bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Acylated Flavonol Glycosides and a Phenolic Profile of Pritzelago alpina, a Forgotten Edible Alpine Plant
Authors: Corradi Elisabetta , De Mieri Maria , Cadisch Larissa , Abbet Christian , Hamburger Matthias , Potterat Olivier 
Published: February 2016

AbstractThirteen acylated flavonoid glycosides, 1–13, including eleven new congeners, 3–13, were isolated from the aerial parts of Pritzelago alpina (Brassicaceae) by a combination of column chromatography on Sephadex LH‐20, and preparative and semi‐preparative HPLC. The structures were established by extensive NMR and MS experiments in combination with acid hydrolysis and sugar analysis by GC/MS. The new compounds were shown to be kaempferol and quercetin glycosides acylated for most of them by a branched short chain fatty acid or a hydroxycinnamic acid residue on the sugar portion. As shown by a HPLC‐DAD analysis of a MeOH extract, these compounds are the main phenolic constituents in the aerial parts of the plant.
Counterion‐Controlled Self‐Sorting in an Amphiphilic Calixarene Micellar System
Authors: Fernández‐Abad Silvia , Pessêgo Márcia , Basílio Nuno , García‐Río Luis 
Published: February 2016

AbstractMolecular recognition of small molecules and ions by artificial receptors in microheterogeneous media such as micelles and vesicles can, in principle, provide better models of biological systems in comparison with bulk solutions. In this work we have investigated the complexation of an organic fluorescent probe with amphiphilic calixarene receptor below and above the critical micelle concentration (CMC). For concentrations below the CMC, the probe forms a host–guest complex with the calixarene behaving like a traditional host–guest system operating in bulk solution. Above the CMC, multiple equilibrium processes are established and the probe can exchange between the recognition site of the calixarene in the monomeric state, micellized state and/or the micellar hydrophobic core. Careful analysis of the results obtained from NMR spectroscopy and fluorescence experiments allowed us to propose a quantitative model to describe the system. The increment of the local concentration of Na+ counterions at the Stern layer displace the dye to the micelle core through competitive binding of Na+ in the cavity of the receptor and is decisive for the observed self‐sorting behavior.
Ultrasmall Superparamagnetic Iron Oxide Nanoparticles with Europium(III) DO3A as a Bimodal Imaging Probe
Authors: Carron Sophie , Bloemen Maarten , Vander Elst Luce , Laurent Sophie , Verbiest Thierry , Parac‐Vogt Tatjana N. 
Published: February 2016

AbstractA new prototype consisting of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles decorated with europium(III) ions encapsulated in a DO3A organic scaffold was designed as a platform for further development of bimodal contrast agents for MRI and optical imaging. The USPIO nanoparticles act as negative MRI contrast agents, whereas the europium(III) ion is a luminophore that is suitable for use in optical imaging detection. The functionalized USPIO nanoparticles were characterized by TEM, DLS, XRD, FTIR, and TXRF analysis, and a full investigation of the relaxometric and optical properties was conducted. The typical luminescence emission of europium(III) was observed and the main red emission wavelength was found at 614 nm. The relaxometric study of these ultrasmall nanoparticles showed r2 values of 114.8 mm−1Fes−1 at 60 MHz, which is nearly double the r2 relaxivity of Sinerem®.
How Interfaces Affect the Acidity of the Anilinium Ion
Authors: Sripradite Jarukorn , Miller Susannah A. , Johnson Michael D. , Tongraar Anan , Crans Debbie C. 
Published: February 2016

AbstractThe acidity of a compound is a fundamental property that dictates molecular speciation and reactivity in solution. Measurements of acidity of simple molecules in interfacial environments are rarely carried out but assumptions often are made that the difference is sufficiently small that the change can be ignored. The effect of oil–surfactant–water interfaces in reverse micellar systems on the pKa value of the anilinium ion was measured using titrations by NMR spectroscopy as the size of the bis(2‐ethylhexyl)sulfosuccinate (AOT)/isooctane reverse micelles decreased. The pKa was observed to drop from 4.85±0.02 to 4.62±0.02 in water as the reverse micelle decreased from w0 10 to 4 (that is down to a reverse micellar radius of about 2 nm). NOSEY experiments demonstrated that the aniline moiety resides within the surfactant interface with the amine/ammonium moiety protruding into the waterpool bridging the interface. The presence of the aniline was found to have modest and variable effect on the size of the reverse micelles as observed using dynamic light scattering. Our experimental results provide information important to theoretical studies, which explore interface phenomena and provide a framework for information on such simple molecules. These studies quantitate the small but significant effect on the pKa values upon placement of an aromatic amine molecule at a hydrophilic–hydrophobic interface.
Iodoindazoles with Selective Magnesiation at Position 3: A Route to Highly Functionalized Indazoles
Authors: Lam Bao Vy , Berhault Yohann , Stiebing Silvia , Fossey Christine , Cailly Thomas , Collot Valérie , Fabis Frédéric 
Published: February 2016

