Electrophile-Induced C-C Bond Activation of Vinylcyclopropanes for the Synthesis of Z-Alkylidenetetrahydrofurans

We present a detailed study on the behavior of vinylcyclopropanes as masked donor acceptor system toward the stereoselective synthesis of Z-alkylidenetetrahydrofurans. Results of bromenium catalyzed indirect activation of C-C bond of vinylcyclopropanes and concomitant cyclization to alkylidenetetrahydrofuran and other heterocycles have been discussed. The stereoselective formation of the Z-isomer is strongly controlled by the extent of destabilization of one of the gauche conformers of the vinylcyclopropane. The ring-opening/cyclization step was found to be stereospecific as in the case of DA cyclopropanes. The activation of the C-C bond leads to a tight-carbocation intermediate, which is evident from the complete retention of the stereochemistry. The retention of configuration has been established by a necessary control experiment that rules out the possibility of a double inversion pathway. The present results serve as direct stereochemical evidence in support of a tight ion-pair intermediate versus the controversial S(N)2 pathway. A 2D potential energy scan has been carried out at B3LYP/6-31G(d) level theory to obtain the relative energies of the conformers. The Z-selectivity observed has been explained on the basis of the relative population of the conformers and modeling the intermediate and transition state involved in the reaction at M06-2x/6-31+G(d) level. Energy profile for the cyclization step was modeled considering various possible pathways through which cyclization can happen. The methodology has been successfully demonstrated on vinylcyclobutanes as well.

Effect of Temperature Cycling on Conduction Mechanisms in CdTe Thin Films

CdTe thin films of 500 thickness prepared by thermal evaporation technique were analyzed for leakage current and conduction mechanisms. Metal-insulator-metal (MIM) capacitors were fabricated using these films as a dielectric. These films have many possible applications, such as passivation for infrared diodes that operate at low temperatures (80 K). Direct-current (DC) current-voltage (I-V) and capacitance-voltage (C-V) measurements were performed on these films. Furthermore, the films were subjected to thermal cycling from 300 K to 80 K and back to 300 K. Typical minimum leakage currents near zero bias at room temperature varied between 0.9 nA and 0.1 mu A, while low-temperature leakage currents were in the range of 9.5 pA to 0.5 nA, corresponding to resistivity values on the order of 10(8) a''broken vertical bar-cm and 10(10) a''broken vertical bar-cm, respectively. Well-known conduction mechanisms from the literature were utilized for fitting of measured I-V data. Our analysis indicates that the conduction mechanism in general is Ohmic for low fields < 5 x 10(4) V cm(-1), while the conduction mechanism for fields > 6 x 10(4) V cm(-1) is modified Poole-Frenkel (MPF) and Fowler-Nordheim (FN) tunneling at room temperature. At 80 K, Schottky-type conduction dominates. A significant observation is that the film did not show any appreciable degradation in leakage current characteristics due to the thermal cycling.

Engagement of CF3 Group in N-H center dot center dot center dot F-C Hydrogen Bond in the Solution State: NMR Spectroscopy and MD Simulation Studies

Unambiguous evidence for the engagement of CF3 group in N-H center dot center dot center dot F-C hydrogen bond in a low polarity solvent, the first observation of its kind, is reported. The presence of such weak molecular interactions in the solution state is convincingly established by one and two-dimensional H-1, F-19, and natural abundant N-15 NMR spectroscopic studies. The strong and direct evidence is derived by the observation of through-space couplings, such as, (1h)J(FH), (1h)J(FN), and (2h)J(FF), where the spin polarization is transmitted through hydrogen bond. In an interesting example of a molecule containing two CF3 groups getting simultaneously involved in hydrogen bond, where hydrogen bond mediated couplings are not reflected in the NMR spectrum, F-19-F-19 NOESY experiment yielded confirmatory evidence. Significant deviations in the strengths of (1)J(NH), variable temperature, and the solvent induced perturbations yielded additional support. The NMR results are corroborated by both DFT calculations and MD simulations, where the quantitative information on different ways of involvement of fluorine in two and three centered hydrogen bonds, their percentage of occurrences, and geometries have been obtained. The hydrogen bond interaction energies have also been calculated.

