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20192173 | Room temperature cross-coupling of highly functionalized organozinc reagents with thiomethylated N-heterocycles by nickel catalysis. | A variety of thiomethyl-substituted N-heterocycles such as pyridines, isoquinolines, pyrimidines, pyrazines, pyridazines, quinazolines, triazines, benzothiazoles, or benzoxazoles undergo smooth Ni-catalyzed cross-coupling reactions with functionalized aryl-, heteroaryl-, alkyl-, and benzylic zinc reagents using an inexpensive Ni(acac)(2)/DPE-Phos catalytic system at 25 degrees C. |
20192174 | Ultrafiltration membranes incorporating amphiphilic comb copolymer additives prevent irreversible adhesion of bacteria. | We examined the resistance to bacterial adhesion of a novel polyacrylonitrile (PAN) ultrafiltration membrane incorporating the b copolymer additive, polyacrylonitrile-graft-polyethylene oxide (PAN-g-PEO). The adhesion of bacteria (E. coli K12) and the reversibility of adhered bacteria were tested with the novel membrane, and the behavior pared to mercial PAN ultrafiltration membrane. Under static (no flow) bacterial adhesion tests, we observed no bacterial adhesion to the PAN/PAN-g-PEO membrane at all ionic strengths tested, even with the addition of calcium ions. In contrast, significant adhesion of bacterial cells was observed on mercial PAN membrane, with increased cell adhesion at higher ionic strengths and in the presence of calcium ions. Under crossflow filtration conditions, initial bacterial deposition rate increased with ionic strength and with addition of calcium ions for both membranes, with generally lower bacterial deposition rate with the PAN/PAN-g-PEO membrane. However, deposited bacteria were readily removed (between 97 and 100%) from the surface of the PAN/PAN-g-PEO membrane upon increasing the crossflow and eliminating the permeate flow (i.e., no applied transmembrane pressure), suggesting reversible adhesion of bacteria. In contrast, bacterial adhesion on mercial PAN membrane was irreversible, with approximately 50% removal of adhered bacteria at moderate ionic strengths (10 and 30 mM) and less than 25% removal at high ionic strength (100 mM). The resistance to bacterial adhesion of the PAN/PAN-g-PEO membrane was further analyzed via measurement of interaction forces with atomic force microscopy (AFM). No adhesion forces were detected between a carboxylated colloid probe and the PAN/PAN-g-PEO membrane, while the probe exhibited strong adhesion to mercial PAN membrane, consistent with the bacterial adhesion tests. The exceptional resistance of the PAN/PAN-g-PEO membrane to bacterial adhesion is attributable to steric repulsion imparted by the dense brush layer of polyethylene oxide (PEO) chains. |
20192176 | Effects of ethanol on the organization of phosphocholine lipid bilayers. | We have investigated the consequences of the addition of ethanol to aqueous solutions containing 100 nm diameter phosphocholine unilamellar vesicles. We have studied the effect of ethanol addition on both gel phase and fluid phase phospholipid bilayers of 1,2-dimyristoyl-sn-phosphatidylcholine (DMPC), using time-resolved fluorescence measurements of perylene incorporated into the vesicles. We observe an increase in the perylene rotational diffusion time constants for ethanol concentrations of ca. 0.6 M in both the gel phase (289 K) and the fluid phase (303 K), indicating a change in the bilayer interacyl chain spacing and/or organization. While the change in rotational diffusion behavior of perylene is seen for both phospholipid phases, the details of the change in chromophore dynamics are not the same for the two phases, likely due to the differing extents of disorder in the phospholipid acyl chain region at the two temperatures. These data provide insight into the effects of ethanol on the local environment of the probe in both gel phase and fluid phase lipid bilayers. |
20192175 | Surface structure of Nafion in vapor and liquid. | The microstructure of Nafion varies in response to changes in hydration. Thus, it undergoes a transition from tightly packed bundles of inverted micelles with aqueous cores and fused hydrophobic shells ("macaroni bundles") at low hydrations to normal type ("spaghetti") micelles at high hydrations. It was postulated recently that a similar "macaroni-spaghetti" transition, i.e., breakup of surface-aligned macaroni to randomly oriented spaghetti, takes place at the polymer surface when the external medium is changed from vapor to liquid water, which can explain some puzzling features of Nafion and similar microphase-separated ionomers. The resulting (nonequilibrium) structures may remain confined to a few nanometers thick surface region. Here, this picture is corroborated using grazing-incidence small-angle X-ray scattering (GISAXS), contact angle, and atomic force microscopy (AFM). The enhanced alignment of bundles adjacent to the surface in vapor, similar to the effect of biaxial stretching, is elucidated by GISAXS of spin-cast Nafion films. It is inferred from the characteristic change in relative intensities and position of the ionomer peak in the X-Y (in-plane) and Z (out-of-plane) directions with varying X-ray penetration depths into the film. However, contact angle measurements show that the relatively smooth and very hydrophobic surface of Nafion in vapor transforms to a hydrophilic surface, when vapor as the external medium is replaced with liquid water. In addition, AFM indicates that the surface roughness significantly increases in liquid. The results demonstrate that the surface region of Nafion and similar microphase-separated materials may be indeed subject to drastic structural variations, even though the extremely slow relaxation of the solid matrix may preclude propagation of such changes into the bulk. These effects may have a profound effect on the macroscopic characteristics of Nafion membranes, such as hydration and conductivity, as well as their functioning as ion-selective barriers in electrochemical and other applications. |
20192177 | Sorption and transport of salicylate in a porous heterogeneous medium of silica quartz and goethite. | Among transport studies of solutes in porous media, few works bined microscopic speciation with macroscopic-scale investigations to describe the impact of antecedent sorbed silica on the transport of organic ligands in porous heterogeneous media. In this study, the sorption of salicylate (SA) to goethite-coated sand (GCS) was investigated under static and dynamic conditions bining batch experiments and column tests with infrared spectroscopy. On the basis of infrared spectra, the salicylate adsorption was described by one type of iron site and a mononuclear bidentate plex. The plexation constant deduced from batch modeling was successfully applied to estimate the sorbed amount under flow through conditions at various water velocities (0.038-0.768 cm/min). The shape of the breakthrough curve of SA was characterized by two fronts in both SA concentration and pH. This behavior could be likely explained by the mobilization of initially adsorbed silica from goethite surface upon SA sorption. The SA breakthrough can be interpreted as retention of SA on available surface sites up to their saturation and then on additional reactive sites, ing free due to silicate desorption. This present work demonstrated the importance of sorbed silicate on Fe-oxides in the prediction of reactive transport of organic species on natural surfaces. |
20192178 | High-performance single cell genetic analysis using microfluidic emulsion generator arrays. | High-throughput genetic and phenotypic analysis at the single cell level is critical to advance our understanding of the molecular mechanisms underlying cellular function and dysfunction. Here we describe a high-performance single cell genetic analysis (SCGA) technique bines high-throughput microfluidic emulsion generation with single cell multiplex polymerase chain reaction (PCR). Microfabricated emulsion generator array (MEGA) devices containing 4, 32, and 96 channels are developed to confer a flexible capability of generating up to 3.4 x 10(6) nanoliter-volume droplets per hour. Hybrid glass-polydimethylsiloxane diaphragm micropumps integrated into the MEGA chips afford uniform droplet formation, controlled generation frequency, and effective transportation and encapsulation of primer functionalized microbeads and cells. A multiplex single cell PCR method is developed to detect and quantify both wild type and mutant/pathogenic cells. In this method, microbeads functionalized with multiple forward primers targeting specific genes from different cell types are used for solid-phase PCR in droplets. Following PCR, the droplets are lysed and the beads are pooled and rapidly analyzed by multicolor flow cytometry. Using Escherichia coli bacterial cells as a model, we show that this technique enables digital detection of pathogenic E. coli O157 cells in a high background of normal K12 cells, with a detection limit on the order of 1/10(5). This result demonstrates that multiplex SCGA is a promising tool for high-throughput quantitative digital analysis of genetic variation plex populations. |
20192179 | Multiple spiking species-specific isotope dilution analysis by molecular mass spectrometry: simultaneous determination of inorganic mercury and methylmercury in fish tissues. | This work demonstrates, for the first time, the applicability of multiple spiking isotope dilution analysis to molecular mass spectrometry exemplified by the speciation analysis of mercury using GC(EI)MS instrumentation. A double spike isotope dilution approach using isotopically enriched mercury isotopes has been applied for the determination of inorganic mercury Hg(II) and methylmercury (MeHg) in fish reference materials. The method is based on the application of isotope pattern deconvolution for the simultaneous determination of degradation-corrected concentrations of methylmercury and inorganic mercury. Mass isotopomer distributions are employed instead of isotope ratios to calculate the corrected concentrations of the Hg species as well as the extent of species degradation reactions. The isotope pattern deconvolution equations developed here allow the calculation of the different molar fractions directly from the GC(EI)MS mass isotopomer distribution pattern and take into account possible impurities present in the spike solutions employed. The procedure has been successfully validated with the analysis of two different certified reference materials (BCR-464 and DOLT-4) and with parison of the results obtained by GC(ICP)MS. For the tuna fish matrix (BCR-464), no interconversion reactions were observed at the optimized conditions of open focused microwave extraction at 70 degrees C during 8 min. However, significant demethylation was found under the same conditions in the case of the certified dogfish liver DOLT-4. Methylation and demethylation factors were confirmed by GC(ICP)MS. Transformation reactions have been found to depend on the sample matrix and on the derivatization reagent employed. Thus, it is not possible to mend optimum extraction conditions suitable for all types of matrices demonstrating the need to apply multiple spiking methodologies for the determination of MeHg and Hg(II) in biological samples. Double spike isotope dilution analysis methodologies using widespread GC(EI)MS instrumentation are proposed here for the routine analysis of inorganic mercury and methylmercury in fish samples. The estimated method detection limits were below 10 ng g(-1) for both mercury species. Precision was evaluated for the concentrations present in the certified reference materials (CRMs) which vary from 0.1 to 5 microg g(-1), achieving values of coefficients of variation ranging from 7% to 2%. The concentrations obtained in both CRMs analyzed were in excellent agreement with the certified values, demonstrating the accuracy of the method at these concentration levels. |
20192180 | Ultrafast electron transfer dynamics of a Zn(II)porphyrin-viologen complex revisited: S2 vs S1 reactions and survival of excess excitation energy. | The photoinduced electron transfer reactions in a self-assembled plex of zinc(II)tetrasulphonatophenylporphyrin (ZnTPPS(4-)) and methylviologen (MV(2+)) in aqueous solution were investigated with transient absorption spectroscopy. ZnTPPS(4-) was excited either in the Soret or one of the two Q-bands, corresponding to excitation into the S(2) and S(1) states, respectively. The resulting electron transfer to MV(2+) occurred, surprisingly, with the same time constant of τ(FET) = 180 fs from both electronic states. The subsequent back electron transfer was rapid, and the kinetics was independent of the initially excited state (τ(BET) = 700 fs). However, ground state reactants in a set of vibrationally excited states were observed. The amount of vibrationally excited ground states detected increased with increasing energy of the initial excited state, showing that excess excitation energy survived a two-step electron transfer reaction in solution. Differences in the ZnTPSS(•3-)/MV(•+) spectra suggest that the forward electron transfer from the S(2) state at least partially produces an electronically excited charge transfer state, which effectively suppresses the influence of the inverted regime. Other possible reasons for the similar electron transfer rates for the different excited states are also discussed. |
20192181 | Concentration-dependent aggregation of CHAPS investigated by NMR spectroscopy. | CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) is a zwitterionic surfactant, which has been extensively used in various biological fields. In the present work, the concentration-dependent aggregation of the surfactant in deuterium oxide solution was investigated by NMR spectroscopy. We have found that two break points exist on the basis of the NMR parameters such as chemical shift difference (Delta delta), self-diffusion coefficient (D), and relaxation rates (R(1), R(2)). The first break point corresponds to the widely accepted normal critical micelle concentration (cmc). The second one is unexpected and ascribed to the second cmc, indicating that there is another type of micelle at higher concentrations. Further analysis using 1D selective NOESY with spin-diffusion quenching reveals that at the concentration above the second cmc CHAPS may form a two-layer spherical structure of micelles, with the aliphatic groups of CHAPS molecules in the inner layer interact with the steroid groups in the outer layer. The existence of two types of micelles has also been supported by our TEM experiment. The dependence of CHAPS micelle size on concentration explains why some proteins are soluble and stable only at concentrations above the second cmc. Therefore, our finding provides a basis for optimizing CHAPS concentration in functional and structural studies of membrane proteins. |
20192184 | Direct catalytic asymmetric vinylogous Mannich-type and Michael reactions of an alpha,beta-unsaturated gamma-butyrolactam under dinuclear nickel catalysis. | Direct catalytic asymmetric vinylogous reactions of an alpha,beta-unsaturated gamma-butyrolactam as a donor are described. A homodinuclear Ni(2)-Schiff plex promoted a vinylogous Mannich-type reaction of N-Boc imines as well as a vinylogous Michael reaction to nitroalkenes selectively at the gamma-position under simple proton-transfer conditions. Vinylogous Mannich adducts were obtained in 5:1-->30:1 dr and 99% ee, and vinylogous Michael adducts were obtained in 16:1-->30:1 dr and 93-99% ee. |