AbstractA unique route to highly functionalized indazoles is described. A regioselective magnesiation at position 3 of 4‐, 5‐, 6‐ and 7‐iodo‐2‐THP‐indazoles (THP=tetrahydropyranyl) has been developed using TMPMgCl⋅LiCl (TMP=2,2,6,6‐tetramethylpiperidyl). The obtained magnesiate can be trapped by different electrophiles to introduce a wide range of functional groups including halogens, thioalkyls, alcohols, aldehydes, ketones, amides, or esters at position 3. Once this position is functionalized, the iodine atoms can be further reacted through metal–halogen exchange or cross‐coupling strategies. Finally, N‐substitution reactions allow the synthesis of a variety of highly functionalized indazoles giving access to these valuable scaffolds through a simple and unique route.
Exploring Regioselective Bond Cleavage and Cross‐Coupling Reactions using a Low‐Valent Nickel Complex
Authors: Desnoyer Addison N. , Friese Florian W. , Chiu Weiling , Drover Marcus W. , Patrick Brian O. , Love Jennifer A. 
Published: February 2016

AbstractRecently, esters have received much attention as transmetalation partners for cross‐coupling reactions. Herein, we report a systematic study of the reactivity of a series of esters and thioesters with [{(dtbpe)Ni}2(μ‐η2:η2‐C6H6)] (dtbpe=1,2‐bis(di‐tert‐butyl)phosphinoethane), which is a source of (dtbpe)nickel(0). Trifluoromethylthioesters were found to form η2‐carbonyl complexes. In contrast, acetylthioesters underwent rapid Cacyl−S bond cleavage followed by decarbonylation to generate methylnickel complexes. This decarbonylation could be pushed backwards by the addition of CO, allowing for regeneration of the thioester. Most of the thioester complexes were found to undergo stoichiometric cross‐coupling with phenylboronic acid to yield sulfides. While ethyl trifluoroacetate was also found to form an η2‐carbonyl complex, phenyl esters were found to predominantly undergo Caryl−O bond cleavage to yield arylnickel complexes. These could also undergo transmetalation to yield biaryls. Attempts to render the reactions catalytic were hindered by ligand scrambling to yield nickel bis(acetate) complexes, the formation of which was supported by independent syntheses. Finally, 2‐naphthyl acetate was also found to undergo clean Caryl−O bond cleavage, and although stoichiometric cross‐coupling with phenylboronic acid proceeded with good yield, catalytic turnover has so far proven elusive.
Synthesis of Bis(pentafluoroethyl)germanes
Authors: Pelzer Stefanie , Neumann Beate , Stammler Hans‐Georg , Ignat'ev Nikolai , Hoge Berthold 
Published: February 2016

AbstractThe chemistry of bis(pentafluoroethyl)germanes (C2F5)2GeX2 is presented. The synthesis of such species requires Br2GePh2, wherein the phenyl substituents function as suitable protecting groups. After treatment with two equivalents of LiC2F5, (C2F5)2GePh2 is produced. The replacement of the phenyl rings is smoothly effected by gaseous HBr or HCl in the presence of a Lewis acidic catalyst. The trigermoxane [(C2F5)2GeO]3 results from the reaction of (C2F5)2GeBr2 with Ag2CO3. Its crystalline 1,10‐phenanthroline adduct was fully characterised by X‐ray diffraction. The combination of (C2F5)2GeBr2 with Bu3SnH gave rise to the formation of (C2F5)2GeH2.
Solvent‐Dependent Structure of Iridium Dihydride Complexes: Different Geometries at Low and High Dielectricity of the Medium
Authors: Polukeev Alexey V. , Marcos Rocío , Ahlquist Mårten S. G. , Wendt Ola F. 
Published: February 2016

