40 CFR 721.10356 - Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-. 721.10356 Section 721.10356 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific...

40 CFR 721.10356 - Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-. 721.10356 Section 721.10356 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific...

40 CFR 721.10356 - Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-. 721.10356 Section 721.10356 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific...

3,3,6,6-Tetra­methyl-9-(2-nitro­phen­yl)-3,4,6,7-tetra­hydro-2H-xanthene-1,8(5H,9H)-dione

PubMed Central

Mo, Yingming; Zang, Hong-Jun; Cheng, Bo-Wen

2010-01-01

In the title compound, C23H25NO5, the pyran ring adopts a flattened boat conformation, while the two cyclo­hexenone rings are in envelope conformations. The 3-nitro­phenyl ring is almost perpendicular to the pyran ring, making a dihedral angle of 87.1 (3)°. PMID:21588418

Reappraising the structures and distribution of metabolites from black aspergilli containing uncommon 2-benzyl-4H-pyran-4-one and 2-benzylpyridin-4(1H)-one systems

PubMed Central

Henrikson, Jon C.; Ellis, Trevor K.; King, Jarrod B.; Cichewicz, Robert H.

2011-01-01

To date, natural products containing 2-benzyl-4H-pyran-4-one and 2-benzylpyridin-4(1H)-one substructures have been encountered in relatively few fungi outside of the black aspergilli clade. While exploring the occurrence of these compounds among Aspergillus spp., it was determined that the structures of the unusual furopyrrols tensidols A and B (5 and 6) and JBIR-86 and JBIR-87 (9 and 10) were incorrect and should be reassigned as 2-benzyl-4H-pyran-4-ones (7, 8, 11e, and 12, respectively). The origin of the unique N-phenyl groups in the 2-benzylpyridin-4(1H)-ones nygerones A and B (1 and 2) was also examined and it was established that N-phenylamides added to the culture medium were suitable substrates for generating these metabolites; however, this phenomenon remained limited to a single fungus in our collection (Aspergillus niger ATCC 1015). A variety of 2-benzyl-4H-pyran-4-ones and 2-benzylpyridin-4(1H)-ones were detected among the black aspergilli, but only pestalamide B (13) was found in all eleven of the tested strains. These metabolites, as well as a group of synthetic analogues demonstrated weak antifungal activity against several Candida strains, Aspergillus flavus, and Aspergillus fumigatus. PMID:21854017

Polarographic study of cadmium 5-hydroxy 2-(hydroxymethyl) 4H-pyran-4-one complex

NASA Technical Reports Server (NTRS)

Wilson, Ray F.; Daniels, Robert C.

1989-01-01

A polarographic study was performed on the products formed in the interaction of cadmium (II) with a 5-hydroxy 2-(hydroxymethyl) 4H-Pyran-4-one, using varying conditions of pH, supporting electrolytes, and concentrations. Measurements using the differential pulse method show that cadmium (II) exhibits a molar combining ratio of complexing agents to cation ranging from 1 to 1 to 3 to 1 depending on the pH and the supporting electrolyte employed.

Thieno[3,2-c]pyran-4-one based novel small molecules: their synthesis, crystal structure analysis and in vitro evaluation as potential anticancer agents.

PubMed

Nakhi, Ali; Adepu, Raju; Rambabu, D; Kishore, Ravada; Vanaja, G R; Kalle, Arunasree M; Pal, Manojit

2012-07-01

Novel thieno[3,2-c]pyran-4-one based small molecules were designed as potential anticancer agents. Expeditious synthesis of these compounds was carried out via a multi-step sequence consisting of few steps such as Gewald reaction, Sandmeyer type iodination, Sonogashira type coupling followed by iodocyclization and then Pd-mediated various C-C bond forming reactions. The overall strategy involved the construction of thiophene ring followed by the fused pyranone moiety and then functionalization at C-7 position of the resultant thieno[3,2-c]pyran-4-one framework. Some of the compounds synthesized showed selective growth inhibition of cancer cells in vitro among which two compounds for example, 5d and 6c showed IC(50) values in the range of 2.0-2.5 μM. The crystal structure analysis of an active compound along with hydrogen bonding patterns and molecular arrangement present within the molecule is described. Copyright © 2012 Elsevier Ltd. All rights reserved.

(E)-4-Meth­oxy-N′-[(6-methyl-4-oxo-4H-chromen-3-yl)methyl­idene]benzo­hydrazide monohydrate

PubMed Central

Ishikawa, Yoshinobu; Watanabe, Kohzoh

2014-01-01

In the title hydrate, C19H16N2O4·H2O, the 4H-chromen-4-one segment is slightly twisted, with a dihedral angle between the two six-membered rings of 3.30 (5)°. The dihedral angles between the plane of the pyran­one ring and the hydrazide plane and between the planes of the pyran­one ring and the benzene ring of the p-meth­oxy­benzene unit are 26.69 (4) and 2.23 (3)°, respectively. The mol­ecule is connected to the solvent water mol­ecule by an N—H⋯O hydrogen bond. In the crystal, there are π–π stacking inter­actions between centrosymmetrically related pyran­one rings [centroid–centroid distance = 3.5394 (9) Å], as well as bridges formed by the water mol­ecules via O—H⋯O hydrogen bonds. PMID:25161570

9-(3,4-Dimeth-oxy-phen-yl)-3,4,5,6,7,9-hexa-hydroxanthene-1,8(2H)-dione.

PubMed

Mehdi, Sayed Hasan; Hashim, Rokiah; Ghalib, Raza Murad; Yeap, Chin Sing; Fun, Hoong-Kun

2011-06-01

In the title compound, C(21)H(22)O(5), the mean planes of the pyran and dimeth-oxy-phenyl rings are nearly perpendicular to one another, with the dihedral angle between them being 88.21 (8)°. The pyran ring adopts a boat conformation whereas the two fused cyclo-hexane rings adopt envelope conformations. In the crystal, mol-ecules are linked into a three-dimensional network by inter-molecular C-H⋯O hydrogen bonds.

Synthesis, X-ray crystal structures and catecholase activity investigation of new chalcone ligands

NASA Astrophysics Data System (ADS)

Thabti, Salima; Djedouani, Amel; Rahmouni, Samra; Touzani, Rachid; Bendaas, Abderrahmen; Mousser, Hénia; Mousser, Abdelhamid

2015-12-01

The reaction of dehydroacetic acid DHA carboxaldehyde and RCHO derivatives (R = quinoleine-8-; indole-3-; pyrrol-2- and 4-(dimethylamino)phenyl - afforded four new chalcone ligands (4-hydroxy-6-methyl-3-[(2E)-3-quinolin-8-ylprop-2-enoyl]-2H-pyran-2-one) L1, (4-hydroxy-3-[(2E)-3-(1H-indol-3-yl)prop-2-enoyl]-6-methyl-2H-pyran-2-one) L2, (4-hydroxy-6-methyl-3-[(2E)-3-(1H-pyrrol-2-yl)prop-2-enoyl]-2H-pyran-2-one) L3, and (3-{(2E)-3-[4-(dimethylamino)phenyl]prop-2-enoyl}-4-hydroxy-6-methyl-2H-pyran-2-one) L4. L3 and L4 were characterized by X-ray crystallography. Molecules crystallize with four and two molecules in the asymmetric unit, respectively and adopt an E conformation about the Cdbnd C bond. Both structures are stabilized by an extended network O-H … O. Furthermore, N-H … O and C-H … O hydrogen bonds are observed in L3 and L4 structures, respectively. The in situ generated copper (II) complexes of the four compounds L1, L2, L3 and L4 were examined for their catalytic activities and were found to catalyze the oxidation reaction of catechol to o-quinone under atmospheric dioxygen. The rates of this oxidation depend on three parameters: ligand, ion salts and solvent nature and the combination L2[Cu (CH3COO)2] leads to the faster catalytic process.

A facile, efficient, and sustainable chitosan/CaHAp catalyst and one-pot synthesis of novel 2,6-diamino-pyran-3,5-dicarbonitriles.

PubMed

Maddila, Suresh; Gangu, Kranthi Kumar; Maddila, Surya Narayana; Jonnalagadda, Sreekantha B

2017-02-01

A simple and versatile one-pot three-component synthetic protocol is devised for heterocycles, viz. 2,6-diamino-4-substituted-4H-pyran-3,5-dicarbonitrile derivatives, in short reaction times ([Formula: see text]30 min) at room temperature using ethanol as a solvent. This method involves the three-component reaction of malononitrile, substituted aldehydes, and cyanoacetamide catalyzed by chitosan-doped calcium hydroxyapatites (CS/CaHAps) giving good to excellent yields (86-96%). Twelve new pyran derivatives (4a-l) were synthesized and their structures were established and confirmed by different spectroscopic methods ([Formula: see text]H NMR, [Formula: see text]C NMR, [Formula: see text]N NMR, and HRMS). The heterogeneous catalyst, CS/CaHAp, was characterized by various instrumental techniques including XRD, TEM, SEM, and FT-IR and TGA spectroscopies. The catalyst was easily separable and reusable for up to six runs without any apparent loss of activity. The reported protocol has many benefits, such as ease of preparation, use of a green solvent, reduced reaction times, excellent product yields, and operational simplicity.

9-(3,4-Dimeth­oxy­phen­yl)-3,4,5,6,7,9-hexa­hydroxanthene-1,8(2H)-dione

PubMed Central

Mehdi, Sayed Hasan; Hashim, Rokiah; Ghalib, Raza Murad; Yeap, Chin Sing; Fun, Hoong-Kun

2011-01-01

In the title compound, C21H22O5, the mean planes of the pyran and dimeth­oxy­phenyl rings are nearly perpendicular to one another, with the dihedral angle between them being 88.21 (8)°. The pyran ring adopts a boat conformation whereas the two fused cyclo­hexane rings adopt envelope conformations. In the crystal, mol­ecules are linked into a three-dimensional network by inter­molecular C—H⋯O hydrogen bonds. PMID:21754824

DIBALH mediated reduction of the acetal moiety on perhydrofuro[2,3-b]pyran derivatives.

PubMed

Marco-Contelles, J; Ruiz-Caro, J

2001-09-21

The reaction of DIBALH with bis(heteroannulated)-pyranosides containing the perhydrofuro[2,3-b]pyran moiety is described. The hydride attack at the anomeric carbon (C-9a) resulted in the exclusive tetrahydrofuran ring opening. The selectivity of this reaction has been evaluated as other benzylidene acetals built on these substrates remain practically or partially unaltered in these conditions depending on the steric volume of the O-protecting group located at C-4 (TBDMS vs. Me). This protocol can be considered as a new entry for the synthesis of chiral and highly functionalized cyclopentanes.

Highly Z- and Enantioselective Ring-Opening/Cross-Metathesis Reactions Catalyzed by Stereogenic-at-Mo Adamantylimido Complexes

PubMed Central

Ibrahem, Ismail; Yu, Miao; Schrock, Richard R.; Hoveyda, Amir H.

2009-01-01

The first highly Z- and enantioselective class of ring-opening/cross-metathesis (ROCM) reactions is presented. Transformations are promoted in the presence of <2 mol % of chiral stereogenic-at-Mo monoaryloxide complexes, which bear an adamantylimido ligand and are prepared and used in situ. Reactions involve meso oxabicyclic substrates and afford the desired pyrans in 50–85% yield and in up to >98:<2 enantiomer ratio (er). Importantly, the desired chiral pyrans are thus obtained bearing a Z olefin either exclusively (>98:<2 Z:E) or predominantly (≥87:13 Z:E). PMID:19249833

Crystal structure of 1,2,3,4-di-O-methyl­ene-α-d-galacto­pyran­ose

PubMed Central

Tiritiris, Ioannis; Tussetschläger, Stefan; Kantlehner, Willi

2015-01-01

The title compound, C8H12O6, was synthesized by de­acetyl­ation of 6-acetyl-1,2,3,4-di-O-methyl­ene-α-d-galactose with sodium methoxide. The central part of the mol­ecule consists of a six-membered C5O pyran­ose ring with a twist-boat conformation. Both fused dioxolane rings adopt an envelope conformation with C and O atoms as the flap. In the crystal, O—H⋯O and C—H⋯O hydrogen bonds are present between adjacent mol­ecules, generating a three-dimensional network. PMID:26870551

14-Meth­oxy-4,6-dimethyl-9-phenyl-8,12-dioxa-4,6-di­aza­tetra­cyclo­[8.8.0.02,7.013,18]octa­deca-2(7),13,15,17-tetra­ene-3,5,11-trione

PubMed Central

Jagadeesan, G; Jayashree, S.; Kannan, D.; Bakthadoss, M.; Aravindhan, S.

2013-01-01

The title compound, C23H20N2O6, crystallizes with two mol­ecules in the asymmetric unit in which the dihedral angles between the mean planes of the pyran and phenyl rings are 66.6 (1) and 61.9 (1) °. The fused pyrone and pyran rings each adopts a sofa conformation. In the crystal, C—H⋯O hydrogen bonds link the mol­ecules, forming a two-dimensional network parallel to [001]. PMID:24109298

14-Eth­oxy-4,6-dimethyl-9-phenyl-8,12-dioxa-4,6-diaza­tetra­cyclo­[8.8.0.02,7.013,18]octa­deca-2(7),13,15,17-tetra­ene-3,5,11-trione

PubMed Central

Jagadeesan, G.; Kannan, D.; Bakthadoss, M.; Aravindhan, S.

2013-01-01

In the title compound, C23H20N2O6, the fused pyrone and pyran rings each adopt a sofa conformation. The dihedral angle between the mean planes of the pyran and phenyl rings is 61.9 (1)°. In the crystal, mol­ecules are linked by two pairs of C—H⋯O hydrogen bonds, forming dimers. These dimers are linked via a third C—H⋯O hydrogen bond, forming a two-dimensional network parallel to (10-2). PMID:23476462

Structure of 7-hy-droxy-3-(2-meth-oxy-phen-yl)-2-tri-fluoro-meth-yl-4H-chromen-4-one.

PubMed

Low, John Nicolson; Gomes, Ligia R; Gaspar, Alexandra; Borges, Fernanda

2017-07-01

Herein, the synthesis and crystal structure of 7-hy-droxy-3-(2-meth-oxy-phen-yl)-2-tri-fluoro-meth-yl-4 H -chromen-4-one, C 17 H 11 F 3 O 4 , are reported. This isoflavone is used as a starting material in the preparation an array of potent and competitive FPR antagonists. The pyran ring significantly deviates from planarity and the dihedral angle between the benzo-pyran mean plane and that of the exocyclic benzene ring is 88.18 (4)°. In the crystal, O-H⋯O hydrogen bonds connect the mol-ecules into C (8) chains propagating in the [010] direction.

Ultrasound mediated, iodine catalyzed green synthesis of novel 2-amino-3-cyano-4H-pyran derivatives.

PubMed

Tabassum, Sumaiya; Govindaraju, Santhosh; Khan, Riyaz-ur-Rahaman; Pasha, Mohamed Afzal

2015-05-01

An efficient synthesis of a novel series of twelve substituted 2-amino-3-cyano-4H-pyran derivatives was achieved by a one-pot three-component cyclocondensation reaction of heteroaryl aldehydes, malononitrile and active methylene compounds catalyzed by iodine in aqueous medium under ultrasound irradiation. In comparison with conventional methods, our protocol is convenient and offers several advantages, such as shorter reaction time, higher yields, milder conditions and environmental friendliness. We have herein successfully demonstrated the synergistic outcome of multi-component reaction (MCR) and sonication to offer a facile route for the design of these derivatives. Copyright © 2014 Elsevier B.V. All rights reserved.

Synthesis and antimalarial and antituberculosis activities of a series of natural and unnatural 4-methoxy-6-styryl-pyran-2-ones, dihydro analogues and photodimers

PubMed Central

McCracken, Stephen T.; Kaiser, Marcel; Boshoff, Helena I.; Boyd, Peter D. W.; Copp, Brent R.

2012-01-01

Previous studies have identified the 3,6-dialkyl-4-hydroxy-pyran-2-one marine microbial metabolites pseudopyronines A and B to be modest growth inhibitors of Mycobacterium tuberculosis and a range of tropical diseases including Plasmodium falciparum and Leishmania donovani. In an effort to expand the structure-activity relationship of this compound class towards. infectious diseases, a library of natural product and natural product-like 4-methoxy-6-styryl-pyran-2-ones and a subset of catalytically reduced examples were synthesised. In addition, the photochemical reactivity of several of the 4-methoxy-6-styryl-pyran-2-ones were investigated yielding head-to-head and head-to-tail cyclobutane dimers as well as examples of asymmetric aniba-dimer A-type dimers. All compounds were evaluated for cytotoxicity and activity against M. tuberculosis, P. falciparum, L. donovani, Trypanosoma brucei rhodesiense and T. cruzi. Of the styryl-pyranones, natural product 3 and non-natural styrene and naphthalene substituted examples 13, 18, 21, 22 and 23 exhibited antimalarial activity (IC50 < 10 μM) with selectivity indices (SI) > 10. Δ7 Dihydro analogues were typically less active or lacked selectivity. Head-to-head and head-to-tail photodimers 5 and 34 exhibited moderate IC50s of 2.3 to 17 μM towards several of the parasitic organisms, while the aniba-dimer-type asymmetric dimers 31 and 33 were identified as being moderately active towards P. falciparum (IC50 1.5 and 1.7 μM) with good selectivity (SI ∼ 80). The 4-tert-butyl aniba-dimer A analogue 33 also exhibited activity towards L. donovani (IC50 4.5 μM), suggesting further elaboration of this latter scaffold could lead to the identification of new leads for the dual treatment of malaria and leishmaniasis. PMID:22285027

Molecular design of donor-acceptor dyes for efficient dye-sensitized solar cells I: a DFT study.

PubMed

El-Shishtawy, Reda M; Asiri, Abdullah M; Aziz, Saadullah G; Elroby, Shaaban A K

2014-06-01

Dye-sensitized solar cells (DSSCs) have drawn great attention as low cost and high performance alternatives to conventional photovoltaic devices. The molecular design presented in this work is based on the use of pyran type dyes as donor based on frontier molecular orbitals (FMO) and theoretical UV-visible spectra in combination with squaraine type dyes as an acceptor. Density functional theory has been used to investigate several derivatives of pyran type dyes for a better dye design based on optimization of absorption, regeneration, and recombination processes in gas phase. The frontier molecular orbital (FMO) of the HOMO and LUMO energy levels plays an important role in the efficiency of DSSCs. These energies contribute to the generation of exciton, charge transfer, dissociation and exciton recombination. The computations of the geometries and electronic structures for the predicted dyes were performed using the B3LYP/6-31+G** level of theory. The FMO energies (EHOMO, ELUMO) of the studied dyes are calculated and analyzed in the terms of the UV-visible absorption spectra, which have been examined using time-dependent density functional theory (TD-DFT) techniques. This study examined absorption properties of pyran based on theoretical UV-visible absorption spectra, with comparisons between TD-DFT using B3LYP, PBE, and TPSSH functionals with 6-31+G (d) and 6-311++G** basis sets. The results provide a valuable guide for the design of donor-acceptor (D-A) dyes with high molar absorptivity and current conversion in DSSCs. The theoretical results indicated 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran dye (D2-Me) can be effectively used as a donor dye for DSSCs. This dye has a low energy gap by itself and a high energy gap with squaraine acceptor type dye, the design that reduces the recombination and improves the photocurrent generation in solar cell.

Evaluation of the bioavailability and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juice.

PubMed

Cerdá, Begoña; Llorach, Rafael; Cerón, José J; Espín, Juan Carlos; Tomás-Barberán, Francisco A

2003-01-01

Punicalagin is an antioxidant ellagitannin of pomegranate juice. This compound is responsible for the high antioxidant activity of this juice. Nothing is known about the bioavailability and metabolism of punicalagin or other food ellagitannins. The present work aims to evaluate the bioavailability and metabolism of punicalagin in the rat as an animal model. Two groups of rats were studied. One fed with standard rat diet (n = 5) and another with the same diet plus 6 % punicalagin (n = 5). Samples of urine and faeces were taken during 37 days and plasma every week. The different metabolites were analysed by HPLC-MS-MS. The daily intake of punicalagin ranged from 0.6 to 1.2 g. Values around 3-6 % the ingested punicalagin were excreted as identified metabolites in faeces and urine. In faeces, punicalagin is transformed to hydrolysis products and partly metabolites by the rat microflora to 6H-dibenzo[b,d]pyran-6-one derivatives. In plasma, punicalagin was detected at concentrations around 30 microg/mL, and glucuronides of methyl ether derivatives of ellagic acid were also detected. 6H-Dibenzo[b,d]pyran-6-one derivatives were also detected especially during the last few weeks of the experiment. In urine, the main metabolites observed were the 6H-dibenzo[b,d]pyran-6-one derivatives, as aglycones or glucuronides. As only 3-6 % of the ingested punicalagin was detected as such or as metabolites in urine and faeces, the majority of this ellagitannin has to be converted to undetectable metabolites (i. e. CO(2)) or accumulated in non-analysed tissues, however with only traces of punicalagin metabolites being detected in liver or kidney. This is the first report on the absorption of an ellagitannin and its presence in plasma. In addition, the transformation of ellagic acid derivatives to 6H-dibenzo[b,d]pyran-6-one derivatives in the rat is also confirmed.

Pyranone natural products as inspirations for catalytic reaction discovery and development.

PubMed

McDonald, Benjamin R; Scheidt, Karl A

2015-04-21

Natural products continue to provide a wealth of opportunities in the areas of chemical and therapeutic development. These structures are effective measuring sticks for the current state of chemical synthesis as a field and constantly inspire new approaches and strategies. Tetrahydropryans and tetrahydropyran-4-ones are found in numerous bioactive marine natural products and medicinal compounds. Our interest in exploring the therapeutic potential of natural products containing these motifs provided the impetus to explore new methods to access highly functionalized, chiral pyran molecules in the most direct and rapid fashion possible. This goal led to exploration and development of a Lewis acid-mediated Prins reaction between a chiral β-hydroxy-dioxinone and aldehyde to produce a pyran-dioxinone fused product that can be processed in a single pot operation to the desired tetrahydropyran-4-ones in excellent yield and stereoselectivity. Although the Prins reaction is a commonly employed approach toward pyrans, this method uniquely provides a 3-carboxy-trisubstituted pyran and utilizes dioxinones in a manner that was underexplored at the time. The 3-carboxy substituent served as a key synthetic handhold when this method was applied to the synthesis of highly functionalized pyrans within the macrocyclic natural products neopeltolide, okilactiomycin, and exiguolide. When employed in challenging macrocyclizations, this tetrahydropyranone forming reaction proved highly stereoselective and robust. Another major thrust in our lab has been the synthesis of benzopyranone natural products, specifically flavonoids, because this broad and diverse family of compounds possesses an equally broad range of biological and medicinal applications. With the goal of developing a broad platform toward the synthesis of enantioenriched flavonoid analogs and natural products, a biomimetic, asymmetric catalytic approach toward the synthesis of 2-aryl benzopyranones was developed. A bifunctional hydrogen bonding/Brønstead base catalyst was ultimately found to enable this transformation in analogous manner to the biosynthesis via the enzyme chalcone isomerase. Employing thiourea catalysts derived from the pseudoenantiomeric quinine and quinidine, alkylidene β-ketoesters can be isomerized to 3-carboxy flavanones and decarboxylated in a single pot operation to stereodivergently provide highly enantioenriched flavanones in excellent yield. This method was applied to the synthesis of the abyssinone family of natural products, as well as the rotenoid, deguelin. An analogous method to isomerize chalcones was developed and applied to the synthesis of isosilybin A. In both of these related endeavors, the need for novel enabling methodologies toward the efficient creation of targeted molecular complexity drove the discovery, development and deployment of these stereoselective catalytic transformations.

Pericocins A-D, New Bioactive Compounds from Periconia sp.

PubMed

Wu, Yue-Hua; Xiao, Gao-Keng; Chen, Guo-Dong; Wang, Chuan-Xi; Hu, Dan; Lian, Yun-Yang; Lin, Feng; Guo, Liang-Dong; Yao, Xin-Sheng; Gao, Hao

2015-12-01

One new dihydroisocoumarin, pericocin A (1), one new chromone, pericocin B (2), and two new α-pyrone derivatives, pericocins C-D (3-4), together with two known compounds, 3-(2-oxo-2H-pyran-6-yl)propanoic acid (5) and (E)-3-(2-oxo-2H-pyran-6-yl)acrylic acid (6), were isolated from the culture of the endolichenic fungus Periconia sp.. Their structures were elucidated by spectroscopic methods. All these compounds are derived from the polyketone biosynthetic pathway. Compound 1 was obtained as a mixture of enantiomers. The antimicrobial activity of compounds 1-5 was tested against Escherichia coli, Staphylococcus aureus, Aspergillus niger, and Candida albicans. Compounds 1-5 showed moderate antimicrobial activity against A. niger and weak activity against C. albicans.

Ultrasound promoted one-pot synthesis of 2-amino-4,8-dihydropyrano[3,2-b]pyran-3-carbonitrile scaffolds in aqueous media: a complementary 'green chemistry' tool to organic synthesis.

PubMed

Banitaba, Sayed Hossein; Safari, Javad; Khalili, Shiva Dehghan

2013-01-01

A green and simple approach to assembling of 2-amino-4,8-dihydropyrano[3,2-b]pyran-3-carbonitrile scaffolds via three-component reaction of kojic acid, malononitrile, and aromatic aldehydes in aqueous media under ultrasound irradiation is described. The combinatorial synthesis was achieved for this methodology with applying ultrasound irradiation while making use of water as green solvent. In comparison to conventional methods, experimental simplicity, good functional group tolerance, excellent yields, short routine, and selectivity without the need for a transition metal or base catalyst are prominent features of this green procedure. Copyright © 2012 Elsevier B.V. All rights reserved.

'Unconventional' coordination chemistry by metal chelating fragments in a metalloprotein active site.

PubMed

Martin, David P; Blachly, Patrick G; Marts, Amy R; Woodruff, Tessa M; de Oliveira, César A F; McCammon, J Andrew; Tierney, David L; Cohen, Seth M

2014-04-09

The binding of three closely related chelators: 5-hydroxy-2-methyl-4H-pyran-4-thione (allothiomaltol, ATM), 3-hydroxy-2-methyl-4H-pyran-4-thione (thiomaltol, TM), and 3-hydroxy-4H-pyran-4-thione (thiopyromeconic acid, TPMA) to the active site of human carbonic anhydrase II (hCAII) has been investigated. Two of these ligands display a monodentate mode of coordination to the active site Zn(2+) ion in hCAII that is not recapitulated in model complexes of the enzyme active site. This unprecedented binding mode in the hCAII-thiomaltol complex has been characterized by both X-ray crystallography and X-ray spectroscopy. In addition, the steric restrictions of the active site force the ligands into a 'flattened' mode of coordination compared with inorganic model complexes. This change in geometry has been shown by density functional computations to significantly decrease the strength of the metal-ligand binding. Collectively, these data demonstrate that the mode of binding by small metal-binding groups can be significantly influenced by the protein active site. Diminishing the strength of the metal-ligand bond results in unconventional modes of metal coordination not found in typical coordination compounds or even carefully engineered active site models, and understanding these effects is critical to the rational design of inhibitors that target clinically relevant metalloproteins.

Crystal structure of diaphorin methanol monosolvate isolated from Diaphorina citri Kuwayama, the insect vector of citrus greening disease.

