerably higher than the photocatalytic rate constant (k(L-H)), indicating that the photocatalysis of AMO is the rate-determining step during the adsorption/photocatalysis process. The 10% IPCA exhibited excellent stability and reusability over four photodegradation cycles.

Control Over the Morphology of Electrospun Microfibrous Mats of a Polymer of Intrinsic Microporosity.

This study reports for the first time the preparation of an electrospun microfibrous mat of PIM-EA-TB. The electrospinning was carried out using a chloroform/n-Propyl-lactate (n-PL) binary solvent system with different chloroform/nPL ratios, in order to control the morphology of the microfibres. With pure chloroform, porous and dumbbell shape fibres were obtained whereas, with the addition on n-PL, circular and thinner fibres have been produced due to the higher boiling point and the higher conductivity of n-PL. The electrospinning process conditions were investigated to evaluate their impact on the fibres' morphology. These microfibrous mats presented potential to be used as breathable/waterproof materials, with a pore diameter of 11 µm, an air resistance of 25.10-7 m-1 and water breakthrough pressure of 50 mBar.

2,6-Bis(trifluoro-meth-yl)benzoic acid.

The title compound, C(9)H(4)F(6)O(2), contains two mol-ecules in the asymmetric unit, one of which exhibits disorder in both of its trifluoro-methyl groups. The dihedral angles between the benzene ring and the carboxyl group are 71.5 (2) and 99.3 (2)° in the two independent mol-ecules. The compound exhibits a catemeric structure resulting from inter-molecular O-H⋯O hydrogen bonding between the carboxyl groups.

A flow platform for degradation-free CuAAC bioconjugation.

The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a cornerstone method for the ligation of biomolecules. However, undesired Cu-mediated oxidation and Cu-contamination in bioconjugates limits biomedical utility. Here, we report a generic CuAAC flow platform for the rapid, robust, and broad-spectrum formation of discrete triazole bioconjugates. This process leverages an engineering problem to chemical advantage: solvent-mediated Cu pipe erosion generates ppm levels of Cu in situ under laminar flow conditions. This is sufficient to catalyze the CuAAC reaction of small molecule alkynes and azides, fluorophores, marketed drug molecules, peptides, DNA, and therapeutic oligonucleotides. This flow approach, not replicated in batch, operates at ambient temperature and pressure, requires short residence times, avoids oxidation of sensitive functional groups, and produces products with very low ppm Cu contamination.

Seasonal and spatial distributions of tributyltin in surface sediment of the Tolka Estuary, Dublin, Ireland.

Aquatic pollution by tributyltin (TBT) is of concern because of its high toxicity to marine life. TBT loadings of estuarine sediments may remain elevated because of long flushing times in estuaries due to their enclosed physicality. The Tolka Estuary, Co. Dublin, Ireland, is a typical Irish urban estuary. It has a significant pollution loading. The results of 12 months' analysis of TBT spatial and temporal distributions in this estuary are presented in this paper. Data from a total of 10 sample points are presented. The concentrations of TBT in the sediment were analysed using differential pulse polarography. Significant seasonal and spatial trends in TBT distribution were observed over the 12-month period. TBT concentrations ranged from 0.1 ppb in winter to 8.6 ppb in summer with a 1.5 ppb average. Organic matter (OM) concentrations of sediment exhibited similar seasonal trends and a positive correlation between OM and TBT distributions was observed.

UV-induced photocatalytic degradation of aqueous acetaminophen: the role of adsorption and reaction kinetics.

Nanostructured titania supported on activated carbon (AC), termed as integrated photocatalytic adsorbents (IPCAs), were prepared by ultrasonication and investigated for the photocatalytic degradation of acetaminophen (AMP), a common analgesic and antipyretic drug. The IPCAs showed high affinity towards AMP (in dark adsorption studies), with the amount adsorbed proportional to the TiO2 content; the highest adsorption was at 10 wt% TiO2. Equilibrium isotherm studies showed that the adsorption followed the Langmuir model, indicating the dependence of the reaction on an initial adsorption step, with maximum adsorption capacity of 28.4 mg/g for 10 % TiO2 IPCA. The effects of initial pH, catalyst amount and initial AMP concentration on the photocatalytic degradation rates were studied. Generally, the AMP photodegradation activity of the IPCAs was better than that of bare TiO2. Kinetic studies on the photocatalytic degradation of AMP under UV suggest that the degradation followed Langmuir-Hinshelwood (L-H) kinetics, with an adsorption rate constant (K) that was considerably higher than the photocatalytic rate constant (k r), indicating that the photocatalysis of AMP is the rate-determining step during the adsorption/photocatalysis process.

Seasonal and spatial distribution of metals in surface sediment of an urban estuary.

Aquatic pollution by metals is of concern because of various toxic effects to marine life. The Tolka Estuary, Co. Dublin, Ireland, is a typical Irish urban estuary. It has a significant metal loading originating from the urban environment. Results of a 25 month analysis of cadmium, copper, lead and zinc spatial and temporal distribution over 10 sample locations in this estuary are presented in this paper. Metal concentrations were analysed using differential pulse polarography. Significant seasonal and spatial trends in metal distribution were observed over the 25 months. Sediment metal concentrations gradually increased (30-120%) in spring to a maximum at the end of summer which was followed by a decrease in winter months (30-60%). Sediment organic matter (OM) concentrations exhibited similar seasonal trends and a positive correlation between OM and metal distributions was observed, implying OM had an influence on metal distributions over time.

Role of speciation in organotin toxicity to the yeast Candida maltosa.

Assessment of organometal pollution requires an understanding of the various processes that influence the bioavailability and toxicity of the contaminant. Organotins may exist as both cationic species and neutral hydroxides in aqueous solution, with the formation of chloride species in the presence of Cl-. Although these species have different chemical properties, there is very little information on the influence of speciation on organotin and microbial cell interactions. Tributyltin (TBT) and triphenyltin (TPT) interactions with the yeast Candida maltosa were investigated between pH 3.5 and 7.5 and in up to 0.5 M NaCl at pH 5.5. Toxicity increased with both pH and NaCl concentration and the mechanisms of interaction depended on the species present in solution. TBT and TPT interacted by different mechanisms, as evidenced by action on membrane fluidity. Furthermore, there was a strong correlation between toxicity and overall octanol-water distribution ratio (D(OW)) of organotin compounds. Triorganotin cations are less toxic than triorganotin hydroxides, which are in turn less toxic than triorganotin chlorides. These findings underline the importance of speciation effects on organotin interactions in the environment.