AbstractThe hydride iridium pincer complex [(PCyP)IrH2] (PCyP=cis‐1,3‐bis[(di‐tert‐butylphosphino)methyl]cyclohexane, 1) reveals remarkably solvent‐dependent hydride chemical shifts, isotope chemical shifts, JHD and T1(min), with rHH increasing upon moving to more polar medium. The only known example of such behaviour (complex [(POCOP)IrH2], POCOP=2,6‐(tBu2PO)2C6H3) was explained by the coordination of a polar solvent molecule to the iridium (J. Am. Chem. Soc. 2006, 128, 17114). Based on the existence of an agostic bond between α‐C−H and iridium in 1 in all solvents, we argue that the coordination of solvent can be rejected. DFT calculations revealed that the structures of 1 and [(POCOP)IrH2] depend on the dielectric permittivity of the medium and these compounds adopt trigonal‐bipyramidal geometries in non‐polar media and square‐pyramidal geometries in polar media.
Visible‐Light‐Promoted Trifluoromethylthiolation of Styrenes by Dual Photoredox/Halide Catalysis
Authors: Honeker Roman , Garza‐Sanchez R. Aleyda , Hopkinson Matthew N. , Glorius Frank 
Published: February 2016

AbstractHerein, we report a new visible‐light‐promoted strategy to access radical trifluoromethylthiolation reactions by combining halide and photoredox catalysis. This approach allows for the synthesis of vinyl–SCF3 compounds of relevance in pharmaceutical chemistry directly from alkenes under mild conditions with irradiation from household light sources. Furthermore, alkyl–SCF3‐containing cyclic ketone and oxindole derivatives can be accessed by radical‐polar crossover semi‐pinacol and cyclization processes. Inexpensive halide salts play a crucial role in activating the trifluoromethylthiolating reagent towards photoredox catalysis and aid the formation of the SCF3 radical.
Synthesis and Utilization of Trialkylammonium‐Substituted Cyclodextrins as Water‐Soluble Chiral NMR Solvating Agents for Anionic Compounds
Authors: Dowey Alison E. , Puentes Cira Mollings , Carey‐Hatch Mira , Sandridge Keyana L. , Krishna Nikhil B. , Wenzel Thomas J. 
Published: February 2016

AbstractCationic trialkylammonium‐substituted α‐, β‐, and γ‐cyclodextrins containing trimethyl‐, triethyl‐, and tri‐n‐propylammonium substituent groups were synthesized and analyzed for utility as water‐soluble chiral nuclear magnetic resonance (NMR) solvating agents. Racemic and enantiomerically pure (3‐chloro‐2‐hydroxypropyl)trimethyl‐, triethyl‐, and tri‐n‐propyl ammonium chloride were synthesized from the corresponding trialkyl amine hydrochloride and either racemic or enantiomerically pure epichlorohydrin. The ammonium salts were then reacted with α‐, β‐, and γ‐cyclodextrins at basic pH to provide the corresponding randomly substituted cationic cyclodextrins. The 1H NMR spectra of a range of anionic, aromatic compounds was recorded with the cationic cyclodextrins. Cyclodextrins with a single stereochemistry at the hydroxy group on the (2‐hydroxypropyl)trialkylammonium chloride substituent were often but not always more effective than the corresponding cyclodextrin in which the C‐2 position was racemic. In several cases, the larger triethyl or tri‐n‐propyl derivatives were more effective than the corresponding trimethyl derivative at causing enantiomeric differentiation. None of the cyclodextrin derivatives were consistently the most effective for all of the anionic compounds studied. Chirality 28:299–305, 2016. © 2016 Wiley Periodicals, Inc.
Guideline‐Directed Medication Use in Patients With Heart Failure With Reduced Ejection Fraction in India: American College of Cardiology's PINNACLE India Quality Improvement Program
Authors: Pokharel Yashashwi , Wei Jessica , Hira Ravi S. , Kalra Ankur , Shore Supriya , Kerkar Prafulla G. , Kumar Ganesh , Risch Samantha , Vicera Veronique , Oetgen William J. , Deswal Anita , Turakhia Mintu P. , Glusenkamp Nathan , Virani Salim S. 
Published: February 2016

