bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous confidence intervals for comparing biodiversity indices estimated from overdispersed count data
Authors: Scherer Ralph , Schaarschmidt Frank , Prescher Sabine , Priesnitz Kai U.
Published: February 2013

Diversity indices might be used to assess the impact of treatments on the relative abundance patterns in species communities. When several treatments are to be compared, simultaneous confidence intervals for the differences of diversity indices between treatments may be used. The simultaneous confidence interval methods described until now are either constructed or validated under the assumption of the multinomial distribution for the abundance counts. Motivated by four example data sets with background in agricultural and marine ecology, we focus on the situation when available replications show that the count data exhibit extra‐multinomial variability. Based on simulated overdispersed count data, we compare previously proposed methods assuming multinomial distribution, a method assuming normal distribution for the replicated observations of the diversity indices and three different bootstrap methods to construct simultaneous confidence intervals for multiple differences of Simpson and Shannon diversity indices. The focus of the simulation study is on comparisons to a control group. The severe failure of asymptotic multinomial methods in overdispersed settings is illustrated. Among the bootstrap methods, the widely known Westfall–Young method performs best for the Simpson index, while for the Shannon index, two methods based on stratified bootstrap and summed count data are preferable. The methods application is illustrated for an example.
Insights into the Roles of Desolvation and π‐Electron Interactions during DNA Polymerization
Authors: Motea Edward A. , Lee Irene , Berdis Anthony J.
Published: February 2013

This report describes the use of several isosteric non‐natural nucleotides as probes to evaluate the roles of nucleobase shape, size, solvation energies, and π‐electron interactions as forces influencing key kinetic steps of the DNA polymerization cycle. Results are provided using representative high‐ and low‐fidelity DNA polymerases. Results generated with the E. coli Klenow fragment reveal that this high‐fidelity polymerase utilizes hydrophobic nucleotide analogues with higher catalytic efficiencies compared to hydrophilic analogues. These data support a major role for nucleobase desolvation during nucleotide selection and insertion. In contrast, the low‐fidelity HIV‐1 reverse transcriptase discriminates against hydrophobic analogues and only tolerates non‐natural nucleotides that are capable of hydrogen‐bonding or π‐stacking interactions. Surprisingly, hydrophobic analogues that function as efficient substrates for the E. coli Klenow fragment behave as noncompetitive or uncompetitive inhibitors against HIV‐1 reverse transcriptase. In these cases, the mode of inhibition depends upon the absence or presence of a templating nucleobase. Molecular modeling studies suggest that these analogues bind to the active site of reverse transcriptase as well as to a nearby hydrophobic binding pocket. Collectively, the studies using these non‐natural nucleotides reveal important mechanistic differences between representative high‐ and low‐fidelity DNA polymerases during nucleotide selection and incorporation.
Are β‐H‐Eliminations or Alkene Insertions Feasible Elementary Steps in Catalytic Cycles Involving Gold(I) Alkyl Species or Gold(I) Hydrides?
Authors: Klatt Günter , Xu Rong , Pernpointner Markus , Molinari Lise , Quang Hung Tran , Rominger Frank , Hashmi A. Stephen K. , Köppel Horst
Published: February 2013

The β‐H‐elimination in the (IPr)AuEt complex and its microscopic reverse, the insertion of ethene into (IPr)AuH, were investigated in a combined experimental and computational study. Our DFT‐D3 calculations predict free‐energy barriers of 49.7 and 36.4 kcal mol−1 for the elimination and insertion process, respectively, which permit an estimation of the rate constants for these reactions according to classical transition‐state theory. The elimination/insertion pathway is found to involve a high‐energy ethene hydride species and is not significantly affected by continuum solvent effects. The high barriers found in the theoretical study were then confirmed experimentally by measuring decomposition temperatures for several different (IPr)AuI‐alkyl complexes which, with a slow decomposition at 180 °C, are significantly higher than those of other transition‐metal alkyl complexes. In addition, at the same temperature, the decomposition of (IPr)AuPh and (IPr)AuMe, both of which cannot undergo β‐H‐elimination, indicates that the pathway for the observed decomposition at 180 °C is not a β‐H‐elimination. According to the calculations, the latter should not occur at temperatures below 200 °C. The microscopic reverse of the β‐H‐elimination, the insertion of ethene into the (IPr)AuH could neither be observed at pressures up to 8 bar at RT nor at 1 bar at 80 °C. The same is true for the strain‐activated norbornene.
Speciation of [Cp*2M2O5] in Polar and Donor Solvents
Authors: Sözen‐Aktaş Pelin , Del Rosal Iker , Manoury Eric , Demirhan Funda , Lledós Agustí , Poli Rinaldo
Published: February 2013

The speciation of compounds [Cp*2M2O5] (M=Mo, W; Cp*=pentamethylcyclopentadienyl) in different protic and aprotic polar solvents (methanol, dimethyl sulfoxide, acetone, acetonitrile), in the presence of variable amounts of water or acid/base, has been investigated by 1H NMR spectrometry and electrical conductivity. Specific hypotheses suggested by the experimental results have been further probed by DFT calculations. The solvent (S)‐assisted ionic dissociation to generate [Cp*MO2(S)]+ and [Cp*MO3]− takes place extensively for both metals only in water/methanol mixtures. Equilibrium amounts of the neutral hydroxido species [Cp*MO2(OH)] are generated in the presence of water, with the relative amount increasing in the order MeCN≈acetone<MeOH<DMSO. Addition of a base (Et3N) converts [Cp*2M2O5] into [Et3NH]+[Cp*MO3]−, for which the presence of a NH⋅⋅⋅OM interaction is revealed by 1H NMR spectroscopy in comparison with the sodium salts, Na+[Cp*MO3]−. These are fully dissociated in DMSO and MeOH, but display a slow equilibrium between free ions and the ion pair in MeCN and acetone. Only one resonance is observed for mixtures of [Cp*MO3]− and [Cp*MO2(OH)] because of a rapid self‐exchange. In the presence of extensive ionic dissociation, only one resonance is observed for mixtures of the cationic [Cp*MO2(S)]+ product and the residual undissociated [Cp*2M2O5] because of a rapid associative exchange via the trinuclear [Cp*3M3O7]+ intermediate. In neat methanol, complex [Cp*2W2O5] reacts to yield extensive amounts of a new species, formulated as the mononuclear methoxido complex [Cp*WO2(OMe)] on the basis of the DFT study. An equivalent product is not observed for the Mo system. The addition of increasing amounts of water results in the rapid decrease of this product in favor of [Cp*2W2O5] and [Cp*WO2(OH)].
Azatrioxa[8]circulenes: Planar Anti‐Aromatic Cyclooctatetraenes
Authors: Nielsen Christian B. , Brock‐Nannestad Theis , Hammershøj Peter , Reenberg Theis K. , Schau‐Magnussen Magnus , Trpcevski Denis , Hensel Thomas , Salcedo Roberto , Baryshnikov Gleb V. , Minaev Boris F. , Pittelkow Michael
Published: February 2013

