bluuebunny/crossref_metadata_2025 huggingface dataset:
Response to Comment on “A Liposomal System Capable of Generating CO2 Bubbles to Induce Transient Cavitation, Lysosomal Rupturing and Cell Necrosis”
Authors: Wan Wei‐Lin , Chung Min‐Fan , Shih Po‐Chien , Sung Hsing‐Wen
Published: August 2017

Leroux et al. performed a set of experiments reported in our study and claim that they failed to reproduce the thermoresponsive liposomal system containing ammonium bicarbonate (ABC) that could trigger drug release under mild heating. We disagree with their assessments and speculate that the different method used by Leroux et al. to prepare the aqueous ABC is the culprit.
Solvation Accounts for the Counterintuitive Nucleophilicity Ordering of Peroxide Anions
Authors: Mayer Robert J. , Tokuyasu Takahiro , Mayer Peter , Gomar Jérôme , Sabelle Stéphane , Mennucci Benedetta , Mayr Herbert , Ofial Armin R.
Published: August 2017

The nucleophilic reactivities (N, sN) of peroxide anions (generated from aromatic and aliphatic peroxy acids or alkyl hydroperoxides) were investigated by following the kinetics of their reactions with a series of benzhydrylium ions (Ar2CH+) in alkaline aqueous solutions at 20 °C. The second‐order rate constants revealed that deprotonated peroxy acids (RCO3−), although they are the considerably weaker Brønsted bases, react much faster than anions of aliphatic hydroperoxides (ROO−). Substitution of the rate constants of their reactions with benzhydrylium ions into the linear free energy relationship lg k=sN(N+E) furnished nucleophilicity parameters (N, sN) of peroxide anions, which were successfully applied to predict the rates of Weitz–Scheffer epoxidations. DFT calculations with inclusion of solvent effects by means of the Integral Equation Formalism version of the Polarizable Continuum Model were performed to rationalize the observed reactivities.
In‐line monitoring of jute fiber–reinforced poly(lactic acid) composite subjected to impact loading using infrared thermography
Authors: Boccardi Simone , Carlomagno Giovanni Maria , Meola Carosena , Russo Pietro , Simeoli Giorgio
Published: August 2017

Poly(lactic acid) (PLA) is receiving ever more attention from both the academic and the industrial communities because it is green, biobased, and complies well with requirements for work safety and environmental safeguards. However, a question may arise regarding the suitability of PLA in replacing conventional plastics. The response requires a complete material characterization and analysis of its performance in service and its resistance to impact loads. This work is focused on monitoring with infrared thermography the impact damage of a biobased thermoplastic composite, in this case a poly(lactic acid) (PLA) matrix reinforced with jute fibers. The visualization of thermal signatures that develop under impact supplies information useful to understanding the material impact damage mechanisms, such as formation of cracks and their propagation and the overall extension of damage. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45579.
Microstructural investigation of butt‐fusion joint in high‐density polyethylene pipes using wide‐ and small‐angle X‐ray scattering
Authors: Kang Min Kwan , Choi Sunwoong , Song Hyun Hoon
Published: August 2017

The melt fusion zone (MFZ) of polyethylene pipe was investigated employing synchrotron wide‐ and small‐angle X‐ray scattering at various locations in MFZ by changing X‐ray incidence angles to probe three‐dimensional structural features. It was determined that the crystals were oriented in two different modes. One is that the polymer chains are oriented parallel to the joint interface line consistently throughout the MFZ. The other is that the crystals are oriented in particular directions depending on the positions in MFZ. The combination of pressure and melt flow during joining process resulted in such a complex structure. It was notable that the boundary of MFZ against the base material was found to be very different depending on the structures involved such as crystallographic unit orientation, lamellae orientation, crystallinity, and spherulitic morphology. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45668.
Iron–Cobalt Phosphomolybdate with High Electrocatalytic Activity for Oxygen Evolution Reaction
Authors: Zhai Haoying , Gao Taotao , Qi Ting , Zhang Yajie , Zeng Guangfeng , Xiao Dan
Published: August 2017

Iron–cobalt phosphomolybdate (FeCoPM12) nanoparticles, which are highly efficient catalytic materials for the oxygen evolution reaction (OER), were fabricated through a coprecipitation route. Compared with iron–cobalt hydroxide and state‐of‐the‐art RuO2 electrocatalysts, the as‐prepared FeCoPM12 sample exhibited robust OER catalytic activity with a low overpotential of 258 mV at a current density of 10 mA cm−2 and a small Tafel slope of 33 mV dec−1. Moreover, the as‐synthesized sample presented preferable stability and after 10 h at 1.52 V the current density degraded by merely 8.3 %. This is ascribed to the high electrochemical stability and small porous structure of FeCoPM12, which provide effective electron transmission and improve the catalytic performance for OER in alkaline media.
Modulatory Functionalization of Gold Nanorods Using Supramolecular Assemblies
Authors: Jeong Sundo , Park Hongrual , Seon Dongmin , Choi Jongwan , Hong Ki Bum , Lee Jiseok , Kim Chaekyu , Kim Jung‐Keun , Park Myoung‐Hwan
Published: August 2017

Supramolecular‐assembly‐mediated functionalization of gold nanorods (GNRs) has been developed by reversible phase transfer between water and oils, which offers a facile method for fabricating robust GNRs with surface‐charge tunability. In this regard, trimethylammonium (TMA) GNRs were initially prepared from conventional cetyltrimethylammonium bromide (CTAB) GNRs by means of a ligand‐exchange reaction in the presence of an excess amount of TMA ligands. To further expand their functionality and potential applications, electrostatic assemblies of positively charged TMA‐GNRs with negatively charged oleate ions were prepared. These assemblies (OA‐GNRs) can undergo facile phase transfer from water to hexane. Interestingly, the reversible electrostatic assembly between the TMA and OA ions fabricated onto GNRs can be easily disrupted by treatment with HCl, which removes the OA ions from the GNRs to re‐form the TMA‐GNRs, which can be made soluble in aqueous media again. In addition, OA‐GNRs can be further used for the synthesis of negatively charged GNRs such as 11‐mercaptoundecanoic acid (MUA) GNRs, which are hard to prepare directly from CTAB‐GNRs. This versatile method for phase transfer and functionalization on GNRs is expected to broaden the scope of their applications in sensing, biomedical imaging, photothermal therapies, and drug delivery systems.
Catalytic Conversion of Dinitrogen into Ammonia under Ambient Reaction Conditions by Using Proton Source from Water
Authors: Tanabe Yoshiaki , Arashiba Kazuya , Nakajima Kazunari , Nishibayashi Yoshiaki
Published: August 2017