AbstractLittle is known about the use of guideline‐directed medical therapy (GDMT) in outpatients with heart failure with reduced left ventricular ejection fraction (HFrEF; ≤40%) in India. Our objective was to understand the use of GDMT in outpatients with HFrEF in India. The Practice Innovation And Clinical Excellence (PINNACLE) India Quality Improvement Program (PIQIP) is a registry for cardiovascular quality improvement in India supported by the American College of Cardiology Foundation. Between January 2008 and September 2014, we evaluated documentation of use of angiotensin‐converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) and β‐blockers, or both, among outpatients with HFrEF seeking care in 10 centers enrolled in the PIQIP registry. Among 75 639 patients in the PIQIP registry, 34 995 had EF reported, and 15 870 had an EF ≤40%. The mean age was 56 years; 23% were female. Hypertension, diabetes, coronary artery disease, and myocardial infarction were present in 37%, 23%, 27%, and 17%, respectively. Use of ACEIs/ARBs, β‐blockers, and both were documented in 33.5%, 34.9%, and 29.6% of patients, respectively. The documentation of GDMT was higher in men, in patients age ≥65 years, and in those with presence of hypertension, diabetes, or coronary artery disease. Documentation of GDMT gradually increased over the study period. Among patients enrolled in the PIQIP registry, about two‐thirds of patients with EF ≤40% did not have documented receipt of GDMT. This study is an initial step toward improving adherence to GDMT in India and highlights the feasibility of examining quality of care in HFrEF in a resource‐limited setting.
Development of Photoactivatable Allosteric Modulators for the Chemokine Receptor CXCR3
Authors: Admas Tizita Haimanot , Bernat Viachaslau , Heinrich Markus R. , Tschammer Nuska 
Published: February 2016

AbstractThe CXCR3 receptor, a class A G protein‐coupled receptor (GPCR), is involved in the regulation and trafficking of various immune cells. CXCR3 antagonists have been proposed to be beneficial for the treatment of a wide range of disorders including but not limited to inflammatory and autoimmune diseases. The structure‐based design of CXCR3 ligands remains, however, hampered by a lack of structural information describing in detail the interactions between an allosteric ligand and the receptor. We designed and synthesized photoactivatable probes for the structural and functional characterization, using photoaffinity labeling followed by mass spectrometry, of the CXCR3 allosteric binding pocket of AMG 487 and RAMX3, two potent and selective CXCR3 negative allosteric modulators. Photoaffinity labeling is a common approach to elucidate binding modes of small‐molecule ligands of GPCRs through the aid of photoactivatable probes that convert to extremely reactive intermediates upon photolysis. The photolabile probe N‐[({1‐[3‐(4‐ethoxyphenyl)‐4‐oxo‐3,4‐dihydropyrido[2,3‐d]pyrimidin‐2‐yl]ethyl}‐2‐[4‐fluoro‐3‐(trifluoromethyl)phenyl]‐N‐{1‐[4‐(3‐(trifluoromethyl)‐3H‐diazirin‐3‐yl]benzyl}piperidin‐4‐yl)methyl]acetamide (10) showed significant labeling of the CXCR3 receptor (80 %) in a [3H]RAMX3 radioligand displacement assay. Compound 10 will serve as an important tool compound for the detailed investigation of the binding pocket of CXCR3 by mass spectrometry.
Novel 8‐Hydroxyquinoline Derivatives as Multitarget Compounds for the Treatment of Alzheimer′s Disease
Authors: Prati Federica , Bergamini Christian , Fato Romana , Soukup Ondrej , Korabecny Jan , Andrisano Vincenza , Bartolini Manuela , Bolognesi Maria Laura 
Published: February 2016

AbstractWe discovered a small series of hit compounds that show multitargeting activities against key targets in Alzheimer′s disease (AD). The compounds were designed by combining the structural features of the anti‐AD drug donepezil with clioquinol, which is able to chelate redox‐active metals, thus decreasing metal‐driven oxidative phenomena and β‐amyloid (Aβ)‐mediated neurotoxicity. The majority of the new hybrid compounds selectively target human butyrylcholinesterase at micromolar concentrations and effectively inhibit Aβ self‐aggregation. In addition, compounds 5‐chloro‐7‐((4‐(2‐methoxybenzyl)piperazin‐1‐yl)methyl)‐8‐hydroxyquinoline (1 b), 7‐((4‐(2‐methoxybenzyl)piperazin‐1‐yl)methyl)‐8‐hydroxyquinoline (2 b), and 7‐(((1‐benzylpiperidin‐4‐yl)amino)methyl)‐5‐chloro‐8‐hydroxyquinoline (3 a) are able to chelate copper(II) and zinc(II) and exert antioxidant activity in vitro. Importantly, in the case of 2 b, the multitarget profile is accompanied by high predicted blood–brain barrier permeability, low cytotoxicity in T67 cells, and acceptable toxicity in HUVEC primary cells.
Dispositional optimism and therapeutic expectations in early‐phase oncology trials
Authors: Jansen Lynn A. , Mahadevan Daruka , Appelbaum Paul S. , Klein William M.P. , Weinstein Neil D. , Mori Motomi , Daffé Racky , Sulmasy Daniel P. 
Published: February 2016