PubMed

Szebenyi, D Marian; Kriksunov, Irina; Howe, Kevin J; Ramsey, John S; Hall, David G; Heck, Michelle L; Krasnoff, Stuart B

2018-04-01

The title compound C 22 H 39 NO 9 ·CH 3 OH [systematic name: ( S )- N -(( S )-{(2 S ,4 R ,6 R )-6-[( S )-2,3-di-hydroxy-prop-yl]-4-hy-droxy-5,5-di-methyl-tetra-hydro-2 H -pyran-2-yl}(hy-droxy)meth-yl)-2-hy-droxy-2-[(2 R ,5 R ,6 R )-2-meth-oxy-5,6-dimeth-yl-4-methyl-ene-tetra-hydro-2 H -pyran-2-yl]acetamide methanol monosolvate], was isolated from the Asian citrus psyllid, Diaphorina citri Kuwayama, and crystallizes in the space group P 2 1 . ' Candidatus Profftella armatura' a bacterial endosymbiont of D. citri , biosynthesizes diaphorin, which is a hybrid polyketide-nonribosomal peptide comprising two highly substituted tetra-hydro-pyran rings joined by an N -acyl aminal bridge [Nakabachi et al. (2013 ▸). Curr. Biol. 23 , 1478-1484]. The crystal structure of the title compound establishes the complete relative configuration of diaphorin, which agrees at all nine chiral centers with the structure of the methanol monosolvate of the di- p -bromo-benzoate derivative of pederin, a biogenically related compound whose crystal structure was reported previously [Furusaki et al. (1968 ▸). Tetra-hedron Lett. 9 , 6301-6304]. Thus, the absolute configuration of diaphorin is proposed by analogy to that of pederin.

Synthesis and characterization of two dehydroacetic acid derivatives and molybdenum(V) complexes: an NMR and crystallographic study

NASA Astrophysics Data System (ADS)

Cindrić, Marina; Vrdoljak, Višnja; Kajfež Novak, Tanja; Ćurić, Manda; Brbot-Šaranović, Ana; Kamenar, Boris

2004-09-01

Two enaminones ethyl 4-(4-hydroxy-6-methyl-2 H-pyran-2-on-3-yl)-2-(tryptamino)-4-oxo-2-butenoate ( HL1) and 3-(1-tryptaminoetylidene)-6-methyl-2 H-pyran-2,4(3H)-dione ( HL2) have been prepared by the reactions of tryptamine with 2-hydroxy-4-(4-hydroxy)-6-methyl)-2 Hbb-pyrane-2-on-3-yl)-4-oxo-2-butenoate (ehmpb) or with dehydroacetic acid (dha). The NMR spectroscopy confirmed that both tautomeric forms of HL1: endo-enol (tautomer A with hydroxyl group at position 4) and exo-enol form (tautomer B with hydroxyl group at position 7) are present in the DMSO- d6 solution. The molecular and crystal structure as well as the NMR data of HL2 showed that the condensation of dha and tryptamine occurs at acetyl-carbonyl and not at the pyrone-carbonyl group. Also new dinuclear [Mo 2O 4(L 1) 2(CH 3OH) 2] ( 1) and hexanuclear molybdenum(V) complexes (C 10H 12NH)[Mo 6O 12(OCH 3) 4(acac) 3] ( 2) have been prepared by the reactions of [Mo 2O 3(acac) 4] (acac=acetilacetonate ion) with HL1 or with tryptamine. All compounds have been characterized also by means of elemental analyses, IR spectroscopy as well as by thermal analyses.

2H-pyran-2-one and 2H-furan-2-one derivatives from the plant endophytic fungus Pestalotiopsis fici.

PubMed

Liu, Shuchun; Liu, Xiangyu; Guo, Liangdong; Che, Yongsheng; Liu, Ling

2013-11-01

Two new α-pyrones (=2H-pyran-2-ones), ficipyrones A and B (1 and 2, resp.), and two new α-furanones (=2H-furan-2-ones), ficifuranones A and B (3 and 4, resp.), together with three known metabolites, antibiotic F 0368 (5), hydroxyseiridin (6), and hydroxyisoseiridin (7), were isolated from solid cultures of the plant endophytic fungus Pestalotiopsis fici. Their structures were elucidated primarily by NMR spectroscopy, and the absolute configuration of 1 was deduced from the circular-dichroism (CD) data. Compound 1 showed antifungal activity against the plant pathogen Gibberella zeae (CGMCC 3.2873) with an IC50 value of 15.9 μM. Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.

9-(3,4-Dimeth-oxy-phen-yl)-3,3,6,6-tetra-methyl-4,5,6,9-tetra-hydro-3H-xanthene-1,8(2H,7H)-dione.

PubMed

Mehdi, Sayed Hasan; Sulaiman, Othman; Ghalib, Raza Murad; Yeap, Chin Sing; Fun, Hoong-Kun

2011-07-01

The asymmetric unit of the title xanthene compound, C(25)H(30)O(5), contains two mol-ecules in which the pyran ring and the dimeth-oxy-phenyl ring are nearly perpendicular to one another [dihedral angles = 86.81 (8) and 84.45 (9)°]. One of the meth-oxy groups in one mol-ecule is twisted away from the phenyl ring [C-O-C-C torsion angle = -103.40 (16)°]. The pyran ring adopts a boat conformation whereas the two fused cyclo-hexane rings adopt envelope conformations in both mol-ecules. In the crystal, mol-ecules are linked into a three-dimensional network by C-H⋯O hydrogen bonds.

Color-tunable, aggregation-induced emission of a butterfly-shaped molecule comprising a pyran skeleton and two cholesteryl wings.

PubMed

Tong, Hui; Hong, Yuning; Dong, Yongqiang; Ren, Yan; Häussler, Matthias; Lam, Jacky W Y; Wong, Kam Sing; Tang, Ben Zhong

2007-03-01

A chiral pyran derivative containing two cholesteryl groups (1) is synthesized, and its optical properties are investigated. Whereas the isolated molecule of 1 is virtually nonluminescent in dilute solutions, it becomes highly emissive with a 2 orders of magnitude increase in fluorescence quantum yield upon aggregation in poor solvents or in solid state, showing a novel phenomenon of aggregation-induced emission (AIE). The color and efficiency of the AIE of 1 can be tuned by varying the morphology of its aggregates: photoluminescence of its aggregates formed in a tetrahydrofuran/water mixture progressively red-shifts (green --> yellow --> red) with increasing water content of the mixture, with the crystalline aggregates emitting bluer lights in higher efficiencies than their amorphous counterparts.

Crystal structure of [(2R,3R,4S)-3,4-bis(acet-yloxy)-5-iodo-3,4-di-hydro-2H-pyran-2-yl]methyl acetate.

PubMed

Zukerman-Schpector, Julio; Caracelli, Ignez; Stefani, Hélio A; Shamim, Anwar; Tiekink, Edward R T

2015-01-01

In the title compound, C12H15IO7, the 3,4-di-hydro-2H-pyran ring is in a distorted half-boat conformation with the atom bearing the acet-yloxy group adjacent to the C atom bearing the methyl-acetate group lying 0.633 (6) Å above the plane of the remaining ring atoms (r.m.s. deviation = 0.0907 Å). In the crystal, mol-ecules are linked into a supra-molecular chain along the a axis through two C-H⋯O inter-actions to the same acceptor carbonyl O atom; these chains pack with no specific inter-molecular inter-actions between them.

New phenylpropanoid and 6H-dibenzo[b,d]pyran-6-one derivatives from the stems of Dasymaschalon rostratum.

PubMed

Yu, Zhang-Xin; Niu, Zhi-Gang; Li, Xiao-Bao; Zheng, Cai-Juan; Song, Xin-Ming; Chen, Guang-Ying; Song, Xiao-Ping; Han, Chang-Ri; Wu, Shu-Xian

2017-04-01

Three new phenylpropanoid derivatives, dasymaroacid A (1), dasymaroesters B and C (2 and 3), and one new polyoxygenated 6H-dibenzo[b,d]pyran-6-one derivative dasymarolactone D (4), together with seven known compounds (5-11), were isolated from the stems of Dasymaschalon rostratum Merr. Compounds 1 and 2 are unusual phenylpropanoid derivatives with a polymethyl substituted cyclopentene conjugated diketone as a substituent, and 3 is a unique cinnamic acid detective with a polymethyl substituted cyclohexene conjugated triketone as a substituent. Their structures were elucidated by extensive spectroscopic methods and chemical method, and 4 was further confirmed by the single crystal X-ray diffraction method. Compounds 1-4 and 7 showed weak anti-HIV-1 activities with EC 50 values ranged from 16.44 to 25.91μM. Copyright © 2017 Elsevier B.V. All rights reserved.

9-(3,4-Dimeth­oxy­phen­yl)-3,3,6,6-tetra­methyl-4,5,6,9-tetra­hydro-3H-xanthene-1,8(2H,7H)-dione

PubMed Central

Mehdi, Sayed Hasan; Sulaiman, Othman; Ghalib, Raza Murad; Yeap, Chin Sing; Fun, Hoong-Kun

2011-01-01

The asymmetric unit of the title xanthene compound, C25H30O5, contains two mol­ecules in which the pyran ring and the dimeth­oxy­phenyl ring are nearly perpendicular to one another [dihedral angles = 86.81 (8) and 84.45 (9)°]. One of the meth­oxy groups in one mol­ecule is twisted away from the phenyl ring [C—O—C—C torsion angle = −103.40 (16)°]. The pyran ring adopts a boat conformation whereas the two fused cyclo­hexane rings adopt envelope conformations in both mol­ecules. In the crystal, mol­ecules are linked into a three-dimensional network by C—H⋯O hydrogen bonds. PMID:21837111

Vicinal 1H-1H NMR coupling constants from density functional theory as reliable tools for stereochemical analysis of highly flexible multichiral center molecules.

PubMed

López-Vallejo, Fabian; Fragoso-Serrano, Mabel; Suárez-Ortiz, Gloria Alejandra; Hernández-Rojas, Adriana C; Cerda-García-Rojas, Carlos M; Pereda-Miranda, Rogelio

2011-08-05

A protocol for stereochemical analysis, based on the systematic comparison between theoretical and experimental vicinal (1)H-(1)H NMR coupling constants, was developed and applied to a series of flexible compounds (1-8) derived from the 6-heptenyl-5,6-dihydro-2H-pyran-2-one framework. The method included a broad conformational search, followed by geometry optimization at the DFT B3LYP/DGDZVP level, calculation of the vibrational frequencies, thermochemical parameters, magnetic shielding tensors, and the total NMR spin-spin coupling constants. Three scaling factors, depending on the carbon atom hybridizations, were found for the (1)H-C-C-(1)H vicinal coupling constants: f((sp3)-(sp3)) = 0.910, f((sp3)-(sp2)) = 0.929, and f((sp2)-(sp2))= 0.977. A remarkable correlation between the theoretical (J(pre)) and experimental (1)H-(1)H NMR (J(exp)) coupling constants for spicigerolide (1), a cytotoxic natural product, and some of its synthetic stereoisomers (2-4) demonstrated the predictive value of this approach for the stereochemical assignment of highly flexible compounds containing multiple chiral centers. The stereochemistry of two natural 6-heptenyl-5,6-dihydro-2H-pyran-2-ones (14 and 15) containing diverse functional groups in the heptenyl side chain was also analyzed by application of this combined theoretical and experimental approach, confirming its reliability. Additionally, a geometrical analysis for the conformations of 1-8 revealed that weak hydrogen bonds substantially guide the conformational behavior of the tetraacyloxy-6-heptenyl-2H-pyran-2-ones.

Dye system for dye laser applications

DOEpatents

Hammond, Peter R.

1991-01-01

A dye of the DCM family, [2-methyl-6-[2-(1,2,3,4-tetrahydro-1-methyl-6-quinolinyl)ethenyl]-4H-pyran -4-ylidene]-propanedinitrile, dissolved in 2-phenoxyethanol, is non-mutagenic, stable and efficient, particularly in a pumped continuous wave laser system.

Solution processable 2-(trityloxy)ethyl and tert-butyl group containing amorphous molecular glasses of pyranylidene derivatives with light-emitting and amplified spontaneous emission properties

NASA Astrophysics Data System (ADS)

Zarins, Elmars; Vembris, Aivars; Misina, Elina; Narels, Martins; Grzibovskis, Raitis; Kokars, Valdis

2015-11-01

Small organic molecules with incorporated 4H-pyran-4-ylidene (pyranylidene) fragment as the π-conjugation system which bonds the electron acceptor fragment (A) with electron donor part (D) in the molecule - also well known as derivatives of 4-(dicyano-methylene)-2-methyl-6-[p-(dimethylamino)styryl]-4H-pyran (DCM) laser dye-have attracted considerable attention of scientists as potential new generation materials for organic photonics and molecular electronics due to their low-cost fabrication possibility, flexibility and low-weight. Six glassy derivatives of 4H-pyran-4-ylidene (pyranylidene) with attached bulky 2-(trityloxy)ethyl and tert-butyl groups are described in this report. Almost all of the synthesized compounds form good optical quality transparent amorphous films from volatile organic solvents and could be obtained in good yields up to 75%. Their light emission in solution and thin solid films is in the range of 600-700 nm, they are thermally stable and show glass transition in the range of 108-158 °C. The amplified spontaneous emission threshold values of the neat films of the glassy pyranylidene derivatives vary from 155 to 450 μJ/cm2 and their HOMO and LUMO energy levels are between of those of tris(8-hydroxy quinolinato) aluminum (Alq3). The photoluminescence quantum yields of the glassy compounds are in the range from 1% to about 7.7% and their electroluminescence properties have been investigated. Therefore, glassy pyranylidene derivatives could be a very potential low-cost solution processable materials for Alq3 hosted light-amplification and light-emitting application studies.

Structural Insights into the Atomistic Mechanisms of Action of Small Molecule Inhibitors Targeting the KCa3.1 Channel Pore

PubMed Central

Nguyen, Hai M.; Singh, Vikrant; Pressly, Brandon; Jenkins, David Paul

2017-01-01

The intermediate-conductance Ca2+-activated K+ channel (KCa3.1) constitutes an attractive pharmacological target for immunosuppression, fibroproliferative disorders, atherosclerosis, and stroke. However, there currently is no available crystal structure of this medically relevant channel that could be used for structure-assisted drug design. Using the Rosetta molecular modeling suite we generated a molecular model of the KCa3.1 pore and tested the model by first confirming previously mapped binding sites and visualizing the mechanism of TRAM-34 (1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole), senicapoc (2,2-bis-(4-fluorophenyl)-2-phenylacetamide), and NS6180 (4-[[3-(trifluoromethyl)phenyl]methyl]-2H-1,4-benzothiazin-3(4H)-one) inhibition at the atomistic level. All three compounds block ion conduction directly by fully or partially occupying the site that would normally be occupied by K+ before it enters the selectivity filter. We then challenged the model to predict the receptor sites and mechanisms of action of the dihydropyridine nifedipine and an isosteric 4-phenyl-pyran. Rosetta predicted receptor sites for nifedipine in the fenestration region and for the 4-phenyl-pyran in the pore lumen, which could both be confirmed by site-directed mutagenesis and electrophysiology. While nifedipine is thus not a pore blocker and might be stabilizing the channel in a nonconducting conformation or interfere with gating, the 4-phenyl-pyran was found to be a classical pore blocker that directly inhibits ion conduction similar to the triarylmethanes TRAM-34 and senicapoc. The Rosetta KCa3.1 pore model explains the mechanism of action of several KCa3.1 blockers at the molecular level and could be used for structure-assisted drug design. PMID:28126850

Synthesis of new 2-amino-4H-pyran-3,5-dicarboxylate derivatives using nanocrystalline MIIZr4(PO4)6 ceramics as reusable and robust catalysts under microwave irradiation

NASA Astrophysics Data System (ADS)

Safaei-Ghomi, Javad; Javidan, Abdollah; Ziarati, Abolfazl; Shahbazi-Alavi, Hossein

2015-08-01

In the present paper, we report the successful synthesis of nanocrystalline MIIZr4(PO4)6 ceramics (M: Mn, Ni, Fe, Co). These nano-structures were characterized by X-ray diffraction, scanning electron microscopy, and vibrating sample magnetometer (VSM). Size of nano-structures was in the range of 20-150 nm. Nano-MIIZr4(PO4)6 as an efficient and green catalyst has been used for the preparation of 2-amino-4H-pyran-3,5-dicarboxylate derivatives by the three-component condensation reaction of ethyl cyanoacetate, ethyl acetoacetate, and various aromatic aldehydes under microwave irradiation. Extraordinarily, the best results were obtained using MnZr4(PO4)6 nanocrystallines as an efficient catalyst. This method provides several advantages including easy work-up, excellent yields, short reaction times, using of microwave as green method, recoverability of the catalyst, and little catalyst loading.

A Novel Schiff Base of 3-acetyl-4-hydroxy-6-methyl-(2H)pyran-2-one and 2,2'-(ethylenedioxy)diethylamine as Potential Corrosion Inhibitor for Mild Steel in Acidic Medium

PubMed Central

Asegbeloyin, Jonnie N.; Ejikeme, Paul M.; Olasunkanmi, Lukman O.; Adekunle, Abolanle S.; Ebenso, Eno E.

2015-01-01

The corrosion inhibition activity of a newly synthesized Schiff base (SB) from 3-acetyl-4-hydroxy-6-methyl-(2H)-pyran-2-one and 2,2'-(ethylenedioxy)diethylamine was investigated on the corrosion of mild steel in 1 M HCl solution using potentiodynamic polarization and electrochemical impedance spectroscopic techniques. Ultraviolet-visible (UV-vis) and Raman spectroscopic techniques were used to study the chemical interactions between SB and mild steel surface. SB was found to be a relatively good inhibitor of mild steel corrosion in 1 M HCl. The inhibition efficiency increases with increase in concentration of SB. The inhibition activity of SB was ascribed to its adsorption onto mild steel surface, through physisorption and chemisorption, and described by the Langmuir adsorption model. Quantum chemical calculations indicated the presence of atomic sites with potential nucleophilic and electrophilic characteristics with which SB can establish electronic interactions with the charged mild steel surface.

Investigating the Influence of Karrikins on Seed Germination

ERIC Educational Resources Information Center

de Beer, Josef

2012-01-01

Recent research has identified a karrikin (a butenolide derative) known as 3-methyl-2H-furo[2,3-c]pyran-2-one, formed from burning cellulose, that stimulates seed germination. Here, I present ideas on how to investigate the influence of karrikins on seed germination in the laboratory.

Benzofuran-pyran hybrids: A new class of potential bone anabolic agents.

PubMed

Gupta, Sampa; Adhikary, Sulekha; Modukuri, Ram K; Choudhary, Dharmendra; Trivedi, Ritu; Sashidhara, Koneni V

2018-06-01

Benzofuran moiety is an important pharmacophore showing positive effects on bone health. In the present study, sixteen benzofuran-pyran hybrids were synthesized and were evaluated for their osteogenic effects on primary osteoblast cells isolated from calvaria. Compounds 22 and 24 were found potent in stimulating osteoblast differentiation as assessed by the alkaline phosphatase activity. These compounds were also found to be nontoxic to osteoblast cells as compared to the control cells in MTT assay. Further, Alizarin Red-S staining for visualization of calcium nodules demonstrated compounds 22 and 34 as active in enhancing mineralization in osteoblast cells. Additionally, transcriptional analysis of these compounds on osteoblast cells revealed that compound 22 up-regulated the expression of osteogenic genes RUNX2, BMP-2, COL-1, thus substantiating that compound 22 having two geminal methyl groups in its R 3 position is a potent osteogenic agent. Additionally, compound 22 enhanced the ability of bone marrow stromal cells to differentiate towards osteoblast lineage and therefore can be further studied in vivo in bone loss model. Copyright © 2018 Elsevier Ltd. All rights reserved.

Characterization and hypoglycemic activity of a β-pyran polysaccharides from bamboo shoot (Leleba oldhami Nakal) shells.

PubMed

Zheng, Yafeng; Zhang, Shuai; Wang, Qi; Lu, Xu; Lin, Liangmei; Tian, Yuting; Xiao, Jianbo; Zheng, Baodong

2016-06-25

The bamboo shoot (Leleba oldhami Nakal) shell is a by-product during bamboo shoot processing. It is a cheap and available resource for dietary polysaccharides. Herein, a novel polysaccharide BSSP2a was isolated and characterized from the bamboo shoot shell polysaccharides, and it was identified as a homogeneous highly-branched beta type pyran polysaccharide with a molecular weight of 1.63×10(4)kDa, which consisted of arabinose, xylose, mannose, glucose and galactose at a molar ratio of 20.4:4.9:1:3.4:20.6. The crude polysaccharides (BSSP) from the bamboo shoots shell showed hypoglycemic activity on the high fat diet and streptozotocin induced diabetic mice in a dose-dependent manner. The administration of high dose BSSP (400mg/kg) improved body weight loss and serum insulin loss, and significantly decreased the blood glucose level, serum triglycerides as well as total cholesterol levels by 48.7%, 34.8% and 26.5%, respectively. The results highlight the potential of the bamboo shoot shell polysaccharides as a natural anti-diabetic agent. Copyright © 2016 Elsevier Ltd. All rights reserved.

A 26-Membered Macrocycle Obtained by a Double Diels-Alder Cycloaddition Between Two 2H-Pyran-2-one Rings and Two 1,1'-(Hexane-1,6-diyl)bis (1H-pyrrole-2,5-dione)s.

PubMed

Turek, Bor Lucijan; Kočevar, Marijan; Kranjc, Krištof; Perdih, Franc

2017-12-01

With the application of a double dienophile 1,1'-(hexane-1,6-diyl)bis(1H-pyrrole-2,5-dione) for a [4+2] cycloaddition with a substituted 2H-pyran-2-one a novel 26-membered tetraaza heteromacrocyclic system 3 was prepared via a direct method under solvent-free conditions with microwave irradiation. The macrocycle prepared is composed of two units of the dienophile and two of the diene. The structure of the macrocycle was characterized on the basis of IR, 1H and 13C NMR and mass spectroscopy, as well as by the elemental analysis and melting point determination. With X-ray diffraction of a single crystal of the macrocycle we have determined that the two acetyl groups (attached to the bridging double bond of the bicyclo[2.2.2]octene fragments) are oriented towards each other (and also towards the inside of the cavity of the macrocycle), therefore, mostly filling it completely.

Design, Synthesis, Structural and Spectroscopic Studies of Push-Pull Two-Photon Absorbing Chromophores with Acceptor Groups of Varying Strength

PubMed Central

Morales, Alma R.; Frazer, Andrew; Woodward, Adam W.; Ahn-White, Hyo-Yang; Fonari, Alexandr; Tongwa, Paul; Timofeeva, Tatiana; Belfield, Kevin D.

2013-01-01

A new series of unsymmetrical diphenylaminofluorene-based chromophores with various strong π-electron acceptors were synthesized and fully characterized. The systematic alteration of the structural design facilitated the investigation of effects such as molecular symmetry and strength of electron-donating and/or withdrawing termini have on optical nonlinearity. In order to determine the electronic and geometrical properties of the novel compounds, a thorough investigation was carried out by a combination of linear and nonlinear spectroscopic techniques, single crystal X-ray diffraction, and quantum chemical calculations. Finally, on the basis of two-photon absorption (2PA) cross sections, the general trend for π -electron accepting ability, i.e., ability to accept charge transfer from diphenylamine was: 2-pyran-4-ylidene malononitrile (pyranone) > dicyanovinyl > bis(dicyanomethylidene)indane > 1-(thiophen-2-yl)propenone > dicyanoethylenyl > 3-(thiophen-2-yl)propenone. An analog with the 2-pyran-4-ylidene malononitrile acceptor group exhibited a nearly three-fold enhancement of the 2PA< δ (1650 GM at 840 nm), relative to other members of the series. PMID:23305555

Annual Research Report, 1 October 1977-30 September 1978.

DTIC Science & Technology

1978-09-30

and other lipid components. Collaboratihe studies with the National Cancer Institute and other medical centers include research on the immunological...copolymer, or glucan were administered intraperitoneally within 2 hours after sublethal X irradiation (600 rads), the adjuvant- induced cytotoxic...concentrations of inducer. When BCG, pyran, or glucan was administered intraperitoneally concurrently with subcutaneous cyclophosphamide, only the ability

Antileukemic alpha-pyrone derivatives from the endophytic fungus Alternaria phragmospora

USDA-ARS?s Scientific Manuscript database

Four new (1–4) and two known (5 and 6)a-pyrone derivatives have been isolated from Alternaria phragmospora, an endophytic fungus from Vinca rosea, leaves. The isolated compounds were chemically identi'ed to be 5-butyl-4-methoxy-6-methyl-2H-pyran-2-one (2) 5-butyl-6-(hydroxymethyl)-4-methoxy-2H-py...

Identification of 5,6-dihydro-6-propyl-2H-pyran-2-one as the Major Volatile Constituent in Mesquite (Prosopis) Flour

USDA-ARS?s Scientific Manuscript database

Mesquite (Prosopis spp.) are woody leguminous plants that belong to the family Leguminosae and grow in arid and semiarid regions of America, Africa and Asia. Prosopis spp. produce indehiscent fruit (pods) that can be milled to yield flour that is sold commercially and is used in pastries and baked ...

Condensed tannins: Quinone methide intermediates in procyanidin synthesis

Treesearch

Richard W. Hemingway; L. Y. Foo

1983-01-01

Proanthocyanidins (condensed tanruns) are widely distributed in plants and are found in sufficiently high concentration in some tree barks to encourage their industrial utilization. These polymers consist of flavanoid units linked through the C-4 of the pyran ring to the C-6 or C-8 carbons of the aromatic A-ring. Recent advances in the chemistry of condensed tannins...

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes

PubMed Central

Engelen, Bernward; Panthöfer, Martin; Deiseroth, Hans-Jörg; Schlirf, Jens

2016-01-01

Summary A one-pot transformation, which involves the reaction of ketones with aldehydes in the presence of metal halides to furnish tetrahydro-2H-pyran-2,4-diols in a highly diastereoselective manner, is investigated thoroughly by experiments and computations. The reaction was also successfully implemented on a flow micro reactor system. PMID:27340472

A Research-Based Undergraduate Organic Laboratory Project: Investigation of a One-Pot, Multicomponent, Environmentally Friendly Prins-Friedel-Crafts-Type Reaction

ERIC Educational Resources Information Center

Dintzner, Matthew R.; Maresh, Justin J.; Kinzie, Charles R.; Arena, Anthony F.; Speltz, Thomas

2012-01-01

Students in the undergraduate organic laboratory synthesize tetrahydro-2-(4-nitrophenyl)-4-phenyl-2"H"-pyran via the Montmorillonite K10 clay-catalyzed reaction of p-nitrobenzaldehye with methanol, 3-buten-1-ol, and benzene. The synthesis comprises an environmentally friendly tandem Prins-Friedel-Crafts-type multicomponent reaction (MCR) and sets…

Comparative evaluation of two Trichoderma harzianum strains for major secondary metabolite production and antifungal activity.

PubMed

Ahluwalia, Vivek; Kumar, Jitendra; Rana, Virendra S; Sati, Om P; Walia, S

2015-01-01

This investigation was undertaken to identify the major secondary metabolite, produced by two Trichoderma harzianum strains (T-4 and T-5) with their antifungal activity against phytopathogenic fungi using poison food technique. The ethyl acetate extract was subjected to column chromatography using n-hexane, ethyl acetate and methanol gradually. Chromatographic separation of ethyl acetate extract of T. harzianum (T-4) resulted in the isolation and identification of palmitic acid (1), 1,8-dihydroxy-3-methylanthraquinone (2), 6-pentyl-2H-pyran-2-one (3), 2(5H)-furanone (4), stigmasterol (5) and β-sitosterol (6), while T. harzianum (T-5) gave palmitic acid (1), 1-hydroxy-3-methylanthraquinone (7), δ-decanolactone (8), 6-pentyl-2H-pyran-2-one (3), ergosterol (9), harzianopyridone (10) and 6-methyl-1,3,8-trihydroxyanthraquinone (11) as major metabolites. Among compounds screened for antifungal activity, compound 10 was found to be most active (EC50 35.9-50.2 μg mL(-1)). In conclusion, the present investigation provided significant information about antifungal activity and compounds isolated from two different strains of T. harzianum obtained from two different Himalayan locations.

Virgatolides A-C, benzannulated spiroketals from the plant endophytic fungus Pestalotiopsis virgatula.