Molybdenum‐catalyzed conversion of molecular dinitrogen into ammonia under ambient reaction conditions has been achieved by using a proton source generated in situ from the ruthenium‐catalyzed oxidation of water in combination with visible light and a photosensitizer. The preset reaction system is considered as a new model for the nitrogen fixation by photosynthetic bacteria.
Graphene Oxide as a Carbocatalyst for a Diels–Alder Reaction in an Aqueous Medium
Authors: Girish Yarabhally R. , Pandit Subrata , Pandit Subhendu , De Mrinmoy
Published: August 2017

The Diels–Alder (DA) reaction, a [4+2] cycloaddition reaction, is highly important in synthetic organic chemistry and is frequently used in the synthesis of natural products containing six‐membered rings. Herein, we report an efficient protocol for the DA reaction between 9‐hydroxymethylanthracene and N‐substituted maleimides using two‐dimensional graphene oxide (GO) as a heterogeneous carbocatalyst in an aqueous medium at room temperature. High yields, a wide substrate scope, low temperature, excellent functional group tolerance, atom economy, and water as a green solvent are noteworthy features of this protocol. The heterogeneous GO catalyst can be easily recovered and used multiple times without any significant loss in catalytic activity.
Zustandserfassung von Stahlbauwerken mithilfe akustischer und elektromagnetischer Verfahren der ZfP
Authors: Boller Christian , Fox Christian , Starke Peter , Wu Haoran , Doktor Markus , Kurz Wolfgang
Published: August 2017

In dem Beitrag wird dargestellt, wie man mit Verfahren der zerstörungsfreien Prüfung (ZfP) Baustähle hinsichtlich ihrer mechanischen Eigenschaften wie auch ihres Schädigungsgrads im anrissfreien Stadium charakterisieren kann. Bei den angewandten ZfP‐Verfahren handelt es sich um den Ultraschall und die Elektromagnetik. Mit der Elektromagnetik lassen sich Baustähle hinsichtlich ihrer Festigkeitsklassen unterscheiden, während mit Ultraschall mechanische Spannungen ermittelt werden, die wiederum als Basis für die Rückrechnung von Schnittgrößen herangezogen werden können. Das vorgestellte Verfahren SteBLife ermöglicht mit nur einer einzigen Werkstoffprobe die Ermittlung einer kompletten Werkstoffwöhlerlinie und unter Anwendung der ZfP‐Verfahren sogar den kompletten nichtlinearen Schadensakkumulationsprozess. Statistische Verfahren runden den Prozess der Evaluierung ab. Die vorgestellten Verfahren bilden die Basis für einen Paradigmensprung im Management alternder Stahlinfrastruktur.
Preliminary results on the photoluminescence and optically stimulated luminescence in Cu‐doped and Ag‐doped ZnB2X4 (B = Li, Na, K: X = Cl, Br) compounds
Authors: Jog Milind , Patil Rajesh , More Yogesh , Kulkarni Mukund , Moharil Sanjiv
Published: August 2017

Photoluminescence, and optically stimulated luminescence in ZnB2X4 (B; Li,Na,K: X; Cl,Br) compounds doped with Cu+ or Ag+ were studied. Double humped emission bands attributable to the activators were observed in all the samples. The observed photoluminescence of Cu+ and Ag+ could be identified with 3d94s1↔3d10 and 4d95s1↔5d10 transitions respectively. The longer wavelength band (400–500 nm range) could be attributed to the Cu+ or Ag+ ion replacing alkali ion at the octahedral alkali site whereas short wavelength band (340–400 nm range) is attributed to a Cu or Ag ion at tetrahedral zinc site. The short wavelength band was found to be intense compared with long wavelength and gave an indication that most of the Cu or Ag ions prefered a tetrahedral Zn site compared with the octahedral alkali site. All the samples exhibit optically stimulated luminescence (OSL). The sensitivity was found to be lattice dependent. The lowest sensitivity of about 1% compared with Al2O3:C was observed in lithium lattices whereas highest the sensitivity of about 290% was observed in the case of Cu‐doped ZnNa2Br4.
Silica‐modified luminescent LaPO4:Eu@LaPO4@SiO2 core/shell nanorods: Synthesis, structural and luminescent properties
Authors: Ansari Anees A.
Published: August 2017

Monoclinic‐type tetragonal LaPO4:Eu (core) and LaPO4:Eu@LaPO4 (core/shell) nanorods (NRs) were successfully prepared using a urea‐based co‐precipitation process under ambient conditions. An amorphous silica layer was coated around the luminescent core/shell NRs via the sol–gel process to improve their solubility and colloidal stability in aqueous and non‐aqueous media. The prepared nano‐products were systematically characterized by X‐ray diffraction pattern, transmission electron microscopy, energy dispersive X‐ray analysis, and FTIR, UV/Vis, and photoluminescence spectroscopy to examine their phase purity, crystal phase, surface chemistry, solubility and luminescence characteristics. The length and diameter of the nano‐products were in the range 80–120 nm and 10–15 nm, respectively. High solubility of the silica‐modified core/shell/Si NRs was found for the aqueous medium. The luminescent core NRs exhibited characteristic excitation and emission transitions in the visible region that were greatly affected by surface growth of insulating LaPO4 and silica layers due to the multiphonon relaxation rate. Our luminescence spectral results clearly show a distinct difference in intensities for core, core/shell, and core/shell/Si NRs. Highly luminescent NRs with good solubility could be useful candidates for a variety of photonic‐based biomedical applications.
The combination of digoxin and GSK2606414 exerts synergistic anticancer activity against leukemia in vitro and in vivo
Authors: Zhang Xue‐Hong , Wang Xin‐Yu , Zhou Zhi‐Wei , Bai Hua , Shi Lin , Yang Yin‐Xue , Zhou Shu‐Feng , Zhang Xiao‐Chun
Published: August 2017

