bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of Structural Determinants for the Substrate Specificity in the Zinc‐Dependent Alcohol Dehydrogenase CPCR2 from Candida parapsilosis
Authors: Loderer Christoph , Dhoke Gaurao V. , Davari Mehdi D. , Kroutil Wolfgang , Schwaneberg Ulrich , Bocola Marco , Ansorge‐Schumacher Marion B. 
Published: June 2015

AbstractZinc‐dependent alcohol dehydrogenases (ADHs) are a class of enzymes applied in different biocatalytic processes ranging from lab to industrial scale. However, one drawback is the limited substrate range, necessitating a whole array of different ADHs for the relevant substrate classes. In this study, we investigated structural determinants of the substrate spectrum in the zinc‐dependent ADH carbonyl reductase 2 from Candida parapsilosis (CPCR2), combining methods of mutational analysis with in silico substrate docking. Assigned active site residues were genetically randomized, and the resulting mutant libraries were screened with a selection of challenging carbonyl substrates. Three variants (C57A, W116K, and L119M) with improved activities toward different substrates were detected at neighboring positions in the active site. Thus, all possible combinations of the mutations were generated and characterized for their substrate specificity, yielding several improved variants. The most interesting were a C57A variant, with a 27‐fold increase in specific activity for 4′‐acetamidoacetophenone, and the double mutant CPCR2 B16‐(C57A, L119M), with a 45‐fold improvement in the kcat⋅KM−1 value. The obtained variants were further investigated by in silico docking experiments. The results indicate that the mentioned residues are structural determinants of the substrate specificity of CPCR2, being major players in the definition of the active site. Comparison of these results with closely related enzymes suggests that these might even be transferred to other ADHs.
A Light‐Controlled TLR4 Agonist and Selectable Activation of Cell Subpopulations
Authors: Stutts Lalisa , Esser‐Kahn Aaron P. 
Published: June 2015

AbstractThe spatial and temporal aspects of immune cell signaling are key parameters in defining the magnitude of an immune response. Toll‐like receptors (TLRs) on innate immune cells are important in the early detection of pathogens and initiation of an immune response. Controlling the spatial and temporal signaling of TLRs would enable further study of immune synergies and assist in the development of new vaccines. Here, we show a light‐based method for the spatial control of TLR4 signaling. A TLR4 agonist, pyrimido[5,4‐b]indole, was protected with a cage at a position critical for receptor binding. This afforded a photocontrollable agonist that was inactive while caged, yet effected NF‐κB activity in cells following UV photocontrolled deprotection. We demonstrated spatial control of NF‐κB activation within a population of cells by treating all cells with the caged TLR4 agonist and constraining light exposure and consequent activation to a region of interest.
Super‐Resolution Imaging and Quantitative Analysis of Membrane Protein/Lipid Raft Clustering Mediated by Cell‐Surface Self‐Assembly of Hybrid Nanoconjugates
Authors: Hartley Jonathan M. , Chu Te‐Wei , Peterson Eric M. , Zhang Rui , Yang Jiyuan , Harris Joel , Kopeček Jindřich 
Published: June 2015

AbstractSuper‐resolution imaging was used to quantify organizational changes in the plasma membrane after treatment with hybrid nanoconjugates. The nanoconjugates crosslinked CD20 on the surface of malignant B cells, thereby inducing apoptosis. Super‐resolution images were analyzed by using pair‐correlation analysis to determine cluster size and to count the average number of molecules in the clusters. The role of lipid rafts was investigated by pre‐treating cells with a cholesterol chelator and actin destabilizer to prevent lipid raft formation. Lipid raft cluster size correlated with apoptosis induction after treatment with the nanoconjugates. Lipid raft clusters had radii of ∼200 nm in cells treated with the hybrid nanoconjugates. Super‐resolution images provided precise molecule location coordinates that could be used to determine density of bound conjugates, cluster size, and number of molecules per cluster.
Low‐dose niacin supplementation modulates GPR109A, niacin index and ameliorates Parkinson's disease symptoms without side effects
Authors: Wakade Chandramohan , Chong Raymond , Bradley Eric , Morgan John C. 
Published: June 2015

Key Clinical MessageA 65‐year‐old male, Parkinson's disease patient, was evaluated for GPR109A expression, niacin index, UPDRS scale, handwriting test, and quality of sleep with and without niacin treatment. The evaluation was repeated 3 months after niacin was stopped. Niacin modulated the abovementioned parameters and showed the overall improvement without side effects.
Severe fludarabine neurotoxicity after reduced intensity conditioning regimen to allogeneic hematopoietic stem cell transplantation: a case report
Authors: Annaloro Claudio , Costa Antonella , Fracchiolla Nicola S , Mometto Gabriella , Artuso Silvia , Saporiti Giorgia , Tagliaferri Elena , Grifoni Federica , Onida Francesco , Cortelezzi Agostino 
Published: June 2015