BACKGROUNDPrior research has identified unrealistic optimism as a bias that might impair informed consent among patient‐subjects in early‐phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient‐subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism.METHODSPatient‐subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception.RESULTSDispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; P<.0001), but was not associated with the therapeutic misconception (Spearman r, ‐0.075; P = .329). Dispositional optimism was found to be weakly associated with unrealistic optimism (Spearman r, 0.215; P = .005). On multivariate analysis, both dispositional optimism (P = .02) and unrealistic optimism (P<.0001) were found to be independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (P = .0001), but not dispositional optimism, was found to be independently associated with the therapeutic misconception.CONCLUSIONSHigh expectations for therapeutic benefit among patient‐subjects in early‐phase oncology trials should not be assumed to result from misunderstanding of specific information regarding the trials. The data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations concerning specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early‐phase oncology research. Cancer 2016;122:1238–46. © 2016 American Cancer Society.
Usefulness of translocation‐associated immunohistochemical stains in the fine‐needle aspiration diagnosis of salivary gland neoplasms
Authors: Foo Wen‐Chi , Jo Vickie Y. , Krane Jeffrey F. 
Published: February 2016

BACKGROUNDFine‐needle aspiration diagnosis of pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) is challenging due to cytologic overlap with one another and with other salivary gland tumors having prominent epithelial and myoepithelial components. Recognition of characteristic chromosomal aberrations in several salivary gland tumors, including PA and ACC, has the potential to resolve diagnostic uncertainty, but molecular diagnostics are not routinely available. To leverage these molecular alterations, the authors examined a panel of commercially available immunostains directed at commonly overexpressed proteins in translocation‐associated PA (PLAG1 and HMGA2) and ACC (MYB) to assess their diagnostic usefulness.METHODSImmunohistochemistry was performed on cell block samples from 74 patients, including 11 ACC specimens and 31 PA specimens with antibodies to MYB, PLAG1, and HMGA2 as well as KIT (previously considered useful in the diagnosis of ACC).RESULTSACCs demonstrated significantly greater staining for KIT compared with non‐ACCs, while PAs had significantly greater staining for PLAG1 than non‐PAs. MYB trended toward significance for ACC (P=.097) and HMGA2 trended toward significance for PA (P=.094). No ACC exhibited positive staining for PLAG1 or HMGA2. Only 12% of PAs were found to be positive for MYB or KIT. Combined positivity for MYB and KIT with negative PLAG1 and HMGA2 demonstrated a specificity and positive predictive value of 1.0 for ACC, whereas a positive PLAG1 or HMGA2 stain with negative MYB and KIT stains showed a sensitivity of 0.75, a specificity of 0.96, and a positive predictive value of 0.95 for PAs.CONCLUSIONSAn immunohistochemical panel of MYB, KIT, PLAG1, and HMGA2 on fine‐needle aspiration cell blocks is useful in distinguishing ACCs and PAs from each other and other salivary gland neoplasms. Cancer Cytopathol 2016;124:397–405. © 2016 American Cancer Society.
Ecohydrological feedbacks in peatlands: an empirical test of the relationship among vegetation, microtopography and water table
Authors: Malhotra Avni , Roulet Nigel T. , Wilson Paul , Giroux‐Bougard Xavier , Harris Lorna I. 
Published: February 2016

AbstractCurrent models and theories of the formation and maintenance of microtopography in ombrotrophic peatlands (bogs) assume autogenic feedbacks between vegetation composition, water table depth (WTD) and microtopography. A hypothesized outcome of autogenic feedbacks is a strong association among spatial variations in vegetation composition, WTD and microtopography. We tested and corroborated this hypothesis using fine spatial scale (<2 × 2 m2) data from two 20 × 20 m2 plots at Mer Bleue, a temperate bog. Furthermore, we partitioned the spatial variation of plant communities into portions explained by WTD as well as fine‐scale and broad‐scale spatial structures using distance‐based Moran's eigenvector maps. We hypothesized that plant distributions are more strongly related to WTD than to microtopography and found that this hypothesis was supported in only one of the two sampled plots, suggesting that the feedbacks among WTD, vegetation and microtopography could be dependent on location within a bog. A plot closer to the centre (apex) of the bog showed stronger relationships among WTD–microtopography and vegetation than a plot closer to the margin. Our results support current models and theories of the development of bogs wherein plant communities, water table and microtopography are strongly associated because of underlying ecohydrological feedbacks but highlight that strength and direction of feedbacks may vary by location within a bog. Affirming the presence of these structural relationships and identifying variability in them is a key step towards better understanding peatland carbon cycling, especially in the context of increasing anthropogenic and natural disturbances to peatlands. Copyright © 2016 John Wiley & Sons, Ltd.