Digoxin is a member of cardiac glycosides and recent studies show that digoxin plays anticancer role in several types of cancer. However, the anticancer effects and mechanism of digoxin in leukemia is largely unknown. Her, our data show that digoxin treatment significantly inhibits leukemia cell viability. In addition, digoxin treatment significantly induced apoptosis and G2/M cell cycle arrest in leukemia cells. Furthermore, we demonstrated that digoxin treatment inactivate that oncogenic pathway Akt/mTOR signaling in leukemia cells. In addition, our data show that digoxin treatment induces activation of unfolded protein response (UPR) signaling in leukemia cells. Interestingly, our in vitro and in vivo experiments show that combination treatment of digoxin and UPR inhibitor can synergistically suppress leukemia growth and induces apoptosis and cell cycle arrest compared to single drug treatment. In summary, our findings indicate that digoxin has potential anticancer effects on leukemia. The combination of digoxin and UPR signaling inhibitor can exerts synergistic anticancer activity against leukemia. © 2017 BioFactors, 43(6):812–820, 2017
Jury awards deaf student damages against Keiser U
Authors: Charmatz Marc
Published: August 2017

A federal jury in Fort Lauderdale, Florida, held that Keiser University intentionally discriminated against a deaf student by denying her admission to the Keiser radiology technician program, and the jury awarded the student $75,000 (Daniel‐Rivera v. Everglades College, d/b/a Keiser University, Case No. 0:16.‐cv‐60044‐WPD (S.D. Florida 04/18/17)).
“A few bad apples” or “rotten to the core”: Perceptions of corporate culture drive brand engagement after corporate scandal
Authors: Guckian Meaghan L. , Chapman Daniel A. , Lickel Brian , Markowitz Ezra M.
Published: August 2017

Following unethical corporate behavior, consumers face decisions on how to engage with brands in the future. Consumers' beliefs about the underlying causes of a corporate scandal may influence future patronage intentions, for example, by influencing perceived likelihood of future wrongdoing. We investigated how beliefs about corporate culture and consumer proximity to the recent Volkswagen diesel emissions scandal influence expectations of future ethical action by Volkswagen Group (VW), feelings of anger, and future brand engagement. Results indicate that beliefs about corporate culture and proximity each independently influence future brand engagement. Specifically, owners who believed “a few bad apples” (rather than a “rotten” corporate culture) caused the scandal reported higher expectations of future ethical action by VW, less anger, and more positive intentions to engage with VW in the future. Those more proximately affected by the scandal, that is, turbocharged direct injection owners, were more likely to be angry and less likely to engage with VW. Expectation of future ethical action and anger mediated the effects of corporate culture on engagement, whereas only anger mediated the effects of proximity. This small set of factors accounted for over half of the observed variance in future brand engagement intentions, highlighting the importance of understanding consumer responses to corporate scandal.
Isolation of the New Antiplasmodial Butanolide, Malleastrumolide A, from Malleastrum sp. (Meliaceae) from Madagascar
Authors: Du Yongle , Abedi Alexander K. , Valenciano Ana Lisa , Fernández‐Murga Maria L. , Cassera Maria B. , Rasamison Vincent E. , Applequist Wendy L. , Miller James S. , Kingston David G. I.
Published: August 2017

An extract of Malleastrum sp. (Meliaceae) collected in Madagascar by the Madagascar International Cooperative Biodiversity Group was found to have antimalarial activity, with an IC50 value between 2.5 and 5 μg ml−1. After purification by liquid‐liquid partition, chromatography on a Diaion open column, C18 SPE and C18 reversed phase HPLC, the new butanolide, malleastrumolide A, was isolated. The structure of malleastrumolide A was determined by mass spectrometry, NMR, and ECD. The double bond position was determined by cross‐metathesis and mass spectrometry. The compound has antiproliferative activity against the A2780 ovarian cancer cell line with an IC50 value of 17.4 μm and antiplasmodial activity against the drug‐resistant Dd2 strain of Plasmodium falciparum with an IC50 value of 2.74 μm.
Differential expression and androgen regulation of microRNAs and metalloprotease 13 in breast cancer cells
Authors: Ahram Mamoun , Mustafa Ebtihal , Zaza Rand , Abu Hammad Shatha , Alhudhud Mariam , Bawadi Randa , Zihlif Malek
Published: August 2017

MicroRNA molecules (miRNAs) play important roles in regulating cell behavior. The expression of certain miRNAs has been shown to be regulated by the androgen receptor (AR), which seems to have a critical role in the tumorigenic process of breast cancer. The differential expression of 84 miRNAs was first examined in three breast cancer cell lines: the luminal MCF‐7 and T47D cells and the molecular apocrine MDA‐MB‐453 cells. Analysis of basal expression of miRNAs revealed that each cell line had distinct miRNA expression where let‐7a and ‐7b were markers of MDA‐MB‐453 cells, whereas miR‐205 was a marker for the luminal cell lines. Treating the cells with the AR agonist, CI‐4AS‐1, resulted in unique alterations in the expression of specific miRNA among the three cell lines. Particularly, the expression of miR‐100 and miR‐125 was reduced in MDA‐MB‐453 cells by five and three folds, respectively. This effect was simultaneous with AR‐induced increase in the expression and extracellular release of metalloprotease‐13 (MMP13). Transfection of cells with either miR‐100 or miR‐125b negated the induction of MMP13 release. Additionally, AR activation induced a morphological alteration of MDA‐MB‐453 cells, which was blocked by miR‐125b only. Collectively, these data indicate that AR may control the biological behavior of breast cancer cells and protein expression via miRNAs.
Distinct Promotive Effects of 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene (DBU) on Polymer Supports in Copper‐Catalyzed Hydrogenation of C=O Bonds
Authors: Watari Ryo , Matsumoto Norio , Kuwata Shigeki , Kayaki Yoshihito
Published: August 2017