Key Clinical MessageWe present a case of severe, irreversible neurotoxicity in a 55‐year‐old‐patient with myelofibrosis undergoing hematopoietic stem cell transplantation following a reduced intensity conditioning including fludarabine. The patient developed progressive sensory‐motor, visual and consciousness disturbances, eventually leading to death. MRI imaging pattern was unique and attributable to fludarabine neurotoxicity.
Divergent Multicomponent Tandem Palladium‐Catalyzed Aminocarbonylation‐Cyclization Approaches to Functionalized Imidazothiazinones and Imidazothiazoles
Authors: Veltri Lucia , Mancuso Raffaella , Altomare Angela , Gabriele Bartolo 
Published: June 2015

AbstractThe reactivity of 2‐(prop‐2‐ynylthio)imidazoles under PdI2/KI‐catalyzed oxidative aminocarbonylation conditions has been studied. Under relatively mild conditions, 0.33–1 mol % of catalyst at 100 °C in MeCN and under 20 atm (at 25 °C) of a 4:1 mixture of CO/air, and in the presence of an equimolar amount of a secondary nucleophilic amine, substrates that are unsubstituted or bear a single substituent on the imidazole ring were converted directly in a multicomponent fashion into functionalized imidazothiazinones. This transformation occurred through a new auto‐tandem catalysis process that involves two concatenated catalytic cycles both catalyzed by PdI2: oxidative aminocarbonylation of the terminal triple bond/cyclocarbonylation. However, in the presence of an excess of secondary amine, 4,5‐disubstituted substrates led selectively to functionalized imidazothiazoles through an oxidative aminocarbonylation/conjugate addition process.
Silver–Cobalt Oxides Derived from Silver Nanoparticles Deposited on Layered Double Hydroxides for Methane Combustion
Authors: Zhao Shen , Li Junhua 
Published: June 2015

AbstractAg nanoparticles (Ag NPs) have been deposited successfully on CoAl‐layered double hydroxide (CoAl‐LDH) layers through a simple and facile self‐redox process to give Ag‐CoAl‐LDHs. Furthermore, the CoAl‐LDHs and the Ag‐CoAl‐LDHs are calcined in air at different temperatures (500, 600, and 700 °C) to give CoAlO‐X and Ag‐CoAlO‐X catalysts for methane combustion (X=500, 600, and 700). The catalytic and characterization results reveal that Ag‐CoAlO‐600 has the highest catalytic activity as it has the highest low‐temperature reducibility and the most abundant surface Co3+ and surface adsorbed oxygen species. In addition, the Ag NP sizes on Ag‐CoAlO and the morphology changes of the CoAlO nanosheet supports affect the catalytic activity of methane combustion.
A Comprehensive Computational Fluid Dynamics Study of Droplet‐Film Impact and Heat Transfer
Authors: Jiang Fan , Wang Yijun , Xiang Jianhua , Liu Zhenzhang 
Published: June 2015

AbstractThe Eulerian multiphase model and continuum surface force (CSF) are employed to simulate the liquid droplet impinging onto a solid wall with a pre‐existing thin film of the same liquid. The numerical results are compared with the experimental data reported in the literature, indicating a reasonable matching. The flow field and splashing behavior of a droplet impinging onto a liquid film are analyzed. The reason for the edge of the crown to eject into secondary drops is found. The splashing behavior can be influenced by the impacting velocity and fluid properties. The effects of impact velocity, droplet diameter, depth of film, liquid property, and droplet and wall temperature on the heat removal are investigated. Numerical results demonstrate that an increase in impact velocity, droplet diameter, film depth, cooling droplet, and wall temperature enhances the dissipated heat. These results can provide a reference for designing spray‐cooling systems.
Power Requirement for Mixing Shear‐Thinning Fluids with a Planetary Mixer
Authors: Auger Frederic , André Christophe , Bouvier Laurent , Redl Andreas , Morel Marie‐Hélène , Delaplace Guillaume 
Published: June 2015

