Light-activated phytotoxic thiophenes in Flaveria linearis L.

Chromatographic analyses of crude leaf extracts of Flaveria linearis L. revealed the presence of four acetylenic monothiophenes. Three of these metabolites were purified and structurally characterized by UV, NMR, IR, and GC-MS. Germination, growth, and survival/mortality studies with and without UVA, the activating wavelengths of these metabolites, were conducted with the crude leaf extracts and the purified compounds (taken individually and combined) against selected crop species (lettuce, radish, and carrot). Results suggest that acetylenic metabolites are phytotoxic against lettuce, carrot, and radish, but with variability in response among species. These variations in sensitivity and the allelopathic potential of F. linearis is discussed.

Field-effect transistors based on self-organized molecular nanostripes

Charge transport properties in organic semiconductors depend strongly on molecular order. Here we demonstrate field-effect transistors where drain current flows through a precisely defined array of nanostripes made of crystalline and highly ordered molecules. The molecular stripes are fabricated across the channel of the transistor by a stamp-assisted deposition of the molecular semiconductors from a solution. As the solvent evaporates, the capillary forces drive the solution to form menisci under the stamp protrusions. The solute precipitates only in the regions where the solution is confined by the menisci once the critical concentration is reached and self-organizes into molecularly ordered stripes 100-200 nm wide and a few monolayers high. The charge mobility measured along the stripes is 2 orders of magnitude larger than the values measured for spin-coated thin films.

Simultaneous enhancement of brightness, efficiency, and switching in RGB organic light emitting transistors

An innovative design strategy for light emitting field effect transistors (LEFETs) to harvest higher luminance and switching is presented. The strategy uses a non-planar electrode geometry in tri-layer LEFETs for simultaneous enhancement of the key parameters of quantum efficiency, brightness, switching, and mobility across the RGB color gamut.

Cation-induced crown porphyrin dimers of oxovanadium(IV)

Oxovanadium(1V) porphyrins appended with crown ether (benzo-15-crown-5) at the 5 (mono), the 5 and 10115 (cis/trans bis), the 5, 10, and 15 (tris), and the 5, 10, 15, and 20 (tetrakis) positions have been synthesized. The cation complexation behavior of these cavity-bearing porphyrins has been studied by using optical aborption and ESR spectral methods. The cations K+, Cs+, NH4+, and Ba2+, which require two crown ether cavities for complexation, induce dimerization of the porphyrins. The cation-induced dimerization constants for a representative tetrasubstituted porphyrin vary as K+ > Ba2+ > Cs+ - NH4+, and the relative stabilities of the dimers are dependent on the type of the substitution, tetrakis > tris > cis bis. ESR spectra recorded at a sample temperature of 77 K have low-field components attributed to Ah& = f 2 transitions, providing further evidence for the existence of dimers in solutions. The eclipsed sandwich dimers have V-V distances in the range 4.70 A. The relative distributions of oxovanadium crown porphyrins in terms of monomeric and dimeric forms rest on the geometric dispositions of the crown ether appendages.

Porphyrins with multiple crown ether voids: novel systems for cation complexation studies

Porphyrins appended with crown ether, benzo-15-crown-5, at the methine positions have been synthesized and characterized. The fully and partially substituted porphyrins and their metallo (Co, Cu, and Zn) derivatives describe one or more ether cavities in the periphery that are capable of recognizing spherical cations. The ability of these macrocycles to complex cations (Na+, K+, Mg2+, Ca2+, Ba2', and NH4+) is investigated by use of visible, 'H NMR, ESR, and emission spectral studies. The tetrasubstituted crown porphyrin (TCP) exhibits very high selectivity for K+. The cations (K', Ba2+, and NH4+) that require two crown ether cavities for complexation promote dimerization of the porphyrins. The ESR study of the cation-induced porphyrin dimers reveals axial symmetry with the porphyrin planes separated by -4.2 A. This distance increases from the fully substituted to partially substituted porphyrins. The cations (K', Ba2+, and NH4') quench efficiently the fluorescence of the free base porphyrins and their metallo derivatives. The quenching process is attributed to the steric geometry of the dimers.

beta-Turn Analogues in Model a ss-Hybrid Peptides: Structural Characterization of Peptides Containing ss 2,2Ac6c and ss 3,3Ac6c Residues