An amidine base‐containing polymer, polystyrene‐bound 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (PS‐DBU), proved to serve as a prominent catalyst support. The combined use of selected copper salts with PS‐DBU in the catalytic hydrogenation of acetophenone qualifies DBU as beneficial to generate catalytically active species and stabilize them on the polymer. Catalyst preparation and characterization reveal that the active copper species is in a low‐valent state and the nanosized particles possibly grow on the amidine structure. The high immobilization ability of PS‐DBU almost entirely prohibited copper leaching to the product over six cycles of hydrogenation and catalyst recovery. The copper catalyst attached to PS‐DBU specifically promotes the hydrogenation of various ketones and aldehydes under 10 atm of H2 at 90 °C to afford alcoholic products in satisfactory yields.
Substrate Effects in Graphene‐Based Electric Double‐Layer Capacitors: The Pivotal Interplays between Ions and Solvents
Authors: Yang Huachao , Bo Zheng , Yang Jinyuan , Kong Jing , Chen Xia , Yan Jianhua , Cen Kefa
Published: August 2017

Graphene has been considered as a promising active material for electric double‐layer capacitors (EDLCs), primarily owing to its extraordinary monolayer properties, whereas the interfacial behaviors are conspicuously impacted by underlying substrates. In this work, substrate effects on the interfacial wettability, EDL structure, and capacitive behavior of graphene‐based EDLCs are delineated with numerical simulation. Unlike previous studies, a partial wetting transparency of topmost graphene is recognized for hydrophilic supports. In particular, a virtually identical capacitance is demonstrated for graphene with various supports, albeit the substantially different EDL structures stemmed from substrate effects. The achieved invariant capacitance is prominently attributed to the counterbalancing correlations between ions and proximal solvents, going beyond traditional views of modulating capacitance preferentially through ion structural evolutions. Specifically, the suppressed permittivity of apparently ordered water dipoles (i. e. detrimental solvent effects) attenuates the beneficial ionic influences (i. e. reinforced population and closer approach) on shielding the external electric fields. The as‐obtained findings demonstrate the paramount importance of the substrate in mediating interfacial behaviors within electrified EDLC systems and highlight that exploiting the pivotal interplay between ions and solvents could be a novel avenue to further manipulate electrochemical performances.
Selectivity‐relaxed classical and inverse least squares calibration and selectivity measures with a unified selectivity coefficient
Authors: Kalivas John H. , Ferré Joan , Tencate Alister J.
Published: August 2017

Two popular calibration strategies are classical least squares (CLS) and inverse least squares (ILS). Underlying CLS is that the net analyte signal used for quantitation is orthogonal to signal from other components (interferents). The CLS orthogonality avoids analyte prediction bias from modeled interferents. Although this orthogonality condition ensures full analyte selectivity, it may increase the mean squared error of prediction. Under certain circumstances, it can be beneficial to relax the CLS orthogonality requisite allowing a small interferent bias if, in return, there is a mean squared error of prediction reduction. The bias magnitude introduced by an interferent for a relaxed model depends on analyte and interferent concentrations in conjunction with analyte and interferent model sensitivities. Presented in this paper is relaxed CLS (rCLS) allowing flexibility in the CLS orthogonality constraints. While ILS models do not inherently maintain orthogonality, also presented is relaxed ILS. From development of rCLS, presented is a significant expansion of the univariate selectivity coefficient definition broadly used in analytical chemistry. The defined selectivity coefficient is applicable to univariate and multivariate CLS and ILS calibrations. As with the univariate selectivity coefficient, the multivariate expression characterizes the bias introduced in a particular sample prediction because of interferent concentrations relative to model sensitivities. Specifically, it answers the question of when can a prediction be made for a sample even though the analyte selectivity is poor? Also introduced are new component‐wise selectivity and sensitivity measures. Trends in several rCLS figures of merit are characterized for a near infrared data set.
Model Catalytic Studies of Novel Liquid Organic Hydrogen Carriers: Indole, Indoline and Octahydroindole on Pt(111)
Authors: Schwarz Matthias , Bachmann Philipp , Silva Thais Nascimento , Mohr Susanne , Scheuermeyer Marlene , Späth Florian , Bauer Udo , Düll Fabian , Steinhauer Johann , Hohner Chantal , Döpper Tibor , Noei Heshmat , Stierle Andreas , Papp Christian , Steinrück H.‐P. , Wasserscheid Peter , Görling Andreas , Libuda Jörg
Published: August 2017

Indole derivatives were recently proposed as potential liquid organic hydrogen carriers (LOHC) for storage of renewable energies. In this work, we have investigated the adsorption, dehydrogenation and degradation mechanisms in the indole/indoline/octahydroindole system on Pt(111). We have combined infrared reflection absorption spectroscopy (IRAS), X‐ray photoelectron spectroscopy (XPS) and DFT calculations. Indole multilayers show a crystallization transition at 200 K, in which the molecules adopt a strongly tilted orientation, before the multilayer desorbs at 220 K. For indoline, a less pronounced restructuring transition occurs at 150 K and multilayer desorption is observed at 200 K. Octahydroindole multilayers desorb already at 185 K, without any indication for restructuring. Adsorbed monolayers of all three compounds are stable up to room temperature and undergo deprotonation at the NH bond above 300 K. For indoline, the reaction is followed by partial dehydrogenation at the 5‐membered ring, leading to the formation of a flat‐lying di‐σ‐indolide in the temperature range from 330–390 K. Noteworthy, the same surface intermediate is formed from indole. In contrast, the reaction of octahydroindole with Pt(111) leads to the formation of a different intermediate, which originates from partial dehydrogenation of the 6‐membered ring. Above 390 K, all three compounds again form the same strongly dehydrogenated and partially decomposed surface species.
An Unprecedented Blue Chromophore Found in Nature using a “Chemistry First” and Molecular Networking Approach: Discovery of Dactylocyanines A–H
Authors: Bonneau Natacha , Chen Guanming , Lachkar David , Boufridi Asmaa , Gallard Jean‐François , Retailleau Pascal , Petek Sylvain , Debitus Cécile , Evanno Laurent , Beniddir Mehdi A. , Poupon Erwan
Published: August 2017