PubMed

Li, Jian; Li, Li; Si, Yikang; Jiang, Xuejun; Guo, Liangdong; Che, Yongsheng

2011-05-20

Virgatolides A-C (1-3), unique metabolites with a 3',4',5',6'-tetrahydrospiro[chroman-2,2'-pyran] core, were isolated from cultures of the plant endophytic fungus Pestalotiopsis virgatula. Compounds 1-3 possess two previously undescribed skeletons originating from a benzannulated 6,6-spiroketal and one (2 and 3) and two (1) γ-lactone units, respectively. The structure of 1 was secured by X-ray crystallography.

Asymmetric conjugate addition of Grignard reagents to pyranones.

PubMed

Mao, Bin; Fañanás-Mastral, Martín; Feringa, Ben L

2013-01-18

An efficient enantioselective synthesis of lactones was developed based on the catalytic asymmetric conjugate addition (ACA) of alkyl Grignard reagents to pyranones. The use of 2H-pyran-2-one for the first time in the ACA with Grignard reagents allows for a variety of further transformations to access highly versatile building blocks such as β-alkyl substituted aldehydes or β-bromo-γ-alkyl substituted alcohols with excellent regio- and stereoselectivity.

Oligomeric flavanoids. Part 15a. Base-catalyzed pyran rearrangements of procyanidin B-2, and evidence for the oxidative transformation of B- to A-type procyanidins

Treesearch

Johann F.W. Burger; Herbert Kolodziej; Richard W. Hemingway; Jan P. Steynberg; Desmond A. Young; Daneel Ferreira

1990-01-01

Procyanidin B-2 3 is subject to facile C-ring isomerizations in 0.1M NaHCO3 solution to form a novel series of 3,4,9,1o-tetrahydro-2H,8H-pyrano[2,3-h]chromenes 7, 9, and 10. The low percentage conversion of B- to A-...

Generation of Maillard compounds from inulin during the thermal processing of Agave tequilana Weber Var. azul.

PubMed

Mancilla-Margalli, Norma A; López, Mercedes G

2002-02-13

During the cooking process of Agave tequilana Weber var. azul to produce tequila, besides the hydrolysis of inulin to generate fermentable sugars, many volatiles, mainly Maillard compounds, are produced, most of which may have a significant impact on the overall flavor of tequila. Exudates (agave juice) from a tequila company were collected periodically, and color, Brix, fructose concentration, and reducing sugars were determined as inulin breakdown took place. Maillard compounds were obtained by extraction with CH(2)Cl(2), and the extracts were analyzed by GC-MS. Increments in color, Brix, and reducing sugars were observed as a function of time, but a decrease in fructose concentration was found. Many Maillard compounds were identified in the exudates, including furans, pyrans, aldehydes, and nitrogen and sulfur compounds. The most abundant Maillard compounds were methyl-2-furoate, 2,3-dihydroxy-3,5-dihydro-6-methyl-4(H)-pyran-4-one, and 5-(hydroxymethyl)furfural. In addition, a series of short- and long-chain fatty acids was also found. A large number of the volatiles in A. tequilana Weber var. azul were also detected in tequila extracts, and most of these have been reported as a powerful odorants, responsible for the unique tequila flavor.

Synthesis and evaluation of 4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran] analogues against both active and dormant Mycobacterium tuberculosis.

PubMed

Alluri, Kiran Kumar; Reshma, Rudraraju Srilakshmi; Suraparaju, Raghuram; Gottapu, Suryanarayana; Sriram, Dharmarajan

2018-05-01

Need for new drugs to fight against tuberculosis (TB) is increasing day by day. In the present work we have taken a spiro compound (GSK 2200150A) reported by GSK as a lead and we modified the structure of the lead to study the antitubercular activity. For structure activity profiling twenty-one molecules have been synthesized, characterized and evaluated for their antimycobacterial potency against both active and dormant TB. Compound 06, 1-((4-methoxyphenyl)sulfonyl)-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran] was found to be the most potent compound (MIC: 8.23 µM) in active TB and was less effective than the lead but more potent than standard first line drug ethambutol. It was also found to be more efficacious than Isoniazid and Rifampicin and equipotent as Moxifloxacin against dormant Mycobacterium tuberculosis (MTB). Compound 06 also showed good inhibitory potential against over expressed latent MTB enzyme lysine ε-amino transferase with an IC 50 of 1.04 ± 0.32 µM. This compound is a good candidate for drug development owing to potential against both active and dormant stages of MTB. Copyright © 2017 Elsevier Ltd. All rights reserved.

Algicidal activity of marine Alteromonas sp. KNS-16 and isolation of active compounds.

PubMed

Cho, Ji Young

2012-01-01

The KNS-16 algicidal strain was isolated from a harmful alga bloom (HAB) area and identified as Alteromonas sp. based on 16S rDNA sequencing. The KNS-16 strain was found to control HABs by producing algicidal compounds in an indirect interaction. Four active compounds were isolated from KNS-16 culture, and their structures were analyzed by interpreting nuclear magnetic resonance and mass spectroscopy data. The structures were identified as 2-undecen-1'-yl-4-quinolone (1), 2-undecyl-4-quinolone (2), 3-hexyl-6-pentyl-4-hydroxyl-2H-pyran-2-one (3), and 6-heptyl-3-hexyl-4-hydroxyl-2H-pyran-2-one (4). Compound 1 was most active against HABs such as Heterosigma akashiwo, Cochlodinium polykrikoides, and Alexandrium tamarense with LC(50) values of 0.5-1.1 µg/mL. The four compounds exhibited high LC(50) values against aquaculture algae such as Tetaselmis suecica, Isochrysis galbana, and Pavlova lutheri at 39-66 µg/mL. Based on toxicity tests on the brine shrimp Artemia salina and the rotifer Brachionus rotundiformis, the four compounds showed ranges of 409-608 and 189-224 µg/mL of LC(50) for the two organisms, respectively. The LC(50) values for juvenile fish of Sebastes schlegelii were 284-304 µg/mL.

Antimicrobial assay and genetic screening of selected freshwater Cyanobacteria and identification of a biomolecule dihydro-2H-pyran-2-one derivative.

PubMed

Srivastava, A; Singh, V K; Patnaik, S; Tripathi, J; Singh, P; Nath, G; Asthana, R K

2017-04-01

Explorations of freshwater Cyanobacteria as antimicrobial (bacteria, fungi and methicillin-resistant Staphylococcus aureus (MRSA) strains) drug resource using bioassay, NRPS (non-ribosomal polypeptide synthetase) and PKS (polyketide synthase) genes, as well as in silico approach. We have bioassayed the extracts of Phormidium CCC727, Geitlerinema CCC728, Arthrospira CCC729, Leptolyngbya CCC732, Phormidium CCC730, Phormidium CCC731 against six pathogenic bacteria comprising Gram (+ve): S. aureus including seven clinical MRSA and Enterococcus faecalis, Gram (-ve): Escherichia coli, Salmonella Typhimurium, Klebsiella pneumoniae and Shigella boydii along with non-pathogenic Enterobacter aerogenes as well as fungal strains (Cryptococcus neoformans and Candida albicans, C. krusei, C. tropicalis and Aspergillus niger) exhibiting antimicrobial potential. The NRPS and PKS genes of the target strains were also amplified and sequenced. The putative protein structures were predicted using bioinformatics approach. PKS gene expression indicated β keto-acyl synthase as one of the important active domains in the biomolecules related to antitumour and antifungal group. The simultaneous identification of the biomolecule (dihydro-2H-pyran-2-one derivative) was also inferred spectroscopically. Freshwater Cyanobacteria are prolific producers of secondary metabolite(s) that may act as the antimicrobial drug resource in addition to their much explored marine counterpart. © 2016 The Society for Applied Microbiology.

Screen-Printed Photochromic Textiles through New Inks Based on SiO2@naphthopyran Nanoparticles.

PubMed

Pinto, Tânia V; Costa, Paula; Sousa, Céu M; Sousa, Carlos A D; Pereira, Clara; Silva, Carla J S M; Pereira, Manuel Fernando R; Coelho, Paulo J; Freire, Cristina

2016-10-26

Photochromic silica nanoparticles (SiO 2 @NPT), fabricated through the covalent immobilization of silylated naphthopyrans (NPTs) based on 2H-naphtho[1,2-b]pyran (S1, S2) and 3H-naphtho[2,1-b]pyran (S3, S4) or through the direct adsorption of the parent naphthopyrans (1, 3) onto silica nanoparticles (SiO 2 NPs), were successfully incorporated onto cotton fabrics by a screen-printing process. Two aqueous acrylic- (AC-) and polyurethane- (PU-) based inks were used as dispersing media. All textiles exhibited reversible photochromism under UV and solar irradiation, developing fast responses and intense coloration. The fabrics coated with SiO 2 @S1 and SiO 2 @S2 showed rapid color changes and high contrasts (ΔE* ab = 39-52), despite presenting slower bleaching kinetics (2-3 h to fade to the original color), whereas the textiles coated with SiO 2 @S3 and SiO 2 @S4 exhibited excellent engagement between coloration and decoloration rates (coloration and fading times of 1 and 2 min, respectively; ΔE* ab = 27-53). The PU-based fabrics showed excellent results during the washing fastness tests, whereas the AC-based textiles evidenced good results only when a protective transfer film was applied over the printed design.

N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor.

PubMed

Hennequin, Laurent F; Allen, Jack; Breed, Jason; Curwen, Jon; Fennell, Michael; Green, Tim P; Lambert-van der Brempt, Christine; Morgentin, Rémy; Norman, Richard A; Olivier, Annie; Otterbein, Ludovic; Plé, Patrick A; Warin, Nicolas; Costello, Gerard

2006-11-02

Src family kinases (SFKs) are nonreceptor tyrosine kinases that are reported to be critical for cancer progression. We report here a novel subseries of C-5-substituted anilinoquinazolines that display high affinity and specificity for the tyrosine kinase domain of the c-Src and Abl enzymes. These compounds exhibit high selectivity for SFKs over a panel of recombinant protein kinases, excellent pharmacokinetics, and in vivo activity following oral dosing. N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine (AZD0530) inhibits c-Src and Abl enzymes at low nanomolar concentrations and is highly selective over a range of kinases. AZD0530 displays excellent pharmacokinetic parameters in animal preclinically and in man (t(1/2) = 40 h). AZD0530 is a potent inhibitor of tumor growth in a c-Src-transfected 3T3-fibroblast xenograft model in vivo and led to a significant increase in survival in a highly aggressive, orthotopic model of human pancreatic cancer when dosed orally once daily. AZD0530 is currently undergoing clinical evaluation in man.

Thctf1 transcription factor of Trichoderma harzianum is involved in 6-pentyl-2H-pyran-2-one production and antifungal activity.

PubMed

Rubio, M Belén; Hermosa, Rosa; Reino, José Luis; Collado, Isidro G; Monte, Enrique

2009-01-01

We describe the cloning and characterization of the Trichoderma harzianum Thctf1 gene, which shows high sequence identity with a transcription factor gene of Fusarium solani f. sp. pisi. In T. harzianum, disruption of the Thctf1 gene by homologous recombination gave rise to transformants that in plate experiments did not show the yellow pigmentation observed in the wild-type strain. In several Trichoderma spp. a yellow pigmentation and a coconut aroma have been related to the production of 6-pentyl-2H-pyran-2-one (6PP) compounds. Prompted by this, we explored whether the loss of pigmentation in the Thctf1 null mutants of T. harzianum might be related to the synthesis of 6PP. Chromatographic and spectroscopic analyses revealed that the disruptants did not produce two secondary metabolites, derived from 6PP and not previously described in the Trichoderma genus, that are present in wild-type culture filtrates. Since 6PP is a recognized antifungal compound, this ability was analyzed in both the disruptants and wild-type, observing that the Thctf1 null mutants of T. harzianum had reduced antimicrobial capacity. Our results point to the significant role of THCTF1 in the production of secondary metabolites and in the antifungal activity of T. harzianum.

SBA-15/hydrotalcite nanocomposite as an efficient support for the immobilization of heteropolyacid: A triply-hybrid catalyst for the synthesis of 2-amino-4H-pyrans in water

NASA Astrophysics Data System (ADS)

Sadjadi, Samahe; Heravi, Majid M.; Zadsirjan, Vahideh; Farzaneh, Vahid

2017-12-01

To circumvent the high solubility and low surface area of heteropolyacid and in attempt to develop a bi-functional heterogeneous catalyst for promoting organic transformations, heteropolyacid was embedded in functionalized SBA-15 and subsequently hybridized with layered double hydroxide. The catalyst could be considered as a bi-functional catalyst with both acidic and basic properties. The acidic properties emerged from the SBA-15 and heteropolyacid component while layered double hydroxide render the catalyst basic. The catalyst was characterized by using SEM/EDX, FT-IR, XRD, ICP-AES, BET and elemental mapping analysis. The catalytic activity of the catalyst was studied for promoting one-pot three-component condensation of aromatic aldehydes, malononitrile or ethyl cyanoacetate and C-H activated acidic molecules in aqueous media for the synthesis of 2-amino-4H-pyran derivatives. The catalyst exhibited high catalytic activity, which was superior to the previously reported ones. Moreover, the reusability of the catalyst was excellent and the leaching of heteropolyacid was dramatically suppressed. High yields, short reaction times, eco-friendly conditions, simplicity of the procedure, reusability of the catalyst and broad substrate scope are the merits of this protocol.

Condensed tannins: Base-catalysed reactions of polymeric procyanidins with toluene-α-thiol, liability of the interflavanoid bond and pyran ring

Treesearch

Peter E. Laks; Richard W. Hemingway

1987-01-01

Reaction of polymeric procyanidins (condensed tannins) with toluene-α-thiol at pH 12.0 and 23°C gave predominantly one stereoisomer of 1.3-bisbenzylthio-1-(3,4-dihydroxyphenyl)-3-(2,4,6-trihydroxyphenyl) propan-2-ol (10) by stereoselective reaction at C-4 and C-2 of the Quinone methide derived from the upper 2,3-cis procyanidin units....

Electrochemical selenium- and iodonium-initiated cyclisation of hydroxy-functionalised 1,4-dienes

PubMed Central

Röse, Philipp; Emge, Steffen; Yoshida, Jun-ichi

2015-01-01

Summary The cobalt(I)-catalysed 1,4-hydrovinylation reaction of allyloxytrimethylsilane and allyl alcohol with substituted 1,3-dienes leads to hydroxy-functionalised 1,4-dienes in excellent regio- and diastereoselective fashion. Those 1,4-dienols can be converted into tetrahydrofuran and pyran derivatives under indirect electrochemical conditions generating selenium or iodonium cations. The reactions proceed in good yields and regioselectivities for the formation of single diastereomers. PMID:25815067

Microbial biotransformation of gentiopicroside by the endophytic fungus Penicillium crustosum 2T01Y01.

PubMed

Zeng, Wen-Liang; Li, Wan-Kui; Han, Han; Tao, Yan-Yan; Yang, Li; Wang, Zheng-Tao; Chen, Kai-Xian

2014-01-01

Endophytic fungi are symbiotic with plants and possess multienzyme systems showing promising metabolite potency with region selectivity and stereoselectivity. The aim of this study was to use these special microorganisms as an in vitro model to mimic the potential mammalian metabolites of a natural iridoid gentiopicroside (GPS, compound 1). The fungi isolated from a medicinal plant, Dendrobium candidum Wall. ex Lindl., were screened for their biotransformation abilities with GPS as the substrate, and one strain with high converting potency was identified as Penicillium crustosum 2T01Y01 on the basis of the sequence of the internal transcribed spacer of the ribosomal DNA region. Upon the optimized incubation of P. crustosum 2T01Y01 with the substrate, seven deglycosylated metabolites were detected by ultraperformance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS). Preparative-scale biotransformation with whole cells of the endophytic fungus resulted in the production of five metabolites, including three novel ones, 5α-(hydroxymethyl)-6β-methyl-3,4,5,6-tetrahydropyrano[3,4-c]pyran-1(8H)-one (compound 2), (Z)-4-(1-hydroxybut-3-en-2-yl)-5,6-dihydropyran-2-one (compound 3), and (E)-4-(1-hydroxybut-3-en-2-yl)-5,6-dihydropyran-2-one (compound 4), along with two known ones, 5α-(hydroxymethyl)-6β-methyl-1H,3H-5,6-dihydropyrano[3,4-c]pyran-1(3H)-one (compound 5) and 5α-(hydroxymethyl)-6α-methyl-5,6-dihydropyrano[3,4-c]pyran-1(3H)-one (compound 6), aided by nuclear magnetic resonance and high-resolution mass spectral analyses. The other two metabolites were tentatively identified by online UPLC/Q-TOF MS as 5-hydroxymethyl-5,6-dihydroisochromen-1-one (compound 7) and 5-hydroxymethyl-3,4,5,6-tetrahydroisochromen-1-one (compound 8), and compound 8 is a new metabolite. To test the metabolic mechanism, the β-glucosidase activity of the fungus P. crustosum 2T01Y01 was assayed with ρ-nitrophenyl-β-d-glucopyranoside as a probe substrate, and the pathway of GPS biotransformation by strain 2T01Y01 is proposed. In addition, the hepatoprotective activities of GPS and metabolite compounds 2, 5, and 6 against human hepatocyte line HL-7702 injury induced by hydrogen peroxide were evaluated.

Microbial Biotransformation of Gentiopicroside by the Endophytic Fungus Penicillium crustosum 2T01Y01

PubMed Central

Zeng, Wen-Liang; Li, Wan-Kui; Han, Han; Tao, Yan-Yan; Yang, Li; Chen, Kai-Xian

2014-01-01

Endophytic fungi are symbiotic with plants and possess multienzyme systems showing promising metabolite potency with region selectivity and stereoselectivity. The aim of this study was to use these special microorganisms as an in vitro model to mimic the potential mammalian metabolites of a natural iridoid gentiopicroside (GPS, compound 1). The fungi isolated from a medicinal plant, Dendrobium candidum Wall. ex Lindl., were screened for their biotransformation abilities with GPS as the substrate, and one strain with high converting potency was identified as Penicillium crustosum 2T01Y01 on the basis of the sequence of the internal transcribed spacer of the ribosomal DNA region. Upon the optimized incubation of P. crustosum 2T01Y01 with the substrate, seven deglycosylated metabolites were detected by ultraperformance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS). Preparative-scale biotransformation with whole cells of the endophytic fungus resulted in the production of five metabolites, including three novel ones, 5α-(hydroxymethyl)-6β-methyl-3,4,5,6-tetrahydropyrano[3,4-c]pyran-1(8H)-one (compound 2), (Z)-4-(1-hydroxybut-3-en-2-yl)-5,6-dihydropyran-2-one (compound 3), and (E)-4-(1-hydroxybut-3-en-2-yl)-5,6-dihydropyran-2-one (compound 4), along with two known ones, 5α-(hydroxymethyl)-6β-methyl-1H,3H-5,6-dihydropyrano[3,4-c]pyran-1(3H)-one (compound 5) and 5α-(hydroxymethyl)-6α-methyl-5,6-dihydropyrano[3,4-c]pyran-1(3H)-one (compound 6), aided by nuclear magnetic resonance and high-resolution mass spectral analyses. The other two metabolites were tentatively identified by online UPLC/Q-TOF MS as 5-hydroxymethyl-5,6-dihydroisochromen-1-one (compound 7) and 5-hydroxymethyl-3,4,5,6-tetrahydroisochromen-1-one (compound 8), and compound 8 is a new metabolite. To test the metabolic mechanism, the β-glucosidase activity of the fungus P. crustosum 2T01Y01 was assayed with ρ-nitrophenyl-β-d-glucopyranoside as a probe substrate, and the pathway of GPS biotransformation by strain 2T01Y01 is proposed. In addition, the hepatoprotective activities of GPS and metabolite compounds 2, 5, and 6 against human hepatocyte line HL-7702 injury induced by hydrogen peroxide were evaluated. PMID:24141132

O-heterocyclic derivatives with antibacterial properties from marine bacterium Bacillus subtilis associated with seaweed, Sargassum myriocystum.

PubMed

Chakraborty, Kajal; Thilakan, Bini; Chakraborty, Rekha Devi; Raola, Vamshi Krishna; Joy, Minju

2017-01-01

The brown seaweed, Sargassum myriocystum associated with heterotrophic bacterium, Bacillus subtilis MTCC 10407 (JF834075) exhibited broad-spectra of potent antibacterial activities against pathogenic bacteria Aeromonas hydrophila, Vibrio vulnificus, and Vibrio parahaemolyticus. B. subtilis MTCC 10407 was found to be positive for polyketide synthetase (pks) gene, and therefore, was considered to characterize secondary metabolites bearing polyketide backbone. Using bioassay-guided fractionation, two new antibacterial O-heterocyclic compounds belonging to pyranyl benzoate analogs of polyketide origin, with activity against pathogenic bacteria, have been isolated from the ethyl acetate extract of B. subtilis MTCC 10407. In the present study, the secondary metabolites of B. subtilis MTCC 10407 with potent antibacterial action against bacterial pathogens was recognized to represent the platform of pks-1 gene-encoded products. Two homologous compounds 3 (3-(methoxycarbonyl)-4-(5-(2-ethylbutyl)-5,6-dihydro-3-methyl-2H-pyran-2-yl)-butyl benzoate) and 4 [2-(8-butyl-3-ethyl-3,4,4a,5,6,8a-hexahydro-2H-chromen-6-yl)-ethyl benzoate] also have been isolated from the ethyl acetate extract of host seaweed S. myriocystum. The two compounds isolated from ethyl acetate extract of S. myriocystum with lesser antibacterial properties shared similar structures with the compounds purified from B. subtilis that suggested the ecological and metabolic relationship between these compounds in seaweed-bacterial relationship. Tetrahydropyran-2-one moiety of the tetrahydropyrano-[3,2b]-pyran-2(3H)-one system of 1 might be cleaved by the metabolic pool of seaweeds to afford methyl 3-(dihydro-3-methyl-2H-pyranyl)-propanoate moiety of 3, which was found to have no significant antibacterial activity. It is therefore imperative that the presence of dihydro-methyl-2H-pyran-2-yl propanoate system is essentially required to impart the greater activity. The direct involvement of polarisability (Pl) with the target bioactivity in 2 implied that inductive (field/polar) rather than the steric effect (parachor) appears to be the key factor influencing the induction of antibacterial activity. The present work may have a footprint on the use of novel O-heterocyclic polyketide products from seaweed-associated bacterium for biotechnological, food, and pharmaceutical applications mainly as novel antimicrobial secondary metabolites.

Two new compounds from the plant endophytic fungus Pestalotiopsis versicolor.

PubMed

Yang, Xiao-Long; Huang, Le; Li, Hai-Ying; Yang, Deng-Feng; Li, Zhuang-Zhuang

2015-01-01

A new coumarin, 4,6-dihydroxy-7-formyl-3-methylcoumarin (1), and an α-pyrone derivative, 6-[(7S,8R)-8-propyloxiran-1-yl]-4-methoxy-pyran-2-one (2), together with four known α-pyrone derivatives (3-6), were isolated from the broth extract of the plant endophytic fungus Pestalotiopsis versicolor. Their structures were elucidated by extensive spectroscopic analysis and by comparison of the chemical shift values with those of related known compounds.

Synthesis of (±)-8-deisopropyladunctin B.

PubMed

Nomura, Sayo; Arimitsu, Kenji; Yamaguchi, Satoshi; Kosuga, Yuya; Kakimoto, Yuko; Komai, Takanori; Hasegawa, Kazumasa; Nakanishi, Akira; Miyoshi, Tamami; Iwasaki, Hiroki; Ozeki, Minoru; Kawasaki, Ikuo; Kurume, Ai; Ohta, Shunsaku; Yamashita, Masayuki

2012-01-01

(±)-8-Deisopropyladunctin B, the deisopropyl form of adunctin B, which was isolated from the leaves of Piper aduncum (Piperaceae) collected in Papua New Guinea, was synthesized in 0.77% overall yield in 17 steps from 5,7-dimethoxycoumarin-3-carboxylate. The key step was our original stereoconvergent skeleton transformation from 1,2,2a,8b-tetrahydro-3H-benzo[b]cyclobuta[d]pyran-3-one to 1,2,4a,9b-tetrahydrodibenzofuran-4-ol with dimethylsulfoxonium methylide.

Acid-catalyzed rearrangements of flavan-4-phloroglucinol derivatives to novel 6-hydroxyphenyl-6a,llb-dihydro-6H-[1]benzofuro[2,3-c]-chromenes and hydroxyphenyl-3,2'-spirobi[dihydro[l]benzofurans

Treesearch

Petrus J. Steynberg; Jan P. Steynberg; Richard W. Hemingway; Daneel Ferreira; G. Wayne McGraw

1997-01-01

Acetic acid-catalyzed cleavage of proanthocyanidins in the presence of phloroglucinol gives a series of 2R procyanidin- and prodelphinidin-phloroglucinol adducts together with a novel 2S all-cis derivative implicating cleavage of the pyran ring and subsequent inversion of stereochernistry at C-2c. These flavan-4-phloroglucinol adducts also suffer dehydration to...

Formal [4+2] cycloaddition of di-tert-butyl 2-ethoxycyclobutane-1,1-dicarboxylate with ketones or aldehydes and tandem lactonization.

PubMed

Okado, Ryohei; Nowaki, Aya; Matsuo, Jun-Ichi; Ishibashi, Hiroyuki

2012-01-01

A catalytic amount of tin(IV) chloride catalyzed formal [4+2] cycloaddition reaction of di-tert-butyl 2-ethoxycyclobutane-1,1-carboxylate with ketones or aldehydes to give diethyl 6-ethoxydihydro-2H-pyran-3,3(4H)-dicarboxylates, whereas two equivalents of trimethylsilyl triflate promoted tandem [4+2] cycloaddition and lactonization to afford 3-oxo-2,6-dioxabicyclo[2.2.2]octane-4-carboxylate esters.

Dihydronepetalactones deter feeding activity by mosquitoes, stable flies, and deer ticks.

PubMed

Feaster, John E; Scialdone, Mark A; Todd, Robin G; Gonzalez, Yamaira I; Foster, Joseph P; Hallahan, David L

2009-07-01

The essential oil of catmint, Nepeta cataria L., contains nepetalactones, that, on hydrogenation, yield the corresponding dihydronepetalactone (DHN) diastereomers. The DHN diastereomer (4R,4aR,7S,7aS)-4,7-dimethylhexahydrocyclopenta[c]pyran-1(3H)-one, DHN 1) was evaluated as mosquito repellent, as was the mixture of diastereomers {mostly (4S,4aR,7S,7aR)-4,7-dimethylhexahydrocyclopenta[c]pyran-1(3H)-one, DHN 2} present after hydrogenation of catmint oil itself. The repellency of these materials to Aedes aegypti L. and Anopheles albimanus Wiedemann mosquitoes was tested in vitro and found to be comparable to that obtained with the well-known insect repellent active ingredient N,N-diethyl-3-methylbenzamide (DEET). DHN 1 and DHN 2 also repelled the stable fly, Stomoxys calcitrans L., in this study. DHN 1, DHN 2, and p-menthane-3,8-diol (PMD), another natural monoterpenoid repellent, gave comparable levels of repellency against An. albimanus and S. calcitrans. Laboratory testing of DHN 1 and DHN 2 using human subjects with An. albimanus mosquitoes was carried out. Both DHN 1 and DHN 2 at 10% (wt:vol) conferred complete protection from bites for significant periods of time (3.5 and 5 h, respectively), with DHN2 conferring protection statistically equivalent to DEET. The DHN 1 and DHN 2 diastereomers were also efficaceous against black-legged tick (Ixodes scapularis Say) nymphs.

Gold(I)-Catalyzed Cascade Cyclization of Allenyl Epoxides

PubMed Central

Tarselli, Michael A.; Lucas Zuccarello, J

2009-01-01

Cationic gold(I) phosphite catalysts activate allenes for epoxide cascade reactions. The system is tolerant of numerous functional groups (sulfones, esters, ethers, sulfonamides) and proceeds at room temperature in dichloromethane. The cyclization pathway is sensitive to the substitution pattern of the epoxide, and the backbone structure of the A-ring. It is capable of producing medium-ring ethers, fused 6-5 bicyclic, and linked pyran-furan structures. The resulting cycloisomers are reminiscent of structures found in numerous polyether natural products. PMID:19588972

Stereoselective protecting group free synthesis of D,L-gulose ethyl glycoside via multicomponent enyne cross metathesis--hetero Diels-Alder reaction.