We describe herein the first synthesis of a new class of anti‐aromatic planar cyclooctatetraenes: the azatrioxa[8]circulenes. This was achieved by treating a suitably functionalised 3,6‐dihydroxycarbazole with 1,4‐benzoquinones or a 1,4‐naphthoquinone. We fully characterised the azatrioxa[8]circulenes by using optical, electrochemical and computational techniques as well as by single‐crystal X‐ray crystallography. The results of a computational study (NICS) suggest that the central planar cyclooctatetraene is anti‐aromatic when the molecules are in neutral or oxidised states (2+), and that the corresponding dianions are aromatic. We discuss the aromatic/anti‐aromatic nature of the planar cyclooctatetraenes and compare them with the isoelectronic tetraoxa[8]circulenes.
E/Z Oxime Isomerism in PhC(NOH)CN
Authors: Bohle D. Scott , Chua Zhijie , Perepichka Inna , Rosadiuk Kristopher
Published: February 2013

The reaction of nitric oxide with benzyl cyanide in the presence of potassium methoxide at low temperature gave the dipotassium salt of a bis‐diazeniumdiolate 2 in excellent yield. Two new stereospecific syntheses of E or Z 2‐(hydroxyimino)‐2‐phenylacetonitrile from 2 have been found. The thermodynamics of the E/Z isomerization has been investigated spectroscopically in solution, in the solid state by differential scanning calorimetry (DSC), and theoretically in the gas phase. Evidence of catalysis by NO of E/Z oxime isomerization has been observed.
Using Calixarenes To Model Polyelectrolyte Surfactant Nucleation Sites
Authors: Basilio Nuno , Gómez Borja , Garcia‐Rio Luis , Francisco Vitor
Published: February 2013

The formation of mixed micelles composed of dodecyltrimethylammonium bromide (C12TAB) and a hexamethylated p‐sulfonatocalix[6]arene (SC6HM) was studied by several techniques. It was found that above the critical aggregation concentration the concentrations of free and micellized surfactant are strongly related to that of SC6HM. When there is free SC6HM in solution, the addition of C12TAB mainly results in an increase in the concentration of micellized surfactant, but when all SC6HM has been aggregated, the addition of C12TAB results in a substantial increase in the concentration of free surfactant in solution. When the concentration of free surfactant is equal to the critical micelle concentration of the pure system, a second independent aggregation process is observed. This aggregation behavior has many features that are similar to those of more complex systems that involve surfactants in the presence of oppositely charged polyelectrolytes. In this way, calixarenes can serve as simple models to mimic polyelectrolytes and to gain insight into the complex behavior displayed by these macromolecules.
Synthesis of the Carbon Framework of Scholarisine A by Intramolecular Oxidative Coupling
Authors: Watanabe Tsugunori , Umezawa Naoki , Kato Nobuki , Higuchi Tsunehiko
Published: February 2013

Scholarisine A, isolated from the leaves of Alstonia scholaris, is a monoterpene indole alkaloid with an unprecedented cage‐like structure. In this paper, preparation of the distinctive cage‐like core skeleton of scholarisine A is described. The key feature of this synthetic strategy is an intramolecular oxidative coupling reaction at the late stage to construct a 10‐oxa‐tricyclo[5.3.1.03, 8]undecan‐9‐one structure fused with indolenine. Intramolecular oxidative coupling by using N‐iodosuccinimide gave the carbon framework of scholarisine A in moderate yield, which is the first example of intramolecular oxidative‐coupling reaction between non‐activated enolate and indole. This study lays the foundation for continued investigations towards the total synthesis of scholarisine A.
Diels–Alder and Retro‐Diels–Alder Cycloadditions of (1,2,3,4,5‐Pentamethyl)cyclopentadiene to La@C2v‐C82: Regioselectivity and Product Stability
Authors: Garcia‐Borràs Marc , Luis Josep M. , Swart Marcel , Solà Miquel
Published: February 2013

One of the most important reactions in fullerene chemistry is the Diels–Alder (DA) reaction. In two previous experimental studies, the DA cycloaddition reactions of cyclopentadiene (Cp) and 1,2,3,4,5‐pentamethylcyclopentadiene (Cp*) with La@C2v‐C82 were investigated. The attack of Cp was proposed to occur on bond 19, whereas that of Cp* was confirmed by X‐ray analysis to be over bond o. Moreover, the stabilities of the Cp and Cp* adducts were found to be significantly different, that is, the decomposition of La@C2v‐C82Cp was one order of magnitude faster than that of La@C2v‐C82Cp*. Herein, we computationally analyze these DA cycloadditions with two main goals: First, to compute the thermodynamics and kinetics of the cycloadditions of Cp and Cp* to different bonds of La@C2v‐C82 to assess and compare the regioselectivity of these two reactions. Second, to understand the origin of the different thermal stabilities of the La@C82Cp and La@C82Cp* adducts. Our results show that the regioselectivity of the two DA cycloadditions is the same, with preferred attack on bond o. This result corrects the previous assumption of the regioselectivity of the Cp attack that was made based only on the shape of the La@C82 singly occupied molecular orbital. In addition, we show that the higher stability of the La@C82Cp* adduct is not due to the electronic effects of the methyl groups on the Cp ring, as previously suggested, but to higher long‐range dispersion interactions in the Cp* case, which enhance the stabilization of the reactant complex, transition state, and products with respect to the separated reactants. This stabilization for the La@C82Cp* case decreases the Gibbs reaction energy, thus allowing competition between the direct and retro reactions and making dissociation more difficult.
Microwave‐Assisted Solid‐Phase Synthesis of Antifreeze Glycopeptides
Authors: Izumi Ryukou , Matsushita Takahiko , Fujitani Naoki , Naruchi Kentaro , Shimizu Hiroki , Tsuda Sakae , Hinou Hiroshi , Nishimura Shin‐Ichiro
Published: February 2013