AbstractThe optimal control of processes dealing with non‐Newtonian liquids requires the knowledge and control of the power demand of the mixing equipment. In this context, an extension of the Metzner and Otto concept to planetary mixers is proposed to adapt this concept to planetary mixers. The theoretical part of this work defines modified expressions of Reynolds and power numbers. These definitions introduce a characteristic velocity uch that is used to define the parameter Ks. A planetary mixer is employed to experimentally ascertain this guideline. Power consumption measurements carried out by mixing shear‐thinning fluids permit to determine the Ks factor. This factor varies only slightly with the flow behavior index and may be regarded as a defined constant for this geometry. Finally, experiments with an additional shear‐thickening fluid confirm the validity of this approach.
Kinetic Modeling of Sunflower Oil Methanolysis Catalyzed by Calcium‐Based Catalysts
Authors: Tasić Marija B. , Miladinović Marija R. , Stamenković Olivera S. , Veljković Vlada B. , Skala Dejan U. 
Published: June 2015

AbstractThe kinetic model originally developed for quicklime‐catalyzed methanolysis of sunflower oil was tested for another three calcium‐based catalysts, namely, neat CaO, Ca(OH)2, and CaO·ZnO. This model includes the changing reaction mechanism and the triacylglycerol (TAG) mass transfer. The applicability and generalization capability of this model for heterogeneous methanolysis reaction catalyzed by calcium‐based catalysts was evaluated. As indicated by the high coefficient of determination and the relatively small mean relative percentage deviation, the model was a reliable predictor of the time variation of TAG conversion degree in the sunflower oil methanolysis over all four calcium‐based catalysts within the ranges of the reaction conditions applied. This model is recommended in general for describing the kinetics of sunflower oil methanolysis over calcium‐based catalysts.
One‐Pot Synthesis of Allylic Sulfones, Ketosulfones, and Triflyl Allylic Alcohols from Domino Reactions of Allylic Alcohols with Sulfinic Acid under Metal‐Free Conditions
Authors: Chu Xue‐Qiang , Meng Hua , Xu Xiao‐Ping , Ji Shun‐Jun 
Published: June 2015

AbstractA metal‐free tandem procedure by using a sulfonylation reaction of aryl allylic alcohols followed by an iodobenzenediacetate (PIDA)‐promoted oxidative functionalization has been established. Allylic sulfones, γ‐ketosulfones, and triflyl allylic alcohols have been constructed in a single operation. The methodology incorporates the sulfonyl (both aryl and triflyl) functionality with a simple work‐up procedure.
Pyrrolo‐dC Metal‐Mediated Base Pairs in the Reverse Watson–Crick Double Helix: Enhanced Stability of Parallel DNA and Impact of 6‐Pyridinyl Residues on Fluorescence and Silver‐Ion Binding
Authors: Yang Haozhe , Mei Hui , Seela Frank 
Published: June 2015

AbstractReverse Watson–Crick DNA with parallel‐strand orientation (ps DNA) has been constructed. Pyrrolo‐dC (PyrdC) nucleosides with phenyl and pyridinyl residues linked to the 6 position of the pyrrolo[2,3‐d]pyrimidine base have been incorporated in 12‐ and 25‐mer oligonucleotide duplexes and utilized as silver‐ion binding sites. Thermal‐stability studies on the parallel DNA strands demonstrated extremely strong silver‐ion binding and strongly enhanced duplex stability. Stoichiometric UV and fluorescence titration experiments verified that a single 2pyPyrdC–2pyPyrdC pair captures two silver ions in ps DNA. A structure for the PyrdC silver‐ion base pair that aligns 7‐deazapurine bases head‐to‐tail instead of head‐to‐head, as suggested for canonical DNA, is proposed. The silver DNA double helix represents the first example of a ps DNA structure built up of bidentate and tridentate reverse Watson–Crick base pairs stabilized by a dinuclear silver‐mediated PyrdC pair.
Diversity in Gold‐Catalyzed Formal Cycloadditions of Ynamides with Azidoalkenes or 2H‐Azirines: [3+2] versus [4+3] Cycloadditions
Authors: Pawar Samir Kundlik , Sahani Rajkumar Lalji , Liu Rai‐Shung 
Published: June 2015

AbstractGold‐catalyzed cycloadditions of ynamides with azidoalkenes or 2H‐azirines give [3+2] or [4+3] formal cycloadducts of three classes. Cycloadditions of ynamides with 2H‐azirine species afford pyrrole products with two regioselectivities when the Cβ‐substituted 2H‐azirine is replaced from an alkyl (or hydrogen) with an ester group. For ynamides substituted with an electron‐rich phenyl group, their reactions with azidoalkenes proceed through novel [4+3] cycloadditions to deliver 1H‐benzo[d]azepine products instead.
Cysteine‐Mediated Intracellular Building of Luciferin to Enhance Probe Retention and Fluorescence Turn‐On
Authors: Zheng Mengmeng , Huang Haixiao , Zhou Mi , Wang Yuqi , Zhang Yan , Ye Deju , Chen Hong‐Yuan 
Published: June 2015