Guided by a “chemistry first” approach using molecular networking, eight new bright‐blue colored natural compounds, namely dactylocyanines A–H (3–10), were isolated from the Polynesian marine sponge Dactylospongia metachromia. Starting from ilimaquinone (1), an hemisynthetic phishing probe (2) was prepared for annotating and matching structurally related natural substances in D. metachromia crude extract network. This strategy allowed characterizing for the first time in Nature the blue zwitterionic quinonoid chromophore. The solvatochromic properties of the latter are reported.
Photoinduced Electron Transfer Switching Mechanism of a Naphthalimide Derivative with its Solvatochromic Behaviour: An Experimental and Theoretical Study with In Cell Investigations
Authors: Singharoy Dipti , Chowdhury Sourav , Mati Soumya Sundar , Ghosh Swadesh , Chattopadhyay Krishnananda , Bhattacharya Subhash Chandra
Published: August 2017

The sole existence of a t‐bone‐shaped naphthalimide derivative [2‐(2‐aminoethyl)‐1H‐benzo[de]isoquinoline‐1,3(2H)dione] (NAP), which gives rise to a photoinduced electron transfer (PET) mechanism, has been established using a combination of experimental and theoretical studies. In parallel an in vitro–in cell PET mechanism has also been shown. To understand the photophysics of NAP, solvent studies have been carried out in different solvents. In addition, theoretical calculations have been conducted to explain the spectroscopic properties through optimized structures. A “turn off” PET mechanism has also been observed in the presence of specific metal ions, namely, Cr3+, Fe3+ and Hg2+ among a series of metal ions. Theoretical studies reveal that NAP–Cr3+, NAP–Fe3+ and NAP–Hg2+ have their HOMO energy states lying in between a HOMO–LUMO energy state of the t‐bone‐type NAP molecule. On the contrary, the HOMO state of the other metal ion–NAP conjugate (NAP–Mn+) does not lie in between the HOMO–LUMO energy gap of the t‐bone‐type NAP molecule. Coupled with in vitro studies, in cell investigations reveal an enhancement of fluorescence intensity of NAP upon cytosolic metal sensing. Furthermore, a very high cell viability of NAP treated cells as tested by MTT assay and a fast permeation of the said compound as revealed by flow cytometry suggest NAP to be a potential candidate in metal sensing and bioimaging applications.
Catalytic Intramolecular Cycloaddition Reactions by Using a Discrete Molecular Architecture
Authors: Roy Bijan , Devaraj Anthonisamy , Saha Rupak , Jharimune Suprita , Chi Ki‐Whan , Mukherjee Partha Sarathi
Published: August 2017

A discrete tetragonal tube‐shaped complex (MT‐1) has been synthesised by coordination‐driven self‐assembly of a carbazole‐based tetraimidazole donor L and a Pd(II) 90° acceptor, that is, [cis‐(dppf)Pd(OTf)2] (dppf=diphenylphosphinoferrocene, OTf=CF3SO3−). Complex MT‐1 was characterised by multinuclear NMR, ESI‐MS and single‐crystal X‐ray diffraction analysis (SCXRD), which showed its symmetrical tetrafacial tube‐shaped architecture possessing a large cavity described by four aromatic walls. This coordination cage was successfully utilised as a molecular vessel to perform intramolecular cycloaddition reactions of O‐allylated benzylidinebarbituric acid derivatives inside its confined nanospace. The presence of a catalytic amount of MT‐1 promoted [4+2] cycloaddition reactions in a regio‐ and stereoselective manner, yielding the corresponding penta/tetracyclouracil derivatives in good yields under mild reaction conditions. This protocol is interesting compared with the literature reports for the synthesis of similar chromenopyran pyrimidinedione derivatives under high‐temperature reflux conditions or solid‐state melt reactions (SSMRs).
Preparation of Robust Metal‐Free Magnetic Nanoemulsions Encapsulating Low‐Molecular‐Weight Nitroxide Radicals and Hydrophobic Drugs Directed Toward MRI‐Visible Targeted Delivery
Authors: Nagura Kota , Takemoto Yusa , Moronaga Satori , Uchida Yoshiaki , Shimono Satoshi , Shiino Akihiko , Tanigaki Kenji , Amano Tsukuru , Yoshino Fumi , Noda Yohei , Koizumi Satoshi , Komatsu Naoki , Kato Tatsuhisa , Yamauchi Jun , Tamura Rui
Published: August 2017