Microwave‐assisted solid‐phase synthesis allows for the rapid and large‐scale preparation and structure–activity characterization of tandem repeating glycopeptides, namely monodispersed synthetic antifreeze glycopeptides (syAFGPs, H‐[Ala‐Thr(Galβ1,3GalNAcα1→)‐Ala]n‐OH, n=2–6). By employing novel AFGP analogues, we have demonstrated that of the monodispersed syAFGPn (n=2–6, degree of polymerization, DP=2–6, Mw=1257–3690 Da), syAFGP5 (DP=5, Mw=3082 Da) and syAFGP6 (DP=6, Mw=3690 Da) exhibit the ability to form typical hexagonal bipyramidal ice crystals and satisfactory thermal hysteresis activity. Structural characterization by NMR and CD spectroscopy revealed that syAFGP6 forms a typical poly‐L‐proline type II helix‐like structure in aqueous solution whereas enzymatic modification by sialic acid of the residues at the C‐3 positions of the nonreducing Gal residues disturbs this conformation and eliminates the antifreeze activity.
Proton‐Assisted Hydrogen Activation on Polyhedral Cations
Authors: Calvo Beatriz , Macías Ramón , Artigas Maria Jose , Lahoz Fernando J. , Oro Luis A.
Published: February 2013

The treatment of [1,1‐(PR3)2‐3‐(Py)‐closo‐1,2‐RhSB9H8] (PR3=PMe3 (2) or PPh3 and PMe3 (3); Py=pyridine) with triflic acid (TfOH) affords [1,3‐μ‐(H)‐1,1‐(PR3)2‐3‐(Py)‐1,2‐RhSB9H8]+ (PR3=PMe3 (4) or PMe3 and PPh3 (5)). These products result from the protonation of the 11‐vertex closo‐cages along the Rh(1)B(3) edge. These unusual cationic rhodathiaboranes are stable in solution and in the solid state and they have been fully characterized by multinuclear NMR spectroscopy. In addition, compound 5 was characterized by single‐crystal X‐ray diffraction. One remarkable feature in these structures is the presence of three {Rh(PPh3)(PMe3)}‐to‐{ηn‐SB9H8(Py)} (n=4 or 5) conformers in the unit cell, thus giving an uncommon case of conformational isomerism. [1,1‐(PPh3)2‐3‐(Py)‐closo‐1,2‐RhSB9H8] (1), that is, the bis‐PPh3‐ligated analogue of compounds 2 and 3, is also protonated by TfOH, but, in marked contrast, the resulting cation, [1,3‐μ‐(H)‐1,1‐(PPh3)2‐3‐(Py)‐1,2‐RhSB9H8]+ (6), is attacked by a triflate anion with the release of a PPh3 ligand and the formation of [8,8‐(OTf)(PPh3)‐9‐(Py)‐nido‐8,7‐RhSB9H9] (9). The result is an equilibrium that involves cationic species 6, neutral OTf‐ligated compound 9, and [HPPh3]+, which is formed upon protonation of the released PPh3 ligand. The resulting ionic system reacts readily with H2 to give cationic species [8,8,8‐(H)(PPh3)2‐9‐(Py)‐nido‐8,7‐RhSB9H9]+ (7). This reactivity is markedly higher than that previously found for compound 1 and it introduces a new example of proton‐assisted H2 activation that occurs on a polyhedral boron‐containing compound.
Chiral Fluorinated α‐Sulfonyl Carbanions: Enantioselective Synthesis and Electrophilic Capture, Racemization Dynamics, and Structure
Authors: Hellmann Gunther , Hack Achim , Thiemermann Eric , Luche Olaf , Raabe Gerhard , Gais Hans‐Joachim
Published: February 2013