20192183 | Enantioselective bromolactonization of conjugated (Z)-enynes. | A catalytic enantioselective syn-1,4-bromolactonization of conjugated (Z)-enynes was reported. Diastereomeric ratios >20:1 and up to 99% enantiomeric excesses were observed. Di-, tri-, and tetra-substituted bromoallenes were prepared together with lactone heterocycles efficiently and stereoselectively. Preliminary investigations suggest that the chiral catalyst may serve as a bifunctional reagent by interacting with both a carboxylic acid nucleophile and NBS electrophile. |
20192182 | Ultrasensitive electrochemical immunosensor for oral cancer biomarker IL-6 using carbon nanotube forest electrodes and multilabel amplification. | Squamous cell carcinomas of head and neck (HNSCC) are associated with immune, inflammatory, and angiogenic responses involving interleukin-6 (IL-6). This article reports an ultrasensitive electrochemical immunosensor for human IL-6 and proof-of-concept studies of IL-6 detection in HNSCC cells. Single wall carbon nanotube (SWNT) forests with attached capture antibodies (Ab(1)) for IL-6 were used in an electrochemical sandwich immunoassay protocol using enzyme label horseradish peroxidase (HRP) to measure very low (<or=30 pg mL(-1)) and elevated levels of IL-6. Two levels of multienzyme labeling were used to measure a broad concentration range of IL-6 in a representative panel of HNSCC cells. Secondary antibodies (Ab(2)) attached to carboxylated multiwall carbon nanotubes with 106 HRP labels per 100 nm gave the highest sensitivity of 19.3 nA mL (pg IL-6)(-1) cm(-2) and the best detection limit (DL) of 0.5 pg mL(-1) (25 fM) for IL-6 in 10 microL of calf serum. For more concentrated samples, biotinylated Ab(2) bound to streptavidin-HRP to provide 14-16 labels per antigen was used. These immunosensors accurately measured secreted IL-6 in a wide range of HNSCC cells demonstrated by excellent correlations with standard enzyme-linked immunosorbent assays (ELISA), suggesting that SWNT bined with multilabel detection have excellent promise for detecting IL-6 in research and clinical applications. |
20192185 | Superoxide ions entrapped in water cages of ionic clathrate hydrates. | In the present work, we first described the stable entrapment of the superoxide ions in gamma-irradiated (Me(4)NOH + O(2)) clathrate hydrate. Owing to peculiar direct guest-guest ionic interaction, the lattice structure of gamma-irradiated (Me(4)NOH + O(2)) clathrate hydrate shows significant change of lattice contraction behavior even at relatively high temperature (120 K). Such findings are expected to provide useful information for a better understanding of unrevealed nature (such as icy nanoreactor concept, ice-based functional material synthesis and lattice tuning by specific ionic guests) of clathrate hydrate fields. |
20192186 | Functionalized C-glycoside ketohydrazones: carbohydrate derivatives that retain the ring integrity of the terminal reducing sugar. | Glycosylation often mediates important biological processes through the interaction of carbohydrates plementary proteins. Most chemical tools for the functional analysis of glycans are highly dependent upon various linkage chemistries that involve the reducing terminus of carbohydrates. However, because of ring opening, the structural integrity of the reducing sugar ring (pyranose or furanose) is lost during these techniques, resulting in derivatized carboydrates that markedly differ from the parent molecule. This paper describes a new aqueous-based, one-pot strategy that involves first converting the sugar to a C-glycoside ketone, followed by conversion to ketohydrazones or oximes. Hence, the C-glycoside ketones are tagged with fluorescence, colored, cationic or biotin-labeled groups or immobilized onto hydrazine-functionalized beads. No activating or protecting groups are required, and the chemistry is mild enough for a wide range of carbohydrates. We demonstrate the versatility of the approach to diverse glycans, including bead immobilization and lectin analysis of acarbose, an antidiabetic drug, to dabsyl-tagged enzyme substrates to screen cellulases, and for the analysis of plant cell wall hemicellulosics. |
20192188 | Self-assembly of linear-dendritic diblock copolymers: from nanofibers to polymersomes. | We report the formation of cylindrical micelles, sheet-like micelles, tubular micelles, as well as polymer vesicles by a new series of amphiphilic linear-dendritic block-copolymers (BCs). The BCs, noted as PEGm-AZOn, posed of poly(ethylene glycol) (PEG) chains of different molecular weights as hydrophilic blocks and the first four generations of azobenzene-containing dendrons based on 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) as hydrophobic blocks (m represents the degree of polymerization of PEG, and n is the number of azobenzene units at the periphery of dendron). The polymeric aggregates were formed by adding water to solutions of the BCs in dioxane. The micellar dispersions in water were finally obtained by removing dioxane via dialysis against water. The morphology of the micellar self-assemblies was studied by transmission electron microscopy (TEM), cryo-electron microscopy (cryo-TEM), and atomic force microscopy (AFM). A generation-dependent aggregation behavior was found for the series of BCs PEG45-AZOn. Core-shell structured nanofibers with an inner diameter of 8 nm were observed for the copolymer PEG45-AZO2 (hydrophilic/hydrophobic weight ratio equal to 67/33). Lyotropic liquid crystalline behavior was detected for the aqueous solution of the nanofibers. The coexistence of sheet-like aggregates and tubular micelles was detected for the copolymer PEG45-AZO8 in which the number of cyanoazobenzene units is increased to 8 (hydrophilic/hydrophobic weight ratio equal to 33/67). The tubular micelles could be intermediates in the sheet-like aggregate-to-vesicle transition. Polymer vesicles (polymersomes) with a diameter in the range 300-800 nm were observed for the copolymer PEG45-AZO16 (hydrophilic/hydrophobic weight ratio equal to 20/80). The membrane of the sheet-like aggregates, tubular micelles, and polymersomes was shown to have a bilayer structure, as revealed by cryo-TEM. UV illumination of the aqueous polymersome dispersion induced the formation of wrinkles in the vesicle membrane, thus showing that this type of polymeric aggregate is photoresponsive. |
20192187 | A chiral wedge molecule inhibits telomerase activity. | In addition to the Watson-Crick double helix, secondary DNA structures are thought to play important roles in a variety of biological processes. One important example is the G-quadruplex structure that is formed at the chromosome ends, which inhibits telomerase activity by blocking its access to telomeres. G-quadruplex structures represent a new class of molecular targets for pounds that may be useful to target telomeres. Here, we reported the first example of enantioselective recognition of quadruplex DNA by a chiral cyclic helicene. We propose a new ligand-binding cleft between two telomeric human G-quadruplexes linked by a TTA linker. We found that the cyclic helicene M1 exhibited potent inhibitory activity against telomerase. |
20192189 | Just a proton: distinguishing the two electronic states of five-coordinate high-spin iron(II) porphyrinates with imidazole/ate coordination. | We report detailed studies on two S = 2 electronic states of high-spin iron(II) porphyrinates. These two states are exemplified by the five-coordinate derivatives with either neutral imidazole or anionic imidazolate as the axial ligand. The application of several physical methods all demonstrate distinctive differences between the two states. These include characteristic molecular structure differences, Mossbauer spectra, magnetic circular dichroism spectroscopy, and integer-spin EPR spectral distinctions. These distinctions are supported by DFT calculations. The two states are characterized by very different spatial properties of the doubly occupied orbital of the high-spin that are consonant with the physical properties. |
20192190 | Elucidation of the structure of the membrane anchor of penicillin-binding protein 5 of Escherichia coli. | Penicillin-binding protein 5 (PBP 5) of Escherichia coli is a membrane-bound cell wall dd-carboxypeptidase, localized in the outer leaflet of the cytosolic membrane of this Gram-negative bacterium. Not only is it the most abundant PBP of E. coli, but it is as well a target for penicillins and is the most studied of the PBP enzymes. PBP 5, as a representative peripheral membrane protein, is anchored to the cytoplasmic membrane by the 21 amino acids of its C-terminus. Although the importance of this terminus as a membrane anchor is well recognized, the structure of this anchor was previously unknown. Using natural isotope abundance NMR, the structure of the PBP 5 anchor peptide within a micelle was determined. The structure conforms to a helix-bend-helix-turn-helix motif and reveals that the anchor enters the membrane so as to form an amphiphilic structure within the interface of the hydrophilic/hydrophobic boundary regions near the lipid head groups. The bend and the turn within the motif allow the C-terminus to exit from the same side of the membrane that is penetrated. The PBP anchor sequences represent extraordinary diversity, passing both N-terminal and C-terminal anchoring domains. This study establishes a surface adherence mechanism for the PBP 5 C-terminus anchor peptide, as the structural basis for further study toward understanding the role of these domains in selecting membrane environments and in the assembly of the multienzyme hyperstructures of bacterial cell wall biosynthesis. |
20192191 | Intramolecular cation-pi interactions as the driving force to restrict the conformation of certain nucleosides. | Despite the well-established importance of intermolecular cation-pi interactions in molecular recognition, intramolecular cation-pi interactions have been less studied. Here we describe how the simultaneous presence of an aromatic ring at the 5'-position of an inosine derivative and a positively charged imidazolium ring in the purine base drive the conformation of the nucleoside toward a very major conformer in solution that is stabilized by an intramolecular cation-pi interaction. Therefore, the cation-pi interaction between imidazolium ions and aromatic rings can also be proposed in the design of small molecules where this type of interaction is desirable. The imidazolium ion can be obtained by a simple acidification of the pH of the media. So a simple change in pH can shift the conformational equilibrium from a random to a restricted conformation stabilized by an intramolecular cation-pi interaction. Thus the here described nucleosides can be considered as a new class of pH-dependent conformationally switchable molecules. |
20192192 | Organic radicals as spin filters. | Molecular spintronics has received extensive interest in recent years. Due to their favorable properties such as long spin coherence lengths and an amenability to fine-tuning via chemical substituents, organic materials play a prominent role in this field. Here we discuss how organic radicals may act as spin filters in the coherent tunneling regime and how they may be tuned to filter either majority- or minority-spin electrons by adding electron-donating or -withdrawing substituents. For a set of benzene-based model systems, we identify dips in the spin-resolved transmission, which may be caused by destructive interference, as a desirable feature when aiming for efficient spin filtering. Furthermore, the qualitative predictions made for our model systems are shown to be transferable to larger stable radicals. |
20192193 | Critical nuclei size, initial particle size and packing effect on the phase stability of sol-peptization-gel-derived nanostructured titania. | The influence of the initial particle size and packing of anatase crystallites on the phase stability of nanostructured titania was investigated. Dried anatase gels with different degrees of particle packing were prepared through the peptization-induced electrostatic stabilization of primary particles in the sol. The initial size of anatase primary particles was varied by precalcination prior to the anatase-rutile phase transformation that occurred during final calcination. In the case of well-packed titania, the initial size of anatase primary particles does not influence the phase-transformation behavior whereas loosely packed titania shows a strong initial anatase primary particle size dependence on the phase-transformation behavior. |
20192194 | Two-component dendritic chain reactions: experiment and theory. | New analytical diagnostic techniques that are based on signal-amplification mechanisms could significantly improve the sensitivity of detection of various analytes. We have developed a new approach to achieving exponential amplification of a diagnostic signal through a ponent dendritic chain reaction. The chain reaction generated the analyte of interest and thereby initiated additional diagnostic cycles. The system was designed for the detection of hydrogen peroxide and produced significantly larger intensity of diagnostic signal than a classic probe. In addition, a mathematical model that simulates the disassembly kinetics of ponent and ponent reactions was developed and shown to correlate well with the observed experimental data. The modularity and flexibility of a ponent detection system should allow extension to the detection of other analytes. |
20192196 | Onset of carbon-carbon bonding in Ta(5)C(y) (y = 0-6) clusters: a threshold photoionization and density functional theory study. | We have used photoionization efficiency spectroscopy to determine ionization energies (IEs) of the gas-phase tantalum-carbide clusters Ta(5)C(y) (y = 0-6). The structures of the clusters observed in the experiment are assigned paring the experimental IEs with those of candidate isomers, calculated by density functional theory. peting geometries of the underlying Ta(5) cluster are found to be present in the assigned Ta(5)C(y) structures; either a "prolate" or "distorted oblate" trigonal bipyramid geometry. The onset of carbon-carbon bonding in the Ta(5)C(y) series is proposed to occur at y = 6, with the structure of Ta(5)C(6) containing two molecular C(2) units. |
20192198 | Reaction of alpha-ene-vinylcyclopropanes: type II intramolecular [5+2] cycloaddition or [3+2] cycloaddition? | Exposure of alpha-ene-VCPs to catalytic [Rh(dppm)]SbF(6) led to the discovery of a novel Rh(I)-catalyzed [3+2] reaction, which was shown to be efficient for the construction of 5/6- and pounds rather than the anticipated type II [5+2] products. |