PubMed

Castagnolo, Daniele; Botta, Lorenzo; Botta, Maurizio

2009-07-27

An efficient and stereoselective synthesis of D,L-gulose was described. The key step of the synthetic route is represented by a multicomponent enyne cross metathesis-hetero Diels-Alder reaction which allows the formation of the pyran ring from cheap and commercially available substrates in a single synthetic step. The synthesis of D,L-gulose was accomplished without the use of protecting groups making this approach highly desirable also in terms of atom economy.

Silver triflate/p-TSA co-catalysed synthesis of 3-substituted isocoumarins from 2-alkynylbenzoates.

PubMed

Gianni, Jonathan; Pirovano, Valentina; Abbiati, Giorgio

2018-05-02

In this paper, we describe the silver triflate/p-toluenesulfonic acid co-catalysed synthesis of seventeen isocoumarins and two thieno[2,3-c]pyran-7-ones starting from 2-alkynylbenzoates and 3-alkynylthiophene-2-carboxylates, respectively. The reaction proceeds with absolute regioselectivity under mild reaction conditions and low catalyst loading, to afford the desired products in good to excellent yields. A conceivable reaction mechanism is proposed and supported by isotope-exchange tests, 1H NMR studies and ad hoc experiments.

[Two novel isocoumarins from Erigeron breviscapus].

PubMed

Li, Jing; Yu, De-Quan

2013-07-01

Two novel isocoumarins, erigeronone C (1) and D (2), were isolated from the ethanol extract of the whole plant of Erigeron breviscapus (Vant.) Hand.-Mazz (Compositae). Their structures were respectively elucidated as 8, 9-dihydroxypyrano [3, 2-c] isochromen-4, 6-dione (1) and 4, 7-dihydroxy-3-(3-hydroxy-4-oxo-4H-pyran-2-yl)-1H-isochromen-1-one (2) on the basis of spectral analyses. Both structures of 1 and 2 possess a gamma-pyrone moiety and that is rare in natural products.

An enantioselective enzymatic desymmetrization route to hexahydro-4H-furopyranol, a high-affinity ligand for HIV-1 protease inhibitors.

PubMed

Ghosh, Arun K; Sarkar, Anindya

2017-08-16

An enantioselective synthesis of ( 3 a S , 4S , 7 a R )-hexahydro-4 H -furo[2,3- b ]pyran-4-ol, a high-affinity nonpeptide ligand for a variety of potent HIV-1 protease inhibitors is described. The key steps involved a highly enantioselective enzymatic desymmetrization of meso -diacetate, an efficient transacetalization, and a highly diastereoselective reduction of a ketone. This route is amenable to large-scale synthesis using readily available starting materials.

A Study on Spectro-Analytical Aspects, DNA - Interaction, Photo-Cleavage, Radical Scavenging, Cytotoxic Activities, Antibacterial and Docking Properties of 3 - (1 - (6 - methoxybenzo [d] thiazol - 2 - ylimino) ethyl) - 6 - methyl - 3H - pyran - 2, 4 - dione and its Metal Complexes.

PubMed

Ravi, Mudavath; Chennam, Kishan Prasad; Ushaiah, B; Eslavath, Ravi Kumar; Perugu, Shyam; Ajumeera, Rajanna; Devi, Ch Sarala

2015-09-01

The focus of the present work is on the design, synthesis, characterization, DNA-interaction, photo-cleavage, radical scavenging, in-vitro cytotoxicity, antimicrobial, docking and kinetic studies of Cu (II), Cd (II), Ce (IV) and Zr (IV) metal complexes of an imine derivative, 3 - (1 - (6 - methoxybenzo [d] thiazol - 2 - ylimino) ethyl) - 6 - methyl - 3H - pyran - 2, 4 - dione. The investigation of metal ligand interactions for the determination of composition of metal complexes, corresponding kinetic studies and antioxidant activity in solution was carried out by spectrophotometric methods. The synthesized metal complexes were characterized by EDX analysis, Mass, IR, (1)H-NMR, (13)C-NMR and UV-Visible spectra. DNA binding studies of metal complexes with Calf thymus (CT) DNA were carried out at room temperature by employing UV-Vis electron absorption, fluorescence emission and viscosity measurement techniques. The results revealed that these complexes interact with DNA through intercalation. The results of in vitro antibacterial studies showed the enhanced activity of chelating agent in metal chelated form and thus inferring scope for further development of new therapeutic drugs. Cell viability experiments indicated that all complexes showed significant dose dependent cytotoxicity in selected cell lines. The molecular modeling and docking studies were carried out with energy minimized structures of metal complexes to identify the receptor to metal interactions.

Two novel bioactive glucosinolates from Broccoli (Brassica oleracea L. var. italica) florets.

PubMed

Survay, Nazneen Shaik; Kumar, Brajesh; Jang, Mi; Yoon, Do-Young; Jung, Yi-Sook; Yang, Deok-Chun; Park, Se Won

2012-09-01

Two novel glucosinolates along with one known glucosinolate were isolated from Broccoli (Brassica oleracea L. var. italica) florets. Their structures were established mainly by 1D ((1)H and (13)C NMR), 2D NMR ((1)H-(1)H COSY, DEPT 135°, HSQC and HMBC), and Tandem MS-MS spectrometric data as 2-mercaptomethyl sulfinyl glucosinolate [(Z)-4-(methylsulfinyl)-N-(sulfooxy)-2-((2'S,3'R,4'S,5'S,6'R)-3',4',5'-trihydroxy-6'(hydroxylmethyl)-2'-mercapto tetrahydro-2H-pyran-2-yl) butane amide] 1, (Z)-1-((2S,5S)-5-hydroxytetra-hydro-2H-pyran-2-ylthio)-2-(1H-indol-3-yl) ethylidene amino sulfate 2 and a known cinnamoyl [6'-O-trans-(4″-hydroxy cinnamoyl)4-(methylsulphinyl)butyl glucosinolate] 3. Compound 1 exhibited scavenging activity against DPPH with an inhibitory concentration IC(50) of 20 mM, whereas compound 3 was a weak antioxidant when compared to the standard quercetin (5 mM) as a positive control. Both the compounds showed a significant and similar antimicrobial activity against Staphylococcus aureus with an IC(50) of <625 μg/mL when compared to antibiotic duricef. Against Salmonella typhimurium the IC(50) of 1 and 3 was determined as <625 μg/mL and <1250 μg/mL, respectively, when compared to ampicillin (IC(50) ≤ 39 μg/mL) as a positive control. Copyright © 2012 Elsevier Ltd. All rights reserved.

Gold(III) chloride catalyzed synthesis of chiral substituted 3-formyl furans from carbohydrates: application in the synthesis of 1,5-dicarbonyl derivatives and furo[3,2-c]pyridine.

PubMed

Mal, Kanchan; Sharma, Abhinandan; Das, Indrajit

2014-09-08

This report describes a gold(III)-catalyzed efficient general route to densely substituted chiral 3-formyl furans under extremely mild conditions from suitably protected 5-(1-alkynyl)-2,3-dihydropyran-4-one using H2 O as a nucleophile. The reaction proceeds through the initial formation of an activated alkyne-gold(III) complex intermediate, followed by either a domino nucleophilic attack/anti-endo-dig cyclization, or the formation of a cyclic oxonium ion with subsequent attack by H2 O. To confirm the proposed mechanistic pathway, we employed MeOH as a nucleophile instead of H2 O to result in a substituted furo[3,2-c]pyran derivative, as anticipated. The similar furo[3,2-c]pyran skeleton with a hybrid carbohydrate-furan derivative has also been achieved through pyridinium dichromate (PDC) oxidation of a substituted chiral 3-formyl furan. The corresponding protected 5-(1-alkynyl)-2,3-dihydropyran-4-one can be synthesized from the monosaccharides (both hexoses and pentose) following oxidation, iodination, and Sonogashira coupling sequences. Furthermore, to demonstrate the potentiality of chiral 3-formyl furan derivatives, a TiBr4 -catalyzed reaction of these derivatives has been shown to offer efficient access to 1,5-dicarbonyl compounds, which on treatment with NH4 OAc in slightly acidic conditions afforded substituted furo[3,2-c]pyridine. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure-activity relationship of karrikin germination stimulants.

PubMed

Flematti, Gavin R; Scaffidi, Adrian; Goddard-Borger, Ethan D; Heath, Charles H; Nelson, David C; Commander, Lucy E; Stick, Robert V; Dixon, Kingsley W; Smith, Steven M; Ghisalberti, Emilio L

2010-08-11

Karrikins (2H-furo[2,3-c]pyran-2-ones) are potent smoke-derived germination promoters for a diverse range of plant species but, to date, their mode of action remains unknown. This paper reports the structure-activity relationship of numerous karrikin analogues to increase understanding of the key structural features of the molecule that are required for biological activity. The results demonstrate that modification at the C5 position is preferred over modification at the C3, C4, or C7 positions for retaining the highest bioactivity.

Novel synthetic kojic acid-methimazole derivatives inhibit mushroom tyrosinase and melanogenesis.

PubMed

Chen, Ming-Jen; Hung, Chih-Chuan; Chen, Yan-Ru; Lai, Shih-Ting; Chan, Chin-Feng

2016-12-01

In this study, two kojic acid-methimazole (2-mercapto-1-methylimidazole, MMI, 1) derivatives, 5-hydroxy-2-{[(1-methyl-1H-imidazol-2-yl)thio]methyl}-4H-pyran-4-one (compound 4) and 5-methoxy-2-{[(1-methyl-1H-imidazol-2-yl)thio]methyl}-4H-pyran-4-one (compound 5), were synthesized to examine their inhibitory kinetics on mushroom tyrosinase. Compound 4 exhibited a potent inhibitory effect on monophenolase activity in a dose-dependent manner, with an IC 50 value of 0.03 mM. On diphenolase activity, compound 4 exhibited a less inhibitory effect (IC 50  = 1.29 mM) but was stronger than kojic acid (IC 50  = 1.80 mM). Kinetic analysis indicated that compound 4 was both as a noncompetitive monophenolase and diphenolase inhibitor. By contrast, compound 5 exhibited no inhibitory effects on mushroom tyrosinase activity. The IC 50 value of compound 4 for the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was 4.09 mM, being much higher than the IC 50 of compound 4 for inhibiting the tyrosinase activity. The results indicated that the antioxidant activity of compound 4 may be partly related to the potent inhibitory effect on mushroom tyrosinase. Compound 4 also exerted a potent inhibitory effect on intracellular melanin formation in B16/F10 murine melanoma cells, and caused no cytotoxicity. Furthermore, compound 4 induced no adverse effects on the Hen's egg test-chorioallantoic membrane (HET-CAM). Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Synthesis and acetylcholinesterase/butyrylcholinesterase inhibition activity of new tacrine-like analogues.

PubMed

Marco, J L; de los Ríos, C; Carreiras, M C; Baños, J E; Badía, A; Vivas, N M

2001-03-01

The synthesis and preliminary results for acetylcholinesterase and butyrylcholinesterase inhibition activity of a series of pyrano[2,3-b]quinolines (2, 3) and benzonaphthyridines (5, 6) derivatives are described. These molecules are tacrine-like analogues which have been prepared from readily available polyfunctionalized ethyl [6-amino-5-cyano-4H-pyrans and 6-amino-5-cyanopyridines]-3-carboxylates via Friedlander condensation with selected ketones. These compounds showed moderate acetylcholinesterase inhibition activity, the more potent (2e, 5b) being 6 times less active than tacrine. The butyrylcholinesterase activity of some of these molecules is also discussed.

Chemotherapeutic Potential of 2-[Piperidinoethoxyphenyl]-3-Phenyl-2H-Benzo(b)pyran in Estrogen Receptor- Negative Breast Cancer Cells: Action via Prevention of EGFR Activation and Combined Inhibition of PI-3-K/Akt/FOXO and MEK/Erk/AP-1 Pathways

PubMed Central

Saxena, Ruchi; Chandra, Vishal; Manohar, Murli; Hajela, Kanchan; Debnath, Utsab; Prabhakar, Yenamandra S.; Saini, Karan Singh; Konwar, Rituraj; Kumar, Sandeep; Megu, Kaling; Roy, Bal Gangadhar; Dwivedi, Anila

2013-01-01

Inhibition of epidermal growth factor receptor (EGFR) signaling is considered to be a promising treatment strategy for estrogen receptor (ER)-negative breast tumors. We have investigated here the anti-breast cancer properties of a novel anti-proliferative benzopyran compound namely, 2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzo(b)pyran (CDRI-85/287) in ER- negative and EGFR- overexpressing breast cancer cells. The benzopyran compound selectively inhibited the EGF-induced growth of MDA-MB 231 cells and ER-negative primary breast cancer cell culture. The compound significantly reduced tumor growth in xenograft of MDA-MB 231 cells in nude mice. The compound displayed better binding affinity for EGFR than inhibitor AG1478 as demonstrated by molecular docking studies. CDRI-85/287 significantly inhibited the activation of EGFR and downstream effectors MEK/Erk and PI-3-K/Akt. Subsequent inhibition of AP-1 promoter activity resulted in decreased transcription activation and expression of c-fos and c-jun. Dephosphorylation of downstream effectors FOXO-3a and NF-κB led to increased expression of p27 and decreased expression of cyclin D1 which was responsible for decreased phosphorylation of Rb and prevented the transcription of E2F- dependent genes involved in cell cycle progression from G1/S phase. The compound induced apoptosis via mitochondrial pathway and it also inhibited EGF-induced invasion of MDA-MB 231 cells as evidenced by decreased activity of MMP-9 and expression of CTGF. These results indicate that benzopyran compound CDRI-85/287 could constitute a powerful new chemotherapeutic agent against ER-negative and EGFR over-expressing breast tumors. PMID:23840429

Novel mechanisms of biotransformation of p-tert-amylphenol by bacteria and fungi with special degradation abilities and simultaneous detoxification of the disinfectant.

PubMed

Schlueter, Rabea; Röder, Anja; Czekalski, Nadine; Gliesche, Daniel; Mikolasch, Annett; Schauer, Frieder

2014-01-01

The compound p-tert-amylphenol (p-(1,1-dimethylpropyl)phenol) is a widely used disinfectant belonging to the group of short branched-chain alkylphenols. It is produced in or imported into the USA with more than one million pounds per year and can be found in the environment in surface water, sediments, and soil. We have investigated for the first time the biotransformation of this disinfectant and the accumulation of metabolites by five bacterial strains, three yeast strains, and three filamentous fungi, selected because of their ability to transform either aromatic or branched-chain compounds. Of the 11 microorganisms tested, one yeast strain and three bacteria could not transform the disinfectant despite of a very low concentration applied (0.005%). None of the other seven organisms was able to degrade the short branched alkyl chain of p-tert-amylphenol. However, two yeast strains, two filamentous fungi, and two bacterial strains attacked the aromatic ring system of the disinfectant via the hydroxylated intermediate 4-(1,1-dimethyl-propyl)-benzene-1,2-diol resulting in two hitherto unknown ring fission products with pyran and furan structures, 4-(1,1-dimethyl-propyl)-6-oxo-6-H-pyran-2-carboxylic acid and 2-[3-(1,1-dimethyl-propyl)-5-oxo-2H-furan-2-yl]acetic acid. While the disinfectant was toxic to the organisms applied, one of the ring cleavage products was not. Thus, a detoxification of the disinfectant was achieved by ring cleavage. Furthermore, one filamentous fungus formed sugar conjugates with p-tert-amylphenol as another mechanism of detoxification of toxic environmental pollutants. With this work, we can also contribute to the allocation of unknown chemical compounds within environmental samples to their parent compounds.

Erythrina excelsa exhibits estrogenic effects in vivo and in vitro and is cytotoxic on breast and colon cancer cell lines.

PubMed

Tchoukouegno Ngueu, Sadrine; Tchoumtchoua, Job; Njamen, Dieudonné; Halabalaki, Maria; Laudenbach-Leschowski, Ute; Diel, Patrick

2016-01-01

Eythrina excelsa Baker (Fabaceae) is a medicinal plant used to treat various ailments including those of the female genital tract. The objective of this study is to investigate the estrogenic and cytotoxic effects of the ethanol extract of the stem bark of E. excelsa. Erythrina excelsa was evaluated in vitro using the yeast estrogen screen (YES). The extract was then tested in a 3-day uterotrophic assay on ovariectomised Wistar rats at doses of 50 and 100 mg/kg BW/d. Cytotoxic effects were assessed on breast (MCF-7) and colon (HT-29) cancer cell lines using the MTT cell viability assay. Additionally, a LC-PDA-ESI (+)-HRMS and HRMS/MS method was developed and applied for the identification of representative secondary metabolites scaffolds in the extract. In the YES, the extract stimulated the transactivation of the estrogen receptor in a dose-dependent manner with an EC50 value of 1.8 μg/mL. In rats, E. excelsa increased uterine wet weight, uterine epithelial height, and the mRNA expression of estrogen-responsive genes in the uterus and liver at 50 whereas at 100 mg/kg BW/d anti-estrogenic effects were observed. In the MTT-assay, a dose-dependent decrease of the viability of both cell lines was observed with EC50 values of 13.6 μg/mL (MCF-7) and 27.7 μg/mL (HT-29). The phytochemical analysis revealed that the extract is rich in isoflavonoids, mainly prenylated and pyran-derivatives thereof. Erythrina excelsa is rich in prenylated and pyran-substituted isoflavonoids, exhibits estrogenic/anti-estrogenic and cytotoxic effects and warrant sufficient interest for deeper investigations.

Regioisomer-Specific Mechanochromism of Naphthopyran in Polymeric Materials.

PubMed

Robb, Maxwell J; Kim, Tae Ann; Halmes, Abigail J; White, Scott R; Sottos, Nancy R; Moore, Jeffrey S

2016-09-28

Transformation of naphthopyran into a colored merocyanine species in polymeric materials is achieved using mechanical force. We demonstrate that the mechanochemical reactivity of naphthopyran is critically dependent on the regiochemistry, with only one particular substitution pattern leading to successful mechanochemical activation. Two alternative regioisomers with different polymer attachment points are demonstrated to be mechanochemically inactive. This trend in reactivity is accurately predicted by DFT calculations, reinforcing predictive capabilities in mechanochemical systems. We rationalize the reactivity differences between naphthopyran regioisomers in terms of the alignment of the target C-O pyran bond with the direction of the applied mechanical force and its effect on mechanochemical transduction along the reaction coordinate.

Influence of dehydrated nanotubed titanic acid on charge transport and luminescent properties of polymer light-emitting diodes with fluorescent dye

NASA Astrophysics Data System (ADS)

Qian, Lei; Bera, Debasis; Jin, Zhen-Sheng; Du, Zu-Liang; Xu, Zheng; Teng, Feng; Liu, Wei

2007-09-01

In this paper, we discuss the influence of dehydrated nanotubed titanic acid (DNTA) on charge transport and luminescent properties of polymer light-emitting diodes (PLEDs) doped with fluorescent dye. Photoluminescence results confirm the efficient energy transfer from PVK to 4-(dicyanom-ethylene)-2- t-butyl-6-(1,1,7,7-tetramethyljulolidyl-9-enyl)-4H-pyran (DCJTB) and tris-(8-hydroxtquinoline) aluminum (Alq 3) in a DNTA-doped device. The device showed lower turn-on voltages and higher charge current by doping with DNTA, which also caused a shift in the exciton's recombination region.

Diversity-oriented synthesis of a library of substituted tetrahydropyrones using oxidative carbon-hydrogen bond activation and click chemistry.

PubMed

Zaware, Nilesh; Laporte, Matthew G; Farid, Ramy; Liu, Lei; Wipf, Peter; Floreancig, Paul E

2011-05-02

Eighteen (2RS,6RS)-2-(4-methoxyphenyl)-6-(substituted ethyl)dihydro-2H-pyran-4(3H)ones were synthesized via a DDQ-mediated oxidative carbon-hydrogen bond activation reaction. Fourteen of these tetrahydropyrans were substituted with triazoles readily assembled via azide-alkyne click-chemistry reactions. Examples of a linked benzotriazole and pyrazole motif were also prepared. To complement the structural diversity, the alcohol substrates were obtained from stereoselective reductions of the tetrahydropyrone. This library provides rapid access to structurally diverse non-natural compounds to be screened against a variety of biological targets.

Phosphine-catalyzed cycloadditions of allenic ketones: new substrates for nucleophilic catalysis.

PubMed

Wallace, Debra J; Sidda, Rachel L; Reamer, Robert A

2007-02-02

A range of phosphine-catalyzed cycloaddition reactions of allenic ketones have been studied, extending the scope of these processes from the more widely used 2,3-butadienoates to allow access to a number of synthetically useful products. Reaction of allenyl methyl ketone 4 with exo-enones afforded spirocyclic compounds in good regioselectivity and promising enantioselectivity via a [2 + 3] cycloaddtion. Aromatic allenyl ketones undergo a phosphine-promoted dimerization to afford functionalized pyrans, leading to a formal [2 + 4] Diels-Alder product, but did not react in the [2 + 3] cycloaddition. The results from other reactions that had found utility with 2,3-butadienoates are also reported.

3-(4-Hy­droxy­phen­yl)-7-meth­oxy­chroman-4-one monohydrate

PubMed Central

Xiao, Zhu-Ping; Peng, Zhu-Yun; Luo, Qun; Wu, Ying; Yang, Ye-Ling

2011-01-01

In the title compound, C16H14O4·H2O, the dihedral angle betwen the benzene rings is 71.4 (6)°. The pyran ring is in a sofa conformation. In the crystal, O—H⋯O hydrogen bonds connect the components into a two-dimensional network parallel to (010), incorporating C 2 2(4) and C 2 2(11) chains. In addition, weak C—H⋯O, C—H⋯π and π–π stacking inter­actions [centroid–centroid distance = 3.768 (2) Å] are present. PMID:22199730

Spectral broadening in electroluminescence of white organic light-emitting diodes based on complementary colors

NASA Astrophysics Data System (ADS)

Kim, Young Min; Park, Young Wook; Choi, Jin Hwan; Ju, Byeong Kwon; Jung, Jae Hoon; Kim, Jai Kyeong

2007-01-01

The authors report the optical and electroluminescent (EL) properties of white organic light-emitting diodes (OLEDs) which have two emitters with similar structures: 1, 1, 4, 4-tetraphenyl-1, 3-butadiene and 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline have an emission peak of 400nm around the near ultraviolet, and tris-(8-hydroxyquinoline) aluminum doped with 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran has an emission peak of 580nm producing a yellow color. The EL spectra of the white OLED have shown a broadening through visual range from 400to780nm. This spectral broadening is related to an exciplex emission at the organic solid interface.

A new coruleoellagic acid derivative from stems of Rhodamnia dumetorum.

PubMed

Lakornwong, Waranya; Kanokmedhakul, Kwanjai; Kanokmedhakul, Somdej

2018-07-01

A new coruleoellagic acid derivative, 3,3',4,4',5'-pentamethylcoruleoellagic acid (1) together with nine known compounds, hexamethylcoruleoellagic acid (2), 3,4,3'-tri-O-methylellagic acid (3), heptaphylline (4), 7-methoxymukonal (5), dentatin (6), sinapaldehyde (7), gallic acid (8), 2,6-dimethoxy-4H-pyran-4-one (9) and β-sitosterol (10) were isolated from the stems of Rhodamnia dumetorum. Their structures were identified by physical and spectroscopic data (IR, 1D and 2D NMR, and MS). Compounds 1, 2 and 7-10 were tested for antibacterial activity against six pathogenic bacterial strains (Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica serovar Typhimurium, Staphylococcus aureus, and Methicillin resistant S. aureus (MRSA)).

Crystal structure of 3-amino-1-(4-meth-oxy-phen-yl)-1H-benzo[f]chromene-2-carbo-nitrile.

PubMed

Mohamed, Shaaban K; Horton, Peter N; Akkurt, Mehmet; Younes, Sabry H H; Albayati, Mustafa R

2015-07-01

In the title compound, C21H16N2O2, the meth-oxy-benzene ring is almost perpendicular to the mean plane of the naphthalene ring system, making a dihedral angle of 83.62 (5)°. The 4H-pyran ring fused with the naphthalene ring system is almost planar [maximum deviation = 0.033 (1) Å]. In the crystal, mol-ecules are linked into inversion dimers by pairs of N-H⋯N hydrogen bonds. N-H⋯O hydrogen bonds connect the dimers, forming a helical supra-molecular chain along the a-axis direction. The crystal packing also features C-H⋯π inter-actions.

Sophoflavanones A and B, two novel prenylated flavanones from the roots of Sophora flavescens.

PubMed

Zhu, Hui; Yang, Ya-Nan; Feng, Zi-Ming; Jiang, Jian-Shuang; Zhang, Pei-Cheng

2018-09-01

In our ongoing investigation of the bioactive compounds from the extract of the roots of Sophora flavescens, two novel prenylated flavanones, named sophoflavanones A (1) and B (2), each with an unusual pyran ring were isolated. Their structures, as well as their absolute configurations, were elucidated based on spectroscopic data including a comparison of their experimental and calculated electronic circular dichroism (ECD) spectra. Additionally, compounds 1 and 2 showed moderate antioxidant activities against Fe 2+ /cysteine-induced toxicity at a concentration of 0.1 µM (inhibition values of 71.65% and 72.49%, respectively, using vitamin C as a positive control (87.83%)). Copyright © 2018 Elsevier Inc. All rights reserved.

Fungal Endophyte Diversity and Bioactivity in the Indian Medicinal Plant Ocimum sanctum Linn

PubMed Central

Chowdhary, Kanika; Kaushik, Nutan

2015-01-01

Endophytic mycopopulation isolated from India’s Queen of herbs Tulsi (Ocimum sanctum) were explored and investigated for their diversity and antiphytopathogenic activity against widespread plant pathogens Botrytis cinerea, Sclerotinia sclerotiorum, Rhizoctonia solani and Fusarium oxysporum. 90 fungal isolates, representing 17 genera were recovered from 313 disease-free and surface sterilised plant segments (leaf and stem tissues) from three different geographic locations (Delhi, Hyderabad and Mukteshwar) during distinct sampling times in consequent years 2010 and 2011 in India. Fungal endophytes were subjected to molecular identification based on rDNA ITS sequence analysis. Plant pathogens such as F. verticillioides, B. maydis, C. coarctatum, R. bataticola, Hypoxylon sp., Diaporthe phaseolorum, Alternaria tenuissima and A. alternata have occurred as endophyte only during second sampling (second sampling in 2011) in the present study. Bi-plot generated by principal component analysis suggested tissue specificity of certain fungal endophytes. Dendrogram revealed species abundance as a function of mean temperature of the location at the time of sampling. Shannon diversity in the first collection is highest in Hyderabad leaf tissues (H' = 1.907) whereas in second collection it was highest from leaf tissues of Delhi (H' = 1.846). Mukteshwar (altitude: 7500 feet) reported least isolation rate in second collection. Nearly 23% of the total fungal isolates were considered as potent biocontrol agent. Hexane extract of M. phaseolina recovered from Hyderabad in first collection demonstrated highest activity against S. sclerotiorum with IC50 value of 0.38 mg/ml. Additionally, its components 2H-pyran-2-one, 5,6-dihydro-6-pentyl and palmitic acid, methyl ester as reported by GC-MS Chromatogram upon evaluation for their antiphytopathogenic activity exhibited IC50 value of 1.002 and 0.662 against respectively S. sclerotiorum indicating their significant role in antiphytopathogenic activity of hexane extract. The production of 2H-pyran-2-one, 5,6-dihydro-6-pentyl from M. phaseolina, an endophytic fungus is being reported for the first time. PMID:26529087

Inhibitory effect of 2-(piperidinoethoxyphenyl)-3-(4-hydroxyphenyl)-2H-benzo(b)pyran (K-1) on human primary endometrial hyperplasial cells mediated via combined suppression of Wnt/β-catenin signaling and PI3K/Akt survival pathway.