Enantiomerically pure triflones R1CH(R2)SO2CF3 have been synthesized starting from the corresponding chiral alcohols via thiols and trifluoromethylsulfanes. Key steps of the syntheses of the sulfanes are the photochemical trifluoromethylation of the thiols with CF3Hal (Hal=halide) or substitution of alkoxyphosphinediamines with CF3SSCF3. The deprotonation of RCH(Me)SO2CF3 (R=CH2Ph, iHex) with nBuLi with the formation of salts [RC(Me)SO2CF3]Li and their electrophilic capture both occurred with high enantioselectivities. Displacement of the SO2CF3 group of (S)‐MeOCH2C(Me)(CH2Ph)SO2CF3 (95 % ee) by an ethyl group through the reaction with AlEt3 gave alkane MeOCH2C(Me)(CH2Ph)Et of 96 % ee. Racemization of salts [R1C(R2)SO2CF3]Li follows first‐order kinetics and is mainly an enthalpic process with small negative activation entropy as revealed by polarimetry and dynamic NMR (DNMR) spectroscopy. This is in accordance with a CαS bond rotation as the rate‐determining step. Lithium α‐(S)‐trifluoromethyl‐ and α‐(S)‐nonafluorobutylsulfonyl carbanion salts have a much higher racemization barrier than the corresponding α‐(S)‐tert‐butylsulfonyl carbanion salts. Whereas [PhCH2C(Me)SO2tBu]Li/DMPU (DMPU = dimethylpropylurea) has a half‐life of racemization at −105 °C of 2.4 h, that of [PhCH2C(Me)SO2CF3]Li at −78 °C is 30 d. DNMR spectroscopy of amides (PhCH2)2NSO2CF3 and (PhCH2)N(Ph)SO2CF3 gave NS rotational barriers that seem to be distinctly higher than those of nonfluorinated sulfonamides. NMR spectroscopy of [PhCH2C(Ph)SO2R]M (M=Li, K, NBu4; R=CF3, tBu) shows for both salts a confinement of the negative charge mainly to the Cα atom and a significant benzylic stabilization that is weaker in the trifluoromethylsulfonyl carbanion. According to crystal structure analyses, the carbanions of salts {[PhCH2C(Ph)SO2CF3]Li⋅L}2 (L=2 THF, tetramethylethylenediamine (TMEDA)) and [PhCH2C(Ph)SO2CF3]NBu4 have the typical chiral CαS conformation of α‐sulfonyl carbanions, planar Cα atoms, and short CαS bonds. Ab initio calculations of [MeC(Ph)SO2tBu]− and [MeC(Ph)SO2CF3]− showed for the fluorinated carbanion stronger nC→σ* and nO→σ* interactions and a weaker benzylic stabilization. According to natural bond orbital (NBO) calculations of [R1C(R2)SO2R]− (R=tBu, CF3) the nC→σ*SR interaction is much stronger for R=CF3. Ab initio calculations gave for [MeC(Ph)SO2tBu]Li⋅2 Me2O an O,Li,Cα contact ion pair (CIP) and for [MeC(Ph)SO2CF3]Li⋅2 Me2O an O,Li,O CIP. According to cryoscopy, [PhCH2C(Ph)SO2CF3]Li, [iHexC(Me)SO2CF3]Li, and [PhCH2C(Ph)SO2CF3]NBu4 predominantly form monomers in tetrahydrofuran (THF) at −108 °C. The NMR spectroscopic data of salts [R1(R2)SO2R3]Li (R3=tBu, CF3) indicate that the dominating monomeric CIPs are devoid of CαLi bonds.
Preparation of Stereodefined Secondary Alkyllithium Compounds
Authors: Seel Stephanie , Dagousset Guillaume , Thaler Tobias , Frischmuth Annette , Karaghiosoff Konstantin , Zipse Hendrik , Knochel Paul
Published: February 2013

We have developed a practical stereoretentive iodine/lithium‐exchange process that allows the stereodefined preparation of cis‐ and trans‐cycloalkyllithium compounds from their corresponding stereodefined iodides. Quenching with electrophiles offers stereospecific access to both cis‐ (up to 96 % cis) and trans‐cycloalkyl derivatives (up to 99 % trans). A detailed study of the thermodynamic stabilities, stereochemical behavior, and reactivities of axially and equatorially substituted cyclohexyllithium reagents is reported. Ab initio calculations demonstrate that the formation of oligomeric cyclohexyllithium structures is pivotal for explaining the observed stereochemical preference.
Evidence for Kinetic Nucleation in Helical Nanofiber Formation Directed by Chiral Solvent for a Perylene Bisimide Organogelator
Authors: Stepanenko Vladimir , Li Xue‐Qing , Gershberg Jana , Würthner Frank
Published: February 2013

The self‐assembly behavior of an achiral perylene bisimide (PBI) organogelator that bears two 3,4,5‐tridodecyloxybenzoylaminoethyl substituents at the imide positions has been investigated in chiral solvents (R)‐ and (S)‐limonene in great detail by circular dichroism (CD) spectroscopy and atomic force microscopy (AFM). CD spectroscopic studies on dilute solutions revealed a preferential population of one‐handed helical assemblies in chiral solvent with an enantiomeric excess close to 100 %, whereas AFM images of more than 100 nanofibers of the organogel obtained from more concentrated solutions were found to consist of both handed helices with an enantiomeric excess of only 20 %. This discrepancy is attributed to the fast gelation process at high dye concentration that evidently proceeds through non‐equilibrated nuclei in a kinetic rather than thermodynamic self‐assembly process. Under these conditions the chiral induction from the homochiral solvent may not be adequate in effectively populating only one‐handed helices.
Copper‐Catalyzed Aerobic Oxidative CH and CC Functionalization of 1‐[2‐(Arylamino)aryl]ethanones Leading to Acridone Derivatives
Authors: Yu Jipan , Yang Haijun , Jiang Yuyang , Fu Hua
Published: February 2013

Efficient copper‐catalyzed aerobic oxidative CH and CC functionalization of 1‐[2‐(arylamino)aryl]ethanones leading to acridones has been developed. The procedure involves cleavage of aromatic CH and acetyl CC bonds with intramolecular formation of a diarylketone bond. The protocol uses inexpensive Cu(O2CCF3)2 as catalyst, pyridine as additive, and economical and environmentally friendly oxygen as the oxidant, and the corresponding acridones with various functional groups were obtained in moderate to good yields.
Fast Reductive Amination by Transfer Hydrogenation “on Water”
Authors: Lei Qian , Wei Yawen , Talwar Dinesh , Wang Chao , Xue Dong , Xiao Jianliang
Published: February 2013

Reductive amination of various ketones and aldehydes by transfer hydrogenation under aqueous conditions has been developed, by using cyclometallated iridium complexes as catalysts and formate as hydrogen source. The pH value of the solution is shown to be critical for a high catalytic chemoselectivity and activity, with the best pH value being 4.8. In comparison with that in organic solvents, the reductive amination in an aqueous phase is faster, and the molar ratio of the substrate to the catalyst (S/C) can be set as high as 1×105, the highest S/C value ever reported in reductive amination reactions. The catalyst is easy to access and the reaction is operationally simple, allowing a wide range of ketones and aldehydes to react with various amines in high yields. The protocol provides a practical and environmental friendly new method for the synthesis of amine compounds.
Effect of Pumice and Sand on the Sustainability of Granular Iron Beds for the Aqueous Removal of CuII, NiII, and ZnII
Authors: Bilardi Stefania , Calabrò Paolo S. , Caré Sabine , Moraci Nicola , Noubactep Chicgoua
Published: February 2013