With a view to developing a theranostic nanomedicine for targeted drug delivery systems visible by magnetic resonance (MR) imaging, robust metal‐free magnetic nanoemulsions (mean particle size less than 20 nm) consisting of a biocompatible surfactant and hydrophobic, low molecular weight 2,2,5‐trimethyl‐5‐(4‐alkoxy)phenylpyrrolidine‐N‐oxyl radicals were prepared in pH 7.4 phosphate‐buffered saline (PBS). The structure of the nanoemulsions was characterized by electron paramagnetic resonance spectroscopy, and dynamic light scattering and small‐angle neutron‐scattering measurements. The nanoemulsions showed high colloidal stability, low cytotoxicity, enough reduction resistance to excess ascorbic acid, and sufficient contrast enhancement in the proton longitudinal relaxation time (T1) weighted MR images in PBS in vitro (and preliminarily in vivo). Furthermore, the hydrophobic anticancer drug paclitaxel could be encapsulated inside the nanoparticles, and the resulting paclitaxel‐loaded nanoemulsions were efficiently incorporated into HeLa cells to suppress cell growth.
Aruncin B: Synthetic Studies, Structural Reassignment and Biological Evaluation
Authors: Ribaucourt Aubert , Towers Christopher , Josa‐Culleré Laia , Willenbrock Frances , Thompson Amber L. , Hodgson David M.
Published: August 2017

A ring‐closing alkene metathesis (RCM)/ oxyselenation‐selenoxide elimination sequence was established to the sodium salts E‐ and Z‐25 of the originally proposed structure for the recently isolated cytotoxin aruncin B (1), as well as to the sodium salt Z‐34 of a related ethyl ether regioisomer; however, none of their corresponding free acids could be obtained. Their acid sensitivity, together with detailed analysis of the spectroscopic data indicated that profound structural revision was necessary. This led to reassignment of aruncin B as a Z‐γ‐alkylidenebutenolide Z‐36. Although a related RCM/ oxyselenation‐selenoxide elimination sequence was used to confirm the γ‐alkylidenebutenolide motif, a β‐iodo Morita‐Baylis–Hillman reaction/ Sonogashira cross‐coupling‐5‐exo‐dig lactonisation sequence was subsequently developed, due to its brevity and flexibility for diversification. Aruncin B (36), together with 14 γ‐alkylidenebutenolide analogues, were generated for biological evaluation.
One‐Pot Self‐Assembly of Peptide‐Based Cage‐Type Nanostructures Using Orthogonal Ligations
Authors: Bartolami Eline , Knoops Jérémie , Bessin Yannick , Fossépré Mathieu , Chamieh Joseph , Dumy Pascal , Surin Mathieu , Ulrich Sébastien
Published: August 2017

The designed arrangement of biomolecular entities within monodisperse nanostructures is an important challenge toward functional biomaterials. We report herein a method for the formation of water‐soluble peptide‐based cages using orthogonal ligation reactions—acylhydrazone condensation and thiol–maleimide addition. The results show that using preorganized cyclic peptides and heterobifunctional spacers as building blocks and a set of orthogonal and chemoselective ligation reactions enable cage formation in one pot from six components and through eight reactions. Molecular modelling simulations reveal the structural dynamics of these structures. Finally, we exploited the reactional dynamics of the acylhydrazone by demonstrating the controlled dissociation of the cage through directed component exchange.
Photochemical and Electrochemical Triggered Bis(hydrazone) Switch
Authors: Gordillo Mónica A. , Soto‐Monsalve Mónica , Carmona‐Vargas Christian C. , Gutiérrez Gustavo , D'vries Richard F. , Lehn Jean‐Marie , Chaur Manuel N.
Published: August 2017

Herein, we report the synthesis of a double hydrazone capable of undergoing photochemical E/Z isomerization through the imine double bonds. The bis(hydrazone) 1‐E,E can be considered as a “two‐arm” system in which the controlled movement of each arm is obtained by photo‐modulation, making possible the appearance of two isolable metastable isomeric states 1‐E,Z and 1‐Z,Z. Such states are characterized by very specific structural, optical, and electrochemical properties. The latter allows the reversible return from either 1‐E,Z or 1‐Z,Z to the 1‐E,E state. Our results are of great importance in the further development of molecular machines and photochemically controlled reactions by introducing for the first time double hydrazones as tunable photochemical switches.
Multivalency Increases the Binding Strength of RGD Peptidomimetic‐Paclitaxel Conjugates to Integrin αVβ3
Authors: Raposo Moreira Dias André , Pina Arianna , Dal Corso Alberto , Arosio Daniela , Belvisi Laura , Pignataro Luca , Caruso Michele , Gennari Cesare
Published: August 2017

This work reports the synthesis of three multimeric RGD peptidomimetic‐paclitaxel conjugates featuring a number of αVβ3 integrin ligands ranging from 2 to 4. These constructs were assembled by conjugation of the integrin αVβ3 ligand cyclo[DKP‐RGD]‐CH2NH2 with paclitaxel via a 2′‐carbamate with a self‐immolative spacer, the lysosomally cleavable Val‐Ala dipeptide linker, a multimeric scaffold, a triazole linkage, and finally a PEG spacer. Two monomeric conjugates were also synthesized as reference compounds. Remarkably, the new multimeric conjugates showed a binding affinity for the purified integrin αVβ3 receptor that increased with the number of integrin ligands (reaching a minimum IC50 value of 1.2 nm for the trimeric), thus demonstrating that multivalency is an effective strategy to strengthen the ligand–target interactions.
Dinaphthotetrathiafulvalene Bisimides: A New Member of the Family of π‐Extended TTF Stable p‐Type Semiconductors
Authors: Yamashita Masataka , Kawano Koki , Matsumoto Akinobu , Aratani Naoki , Hayashi Hironobu , Suzuki Mitsuharu , Zhang Lei , Briseno Alejandro L. , Yamada Hiroko
Published: August 2017

Invited for the cover of this issue is the group of Hiroko Yamada at Nara Institute of Science and Technology. The image depicts the structure of tetrathiafulvalene, an organic semiconductor, upon a background of Japanese pampas grass on the Soni plateau. Read the full text of the article at 10.1002/chem.201702657.
High‐Energy‐Resolution X‐ray Absorption Spectroscopy for Identification of Reactive Surface Species on Supported Single‐Site Iridium Catalysts
Authors: Hoffman Adam S. , Sokaras Dimosthenis , Zhang Shengjie , Debefve Louise M. , Fang Chia‐Yu , Gallo Alessandro , Kroll Thomas , Dixon David A. , Bare Simon R. , Gates Bruce C.
Published: August 2017