Site-specific N-Linked Glycosylation of Receptor Guanylyl Cyclase C Regulates Ligand Binding, Ligand-mediated Activation and Interaction with Vesicular Integral Membrane Protein 36, VIP36

Guanylyl cyclase C (GC-C) is a multidomain, membrane-associated receptor guanylyl cyclase. GC-C is primarily expressed in the gastrointestinal tract, where it mediates fluid-ion homeostasis, intestinal inflammation, and cell proliferation in a cGMP-dependent manner, following activation by its ligands guanylin, uroguanylin, or the heat-stable enterotoxin peptide (ST). GC-C is also expressed in neurons, where it plays a role in satiation and attention deficiency/hyperactive behavior. GC-C is glycosylated in the extracellular domain, and differentially glycosylated forms that are resident in the endoplasmic reticulum (130 kDa) and the plasma membrane (145 kDa) bind the ST peptide with equal affinity. When glycosylation of human GC-C was prevented, either by pharmacological intervention or by mutation of all of the 10 predicted glycosylation sites, ST binding and surface localization was abolished. Systematic mutagenesis of each of the 10 sites of glycosylation in GC-C, either singly or in combination, identified two sites that were critical for ligand binding and two that regulated ST-mediated activation. We also show that GC-C is the first identified receptor client of the lectin chaperone vesicular integral membrane protein, VIP36. Interaction with VIP36 is dependent on glycosylation at the same sites that allow GC-C to fold and bind ligand. Because glycosylation of proteins is altered in many diseases and in a tissue-dependent manner, the activity and/or glycan-mediated interactions of GC-C may have a crucial role to play in its functions in different cell types.

Monoclonal Antibodies against Hepatitis C Genotype 3a Virus Like Particle Inhibit Virus Entry in Cell Culture System

The envelope protein (E1-E2) of Hepatitis C virus (HCV) is a major component of the viral structure. The glycosylated envelope protein is considered to be important for initiation of infection by binding to cellular receptor(s) and also known as one of the major antigenic targets to host immune response. The present study was aimed at identifying mouse monoclonal antibodies which inhibit binding of virus like particles of HCV to target cells. The first step in this direction was to generate recombinant HCV-like particles (HCV-LPs) specific for genotypes 3a of HCV (prevalent in India) using the genes encoding core, E1 and E2 envelop proteins in a baculovirus expression system. The purified HCV-LPs were characterized by ELISA and electron microscopy and were used to generate monoclonal antibodies (mAbs) in mice. Two monoclonal antibodies (E8G9 and H1H10) specific for the E2 region of envelope protein of HCV genotype 3a, were found to reduce the virus binding to Huh7 cells. However, the mAbs generated against HCV genotype 1b (D2H3, G2C7, E1B11) were not so effective. More importantly, mAb E8G9 showed significant inhibition of the virus entry in HCV JFH1 cell culture system. Finally, the epitopic regions on E2 protein which bind to the mAbs have also been identified. Results suggest a new therapeutic strategy and provide the proof of concept that mAb against HCV-LP could be effective in preventing virus entry into liver cells to block HCV replication.

Context aware M-commerce services: C-IOB model approach

Context-aware computing is useful in providing individualized services focusing mainly on acquiring surrounding context of user. By comparison, only very little research has been completed in integrating context from different environments, despite of its usefulness in diverse applications such as healthcare, M-commerce and tourist guide applications. In particular, one of the most important criteria in providing personalized service in a highly dynamic environment and constantly changing user environment, is to develop a context model which aggregates context from different domains to infer context of an entity at the more abstract level. Hence, the purpose of this paper is to propose a context model based on cognitive aspects to relate contextual information that better captures the observation of certain worlds of interest for a more sophisticated context-aware service. We developed a C-IOB (Context-Information, Observation, Belief) conceptual model to analyze the context data from physical, system, application, and social domains to infer context at the more abstract level. The beliefs developed about an entity (person, place, things) are primitive in most theories of decision making so that applications can use these beliefs in addition to history of transaction for providing intelligent service. We enhance our proposed context model by further classifying context information into three categories: a well-defined, a qualitative and credible context information to make the system more realistic towards real world implementation. The proposed model is deployed to assist a M-commerce application. The simulation results show that the service selection and service delivery of the system are high compared to traditional system.