AbstractThe development of sensitive and selective small molecular probes that enable real‐time detection of endogenous cysteine (Cys) has become an attractive topic because of the essential roles played by Cys in controlling the cellular nitrogen balance and in maintaining biological redox homeostasis. Herein, we report a Cys‐specific probe, 2‐cyanobenzothiazol‐6‐yl acrylate (CBTOA), that shows not only fluorescence turn‐on for sensitive detection of endogenous Cys but also enhanced probe retention inside cells for real‐time monitoring of Cys levels upon external stimulation. Cys‐mediated intracellular formation of luciferin from CBTOA was the key strategy leading to this new type of fluorogenic probe. CBTOA showed fast response to Cys in living cells and liver tissue slices with high sensitivity and selectivity. By using CBTOA as a real‐time probe, we were able to monitor the change in Cys levels in living HeLa cells under ROS‐induced oxidative stress as well as in human mesenchymal stem cells during adipogenic differentiation.
Conformational Plasticity in Glycomimetics: Fluorocarbamethyl‐L‐idopyranosides Mimic the Intrinsic Dynamic Behaviour of Natural Idose Rings
Authors: Unione Luca , Xu Bixue , Díaz Dolores , Martín‐Santamaría Sonsoles , Poveda Ana , Sardinha João , Rauter Amelia Pilar , Blériot Yves , Zhang Yongmin , Cañada F. Javier , Sollogoub Matthieu , Jiménez‐Barbero Jesus 
Published: June 2015

AbstractSugar function, structure and dynamics are intricately correlated. Ring flexibility is intrinsically related to biological activity; actually plasticity in L‐iduronic rings modulates their interactions with biological receptors. However, the access to the experimental values of the energy barriers and free‐energy difference for conformer interconversion in water solution has been elusive. Here, a new generation of fluorine‐containing glycomimetics is presented. We have applied a combination of organic synthesis, NMR spectroscopy and computational methods to investigate the conformational behaviour of idose‐ and glucose‐like rings. We have used low‐temperature NMR spectroscopic experiments to slow down the conformational exchange of the idose‐like rings. Under these conditions, the exchange rate becomes slow in the 19F NMR spectroscopic chemical shift timescale and allows shedding light on the thermodynamic and kinetic features of the equilibrium. Despite the minimal structural differences between these compounds, a remarkable difference in their dynamic behaviour indeed occurs. The importance of introducing fluorine atoms in these sugars mimics is also highlighted. Only the use of 19F NMR spectroscopic experiments has permitted the unveiling of key features of the conformational equilibrium that would have otherwise remained unobserved.
Dendrimers with Oligospiroketal (OSK) Building Blocks: Synthesis and Properties
Authors: Wessig Pablo , Budach Dennis , Thünemann Andreas F. 
Published: June 2015

AbstractThe development of novel dendrimers containing oligospiroketal (OSK) rods as building blocks is described. The linkage between the core unit (CU), branching units (BU), and OSK rods relies on the CuAAC reaction between terminal alkynes and azides. Two different strategies of dendrimer synthesis were investigated and it was found that the convergent approach is clearly superior to the divergent one. SAXS measurements and MD simulations indicate that the obtained dendrimer features a globular structure with very low density. Obviously, the OSK rods stabilize a rather loose mass‐fractal structure.
Total Synthesis, Stereochemical Revision, and Biological Reassessment of Mandelalide A: Chemical Mimicry of Intrafamily Relationships
Authors: Willwacher Jens , Heggen Berit , Wirtz Conny , Thiel Walter , Fürstner Alois 
Published: June 2015