The effect of gem-dialkyl substituents on the backbone conformations of beta-amino acid residues in peptides has been investigated by using four model peptides: Boc-Xxx-beta 2,2Ac6c(1-aminomethylcyclohexanecarboxylic acid)-NHMe (Xxx=Leu (1), Phe (2); Boc=tert-butyloxycarbonyl) and Boc-Xxx-beta 3,3Ac6c(1-aminocyclohexaneacetic acid)-NHMe (Xxx=Leu (3), Phe (4)). Tetrasubstituted carbon atoms restrict the ranges of stereochemically allowed conformations about flanking single bonds. The crystal structure of Boc-Leu-beta 2,2Ac6c-NHMe (1) established a C11 hydrogen-bonded turn in the a beta-hybrid sequence. The observed torsion angles (a(similar to-60 degrees, similar to-30 degrees), beta(similar to-90 degrees, similar to 60 degrees, similar to-90 degrees)) corresponded to a C11 helical turn, which was a backbone-expanded analogue of the type III beta turn in aa sequences. The crystal structure of the peptide Boc-Phe-beta 3,3Ac6c-NHMe (4) established a C11 hydrogen-bonded turn with distinctly different backbone torsion angles (a(similar to-60 degrees, similar to 120 degrees), beta(similar to 60 degrees, ?60 degrees, similar to-60 degrees)), which corresponded to a backbone-expanded analogue of the type II beta turn observed in aa sequences. In peptide 4, the two molecules in the asymmetric unit adopted backbone torsion angles of opposite signs. In one of the molecules, the Phe residue adopted an unfavorable backbone conformation, with the energetic penalty being offset by a favorable aromatic interaction between proximal molecules in the crystal. NMR spectroscopy studies provided evidence for the maintenance of folded structures in solution in these a beta-hybrid sequences.

Palladium-Catalyzed Decarboxylative and Decarbonylative Transformations in the Synthesis of Fine and Commodity Chemicals

Decarboxylation and decarbonylation are important reactions in synthetic organic chemistry, transforming readily available carboxylic acids and their derivatives into various products through loss of carbon dioxide or carbon monoxide. In the past few decades, palladium-catalyzed decarboxylative and decarbonylative reactions experienced tremendous growth due to the excellent catalytic activity of palladium. Development of new reactions in this category for fine and commodity chemical synthesis continues to draw attention from the chemistry community.

The Stoltz laboratory has established a palladium-catalyzed enantioselective decarboxylative allylic alkylation of β-keto esters for the synthesis of α-quaternary ketones since 2005. Recently, we extended this chemistry to lactams due to the ubiquity and importance of nitrogen-containing heterocycles. A wide variety of α-quaternary and tetrasubstituted α-tertiary lactams were obtained in excellent yields and exceptional enantioselectivities using our palladium-catalyzed decarboxylative allylic alkylation chemistry. Enantioenriched α-quaternary carbonyl compounds are versatile building blocks that can be further elaborated to intercept synthetic intermediates en route to many classical natural products. Thus our chemistry enables catalytic asymmetric formal synthesis of these complex molecules.

In addition to fine chemicals, we became interested in commodity chemical synthesis using renewable feedstocks. In collaboration with the Grubbs group, we developed a palladium-catalyzed decarbonylative dehydration reaction that converts abundant and inexpensive fatty acids into value-added linear alpha olefins. The chemistry proceeds under relatively mild conditions, requires very low catalyst loading, tolerates a variety of functional groups, and is easily performed on a large scale. An additional advantage of this chemistry is that it provides access to expensive odd-numbered alpha olefins.

Finally, combining features of both projects, we applied a small-scale decarbonylative dehydration reaction to the synthesis of α-vinyl carbonyl compounds. Direct α-vinylation is challenging, and asymmetric vinylations are rare. Taking advantage of our decarbonylative dehydration chemistry, we were able to transform enantioenriched δ-oxocarboxylic acids into quaternary α-vinyl carbonyl compounds in good yields with complete retention of stereochemistry. Our explorations culminated in the catalytic enantioselective total synthesis of (–)-aspewentin B, a terpenoid natural product featuring a quaternary α-vinyl ketone. Both decarboxylative and decarbonylative chemistries found application in the late stage of the total synthesis.