Dramatic Structural Changes Resulting from the Loss of a Crucial Hydrogen Bond in the Hinge Region Involved in C-Terminal Helix Swapping in SurE: A Survival Protein from Salmonella typhimurium

Domain swapping is an interesting feature of some oligomeric proteins in which each protomer of the oligomer provides an identical surface for exclusive interaction with a segment or domain belonging to another protomer. Here we report results of mutagenesis experiments on the structure of C-terminal helix swapped dimer of a stationary phase survival protein from Salmonella typhimurium (StSurE). Wild type StSurE is a dimer in which a large helical segment at the C-terminus and a tetramerization loop comprising two beta strands are swapped between the protomers. Key residues in StSurE that might promote C-terminal helix swapping were identified by sequence and structural comparisons. Three mutants in which the helix swapping is likely to be avoided were constructed and expressed in E. coli. Three-dimensional X-ray crystal structures of the mutants H234A and D230A/H234A could be determined at 2.1 angstrom and 2.35 angstrom resolutions, respectively. Contrary to expectations, helix swapping was mostly retained in both the mutants. The loss of the crucial D230 OD2- H234 NE2 hydrogen bond (2.89 angstrom in the wild type structure) in the hinge region was compensated by new inter and intra-chain interactions. However, the two fold molecular symmetry was lost and there were large conformational changes throughout the polypeptide. In spite of these changes, the dimeric structure and an approximate tetrameric organization were retained, probably due to the interactions involving the tetramerization loop. Mutants were mostly functionally inactive, highlighting the importance of precise inter-subunit interactions for the symmetry and function of StSurE.

A Versatile C-H Functionalization of Tetrahydroisoquinolines Catalyzed by Iodine at Aerobic Conditions

A versatile aerobic catalytic system (I-2 and O-2/TBHP) for C-H functionalization is reported. This CDC (cross-dehydrogentive coupling) reaction is compatible with a large number of nucleophiles and is performed under ambient reaction conditions. The scope of the metal-free CDC is illustrated by synthesizing a variety of functionalized tetrahydroisoquinolines and N,N-dimethylaniline. The highlight of the method is a Friedel-Crafts reaction of phenols and indole with tertiary amines.

An Expeditious Enantiospecific Total Synthesis of (-)-Crassalactone C

A concise and expeditious approach for the total synthesis of bioactive styryllactone (-)-crassalactone C is presented from tartaric acid. The main features of the synthesis include the desymmetrization of dimethylamide of tartaric acid and the effective use of cinnamoyl ester as a protecting group as well as a reactant in the ring-closing metathesis reaction.

A fully discrete C-0 interior penalty Galerkin approximation of the extended Fisher-Kolmogorov equation

A fully discrete C-0 interior penalty finite element method is proposed and analyzed for the Extended Fisher-Kolmogorov (EFK) equation u(t) + gamma Delta(2)u - Delta u + u(3) - u = 0 with appropriate initial and boundary conditions, where gamma is a positive constant. We derive a regularity estimate for the solution u of the EFK equation that is explicit in gamma and as a consequence we derive a priori error estimates that are robust in gamma. (C) 2013 Elsevier B.V. All rights reserved.

A unified model for the dynamics of driven ribbon with strain and magnetic order parameters

We develop a unified model to explain the dynamics of driven one dimensional ribbon for materials with strain and magnetic order parameters. We show that the model equations in their most general form explain several results on driven magnetostrictive metallic glass ribbons such as the period doubling route to chaos as a function of a dc magnetic field in the presence of a sinusoidal field, the quasiperiodic route to chaos as a function of the sinusoidal field for a fixed dc field, and induced and suppressed chaos in the presence of an additional low amplitude near resonant sinusoidal field. We also investigate the influence of a low amplitude near resonant field on the period doubling route. The model equations also exhibit symmetry restoring crisis with an exponent close to unity. The model can be adopted to explain certain results on magnetoelastic beam and martensitic ribbon under sinusoidal driving conditions. In the latter case, we find interesting dynamics of a periodic one orbit switching between two equivalent wells as a function of an ac magnetic field that eventually makes a direct transition to chaos under resonant driving condition. The model is also applicable to magnetomartensites and materials with two order parameters. (C) 2013 American Institute of Physics. http://dx.doi.org/10.1063/1.4790845]

