Observational constraints on multimessenger sources of gravitational waves and high-energy neutrinos

Many astronomical sources of intense bursts of photons are also predicted to be strong emitters of gravitational waves (GWs) and high-energy neutrinos (HENs). Moreover some suspected classes, e.g., choked gamma-ray bursts, may only be identifiable via nonphoton messengers. Here we explore the reach of current and planned experiments to address this question. We derive constraints on the rate of GW and HEN bursts based on independent observations by the initial LIGO and Virgo GW detectors and the partially completed IceCube (40-string) HEN detector. We then estimate the reach of joint GW+HEN searches using advanced GW detectors and the completed km(3) IceCube detector to probe the joint parameter space. We show that searches undertaken by advanced detectors will be capable of detecting, constraining, or excluding, several existing models with 1 yr of observation.     

Resolution of carboxylate protonation microequilibria of NTA, EDTA and related complexones

Potentiometric and NMR-pH titrations were carried out on four classical complexones to elucidate their overall and site-specific basicities. NMR-pH profiles and Bjerrum's functions were adjusted to compound-specific symmetries and appropriate evaluation methods were developed. Symmetry-modulated relationships between the macro- and microconstants were deduced and self-consistent sets of microconstants were determined. The inherent basicity of carboxylates surrounded by adjacent, intramolecular ammonium and carboxylate sites have been found to be in the range of 1.83-2.02logk units, which are reduced by 0.05-0.12logk units upon a nearby carboxylate protonation.     

Investigation of Euphrasia rostkoviana Hayne Using GC–MS and LC–MS

Gas and liquid chromatography coupled with mass spectrometry was applied to solve difficulties and reinvestigate the serious matrix problems affecting analysis of the active compounds in Euphrasia rostkoviana Hayne. The main groups of compounds were obtained by extracting the herb stepwise with n-hexane, chloroform, ethyl acetate and methanol. Polyamide column chromatography facilitated further separation. Phenolic/flavonoid- and terpenoid-type molecules were studied by GC–MS, HPLC and LC–MS–MS. The β-sitosterol content of the herb was determined by gas chromatography with flame ionisation detection (GC-FID). Caffeic acid, chlorogenic acid, coumaric acid and flavonoid glycosides of apigenin, luteolin, rhamnetine (hexoside), kaempferol (both hexoside and rutinoside) and quercetin (rutinoside) were identified in the fractions of the methanolic extract.     

Development and validation of a cyclodextrin‐modified capillary electrophoresis method for the enantiomeric separation of vildagliptin enantiomers

The enantiomers of vildagliptin, an orally available and selective dipeptidyl‐peptidase‐4 inhibitor used for the treatment of type II diabetes, have been separated by CD‐modified CZE, using uncoated fused‐silica capillary. After screening 13 negatively charged CD derivatives as potential chiral selectors, sulfobutyl‐ether‐α‐CD (SBE‐α‐CD) was selected for the enantioseparation. For the optimization, a factorial analysis study was performed by orthogonal experimental design. Six experimental factors were chosen as variable parameters: temperature, applied voltage, chiral selector and BGE concentrations, pH, and the parameters of the hydrodynamic injection. The optimized system still was not considered final as the second peak (S‐enantiomer) migrated too close to the EOF, resulting in a potential inaccuracy during the determination of the chiral impurity. To fine‐tune the method “one factor at a time” variation approach was applied. The final method (applying 15°C capillary temperature, 40 mbar × 4 s hydrodynamic injection, 25 kV voltage in 75 mM acetate‐Tris buffer [pH 4.75] containing 20 mM SBE‐α‐CD as chiral selector) was validated according to the ICH guideline. RSD percentage of the resolution value, migration times, and corrected peak areas were below 5% during testing repeatability and intermediate precision. LOD and LOQ values were found to be 2.5 and 7.5 μg/mL, respectively. The method is considered linear in the 7.5–180 μg/mL range for the R‐enantiomer. The robustness of the method was justified using Plackett–Burmann statistical experimental design.     