20192195 | Computational design and elaboration of a de novo heterotetrameric alpha-helical protein that selectively binds an emissive abiological (porphinato)zinc chromophore. | The first example of putationally de novo designed protein that binds an emissive abiological chromophore is presented, in which a sophisticated level of cofactor discrimination is pre-engineered. This heterotetrameric, C(2)-symmetric bundle, A(His):B(Thr), uniquely binds (5,15-di[(4-carboxymethyleneoxy)phenyl]porphinato)zinc [(DPP)Zn] via histidine coordination plementary noncovalent interactions. The A(2)B(2) heterotetrameric protein reflects ligand-directed elements of both positive and negative design, including hydrogen bonds to second-shell ligands. Experimental support for the appropriate formulation of [(DPP)Zn:A(His):B(Thr)](2) is provided by UV/visible and circular dichroism spectroscopies, size exclusion chromatography, and analytical ultracentrifugation. Time-resolved transient absorption and fluorescence spectroscopic data reveal classic excited-state singlet and triplet PZn photophysics for the A(His):B(Thr):(DPP)Zn protein (k(fluorescence) = 4 x 10(8) s(-1); tau(triplet) = 5 ms). The A(2)B(2) apoprotein has immeasurably low binding affinities for related [porphinato]metal chromophores that include a (DPP)Fe(III) cofactor and the zinc metal ion hemin derivative [(PPIX)Zn], underscoring the exquisite active-site binding discrimination realized in putationally designed protein. Importantly, elements of design in the A(His):B(Thr) protein ensure that interactions within the tetra-alpha-helical bundle are such that only the heterotetramer is stable in solution; corresponding homomeric bundles present unfavorable ligand-binding environments and thus preclude protein structural rearrangements that could lead to binding of (porphinato)iron cofactors. |
20192197 | Nickel, manganese, cobalt, and iron-catalyzed deprotonative arene dimerization. | A number of first-row transition metal salts catalyze deprotonative dimerization of acidic arenes. Under the atmosphere of oxygen, nickel, manganese, cobalt, and iron chlorides have been shown to dimerize five- and six-membered ring heterocycles as well as electron-poor arenes. Both tetramethylpiperidide and dicyclohexylamide bases can be employed; however, the former afford slightly higher yields. |
20192200 | Magnetic properties of transition-metal-doped tubular gold clusters: M@Au(24) (M = V, Cr, Mn, Fe, Co, and Ni). | The energetic and magnetic properties of the tubular cluster Au(24), doped endohedrally by a 3d transition-metal atom M (M = V, Cr, Mn, Fe, Co, and Ni) have been investigated by the scalar relativistic density functional simulations. It is found that (1) these 3d transition-metal atoms can be encapsulated stably into the tubular Au(24) and do not significantly perturb the atomic and electronic structures of the parent tubular Au(24), (2) the infrared (IR) spectra of the tubular Au(24) cluster are significantly changed by the dopant atoms, inducing a characteristic absorption peak in the IR spectra of all the M@Au(24), and (3) protected by the tubular Au(24), the 3d states of the dopant atoms are largely localized, and the atom-like magnetism is retained for all the doped gold clusters, exhibiting 3, 6, 5, 4, 3, and 2 mu(B) for V-Ni, respectively. |
20192199 | Nanomagnetic competition assay for low-abundance protein biomarker quantification in unprocessed human sera. | A novel giant magnetoresistive sensor and uniform high-magnetic-moment FeCo nanoparticles (12.8 nm)-based detecting platform with minimized detecting distance was developed for rapid biomolecule quantification from body fluids. Such a system demonstrates specific, accurate, and quick detection and quantification of interleukin-6, a low-abundance protein and a potential cancer biomarker, directly in 4 muL of unprocessed human sera. This platform is expected to facilitate the identification and validation of disease biomarkers. It may eventually lead to a low-cost personal medical device for chronic disease early detection, diagnosis, and prognosis. |
20192201 | BF3-promoted synthesis of diarylhexahydrobenzo[f]isoquinoline. | An easy and straightforward synthesis of 6,10b-diarylhexahydrobenzo[f]isoquinoline by the repeated treatment of boron trifluoride etherate (BF(3) x OEt(2)) is reported. The overall transformation from 4-arylpiperidin-3-one to benzo[f]isoquinoline proceeds via ring contraction, chain elongation, and intramolecular electrophilic cyclization in moderate yields. It presents a novel rearrangement reaction catalyzed by boron trifluoride etherate and broadens the scope of application. |
20192202 | Substituent effects on dynamics at conical intersections: cyclopentadienes. | Substituent effects on dynamics at conical intersections are investigated by means of femtosecond time-resolved photoelectron spectroscopy for cyclopentadiene and its substituted analogues 1,2,3,4-tetramethylcyclopentadiene, 1,2,3,4,5-pentamethylcyclopentadiene, and 1,2,3,4-tetramethyl-5-propylcyclopentadiene. By UV excitation to the S(2) (1(1)B(2)) state, the influence of these substitutions on dynamics for the initially excited S(2) (1(1)B(2)) surface and the spectroscopically dark S(1) (2(1)A(1)) surface were investigated. We observed that the dynamics depend only on a small number of specific vibrations. Whereas dynamics at the S(2)/S(1)-conical intersection are independent of substitution at the 5-position, internal conversion dynamics on the S(1) (2(1)A(1)) surface slow down as the inertia of the 5-substituent increases. Contrary to the expectations of simple models of radiationless transitions, an increasing density of states does not lead to faster processes, suggesting that a true dynamical picture of vibrational motions at conical intersections will be required. |
20192203 | Z-selective intramolecular Horner-Wadsworth-Emmons reaction for the synthesis of macrocyclic lactones. | When the substrates (ArO)(2)P(O)CH(2)CO(2)---CHO (Ar = Ph, o-t-BuPh) were added to a THF solution containing 3 equiv of NaH at 0 degrees C or NaI-DBU at rt over 1-10 h, the intramolecular Horner-Wadsworth-Emmons reaction proceeded efficiently to give the 12-18-membered-ring lactones in 69-93% yields with 89-100% Z selectivity. On the other hand, (EtO)(2)P(O)CH(2)CO(2)---CHO gave the 13-18-membered-ring lactones in 52-82% yields with 89-99% E selectivity using LiCl-DBU in MeCN or THF. |
20192204 | Effects of cooking and subcellular distribution on the bioaccessibility of trace elements in two marine fish species. | In current human health risk assessment, the maximum acceptable concentrations of contaminants in food are mostly based on the total concentrations. However, the total concentration of contaminants may not always reflect the available amount. Bioaccessibility determination is thus required to improve the risk assessment of contaminants. This study used an in vitro digestion model to assess the bioaccessibility of several trace elements (As, Cd, Cu, Fe, Se, and Zn) in the muscles of two farmed marine fish species (seabass Lateolabrax japonicus and red seabream Pagrosomus major ) of different body sizes. The total concentrations and subcellular distributions of these trace elements in fish muscles were also determined. Bioaccessibility of these trace elements was generally high (>45%), and the lowest bioaccessibility was observed for Fe. Cooking processes, including boiling, steaming, frying, and grilling, generally decreased the bioaccessibility of these trace elements, especially for Cu and Zn. The influences of frying and grilling were greater than those of boiling and steaming. The relationship of bioaccessibility and total concentration varied with the elements. A positive correlation was found for As and Cu and a negative correlation for Fe, whereas no correlation was found for Cd, Se, and Zn. A significant positive relationship was demonstrated between the bioaccessibility and the elemental partitioning in the heat stable protein fraction and in the trophically available fraction, and a negative correlation was observed between the bioaccessibility and the elemental partitioning in metal-rich granule fraction. Subcellular distribution may thus affect the bioaccessibility of metals and should be considered in the risk assessment for seafood safety. |
20192205 | Fruiting body of Niuchangchih (Antrodia camphorata) protects livers against chronic alcohol consumption damage. | An alcoholic fatty liver disease was induced by drinking water containing 20% (w/w) alcohol. Therapeutic groups were orally administrated dosages of 0.25 g silymarin/kg body weight (BW) and a low dosage of Niuchangchih (Antrodia camphorata) (0.025 g/kg BW) and a high dosage of Niuchangchih (0.1 g/kg BW) per day. Niuchangchih, especially at the high dosage, not only showed a hypercholesterolemic effect (p < 0.05) but also reduced (p < 0.05) hepatic lipids in alcohol-fed rats. Those beneficial effects could be partially attributed to higher (p < 0.05) fecal cholesterol and bile acid outputs, as well as downregulations (p < 0.05) of 3-hydroxy-3-methylglutaryl-CoA reductase, sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase, fatty acid synthase, and malic enzyme gene expressions; meanwhile, there was an upregulation of low-density lipoprotein receptor and peroxisome proliferator-activated alpha gene expression. Besides, Niuchangchih also enhanced (p < 0.05) the liver glutathione, Trolox equivalent antioxidant capacity, and activities of superoxide dismutase, catalase, and glutathione peroxidase and decreased the liver malondialdehyde content, which also partially contributed to the lowered (p < 0.05) serum aspartate aminotransferase levels and no observed lesion in the histological examination of alcohol-fed rats. |
20192206 | Bound volatile precursors in genotypes in the pedigree of 'Marion' blackberry (Rubus sp.). | Glycosidically bound volatiles and precursors in genotypes representing the pedigree for 'Marion' blackberry were investigated over two growing seasons. The volatile precursors were isolated using a C18 solid-phase extraction column. After enzymatic hydrolysis, the released volatiles were analyzed using stir bar sorptive extraction gas chromatography-mass spectrometry (GC-MS) and direct microvial insert thermal desorption GC-MS. The most abundant volatile precursors in the genotypes were alcohols, followed by shikimic acid derivatives. High amounts of furanone glycosides were also detected, while norisoprenoids only existed in a small amount in blackberries. The volatile position in the genotypes in the 'Marion' pedigree was very similar to their free volatile distribution. 'Logan' and 'Olallie' predominantly had bound norisoprenoids. Wild 'Himalaya' predominated with terpene alcohol and furaneol glycosides, whereas 'Santiam' and 'Chehalem' contained a high level of terpene alcohol glycosides. A similar inheritance pattern was also observed for some volatile precursors in the genotypes in the 'Marion' pedigree. A high content of linalool, hydroxylinalool, and alpha-ionol glycosides in 'Olallie' and a low content in 'Chehalem' resulted in a moderate level in their offspring 'Marion', while a low content of (E)-linalool oxide precursor in 'Olallie' and a high content in 'Chehalem' also resulted in a moderate level in 'Marion'. However, the concentration of furaneol glycosides in 'Marion' exceeded that of its two parents. |
20192207 | Conversion of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (F-BODIPYs) to dipyrrins with a microwave-promoted deprotection strategy. | 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacenes (F-BODIPYs) have been deprotected to give the corresponding free-base dipyrrins by heating a solution of the F-BODIPY in tert-butanol under 600 W of microwave irradiation in the presence of 6 equiv of potassium tert-butoxide for 40 min at 92 degrees C. Investigations of BODIPY modification at the meso position have also been undertaken and a meso-butyl product has been isolated. |
20192208 | 3,4-Propylenedioxypyrrole-based conjugated oligomers via Pd-mediated decarboxylative cross coupling. | An effective decarboxylative cross-coupling involving a 3,4-dioxypyrrole is reported. Several conjugated oligomers were synthesized in high yields using various aryl bromides. No copper salt or other transmetalating agent was required. The reaction conditions employed displayed relatively low sensitivity toward the presence of water. |
20192210 | First report on Cydonia oblonga Miller anticancer potential: differential antiproliferative effect against human kidney and colon cancer cells. | The present study reports the phenolic profile and antiproliferative properties of quince (Cydonia oblonga Miller) leaf and fruit (pulp, peel, and seed) against human kidney and colon cancer cells. The phenolic profiles of quince methanolic extracts were determined by high-performance liquid chromatography (HPLC)/diode array detector (DAD). 5-O-Caffeoylquinic acid was always one of the two major pounds present in all extracts, except for seed. Our results revealed that quince leaf and fruit extracts exhibited distinctive antiproliferative activities. The extracts from quince leaf showed concentration-dependent growth inhibitory activity toward human colon cancer cells (IC(50) = 239.7 +/- 43.2 microg/mL), while no effect was observed in renal adenocarcinoma cells. Concerning the fruit, seed extracts exhibited no effect on colon cancer cell growth, whereas strong antiproliferative efficiency against renal cancer cells was observed for the highest concentration assayed (500 microg/mL). The antiproliferative activity of pulp and peel extracts was low or absent in the selected range of extract concentrations. This is the first report showing that C. oblonga may be useful as a cancer chemopreventive and/or chemotherapeutic agent. |
20192209 | Ga(III)-catalyzed cycloisomerization approach to (+/-)-icetexone and (+/-)-epi-icetexone. | A Ga(III)-catalyzed cycloisomerization reaction provides expedient access to a benzannulated cycloheptadiene bearing a cyano group, which has been applied to the syntheses of several icetexane diterpenoids including icetexone and epi-icetexone. Key to the synthesis is a novel in situ generated diazene rearrangement. |
20192211 | Rigid hydrophilic structures for improved properties of conjugated polymers and nitrotyrosine sensing in water. | The efficient synthesis of a hydrophilic monomer bearing a three-dimensional pliant array of hydroxyl groups is described that prevents water-driven excimer features of hydrophobic poly(p-phenylene ethynylene) backbones. Sensitivity of the polymer to 3-nitrotyrosine is also discussed. |
20192212 | Determination of chloramphenicol residues in milk by enzyme-linked immunosorbent assay: improvement by biotin-streptavidin-amplified system. | A sensitive biotin-streptavidin amplified enzyme-linked immunosorbent assay (BA-ELISA) method was developed for the determination of chloramphenicol residues in milk. The biotin-streptavidin system was applied to enhance the sensitivity. After optimization, the detection limit of the method was found to be 0.042 +/- 0.006 ng mL(-1), which is 8-fold more sensitive than the petitive ELISA using the same antibody and coating antigen. The amplification mechanism of the biotin-streptavidin system and the major factors affecting the sensitivity of detection are discussed. This method was successfully applied to determine the chloramphenicol residues in milk samples with a simple and rapid extraction procedure, and good recoveries (85.66-109.67%) were obtained. The result indicated that the biotin-streptavidin system may be a valuable tool to improve the specific detection of trace veterinary drug residues and could be widely used for routine monitoring of food samples. |