Analysis of sulfur-containing compounds in crude oils by comprehensive two-dimensional gas chromatography with sulfur chemiluminescence detection

This paper reports an analytical method for separating, identifying, and quantifying sulfur-containing compounds in crude oil fraction (IBP-360degreesC) samples based on comprehensive two-dimensional gas chromatography coupled with a sulfur chemiluminescence detector. Various sulfur-containing compounds and their groups were analyzed with one direct injection. 3620 peaks were detected including 1722 thiols/thioethers/ disulfides/1-ring thiophenes, 953 benzothiophenes, 704 dibenzothiophenes, and 241 benzonaphthothiophenes. The target sulfur compounds and their groups were identified based on the group separation feature and structured retention of comprehensive two-dimensional gas chromatography as well as standard substances. The quantitative analysis of major sulfur-containing compounds and total sulfur was based on the linear response of the sulfur chemiluminescence detector using the internal standard method. The sulfur contents of target sulfur compounds and their groups in 4 crude oil fractions were also determined. The recoveries for standard sulfur-containing compounds were in the range of 90-102%. The quantitative result of total sulfur in the Oman crude oil fraction sample was compared with those from ASTM D 4294 standard method (total S by X-ray fluorescence spectrometry), the relative deviation (RD%) was 4.2% and the precision of the method satisfactory.

Efficient synthesis of trimethylsilyl-substituted dithieno[2,3-b:3',2'-d]thiophene,tetra[2,3-thienylene] and hexa[2,3-thienylene] from substituted [3,3']Bithiophenyl

Efficient synthetic procedures for the preparation of beta-trithiophenes (dithieno[2,3-b:3',2'-d]thiophene) and two macrocyclic compounds, tetra[2,3-thienylene] and hexa[2,3-thienylene] bearing trimethylsilyl (TMS) groups from 2,2'-dibromo-5,5'-bistrimethylsilanyl[3,3']bithiophenyl are reported. The UV-Vis spectra property and crystal structures of these macrocyclic oligothiophenes are described.