Enantioseparation of solriamfetol and its major impurity phenylalaninol by capillary electrophoresis using sulfated gamma cyclodextrin

R-solriamfetol is a recently approved drug used for the treatment of excessive sleepiness associated with narcolepsy and sleep apnea. Herein, a capillary electrophoretic method was developed, enabling the simultaneous analysis of the API and its S-enantiomer in addition to the enantiomers of its major impurity phenylalaninol. Twenty-nine different cyclodextrins (CDs), including native, neutral, and charged ones were screened as potential chiral selectors, and the best results were obtained with sulfated CDs. Randomly sulfated-β-CD exhibited outstanding enantioresolution, the peaks of phenylalaninol enantiomers inserted between the two peaks of solriamfetol enantiomers, while sulfated-γ-CD (S-γ-CD) showed remarkable resolution values in a much shorter analysis time with the optimal enantiomer migration order. Among the single isomer sulfated CD derivatives, substituent dependent enantiomer migration order reversal could also be observed in the case of heptakis(6-O-sulfo)-β-CD (HS-β-CD) or heptakis(2,3-O-dimethyl-6-O-sulfo)-β-CD (HDMS-β-CD) with R-,S-solriamfetol, and heptakis(2,3-O-diacetyl-6-O-sulfo)-β-CD (HDAS-β-CD) resulting S-,R-solriamfetol migration order. The sulfated-γ-CD system was chosen for method optimization applying orthogonal experimental design. The optimized method (45 mM Tris-acetate buffer, pH 4.5, 4 mM S-γ-CD, 21°C, +19.5 kV) was capable for the baseline separation of solriamfetol and phenylalaninol enantiomers within 7 min. The optimized method was validated according to the ICH guidelines and successfully applied for the analysis of pharmaceutical preparation (Sunosi^® 75 mg tablet), thus it may serve as a routine procedure for the laboratories of regulatory authorities as well as in Pharmacopoeias.     

Chip‐based nanoelectrospray ionization with Fourier transform mass spectrometric detection to screen for local anesthetics intended to mask limb sore in walking horses

We report a high‐throughput chip‐based nanoelectrospray ionization method coupled with Fourier transform mass spectrometry to screen for local anesthetics in samples collected by swabbing. These drugs have been used to mask pain on the limbs of walking horses after forbidden practices of soring or physical abuse. Optimized for lidocaine, the method afforded sub‐ppm mass accuracy for nine local anesthetics included in the study. From doped cotton swabs, two third and all of the analytes were detected after adding 10 ng and 100 ng of each drug, respectively. Benzocaine and/or lidocaine were found on positive swab samples collected during walking horse competitions. Copyright © 2015 John Wiley & Sons, Ltd.     

Evaluation of the interaction between sitagliptin and cyclodextrin derivatives by capillary electrophoresis and nuclear magnetic resonance spectroscopy

An aqueous capillary electrophoretic method was developed for chiral analysis of the novel anti-diabetic drug, sitagliptin. The acid-base profiling of the analyte was carried out using both capillary electrophoresis and nuclear magnetic resonance pH titrations. The apparent complex stability and chiral separation properties were investigated with 30 different cyclodextrins under acidic conditions. The effect of concentration and pH of the BGE, temperature of the capillary, and the type and concentration of the chiral selector on the enantiomer resolution were thoroughly investigated. The effects of dual cyclodextrin systems on separation were also extensively studied. Complete separation of racemic sitagliptin with good resolution (R(S)=2.24) was achieved within a short time (15 min) with optimized parameters (10°C, pH=4.4, 40 mM phosphate buffer) of a sulfobutylether-β-cyclodextrin (averaged degree of substitution ~4) and native β-cyclodextrin dual system. The averaged stoichiometry of the inclusion complex was determined using the Job plot method with both (1)H and (19)F NMR experiments and resulted in a 1:1 complex. The structure of the inclusion complex was elucidated using 2-D ROESY NMR experiments.     

Oxidoreductive coupling of thiols with aryl halides catalyzed by copper on iron

Synthesis and utilization of a simple copper on iron catalyst in the coupling of aryl halides with thiols through disulfide intermediate is reported. The iron support of copper catalyst ensures reductive media for the coupling, allows easy removal of the metals by outer magnetic field and enables the recycling of the catalyst.