Current knowledge of the basic principles underlying the design of Fe0 beds is weak. The volumetric expansive nature of iron corrosion was identified as the major factor determining the sustainability of Fe0 beds. This work attempts to systematically verify developed concepts. Pumice and sand were admixed to 200 g of Fe0 in column studies (50:50 volumetric proportion). Reference systems containing 100% of each material have been also investigated. The mean grain size of the used materials (in mm) were 0.28 (sand), 0.30 (pumice), and 0.50 (Fe0). The five studied systems were characterized (i) by the time dependent evolution of their hydraulic conductivity (permeability) and (ii) for their efficiency for aqueous removal of CuII, NiII, and ZnII (about 0.3 mM of each). Results showed unequivocally that (i) quantitative contaminant removal was coupled to the presence of Fe0, (ii) additive admixture lengthened the service life of Fe0 beds, and (iii) pumice was the best admixing agent for sustaining permeability while the Fe0/sand column was the most efficient for contaminant removal. The evolution of the permeability was well‐fitted by the approach that the inflowing solution contained dissolved O2. The achieved results are regarded as starting point for a systematic research to optimize/support Fe0 filter design.
Monitoring Binding of HIV‐1 Capsid Assembly Inhibitors Using 19F Ligand‐and 15N Protein‐Based NMR and X‐ray Crystallography: Early Hit Validation of a Benzodiazepine Series
Authors: Goudreau Nathalie , Coulombe René , Faucher Anne‐Marie , Grand‐Maître Chantal , Lacoste Jean‐Eric , Lemke Christopher T. , Malenfant Eric , Bousquet Yves , Fader Lee , Simoneau Bruno , Mercier Jean‐François , Titolo Steve , Mason Stephen W.
Published: February 2013

The emergence of resistance to existing classes of antiretroviral drugs underlines the need to find novel human immunodeficiency virus (HIV)‐1 targets for drug discovery. The viral capsid protein (CA) represents one such potential target. Recently, a series of benzodiazepine inhibitors was identified via high‐throughput screening using an in vitro capsid assembly assay (CAA). Here, we demonstrate how a combination of NMR and X‐ray co‐crystallography allowed for the rapid characterization of the early hits from this inhibitor series. Ligand‐based 19F NMR was used to confirm inhibitor binding specificity and reversibility as well as to identify the N‐terminal domain of the capsid (CANTD) as its molecular target. Protein‐based NMR (1H and 15N chemical shift perturbation analysis) identified key residues within the CANTD involved in inhibitor binding, while X‐ray co‐crystallography confirmed the inhibitor binding site and its binding mode. Based on these results, two conformationally restricted cyclic inhibitors were designed to further validate the possible binding modes. These studies were crucial to early hit confirmation and subsequent lead optimization.
Experimental and Theoretical Study of the n‐Doped Successive Polyanions of Oligocruciform Molecular Wires: Up to Five Units of Charge
Authors: Al Ouahabi Abdelaziz , Baxter Paul , Mathis Claude , Bernard Maxime , Vileno Bertrand , Gisselbrecht Jean‐Paul , Turek Philippe , Mouesca Jean‐Marie , Choua Sylvie
Published: February 2013

The electronic structure of polyanions of sterically encumbered triisopropylsilyl‐substituted linear and cyclic oligo(phenyleneethynylene)s (Monomer, Trimer, Pentamer, and Triangle) is investigated by electron paramagnetic resonance (EPR), electron nuclear double resonance (ENDOR), and UV/Vis–near‐infrared (NIR) spectroscopies, cyclic voltammetry, and theoretical calculations (DFT). Increasing anion orders are generated sequentially in vacuo at room temperature by chemical reaction with potassium metal up to the pentaanion. The relevance of these compounds acting as electron reservoirs is thus demonstrated. Even‐order anions are EPR silent, whereas the odd species exhibit different signatures, which are identified after comparison of the measured hyperfine couplings by ENDOR spectroscopy with those predicted by DFT calculations. With increasing size of the oligomers the electron spin density is first distributed over the backbone carbon atoms for the monoanions, and then further localized at the outer phenyl rings for the trianion species. Examination of the UV/Vis‐NIR spectra indicates that the monoanions (T.−, P.−) exhibit two transitions in the Vis‐NIR region, whereas a strong absorption in the IR region is solely observed for higher reduced states. Electronic transitions of the neutral monoanions and trianions are redshifted with increasing oligomer size, whereas for a given oligomer a blueshift is observed upon increasing the charge, which suggests a localization of the spin density.
Competitive Bond Rupture in the Photodissociation of Bromoacetyl Chloride and 2‐ and 3‐Bromopropionyl Chloride: Adiabatic versus Diabatic Dissociation
Authors: Hsu Ming‐Yi , Tsai Po‐Yu , Wei Zheng‐Rong , Chao Meng‐Hsuan , Zhang Bing , Kasai Toshio , Lin King‐Chuen
Published: February 2013

Competitive bond dissociation mechanisms for bromoacetyl chloride and 2‐ and 3‐bromopropionyl chloride following the 1[n(O)→π*(CO)] transition at 234–235 nm are investigated. Branching ratios for CBr/CCl bond fission are found by using the (2+1) resonance‐enhanced multiphoton ionization (REMPI) technique coupled with velocity ion imaging. The fragment branching ratios depend mainly on the dissociation pathways and the distances between the orbitals of Br and the CO chromophore. CCl bond fission is anticipated to follow an adiabatic potential surface for a strong diabatic coupling between the n(O)π*(CO) and np(Cl)σ*(CCl) bands. In contrast, CBr bond fission is subject to much weaker coupling between n(O)π*(CO) and np(Br)σ*(CBr). Thus, a diabatic pathway is preferred for bromoacetyl chloride and 2‐bromopropionyl chloride, which leads to excited‐state products. For 3‐bromopropionyl chloride, the available energy is not high enough to reach the excited‐state products such that CBr bond fission must proceed through an adiabatic pathway with severe suppression by nonadiabatic coupling. The fragment translational energies and anisotropy parameters for the three molecules are also analyzed and appropriately interpreted.
Triarylamine‐Substituted Imidazole‐ and Quinoxaline‐Fused Push–Pull Porphyrins for Dye‐Sensitized Solar Cells
Authors: Hayashi Hironobu , Touchy Abeda Sultana , Kinjo Yuriko , Kurotobi Kei , Toude Yuuki , Ito Seigo , Saarenpää Hanna , Tkachenko Nikolai V. , Lemmetyinen Helge , Imahori Hiroshi
Published: February 2013