PubMed

Chandra, V; Fatima, I; Manohar, M; Popli, P; Sirohi, V K; Hussain, M K; Hajela, K; Sankhwar, P; Dwivedi, A

2014-08-21

Endometrial hyperplasia is a precursor to the most common gynecologic cancer diagnosed in women. Apart from estrogenic induction, aberrant activation of the Wnt/β-catenin signal is well known to correlate with endometrial hyperplasia and its carcinoma. The benzopyran compound 2-(piperidinoethoxyphenyl)-3-(4-hydroxyphenyl)-2H-benzo (b) pyran(K-1), a potent antiestrogenic agent, has been shown to have apoptosis-inducing activity in rat uterine hyperplasia. The current study was undertaken to explore the effect of the benzopyran compound K-1 on growth and Wnt signaling in human endometrial hyperplasial cells. Primary culture of atypical endometrial hyperplasial cells was characterized by the epithelial cell marker cytokeratin-7. Results revealed that compound K-1 reduced the viability of primary endometrial hyperplasial cells and expression of ERα, PR, PCNA, Wnt7a, FZD6, pGsk3β and β-catenin without affecting the growth of the primary culture of normal endometrial cells. The β-catenin target genes CyclinD1 and c-myc were also found to be reduced, whereas the expression of axin2 and Wnt/β-catenin signaling inhibitor Dkk-1 was found to be upregulated, which caused the reduced interaction of Wnt7a and FZD6. Nuclear accumulation of β-catenin was found to be decreased by compound K-1. K-1 also suppressed the pPI3K/pAkt survival pathway and induced the cleavage of caspases and PARP, thus subsequently causing the apoptosis of endometrial hyperplasial cells. In conclusion, compound K-1 suppressed the growth of human primary endometrial hyperplasial cells through discontinued Wnt/β-catenin signaling and induced apoptosis via inhibiting the PI3K/Akt survival pathway.

Anti-tumorigenic action of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran: evidence for involvement of GPR30/EGFR signaling pathway.

PubMed

Chandra, V; Fatima, I; Saxena, R; Hussain, M K; Hajela, K; Sankhwar, P; Roy, B G; Chandna, S; Dwivedi, A

2013-05-01

The aim of the present study was to investigate the effect of non-steroidal, pure antiestrogenic benzopyran derivative i.e., 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) on the growth of human endometrial cancer cells in vivo and in vitro and to elucidate its mechanism of action. Cell proliferation was assayed by measuring the incorporation of 5'-bromo-2'-deoxyuridine in Ishikawa and primary endometrial cancer cells. The expression of proliferation and apoptotic markers was analyzed by immunoblotting. The effect of K-1 on GPR30-regulated proteins was analyzed by ELISA and by immunoblotting. Nude mice bearing subcutaneous implanted-Ishikawa tumors, were treated for 14days with K-1 (200μg/kg body weight/day/orally). The proliferation markers, GPR30-regulated proteins and apoptotic markers were analyzed by immunoblotting in tumor xenograft. The apoptotic effect of compound K-1 was determined by TUNEL assay. Compound K-1 inhibited proliferation of endometrial adenocarcinoma cells and decreased the expression of proliferation markers. It caused apoptosis by increasing the expression of apoptotic markers (NOXA, PUMAα) and reducing the expression of p-CREB and BclxL. Compound interfered with GPR30-regulated-EGFR activation, decreased p-ERK, p-c-jun, c-fos, cyclinD1 and c-myc expression. Treatment of tumor-bearing mice with K-1 resulted in a significant decrease in tumor volume and weight. Decreased expression of p-ERK and its downstream molecules and increased expression of apoptotic markers were observed in tumor in K-1 treated animals. Findings suggest the potent inhibitory effect of compound K-1 on endometrial cancer cellular growth (in-vitro) and on tumor size (in-vivo) which is mediated at least, in part, by interference with GPR30-signaling. Copyright © 2013 Elsevier Inc. All rights reserved.

Method to convert biomass to 5-(hydroxymethyl)-furfural (HMF) and furfural using lactones, furans, and pyrans as solvents

DOEpatents

Dumesic, James A.; Ribeiro Gallo, Jean Marcel; Alonso, David

2014-07-08

Described is a process to produce hydroxymethyl furfural (HMF) from biomass-derived sugars. The process includes the steps of reacting a C5 and/or C6 sugar-containing reactant derived from biomass in a monophasic or biphasic reaction solution comprising water and a co-solvent. The co-solvent can be beta-, gamma-, and/or delta-lactones derived from biomass, tetrahydrofuran (THF) derived from biomass, and/or methyltetrahydrofuran (MTHF) derived from biomass. The reaction takes place in the presence of an acid catalyst and a dehydration catalyst for a time and under conditions such that at least a portion of glucose or fructose present in the reactant is converted to HMF.

Pentafluorophenylammonium triflate (PFPAT) catalyzed facile construction of substituted chromeno[2,3-d]pyrimidinone derivatives and their antimicrobial activity

PubMed Central

Ghashang, Majid; Mansoor, Syed Sheik; Aswin, Krishnamoorthy

2013-01-01

A new, simple thermally efficient and solvent-free condensation of 2-amino-3-cyano-6-methyl-4-phenyl-4H-pyran-5-ethylcarboxylate derivatives with coumarin-3-carboxylic acid employing pentafluorophenylammonium triflate (PFPAT) as an inexpensive organocatalyst for the synthesis of a series of ethyl 4,5-dihydro 7-methyl-2-(2-oxo-2H-chromen-3-yl)-4-oxo-5-aryl-3H-chromeno[2,3-d]pyrimidine-6-carboxylate derivatives is described. This method has the advantages of high yields, a cleaner reaction, simple methodology, short reaction times, easy workup, and greener conditions. All the compounds were evaluated for their in vitro antimicrobial activity against different bacterial and fungal strains. PMID:25685489

The [2 + 2] Cycloaddition-Retroelectrocyclization and [4 + 2] Hetero-Diels-Alder Reactions of 2-(Dicyanomethylene)indan-1,3-dione with Electron-Rich Alkynes: Influence of Lewis Acids on Reactivity.

PubMed

Donckele, Etienne J; Finke, Aaron D; Ruhlmann, Laurent; Boudon, Corinne; Trapp, Nils; Diederich, François

2015-07-17

The reaction of electrophilic 2-(dicyanomethylene)indan-1,3-dione (DCID) with substituted, electron-rich alkynes provides two classes of push-pull chromophores with interesting optoelectronic properties. The formal [2 + 2] cycloaddition-retroelectrocyclization reaction at the exocyclic double bond of DCID gives cyanobuta-1,3-dienes, and the formal [4 + 2] hetero-Diels-Alder (HDA) reaction at an enone moiety of DCID generates fused 4H-pyran heterocycles. Both products can be obtained in good yield and excellent selectivity by carefully tuning the reaction conditions; in particular, the use of Lewis acids dramatically enhances formation of the HDA adduct.

Determination of some pure compound ideal-gas enthalpies of formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steele, W. V.; Chirico, R. D.; Nguyen, A.

1989-06-01

The results of a study aimed at improvement of group-additivity methodology for estimation of thermodynamic properties of organic substances are reported. Specific weaknesses where ring corrections were unknown or next-nearest-neighbor interactions were only estimated because of lack of experimental data are addressed by experimental studies of enthalpies of combustion in the condensed- phase and vapor pressure measurements. Ideal-gas enthalpies of formation are reported for acrylamide, succinimide, ..gamma..-butyrolactone, 2-pyrrolidone, 2,3-dihydrofuran, 3,4-dihydro-2H-pyran, 1,3-cyclohexadiene, 1,4-cyclohexadiene, and 1-methyl-1-phenylhydrazine. Ring corrections, group terms, and next-nearest-neighbor interaction terms useful in the application of group additivity correlations are derived. 44 refs., 2 figs., 59 tabs.

Discovery and Characterization of CD12681, a Potent RORγ Inverse Agonist, Preclinical Candidate for the Topical Treatment of Psoriasis.

PubMed

Ouvry, Gilles; Atrux-Tallau, Nicolas; Bihl, Franck; Bondu, Aline; Bouix-Peter, Claire; Carlavan, Isabelle; Christin, Olivier; Cuadrado, Marie-Josée; Defoin-Platel, Claire; Deret, Sophie; Duvert, Denis; Feret, Christophe; Forissier, Mathieu; Fournier, Jean-François; Froude, David; Hacini-Rachinel, Fériel; Harris, Craig Steven; Hervouet, Catherine; Huguet, Hélène; Lafitte, Guillaume; Luzy, Anne-Pascale; Musicki, Branislav; Orfila, Danielle; Ozello, Benjamin; Pascau, Coralie; Pascau, Jonathan; Parnet, Véronique; Peluchon, Guillaume; Pierre, Romain; Piwnica, David; Raffin, Catherine; Rossio, Patricia; Spiesse, Delphine; Taquet, Nathalie; Thoreau, Etienne; Vatinel, Rodolphe; Vial, Emmanuel; Hennequin, Laurent François

2018-02-20

With possible implications in multiple autoimmune diseases, the retinoic acid receptor-related orphan receptor RORγ has become a sought-after target in the pharmaceutical industry. Herein are described the efforts to identify a potent RORγ inverse agonist compatible with topical application for the treatment of skin diseases. These efforts culminated in the discovery of N-(2,4-dimethylphenyl)-N-isobutyl-2-oxo-1-[(tetrahydro-2H-pyran-4-yl)methyl]-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (CD12681), a potent inverse agonist with in vivo activity in an IL-23-induced mouse skin inflammation model. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical Constituents of Luffa acutangula (L.) Roxb Fruit

NASA Astrophysics Data System (ADS)

Suryanti, V.; Marliyana, S. D.; Astuti, I. Y.

2017-04-01

The phytochemical screening conducted on ethanol extract of Luffa acutangula (L.) Roxb’s fruit revealed the presence of alkaloids, saponins, carotenoids and terpenoids and the absence of flavonoids, tannins and anthraquinones. The GC-MS of the analysis L. acutangula (L.) Roxb’s fraction resulted in the identification of six compounds. The compounds that could be identified were 2,3-dihydro,3,5-dihydroxy-6-methyl-(4H)-pyran-4-one; 3,7,11,15-tetramethyl-2-hexadecen-1-ol; (3β, 20R)-cholest-5-en-3-ol; n-hexadecanoic acid; 9, 12, 15-octadecatrienoic acid methyl ester and citronellyl tiglate. The present study provides evidence that L. acutangula’s fruit contains medicinally important bioactive compounds and this justifies the possibly use of these fruits as traditional medicine for treatment of various diseases.

ent-Kaurane-Based Regio- and Stereoselective Inverse Electron Demand Hetero-Diels-Alder Reactions: Synthesis of Dihydropyran-Fused Diterpenoids†

PubMed Central

Ding, Chunyong; Wang, Lili; Chen, Haijun; Wild, Christopher; Ye, Na; Ding, Ye; Wang, Tianzhi; White, Mark A.; Shen, Qiang; Zhou, Jia

2014-01-01

A mild and concise approach for the construction of 3,4-dihydro-2H-pyran ring integrated into the A-ring of the natural product oridonin using an optimized inverse electron demand hetero-Diels-Alder (IED HDA) reaction is reported herein. A self-dimerization of the exocyclic enone installed in the A-ring through a homo-HDA reaction was identified to exclusively give a dimeric ent-kaurane diterpenoid with the spirochroman core. Moreover, the efficient cross-HDA cycloadditions of this enone with various vinyl ethers or vinyl sulfides, instead of its own homo-HDA dimerization, were achieved in regio- and stereoselective manners, thus providing the access to novel dihydropyran-fused diterpenoids as potential anticancer agents to overcome chemoresistance. PMID:25225052

Ultrasound promoted one pot synthesis of novel fluorescent triazolyl spirocyclic oxindoles using DBU based task specific ionic liquids and their antimicrobial activity.

PubMed

Singh, Harjinder; Sindhu, Jayant; Khurana, Jitender M; Sharma, Chetan; Aneja, K R

2014-04-22

Spirocyclic oxindoles and triazolyl derivatives posses remarkable biological activities. In present work, we have described an efficient one pot four-component domino reaction of 1-(prop-2-ynyl)indoline-2,3-dione, cyclic 1,3-diketones, malononitrile and various aryl azides in DBU based ionic liquids [DBU-H]OAc and [DBU-Bu]OH under ultrasonic irradiation for the construction of heterocycles, comprising spiro-oxindole, 2-amino-4H-pyran, and 1,2,3-triazoles substructures. The antimicrobial activity of all compounds has been investigated against six microbial strains. All compounds showed good antimicrobial activity. All newly synthesized compounds exhibit fluorescence in methanol with large stoke shift. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Dinardokanshones C-E, isonardoeudesmols A-D and nardoeudesmol D from Nardostachys jatamansi DC.

PubMed

Wu, Hong-Hua; Deng, Xu; Zhang, Hu; Chen, Ying-Peng; Ying, Shu-Song; Wu, Yi-Jing; Liu, Yan-Ting; Zhu, Yan; Gao, Xiu-Mei; Xu, Yan-Tong; Li, Li

2018-06-01

Dinardokanshones C-E, three sesquiterpenoid dimers comprising an unusual nornardosinane-type sesquiterpenoid core and an aristolane-type sesquiterpenoid unit conjugated by an extra pyran or furan ring, together with monomeric sesquiterpenoids isonardoeudesmols A-D and nardoeudesmol D, were isolated from the underground parts of Nardostachys jatamansi DC. Structures of the eight compounds were elucidated by analysis of the extensive spectroscopic data, and their absolute configurations were established by analysis of NOESY and X-ray diffraction data, combined with computational electronic circular dichroism (ECD) calculations. The results of SERT activity assay revealed that isonardoeudesmol D and nardoeudesmol D significantly inhibited SERT activity, while dinardokanshones D-E and isonardoeudesmols B-C significantly enhanced SERT activity, among which dinardokanshone D exhibited the strongest effect. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ecocatalysis for 2H-chromenes synthesis: an integrated approach for phytomanagement of polluted ecosystems.

PubMed

Escande, Vincent; Velati, Alicia; Grison, Claude

2015-04-01

A direct, general and efficient method to synthesize 2H-chromenes (2H-benzo[b]pyrans), identified as environmentally friendly pesticides, has been developed. This approach lays on the new concept of ecocatalysis, which involves the use of biomass from phytoextraction processes, as a valuable source of metallic elements for chemical synthesis. This methodology is similar or superior to known methods, affording 2H-chromenes with good to excellent yields (60-98%), including the preparation of precocene I, a natural insect growth regulator, with 91% yield. The approach is ideal for poor reactive substrates such as phenol or naphthol, classically transformed into 2H-chromenes by methodologies associated with environmental issues. These results illustrate the interest of combining phytoextraction and green synthesis of natural insecticides.

The isolation and antioxidant activity of polysaccharides from the marine microalgae Isochrysis galbana.

PubMed

Sun, Yingying; Wang, Hui; Guo, Ganlin; Pu, Yinfang; Yan, Binlun

2014-11-26

Three polysaccharides, IPSI-A, IPSI-B and IPSII, were successfully isolated from the marine microalgae Isochrysis galbana through a combination of anion-exchange column chromatography and repeated gel chromatography. These three polysaccharides were demonstrated to have moderate scavenging activities against superoxide and hydroxyl radicals and moderate reductive power in a concentration-dependent manner. The IPSII demonstrated more effective antioxidant activities than IPSI-A and IPSI-B. IPSII had a molecular weight of 15.934 kDa belonging to a β-type heteropolysaccharide with a pyran group and primarily contained mannose with variable amounts of glucose, galactose and rhamnose based on an analysis of infrared spectroscopy (IR), electrospray ionization-mass spectrometry (ESI-MS) and (1)H nuclear magnetic resonance ((1)H NMR). Copyright © 2014 Elsevier Ltd. All rights reserved.

Antiviral Activity of Polyacrylic and Polymethacrylic Acids

PubMed Central

De Somer, P.; De Clercq, E.; Billiau, A.; Schonne, E.; Claesen, M.

1968-01-01

A marked virus-inhibiting potency is obtained in the serum after intraperitoneal injection of polyacrylic acid (PAA) and polymethacrylic acid (PMAA) in mice. Much higher antiviral levels were reached than for other related polymers including dextran sulfate, heparin, polyvinyl sulfate, pyran copolymer, polystyrene sulfonate, and macrodex. The broad antiviral action of PAA and PMAA was attributed both to a direct interference with the virus-cell interaction and the viral ribonucleic acid metabolism and to the formation of an interferon-like factor. Both polyanions differed in interferon-inducing ability: highest serum interferon titer was obtained 18 hr after the intraperitoneal injection of PAA. The mechanism of interferon production by PAA and PMAA is discussed. As described previously for Sindbis virus and endotoxin, the animals also became hyporeactive after injection of PAA. PMID:5725320

Discovery of Selective Phosphodiesterase 1 Inhibitors with Memory Enhancing Properties.

PubMed

Dyck, Brian; Branstetter, Bryan; Gharbaoui, Tawfik; Hudson, Andrew R; Breitenbucher, J Guy; Gomez, Laurent; Botrous, Iriny; Marrone, Tami; Barido, Richard; Allerston, Charles K; Cedervall, E Peder; Xu, Rui; Sridhar, Vandana; Barker, Ryan; Aertgeerts, Kathleen; Schmelzer, Kara; Neul, David; Lee, Dong; Massari, Mark Eben; Andersen, Carsten B; Sebring, Kristen; Zhou, Xianbo; Petroski, Robert; Limberis, James; Augustin, Martin; Chun, Lawrence E; Edwards, Thomas E; Peters, Marco; Tabatabaei, Ali

2017-04-27

A series of potent thienotriazolopyrimidinone-based PDE1 inhibitors was discovered. X-ray crystal structures of example compounds from this series in complex with the catalytic domain of PDE1B and PDE10A were determined, allowing optimization of PDE1B potency and PDE selectivity. Reduction of hERG affinity led to greater than a 3000-fold selectivity for PDE1B over hERG. 6-(4-Methoxybenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[4',3':4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one was identified as an orally bioavailable and brain penetrating PDE1B enzyme inhibitor with potent memory-enhancing effects in a rat model of object recognition memory.

Threshold effect under nonlinear limitation of the intensity of high-power light

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tereshchenko, S A; Podgaetskii, V M; Gerasimenko, A Yu

2015-04-30

A model is proposed to describe the properties of limiters of high-power laser radiation, which takes into account the threshold character of nonlinear interaction of radiation with the working medium of the limiter. The generally accepted non-threshold model is a particular case of the threshold model if the threshold radiation intensity is zero. Experimental z-scan data are used to determine the nonlinear optical characteristics of media with carbon nanotubes, polymethine and pyran dyes, zinc selenide, porphyrin-graphene and fullerene-graphene. A threshold effect of nonlinear interaction between laser radiation and some of investigated working media of limiters is revealed. It is shownmore » that the threshold model more adequately describes experimental z-scan data. (nonlinear optical phenomena)« less

Assembly of Four Diverse Heterocyclic Libraries Enabled by Prins Cyclization, Au-Catalyzed Enyne Cycloisomerization, and Automated Amide Synthesis

PubMed Central

Cui, Jiayue; Chai, David I.; Miller, Christopher; Hao, Jason; Thomas, Christopher; Wang, JingQi; Scheidt, Karl A.; Kozmin, Sergey A.

2013-01-01

We describe a unified synthetic strategy for efficient assembly of four new heterocyclic libraries. The synthesis began by creating a range of structurally diverse pyrrolidinones or piperidinones. Such compounds were obtained in a simple one-flask operation starting with readily available amines, ketoesters, and unsaturated anhydrides. The use of tetrahydropyran-containing ketoesters, which were rapidly assembled by our Prins cyclization protocol, enabled efficient fusion of pyran and piperidinone cores. A newly developed Au(I)-catalyzed cycloisomerization of alkyne-containing enamides further expanded heterocyclic diversity by providing rapid entry into a wide range of bicyclic and tricyclic dienamides. The final stage of the process entailed diversification of each of the initially produced carboxylic acids using a fully automated platform for amide synthesis, which delivered 1872 compounds in high diastereomeric and chemical purity. PMID:22860634

Rhodomollacetals A-C, PTP1B Inhibitory Diterpenoids with a 2,3:5,6-Di-seco-grayanane Skeleton from the Leaves of Rhododendron molle.

PubMed

Zhou, Junfei; Sun, Na; Zhang, Hanqi; Zheng, Guijuan; Liu, Junjun; Yao, Guangmin

2017-10-06

Three novel diterpenoids with an unprecedented 2,3:5,6-di-seco-grayanane carbon skeleton, rhodomollacetals A-C (1-3), are isolated from the leaves of Rhododendron molle. Their structures are elucidated by comprehensive spectroscopic techniques and single-crystal X-ray diffraction. Rhodomollacetal A (1) possesses a novel cis/cis/cis/cis-fused 6/6/6/6/5 pentacyclic ring system, featuring an unprecedented 11,13,18-trioxa-pentacyclo [8.7.1.1 5,8 .0 2,8 .0 12,17 ]nonadecane scaffold. Compounds 2 and 3 have a rare 4-oxatricyclo[7.2.1.0 1,6 ]dodecane moiety and a 2,3-dihydro-4H-pyran-4-one unit. Compounds 1-3 showed moderate PTP1B inhibitory activities, and their molecular dockings were investigated.

Methyl 6-eth-oxy-3-phenyl-3a,4-dihydro-3H-chromeno[4,3-c]isoxazole-3a-car-boxylate.

PubMed

Suresh, G; Srinivasan, J; Bakthadoss, M; Aravindhan, S

2013-02-01

In the title compound, C(20)H(19)NO(5), the dihedral angle between the mean plane of the pyran ring (which has a half-chair conformation) and the benzene ring of the chromeno ring system is 7.21 (7)°. The dihedral angle between the mean plane of the chromeno ring system and the isoxazole ring is 21.78 (6)°, while the isoxazole ring forms a dihedral angle of 72.60 (8)° with the attached phenyl ring. In the crystal, mol-ecules are linked via pairs of C-H⋯O hydrogen bonds, forming inversion dimers with an R(2) (2)(10) ring motif. These dimers are linked via C-H⋯N hydrogen bonds, forming chains along [001].

Spectral evolution of distributed feedback laser of gold nanoparticles doped solid-state dye laser medium

NASA Astrophysics Data System (ADS)

An, N. T. M.; Lien, N. T. H.; Hoang, N. D.; Nghia, N. T.; Hoa, D. Q.

2017-10-01

Characteristics of suppressed relaxation oscillation of a distributed feedback dye laser (DFDL) based on the energy transfer process in a mixture of spherical gold nanoparticles-doped solid-state polymethylmetacrylate dissolved 4-(Dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran dye was theoretically and experimentally studied. Single pulse generation regime of the DFDL can be obtained with a suitable gold nanoparticle concentration and ratio of pump power over lasing threshold. Numerical analysis and experimental approach showed that in this regime, the first-pulse laser pulsewidth is rather unchanged while varying the gold nanoparticles concentration in the range of 2.0 × 109-2.0 × 1010 par cm-3. The enhancement of first pulse and the suppression of the secondary pulses by bi-direction energy transfer of spherical gold nanoparticles were experimentally observed.

Polyethyleneimine-modified superparamagnetic Fe3O4 nanoparticles: An efficient, reusable and water tolerance nanocatalyst

NASA Astrophysics Data System (ADS)

Khoobi, Mehdi; Delshad, Tayebeh Modiri; Vosooghi, Mohsen; Alipour, Masoumeh; Hamadi, Hosein; Alipour, Eskandar; Hamedani, Majid Pirali; Sadat ebrahimi, Seyed Esmaeil; Safaei, Zahra; Foroumadi, Alireza; Shafiee, Abbas

2015-02-01

A novel magnetically separable catalyst was prepared based on surface modification of Fe3O4 magnetic nanoparticle (MNPs) with polyethyleneimine (PEI) via covalent bonding. [3-(2,3-Epoxypropoxy)propyl]trimethoxysilane (EPO) was used as cross linker to bond PEI on the surface of MNPs with permanent stability in contrast to PEI coating via electrostatic interactions. The synthesized catalyst was characterized by Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and vibrating sample magnetometry (VSM). The catalyst show high efficiency for one-pot synthesis of 2-amino-3-cyano-4H-pyran derivatives via multi-component reaction (MCR). This procedure offers the advantages of green reaction media, high yield, short reaction time, easy purification of the products and simple recovery and reuse of the catalyst by simple magnetic decantation without significant loss of catalytic activity.

[Optical and morphological investigation on the interaction of dual dopants in poly (N-vinylcarzole)].

PubMed

Zhang, Ting; Xu, Zheng; Teng, Feng; Qian, Lei; Wang, Yong-Sheng; Xu, Xu-Rong

2006-05-01

The effect of optical and electrical properties of poly(N-vinylcarzole) (PVK) doped with two dyes, i. e. 8-tris-hydroxyquinoline (Alq3) and 4-(dicyanomethylene)-2-tert-butyl-6 (1, 1, 7, 7-tetramethyljulolidyl-9-enyl)-4H-pyran (DCJTB), on the energy transfer and charge trapping processes was investigated. The phase separation in blends film at different doping concentration was also studied. More homogeneous dispersion of dyes in PVK with increasing doping concentration was showed. The results indicate that there is a certain interaction of Alq3 and DCJTB in this dual-doped system. It is the incorporation of DCJTB that untangled the aggregation of Alq3 owing to the interaction of DCJTB and Alq3. But for higher doping concentration, DCJTB results in an isolated charge transport channel that decreases the electroluminescence (EL) operating voltage.

8-Fluoro-4-oxo-4H-chromene-3-carbalde­hyde

PubMed Central

Ishikawa, Yoshinobu

2014-01-01

In the title compound, C10H5FO3, the non-H atoms of the 8-fluoro­chromone unit are essentially coplanar (r.m.s. deviation = 0.0259 Å), with a largest deviation from the mean plane of 0.0660 (12) Å for the chromone carbonyl O atom. The formyl group is twisted with respect to the attached ring [C—C—C—O torsion angles = −11.00 (19) and 170.81 (11)°]. In the crystal, mol­ecules are linked via weak C—H⋯O hydrogen bonds along the a axis and [-101], forming corrugated layers parallel to (010). In addition, π–π stacking inter­actions [centroid–centroid distance between the planes of the pyran and benzene rings = 3.519 (2) Å] are observed between these layers. PMID:25161562

Structure elucidation and chemical synthesis of stigmolone, a novel type of prokaryotic pheromone.

PubMed

Hull, W E; Berkessel, A; Plaga, W

1998-09-15

Approximately 2 micromol of a novel prokaryotic pheromone, involved in starvation-induced aggregation and formation of fruiting bodies by the myxobacterium Stigmatella aurantiaca, were isolated by a large-scale elution procedure. The pheromone was purified by HPLC, and high-resolution MS, IR, 1H-NMR, and 13C-NMR were used to identify the active substance as the hydroxy ketone 2,5, 8-trimethyl-8-hydroxy-nonan-4-one, which has been named stigmolone. The analysis was complicated by a solvent-dependent equilibrium between stigmolone and the cyclic enol-ether 3,4-dihydro-2,2, 5-trimethyl-6-(2-methylpropyl)-2H-pyran formed by intramolecular nucleophilic attack of the 8-OH group at the ketone C4 followed by loss of H2O. Both compounds were synthesized chemically, and their structures were confirmed by NMR analysis. Natural and synthetic stigmolone have the same biological activity at ca. 1 nM concentration.