AbstractMandelalide A and three congeners had recently been isolated as the supposedly highly cytotoxic principles of an ascidian collected off the South African coastline. Since these compounds are hardly available from the natural source, a concise synthesis route was developed, targeting structure 1 as the purported representation of mandelalide A. The sequence involves an iridium‐catalyzed two‐directional Krische allylation and a cobalt‐catalyzed carbonylative epoxide opening as entry points for the preparation of the major building blocks. The final stages feature the first implementation of terminal acetylene metathesis into natural product total synthesis, which is remarkable in that this class of substrates had been beyond the reach of alkyne metathesis for decades. Synthetic 1, however, proved not to be identical with the natural product. In an attempt to clarify this issue, NMR spectra were simulated for 20 conceivable diastereomers by using DFT followed by DP4 analysis; however, this did not provide a reliable assignment either. The puzzle was ultimately solved by the preparation of three diastereomers, of which compound 6 proved identical with mandelalide A in all analytical and spectroscopic regards. As the entire “northern sector” about the tetrahydrofuran ring in 6 shows the opposite configuration of what had originally been assigned, it is highly likely that the stereostructures of the sister compounds mandelalides B–D must be corrected analogously; we propose that these natural products are accurately represented by structures 68–70. In an attempt to prove this reassignment, an entry into mandelalides C and D was sought by subjecting an advanced intermediate of the synthesis of 6 to a largely unprecedented intramolecular Morita–Baylis–Hillman reaction, which furnished the γ‐lactone derivative 74 as a mixture of diastereomers. Whereas (24R)‐74 was amenable to a hydroxyl‐directed dihydroxylation by using OsO4/TMEDA as the reagent, the sister compound (24S)‐74 did not follow a directed path but simply obeyed Kishi’s rule; only this unexpected escape precluded the preparation of mandelalides C and D by this route. A combined spectroscopic and computational (DFT) study showed that the reasons for this strikingly different behavior of the two diastereomers of 74 are rooted in their conformational peculiarities. This aspect apart, our results show that the OsO4/TMEDA complex reacts preferentially with electron deficient double bonds even if other alkenes are present that are more electron rich and less encumbered. Finally, in a brief biological survey authentic mandelalide A (6) was found to exhibit appreciable cytotoxicity only against one out of three tested human cancer cell lines and all synthetic congeners were hardly active. No significant fungicidal properties were observed.
ChemInform Abstract: Nickel‐Rich Layered Lithium Transition‐Metal Oxide for High‐Energy Lithium‐Ion Batteries
Authors: Liu Wen , Oh Pilgun , Liu Xien , Lee Min‐Joon , Cho Woongrae , Chae Sujong , Kim Youngsik , Cho Jaephil 
Published: June 2015

AbstractReview: [structure, cathode material performance enhancement, solid electrolyte interface engineering, safety; 89 refs.
Enhanced Anticancer Cells Effects of Optimized Suspension Stable As2O3‐Loaded Poly(lactic‐co‐glycolic acid) Nanocapsules
Authors: Song Xiaoli , You Juan , Xu Chunlan , Zhu Aiping , Yan Caifeng , Guo Rong 
Published: June 2015

AbstractThis study is to prepare a nanosuspension based on poly(lactic‐co‐glycolic acid) (PLGA) for delivery, controlled release and enhanced anti‐solid tumor effects of As2O3. As2O3‐loaded PLGA nanocapsules (As2O3‐PLGA NCs) were prepared by double emulsion‐solvent evaporation method and were optimized by univariate analysis in combination with orthogonal experimental according to several factors. The optimized As2O3‐PLGA NCs presented suitable physical stability, favorable size of (200.2±10.6) nm (PDI=0.117±0.008), spherical shape, and high encapsulation efficiency (92.48%±2.14%). The in vitro suspension stability of the NCs was excellent. The release of As2O3 from the NCs showed pH responsive release characteristics. The NCs can be efficiently taken up by SMMC‐7721 cell and showed excellent antitumor efficacy against SMMC‐7721 cell line. Then, As2O3‐PLGA NCs could be considered as a promising formulation for the pH dependent release of As2O3 in cancer cells and enhance the anti‐solid tumor effects of As2O3.
A Silole‐Based Efficient Electroluminescent Material with Good Electron‐Transporting Potential
Authors: Quan Changyun , Nie Han , Hu Rongrong , Qin Anjun , Zhao Zujin , Tang Ben Zhong 
Published: June 2015

AbstractA new silole derivative, 2,5‐bis(7‐(dimesitylboranyl)‐9,9‐dimethylfluoren‐2‐yl)‐1‐methyl‐1,3,4‐triphenylsilole ((MesBF)2MTPS), is synthesized and characterized. (MesBF)2MTPS shows a good fluorescence efficiency of 15% in THF solution and a higher efficiency of 86% in solid film, presenting an aggregation‐enhanced emission characteristic. It is thermally and morphologically stable, with high decomposition and glass‐transition temperatures of 257 and 171°C, respectively. The LUMO energy level (−2.96 eV) of (MesBF)2MTPS is lower than that of TPBi, revealing its electron‐transporting potential. Efficient organic light‐emitting diodes (OLEDs) are fabricated using (MesBF)2MTPS as emitter, which radiates yellow light at 554 nm, and affords high maximum luminance, current efficiency, and external quantum efficiency of 48348 cd·m−2, 12.3 cd·A−1, and 4.1%, respectively.