20192213 | Two-step total syntheses of canthin-6-one alkaloids: new one-pot sequential Pd-catalyzed Suzuki-Miyaura coupling and Cu-catalyzed amidation reaction. | Canthin-6-one (1) and nine analogues including the naturally occurring 9-methoxycanthin-6-one (2) and amaroridine (3) are prepared rapidly and in high yields via a convergent "non-classical" strategy that focuses on construction of the central ring B. The strategy relies on itant Pd-catalyzed Suzuki-Miyaura C-C coupling followed by a Cu-catalyzed C-N coupling that can be achieved either stepwise or in a new one-pot protocol starting from the appropriate 8-bromo-1,5-naphthyridine. |
20192214 | Redox-active ligands facilitate bimetallic O2 homolysis at five-coordinate oxorhenium(V) centers. | Five-coordinate oxorhenium(V) anions with redox-active catecholate and amidophenolate ligands are shown to effect clean bimetallic cleavage of O(2) to give dioxorhenium(VII) products. A structural homologue with redox-inert oxalate ligands does not react with O(2). Redox-active ligands lower the kinetic barrier to bimetallic O(2) homolysis at five-coordinate oxorhenium(V) by facilitating formation and stabilization of intermediate O(2) adducts. O(2) activation occurs by two sequential Re-O bond forming reactions, which generate mononuclear eta(1)-superoxo species, and then binuclear plexes. Formation of both Re-O bonds requires trapping of a triplet radical dioxygen species by a cis-[Re(V)(O)(cat)(2)](-) anion. In each reaction the dioxygen fragment is reduced by 1e(-), so generation of each new Re-O bond requires that an oxometal fragment is oxidized by 1e(-). Complexes containing a redox-active ligand access a lower energy reaction pathway for the 1e(-) Re-O bond forming reaction because the metal fragment can be oxidized without a change in formal rhenium oxidation state. It is also likely that redox-active ligands facilitate O(2) homolysis by lowering the barrier to the formally spin-forbidden reactions of triplet dioxygen with the closed shell oxorhenium(V) anions. By orthogonalizing 1e(-) and 2e(-) redox at oxorhenium(V), the redox-active ligand allows high-valent rhenium to utilize a mechanism for O(2) activation that is atypical of oxorhenium(V) but more typical for oxygenase enzymes and models based on 3d transition metal ions: O(2) cleavage occurs by a net 2e(-) process through a series of 1e(-) steps. The implications for design of new multielectron catalysts for oxygenase-type O(2) activation, as well as the microscopic reverse reaction, O-O bond formation from coupling of two M=O fragments for catalytic water oxidation, are discussed. |
20192215 | Adsorption equilibria of water vapor on cork. | We report here for the first time plete thermodynamic study of water vapor adsorption on crude cork powder and plate. Adsorption-desorption isotherms were accurately measured by thermogravimetry at 283, 298, and 313 K in a large range of relative pressure. Adsorption enthalpies were determined by calorimetry as a function of loading. Adsorption-desorption isotherms exhibit a hysteresis due to the swelling of the material. The influence of the presence of lenticels on the adsorption properties of cork is found to be negligible. A detailed analysis and interpretation of adsorption data allow proposal of an adsorption mechanism in two steps. (i) First, water adsorbs on hydrophilic sites constituted by hydroxyl and methoxyl groups. (ii) Then water adsorption continues by clusters formation around the hydrophilic sites. |
20192216 | Combined use of thermomechanics and UV spectroscopy to rationalize the kinetics of bioactive compound (caffeine) mobility in a high solids matrix. | An investigation of the diffusional mobility of a pound (caffeine) within a carbohydrate matrix (glucose syrup) at a glassy consistency is reported. The experimental temperature range was from 30 to - 70 degrees C, and the techniques of modulated differential scanning calorimetry, small-deformation dynamic oscillation on shear, and UV spectrometry were employed. It is not a straightforward matter to identify the relaxation dynamics of such a glassy matrix. This makes suggestions of the relationship between the structural properties of the matrix and the diffusional mobility of pounds reported earlier in the literature rather tenuous. To address this issue, we recorded mechanical spectra over the aforementioned temperature range and utilized bined framework of the Williams, Landel, and Ferry (WLF) equation with the time-temperature superposition principle to rationalize results. The protocol produced a fundamental definition of the glass transition temperature and free volume parameters of the glucose syrup sample within the glass transition region. Results were related to the kinetic rates of caffeine diffusion derived by UV spectroscopy leading to the conclusion that the diffusional mobility of the chemical substance is independent of the carbohydrate matrix. This conclusion was further supported by the high level of fractional free volume of caffeine, which is congruent with the predictions of the reaction rate theory (modified Arrhenius equation), pared to the collapsing levels of free volume in the glucose-syrup matrix that make appropriate WLF considerations. |
20192217 | Anti-inflammatory bioactivities of honokiol through inhibition of protein kinase C, mitogen-activated protein kinase, and the NF-kappaB pathway to reduce LPS-induced TNFalpha and NO expression. | Much recent research has demonstrated that honokiol, a pound originally isolated from Magnolia officinalis, has potent anticancer activities; however, the detailed molecular mechanism of its anti-inflammatory activity has not yet been fully addressed. In this study we demonstrated that honokiol inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha secretion in macrophages, without affecting the activity of the tumor necrosis factor-alpha converting enzyme. At the same time, honokiol not only inhibited nitric oxide expression in LPS-stimulated murine macrophages but also inhibited the LPS-induced phosphorylation of ERK1/2, JNK1/2, and p38. By means of confocal microscope analysis we demonstrated that phosphorylation and membrane translocation of protein kinase C-alpha, as well as NF-kappaB activation, were inhibited by honokiol in LPS-stimulated macrophages. Furthermore, it was found that honokiol neither antagonizes the binding of LPS to cells nor alters the cell surface expression of toll-like receptor 4 and CD14. Our current results have exhaustively described the anti-inflammatory properties of honokiol, which could lead to the possibility of its future pharmaceutical application in the realm of immunomodulation. |
20192218 | Long-chain N-vanillyl-acylamides from Capsicum oleoresin. | N-Vanillyl-acylamides (NVAs) naturally occur as capsaicinoids in Capsicum plants. NVAs with a longer chain acyl moiety (LCNVAs) have been developed as attractive tools for medicinal usage because of their capsaicin-like bioactive and physiological properties, without harmful irritancy. In this study, we isolated four LCNVAs from Capsicum oleoresin. Their structures were determined to be N-vanillyl-hexadecanamide (palvanil, 2), N-vanillyl-octadecanamide (stevanil, 3), N-vanillyl-9E-octadecenamide (olvanil, 4), and N-vanillyl-9E,12E-octadecadienamide (livanil, 5) by spectroscopic analysis and gas chromatography-mass spectrometry analysis of their methanolysis products. Furthermore, the existence of two LCNVAs in oleoresin, N-vanillyl-tetradecanamide (myrvanil, 1) and N-vanillyl-9E,12E,15E-octadecatrienamide (linvanil, 6), was suggested. The contents of these LCNVAs and the major capsaicinoids-capsaicin and dihydrocapsaicin-in three Capsicum oleoresins and the fresh fruits of two hot peppers were measured by a liquid chromatography-tandem mass spectrometry system. The content ratios of the total LCNVAs, except for myrvanil, versus the capsaicin in the oleoresins (0.1-41%) was significantly larger than that in fresh fruits (<0.01%). position of these LCNVAs in each oleoresin was similar to that of fatty acids in the oil fraction of each oleoresin. We observed no relationship between position of these LCNVAs in the fresh fruits. |
20192219 | Acrolein in wine: importance of 3-hydroxypropionaldehyde and derivatives in production and detection. | Certain lactic acid bacteria strains belonging to the genus Lactobacillus have been implicated in the accumulation of 3-hydroxypropionaldehyde (3-HPA) during anaerobic glycerol fermentation. In aqueous solution 3-HPA undergoes reversible dimerization and hydration, resulting in an equilibrium state between different derivatives. Wine quality may promised by the presence of 3-HPA due to the potential for spontaneous conversion into acrolein under winemaking conditions. Acrolein is highly toxic and has been implicated in the development of bitterness in wine. Interconversion between 3-HPA derivatives and acrolein is plex and highly dynamic process driven by hydration and dehydration reactions. Acrolein is furthermore highly reactive and its steady-state concentration plex systems very low. As a result, analytical detection and quantification in solution is problematic. This paper reviews the biochemical and environmental conditions leading to accumulation of its precursor, 3-HPA. Recent advances in analytical detection are summarized, and the roles played by natural chemical derivatives are highlighted. |
20192220 | Bioactive compounds of four hot pepper varieties (Capsicum annuum L.), antioxidant capacity, and intestinal bioaccessibility. | Pepper fruits (Capsicum annuum) contain a wide array of phytochemicals with well-known antioxidant properties. Since pounds depend on their bioavailability to exert beneficial effects, it was crucial to estimate the extent of release from the food matrix and thus their bioaccessibility. Accordingly, we determined the individual carotenoid and phenolic content as well as the antioxidant properties of four red hot dried cultivars (Capsicum annuum L.) of high consumption in Mexico and estimated the extent of intestinal bioaccessibility of carotenoids with significance in human health, beta-carotene, beta-cryptoxanthin, and zeaxanthin, using an in vitro gastrointestinal model. Hot dried peppers at ripe stage had a high content of pounds that exhibited significant antioxidant properties (26-80 micromol trolox equivalents/g of dry matter), such as polyphenols (>2000 mg/100 g of dry matter) and carotenoids (95-437 mg/100 g of dry matter), which were partially bioaccessible. The amount released from the food matrix by the action of digestive enzymes was about 75% for total polyphenols, up to 49% for both beta-carotene and zeaxanthin, and up to 41% for beta-cryptoxanthin. The results suggest that from 50 to 80% of these carotenoids could reach the colon to be potentially fermented or could remain unavailable. |
20192221 | Highly diastereoselective synthesis of substituted pyrrolidines using a sequence of azomethine ylide cycloaddition and nucleophilic cyclization. | Although cycloadditions of azomethine ylides usually give mixtures of endo/exo adducts, we successfully tuned the mechanistic path of a new reaction cascade to afford substituted pyrrolidines in high yields and diastereomeric purity. This was achieved by forcing the demetalation of tin- or silicon-substituted iminium ions, followed by azomethine ylide cycloaddition and nucleophilic cyclization. plexity is thus built rapidly in a fully controlled one-pot reaction cascade. |
20192222 | Metalla-cope rearrangements: bridging organic and inorganic chemistry. | Density functional theory calculations are performed to explore both concerted chairlike and boatlike as well as stepwise mechanisms of the Cope rearrangement of two hypothetical metalladienes. An osma-1,5-hexadiene is designed by substituting CH(2) in 1,5-hexadiene by its isolobal analogue, 16-electron Os(PH(3))(4). The energy of activation corresponding to the rearrangement of osma-1,5-hexadiene involving the chairlike saddle point puted as 37.4 kcal/mol, 3.9 kcal/mol above the energy barrier of the parent 1,5-hexadiene calculated with the same method and basis set, and is 4.5 kcal/mol below that of the boatlike pathway. In another isolobal replacement, the CH in 1,5-hexadiene is substituted by a 15-electron Re(PH(3))(3) fragment. Now the chairlike rearrangement of the rhenia-1,5-hexadiene has an E(a) value of 23.0 kcal/mol, 10.8 kcal/mol less than the energy barrier of the parent 1,5-hexadiene calculated at the same level of theory. The ring inversion of the chair and osma-chair diradical intermediates of the stepwise reaction pathway is also examined and is found in both cases to proceed through a very flat potential energy surface involving twist intermediates. |
20192223 | Agonists and antagonists of antennal responses of gypsy moth (Lymantria dispar) to the pheromone (+)-disparlure and other odorants. | Insects use the sense of smell to guide many behaviors that are important for their survival. The gypsy moth uses a pheromone to bring females and males together over long distances. Male moth antennae are equipped with innervated sensory hairs that selectively respond to ponents and other odors. Host plant odors, in particular, are detected by moths and sometimes cause an enhancement of the antennal and behavioral responses of the moths to their pheromone. Inspired by naturally occurring agonists and antagonists of insect pheromone responses, we have screened, by electroantennogram (EAG) recordings, a collection pound sets and of pounds. We have detected interference of pounds with the EAG responses of male gypsy moth antennae to the pheromone. We describe three activities: (1) short-term inhibition or enhancement of pound + pheromone plumes, (2) long-term inhibition of pure pheromone plumes following a pound + pheromone plume, and (3) inhibition of the recovery phase of pound + pheromone plumes. Long-term inhibition was robust, decayed within 30 s, and correlated with the inhibition of recovery; for both activities clear structure-activity patterns were detected. mercial repellent N,N-diethyltoluamide (DEET) was included parison. The most active and reproducible short-term inhibitor was a mixture of 1-allyl-2,4-dimethoxybenzene and 2-allyl-1,3-dimethoxybenzene. The most active long-term inhibitors were a set of 1-alkoxy-4-propoxybenzenes, DEET, and 1-ethoxy-4-propoxybenzene. DEET was more specific in the olfactory responses it inhibited than 1-ethoxy-4-propoxybenzene, and DEET did not inhibit recovery, whereas 1-ethoxy-4-propoxybenzene did. Target sites for the three activities are discussed. |
20192224 | Fragment-based deconstruction of Bcl-xL inhibitors. | Fragment-based drug design consists of screening pounds in order to identify low-affinity ligands that are then modified or linked to yield potent inhibitors. The method thus attempts to build bioactive molecules in a modular way and relies on the hypothesis that the fragment binding mode will be conserved upon elaboration of the active molecule. If the inverse process is considered, do the fragments resulting from the deconstruction of high-affinity inhibitors recapitulate their binding mode in the large molecule? Few studies deal with this issue. Here, we report the analysis of 22 fragments resulting from the dissection of 9 inhibitors of the antiapoptotic protein Bcl-x(L). To determine if the fragments retained affinity toward the protein and identify their binding site, ligand-observed and protein-observed NMR experiments were used. The analysis of the fragments behavior illustrates plexity of low-affinity protein-ligand interactions involved in the fragment-based construction of bioactive molecules. |