We have prepared a push–pull porphyrin with an electron‐donating triarylamino group at the β,β′‐edge through a fused imidazole group and an electron‐withdrawing carboxyquinoxalino anchoring group at the opposite β,β′‐edge (ZnPQI) and evaluated the effects of the push–pull structure of ZnPQI on optical, electrochemical, and photovoltaic properties. ZnPQI showed red‐shifted Soret and Q bands relative to a reference porphyrin with only an electron‐withdrawing group (ZnPQ), thus demonstrating the improved light‐harvesting property of ZnPQI. The optical HOMO–LUMO gap was consistent with that estimated by DFT calculations. The ZnPQI‐sensitized solar cell exhibited a relatively high power conversion efficiency (η) of 6.8 %, which is larger than that of the ZnPQ‐sensitized solar cell (η=6.3 %) under optimized conditions. The short‐circuit current and fill factor of the ZnPQI‐sensitized solar cell are larger than those of the ZnPQ‐sensitized solar cell, whereas the open circuit potential of the ZnPQI‐sensitized cell is smaller than that of the ZnPQ‐sensitized cell, leading to an overall improved cell performance of ZnPQI. Such fundamental information provides a new tool for the rational molecular design of highly efficient dye‐sensitized solar cells based on push–pull porphyrins.
Ilexgenin A Obtained from Ilex hainanensis Merr. Improves Diet‐Induced Non‐Alcoholic Fatty Liver Disease in Rats
Authors: Cui Wei‐xi , Li Jing‐Jing , Chen Xiao‐qing , Mao Qian , Wei Xiang‐lan , Wen Xiao‐dong , Yang Jie , Wang Qiang
Published: February 2013

Preclinical Research

Nonalcoholic fatty liver disease (NAFLD) is a common aspect of metabolic syndrome, which includes a wide spectrum of liver damage and is closely associated with insulin resistance and lipid peroxidation. The current study aimed to evaluate the protective effect of Ilexgenin A (IA), obtained from Ilex hainanensis Merr., on NAFLD and investigate the underlying mechanisms. Sprague‐Dawley rats were fed a high‐fat (HF) diet for 3 weeks to induce NAFLD. They were divided into HF diet rats and HF‐IA‐treated rats, which were treated with IA (80 mg/kg p.o.) for 2 weeks. IA alleviated hepatic steatosis and insulin resistance and reduced plasma levels of alanine transaminase, aspartate aminotransferase, triglyceride, total cholesterol, low‐density lipoprotein‐cholesterol, malondialdehyde, interleukin 6, and tumor necrosis factor‐α, while increasing plasma levels of high‐density lipoprotein‐cholesterol and superoxide dismutase (SOD). IA decreased hepatic triglycerides, total cholesterol, malondialdehyde, and restored the abnormal down‐regulation of SOD. IA also decreased Cytochrome P450 2E1 expression and up‐regulated peroxisome proliferator‐activated receptor α (PPARα) expression in liver. These results suggested that IA had the potential to attenuate NAFLD by improving lipid metabolism, insulin resistance, inflammation, and oxidative stress, as well as adjusting the expression of Cytochrome P450 2E1 and PPARα.
Ecohydrology of street trees: design and irrigation requirements for sustainable water use
Authors: Vico Giulia , Revelli Roberto , Porporato Amilcare
Published: February 2013

Whereas the beneficial effects of urban vegetation have long been recognized, growing conditions in urban environments, especially for street trees, are typically harsh and limited by low water availability. Supplemental irrigation may be used to preserve aesthetic quality and ability to provide ecosystem services of urban vegetation but requires careful management of available economic and water resources to reduce urban water footprint. To this purpose, decision makers need quantitative tools, requiring few, physically based parameters and accounting for the uncertainties and future scenarios of the hydroclimatic forcing. Focusing on in‐row and isolated trees, a minimalist description of street tree water balance is proposed here, including rainfed and irrigated conditions, and explicitly accounting for tree water requirements, growing conditions (in terms of soil properties and extension of bare soil, permeable and impervious pavements surrounding the tree) and rainfall unpredictability. The proposed model allows the quantification of tree cooling capacity, water stress occurrence and irrigation requirements, as a function of soil, plant and climate characteristics, thus providing indications regarding the tree ability to provide ecosystem services and management costs. In particular, an analysis of different planting designs suggests that a balanced design consisting in bare soil and permeable pavement with size equal to the lateral canopy extension is optimal for water conservation, tree cooling capacity and health. The proposed model provides useful indications towards the definition of site‐specific guidelines for species selection and planting design, for sustainable urban vegetation. Copyright © 2013 John Wiley & Sons, Ltd.
Adiponectin modulates NK‐cell function
Authors: Wilk Sabrina , Jenke Alexander , Stehr Jenny , Yang Chin‐An , Bauer Sandra , Göldner Katrin , Kotsch Katja , Volk Hans‐Dieter , Poller Wolfgang , Schultheiss Heinz‐Peter , Skurk Carsten , Scheibenbogen Carmen
Published: February 2013

Adiponectin (APN) has been shown to exert antiinflammatory effects in various disease models but little is known concerning its regulation of NK‐cell function. Here, we show that the majority of human CD56dim NK cells express surface Adiponectin receptor (AdipoR) 1 and 2 while most CD56high NK cells are AdipoR‐negative. Toll‐like receptor (TLR) ligand‐induced IFN‐γ production was diminished by APN while it had no influence on NK‐cell cytotoxicity. In contrast only a small subpopulation of murine NK cells expresses surface AdipoRs, but about 90% store them intracellularly. APN‐deficient knockout (KO) mice had elevated frequencies of NK cells. However, cytotoxic degranulation of NK cells was decreased in APN knockout (APN‐KO) animals. Accordingly, frequencies of CD11bhighCD27high and CD94high effector NK cells and expression of NKG2D were lower in APN‐KO mice. Upon CVB3 infection NK‐cell function was restored in APN‐KO mice. Our data suggest that in addition to its antiinflammatory effects APN also influences the numerical and differentiation status of NK cells, which may further impact the outcome of immune‐mediated diseases in APN‐KO mice.
The Prins Cascade Cyclization Reaction for the Synthesis of Angularly‐Fused Tetrahydropyran and Piperidine Derivatives
Authors: Subba Reddy B. V. , Kumar Harish , Borkar Prashant , Yadav J. S. , Sridhar B.
Published: February 2013