富硫流体的成因与硫酸盐还原作用研究

Origins of H_2S, thiols, thiophenes in natural gases and sulphur-enriched oils are complicated and thus some debates exist on them. The post-doctoral research is based upon oil- and gas-field data. Cases for study include Triassic Jianglingjiang Formation natural gases, Wolonghe Field, Sichuan Basin, Paleozoic oils and bitumen, Central Tarim, gases reserviored nearby Carboniferious - Ordovician unconformity, Hetianhe Field, Tarim Basin and sulphur-enriched oils in Tertiary reserviors in Jinxian Sag, Bohai Bay Basin. We have carried out analyses on the oils and gases for chemistry, δ~(13)C, δ~(34)S, and molecular composition of biomarkers, analyzed authigenetic pyrite forδ~(34)S, formation water for chemistry and δD and δ~(18)O along with petroleum system and burial history analyses, The aims are to assess the origins of the H2S and authigenetic pyrite, to discuss the possibility of reduced sulphur incorporation into hydrocarbons and to determine the mechanisms of hydrocarbon secondary alteration in the above four cases by comparison. The research shows that the reduced sulphur in the four cases is the result of thermochemical and biological sulphate reduction., TSR and BSR, respectively. No evidence indicates an origin of decomposition of organic matter or mantle - derived H2S in the cases. Elevated H_2S contents (up to 32%) in the Triassic Jialingjiang Formation are considered to result from TSR while relatively low H_2S (up to 2000ppm) in the Hetianhe Field resulted from BSR. However, it is not the case for the Central Tarim where relatively low H2S but abundant authigenetic pyrite occurr. Part of the H_2S in the Central Tarim reservoirs has reacted with iron released from clay minerals to precipitate pyrite. Thus, reduced sulphur δ~(34)S and reservoir temperatures rather than the H2S amount are reliable parameters to distinguish between TSR and BSR. TSR in Sichuan Basin Triassic Jialingjiang Formation and Central Tarim Paleozoic reservoirs are showed to take place at more than 125℃. the H2S and authigenetic pyrite have δ~(34)S close to parent anhydrite. In contrast, BSR in the reservoirs near the Carboniferous - Ordovician unconformity in the Hetianhe Field and in the Tertiary in the Jinxian Sag took place at temperatures less than 80℃with sulphide δ~(34)S as light as -24.9‰ and -12.5‰, anhydrite δ~(34)S as heavy as +26‰and +3 5-+40‰, respectively. Chemistry and isotopic composition of the natural gases change as the result of sulphate reduction. It has been observed that relative composition of light hydrocarbon gases is changed along with a rise in H_2S and CO_2. TSR in the Triassic Jialingjiang Formation and BSR in the Hetianhe Field result in a greater degree of preferential depletion of methane than larger molecular hydrocarbon gases. As TSR or BSR proceeds, hydrocarbon gases evolved to heavier carbon isotope as the result of kinetic isotopic fractionation, i.e., selective anaerobic oxidation of ~(12)C. Using the model of residual methane (Whiticar, 1999) to describe the relationship among the proportion of methane oxidation, isotopic shift and fraction factor, about 30% methane is calculated to have been oxidized during BSR in the western part of the Hetianhe Field. From the above, it can be concluded that in the area where H_2S is abundant, empiricalδ~(13)C -Ro relationships do not work. Sulphate reduction results in a rise in sulphur content, gravity and viscosity of an oil as well as changes in δ~(13)C and δ~(34)S. On special conditions, the reduced sulphur from sulphates might be incorporated into oils, i.e., the increasing sulphur is derived from secondarily reduced sulphur. A positive correlative relationship exists between sulphur content and δ~(34)S in the oils in Paleozoic reservoirs in Central Tarim, indicating that enhanced sulphur is ~(34)S-enriched, originated from TSR. The Jinxian oil with the highest sulphur content has the lightest δ~(34)S, suggesting part of the sulphur in the oil is ~(34)S-depleted, originated from BSR. In the Jinxian oil with increasing sulphur content, asphaltenes shows higher content and more negative δ~(13)C, and saturates shows evidence of biodegradetion and a decreasing content and a positive δ~(13)C shift. Thus, asphaltenes have δ~(13)C values closer to saturates. All the above indicate that the reduced sulphur has been incorporated into biodegradated saturates to generate new asphaltenes with relatively light δ~(13)C of saturates. Thiols and thiophenes in natural gases in the Triassic Jialingjiang Formation may result from reaction of H_2S with hydrocarbon. In the Jialingjiang Formation hydrocarbon gases are dominated by methane thus have a high dryness coefficient and thiols are showed to be positively related to H_2S content, suggesting that the thiols may result from H_2S reaction with short chain hydrocarbons. In contrast, high thiophenes occur in wet gases in Jurassic reservoirs with their source rock from sulphur - depleted type I kerogen, indicating that thiophenes may be a product of reaction of H2S with longer chain hydrocarbons.

Early clopidogrel versus prasugrel use among contemporary STEMI and NSTEMI patients in the US: insights from the National Cardiovascular Data Registry.

BACKGROUND: P2Y12 antagonist therapy improves outcomes in acute myocardial infarction (MI) patients. Novel agents in this class are now available in the US. We studied the introduction of prasugrel into contemporary MI practice to understand the appropriateness of its use and assess for changes in antiplatelet management practices. METHODS AND RESULTS: Using ACTION Registry-GWTG (Get-with-the-Guidelines), we evaluated patterns of P2Y12 antagonist use within 24 hours of admission in 100 228 ST elevation myocardial infarction (STEMI) and 158 492 Non-ST elevation myocardial infarction (NSTEMI) patients at 548 hospitals between October 2009 and September 2012. Rates of early P2Y12 antagonist use were approximately 90% among STEMI and 57% among NSTEMI patients. From 2009 to 2012, prasugrel use increased significantly from 3% to 18% (5% to 30% in STEMI; 2% to 10% in NSTEMI; P for trend <0.001 for all). During the same period, we observed a decrease in use of early but not discharge P2Y12 antagonist among NSTEMI patients. Although contraindicated, 3.0% of patients with prior stroke received prasugrel. Prasugrel was used in 1.9% of patients ≥75 years and 4.5% of patients with weight <60 kg. In both STEMI and NSTEMI, prasugrel was most frequently used in patients at the lowest predicted risk for bleeding and mortality. Despite lack of supporting evidence, prasugrel was initiated before cardiac catheterization in 18% of NSTEMI patients. CONCLUSIONS: With prasugrel as an antiplatelet treatment option, contemporary practice shows low uptake of prasugrel and delays in P2Y12 antagonist initiation among NSTEMI patients. We also note concerning evidence of inappropriate use of prasugrel, and inadequate targeting of this more potent therapy to maximize the benefit/risk ratio.