Random lasing from dye-doped negative liquid crystals using ZnO nanoparticles as tunable scatters

NASA Astrophysics Data System (ADS)

Li, Long-Wu; Shang, Zhen-Zhen; Deng, Luogen

2016-09-01

This work demonstrates the realization of a lasing in scattering media, which contains dispersive solution of ZnO nanoparticles (NPs) and laser dye 4-dicyanomethylene-2-methyle-6-(p-dimethylaminostyryl)-4H-pyran(DCM) in negative liquid crystals (LCs) that was injected into a cell. The lasing intensity of the dye-doped negative LC laser can be tuned from low to high if the NPs concentration is increased. The tunability of the laser is attributable to the clusters-sensitive feature in effective refractive index of the negative LCs. Such a tunable negative liquid crystal laser can be used in the fabrication of new optical sources, optical communication, and liquid crystal laser displays. Project supported by the Doctoral Science Research Start-up Funding of Guizhou Normal University, China (Grant No. 11904-0514162) and the National Natural Science Foundation of China (Grant No. 11474021).

Microwave-assisted synthesis and tyrosinase inhibitory activity of chalcone derivatives.

PubMed

Liu, Jinbing; Chen, Changhong; Wu, Fengyan; Zhao, Liangzhong

2013-07-01

A series of chalcones and their derivatives were synthesized, and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were evaluated. The results showed that some of the synthesized compounds exhibited significant inhibitory activity, and four compounds exhibited more potent tyrosinase inhibitory activity than the reference standard inhibitor kojic acid (5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one). Specifically, 1-(-1-(4-methoxyphen- yl)-3-phenylallylidene)thiosemicarbazide (18) exhibited the most potent tyrosinase inhibitory activity with IC₅₀ value of 0.274 μM. The inhibition mechanism analysis of 1-(-1-(2,4-dihydroxyphenyl)-3-phenylallylidene) thiosemicarbazide (16) and 1-(-1-(4-methoxyphenyl)-3-phenylallylidene) thiosemicarbazide (18) demonstrated that the inhibitory effects of the two compounds on the tyrosinase were irreversible. Preliminary structure activity relationships' analysis suggested that further development of such compounds might be of interest. © 2013 John Wiley & Sons A/S.

Improving the Performance of Gold-Nanoparticle-Doped Solid-State Dye Laser Using Thermal Conversion Effect

NASA Astrophysics Data System (ADS)

An, N. T. M.; Lien, N. T. H.; Hoang, N. D.; Hoa, D. Q.

2018-04-01

Energy transfer between spherical gold nanoparticles with size of more than 15 nm and molecules of organic dye 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4 H-pyran (DCM) has been studied. Such radiative energy transfer led to high local temperature, giving rise to a bleaching effect that resulted in rapid degradation of the laser medium. Gold nanoparticles were dispersed at concentrations from 5 × 109 particles/mL to 5 × 1010 particles/mL in DCM polymethylmethacrylate polymer using a radical polymerization process with 2,2'-azobis(isobutyronitrile) (AIBN) as initiator. Using the fast thermoelectric cooling method, the laser medium stability was significantly improved. The output stability of a distributed feedback dye laser pumped by second-harmonic generation from a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser was investigated. Moreover, bidirectional energy transfer between gold nanoparticles and dye molecules was observed.

Structure analysis and laxative effects of oligosaccharides isolated from bananas.

PubMed

Wang, Juan; Huang, Hui Hua; Cheng, Yan Feng; Yang, Gong Ming

2012-10-01

Banana oligosaccharides (BOS) were extracted with water, and then separated and purified using column chromatography. Gel penetration chromatography was used to determine the molecular weights. Thin layer chromatogram and capillary electrophoresis were employed to analyze the monosaccharide composition. The indican bond and structure of the BOS molecule were determined using Fourier transform infrared spectroscopy and nuclear magnetic resonance. Results showed that BOS were probably composed of eight β-D-pyran glucose units linked with 1→6 indican bonds. The laxative effects of BOS were investigated in mice using the method described in "Handbook of Technical Standards for Testing and Assessment of Health Food in China." The length of the small intestine over which a carbon suspension solution advanced in mice treated with low-, middle-, and high-dose BOS was significantly greater than that in the model group, suggesting that BOS are effective in accelerating the movement of the small intestine.

The Structure–Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation

PubMed Central

Bow, Eric W.; Rimoldi, John M.

2016-01-01

The cannabinoids are members of a deceptively simple class of terpenophenolic secondary metabolites isolated from Cannabis sativa highlighted by (−)-Δ9-tetrahydrocannabinol (THC), eliciting distinct pharmacological effects mediated largely by cannabinoid receptor (CB1 or CB2) signaling. Since the initial discovery of THC and related cannabinoids, synthetic and semisynthetic classical cannabinoid analogs have been evaluated to help define receptor binding modes and structure–CB1/CB2 functional activity relationships. This perspective will examine the classical cannabinoids, with particular emphasis on the structure–activity relationship of five regions: C3 side chain, phenolic hydroxyl, aromatic A-ring, pyran B-ring, and cyclohexenyl C-ring. Cumulative structure–activity relationship studies to date have helped define the critical structural elements required for potency and selectivity toward CB1 and CB2 and, more importantly, ushered the discovery and development of contemporary nonclassical cannabinoid modulators with enhanced physicochemical and pharmacological profiles. PMID:27398024

Wavelength-modulated differential photothermal radiometry: Theory and experimental applications to glucose detection in water

NASA Astrophysics Data System (ADS)

Mandelis, Andreas; Guo, Xinxin

2011-10-01

A differential photothermal radiometry method, wavelength-modulated differential photothermal radiometry (WM-DPTR), has been developed theoretically and experimentally for noninvasive, noncontact biological analyte detection, such as blood glucose monitoring. WM-DPTR features analyte specificity and sensitivity by combining laser excitation by two out-of-phase modulated beams at wavelengths near the peak and the base line of a prominent and isolated mid-IR analyte absorption band (here the carbon-oxygen-carbon bond in the pyran ring of the glucose molecule). A theoretical photothermal model of WM-DPTR signal generation and detection has been developed. Simulation results on water-glucose phantoms with the human blood range (0-300 mg/dl) glucose concentration demonstrated high sensitivity and resolution to meet wide clinical detection requirements. The model has also been validated by experimental data of the glucose-water system obtained using WM-DPTR.

Plastic lab-on-a-chip for fluorescence excitation with integrated organic semiconductor lasers.

PubMed

Vannahme, Christoph; Klinkhammer, Sönke; Lemmer, Uli; Mappes, Timo

2011-04-25

Laser light excitation of fluorescent markers offers highly sensitive and specific analysis for bio-medical or chemical analysis. To profit from these advantages for applications in the field or at the point-of-care, a plastic lab-on-a-chip with integrated organic semiconductor lasers is presented here. First order distributed feedback lasers based on the organic semiconductor tris(8-hydroxyquinoline) aluminum (Alq3) doped with the laser dye 4-dicyanomethylene-2-methyl-6-(p-dimethylaminostyril)-4H-pyrane (DCM), deep ultraviolet induced waveguides, and a nanostructured microfluidic channel are integrated into a poly(methyl methacrylate) (PMMA) substrate. A simple and parallel fabrication process is used comprising thermal imprint, DUV exposure, evaporation of the laser material, and sealing by thermal bonding. The excitation of two fluorescent marker model systems including labeled antibodies with light emitted by integrated lasers is demonstrated.

Extension of the SAFT-VR Mie EoS To Model Homonuclear Rings and Its Parametrization Based on the Principle of Corresponding States.

PubMed

Müller, Erich A; Mejía, Andrés

2017-10-24

The statistical associating fluid theory of variable range employing a Mie potential (SAFT-VR-Mie) proposed by Lafitte et al. (J. Chem Phys. 2013, 139, 154504) is one of the latest versions of the SAFT family. This particular version has been shown to have a remarkable capability to connect experimental determinations, theoretical calculations, and molecular simulations results. However, the theoretical development restricts the model to chains of beads connected in a linear fashion. In this work, the capabilities of the SAFT-VR Mie equation of state for modeling phase equilibria are extended for the case of planar ring compounds. This modification proposed replaces the Helmholtz energy of chain formation by an empirical contribution based on a parallelism to the second-order thermodynamic perturbation theory for hard sphere trimers. The proposed expression is given in terms of an extra parameter, χ, that depends on the number of beads, m s , and the geometry of the ring. The model is used to describe the phase equilibrium for planar ring compounds formed of Mie isotropic segments for the cases of m s equals to 3, 4, 5 (two configurations), and 7 (two configurations). The resulting molecular model is further parametrized, invoking a corresponding states principle resulting in sets of parameters that can be used indistinctively in theoretical calculations or in molecular simulations without any further refinements. The extent and performance of the methodology has been exemplified by predicting the phase equilibria and vapor pressure curves for aromatic hydrocarbons (benzene, hexafluorobenzene, toluene), heterocyclic molecules (2,5-dimethylfuran, sulfolane, tetrahydro-2H-pyran, tetrahydrofuran), and polycyclic aromatic hydrocarbons (naphthalene, pyrene, anthracene, pentacene, and coronene). An important aspect of the theory is that the parameters of the model can be used directly in molecular dynamics (MD) simulations to calculate equilibrium phase properties and interfacial tensions with an accuracy that rivals other coarse grained and united atom models, for example, liquid densities, are predicted, with a maximum absolute average deviation of 3% from both the theory and the MD simulations, while the interfacial tension is predicted, with a maximum absolute average of 8%. The extension to mixtures is exemplified by considering a binary system of hexane (chain fluid) and tetrahydro-2H-pyran (ring fluid).

Essential oil composition, antioxidant and antifungal activities of Salvia sclarea L. from Munzur Valley in Tunceli, Turkey.

PubMed

Yuce, E; Yildirim, N; Yildirim, N C; Paksoy, M Y; Bagci, E

2014-06-15

The essential oil composition and in vitro antioxidant and antifungal activity of the Salvia sclarea L. from Munzur Valley in Tunceli, Turkey were evaluated in this research. The in vitro antifungal activity of ethanol, hexane and aqueous extracts of S. sclarea against pathogen fungi Epicoccum nigrum and Colletotrichum coccodes were investigated. The essential oil of aerial parts of S. sclarea was obtained by hydrodistillation and was analysed by GC and GC—MS. Total antioxidant status was determined by using Rel assay diagnostics TAS assay kit (Lot.RL024) by Multiscan FC (Thermo). 33 compounds were identified representing the 85.0% of the total oil. The most abundant components (>5%) of the S. sclarea essential oils were caryophyllene oxide (24.1%), sclareol (11.5%), spathulenol (11.4%), 1H-naphtho (2,1,6) pyran (8.6%) and b—caryophyllene (5.1%). The best antifungal and antioxidant effect was seen in ethanolic S. sclarea extract. It can be said that Salvia sclerae could be used as natural antioxidant.

Multicolored Emission and Lasing in DCM-Adamantane Plasma Nanocomposite Optical Films.

PubMed

Alcaire, María; Cerdán, Luis; Zamarro, Fernando Lahoz; Aparicio, Francisco J; González, Juan Carlos; Ferrer, Francisco J; Borras, Ana; Espinós, Juan Pedro; Barranco, Angel

2017-03-15

We present a low-temperature versatile protocol for the fabrication of plasma nanocomposite thin films to act as tunable emitters and optical gain media. The films are obtained by the remote plasma-assisted deposition of a 4-(dicyano-methylene)-2-methyl-6-(4-dimethylamino-styryl)-4H-pyran (DCM) laser dye alongside adamantane. The experimental parameters that determine the concentration of the dye in the films and their optical properties, including light absorption, the refractive index, and luminescence, are evaluated. Amplified spontaneous emission experiments in the DCM/adamantane nanocomposite waveguides show the improvement of the copolymerized nanocomposites' properties compared to films that were deposited with DCM as the sole precursor. Moreover, one-dimensional distributed feed-back laser emission is demonstrated and characterized in some of the nanocomposite films that are studied. These results open new paths for the optimization of the optical and lasing properties of plasma nanocomposite polymers, which can be straightforwardly integrated as active components in optoelectronic devices.

4,5,7,8,17-Penta-hydr-oxy-14,18-dimethyl-6-methyl-ene-3,10-dioxapenta-cyclo-[9.8.0.0.0.0]nona-dec-14-ene-9,16-dione methanol solvate dihydrate.

PubMed

Teh, Chin Hoe; Teoh, Siew Chin; Yeap, Chin Sing; Chan, Kit Lam; Fun, Hoong-Kun

2009-03-28

The title quassinoid compound, C(20)H(24)O(9)·CH(3)OH·2H(2)O, is a natural eurycomanone isolated from the roots of Eurycoma longifolia. The mol-ecules contain a fused five-ring system, with one tetra-hydro-furan ring adopting an envelope conformation, one tetra-hydro-pyran-2-one ring in a screw boat conformation, one cyclo-hexenone ring in a half-chair conformation and two cyclo-hexane rings in chair conformations. Intra-molecular C-H⋯O inter-actions generate S(5) ring motifs and an O-H⋯O inter-action generates an S(7) ring motif. In the crystal, mol-ecules are linked via inter-molecular O-H⋯O inter-actions along the b axis and further stacked along a axis. The absolute configuration of the title compound was inferred from previously solved structures of its analogues.

Visual detection and sequential injection determination of aluminium using a cinnamoyl derivative.

PubMed

Elečková, Lenka; Alexovič, Michal; Kuchár, Juraj; Balogh, Ioseph S; Andruch, Vasil

2015-02-01

A cinnamoyl derivative, 3-[4-(dimethylamino)cinnamoyl]-4-hydroxy-6-methyl-3,4-2H-pyran-2-one, was used as a ligand for the determination of aluminium. Upon the addition of an acetonitrile solution of the ligand to an aqueous solution containing Al(III) and a buffer solution at pH 8, a marked change in colour from yellow to orange is observed. The colour intensity is proportional to the concentration of Al(III); thus, the 'naked-eye' detection of aluminium is possible. The reaction is also applied for sequential injection determination of aluminium. Beer׳s law is obeyed in the range from 0.055 to 0.66 mg L(-1) of Al(III). The limit of detection, calculated as three times the standard deviation of the blank test (n=10), was found to be 4 μg L(-1) for Al(III). The method was applied for the determination of aluminium in spiked water samples and pharmaceutical preparations. Copyright © 2014 Elsevier B.V. All rights reserved.

Structural basis of malaria parasite lysyl-tRNA synthetase inhibition by cladosporin.

PubMed

Khan, Sameena; Sharma, Arvind; Belrhali, Hassan; Yogavel, Manickam; Sharma, Amit

2014-06-01

Malaria parasites inevitably develop drug resistance to anti-malarials over time. Hence the immediacy for discovering new chemical scaffolds to include in combination malaria drug therapy. The desirable attributes of new chemotherapeutic agents currently include activity against both liver and blood stage malaria parasites. One such recently discovered compound called cladosporin abrogates parasite growth via inhibition of Plasmodium falciparum lysyl-tRNA synthetase (PfKRS), an enzyme central to protein translation. Here, we present crystal structure of ternary PfKRS-lysine-cladosporin (PfKRS-K-C) complex that reveals cladosporin's remarkable ability to mimic the natural substrate adenosine and thereby colonize PfKRS active site. The isocoumarin fragment of cladosporin sandwiches between critical adenine-recognizing residues while its pyran ring fits snugly in the ribose-recognizing cavity. PfKRS-K-C structure highlights ample space within PfKRS active site for further chemical derivatization of cladosporin. Such derivatives may be useful against additional human pathogens that retain high conservation in cladosporin chelating residues within their lysyl-tRNA synthetase.

Tunable organic distributed feedback dye laser device excited through Förster mechanism

NASA Astrophysics Data System (ADS)

Tsutsumi, Naoto; Hinode, Taiki

2017-03-01

Tunable organic distributed feedback (DFB) dye laser performances are re-investigated and characterized. The slab-type waveguide DFB device consists of air/active layer/glass substrate. Active layer consisted of tris(8-quinolinolato)aluminum (Alq3), 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCM) dye, and polystyrene (PS) matrix. Effective energy transfer from Alq3 to DCM through Förster mechanism enhances the laser emission. Slope efficiency in the range of 4.9 and 10% is observed at pump energy region higher than 0.10-0.15 mJ cm-2 (lower threshold), which is due to the amplified spontaneous emission (ASE) and lasing. Typical slope efficiency for lasing in the range of 2.0 and 3.0% is observed at pump energy region higher than 0.25-0.30 mJ cm-2 (higher threshold). The tuning wavelength for the laser emission is ranged from 620 to 645 nm depending on the ASE region.

Structure elucidation and chemical synthesis of stigmolone, a novel type of prokaryotic pheromone

PubMed Central

Hull, William E.; Berkessel, Albrecht; Plaga, Wulf

1998-01-01

Approximately 2 μmol of a novel prokaryotic pheromone, involved in starvation-induced aggregation and formation of fruiting bodies by the myxobacterium Stigmatella aurantiaca, were isolated by a large-scale elution procedure. The pheromone was purified by HPLC, and high-resolution MS, IR, 1H-NMR, and 13C-NMR were used to identify the active substance as the hydroxy ketone 2,5,8-trimethyl-8-hydroxy-nonan-4-one, which has been named stigmolone. The analysis was complicated by a solvent-dependent equilibrium between stigmolone and the cyclic enol-ether 3,4-dihydro-2,2,5-trimethyl-6-(2-methylpropyl)-2H-pyran formed by intramolecular nucleophilic attack of the 8-OH group at the ketone C4 followed by loss of H2O. Both compounds were synthesized chemically, and their structures were confirmed by NMR analysis. Natural and synthetic stigmolone have the same biological activity at ca. 1 nM concentration. PMID:9736725

Discovery of chiral dihydropyridopyrimidinones as potent, selective and orally bioavailable inhibitors of AKT.

PubMed

Parthasarathy, Saravanan; Henry, Kenneth; Pei, Huaxing; Clayton, Josh; Rempala, Mark; Johns, Deidre; De Frutos, Oscar; Garcia, Pablo; Mateos, Carlos; Pleite, Sehila; Wang, Yong; Stout, Stephanie; Condon, Bradley; Ashok, Sheela; Lu, Zhohai; Ehlhardt, William; Raub, Tom; Lai, Mei; Geeganage, Sandaruwan; Burkholder, Timothy P

2018-06-01

During the course of our research efforts to develop potent and selective AKT inhibitors, we discovered enatiomerically pure substituted dihydropyridopyrimidinones (DHP) as potent inhibitors of protein kinase B/AKT with excellent selectivity against ROCK 2 . A key challenge in this program was the poor physicochemical properties of the initial lead compound 5. Integration of structure-based drug design and physical properties-based design resulted in replacement of a highly hydrophobic poly fluorinated aryl ring by a simple trifluoromethyl that led to identification of compound 6 with much improved physicochemical properties. Subsequent SAR studies led to the synthesis of new pyran analog 7 with improved cell potency. Further optimization of pharmacokintetics properties by increasing permeability with appropriate fluorinated alkyl led to compound 8 as a potent, selective AKT inhibitors that blocks the phosphorylation of GSK3β in vivo and had robust, dose and concentration dependent efficacy in the U87MG tumor xenograft model. Copyright © 2018 Elsevier Ltd. All rights reserved.

Sulfur-containing constituents and one 1H-pyrrole-2-carboxylic acid derivative from pineapple [Ananas comosus (L.) Merr.] fruit.

PubMed

Zheng, Zong-Ping; Ma, Jinyu; Cheng, Ka-Wing; Chao, Jianfei; Zhu, Qin; Chang, Raymond Chuen-Chung; Zhao, Ming; Lin, Zhi-Xiu; Wang, Mingfu

2010-12-01

Two sulfur-containing compounds, (S)-2-amino-5-((R)-1-carboxy-2-((E)-3-(4-hydroxy-3-methoxyphenyl)allylthio)ethyl-amino)-5-oxopentanoic acid (1) and (S)-2-amino-5-((R)-1-(carboxymethylamino)-3-((E)-3-(4-hydroxyphenyl)allylthio)-1-oxopropan-2-ylamino)-5-oxopentanoic acid (2), and one 1H-pyrrole-2-carboxylic acid derivative, 6-(3-(1H-pyrrole-2-carbonyloxy)-2-hydroxypropoxy)-3,4,5-trihydroxy-tetrahydro-2H-pyran-2-carboxylic acid (3), together with eighteen known phenolic compounds, were isolated from the fruits of pineapple. Their structures were elucidated by a combination of spectroscopic analyses. Some of these compounds showed inhibitory activities against tyrosinase. The half maximal inhibitory concentration values of compounds 1, 4, 5, 6, 7 are lower than 1 mM. These compounds may contribute to the well-known anti-browning effect of pineapple juice and be potential skin whitening agents in cosmetic applications. Copyright © 2010 Elsevier Ltd. All rights reserved.

Analysis of alternariol and alternariol monomethyl ether in foodstuffs by molecularly imprinted solid-phase extraction and ultra-high-performance liquid chromatography tandem mass spectrometry.

PubMed

Rico-Yuste, A; Walravens, J; Urraca, J L; Abou-Hany, R A G; Descalzo, A B; Orellana, G; Rychlik, M; De Saeger, S; Moreno-Bondi, M C

2018-03-15

Molecularly imprinted porous polymer microspheres selective to Alternaria mycotoxins, alternariol (AOH) and alternariol monomethyl ether (AME), were synthesized and applied to the extraction of both mycotoxins in food samples. The polymer was prepared using 4-vinylpiridine (VIPY) and methacrylamide (MAM) as functional monomers, ethylene glycol dimethacrylate (EDMA) as cross-linker and 3,8,9-trihydroxy-6H-dibenzo[b,d]pyran-6-one (S2) as AOH surrogate template. A molecularly imprinted solid phase extraction (MISPE) method has been optimized for the selective isolation of the mycotoxins from aqueous samples coupled to HPLC with fluorescence (λ ex =258nm; λ em =440nm) or MS/MS analysis. The MISPE method was validated by UPLC-MS/MS for the determination of AOH and AME in tomato juice and sesame oil based on the European Commission Decision 2002/657/EC. Method performance was satisfactory with recoveries from 92.5% to 106.2% and limits of quantification within the 1.1-2.8µgkg -1 range in both samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reducing patulin contamination in apple juice by using inactive yeast.

PubMed

Yue, Tianli; Dong, Qinfang; Guo, Caixia; Worobo, Randy W

2011-01-01

The mycotoxin, patulin (4-hydroxy-4H-furo[3,2c]pyran-2[6H]-one), is a secondary metabolite produced mainly in rotten parts of fruits and vegetables, most notably apples and apple products, by a wide range of fungal species in the genera Penicillium, Aspergillus, and Byssochlamys. Due to its mutagenic and teratogenic nature and possible health risks to consumers, many countries have regulations to reduce levels of patulin in apple products. In the present study, reduction of patulin contamination in apple juice by using 10 different inactivated yeast strains was assessed. Our results indicated that nearly twofold differences in biomass existed among the 10 yeast strains. Eight of the 10 inactivated yeast strains could provide >50% patulin reduction in apple juice within 24 h, with the highest reduction rate being >72%. Furthermore, juice quality parameters, i.e., degrees Brix, total sugar, titratable acidity, color value, and clarity, of the treated apple juice were very similar to those of the untreated patulin-free juice. Potential applications of using inactivated yeast strain for patulin control are also discussed.

Volatile constituents of roasted tigernut oil (Cyperus esculentus L.).

PubMed

Lasekan, Ola

2013-03-30

Volatile compounds play a key role in determining the sensory appreciation of vegetable oils. In this study a systematic evaluation of odorants responsible for the characteristic flavour of roasted tigernut oil was carried out. A total of 75 odour-active volatiles were identified. From these, 13 aroma compounds showing high flavour dilution factors in the range of 16 to 128 were quantified by their odour activity values (OAVs). On the basis of high OAVs in oil, the following aroma compounds [vanillin (chocolate, sweet vanilla), 5-ethylfurfural (caramel, spicy), 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (caramel), phenyl acetaldehyde (honey-like), ethanone, 1-(4-hydroxy-3-methoxyphenyl) (faint vanilla)] were elucidated as important contributors to the overall chocolate, sweet vanilla, butterscotch aroma of the oil. Odorants with high concentrations in the roasted tigernut oil such as 5-hydroxymethylfurfural, ethyl hexadecanoate, n-propyl-9,12-octadecadienoate gave relatively low OAVs, so their contributions to the overall orthonasal aroma impression of roasted tigernut oil can be assumed to be low. © 2012 Society of Chemical Industry.

High-efficient and brightness white organic light-emitting diodes operated at low bias voltage

NASA Astrophysics Data System (ADS)

Zhang, Lei; Yu, Junsheng; Yuan, Kai; Jian, Yadong

2010-10-01

White organic light-emitting diodes (OLEDs) used for display application and lighting need to possess high efficiency, high brightness, and low driving voltage. In this work, white OLEDs consisted of ambipolar 9,10-bis 2-naphthyl anthracene (ADN) as a host of blue light-emitting layer (EML) doped with tetrabutyleperlene (TBPe) and a thin codoped layer consisted of N, N'-bis(naphthalen-1-yl)-N,N'-bis(phenyl)-benzidine (NPB) as a host of yellow light-emitting layer doped with 4-(dicyanomethylene)-2-tert-butyl-6-(1,1,7,7-tetramethyljulolidin-4-yl-vinyl)-4H-pyran (DCJTB) were investigated. With appropriate tuning in the film thickness, position, and dopant concentration of the co-doped layer, a white OLED with a luminance yield of 10.02 cd/A with the CIE coordinates of (0.29, 0.33) has been achieved at a bias voltage of 9 V and a luminance level of over 10,000 cd/m2. By introducing the PIN structure with both HIL and bis(10- hydroxybenzo-quinolinato)-beryllium (BeBq2) ETL, the power efficiency of white OLED was improved.

Callipeltosides A, B and C: Total Syntheses and Structural Confirmation

PubMed Central

Frost, James R; Pearson, Colin M; Snaddon, Thomas N; Booth, Richard A; Turner, Richard M; Gold, Johan; Shaw, David M; Gaunt, Matthew J; Ley, Steven V

2015-01-01

Since their isolation almost 20 years ago, the callipeltosides have been of long standing interest to the synthetic community owing to their unique structural features and inherent biological activity. Herein we present our full research effort that has led to the synthesis of these molecules. Key aspects of our final strategy include 1) synthesis of the C1–C9 pyran core (5) using an AuCl3-catalysed cyclisation; 2) formation of C10–C22 vinyl iodide (55) by sequential bidirectional Stille reactions and 3) diastereoselective union of these advanced fragments by means of an alkenylzinc addition (d.r.=91:9 at C9). The common callipeltoside aglycon (4) was completed in a further five steps. Following this, all three sugar fragments were appended to provide the entire callipeltoside family. In addition to this, D-configured callipeltose B was synthesised and appended to the callipeltoside aglycon. The 1H NMR spectrum of this molecule was found to be significantly different to the natural isolate, further supporting our assignment of callipeltoside B (2). PMID:26230615

Characterization of hydrophobic interaction and antioxidant properties of the phenothiazine nucleus in mitochondrial and model membranes.

PubMed

Borges, Marcelo B D; Dos Santos, Carolina G; Yokomizo, César H; Sood, Rohit; Vitovic, Pavol; Kinnunen, Paavo K J; Rodrigues, Tiago; Nantes, Iseli L

2010-09-01

The antioxidant properties of the phenothiazine nucleus (PHT) associated with mitochondrial membranes and liposomes were investigated. PHT exhibited hydrophobic interaction with lipid bilayers, as shown by the quenching of excited states of 1-palmitoyl-2[10-pyran-1-yl)]-decanoyl-sn-glycero-3-phophocholine (PPDPC) incorporated in phosphatidylcholine/phosphatidylethanolamine/cardiolipin liposomes, observed even in high ionic strength; and by the spectral changes of PHT following the addition of mitochondrial membranes. Inserted into bilayers, 5 microM PHT was able to protect lipids and cytochrome c against pro-oxidant agents and exhibited spectral changes suggestive of oxidative modifications promoted by the trapping of the reactive species. In this regard, PHT exhibited the ability to scavenge DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical. PHT was also able to protect rat liver mitochondria against peroxide- and iron-induced oxidative damage and consequent swelling. At the concentration range in which the antioxidant properties were observed, PHT did not cause alterations in the membrane structure and function. This study contributes to the comprehension of the correlation structure and function of phenothiazines and antioxidant properties.