20192225 | Synthesis and QSAR of quinazoline sulfonamides as highly potent human histamine H4 receptor inverse agonists. | Hit optimization of the class of quinazoline containing histamine H(4) receptor (H(4)R) ligands resulted in a sulfonamide substituted analogue with high affinity for the H(4)R. This moiety leads to improved physicochemical properties and is believed to probe a distinct H(4)R binding pocket that was previously identified using pharmacophore modeling. By introducing a variety of sulfonamide substituents, the H(4)R affinity was optimized. The interaction of the new ligands, bination with a set of previously published pounds, was described by a QSAR equation. Pharmacological studies revealed that the sulfonamide analogues have excellent H(4)R affinity and behave as inverse agonists at the human H(4)R. In vivo evaluation of the potent 2-(6-chloro-2-(4-methylpiperazin-1-yl)quinazoline-4-amino)-N-phenylethanesulfonamide (54) (pK(i) = 8.31 +/- 0.10) revealed it to have anti-inflammatory activity in an animal model of acute inflammation. |
20192227 | A unique nickel system having versatile catalytic activity of biological significance. | A new dinuclear plex, [Ni(2)(LH(2))(H(2)O)(2)(OH)(NO(3))](NO(3))(3) (1), of an partmental ligand 2,6-bis(N-ethylpiperazine-iminomethyl)-4-methyl-phenolato, has been synthesized and structurally characterized. The X-ray single crystal structure analysis shows that the piperazine moieties assume the expected chair conformation and are protonated. plex 1 exhibits versatile catalytic activities of biological significance, viz. catecholase, phosphatase, and DNA cleavage activities, etc. The catecholase activity of plex observed is very dependent on the nature of the solvent. In acetonitrile medium, plex is inactive to exhibit catecholase activity. On the other hand, in methanol, it catalyzes not only the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) but also tetrachlorocatechol (TCC), a catechol which is very difficult to oxidize, under aerobic conditions. UV-vis spectroscopic investigation shows that TCC oxidation proceeds through the formation of an intermediate. The intermediate has been characterized by an electron spray ionizaton-mass spectrometry study, which suggests a bidentate rather than a monodentate mode of TCC coordination in that intermediate, and this proposition have been verified by density functional theory calculation. plex also exhibits phosphatase (with substrate p-nitrophenylphosphate) and DNA cleavage activities. The DNA cleavage activity exhibited plex 1 most probably proceeds through a hydroxyl radical pathway. The bioactivity study suggests the possible applications plex 1 as a site specific recognition of DNA and/or as an anticancer agent. |
20192228 | Theoretical study on the possibility of using frustrated lewis pairs as bifunctional metal-free dehydrogenation catalysts of ammonia-borane. | Density functional theory calculations have been carried out to study the possibility of using "frustrated Lewis pairs" (FLPs) as bifunctional metal-free dehydrogenation catalysts of ammonia-borane, NH(3)BH(3) (AB), according to the following points: (1) some FLPs react with H(2) at low temperature and the hydrogenated products release H(2) at high temperature; (2) some FLPs hydrogenate imines by taking the protic (N-bound) and hydridic (B-bound) H atoms of AB. In this work, the N/B pair (N-PMTN-CH(2)C(6)H(4)B(C(6)F(5))(2)) is chosen to explore the possibility that FLPs release H(2) from AB. Two steps are involved in the proposed mechanism: first, AB is dehydrogenated by the N/B pair to form the pound and NH(2)BH(2) at low temperature, and then H(2) is released from the pound at 110 degrees C and the N/B pair regenerates. petitive reaction channels have been considered. The calculational results show that the dehydrogenation of AB by the N/B pair has the lowest free-energy barrier. On the basis of the experimental N/B pair, a new dehydrogenation catalyst of AB has been designed, which can release H(2) from AB under milder conditions than the former. This work may be helpful for the experimental chemists to broaden the application of FLPs and to design new dehydrogenation catalysts of AB. |
20192226 | Partial steps of charge translocation in the nonpumping N139L mutant of Rhodobacter sphaeroides cytochrome c oxidase with a blocked D-channel. | The N139L substitution in the D-channel of cytochrome oxidase from Rhodobacter sphaeroides results in an approximately 15-fold decrease in the turnover number and a loss of proton pumping. Time-resolved absorption and electrometric assays of the F --> O transition in the N139L mutant oxidase result in three major findings. (1) Oxidation of the reduced enzyme by O(2) shows approximately 200-fold inhibition of the F --> O step (k approximately 2 s(-1) at pH 8) which is patible with enzyme turnover ( approximately 30 s(-1)). Presumably, an abnormal intermediate F(deprotonated) is formed under these conditions, one proton-deficient relative to a normal F state. In contrast, the F --> O transition in N139L oxidase induced by single-electron photoreduction of intermediate F, generated by reaction of the oxidized enzyme with H(2)O(2), decelerates to an patible with enzyme turnover. (2) In the N139L mutant, the protonic phase of Deltapsi generation coupled to the flash-induced F --> O transition greatly decreases in rate and magnitude and can be assigned to the movement of a proton from E286 to the binuclear site, required for reduction of heme a(3) from the Fe(4+) horizontal lineO(2-) state to the Fe(3+)-OH(-) state. Electrogenic reprotonation of E286 from the inner aqueous phase is missing from the F --> O step in the mutant. (3) In the N139L mutant, the KCN-insensitive rapid electrogenic phase may posed of ponents with lifetimes of approximately 10 and approximately 40 mus and a magnitude ratio of approximately 3:2. The 10 mus phase matches vectorial electron transfer from Cu(A) to heme a, whereas the 40 ponent is assigned to intraprotein proton displacement across approximately 20% of the membrane dielectric thickness. This proton displacement might be triggered by rotation of the charged K362 side chain coupled to heme a reduction. The ponents of the rapid electrogenic phase have been resolved subsequently with other D-channel mutants as well as with cyanide-inhibited wild-type oxidase. The finding helps to reconcile the unusually high relative contribution of the microsecond electrogenic phase in the bacterial enzyme ( approximately 30%) with the net electrogenicity of the F --> O transition coupled to transmembrane transfer of two charges per electron. |
20192230 | Nanoscale memristor device as synapse in neuromorphic systems. | A memristor is a two-terminal electronic device whose conductance can be precisely modulated by charge or flux through it. Here we experimentally demonstrate a nanoscale silicon-based memristor device and show that a hybrid posed plementary metal-oxide semiconductor neurons and memristor synapses can support important synaptic functions such as spike timing dependent plasticity. Using memristors as synapses in neuromorphic circuits can potentially offer both high connectivity and high density required for puting. |
20192229 | Fabrication and characterization of large-area, semiconducting nanoperforated graphene materials. | We demonstrate the fabrication of nanoperforated graphene materials with sub-20-nm features using cylinder-forming diblock copolymer templates across >1 mm(2) areas. Hexagonal arrays of holes are etched into graphene membranes, and the remaining constrictions between holes interconnect forming a b structure. Quantum confinement, disorder, and localization effects modulate the electronic structure, opening an effective energy gap of 100 meV in the nanopatterned material. The field-effect conductivity can be modulated by 40x (200x) at room temperature (T = 105 K) as a result. A room temperature hole mobility of 1 cm(2) V(-1) s(-1) was measured in the fabricated nanoperforated graphene field effect transistors. This scalable strategy for modulating the electronic structure of graphene is expected to facilitate applications of graphene in electronics, optoelectronics, and sensing. |
20192231 | Probing strain in bent semiconductor nanowires with Raman spectroscopy. | We present a noninvasive optical method to determine the local strain in individual semiconductor nanowires. InP nanowires were intentionally bent with an atomic force microscope and variations in the optical phonon frequency along the wires were mapped using Raman spectroscopy. Sections of the nanowires with a high curvature showed significantly broadened phonon lines. These observations together with deformation potential theory show pressive and tensile strain inside the nanowires is the physical origin of the observed phonon energy variations. |
20192232 | Photovoltaics with piezoelectric core-shell nanowires. | We report on a theoretical discovery of a generic piezoelectric field in strained pound semiconductor nanowires. We show, using both an analytical model and numerical simulations based on fully electroelastically coupled continuum elasticity theory, that lattice-mismatch-induced strain in an epitaxial core-shell nanowire gives rise to an internal electric field along the axis of the nanowire. This piezoelectric field results predominantly from atomic layer displacements along the nanowire axis within both the core and shell materials and can appear in both zinc blende and wurtzite crystalline core-shell nanowires. The effect can be employed to separate photon-generated electron-hole pairs in the core-shell nanowires and thus offers a new device concept for solar energy conversion. |
20192235 | Controlling half-metallicity of graphene nanoribbons by using a ferroelectric polymer. | On the basis of putational approaches, we present a new method to drive zigzag graphene nanoribons (ZGNRs) into the half-metallic state using a ferroelectric material, poly(vinylidene fluoride) (PVDF). Owing to strong dipole moments of PVDFs, the ground state of the ZGNR es half-metallic when a critical coverage of PVDFs is achieved on the ZGNR. Since ferroelectric polymers are physisorbed, the direction of the dipole field in PVDFs can be rotated by relatively small external electric fields, and the switching between half-metallic and insulating states may be achieved. Our results suggest that, without excessively large external gate electric fields, half-metallic states of ZGNRs are realizable through the deposition of ferroelectric polymers and their electronic and magnetic properties are controllable via noninvasive mutual interactions. |
20192233 | Engineering advanced capsosomes: maximizing the number of subcompartments, cargo retention, and temperature-triggered reaction. | Advanced mimics of cells require a large yet controllable number of partments encapsulated within a scaffold, equipped with a trigger to initiate, terminate, and potentially restart an enzymatic reaction. Recently introduced capsosomes, polymer capsules containing thousands of liposomes, are a promising platform for the creation of artificial cells. Capsosomes are formed by sequentially layering liposomes and polymers onto particle templates, followed by removal of the template cores. Herein, we engineer advanced capsosomes and demonstrate the ability to control the number of partments and hence the degree of cargo loading. To achieve this, we employ a range of polymer separation layers and liposomes to form functional prising multiple layers of enzyme-loaded liposomes. Differences in conversion rates of an enzymatic assay are used to verify that multilayers of intact enzyme-loaded liposomes are assembled within a polymer hydrogel capsule. The size-dependent retention of the cargo encapsulated within the liposomal partments during capsosome assembly and its dependence on environmental pH changes are also examined. We further show that temperature can be used to trigger an enzymatic reaction at the phase transition temperature of the liposomal partments, and that the encapsulated enzymes can be utilized repeatedly in several subsequent conversions. These engineered capsosomes with tailored properties present new opportunities en route to the development of functional artificial cells. |
20192234 | Photoreduction at a distance: facile, nonlocal photoreduction of Ag ions in solution by plasmon-mediated photoemitted electrons. | Surface-immobilized, densely packed gold nanoparticles in contact with aqueous silver ions and exposed to red light rapidly photoreduce silver ions in solution producing radially symmetric metal deposits with diameters many times larger than the diameter of the illuminating laser beam. The average particle sizes in the deposit increase with radial distance from the center of the deposit. This reduction-at-a-distance effect arises from surface-plasmon-mediated photoemission, with the photoemitted electrons conducting along percolating silver pathways, reducing silver ions along these conducting channels and especially at their periphery, thereby propagating the effect of the illuminating laser outward. |
20192236 | Terpenoids from Daphne aurantiaca and their potential anti-inflammatory activity. | Phytochemical examination of the methanolic extract from the stem bark of Daphne aurantiaca led to the isolation of six new sesquiterpenoids, dauca-3,11-dien-2alpha,15-diol (1), 3-oxoguai-4-ene-11,12-diol (2), 4alpha,5alpha,8alpha,11alphaH-3-oxoguai-1(10)-en-12,8-olide-7alpha-diol (3), 4alpha,5alpha,8alpha,11betaH-3-oxoguai-1(10)-en-12,8-olide-7beta-diol (4), 4alpha,5betaH-guai-9,7(11)-dien-12,8-olide-1alpha,8alpha-diol (5), 4alpha,5alphaH-guai-9,7(11)-dien-12,8-olide-1alpha,8alpha-diol (6), and a new diterpenoid, 12-O-benzoylphorbol 13-nonanoate (7), together with 10 known terpenoids. pounds were tested for inhibitory activity against LPS-induced NO production in RAW 264.7 macrophages. Compounds 7, 8, 9, 10, and 11 showed potent inhibitory activities against NO production with IC(50) values of 0.01, 0.01, 0.06, 0.07, and 0.03 microM, respectively. |
20192238 | Synergistic effects on second harmonic generation of hybrid CdSe-Au nanoparticles. | Hybrid semiconductor-metal nanoparticles exhibit bination of properties from the ponents or even, more interestingly, synergetic properties which arise from the coupling between the two materials. In this work, we study the second harmonic generation (SHG) in CdSe-Au hybrid nanoparticles parison with ponents, using the Hyper-Rayleigh scattering (HRS) method. Possible contribution of symmetry effects was studied paring symmetric two-sided gold-tipped CdSe nanodumbbells with asymmetric one-sided quantum dot-Au (QD-Au) hybrids. A simplistic view of a symmetry effect is disproved in this case by the experimental data, which shows an unexpected reduction in the SHG response in both pared to the respective mixtures of Au and CdSe nanoparticles. For CdSe-Au hybrids with a long semiconductor rod segment, we find that the SHG response corresponds to a sum of the contributions from the semiconductor and the ponents. However, for QD-Au and smaller dumbbells, the SHG response is smaller than expected from a simple sum of the contribution from ponents. This reduction is assigned to the effects related to the CdSe-Au interfacial region within these hybrids. A first plausible contribution to the reduction is the dephasing induced by the gold, leading to diminished SHG from the ponent. This reduced response of the ponent is panied by reduced SHG from the ponent which is assigned to a partial change of the surface of the gold once an interface with CdSe is formed. These observations regarding the SHG response manifest the unique properties that arise from bination of a semiconductor and a metal within one hybrid nanoparticle. |