2‐Arylethylbut‐3‐en‐1‐ol is found to undergo smooth Prins cascade reactions with various aldehydes in the presence of Sc(OTf)3 (10 mol‐%) and a stoichiometric amount of TsOH to afford the corresponding trans‐fused hexahydro‐1H‐benzo[f]isochromenes in good yields with excellent selectivity. Likewise, N‐tosyl‐2‐phenethylbut‐3‐en‐1‐amine gives trans‐fused octahydrobenzo[f]isoquinoline derivatives under similar conditions. This is the first example of the synthesis of hexahydro‐1H‐benzo[f]isochromene and octahydrobenzo‐[f]isoquinoline from 2‐arylethylbut‐3‐en‐1‐ol and N‐tosyl‐2‐phenethylbut‐3‐en‐1‐amine, respectively.
The First Enantioselective Approach to 13a‐Methyl‐14‐hydroxyphenanthroindolizidine Alkaloids – Synthetic Studies towards Hypoestestatin 2
Authors: Su Bo , Deng Meng , Wang Qingmin
Published: February 2013

The first enantioselective approach to 13a‐methyl‐14‐hydroxyphenanthroindolizidine alkaloids was achieved in six linear steps from phenanthryl alcohol and features a highly substrate‐dependent Parham cycloacylation and Seebach's enantioselective alkylation as the key steps. The route is concise, protecting‐group free, provides access to all stereoisomers, and works on a gram scale. In addition to the putative structure of hypoestestatin 2, the other three stereoisomers and two structurally related analogues were synthesized, none of which shows identical NMR spectra to those reported for natural hypoestestatin 2, which indicates that further structure revision is required.
Regio‐ and Stereoselective Olefination of Phenol Carbamates through C–H Bond Functionalization
Authors: Li Bin , Ma Jianfeng , Liang Yujie , Wang Nuancheng , Xu Shansheng , Song Haibin , Wang Baiquan
Published: February 2013

Two pathways that can be used to access ortho‐olefinated phenol carbamate, including a ruthenium(II)‐catalyzed oxidative olefination of phenol carbamate with acrylates and a rhodium(III)‐catalyzed alkyne hydroarylation of phenol carbamate with internal alkynes through direct C–H activation, are reported. Both reactions afford substituted alkenes in a highly regio‐ and stereoselective manner.
Reexamination of the Direct Electrochemical Reduction of S‐Nitrosothiols
Authors: Peng Bo , Meyerhoff Mark E.
Published: February 2013

We report here on the electrochemical reduction of S‐nitrosothiol species (RSNO). Nitric oxide (NO) is the reported common product from electrochemically reduced RSNOs at physiological pH. However, studies here at pH 7.4 show that during the reduction of RSNOs (−0.6 V to −0.9 V, vs. Ag/AgCl), no significant amount of NO is detected. Gas analysis suggests RSNO are reduced to nitrous oxide (N2O) at pH 7.4 and can only be converted back to NO at more oxidizing voltages. Interestingly, at pH 4.0, a direct one‐electron reduction of RSNOs appears to occur and generates significant amounts of NO from RSNO species.
MWCNT Modified Glassy Carbon Electrode: Probing Furazolidone‐DNA Interactions and DNA Determination
Authors: Fotouhi Lida , Bahmani Farzaneh
Published: February 2013

The interactions of furazolidone (Fu) with double‐stranded calf thymus DNA (dsDNA) on the multiwalled carbon nanotubes modified glassy carbon electrode (MWCNT/GCE) have been studied by voltammetry and UV‐vis spectroscopy. The binding constants of Fu with DNA and the stoichiometric coefficient according to the Hill’s model have been determined. A detailed analysis of cyclic voltammograms gave fundamental electrochemical parameters including the electroactive surface coverage (Γ), the transfer coefficient (α), and the heterogeneous rate constant (ks). Two linear calibration curves were obtained for DNA detection in the concentration ranges of 40–100 µ L−1 and 100–1000 µg L−1 with a detection limit of 25 µg L−1.
Validation of a New Analytical Method for the Measurement of Free Fatty Acids in Biodiesel
Authors: da Silva Figueiredo Elizabeth , de Castro Vieira Eduardo , de Siqueira Cavalcanti Eduardo Homem , D'Elia Eliane
Published: February 2013

International and Brazilian standards have in common the acid number as the main qualification parameter for biodiesel. Free fatty acids lead to engine corrosion and contribute to the formation of gum. The analytical methods specified for analysis are based on colorimetric and potentiometric titrations, which are characterised by lack of selectivity. This article proposes a new method based on the electrochemical reduction of quinones in the presence of the free fatty acids found in biodiesel on the glassy carbon electrode surface in the range of 0.4 V to −0.65 V versus Ag/AgCl/Cl− (3 mol L−1). The proposed method was validated.
Facilitated Ion Transfers at the Micro‐Water/1,2‐Dichloroethane Interface by Crown Ether Derivatives
Authors: Qiao Yonghui , Zhang Ben , Zhu Xinyu , Ji Tianrong , Li Bo , Li Qing , Chen Erqiang , Shao Yuanhua
Published: February 2013