Characterization of a thymidylate synthase (TS)-inducible cell line: a model system for studying sensitivity to TS- and non-TS-targeted chemotherapies

Thymidylate synthase (TS) is responsible for the de novo synthesis of thymidylate, which is required for DNA synthesis and repair and which is an important target for fluoropyrimidines such as 5-fluorouracil (5-FU), and antifolates such as Tomudex (TDX), ZD9331, and multitargeted antifolate (MTA). To study the importance of TS expression in determining resistance to these agents, we have developed an MDA435 breast cancer-derived cell line with tetracycline-regulated expression of TS termed MTS-5. We have demonstrated that inducible expression of TS increased the IC(50) dose of the TS-targeted therapeutic agents 5-FU, TDX, and ZD9331 by 2-, 9- and 24-fold respectively. An IC(50) dose for MTA was unobtainable when TS was overexpressed in these cells, which indicated that MTA toxicity is highly sensitive to increased TS expression levels. The growth inhibitory effects of the chemotherapeutic agents CPT-11, cisplatin, oxaliplatin, and Taxol were unaffected by TS up-regulation. Cell cycle analyses revealed that IC(50) doses of 5-FU, TDX and MTA caused an S-phase arrest in cells that did not overexpress TS, and this arrest was overcome when TS was up-regulated. Furthermore, the S-phase arrest was accompanied by 2- to 4-fold increased expression of the cell cycle regulatory genes cyclin E, cyclin A, and cyclin dependent kinase 2 (cdk2). These results indicate that acute increases in TS expression levels play a key role in determining cellular sensitivity to TS-directed chemotherapeutic drugs by modulating the degree of S-phase arrest caused by these agents. Moreover, CPT-11, cisplatin, oxaliplatin, and Taxol remain highly cytotoxic in cells that overexpress TS.

Effect of pH and temperature on the formation of volatile compounds in cysteine/reducing sugar/starch mixtures during extrusion cooking

Mixtures of cysteine, reducing sugar (xylose or glucose), and starch were extrusion cooked using feed pH values of 5.5, 6.5, and 7.5 and target die temperatures of 120, 150, and 180 degreesC. Volatile compounds were isolated by headspace trapping onto Tenax and analyzed by gas chromatography-mass spectrometry. Eighty and 38 compounds, respectively, were identified from extrudates prepared using glucose and xylose. Amounts of most compounds increased with temperature and pH. Aliphatic sulfur compounds, thiophenes, pyrazines, and thiazoles were the most abundant chemical classes for the glucose samples, whereas for xylose extrudates highest levels were obtained for non-sulfur-containing furans, thiophenes, sulfur-containing furans, and pyrazines. 2-Furanmethanethiol and 2-methyl-3-furanthiol were present in extrudates prepared using both sugars, but levels were higher in xylose samples. The profiles of reaction products were different from those obtained from aqueous or reduced-moisture systems based on cysteine and either glucose or ribose.

Tri- and tetra-substituted naphthalene diimides as potent G-quadruplex ligands.

A series of tri- and tetra-substituted naphthalene diimides have been designed and synthesized. Several compounds show exceptional affinity for telomeric G-quadruplex DNA in classical and competition FRET assays and SPR studies. They inhibit telomerase in the TRAP assay, and show potent senescence-based short-term anti-proliferative effects on MCF7 and A549 cancer cell lines, and localize in the nucleus and particularly the nucleolus of MCF7 cells.

Enantioselective dioxygenase-catalysed formation and thermal racemisation of chiral thiophene sulfoxides

Substituted chiral thiophene 1-oxides and their cycloadducts of variable enantiopurity have been isolated as products of dioxygenase-catalysed sulfoxidation of the corresponding thiophenes using intact cells of Pseudomonas putida; thermal racemization (Delta G(double dagger) = 25.1 kcal mol(-1)) of the enantiopure metabolite (1R)-2-methylbenzo[b]thiophene 1-oxide has been observed.