20192237 | Hyaluronidase inhibitors from "Cimicifugae Rhizoma" (a mixture of the rhizomes of Cimicifuga dahurica and C. heracleifolia). | From the 80% acetone extract of "Cimicifugae Rhizoma" (a mixture of Cimicifuga dahurica and C. heracleifolia used medicinally), seven new fukiic acid derivatives (1-7) and a new phenylethanoid derivative (8) were isolated along with eight pounds (9-16). Fukinolic acid (9) and cimicifugic acids A-J (10-16, 5-7) showed stronger hyaluronidase inhibitory activities than the positive control, rosmarinic acid. |
20192239 | Antiangiogenic metabolites from a marine-derived fungus, Hypocrea vinosa. | The aims of this study were to investigate the role of tyrosine kinase in intracellular signaling and to search for pounds with tyrosine kinase inhibitory activity from metabolites of marine-derived fungi. We initially prepared 400 extracts from 200 species of marine fungi and then subjected them to a tyrosine kinase screening assay using human umbilical vein endothelial cell lysate. Tyrosine kinase inhibitory activity was observed among certain metabolites of Hypocrea vinosa. We isolated one pound, SC2051 (1), as well as two pounds, hypochromins A (2) and B (3), which have a bis(naphtho-gamma-pyrone) skeleton. Compounds 1-3 showed tyrosine kinase inhibitory activity, with IC(50) values of 42.1, 58.7, and 18.0 microMu, respectively. pounds 1-3 exhibited inhibitory effects on proliferation, migration, and tubule formation. |
20192240 | Tetracenoquinocin and 5-iminoaranciamycin from a sponge-derived Streptomyces sp. Sp080513GE-26. | Two new anthracyclines, tetracenoquinocin (1) and 5-iminoaranciamycin (2), together with the pounds aranciamycin (3) and antibiotic SM 173B were isolated from the culture of Streptomyces sp. Sp080513GE-26 associated with a marine sponge, Haliclona sp. The structures of 1 and 2 were established on the basis of extensive NMR and MS analyses along with (13)C-labeling experiments. pounds 1-3 were evaluated for cytotoxicity against two cancer cell lines. |
20192241 | Role of magic-sized clusters in the synthesis of CdSe nanorods. | The dynamics of the CdSe nanorod synthesis reaction have been studied, giving attention to the kinetics of magic-sized clusters (MSCs) that form as intermediates in the overall reaction. The MSCs have a distinct absorption peak, and the kinetics of this peak give insight into the overall reaction mechanism. In these studies, the reaction mixture consists primarily of Cd(phosphonate)(2) and trioctyl phosphine selenium in a solution of trioctylphosphine (TOP) and trioctylphosphine oxide (TOPO). We find that the rate at which precursors react to form CdSe monomers and the rates at which monomers react to form nanoparticles can be varied by changing the chemistry of the reaction mixture. Decreasing the TOP concentration decreases the extent to which selenium is bound, both in the precursors and on the particles' surfaces, and thereby increases both the precursor to monomer and monomer to particle reaction rates. Decreasing the phosphonate concentration decreases the extent to which phosphonate binds cadmium in the precursors and on the surface of the nanoparticles, also increasing the rates of both reactions. This is also plished by the addition of inorganic acids which protonate the phosphonates. The presence of inorganic acids (impurities) is the primary reason that the overall synthesis reaction is faster in solutions made with technical grade rather than purified TOPO. The TOP and phosphonic acid concentrations are coupled because excess phosphonic acids react with TOP, forming TOPO and less strongly binding species, specifically phosphinic acids, phosphine oxides, and phosphines. |
20192242 | Gneyulins A and B, stilbene trimers, and noidesols A and B, dihydroflavonol-C-glucosides, from the bark of Gnetum gnemonoides. | Gneyulins A (1) and B (2), two new stilbene trimers consisting of oxyresveratrol constituent units, and noidesols A (3) and B (4), two new dihydroflavonol-C-glucosides, were isolated from the bark of Gnetum gnemonoides. The structures and configurations of 1-4 were elucidated on the basis of 2D NMR correlations and X-ray analysis. Gneyulins A (1) and B (2) showed inhibition of Na(+)-glucose transporters (SGLT-1 and SGLT-2). |
20192243 | Toolbox for regioselective lithiations of furo[2,3-c]pyridine. | A detailed procedure for successive regioselective lithiations of furo[2,3-c]pyridine is described by using n-BuLi and the [n-BuLi/LiDMAE] superbase. Several polysubstituted furo[2,3-c]pyridines have been efficiently synthesized and some of them were engaged in Pd- or Ni-catalyzed coupling reactions leading to 2,2'- or 7,7'-bifuro[2,3-c]pyridine ligands. |
20192244 | Differential metabolomics for quantitative assessment of oxidative stress with strenuous exercise and nutritional intervention: thiol-specific regulation of cellular metabolism with N-acetyl-L-cysteine pretreatment. | Despite several decades of active research, the success of large-scale clinical trials involving antioxidants remains equivocal given plex biological interactions of reactive oxygen/nitrogen species in human health. Herein, we outline a differential metabolomics strategy by capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) to assess the efficacy of nutritional intervention to attenuate oxidative stress induced by strenuous exercise. A healthy volunteer was recruited to perform a submaximal prolonged ergometer cycling trial until volitional exhaustion with frequent blood collection over a 6 h time interval, which included pre-, during, and postexercise periods while at rest. A follow-up study was subsequently performed by the same subject after high-dose oral intake of N-acetyl-L-cysteine (NAC) prior to performing the same exercise protocol under standardized conditions. Time-dependent changes in global metabolism of filtered red blood cell lysates by CE-ESI-MS were measured to reveal a significant attenuation of cellular oxidation associated with high-dose oral NAC intake relative to a control. Untargeted metabolite profiling allowed for the identification and quantification of several putative early- and late-stage biomarkers that reflected oxidative stress inhibition due to nutritional intervention, including oxidized glutathione (GSSG), reduced glutathione (GSH), 3-methylhistidine (3-MeHis), L-carnitine (C0), O-acetyl-L-carnitine (C2), and creatine (Cre). Our work demonstrates the proof-of-principle that NAC pretreatment is effective at dampening acute episodes of oxidative stress by reversible perturbations in global metabolism that can provide deeper insight into the mechanisms of thiol-specific protein inhibition relevant to its successful translation as a prophylaxis in clinical medicine. |
20192245 | Rolling circle amplification combined with gold nanoparticle aggregates for highly sensitive identification of single-nucleotide polymorphisms. | A highly sensitive and specific colorimetry-based rolling circle amplification (RCA) assay method for single-nucleotide polymorphism genotyping has been developed. A circular template is generated by ligation upon the recognition of a point mutation on DNA targets. An RCA amplification is then initiated using the circular template in the presence of Phi29 polymerase. The RCA product can be digested by a restricting endonuclease, and the cleaved DNA fragments can mediate the aggregation of gold nanoparticle-tagged DNA probes. This causes a colorimetric change of the solution as the indicator of the mutation occurrence, which can be detected using UV-vis spectroscopy or viewed by naked eyes. On the basis of the high amplification efficiency of Phi29 polymerase, a mutated target of approximately 70 fM can be detected in this assay. In addition, the protection of the circle template using phosphorothioated nucleotides allows the digestion reaction to be performed simultaneously in RCA. Moreover, DNA ligase offers high fidelity in distinguishing the mismatched bases at the ligation site, resulting in positive detection of mutant targets even when the ratio of the wild-type to the mutant is 10,000:1. The developed RCA-based colorimetric detection scheme was demonstrated for SNP typing of beta-thalassemia gene at position -28 in genomic DNA. |
20192246 | Electrically controlled giant piezoresistance in silicon nanowires. | Herein we demonstrate giant piezoresistance in silicon nanowires (NWs) by the modulation of an electric field-induced with an external electrical bias. Positive bias for a p-type device (negative for an n-type) partially depleted the NWs forming a pinch-off region, which resembled a funnel through which the electrical current squeezed. This region determined the total current flowing through the NWs. In this report, bined the electrical biasing with the application of mechanical stress, which impacts the charge carriers' concentration, to achieve an electrically controlled giant piezoresistance in nanowires. This phenomenon was used to create a stress-gated field-effect transistor, exhibiting a maximum gauge factor of 5000, 2 orders of magnitude increase over bulk value. Giant piezoresistance can be tailored to create highly sensitive mechanical sensors operating in a discrete mode such as nanoelectromechanical switches. |
20192247 | Cytotoxic activities of several geranyl-substituted flavanones. | Nine geranylated flavanones isolated from the fruits of Paulownia tomentosa (4-12) and two from the roots of Morus alba (13 and 14) were examined for cytotoxicity to selected human cancer cell lines and normal human fibroblasts. Cytotoxicity was determined in vitro using a calcein AM cytotoxicity assay. Cytotoxicity for the THP-1 monocytic leukemia cell line was tested using erythrosin B cell staining. The pounds tested pared with the known simple flavanone standards taxifolin (1), naringenin (2), and hesperetin (3) and with the standard anticancer drugs olomoucine II, diaziquone, and oxaliplatin and the pound camptothecin, and showed different levels of cytotoxicity. The effects of structural changes on cytotoxic activity, including geranyl substitution of the flavanone skeleton and the oxidation pattern of ring B of the flavanones, are discussed. |
20192248 | Subcellular localization of a fluorescent artemisinin derivative to endoplasmic reticulum. | A cytotoxic artemisinin derivative conjugated with a fluorescent dansyl moiety was synthesized and its subcellular localization in Hep3B cells was examined. Comparison of the localization signals of the fluorescent artemisinin derivative with organelle specific dyes revealed that endoplasmic reticulum (ER) is the main site of its accumulation. |
20192249 | A comprehensive approach to the profiling of the cooked meat carcinogens 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, and their metabolites in human urine. | A targeted liquid chromatography/tandem mass spectrometry-based metabolomics type approach, employing a triple stage quadrupole mass spectrometer in the product ion scan and selected reaction monitoring modes, was established to profile 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and their principal metabolites in the urine of omnivores. A mixed-mode reverse phase cation exchange resin enrichment procedure was employed to isolate MeIQx and its oxidized metabolites, 2-amino-8-(hydroxymethyl)-3-methylimidazo[4,5-f]quinoxaline (8-CH(2)OH-IQx) and 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid (IQx-8-COOH), which are produced by cytochrome P450 1A2 (P450 1A2). The phase II conjugates N(2)-(beta-1-glucosiduronyl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and N(2)-(3,8-dimethylimidazo[4,5-f]quinoxalin-2-yl)-sulfamic acid were measured indirectly, following acid hydrolysis to form MeIQx. The enrichment procedure permitted the simultaneous analysis of PhIP, N(2)-(beta-1-glucosidurony1)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, N3-(beta-1-glucosidurony1)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-1-methyl-6-(4'-hydroxy)-phenylimidazo[4,5-b]pyridine (4'-HO-PhIP), and the isomeric N(2)- and N3-glucuronide conjugates of the carcinogenic metabolite, 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), which is formed by P450 1A2. The limit of quantification (LOQ) for MeIQx, PhIP, and 4'-HO-PhIP was approximately 5 pg/mL; the LOQ values for 8-CH(2)OH-IQx and IQx-8-COOH were, respectively, <15 and <25 pg/mL, and the LOQ values for the glucuronide conjugates of PhIP and HONH-PhIP were 50 pg/mL. The metabolism was extensive; less than 9% of the dose was eliminated in urine as unaltered MeIQx, and <1% was eliminated as unaltered PhIP. Phase II conjugates of the parent amines accounted for up to 12% of the dose of MeIQx and up to 2% of the dose of PhIP. 8-CH(2)OH-IQx and IQx-8-COOH accounted for up to 76% of the dose of MeIQx, and the isomeric glucuronide conjugates of HONH-PhIP accounted for up to 33% of the dose of PhIP that were eliminated in urine within 10 h of meat consumption. P450 1A2 significantly contributes to the metabolism of both HAAs but with marked differences in substrate specificity. P450 1A2 primarily catalyzes the detoxification of MeIQx by oxidation of the 8-methyl group, whereas it catalyzes the bioactivation of PhIP by oxidation of the exocyclic amine group. |
20192250 | Modeling liver-related adverse effects of drugs using knearest neighbor quantitative structure-activity relationship method. | Adverse effects of drugs (AEDs) continue to be a major cause of drug withdrawals in both development and postmarketing. While liver-related AEDs are a major concern for drug safety, there are few in silico models for predicting human liver toxicity for drug candidates. We have applied the quantitative structure-activity relationship (QSAR) approach to model liver AEDs. In this study, we aimed to construct a QSAR model capable of binary classification (active vs inactive) of drugs for liver AEDs based on chemical structure. To build QSAR models, we have employed an FDA spontaneous reporting database of human liver AEDs (elevations in activity of serum liver enzymes), which contains data on approximately 500 approved drugs. Approximately pounds with wide clinical data coverage, structural similarity, and balanced (40/60) active/inactive ratios were selected for modeling and divided into multiple training/test and external validation sets. QSAR models were developed using the k nearest neighbor method and validated using external data sets. Models with high sensitivity (>73%) and specificity (>94%) for the prediction of liver AEDs in external validation sets were developed. To test applicability of the models, three chemical databases (World Drug Index, Prestwick Chemical Library, and Biowisdom Liver Intelligence Module) were screened in silico, and the validity of predictions was determined, where possible, paring model-based classification with assertions in publicly available literature. Validated QSAR models of liver AEDs based on the data from the FDA spontaneous reporting system can be employed as sensitive and specific predictors of AEDs in preclinical screening of drug candidates for potential hepatotoxicity in humans. |