Improvement of amplified spontaneous emission performance by doping tris(8-hydroxyquinoline) aluminum (Alq3) in dye-doped polymer thin films.

PubMed

Lu, Wu; You, Han; Fang, Junfeng; Ma, Dongge

2007-04-20

A well-known red fluorescent dye 4-(dicy-anomethylene)-2-t-butyl-6(1,1,7,7-tetramethyljulolidyl-9-enyl)-4H-pyran (DCJTB) was codoped with an electron transport organic molecule tris(8-hydroxyquinoline) aluminum (Alq(3)) in a host matrix of polystyrene (PS), and the amplified spontaneous emission (ASE) was studied by optically pumping. It was found that the ASE performance was significantly improved by the introduction of Alq(3). The Alq(3):DCJTB:PS blending thin films showed a low threshold (2.4 microJ/pulse) and a high net gain coefficient (109.95 cm(-1)) compared with the pure DCJTB:PS system (threshold of 15.2 microJ/pulse and gain of 35.94 cm(-1)). The improvement of the ASE performance was considered to be attributable to the effective Föster energy transfer from Alq(3) to DCJTB. Our results demonstrate that the Alq(3):DCJTB could be a promising candidate as gain medium for red organic diode lasers.

PET imaging of T cells: Target identification and feasibility assessment.

PubMed

Auberson, Yves P; Briard, Emmanuelle; Rudolph, Bettina; Kaupmann, Klemen; Smith, Paul; Oberhauser, Berndt

2018-06-01

Imaging T cells using positron emission tomography (PET) would be highly useful for diagnosis and monitoring in immunology and oncology patients. There are however no obvious targets that can be used to develop imaging agents for this purpose. We evaluated several potential target proteins with selective expression in T cells, and for which lead molecules were available: PKC , Lck, ZAP70 and Itk. Ultimately, we focused on Itk (interleukin-2-inducible T cell kinase) and identified a tool molecule with properties suitable for in vivo imaging of T cells, (5aR)-5,5-difluoro-5a-methyl-N-(1-((S)-3-(methylsulfonyl)-phenyl)(tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)-1,4,4a,5,5a,6-hexahydro-cyclopropa[f]-indazole-3-carboxamide (23). While not having the optimal profile for clinical use, this molecule indicates that it might be possible to develop Itk-selective PET ligands for imaging the distribution of T cells in patients. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Metabolomics by Proton High-Resolution Magic-Angle-Spinning Nuclear Magnetic Resonance of Tomato Plants Treated with Two Secondary Metabolites Isolated from Trichoderma.

PubMed

Mazzei, Pierluigi; Vinale, Francesco; Woo, Sheridan Lois; Pascale, Alberto; Lorito, Matteo; Piccolo, Alessandro

2016-05-11

Trichoderma fungi release 6-pentyl-2H-pyran-2-one (1) and harzianic acid (2) secondary metabolites to improve plant growth and health protection. We isolated metabolites 1 and 2 from Trichoderma strains, whose different concentrations were used to treat seeds of Solanum lycopersicum. The metabolic profile in the resulting 15 day old tomato leaves was studied by high-resolution magic-angle-spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy directly on the whole samples without any preliminary extraction. Principal component analysis (PCA) of HRMAS NMR showed significantly enhanced acetylcholine and γ-aminobutyric acid (GABA) content accompanied by variable amount of amino acids in samples treated with both Trichoderma secondary metabolites. Seed germination rates, seedling fresh weight, and the metabolome of tomato leaves were also dependent upon doses of metabolites 1 and 2 treatments. HRMAS NMR spectroscopy was proven to represent a rapid and reliable technique for evaluating specific changes in the metabolome of plant leaves and calibrating the best concentration of bioactive compounds required to stimulate plant growth.

The profile of volatile compounds in the outer and inner parts of broiled pork neck is strongly influenced by the acetic-acid marination conditions.

PubMed

Biller, Elżbieta; Boselli, Emanuele; Obiedziński, Mieczysław; Karpiński, Piotr; Waszkiewicz-Robak, Bożena

2016-11-01

Raw pork neck cutlets were marinated in an aqueous solution of acetic acid (pH4, 24h, 4°C) without (M) or with 1% (w/w) of glucose. The control (K) was formed by non-treated raw pork neck. The cutlets were then broiled (185°C, 30min). In all K cutlets, significant higher amounts of volatile compounds (VCs) were developed after broiling than the other samples. Significant more aldehydes and alcohols were present in the inner parts than in the surface. The correlation between surface and internal layers was high only for aldehydes. Marinating decreased the differences among VCs and led to the standardization of the processed meat. The addition of glucose to the marinade led to more volatile aldehydes, carboxylic acids, esters, furan, pyran, pyrazine, pyrrol and pyridine derivatives than in M samples. Several (53) specific VCs explained the differences among the surface samples related to the marinating process. However, only 16 VCs explained the variance among the inner parts. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spectroscopic and biological activities studies of bivalent transition metal complexes of Schiff bases derived from condensation of 1,4-phenylenediamine and benzopyrone derivatives.

PubMed

Sherif, Omaima E; Abdel-Kader, Nora S

2014-01-03

Many tools of analysis such as elemental analyses, infrared, ultraviolet-visible, electron spin resonance (ESR) and thermal analysis, as well as conductivity and magnetic susceptibility measurements were used to elucidate the structures of the newly prepared Co(II), Ni(II) and Cu(II) complexes with Schiff bases derived from the condensation of 1,4-phenylenediamine with 6-formyl-7-hydroxy-5-methoxy-2-methylbenzo-pyran-4-one (H2L) or 5,7-dihydroxy-6-formyl-2-methylbenzopyran-4-one (H4L). The data showed that all formed complexes are 1:1 or 2:2 (M:L) and non-electrolyte chelates. The Co(II) and Cu(II) complexes of the two Schiff bases were screened for antibacterial activities by the disk diffusion method. The antibacterial activity was screened using Escherichia coli and Staphylococcus capitis but the antifungal activity was examined by using Aspergillus flavus and Candida albicans. The Results showed that the tested complexes have antibacterial, except CuH4L, but not antifungal activities. Copyright © 2013 Elsevier B.V. All rights reserved.

A new methodology capable of characterizing most volatile and less volatile minor edible oils components in a single chromatographic run without solvents or reagents. Detection of new components.

PubMed

Alberdi-Cedeño, Jon; Ibargoitia, María L; Cristillo, Giovanna; Sopelana, Patricia; Guillén, María D

2017-04-15

The possibilities offered by a new methodology to determine minor components in edible oils are described. This is based on immersion of a solid-phase microextraction fiber of PDMS/DVB into the oil matrix, followed by Gas Chromatography/Mass Spectrometry. It enables characterization and differentiation of edible oils in a simple way, without either solvents or sample modification. This methodology allows simultaneous identification and quantification of sterols, tocols, hydrocarbons of different natures, fatty acids, esters, monoglycerides, fatty amides, aldehydes, ketones, alcohols, epoxides, furans, pyrans and terpenic oxygenated derivatives. The broad information provided by this methodology is useful for different areas of interest such as nutritional value, oxidative stability, technological performance, quality, processing, safety and even the prevention of fraudulent practices. Furthermore, for the first time, certain fatty amides, gamma- and delta-lactones of high molecular weight, and other aromatic compounds such as some esters derived from cinnamic acid have been detected in edible oils. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rapid synthesis of carbohydrate derivatives, including mimetics of C-linked disaccharides and C-linked aza disaccharides, using the hetero-Diels-Alder reaction.

PubMed

Burland, Peter A; Coisson, David; Osborn, Helen M I

2010-11-05

In this work we demonstrate the value of performing a hetero-Diels-Alder reaction (HDAR) between Danishefsky's diene and a range of aldehydes or imines, under microwave irradiation. By using a range of aldehydes and imines, including those derived from carbohydrates, access to functionalized 2,3-dihydro-4H-pyran-4-ones or 2,3-dihydro-4-pyridinones in good to excellent synthetic yields is possible. A particular strength of the methodology is its ability to access mimetics of C-linked disaccharides and C-linked aza disaccharides, targets of current therapeutic interest, in a rapid, convenient, and diastereoselective manner. The effect of high pressure on the HDARs involving carbohydrate-derived aldehydes and imines is also explored, with enhancement in yields occurring for the aldehyde substrates. Finally, HDARs using carbohydrate derived ketones, enones, and enals are described under a range of conditions. Optimum results were obtained under high-pressure conditions, with highly functionalized carbohydrate derivatives being afforded, in good yields, in this way.

GC-MS Profiling of Volatile Components in Different Fermentation Products of Cordyceps Sinensis Mycelia.

PubMed

Zhang, Hongyang; Li, Yahui; Mi, Jianing; Zhang, Min; Wang, Yuerong; Jiang, Zhihong; Hu, Ping

2017-10-24

The fermentation products of Cordyceps sinensis ( C. sinensis ) mycelia are sustainable substitutes for natural C. sinensis . However, the volatile compositions of the commercial products are still unclear. In this paper, we have developed a simultaneous distillation-extraction (SDE) and gas chromatography-mass spectrometry (GC-MS) method for the profiling of volatile components in five fermentation products. A total of 64, 39, 56, 52, and 44 components were identified in the essential oils of Jinshuibao capsule (JSBC), Bailing capsule (BLC), Zhiling capsule (ZLC), Ningxinbao capsule (NXBC), and Xinganbao capsule (XGBC), respectively. 5,6-Dihydro-6-pentyl-2H-pyran-2-one (massoia lactone) was first discovered as the dominant component in JSBC volatiles. Fatty acids including palmitic acid (C16:0) and linoleic acid (C18:2) were also found to be major volatile compositions of the fermentation products. The multivariate partial least squares-discriminant analysis (PLS-DA) showed a clear discrimination among the different commercial products as well as the counterfeits. This study may provide further chemical evidences for the quality evaluation of the fermentation products of C. sinensis mycelia.

CRM1 inhibitory and antiproliferative activities of novel 4'-alkyl substituted klavuzon derivatives.

PubMed

Kanbur, Tuğçe; Kara, Murat; Kutluer, Meltem; Şen, Ayhan; Delman, Murat; Alkan, Aylin; Otaş, Hasan Ozan; Akçok, İsmail; Çağır, Ali

2017-08-15

Klavuzons are 6-(naphthalen-1-yl) substituted 5,6-dihydro-2H-pyran-2-one derivatives showing promising antiproliferative activities in variety of cancer cell lines. In this work, racemic syntheses of nine novel 4'-alkyl substituted klavuzon derivatives were completed in eight steps and anticancer properties of these compounds were evaluated. It is found that size of the substituent has dramatic effect over the potency and selectivity of the cytotoxic activity in cancerous and healthy pancreatic cell lines. The size of the substituent can also effect the CRM1 inhibitory properties of klavuzon derivatives. Strong cytotoxic activity and CRM1 inhibition can be observed only when a small substituent present at 4'-position of naphthalen-1-yl group. However, these substituents makes the molecule more cytotoxic in healthy pancreatic cells rather than cancerous pancreatic cells. Among the tested compounds 1,2,3,4-tetrahydrophenanthren-9-yl substituted lactone was the most cytotoxic compound and its antiproliferative activity was also tested in 3D spheroids generated from HuH-7 cell lines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Organic Solid-State Tri-Wavelength Lasing from Holographic Polymer-Dispersed Liquid Crystal and a Distributed Feedback Laser with a Doped Laser Dye and a Semiconducting Polymer Film.

PubMed

Liu, Minghuan; Liu, Yonggang; Peng, Zenghui; Wang, Shaoxin; Wang, Qidong; Mu, Quanquan; Cao, Zhaoliang; Xuan, Li

2017-05-07

Organic solid-state tri-wavelength lasing was demonstrated from dye-doped holographic polymer-dispersed liquid crystal (HPDLC) distributed feedback (DFB) laser with semiconducting polymer poly[-methoxy-5-(2'-ethyl-hexyloxy)-1,4-phenylene-vinylene] (MEH-PPV) and laser dye [4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran] (DCM) by a one-step holography technique, which centered at 605.5 nm, 611.9 nm, and 671.1 nm. The temperature-dependence tuning range for the tri-wavelength dye-doped HPDLC DFB laser was as high as 8 nm. The lasing emission from the 9th order HPDLC DFB laser with MEH-PPV as active medium was also investigated, which showed excellent s-polarization characterization. The diffraction order is 9th and 8th for the dual-wavelength lasing with DCM as the active medium. The results of this work provide a method for constructing the compact and cost-effective all solid-state smart laser systems, which may find application in scientific and applied research where multi-wavelength radiation is required.

The Combined Use of Proteomics and Transcriptomics Reveals a Complex Secondary Metabolite Network in Peperomia obtusifolia.

PubMed

Batista, Andrea N L; Santos-Pinto, José Roberto A Dos; Batista, João M; Souza-Moreira, Tatiana M; Santoni, Mariana M; Zanelli, Cleslei F; Kato, Massuo J; López, Silvia N; Palma, Mario S; Furlan, Maysa

2017-05-26

Peperomia obtusifolia, an ornamental plant from the Piperaceae family, accumulates a series of secondary metabolites with interesting biological properties. From a biosynthesis standpoint, this species produces several benzopyrans derived from orsellinic acid, which is a polyketide typically found in fungi. Additionally, the chiral benzopyrans were reported as racemic and/or as diastereomeric mixtures, which raises questions about the level of enzymatic control in the cyclization step for the formation of the 3,4-dihydro-2H-pyran moiety. Therefore, this article describes the use of shotgun proteomic and transcriptome studies as well as phytochemical profiling for the characterization of the main biosynthesis pathways active in P. obtusifolia. This combined approach resulted in the identification of a series of proteins involved in its secondary metabolism, including tocopherol cyclase and prenyltransferases. The activity of these enzymes was supported by the phytochemical profiling performed in different organs of P. obtusifolia. However, the polyketide synthases possibly involved in the production of orsellinic acid could not be identified, suggesting that orsellinic acid may be produced by endophytes intimately associated with the plant.

Constituents of Musa x paradisiaca cultivar with the potential to induce the phase II enzyme, quinone reductase.

PubMed

Jang, Dae Sik; Park, Eun Jung; Hawthorne, Michael E; Vigo, Jose Schunke; Graham, James G; Cabieses, Fernando; Santarsiero, Bernard D; Mesecar, Andrew D; Fong, Harry H S; Mehta, Rajendra G; Pezzuto, John M; Kinghorn, A Douglas

2002-10-23

A new bicyclic diarylheptanoid, rel-(3S,4aR,10bR)-8-hydroxy-3-(4-hydroxyphenyl)-9-methoxy-4a,5,6,10b-tetrahydro-3H-naphtho[2,1-b]pyran (1), as well as four known compounds, 1,2-dihydro-1,2,3-trihydroxy-9-(4-methoxyphenyl)phenalene (2), hydroxyanigorufone (3), 2-(4-hydroxyphenyl)naphthalic anhydride (4), and 1,7-bis(4-hydroxyphenyl)hepta-4(E),6(E)-dien-3-one (5), were isolated from an ethyl acetate-soluble fraction of the methanol extract of the fruits of Musa x paradisiaca cultivar, using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa1c1c7 mouse hepatoma cells to monitor chromatographic fractionation. The structure and relative stereochemistry of compound 1 were elucidated unambiguously by one- and two-dimensional NMR experiments ((1)H NMR, (13)C NMR, DEPT, COSY, HMQC, HMBC, and NOESY) and single-crystal X-ray diffraction analysis. Isolates 1-5 were evaluated for their potential cancer chemopreventive properties utilizing an in vitro assay to determine quinone reductase induction and a mouse mammary organ culture assay.

Synthesis of alkyl-substituted six-membered lactones through ring-closing metathesis of homoallyl acrylates. An easy route to pyran-2-ones, constituents of tobacco flavor.

PubMed

D'Annibale, Andrea; Ciaralli, Laura; Bassetti, Mauro; Pasquini, Chiara

2007-08-03

The ring-closing metathesis (RCM) reactions of homoallylic acrylates bearing alkyl substituents on various positions of their skeleton afford the corresponding pentenolides in the presence of carbene ruthenium catalysts. For R3 = R4 = H, or R3 = Me, R4 = H, the reactions are catalyzed by complex [RuCl2(PCy3)2(=CHPh)], while a second-generation Grubbs catalyst is required when R3 = H and R4 = Me, R3 = R4 = Me, or R3 = i-Pr and R4 = H. Alkyl substitution at the homoallylic carbon (R1, R2) increases the yield of the reaction when both the acrylic and/or homoallylic double bonds are methyl-substituted. The interaction of the catalyst with the substrate in the initiation stage involves the homoallylic double bond rather than the acrylic moiety, and the resulting alkylidene species from the first-generation Grubbs catalyst can be observed by 1H and 31P NMR. The racemic tobacco constituents 4-isopropyl-5,6-dihydropyran-2-one and 4-isopropyltetrahydropyran-2-one are prepared via a short reaction sequence, involving the RCM reaction as the key transformation.

Quantum efficiency harmonic analysis of exciton annihilation in organic light emitting diodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, J. S.; Giebink, N. C., E-mail: ncg2@psu.edu

2015-06-29

Various exciton annihilation processes are known to impact the efficiency roll-off of organic light emitting diodes (OLEDs); however, isolating and quantifying their contribution in the presence of other factors such as changing charge balance continue to be a challenge for routine device characterization. Here, we analyze OLED electroluminescence resulting from a sinusoidal dither superimposed on the device bias and show that nonlinearity between recombination current and light output arising from annihilation mixes the quantum efficiency measured at different dither harmonics in a manner that depends uniquely on the type and magnitude of the annihilation process. We derive a series ofmore » analytical relations involving the DC and first harmonic external quantum efficiency that enable annihilation rates to be quantified through linear regression independent of changing charge balance and evaluate them for prototypical fluorescent and phosphorescent OLEDs based on the emitters 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran and platinum octaethylporphyrin, respectively. We go on to show that, in most cases, it is sufficient to calculate the needed quantum efficiency harmonics directly from derivatives of the DC light versus current curve, thus enabling this analysis to be conducted solely from standard light-current-voltage measurement data.« less

4,5,7,8,17-Penta­hydr­oxy-14,18-dimethyl-6-methyl­ene-3,10-dioxapenta­cyclo­[9.8.0.01,7.04,19.013,18]nona­dec-14-ene-9,16-dione methanol solvate dihydrate

PubMed Central

Teh, Chin Hoe; Teoh, Siew Chin; Yeap, Chin Sing; Chan, Kit Lam; Fun, Hoong-Kun

2009-01-01

The title quassinoid compound, C20H24O9·CH3OH·2H2O, is a natural eurycomanone isolated from the roots of Eurycoma longifolia. The mol­ecules contain a fused five-ring system, with one tetra­hydro­furan ring adopting an envelope conformation, one tetra­hydro­pyran-2-one ring in a screw boat conformation, one cyclo­hexenone ring in a half-chair conformation and two cyclo­hexane rings in chair conformations. Intra­molecular C—H⋯O inter­actions generate S(5) ring motifs and an O—H⋯O inter­action generates an S(7) ring motif. In the crystal, mol­ecules are linked via inter­molecular O—H⋯O inter­actions along the b axis and further stacked along a axis. The absolute configuration of the title compound was inferred from previously solved structures of its analogues. PMID:21582604

A polymer tandem solar cell with 10.6% power conversion efficiency.

PubMed

You, Jingbi; Dou, Letian; Yoshimura, Ken; Kato, Takehito; Ohya, Kenichiro; Moriarty, Tom; Emery, Keith; Chen, Chun-Chao; Gao, Jing; Li, Gang; Yang, Yang

2013-01-01

An effective way to improve polymer solar cell efficiency is to use a tandem structure, as a broader part of the spectrum of solar radiation is used and the thermalization loss of photon energy is minimized. In the past, the lack of high-performance low-bandgap polymers was the major limiting factor for achieving high-performance tandem solar cell. Here we report the development of a high-performance low bandgap polymer (bandgap <1.4 eV), poly[2,7-(5,5-bis-(3,7-dimethyloctyl)-5H-dithieno[3,2-b:2',3'-d]pyran)-alt-4,7-(5,6-difluoro-2,1,3-benzothia diazole)] with a bandgap of 1.38 eV, high mobility, deep highest occupied molecular orbital. As a result, a single-junction device shows high external quantum efficiency of >60% and spectral response that extends to 900 nm, with a power conversion efficiency of 7.9%. The polymer enables a solution processed tandem solar cell with certified 10.6% power conversion efficiency under standard reporting conditions (25 °C, 1,000 Wm(-2), IEC 60904-3 global), which is the first certified polymer solar cell efficiency over 10%.

A polymer tandem solar cell with 10.6% power conversion efficiency

PubMed Central

You, Jingbi; Dou, Letian; Yoshimura, Ken; Kato, Takehito; Ohya, Kenichiro; Moriarty, Tom; Emery, Keith; Chen, Chun-Chao; Gao, Jing; Li, Gang; Yang, Yang

2013-01-01

An effective way to improve polymer solar cell efficiency is to use a tandem structure, as a broader part of the spectrum of solar radiation is used and the thermalization loss of photon energy is minimized. In the past, the lack of high-performance low-bandgap polymers was the major limiting factor for achieving high-performance tandem solar cell. Here we report the development of a high-performance low bandgap polymer (bandgap <1.4 eV), poly[2,7-(5,5-bis-(3,7-dimethyloctyl)-5H-dithieno[3,2-b:2′,3′-d]pyran)-alt-4,7-(5,6-difluoro-2,1,3-benzothia diazole)] with a bandgap of 1.38 eV, high mobility, deep highest occupied molecular orbital. As a result, a single-junction device shows high external quantum efficiency of >60% and spectral response that extends to 900 nm, with a power conversion efficiency of 7.9%. The polymer enables a solution processed tandem solar cell with certified 10.6% power conversion efficiency under standard reporting conditions (25 °C, 1,000 Wm−2, IEC 60904-3 global), which is the first certified polymer solar cell efficiency over 10%. PMID:23385590

Molecular imprinted polymer-coated optical fiber sensor for the identification of low molecular weight molecules.

PubMed

Lépinay, Sandrine; Ianoul, Anatoli; Albert, Jacques

2014-10-01

A biomimetic optical probe for detecting low molecular weight molecules (maltol, 3-hydroxy-2-methyl-4H-pyran-4-one, molecular weight of 126.11 g/mol), was designed, fabricated, and characterized. The sensor couples a molecular imprinted polymer (MIP) and the Bragg grating refractometry technology into an optical fiber. The probe is fabricated first by inscribing tilted grating planes in the core of the fiber, and then by photopolymerization to immobilize a maltol imprinted MIP on the fiber cladding surface over the Bragg grating. The sensor response to the presence of maltol in different media is obtained by spectral interrogation of the fiber transmission signal. The results showed that the limit of detection of the sensor reached 1 ng/mL in pure water with a sensitivity of 6.3 × 10(8)pm/M. The selectivity of the sensor against other compounds and its reusability were also studied experimentally. Finally, the unambiguous detection of concentrations as little as 10nM of maltol in complex media (real food samples) by the MIP-coated tilted fiber Bragg grating sensor was demonstrated. Copyright © 2014 Elsevier B.V. All rights reserved.

NMR structural and kinetic assignment of fluoro-3H-naphthopyran photomerocyanines.

PubMed

Delbaere, S; Micheau, J C; Teral, Y; Bochu, C; Campredon, M; Vermeersch, G

2001-11-01

The kinetic and structural behavior of a photochromic compound, 3-(2-fluorophenyl)-3-phenyl-3H-naphtho[2,1-b]pyran (F-Py), was investigated using 1H and 19F nuclear magnetic resonance (NMR) spectroscopy. Upon irradiation, the four theoretically predicted photomerocyanines appear along with a fifth form X, whose final structure has not been elucidated. This last form and two of the photomerocyanines are thermally labile, whereas the other two do not show any signs of decay. The system has been analyzed by NMR spectroscopy. This led to the structural assignment of each photomerocyanine. The kinetics of the thermal bleaching were monitored by directly and separately measuring the concentrations of each species at regular time intervals using 19F NMR spectroscopy. We therefore propose a plausible reaction mechanism. On the basis of this mechanism, the mathematical treatment and the study of the effects of temperature led to the determination of the kinetic and thermodynamic parameters (rate coefficients, enthalpy and entropy of activation) of this photochromic system. The leading role of the labile intermediate X on the formation of trans-transoid-cis (TTC) and cis-transoid-cis (CTC) photomerocyanines is pointed out.

Radiolytic degradation of a new diglycol-diamide ligand for actinide and lanthanide co-extraction from spent nuclear fuel

NASA Astrophysics Data System (ADS)

Ossola, Annalisa; Macerata, Elena; Tinonin, Dario A.; Faroldi, Federica; Giola, Marco; Mariani, Mario; Casnati, Alessandro

2016-07-01

Within the Partitioning and Transmutation strategies, great efforts have been devoted in the last decades to the development of lipophilic ligands able to co-extract trivalent Lanthanides (Ln) and Actinides (An) from spent nuclear fuel. Because of the harsh working conditions these ligands undergo, it is important to prove their chemical and radiolytic stability during the counter-current multi-stage extraction process. In the present work the hydrolytic and radiolytic resistance of the freshly prepared and aged organic solutions containing the new ligand (2,6-bis[(N-methyl-N-dodecyl)carboxamide]-4-methoxy-tetrahydro-pyran) were investigated in order to evaluate the impact on the safety and efficiency of the process. Liquid-liquid extraction tests with spiked solutions showed that the ligand extracting performances are strongly impaired by storing the samples at room temperature and in the light. Moreover, the extracting efficiency of the irradiated samples resulted to be influenced by gamma irradiation, while selectivity remains unchanged. Preliminary mass spectrometric data showed that degradation is mainly due to the acid-catalysed reaction of the ligand carboxamide and ether groups with the 1-octanol present in the diluent.

Ultra-broad range organic solid-state laser from a dye-doped holographic grating quasi-waveguide configuration

NASA Astrophysics Data System (ADS)

Liu, Minghuan; Liu, Yonggang; Peng, Zenghui; Mu, Quanquan; Cao, Zhaoliang; Lu, Xinghai; Ma, Ji; Xuan, Li

2017-08-01

This paper reports the ultra-broad 149.1 nm lasing emission from 573.2 to 722.3 nm using a simple [4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran] (DCM)-doped holographic polymer-dispersed liquid crystal (HPDLC) grating quasi-waveguide configuration by varying the grating period. The lasing emission beams show s-polarization property. The quasi-waveguide structure, which contained the cover glass, the DCM-doped HPDLC grating, the semiconducting polymer film poly[-methoxy-5-(2‧-ethyl-hexyloxy)-1,4-phenylene-vinylene] (MEH-PPV), and the substrate were confirmed to decrease lasing threshold and broaden lasing wavelength. The operational lifetime of the device is 240 000 pulses, which corresponds to an overall laser duration of more than 6 h at a repetition rate of 10 Hz. In addition, the dual-wavelength lasing range from the 8th and 9th order is over 40 nm. The electrical tunability of the dual-wavelength lasing emission is over 1 nm. The experimental results facilitated the decreased lasing threshold and broadened lasing wavelength range of organic solid-state lasers.

Single step synthesis of strigolactone analogues from cyclic keto enols, germination stimulants for seeds of parasitic weeds.

PubMed

Mwakaboko, Alinanuswe S; Zwanenburg, Binne

2011-08-15

The single step synthesis of a newly designed series of strigolactones (SLs) from cyclic keto enols is described. The germinating activity of these SL analogues towards seeds of the parasitic weeds Striga and Orobanche spp. is reported. The first of these SL analogues are derived from the hydroxyl γ-pyrones kojic acid and maltol, the second type from hydroxyl α-pyrones, namely, 4-hydroxy-6-methyl-2H-pyran-2-one and 4-hydroxy-coumarin and the third type from 1,3-diketones, namely, 1,3-cyclohexane-dione (dimedone) and tricyclic 1,3-dione. All keto enols are coupled in a single step with the appropriate D-ring precursor in the presence of a base to give the desired SL analogues. All SL analogues are acceptably biologically active in inducing the germination of seeds of Striga hermonthica and Orobanchecernua. Most interesting are the analogues derived from 4-hydroxy coumarin and dimedone, as they have a remarkably high biological activity towards the seeds of parasitic weeds at relatively low concentrations, comparable with that of the general standard stimulant GR24. Copyright © 2011 Elsevier Ltd. All rights reserved.