Evidence of collective relaxation behavior in the reentrant phase of oxygen-rich LaMnO3

The reentrant low temperature phase of the perovskite manganite LaMnO3+delta (delta=0.22) has been investigated with ac susceptibility and dc magnetization studies. A critical examination of the memory effects in ac susceptibility leads us to the conclusion that the slow dynamics in the system is a consequence of collective relaxation processes resulting from interactions between ferromagnetic clusters, whose presence was indicated in earlier studies. Here, we postulate that the collective behavior is due to the existence of long-range (dipolar) interactions between the large ferromagnetic `superspins'. This is also confirmed by an abnormally large microscopic spin-flip time (similar to 10(-9) s) compared to a canonical spin glass. (C) 2013 Elsevier B.V. All rights reserved.

A cyclic peptide mimic of an RNA recognition motif of human La protein is a potent inhibitor of hepatitis C virus

Due to limited available therapeutic options, developing new lead compounds against hepatitis C virus is an urgent need. Human La protein stimulates hepatitis C virus translation through interaction with the hepatitis C viral RNA. A cyclic peptide mimicking the beta-turn of the human La protein that interacts with the viral RNA was synthesized. It inhibits hepatitis C viral RNA translation significantly better than the corresponding linear peptide at longer post-treatment times. The cyclic peptide also inhibited replication as measured by replicon RNA levels using real time RT-PCR. The cyclic peptide emerges as a promising lead compound against hepatitis C.

Durability of Pt/C and Pt/MC-PEDOT catalysts under simulated start-stop cycles in polymer electrolyte fuel cells

A composite of mesoporous carbon (MC) with poly(3,4-ethylenedioxythiophene) (PEDOT) is studied as catalyst support for platinum nanoparticles. The durability of commercial Pt/carbon and Pt/MC-PEDOT as cathode catalyst is investigated by invoking air-fuel boundary at the anode side so as to foster carbon corrosion at the cathode side of a polymer electrolyte fuel cell (PEFC). Pt/MC-PEDOT shows higher resistance to carbon corrosion in relation to Pt/C. Electrochemical techniques such as cyclic voltammetry (CV) and impedance measurements are used to evaluate the extent of degradation in the catalyst layer. It is surmised that the resistance of MC-PEDOT as catalyst support toward electrochemical oxidation makes Pt/MC-PEDOT a suitable and stable cathode catalyst for PEFCs.

Electrocatalytic oxidation of C-3-aliphatic alcohols on electrodeposited Pd-PEDOT nanodendrites in Alkaline medium

Nanodendritic Pd is electrodeposited on poly(3,4-ethylenedioxythiophene) (PEDOT) coated carbon paper electrode. Electrodeposited Pd is non-dendritic in the absence of PEDOT. The electrooxidation of C-3-aliphatic alcohols, namely, propanol (PA), 1,2- propanediol (1, 2-PD), 1, 3-propanediol (1, 3-PD), and glycerol (GL) is studied in 1.0 M NaOH. The catalytic activity of nanodendritic Pd is greater than that of non-dendritic Pd for oxidation of the four alcohols molecules. Among those molecules the oxidation rate increases as: PA< 1, 2-PD < 1, 3-PD < GL. The cyclic voltammetric oxidation current peak appearing in the reverse direction of the sweep is greatly influenced by the nature of alcohol. The reduction of oxide film on Pd surface is attributed to affect the magnitude of backward peak current density. The amperometry and repeated cyclic voltammetry data suggest a high stability of nanodendritic Pd in alkaline medium. Glycerol is expected to be an appropriate alcohol for application as a fuel in alkaline fuel cells at nanodendritic electrodeposited Pd.