Invited for the cover of this issue are the groups of David A. Dixon at the University of Alabama, Simon R. Bare at Stanford Synchrotron Radiation Lightsource and Bruce C. Gates at the University of California, Davis. The image depicts a visual representation of the key conclusion of the work. Read the full text of the article at 10.1002/chem.201701459.
Inside Cover: Study of Karstedt's Catalyst for Hydrosilylation of a Wide Variety of Functionalized Alkenes with Triethoxysilane and Trimethoxysilane (Chin. J. Chem. 8/2017)
Authors: Pan Zhenhuan , Liu Minglun , Zheng Chaoyue , Gao Deqing , Huang Wei
Published: August 2017

The inside cover picture shows the excellent catalytic performance of Karstedt's catalyst for the hydrosilylation of olefins terminated with various functional groups (amino, alkoxyl, carboxylic, hydroxyl, aldehyde, etc.) with the trimethoxysilane and triethoxysilane reagents in terms of the yield and selectivity. More details are discussed in the article by Gao et al. on page 1227–1230.

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Inside Back Cover: Allosteric Modulation of Human Serum Albumin Induced by Peptide Ligand (Chin. J. Chem. 8/2017)
Authors: Hou Jingfei , Peng Jiaxi , Yu Yue , Lin Yuchen , Liu Changliang , Duan Hongyang , Yang Yanlian , Wang Chen
Published: August 2017

The inside back cover picture shows the allosteric modulation of human serum albumin (HSA) induced by the Peptide SA06 ligand. Peptide SA06 is a reported peptide ligand comprising 20 amino acids, and is known to non‐covalently bind with HSA to extend the lifetime and improve the pharmacokinetic performance of drug molecules. The structural evidence on the allosteric interaction between peptide ligand and HSA, and the structure‐affinity relations of the binding mechanism have been revealed in this work, which can also shed light on optimization of therapeutic properties in the affinity‐controlled delivery systems. More details are discussed in the article by Wang et al. on page 1270–1277.

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Prediction and prognosis of ventricular tachycardia recurrence after catheter ablation with remote magnetic navigation for electrical storm in patients with ischemic cardiomyopathy
Authors: Jin Qi , Jacobsen Peter Karl , Pehrson Steen , Chen Xu
Published: August 2017

Background

Ventricular tachycardia (VT) recurrence after catheter ablation for electrical storm is commonly seen in patients with ischemic cardiomyopathy (ICM).

Hypothesis

We hypothesized that VT recurrence can be predicted and be related to the all‐cause death after VT storm ablation guided by remote magnetic navigation (RMN) in patients with ICM.

Methods

A total of 54 ICM patients (87% male; mean age, 65 ± 7.1 years) presenting with VT storm undergoing acute ablation using RMN were enrolled. Acute complete ablation success was defined as noninducibility of any sustained monomorphic VT at the end of the procedure. Early VT recurrence was defined as the occurrence of sustained VT within 1 month after the first ablation.

Results

After a mean follow‐up of 17.1 months, 27 patients (50%) had freedom from VT recurrence. Sustained VT recurred in 12 patients (22%) within 1 month following the first ablation. In univariate analysis, VT recurrence was associated with incomplete procedural success (hazard ratio [HR]: 6.25, 95% confidence interval [CI]: 1.20‐32.47, P = 0.029), lack of amiodarone usage before ablation (HR: 4.71, 95% CI: 1.12‐19.7, P = 0.034), and a longer procedural time (HR: 1.023, 95% CI: 1.00‐1.05, P = 0.05). The mortality of patients with early VT recurrence was higher than that of patients without recurrence (P < 0.01).

Conclusions

Inducibility of any VT at the end of procedure for VT storm guided by RMN is the strongest predictor of VT recurrence. ICM patients who have early recurrences after VT storm ablation are at high risk of all‐cause death.
A Phase 1 and 2 study of Filanesib alone and in combination with low‐dose dexamethasone in relapsed/refractory multiple myeloma
Authors: Shah Jatin J. , Kaufman Jonathan L. , Zonder Jeffrey A. , Cohen Adam D. , Bensinger William I. , Hilder Brandi W. , Rush Selena A. , Walker Duncan H. , Tunquist Brian J. , Litwiler Kevin S. , Ptaszynski Mieke , Orlowski Robert Z. , Lonial Sagar
Published: August 2017

BACKGROUND

Filanesib (ARRY‐520) is a highly selective inhibitor of kinesin spindle protein, which has demonstrated preclinical antimyeloma activity.

METHODS

This open‐label Phase 1/2 study determined the maximum tolerated dose of Filanesib administered on Days 1 and 2 of 14‐Day Cycles in patients with multiple myeloma (MM) and included expansion cohorts with and without dexamethasone (40 mg/week). Patients in the dose‐escalation (N = 31) and Phase 2 single‐agent (N = 32) cohorts had received prior bortezomib as well as prior thalidomide and/or lenalidomide. Patients in the Phase 2 Filanesib plus dexamethasone cohort (N = 55) had received prior alkylator therapy and had disease refractory to lenalidomide, bortezomib, and dexamethasone. Prophylactic filgrastim was incorporated during dose escalation and was used throughout Phase 2.

RESULTS

Patients in each cohort had received a median of ≥6 prior therapies. The most common dose‐limiting toxicities were febrile neutropenia and mucosal inflammation. In Phase 2, Grade 3 and 4 cytopenias were reported in approximately 50% of patients. Nonhematologic toxicities were infrequent. Phase 2 response rates (partial responses or better) were 16% (single agent) and 15% (Filanesib plus dexamethasone). All responding patients had low baseline levels of α1‐acid glycoprotein, a potential selective biomarker.