20192251 | Mitochondrial toxicity of microcystin-LR on cultured cells: application to the analysis of contaminated water samples. | Microcystins (MC) are potent hepatic toxins delivered into the cells by organic anion transporting peptides (OATP) where they target protein phosphatases and mitochondria. We analyzed the effects of MC-LR on primary hepatocytes, HepG2, and Jurkat T cells, and isolated rat liver mitochondria by measuring changes in O(2) consumption by optical oxygen sensing technique. Respiration of fresh primary hepatocytes was inhibited by MC-LR with EC50 = 2.74 +/- 0.65 nM, whereas an uncoupling effect on mitochondrial state 2 and state 3 respiration was observed with glutamate/malate as a substrate. HepG2 and Jurkat T cells lacking OATP showed no sensitivity to MC-LR; however, facilitated delivery of MC-LR resulted in a marked enhancement of HepG2 O(2) consumption and inhibition of Jurkat O(2) consumption at >or=0.1 nM. The respiratory response did not coincide with changes in viability, total cellular ATP, extracellular acidification, ROS formation, or protein phosphorylation, which were detectable at higher MC-LR doses. Such prominent effect on cellular respiration was therefore used for the detection of MC-LR in environmental samples. A simple and sensitive screening assay for MC-LR toxicity was developed, which uses Jurkat cells, facilitated delivery of the toxin(s) and measurement on a fluorescent reader. The assay was applied to a panel of environmental samples suspected to contain MC and benchmarked against the ELISA test. It allowed identification of toxic samples and quantification of both nonspecific and MC-LR type of toxicity. |
20192253 | Phenol groups in northeastern U.S. submicrometer aerosol particles produced from seawater sources. | Atmospheric particles collected during the ICARTT 2004 field experiment at ground based sites at Appledore Island (AI), New Hampshire, Chebogue Point (CP), Nova Scotia, and aboard the R/V Ronald Brown (RB) were analyzed using Fourier transform infrared (FTIR) spectroscopy to quantify organic mass (OM) and organic functional groups. Several of these spectra contain a unique absorbance peak at 3500 cm(-1). Laboratory calibrations identify this peak with phenol functional groups. The phenol groups are associated with seawater-derived emissions based on correlations with tracer volatile pounds (VOCs) and ions, and potential source contribution function (PSCF) analysis. On the basis of the measured absorptivities, the project average phenol group concentrations are 0.24 +/- 0.18 microg m(-3) (4% of the total OM) at AI, 0.10 +/- 0.6 microg m(-3) (5% of the total OM) at CP, and 0.08 +/- 0.09 microg m(-3) (2% of the total OM) on board the RB, with detection limits typically between 0.06 and 0.11 microg m(-3). The spectra were partitioned into three primary factors using positive matrix factorization (PMF) sufficient to explain more than 95% of the measured OM. The fossil bustion factor contributed 40% (AI), 34% (CP), and 43% (RB) of the total OM; the terrestrial biogenic factor contributed 20% (AI), 30% (CP), and 27% (RB). The seawater-derived factor contributed 40% (AI), 36% (CP) and 29% (RB) of the OM and showed similar correlations to tracers as the phenol group. |
20192252 | Hydrothermal fabrication and catalytic properties of La(1-x)Sr(x)M(1-y)Fe(y)O(3) (M = Mn, Co) that are highly active for the removal of toluene. | A series of La(1-x)Sr(x)M(1-y)Fe(y)O(3) (M = Mn, Co; x = 0, 0.4; y = 0.1, 1.0) perovskite-type oxide catalysts have been fabricated via a strategy of citric plexation coupled with hydrothermal treatment. The materials are characterized by a number of analytical techniques. The oxidation of toluene is used as a probe reaction for the evaluation of catalytic performance. It is found that both La(0.6)Sr(0.4)FeO(3) and LaFeO(3) exhibit high activities. The partial substitution of manganese and cobalt with iron can significantly improve the catalytic performance of La(0.6)Sr(0.4)MnO(3) and La(0.6)Sr(0.4)CoO(3). At toluene/O(2) molar ratio = 1/200 and space velocity = 20,000 h(-1), the catalytic activity decreases in the sequence of La(0.6)Sr(0.4)Co(0.9)Fe(0.1)O(3) > La(0.6)Sr(0.4)FeO(3) > La(0.6)Sr(0.4)Mn(0.9)Fe(0.1)O(3) > LaFeO(3) > La(0.6)Sr(0.4)CoO(3) > La(0.6)Sr(0.4)MnO(3). Compared to the Fe-free counterparts, the La(0.6)Sr(0.4)Mn(0.9)Fe(0.1)O(3) and La(0.6)Sr(0.4)Co(0.9)Fe(0.1)O(3) catalysts are, respectively, 50 and 85 degrees C lower with regard to the temperature required plete toluene oxidation. Toluene can pletely oxidized at 245 degrees C over La(0.6)Sr(0.4)Co(0.9)Fe(0.1)O(3). The excellent catalytic performance of La(0.6)Sr(0.4)Co(0.9)Fe(0.1)O(3) can be attributed to the presence of (i) Fe(3+)-O-Fe(4+) couples, (ii) a transition of electronic structure, and (iii) a trace amount of Co(3)O(4). |
20192254 | Polychlorinated biphenyl and low polybrominated diphenyl ether transfer to milk in lactating goats chronically exposed to contaminated soil. | This study investigated milk excretion kinetics of PCBs, tetra-BDE (BDE 47), and penta-BDE (BDE 99) in goats exposed to contaminated soil under controlled conditions. The animals were fed (80 days) with feed containing 5% of contaminated soil. During this exposure period, milk was analyzed weekly. At the end of the experiment the PCBs and PBDEs retained in hepatic and adipose tissues were also determined. The soil-milk carry over rates (CORs) of PCBs ranged from 6 to 62%. This result suggests that a large part of ingested soil-bound PCBs was recovered in milk. Significantly different levels between the congeners were reported in the tissues (fat, liver). BDE 47 and 99 excretions in milk achieved a plateau after 2 weeks of exposure, and their corresponding CORs were about 30%. These two congeners showed a significantly (P < 0.05) lower accumulation in the adipose tissue than the major PCB congeners. The concentrations of BDE 47 and 99 in the liver were the same as PCB concentrations. This result suggests that the low brominated congeners are submitted to the metabolism more extensively than the major PCBs. |
20192257 | Microwave catalysis revisited: an analytical solution. | In our previous work [Bren, U., et al. J. Phys. Chem. A 2008, 112, 166] we proposed a novel physical mechanism for microwave catalysis based on rotationally hot reactive species and verified its validity through a Monte Carlo simulation of a realistic chemical reaction: neutral ester hydrolysis. This article represents a continuation of our ongoing effort toward quantitative understanding of the microwave catalytic effect. It provides a derivation of an analytical solution for the microwave catalysis. The obtained expression pared with the results of the Monte Carlo simulation and is applied to reproduce the microwave catalytic effect experimentally observed in the polyethylene terephthalate solvolysis. Implications for the interactions of microwaves with living organisms in the context of widespread mobile telephony are also discussed. |
20192255 | Heterogeneous chemistry of alkylamines with sulfuric acid: implications for atmospheric formation of alkylaminium sulfates. | The heterogeneous interaction of alkylamines with sulfuric acid has been investigated to assess the role of amines in aerosol growth through the formation of alkylaminium sulfates. The kinetic experiments were conducted in a low-pressure fast flow reactor coupled to an ion drift-chemical ionization mass spectrometer (ID-CIMS). The measurements of heterogeneous uptake of methylamine, dimethylamine, and trimethylamine were performed in the acidity range of 59-82 wt % H(2)SO(4) and between 243 and 283 K. Irreversible reactive uptakes were observed for all three alkylamines, parable uptake coefficients (gamma) in the range of 2.0 x 10(-2) to 4.4 x 10(-2). The measured gamma value was slightly higher in more concentrated sulfuric acid and at lower temperatures. The results imply that the heterogeneous reactions of alkylamines contribute effectively to the growth of atmospheric acidic particles and, hence, secondary organic aerosol formation. |
20192256 | Lead substitution in synaptotagmin: a case study. | Quantum putations have been used to investigate the possibility of a Pb(2+)/Ca(2+) substitution in the three calcium sites of the synaptotagmin enzyme. Provided explicit cation solvation is taken into account, it is shown that the substitution is energetically feasible and induces a strong reorganization of the Ca(2+)-coordinating sites, which may preclude the enzyme for any efficient role when lead poisoning occurs. |
20192258 | Excited state processes of 2-butylamino-6-methyl-4-nitropyridine N-oxide in nonpolar solvents. A transient absorption spectroscopy study. | Earlier steady-state fluorescence studies showed that 2-butylamino-6-methyl-4-nitropyridine N-oxide (2B6M) can undergo fast excited-state intramolecular proton transfer (ESIPT). In a nonpolar solvent such as n-octane, both normal and tautomeric fluorescence was observed. Strikingly, the relative ratio of those two emission bands and the fluorescence quantum yield of the normal emission were found to depend on the excitation wavelength in violation of the Kasha-Vavilov rule. In this work, the system was investigated further by means of transient absorption spectroscopy, followed by global and target analysis. Upon excitation at 420 nm, a normal excited singlet state S(1)(N) is reached, which decays in about 12 ps via fluorescence and ESIPT (minor pathways) and to a long-lived "dark" state (major pathway) that is most probably the triplet T(1)(N). Upon 330 nm excitation, however, a plex pattern emerges and additional decay channels are opened. A set of four excited-state species is required to model the data, including a hot state S(1)(N)* that decays in about 3 ps to the tautomer, to the long-lived "dark" state and to the relaxed S(1)(N) state. A kinetic scheme is presented that can explain the observed transient absorption results as well as the earlier fluorescence data. |
20192259 | An expedient procedure for the oxidative cleavage of olefinic bonds with PhI(OAc)2, NMO, and catalytic OsO4. | PhI(OAc)(2) in the presence of OsO(4) (cat.) and 2,6-lutidine cleaves olefinic bonds to yield the corresponding pounds, albeit, in some cases, with alpha-hydroxy ketones as byproduct. A more practical and clean protocol to effect oxidative cleavage of olefinic bonds involves NMO, OsO(4) (cat.), 2,6-lutidine, and PhI(OAc)(2). |
20192261 | Nuclear field shift effect in isotope fractionation of mercury during abiotic reduction in the absence of light. | We investigated the abiotic reduction of inorganic Hg(II) by dissolved organic matter (DOM) and stannous(II) chloride (SnCl(2)) in the absence of light and quantified fractionation of Hg isotopes during these processes. The kinetics of reduction by DOM was characterized using multiple parallel pseudo-first-order reactions, implying different reactive Hg(II) species resulting from plexation. Significant mass independent isotopic anomalies were observed in reduction by both reducing reagents. Isotopes with odd atomic masses ((199)Hg and (201)Hg) showed less enrichment in reactants Hg(II) than expected for a mass dependent fractionation process. The fractionation factors (alpha) showed an odd-even staggering pattern that resembles the variation of nuclear charge radii. We demonstrated that these isotopic anomalies originated from nuclear field shift effect (NFS). The contribution of NFS to the measured fractionation factors was estimated and found to be as significant as the mass dependent effect. The observed Delta(199)Hg/Delta(201)Hg slope was explained by NFS and determined to be between 1.5 and 1.6 in abiotic nonphotochemical reduction, which is distinguishable from slopes determined for photochemical reduction. Therefore, we first demonstrated experimentally the significance of the nuclear field shift effect during reduction of Hg(II) and showed the application of isotope fractionation to distinguish between different reduction pathways. |
20192260 | Characterization of the ubiquinone binding site in the alternative NADH-quinone oxidoreductase of Saccharomyces cerevisiae by photoaffinity labeling. | The Ndi1 enzyme found in the mitochondrial membrane of Saccharomyces cerevisiae is an NDH-2-type alternative NADH-quinone oxidoreductase. As Ndi1 is expected to be a possible remedy plex I defects of mammalian mitochondria, a detailed biochemical characterization of the enzyme is needed. To identify the ubiquinone (UQ) binding site in Ndi1, we conducted photoaffinity labeling using a photoreactive biotinylated UQ mimic (compound 2) synthesized following a concept of the least possible modification of the substituents on the quinone ring. Cleavage with CNBr of Ndi1 cross-linked by 2 revealed the UQ ring of 2 to be specifically cross-linked to the Phe281-Met410 region (130 amino acids). Digestion of the CNBr fragment with V8 protease and lysylendopeptidase (Lys-C) gave approximately 8 and approximately 4 kDa peptides, respectively. The approximately 8 kDa V8 digest was identified as the Thr329-Glu399 region (71 amino acids) by an N-terminal sequence analysis. Although the approximately 4 kDa Lys-C digest could not be identified by N-terminal sequence analysis, the band was thought to cover the Gly374-Lys405 region (32 amino acids). Taken together, the binding site of the Q ring of 2 must be located in mon region of the V8 protease, and Lys-C digests Gly374-Glu399 (26 amino acids). Superimposition of the Ndi1 sequence onto a three-dimensional structural model of NDH-2 from Escherichia coli suggested that the C-terminal portion of this region is close to the isoalloxazine ring of FAD. |
20192262 | Metal-directed protein self-assembly. | Proteins are nature's premier building blocks for constructing sophisticated nanoscale architectures that carry plex tasks and chemical transformations. Some 70%-80% of all proteins are thought to be permanently oligomeric; that is, they posed of multiple proteins that are held together in precise spatial organization through noncovalent interactions. Although it is of great fundamental interest to understand the physicochemical basis of protein self-assembly, the mastery of protein-protein interactions (PPIs) would also allow access to novel biomaterials with nature's favorite and most versatile building block. In this Account, we describe a new approach we have developed with this possibility in mind, metal-directed protein self-assembly (MDPSA), which utilizes the strength, directionality, and selectivity of metal-ligand interactions to control PPIs. At its core, MDPSA is inspired by supramolecular coordination chemistry, which exploits metal coordination for the self-assembly of small molecules into discrete, more-or-less predictable higher order structures. Proteins, however, are not exactly small molecules or simple metal ligands: they feature extensive, heterogeneous surfaces that can interact with each other and with metal ions in unpredictable ways. We begin by first describing the challenges of using entire proteins as molecular building blocks. We follow with an examination of our work on a model protein (cytochrome cb(562)), highlighting challenges toward establishing ground rules for MDPSA as well as progress in ing these challenges. Proteins are also nature's metal ligands of choice. In MDPSA, once metal ions guide proteins into forming large assemblies, they are by definition embedded within extensive interfaces formed between protein surfaces. plex surfaces make an inorganic chemist's life somewhat difficult, yet they also provide a wide platform to modulate the metal coordination environment through distant, noncovalent interactions, exactly as natural metalloproteins and enzymes do. We describe putational and experimental efforts toward restructuring the noncovalent interaction network formed between proteins surrounding the interfacial metal centers. This approach, of metal templating followed by the redesign of protein interfaces (metal-templated interface redesign, MeTIR), not only provides a route to engineer de novo PPIs and novel metal coordination environments but also suggests possible parallels with the evolution of metalloproteins. |