The transfers of potassium ion (K+) facilitated by 3,3′,6,6′‐tetrakis[p‐(n‐dodecyloxy)benzoyloxymethyl]dibenzo‐18‐crown‐6 (L1) and of sodium ion (Na+) facilitated by 3′,6′‐bis{3′′,4′′,5′′‐tris[p‐(n‐dodecyloxy)benzyloxy]benzoyloxymethyl}benzo‐15‐crown‐5 (L2) have been investigated at the micro‐water/1.2‐dichloroethane (micro‐W/DCE) interface supported at the tip of a micropipette by cyclic voltammetry and chronoamperometry. The experimental results demonstrate that the mechanisms of both facilitated ion transfer (FIT) processes correspond to the transfer by an interfacial complexation (TIC) and the transfer by an interfacial dissociation (TID) processes. Some thermodynamic parameters, such as, stoichiometry, diffusion coefficient and the association constants are evaluated by cyclic voltammetry. Furthermore, the chronoamperometry has been employed to explore the roughness of the interface supported at the micropipette by analysis of the current‐time curves based on the system of facilitated Na+ transfer by L2 at the water/DCE interface.
Preparation of Liposomal Progesterone and Its Application on the Measurement of Progesterone Interpreted via Electrochemical and Colorimetric Sensing Platforms
Authors: Tien Chia‐Ying , Jou Amily Fang‐ju , Fan Nien‐Chu , Chuang Min‐Chieh , Ho Ja‐an Annie
Published: February 2013

We herein demonstrate a successful synthesis of methylene blue (MB)‐encapsulated liposomal progesterone (LP) with an amplification merit beneficial for analytical applications. Both colormetric and electrochemical immunosensing strips for the leveling of progesterone, a hormone that helps to regulate the menstrual cycle of women, were achieved and characterized. Particular attention was given to the incorporation of an electrochemical screen‐printed electrode toward disposable and deployed diagnostics, enabling the reliable quantification of progesterone in connection to a LOD of 0.83 pg/mL. The novel, simple and specific amplification approach holds the promise to endorse a fast and high‐fidelity diagnostics required for immediate therapeutic attempts.
Interfacial Electron Transfer from CdSe/ZnS Quantum Dots to TiO2 Nanoparticles: Linker Dependence at Single Molecule Level
Authors: Chang Yu‐Pin , Tsai Po‐Yu , Lee Hsin‐Lung , Lin King‐Chuen
Published: February 2013

We utilize single molecule spectroscopy combined with time‐correlated single‐photon counting to probe electron transfer (ET) kinetics from CdSe/ZnS (core/shell) quantum dots (QDs) to TiO2 through various lengths of linker molecules. The QD‐linker‐TiO2 complexes with varied linker length, linker structure, and QD size are fabricated by a surface‐based stepwise method to show control of the rate and of the magnitude of fluctuations of photo‐induced ET at the single molecule level. The ET rate constants are determined to be 2.8×107, 1.9×107, and 3.5×106 s−1 for the chain length of 1.5, 6.2 and 13.8 Å, respectively. The electronic coupling strengths between QDs and TiO2 are further calculated to be 3.68, 3.60, and 1.59 cm−1 for the three different chain lengths by using the Marcus ET model.
Reinforced Electrode Architecture for a Flexible Battery with Paperlike Characteristics
Authors: Gaikwad Abhinav M. , Chu Howie N. , Qeraj Rigers , Zamarayeva Alla M. , Steingart Daniel A.
Published: February 2013

Compliant energy storage has not kept pace with flexible electronics. Herein we demonstrate a technique to reinforce arbitrary battery electrodes by supporting them with mechanically tough, low‐cost fibrous membranes, which also serve as the separator. The membranes were laminated to form a full cell, and this stacked membrane reinforcement bears the loads during flexing. This technique was used to make a high energy density, nontoxic Zn–MnO2 battery with printed current collectors. The Zn and MnO2 electrodes were prepared by using a solution‐based embedding process. The cell had a nominal potential of 1.5 V and an effective capacity of approximately 3 mA h cm−2. We investigated the effect of bending and fatigue on the electrochemical performance and mechanical integrity of the battery. The battery was able to maintain its capacity even after 1000 flex cycles to a bend radius of 2.54 cm. The battery showed an improvement in discharge capacity (ca. 10 %) if the MnO2 electrode was flexed to tension as a result of the improvement of particle‐to‐particle contact. In a demonstration, the flexible battery was used to power a light‐emitting diode display integrated with a strain sensor and microcontroller.
Polymeric Ionic Hybrid as Solid Acid Catalyst for the Selective Conversion of Fructose and Glucose to 5‐Hydroxymethylfurfural
Authors: Li Hu , He Xudong , Zhang Qiuyun , Chang Fei , Xue Wei , Zhang Yuping , Yang Song
Published: February 2013

The dehydration of fructose to 5‐hydroxymethylfurfural (HMF) in the presence of a SO3H‐functionalized heteropolyanion‐based polymeric hybrid catalyst is investigated. Poly(1‐vinyl‐3‐propane sulfonate imidazolium)‐H3PW12O40 [poly(VMPS)‐PW], a supported ionic liquid catalyst (SILC) was prepared and used as a heterogeneous Brønsted‐acidic catalyst. We demonstrate that an 83% yield of HMF can be obtained at 130 ºC after 60 min using DMSO as the solvent, under atmospheric pressure. The catalytic scope of poly(VMPS)‐PW is studied by using it as a catalyst for the dehydration of glucose. We demonstrate that the catalyst is also suitable for conversion of glucose to HMF, with a yield of 26 % under mild conditions. Moreover, the acidic hybrid catalyst is easily separated from the reaction mixture by centrifugation. The ability to recycle the catalyst is demonstrated and poly(VMPS)‐PW is reused five times without significant loss of activity.
Explicit reduced‐order models for the stabilized finite element approximation of the incompressible Navier–Stokes equations
Authors: Baiges Joan , Codina Ramon , Idelsohn Sergio
Published: February 2013

In this paper, we present an explicit formulation for reduced‐order models of the stabilized finite element approximation of the incompressible Navier–Stokes equations. The basic idea is to build a reduced‐order model based on a proper orthogonal decomposition and a Galerkin projection and treat all the terms in an explicit way in the time integration scheme, including the pressure. This is possible because the reduced model snapshots do already fulfill the continuity equation. The pressure field is automatically recovered from the reduced‐order basis and solution coefficients. The main advantage of this explicit treatment of the incompressible Navier–Stokes equations is that it allows for the easy use of hyper‐reduced order models, because only the right‐hand side vector needs to be recovered by means of a gappy data reconstruction procedure. A method for choosing the optimal set of sampling points at the discrete level in the gappy procedure is also presented. Numerical examples show the performance of the proposed strategy. Copyright © 2013 John Wiley & Sons, Ltd.