CONCLUSIONS

Filanesib 1.50 mg/m2/day administered with prophylactic filgrastim has a manageable safety profile and encouraging activity in heavily pretreated patients This study is registered at www.clinicaltrials.gov as NCT00821249. Cancer 2017;123:4617‐4630. © 2017 American Cancer Society.
Preventable and mitigable adverse events in cancer care: Measuring risk and harm across the continuum
Authors: Lipitz‐Snyderman Allison , Pfister David , Classen David , Atoria Coral L. , Killen Aileen , Epstein Andrew S. , Anderson Christopher , Fortier Elizabeth , Weingart Saul N.
Published: August 2017

BACKGROUND

Patient safety is a critical concern in clinical oncology, but the ability to measure adverse events (AEs) across cancer care is limited by a narrow focus on treatment‐related toxicities. The objective of this study was to assess the nature and extent of AEs among cancer patients across inpatient and outpatient settings.

METHODS

This was a retrospective cohort study of 400 adult patients selected by stratified random sampling who had breast (n = 128), colorectal (n = 136), or lung cancer (n = 136) treated at a comprehensive cancer center in 2012. Candidate AEs, or injuries due to medical care, were identified by trained nurse reviewers over the course of 1 year from medical records and safety‐reporting databases. Physicians determined the AE harm severity and the likelihood of preventability and harm mitigation.

RESULTS

The 400‐patient sample represented 133,358 days of follow‐up. Three hundred four AEs were identified for an overall rate of 2.3 events per 1000 patient days (91.2 per 1000 inpatient days and 0.9 per 1000 outpatient days). Thirty‐four percent of the patients had 1 or more AEs (95% confidence interval, 29%‐39%), and 16% of the patients had 1 or more preventable or mitigable AEs (95% confidence interval, 13%‐20%). The AE rate for patients with breast cancer was lower than the rate for patients with colorectal or lung cancer (P ≤ .001). The preventable or mitigable AE rate was 0.9 per 1000 patient days. Six percent of AEs and 4% of preventable AEs resulted in serious harm. Examples included lymphedema, abscess, and renal failure.

CONCLUSIONS

A heavy burden of AEs, including preventable or mitigable events, has been identified. Future research should examine risk factors and improvement strategies for reducing their burden. Cancer 2017;123:4728‐4736. © 2017 American Cancer Society.
Changes in standardized mortality rates from thyroid cancer in Korea between 1985 and 2015: Analysis of Korean national data
Authors: Choi Yun Mi , Kim Won Gu , Kwon Hyemi , Jeon Min Ji , Han Minkyu , Kim Tae Yong , Shong Young Kee , Hong Sang Mo , Hong Eun‐Gyoung , Kim Won Bae
Published: August 2017

BACKGROUND

The incidence of thyroid cancer has increased very rapidly in Korea; however, most previous studies suggested that the mortality rate for thyroid cancer remained stable. The objective of the current study was to evaluate recent changes in standardized thyroid cancer mortality using data from Statistics Korea.

METHODS

Population and mortality data from 1985 through 2015 were obtained from Statistics Korea. Age‐standardized mortality rates (ASMRs) from thyroid cancer per 100,000 population were calculated based on the World Health Organization standard population.

RESULTS

In Korea, the ASMRs from thyroid cancer increased from 0.17 (95% confidence interval [CI], 0.17‐0.18) per 100,000 in 1985 to 0.85 (95% CI, 0.83‐0.86) per 100,000 in 2004, which was the highest among all countries. Subsequently, the ASMRs continuously decreased to 0.42 (95% CI, 0.41‐0.43) per 100,000 between 2004 and 2015. The estimated annual percent change (APC) from 1985 to 2004 was 7.94 (95% CI, 6.43‐9.46), and the corresponding value from 2004 to 2015 was −4.10 (95% CI, −5.76 to −2.40). Changes in the ASMRs reflected similar patterns in men (1985‐2003: APC, 8.51; 2003‐2015: APC, −4.32) and women (1985‐2004: APC, 7.62; 2004‐2015: APC, −4.38) and were also observed in older patients (aged ≥ 55 years).

CONCLUSIONS

Thyroid cancer mortality in Korea increased until 2004 and then continuously decreased until 2015. Increases in the early diagnosis of thyroid cancer, changes in exposure to risk factors, and standardization in diagnosis and treatment may be associated with the decrease in thyroid cancer mortality in Korea. Cancer 2017; 123:4808‐14. © 2017 American Cancer Society.
Selection of 12‐Hour Sustained‐Release Acetaminophen (Paracetamol) Formulation Through Comparison of Pharmacokinetic Profiles of 4 Sustained‐Release Prototype Formulations and Standard Acetaminophen Formulation: An Open‐Label, Randomized, Proof‐of‐Principle Pharmacokinetic Study
Authors: Yue Yong , Liu Dongzhou J.
Published: August 2017

Acetaminophen (APAP; paracetamol), a widely used analgesic and antipyretic, is available in modified‐release and immediate‐release (IR) formulations requiring 3‐ or 4‐times‐daily dosing. This phase 1 open‐label crossover study compared pharmacokinetic profiles of single 2000‐mg doses of 4 different sustained‐release (SR) formulations of APAP (designed to allow twice‐daily dosing) against two 1000‐mg doses (taken 6 hours apart) of standard IR APAP in 14 healthy volunteers. The primary end point was duration of time that plasma APAP concentration exceeded a plasma concentration (TC) of 4 μg/mL. Of the 4 SR APAP formulations studied, a single 2000‐mg dose of a bilayer SR formulation had the longest mean TC>4μg/mL (8.1 hours), similar to that of 2 doses of IR APAP (8.3 hours). Mean TC>4μg/mL was 7.3 hours with a single‐layer SR APAP, 7.5 hours with another single‐layer SR APAP formulation using a different excipient, and 7.1 hours with an enteric‐coated SR APAP coupled with a fast‐dissolving IR APAP. Secondary pharmacokinetic analyses showed a similar extent of absorption and lower peak concentration for the bilayer SR formulation compared with IR APAP. Adverse events were all mild. Based on these results, the bilayer SR APAP formulation was selected for further development.