20192263 | CopK from Cupriavidus metallidurans CH34 binds Cu(I) in a tetrathioether site: characterization by X-ray absorption and NMR spectroscopy. | Cupriavidus metallidurans CH34 is a bacterium that is resistant to high metal concentrations in the environment. Increased copper resistance is associated with the cop cluster on the large plasmid pMOL30 that posed of at least 21 genes. The copK gene encodes a 74 residue periplasmic protein whose expression is strongly upregulated in the presence of copper. CopK was previously shown to cooperatively bind Cu(I) and Cu(II) in distinct, specific sites. The solution structure of Cu(I)-CopK and the characterization of the Cu(I) site by X-ray absorption spectroscopy and NMR are reported here. EXAFS spectra are in agreement with a tetrathioether Cu(I) site, providing so far unique spectral information on a 4S-coordinated Cu(I) in a protein. The methionine residues forming the Cu(I) site, M28, M38, M44, and M54, are identified by NMR. We propose the chemical shift of the methionine C(epsilon) as a new and sensitive probe for the detection of Cu(I) bound to thioether groups. The solution structure of Cu(I)-CopK demonstrates that Cu(I) binding induces plete structural modification with the disruption of the second beta-sheet and a rotation of the C-terminal part of nearly 180 degrees around a hinge formed by asparagine 57. This conformational change is directly related to the loss of the dimer interface and most probably to the formation of the Cu(II) site involving histidine 70. The solution structure of Cu(I)-CopK therefore provides the molecular basis for the understanding of the Cu(I)/Cu(II) binding cooperativity. |
20192264 | Protein-protein interactions in ovalbumin solutions studied by small-angle scattering: effect of ionic strength and the chemical nature of cations. | The influence of ionic strength and of the chemical nature of cations on the protein-protein interactions in ovalbumin solution was studied using small-angle X-ray and neutron scattering (SAXS/SANS). The globular protein ovalbumin is found in dimeric form in solutions as suggested by SANS/SAXS experiments. Due to the negative charge of the proteins at neutral pH, the protein-protein interactions without any salt addition are dominated by electrostatic repulsion. A structure factor related to screened Coulombic interactions together with an ellipsoid form factor was used to fit the scattering intensity. A monovalent salt (NaCl) and a trivalent salt (YCl(3)) were used to study the effect of the chemical nature of cations on the interaction in protein solutions. Upon addition of NaCl, with ionic strength below that of physiological conditions (150 mM), the effective interactions are still dominated by the surface charge of the proteins and the scattering data can be understood using the same model. When yttrium chloride was used, a reentrant condensation behavior, i.e., aggregation and subsequent redissolution of proteins with increasing salt concentration, was observed. SAXS measurements reveal a transition from effective repulsion to attraction with increasing salt concentration. The solutions in the reentrant regime e unstable after long times (several days). The results are discussed pared with those from bovine serum albumin (BSA) in solutions. |
20192265 | Bioorthogonal chemical reporters for monitoring protein acetylation. | Protein acetylation is a key post-translational modification that regulates diverse biological activities in eukaryotes. Here we report bioorthogonal chemical reporters that enable direct in-gel fluorescent visualization and proteome-wide identification of acetylated proteins via Cu(I)-catalyzed azide-alkyne cycloaddition, often termed "click chemistry". We demonstrate that two alkynyl-acetyl-CoA analogues, 4-pentynoyl-CoA and 5-hexynoyl-CoA, function as efficient substrates of lysine acetyltransferase p300 and serve as sensitive reagents for monitoring p300-catalyzed protein acetylation in vitro. In addition, we demonstrate that three alkynylacetate analogues, sodium 3-butynoate, sodium 4-pentynoate, and sodium 5-hexynoate, can be metabolically incorporated onto cellular proteins through biosynthetic mechanisms for profiling of acetylated proteins in diverse cell types. Mass spectrometry analysis of the enriched 4-pentynoate-labeled proteins revealed many reported as well as new candidate acetylated proteins from Jurkat T cells and specific sites of lysine acetylation. The bioorthogonal chemical reporters described here should serve as powerful tools for investigating protein acetylation. |
20192267 | [ReCl4(CN)2]2-: a high magnetic anisotropy building unit giving rise to the single-chain magnets (DMF)4MReCl4(CN)2 (M = Mn, Fe, Co, Ni). | An S = 3/2, high-anisotropy building unit, trans-[ReCl(4)(CN)(2)](2-), representing the first plex with a mixture of just cyanide and halide ligands, has been synthesized through the reaction of (Bu(4)N)CN with ReCl(4)(THF)(2). This species is characterized in detail and employed in directing the formation of a series of one-dimensional coordination solids of formula (DMF)(4)MReCl(4)(CN)(2) (M = Mn (2), Fe (3), Co (4), Ni (5)). Variable-temperature dc magnetic susceptibility measurements demonstrate the presence of intrachain antiferromagnetic (2) and ferromagnetic (3-5) exchange coupling within these solids. In addition, probing the ac magnetic susceptibility as a function of both temperature and frequency reveals that all of the pounds exhibit slow relaxation of the magnetization. The relaxation time is shown to be thermally activated, with energy barriers to relaxation of Delta(tau) = 31, 56, 17, and 20 cm(-1) for 2-5, respectively. Notably, the field-dependent magnetization of the iron congener exhibits a significant hysteresis effect at low temperature, with a coercive field of H(C) = 1.0 T, thus demonstrating magnetlike behavior in this one-dimensional system. Finally, the magnetization dynamics of all solids occur within the finite-size regime, where the magnetic domain growth is limited due to physical defects along the chains within the crystals. |
20192266 | Application of the lithiation-borylation reaction to the preparation of enantioenriched allylic boron reagents and subsequent in situ conversion into 1,2,4-trisubstituted homoallylic alcohols with complete control over all elements of stereochemistry. | The reactions of Hoppe's lithiated carbamates with vinylboranes and boronic esters give allylic boranes/boronic esters, and subsequent addition of aldehydes provides a new route to enantioenriched homoallylic alcohols with high enantiomeric ratios and diastereomeric ratios. Specifically, reactions of plexed lithiated carbamates with trans-alkenyl-9-BBN derivatives followed by addition of aldehydes gave (Z)-anti-homoallylic alcohols in greater than 95:5 er and 99:1 dr. However, in the special case of the methyl-substituted lithiated carbamate, diamine-free conditions were required to achieve high selectivity. Reactions of plexed lithiated carbamates with (Z)-alkenyl pinacol boronic esters and (E)-alkenyl neopentyl boronic esters gave (E)-syn- and (E)-anti-homoallylic alcohols, respectively, in greater than 96:4 er and 98:2 dr. In these reactions, a Lewis acid (MgBr(2) or BF(3) x OEt(2)) was required to promote both the 1,2-metalate rearrangement and the addition of the intermediate allylic boronic ester to the aldehyde. This methodology provides a general route to each of the three classes of homoallylic alcohols with high selectivity. |
20192268 | Oligonucleotide duplexes and multistrand assemblies with 8-aza-2'-deoxyisoguanosine: a fluorescent isoG(d) shape mimic expanding the genetic alphabet and forming ionophores. | 8-Aza-2'-deoxyisoguanosine (4) is the first fluorescent shape mimic of 2'-deoxyisoguanosine (1a); its fluorescence is stronger in alkaline medium than under neutral conditions. Nucleoside 4, which was synthesized from 8-aza-2'-deoxyguanosine via a 4,6-diamino intermediate after selective deamination, was incorporated in oligodeoxyribonucleotides using phosphoramidite 11. Duplexes with 4 x m(5)iC(d) (5-methyl-2'-deoxyisocytidine) base pairs are more stable than those incorporating dG-dC pairs, thereby expanding the genetic alphabet by a fluorescent orthogonal base pair. As demonstrated by T(m) measurements, the base pair stability decreases in the order m(5)iC(d) x 4 >> dG x 4 > dT x 4 > or = dC x 4 >> dA x 4. A better base pairing selectivity of 4 against the canonical nucleosides dT, dC, dA, and dG is observed than for the degenerated base pairing of 1a. The base pair stability changes can be monitored by nucleobase anion fluorescence sensing. The fluorescence change correlates to the DNA base pair stability. Oligonucleotide 5'-d(T(4)4(4)T(4)) (22), containing short runs of nucleoside 4, forms stable multistranded assemblies (ionophores) with K(+) in the central cavity. They are quite stable at elevated temperature but are destroyed at high pH value. |
20192269 | Modeling relationships among active components in black raspberry (Rubus occidentalis L.) fruit extracts using high-resolution (1)H nuclear magnetic resonance (NMR) spectroscopy and multivariate statistical analysis. | A process was developed to ascertain the ponents of black raspberry (Rubus occidentalis L.) fruit extracts by relating chemical constituents determined by high-field nuclear magnetic resonance (NMR) spectroscopy to biological responses using partial least-squares regression analysis. To validate our approach, we outlined relationships between phenolic signals in NMR spectra and chemical data for total monomeric anthocyanin (TMA) content and antioxidant capacity by the ferric-reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. Anthocyanins, cyanidin 3-O-rutinoside (Cy 3-rut), cyanidin 3-O-(2(G))-xylosylrutinoside (Cy 3-xylrut), and cyanidin 3-O-glucoside (Cy 3-glc), were significant contributors to the variability in assay results, with the two most important NMR bins corresponding to the methyl peaks in Cy 3-rut (6''') and/or Cy 3-xylrut (6(IV)). Many statistically important bins mon among assay models, but differences in structure-activity relationships resulted in changes in bin ranking. The specificity of these results supported the application of the process to investigate relationships among health-beneficial natural products and potential biological activity. |
20192270 | Structure-activity relationship of (N)-Methanocarba phosphonate analogues of 5'-AMP as cardioprotective agents acting through a cardiac P2X receptor. | P2X receptor activation protects in heart failure models. MRS2339 3, a 2-chloro-AMP derivative containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system, activates this cardioprotective channel. Michaelis-Arbuzov and Wittig reactions provided phosphonate analogues of 3, expected to be stable in vivo due to the C-P bond. After chronic administration via a mini-osmotic pump (Alzet), some analogues significantly increased intact heart contractile function in calsequestrin-overexpressing mice (genetic model of heart pared to vehicle-infused mice (all inactive at the vasodilatory P2Y(1) receptor). Two phosphonates, (1'S,2'R,3'S,4'R,5'S)-4'-(6-amino-2-chloropurin-9-yl)-2',3'-(dihydroxy)-1'-(phosphonomethylene)-bicyclo[3.1.0]hexane, 4 (MRS2775), and its homologue 9 (MRS2935), both 5'-saturated, containing a 2-Cl substitution, improved echocardiography-derived fractional shortening (20.25% and 19.26%, respectively, versus 13.78% in controls), while unsaturated 5'-extended phosphonates, all 2-H analogues, and a CH(3)-phosphonate were inactive. Thus, chronic administration of nucleotidase-resistant phosphonates conferred a beneficial effect, likely via cardiac P2X receptor activation. Thus, we have greatly expanded the range of carbocyclic nucleotide analogues that represent potential candidates for the treatment of heart failure. |
20192272 | Chiral discrimination among aminotransferases: inactivation by 4-amino-4,5-dihydrothiophenecarboxylic acid. | Mechanism-based inhibitors such as cycloserine and gabaculine can inactivate aminotransferases via reactions of pounds with the pyridoxal phosphate cofactor forming an irreversible adduct. The reaction is chirally specific in that any one enzyme usually only recognizes one enantiomer of the inactivator. For instance, l-aspartate aminotransferase (l-AspAT) is inactivated by 4-amino-4,5-dihydro-2-thiophenecarboxylic acid (ADTA), however, only by the S-isomer. We have now shown that d-amino acid aminotransferase (d-a-AT) is irreversibly inactivated by the R-isomer of the pound. The X-ray crystal structure (PDB code: 3LQS ) of the inactivated enzyme shows that in the product the enzyme no longer makes a Schiff base linkage to the pyridoxal 5'-phosphate (PLP) cofactor, and instead pound has formed a derivative of the cofactor. The adduct is similar to that formed between d-cycloserine and d-a-AT or alanine racemase (Ala-Rac) in that the thiophene ring of R-ADTA is intact and seems to be aromatic. The plane of the ring is rotated by nearly 90 degrees with respect to the plane of the pyridine ring of the cofactor, parison with the enzyme inactivated by cycloserine. Based on the structure of the product, the mechanism of inactivation most probably involves a transamination followed by aromatization to form an aromatic thiophene ring. |
20192273 | Theoretical study of the lactic acid-water system: importance of two- and three-body interactions. | Optimal structures, interaction energies, harmonic and anharmonic vibrational frequencies, and NMR chemical shifts of the dimers LA...H(2)O and trimers LA...(H(2)O)(2) (where LA is lactic acid) have been determined from the second-order Møller-Plesset perturbation theory and B3LYP with the aug-cc-pVDZ calculations. The nature of the pairwise and nonadditive three-body interactions was investigated by the SAPT method. As revealed by SAPT analysis, the main two-body binding contributions in the LA...H(2)O dimers and LA...(H(2)O)(2) trimers result from a delicate balance of the attractive and repulsive terms. The three-body nonadditivity for LA...(H(2)O)(2) is stabilizing and dominated by the exchange and induction effects but small. |
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