Establishing a molecular relationship between chondritic and cometary organic solids

PubMed Central

Cody, George D.; Heying, Emily; Alexander, Conel M. O.; Nittler, Larry R.; Kilcoyne, A. L. David; Sandford, Scott A.

2011-01-01

Multidimensional solid-state NMR spectroscopy is used to refine the identification and abundance determination of functional groups in insoluble organic matter (IOM) isolated from a carbonaceous chondrite (Murchison, CM2). It is shown that IOM is composed primarily of highly substituted single ring aromatics, substituted furan/pyran moieties, highly branched oxygenated aliphatics, and carbonyl groups. A pathway for producing an IOM-like molecular structure through formaldehyde polymerization is proposed and tested experimentally. Solid-state 13C NMR analysis of aqueously altered formaldehyde polymer reveals considerable similarity with chondritic IOM. Carbon X-ray absorption near edge structure spectroscopy of formaldehyde polymer reveals the presence of similar functional groups across certain Comet 81P/Wild 2 organic solids, interplanetary dust particles, and primitive IOM. Variation in functional group concentration amongst these extraterrestrial materials is understood to be a result of various degrees of processing in the parent bodies, in space, during atmospheric entry, etc. These results support the hypothesis that chondritic IOM and cometary refractory organic solids are related chemically and likely were derived from formaldehyde polymer. The fine-scale morphology of formaldehyde polymer produced in the experiment reveals abundant nanospherules that are similar in size and shape to organic nanoglobules that are ubiquitous in primitive chondrites. PMID:21464292

New Cu (II), Co(II) and Ni(II) complexes of chalcone derivatives: Synthesis, X-ray crystal structure, electrochemical properties and DFT computational studies

NASA Astrophysics Data System (ADS)

Tabti, Salima; Djedouani, Amel; Aggoun, Djouhra; Warad, Ismail; Rahmouni, Samra; Romdhane, Samir; Fouzi, Hosni

2018-03-01

The reaction of nickel(II), copper(II) and cobalt(II) with 4-hydroxy-3-[(2E)-3-(1H-indol-3-yl)prop-2-enoyl]-6-methyl-2H-pyran-2-one (HL) leads to a series of new complexes: Ni(L)2(NH3), Cu(L)2(DMF)2 and Co(L)2(H2O). The crystal structure of the Cu(L)2(DMF)2 complex have been determined by X-ray diffraction methods. The Cu(II) lying on an inversion centre is coordinated to six oxygen atoms forming an octahedral elongated. Additionally, the electrochemical behavior of the metal complexes were investigated by cyclic voltammetry at a glassy carbon electrode (GC) in CH3CN solutions, showing the quasi-reversible redox process ascribed to the reduction of the MII/MI couples. The X-ray single crystal structure data of the complex was matched excellently with the optimized monomer structure of the desired compound; Hirschfeld surface analysis supported the packed crystal lattice 3D network intermolecular forces. HOMO/LUMO energy level and the global reactivity descriptors quantum parameters are also calculated. The electrophilic and nucleophilic potions in the complex surface are theoretically evaluated by molecular electrostatic potential and Mulliken atomic charges analysis.

Exploration of flexible phenylpropylurea scaffold as novel cardiac myosin activators for the treatment of systolic heart failure.

PubMed

Manickam, Manoj; Jalani, Hitesh B; Pillaiyar, Thanigaimalai; Sharma, Niti; Boggu, Pulla Reddy; Venkateswararao, Eeda; Lee, You-Jung; Jeon, Eun-Seok; Jung, Sang-Hun

2017-07-07

A series of flexible urea derivatives have been synthesized and demonstrated as selective cardiac myosin ATPase activator. Among them 1-phenethyl-3-(3-phenylpropyl)urea (1, cardiac myosin ATPase activation at 10 μM = 51.1%; FS = 18.90; EF = 12.15) and 1-benzyl-3-(3-phenylpropyl)urea (9, cardiac myosin ATPase activation = 53.3%; FS = 30.04; EF = 18.27) showed significant activity in vitro and in vivo. The change of phenyl ring with tetrahydropyran-4-yl moiety viz., 1-(3-phenylpropyl)-3-((tetrahydro-2H-pyran-4-yl)methyl)urea (14, cardiac myosin ATPase activation = 81.4%; FS = 20.50; EF = 13.10), and morpholine moiety viz., 1-(2-morpholinoethyl)-3-(3-phenylpropyl)urea (21, cardiac myosin ATPase activation = 44.0%; FS = 24.79; EF = 15.65), proved to be efficient to activate the cardiac myosin. The potent compounds 1, 9, 14 and 21 were found to be selective for cardiac myosin over skeletal and smooth myosins. Thus, these urea derivatives are potent scaffold to develop as a newer cardiac myosin activator for the treatment of systolic heart failure. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Synthesis and Evaluation of Radioligands for Imaging Brain Nociceptin/Orphanin FQ Peptide (NOP) Receptors with Positron Emission Tomography

PubMed Central

Pike, Victor W.; Rash, Karen S.; Chen, Zhaogen; Pedregal, Concepción; Statnick, Michael A.; Kimura, Yasuyuki; Hong, Jinsoo; Zoghbi, Sami S.; Fujita, Masahiro; Toledo, Miguel A.; Diaz, Nuria; Gackenheimer, Susan L.; Tauscher, Johannes T.; Barth, Vanessa N.; Innis, Robert B.

2011-01-01

Positron emission tomography (PET) coupled to an effective radioligand could provide an important tool for understanding possible links between neuropsychiatric disorders and brain NOP (nociceptin/orphanin FQ peptide) receptors. We sought to develop such a PET radioligand. High-affinity NOP ligands were synthesized based on a 3-(2'-fluoro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]-1-yl)-2(2-halobenzyl)-N-alkylpropanamide scaffold and from experimental screens in rats, with ex vivo LC-MS/MS measures, three ligands were identified for labeling with carbon-11 and evaluation with PET in monkey. Each ligand was labeled by 11C-methylation of an N-desmethyl precursor and studied in monkey under baseline and NOP receptor-preblock conditions. The three radioligands, [11C](S)-10a–c, gave similar results. Baseline scans showed high entry of radioactivity into brain to give a distribution reflecting that expected for NOP receptors. Pre-block experiments showed high early peak levels of brain radioactivity which rapidly declined to a much lower level than seen in baseline scans, thereby indicating a high level of receptor-specific binding in baseline experiments. Overall, [11C](S)-10c showed the most favorable receptor-specific signal and kinetics and is now selected for evaluation in human subjects. PMID:21438532

In situ IR and X-ray high spatial-resolution microspectroscopy measurements of multistep organic transformation in flow microreactor catalyzed by Au nanoclusters.

PubMed

Gross, Elad; Shu, Xing-Zhong; Alayoglu, Selim; Bechtel, Hans A; Martin, Michael C; Toste, F Dean; Somorjai, Gabor A

2014-03-05

Analysis of catalytic organic transformations in flow reactors and detection of short-lived intermediates are essential for optimization of these complex reactions. In this study, spectral mapping of a multistep catalytic reaction in a flow microreactor was performed with a spatial resolution of 15 μm, employing micrometer-sized synchrotron-based IR and X-ray beams. Two nanometer sized Au nanoclusters were supported on mesoporous SiO2, packed in a flow microreactor, and activated toward the cascade reaction of pyran formation. High catalytic conversion and tunable products selectivity were achieved under continuous flow conditions. In situ synchrotron-sourced IR microspectroscopy detected the evolution of the reactant, vinyl ether, into the primary product, allenic aldehyde, which then catalytically transformed into acetal, the secondary product. By tuning the residence time of the reactants in a flow microreactor a detailed analysis of the reaction kinetics was performed. An in situ micrometer X-ray absorption spectroscopy scan along the flow reactor correlated locally enhanced catalytic conversion, as detected by IR microspectroscopy, to areas with high concentration of Au(III), the catalytically active species. These results demonstrate the fundamental understanding of the mechanism of catalytic reactions which can be achieved by the detailed mapping of organic transformations in flow reactors.

Experimental design-based isotope-dilution SPME-GC/MS method development for the analysis of smoke flavouring products.

PubMed

Giri, Anupam; Zelinkova, Zuzana; Wenzl, Thomas

2017-12-01

For the implementation of Regulation (EC) No 2065/2003 related to smoke flavourings used or intended for use in or on foods a method based on solid-phase micro extraction (SPME) GC/MS was developed for the characterisation of liquid smoke products. A statistically based experimental design (DoE) was used for method optimisation. The best general conditions to quantitatively analyse the liquid smoke compounds were obtained with a polydimethylsiloxane/divinylbenzene (PDMS/DVB) fibre, 60°C extraction temperature, 30 min extraction time, 250°C desorption temperature, 180 s desorption time, 15 s agitation time, and 250 rpm agitation speed. Under the optimised conditions, 119 wood pyrolysis products including furan/pyran derivatives, phenols, guaiacol, syringol, benzenediol, and their derivatives, cyclic ketones, and several other heterocyclic compounds were identified. The proposed method was repeatable (RSD% <5) and the calibration functions were linear for all compounds under study. Nine isotopically labelled internal standards were used for improving quantification of analytes by compensating matrix effects that might affect headspace equilibrium and extractability of compounds. The optimised isotope dilution SPME-GC/MS based analytical method proved to be fit for purpose, allowing the rapid identification and quantification of volatile compounds in liquid smoke flavourings.

Metabolites of Trichoderma species isolated from damp building materials.

PubMed

McMullin, David R; Renaud, Justin B; Barasubiye, Tharcisse; Sumarah, Mark W; Miller, J David

2017-07-01

Buildings that have been flooded often have high concentrations of Trichoderma spores in the air while drying. Inhaled spores and spore and mycelial fragments contain large amounts of fungal glucan and natural products that contribute to the symptoms associated with indoor mould exposures. In this study, we considered both small molecules and peptaibol profiles of T. atroviride, T. koningiopsis, T. citrinoviride, and T. harzianum strains obtained from damp buildings in eastern Canada. Twenty-residue peptaibols and sorbicillin-derived metabolites (1-6) including a new structure, (R)-vertinolide (1), were characterized from T. citrinoviride. Trichoderma koningiopsis produced several koninginins (7-10), trikoningin KA V, and the 11-residue lipopeptaibols trikoningin KB I and trikoningin KB II. Trichoderma atroviride biosynthesized a mixture of 19-residue trichorzianine-like peptaibols, whereas T. harzianum produced 18-residue trichokindin-like peptaibols and the 11-residue harzianin HB I that was subsequently identified from the studied T. citrinoviride strain. Two α-pyrones, 6-pentyl-pyran-2-one (11) and an oxidized analog (12), were produced by both T. atroviride and T. harzianum. Aside from exposure to low molecular weight natural products, inhalation of Trichoderma spores and mycelial fragments may result in exposure to membrane-disrupting peptaibols. This investigation contributes to a more comprehensive understanding of the biologically active natural products produced by fungi commonly found in damp buildings.

Design and Discovery of N -(2-Methyl-5'-morpholino-6'-((tetrahydro-2 H -pyran-4-yl)oxy)-[3,3'-bipyridin]-5-yl)-3-(trifluoromethyl)benzamide (RAF709): A Potent, Selective, and Efficacious RAF Inhibitor Targeting RAS Mutant Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishiguchi, Gisele A.; Rico, Alice; Tanner, Huw

RAS oncogenes have been implicated in >30% of human cancers, all representing high unmet medical need. The exquisite dependency on CRAF kinase in KRAS mutant tumors has been established in genetically engineered mouse models and human tumor cells. To date, many small molecule approaches are under investigation to target CRAF, yet kinase-selective and cellular potent inhibitors remain challenging to identify. Herein, we describe 14 (RAF709) [Aversa, Biaryl amide compounds as kinase inhibitors and their preparation. WO 2014151616, 2014], a selective B/C RAF inhibitor, which was developed through a hypothesis-driven approach focusing on drug-like properties. A key challenge encountered in themore » medicinal chemistry campaign was maintaining a balance between good solubility and potent cellular activity (suppression of pMEK and proliferation) in KRAS mutant tumor cell lines. We investigated the small molecule crystal structure of lead molecule 7 and hypothesized that disruption of the crystal packing would improve solubility, which led to a change from N-methylpyridone to a tetrahydropyranyl oxy-pyridine derivative. 14 proved to be soluble, kinase selective, and efficacious in a KRAS mutant xenograft model.« less

Synthesis, biological evaluation and molecular modelling of diversely functionalized heterocyclic derivatives as inhibitors of acetylcholinesterase/butyrylcholinesterase and modulators of Ca2+ channels and nicotinic receptors.

PubMed

Marco, José L; de los Ríos, Cristóbal; García, Antonio G; Villarroya, Mercedes; Carreiras, M Carmo; Martins, Carla; Eleutério, Ana; Morreale, Antonio; Orozco, M; Luque, F Javier

2004-05-01

The synthesis and the biological activity of compounds 5-40 as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as modulators of voltage-dependent Ca(2+) channels and nicotinic receptors, are described. These molecules are tacrine analogues, which have been prepared from polyfunctionalized 6-amino-5-cyano-4H-pyrans, 6-amino-5-cyano-pyridines and 5-amino-2-aryl-3-cyano-1,3-oxazoles via Friedländer reaction with selected cycloalkanones. These compounds are moderate acetylcholinesterase and butyrylcholinesterase inhibitors, the BuChE/AChE selectivity of the most active molecules ranges from 10.0 (compound 29) to 76.9 (compound 16). Interestingly, the 'oxazolo-tacrine' derivatives are devoid of any activity. All compounds showed an important inhibitory effect on the nicotinic acetylcholine receptor. Most of them also blocked L-type Ca(2+) channels, and three of them, 64, 19 and 67, the non-L type of Ca(2+) channels. Molecular modelling studies suggest that these compounds might bind at the peripheral binding site of AChE, which opens the possibility to design inhibitors able to bind at both, the catalytic and peripheral binding sites of the enzyme.

Recent developments in the synthesis of acetylcholinesterase inhibitors.

PubMed

Marco, José L; Carreiras, M Carmo

2003-09-01

The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described. These compounds are tacrine analogues that have been prepared from readily available polyfunctionalized ethyl [6-amino-5-cyano-4H-pyran]-3-carboxylates (9, 10), ethyl [6-amino-5-cyanopyridine]-3-carboxylates (7, 8), 2-amino-3-cyano-4,5-diarylfurans (17-19) and 2-amino-3-cyano-4,5-diphenylthiophene (20) via Friedländer condensation with selected ketones. These compounds are competitive and, in a few cases, non-competitive inhibitors for AChE, the most potent being compound (14), though three-fold less active than tacrine. The BuChE inhibitory activity is only significant in compounds 11 and 14, ten-fold less active than tacrine. Furthermore, the products 12 and 13 are selective and moderate AChE inhibitors.

Physical and optical properties of DCJTB dye for OLED display applications: Experimental and theoretical investigation

NASA Astrophysics Data System (ADS)

Kurban, Mustafa; Gündüz, Bayram

2017-06-01

In this study, 4-(dicyanomethylene)-2-tert-butyl-6-(1,1,7,7-tetramethyljulolidin-4-yl-vinyl)-4H-pyran (DCJTB) was achieved using the experimental and theoretical studies. The electronic, optical and spectroscopic properties of DCJTB molecule were first investigated by performing experimental both solution and thin film techniques and then theoretical calculations. Theoretical results showed that one intense electronic transition is 505.26 nm a quite reasonable and agreement with the measured experimental data 505.00 and 503 nm with solution technique and film technique, respectively. Experimental and simple models were also taken into consideration to calculate the optical refractive index (n) of DCJTB molecule. The structural and electronic properties were next calculated using density functional theory (DFT) with B3LYP/6-311G (d, p) basis set. UV, FT-IR spectra characteristics and the electronic properties, such as frontier orbitals, and band gap energy (Eg) of DCJTB were also recorded time-dependent (TD) DFT approach. The theoretical Eg value were found to be 2.269 eV which is consistent with experimental results obtained from solution technique for THF solvent (2.155 eV) and literature (2.16 eV). The results herein obtained reveal that solution is simple, cost-efficient and safe for optoelectronic applications when compared with film technique.

TOPICAL REVIEW: Tetrathiapentalene-based organic conductors

NASA Astrophysics Data System (ADS)

Misaki, Yohji

2009-04-01

The synthesis, structure and properties of tetrathiapentalene-based (TTP) organic conductors are reviewed. Among various TTP-type donors, bis-fused tetrathiafulvalene, 2,5-bis(1,3-dithiol-2-ylidene)-1,3,4,6-tetrathiapentalene (BDT-TTP) and its derivatives afford many metallic radical cation salts stable down to low temperatures, regardless of the size and shape of the counter anions. Most BDT-TTP conductors have a β-type donor arrangement with almost uniform stacks. Introduction of appropriate substituents results in molecular packing that differs from the β-type. A vinylogous TTP, 2-(1,3-dithiol-2-ylidene)-5-(2-ethanediylidene-1,3-dithiole)-1,3,4,6-tetrathiapentalene (DTEDT) has yielded an organic superconductor (DTEDT)3Au(CN)2 as well as metallic radical cation salts, regardless of the counter anions. (Thio)pyran analogs of TTP, namely (T)PDT-TTP and its derivatives produce molecular conductors with novel molecular arrangements. A TTP analog with reduced π-electron system 2,5-bis(1,3-dithian-2-ylidene)-1,3,4,6-tetrathiapentalene (BDA-TTP) has afforded several organic superconductors. Highly conducting molecular metals with unusual oxidation states (+1, +5/3 and neutral) have been developed on the basis of 2,5-bis(1,3-dithiol-2-ylidene)-1,3,4,6-tetrathiapentalene (BDT-TTP) derivatives and analogous metal derivatives M(dt)2 (M = Ni, Au).

A Novel Bat-Shaped Dicyanomethylene-4H-pyran-Functionalized Naphthalimide for Highly Efficient Solution-Processed Multilevel Memory Devices.

PubMed

Zhang, Qi-Jian; Miao, Shi-Feng; Li, Hua; He, Jing-Hui; Li, Na-Jun; Xu, Qing-Feng; Chen, Dong-Yun; Lu, Jian-Mei

2017-06-19

Small-molecule-based multilevel memory devices have attracted increasing attention because of their advantages, such as super-high storage density, fast reading speed, light weight, low energy consumption, and shock resistance. However, the fabrication of small-molecule-based devices always requires expensive vacuum-deposition techniques or high temperatures for spin-coating. Herein, through rational tailoring of a previous molecule, DPCNCANA (4,4'-(6,6'-bis(2-octyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-9H,9'H-[3,3'-bicarbazole]-9,9'-diyl)dibenzonitrile), a novel bat-shaped A-D-A-type (A-D-A=acceptor-donor-acceptor) symmetric framework has been successfully synthesized and can be dissolved in common solvents at room temperature. Additionally, it has a low-energy bandgap and dense intramolecular stacking in the film state. The solution-processed memory devices exhibited high-performance nonvolatile multilevel data-storage properties with low switching threshold voltages of about -1.3 and -2.7 V, which is beneficial for low power consumption. Our result should prompt the study of highly efficient solution-processed multilevel memory devices in the field of organic electronics. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Detection of phytoconstituents in column fractions of n-hexane extract of Goldcrest honey exhibiting anti-Helicobacter pylori activity.

PubMed

Manyi-Loh, Christy E; Clarke, Anna M; Ndip, Roland N

2012-04-01

Alternative therapy for Helicobacter pylori eradication from natural products is gaining much attention. This study sought to isolate and characterize the fraction responsible for the antibacterial activity in Goldcrest (GC) n-hexane extract. Thin-layer chromatography (TLC) of the extract was carried out on Silica gel plates to determine the presence of chemical compounds, which were separated and partially purified by column chromatography. The obtained fractions GCCL, GCF2, GCF3 and GCF4 were tested for anti-H. pylori activity using the broth microdilution method. Volatile compounds in the active fractions were identified by gas chromatography-mass spectrometry (GC-MS) analysis. MINITAB was used for statistical analysis at 95% confidence interval. The best antibacterial activity was exhibited by GCF3 (5 mg/mL), which was composed of many compounds with known antimicrobial and antioxidant properties. A total of 16 volatile compounds were identified from fractions GCF2, GCF3 and GCF4 into the following families; alcohol, ketone, aliphatic acid, benzene compound, hydrocarbon, furan and pyran derivatives. The demonstration of antibacterial activity by the column fractions of GC n-hexane extract may provide new lead molecules that could serve as selective agents for H. pylori chemotherapy and control. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

Characterization of substituted aryl meroterpenoids from red seaweed Hypnea musciformis as potential antioxidants.

PubMed

Chakraborty, Kajal; Joseph, Deepu; Joy, Minju; Raola, Vamshi Krishna

2016-12-01

The ethyl acetate fraction of red seaweed Hypnea musciformis was purified to yield three substituted aryl meroterpenoids, namely, 2-(tetrahydro-5-(4-hydroxyphenyl)-4-pentylfuran-3-yl)-ethyl-4-hydroxybenzoate (1), 2-2-[(4-hydroxybenzoyl)-oxy]-ethyl-4-methoxy-4-2-[(4-methylpentyl)oxy]-3,4-dihydro-2H-6-pyranylbutanoic acid (2) and 3-((5-butyl-3-methyl-5,6-dihydro-2H-pyran-2-yl)-methyl)-4-methoxy-4-oxobutyl benzoate (3). The structures of these compounds, as well as their relative stereochemistries, were confirmed by exhaustive NMR spectroscopic data analyses. Compound 1 exhibited similar 2,2'-diphenylpicrylhydrazyl radical inhibiting and Fe(2+) ion chelating activities (IC50 25.05 and 350.7μM, respectively) as that of commercial antioxidant gallic acid (IC50 32.3 and 646.6μM, respectively), followed by 3 (IC50 231.2 and 667.9μM, respectively), and 2 (IC50 322.4 and 5115.3μM, respectively), in descending order of activities. Structure-activity relationship analysis revealed that the antioxidant activities of these compounds were directly proportional to the steric and hydrophobic parameters. The seaweed derived aryl meroterpenoids might serve as potential lead antioxidative molecules for use in pharmaceutical and food industries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Changes of Metabolomic Profile in Helianthus annuus under Exposure to Chromium(VI) Studied by capHPLC-ESI-QTOF-MS and MS/MS

PubMed Central

Gonzalez Ibarra, Alan Alexander; Wrobel, Kazimierz; Yanez Barrientos, Eunice; Corrales Escobosa, Alma Rosa; Gutierrez Corona, J. Felix; Enciso Donis, Israel

2017-01-01

The application of capHPLC-ESI-QTOF-MS and MS/MS to study the impact of Cr(VI) on metabolites profile in Helianthus annuus is reported. Germinated seeds were grown hydroponically in the presence of Cr(VI) (25 mgCr/L) and root extracts of the exposed and control plants were analyzed by untargeted metabolomic approach. The main goal was to detect which metabolite groups were mostly affected by Cr(VI) stress; two data analysis tools (ProfileAnalysis, Bruker, and online XCMS) were used under criteria of intensity threshold 5 · 104 cps, fold change ≥ 5, and p ≤ 0.01, yielding precursor ions. Molecular formulas were assigned based on data processing with two computational tools (SIRIUS and MS-Finder); annotation of candidate structures was performed by database search using CSI:FingerID and MS-Finder. Even though ultimate identification has not been achieved, it was demonstrated that secondary metabolism became activated under Cr(VI) stress. Among 42 candidate compounds returned from database search for seven molecular formulas, ten structures corresponded to isocoumarin derivatives and eleven were sesquiterpenes or sesquiterpene lactones; three benzofurans and four glycoside or pyrane derivatives of phenolic compounds were also suggested. To gain further insight on the effect of Cr(VI) in sunflower, isocoumarins and sesquiterpenes were selected as the target compounds for future study. PMID:29359067

Evaluation of Extraction and Degradation Methods to Obtain Chickpeasaponin B1 from Chickpea (Cicer arietinum L.).

PubMed

Cheng, Kun; Gao, Hua; Wang, Rong-Rong; Liu, Yang; Hou, Yu-Xue; Liu, Xiao-Hong; Liu, Kun; Wang, Wei

2017-02-21

The objective of this research is to implement extraction and degradation methods for the obtainment of 3- O -[α-l-rhamnopyranosyl-(1→2)-β-d-galactopyranosyl] soyasapogenol B (chickpeasaponin B1) from chickpea. The effects of microwave-assisted extraction (MAE) processing parameters-such as ethanol concentration, solvent/solid ratio, extraction temperature, microwave irradiation power, and irradiation time-were evaluated. Using 1g of material with 8 mL of 70% aqueous ethanol and an extraction time of 10 min at 70 °C under irradiation power 400W provided optimal extraction conditions. Compared with the conventional extraction techniques, including heat reflux extraction (HRE), Soxhlet extraction (SE), and ultrasonic extraction (UE), MAE produced higher extraction efficiency under a lower extraction time. DDMP (2,3-dihydro-2,5-dihydroxy-6-methyl-4 H -pyran-4-one) saponin can be degraded to structurally stable saponin B by the loss of its DDMP group. The influence of pH and the concentration of potassium hydroxide on transformation efficiency of the target compound was investigated. A solution of 0.25 M potassium hydroxide in 75% aqueous ethanol was suitable for converting the corresponding DDMP saponins of chickpeasaponin B1. The implementation by the combining MAE technique and alkaline hydrolysis method for preparing chickpeasaponin B1 provides a convenient technology for future applications.

Discovery and Validation of a New Class of Small Molecule Toll-Like Receptor 4 (TLR4) Inhibitors

PubMed Central

Neal, Matthew D.; Jia, Hongpeng; Eyer, Benjamin; Good, Misty; Guerriero, Christopher J.; Sodhi, Chhinder P.; Afrazi, Amin; Prindle, Thomas; Ma, Congrong; Branca, Maria; Ozolek, John; Brodsky, Jeffrey L.; Wipf, Peter; Hackam, David J.

2013-01-01

Many inflammatory diseases may be linked to pathologically elevated signaling via the receptor for lipopolysaccharide (LPS), toll-like receptor 4 (TLR4). There has thus been great interest in the discovery of TLR4 inhibitors as potential anti-inflammatory agents. Recently, the structure of TLR4 bound to the inhibitor E5564 was solved, raising the possibility that novel TLR4 inhibitors that target the E5564-binding domain could be designed. We utilized a similarity search algorithm in conjunction with a limited screening approach of small molecule libraries to identify compounds that bind to the E5564 site and inhibit TLR4. Our lead compound, C34, is a 2-acetamidopyranoside (MW 389) with the formula C17H27NO9, which inhibited TLR4 in enterocytes and macrophages in vitro, and reduced systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. Molecular docking of C34 to the hydrophobic internal pocket of the TLR4 co-receptor MD-2 demonstrated a tight fit, embedding the pyran ring deep inside the pocket. Strikingly, C34 inhibited LPS signaling ex-vivo in human ileum that was resected from infants with necrotizing enterocolitis. These findings identify C34 and the β-anomeric cyclohexyl analog C35 as novel leads for small molecule TLR4 inhibitors that have potential therapeutic benefit for TLR4-mediated inflammatory diseases. PMID:23776545

Prenylated flavonoids as potent phosphodiesterase-4 inhibitors from Morus alba: Isolation, modification, and structure-activity relationship study.

PubMed

Guo, Yan-Qiong; Tang, Gui-Hua; Lou, Lan-Lan; Li, Wei; Zhang, Bei; Liu, Bo; Yin, Sheng

2018-01-20

The bioassay-guided phytochemical study of a traditional Chinese medicine Morus alba led to the isolation of 18 prenylated flavonoids (1-18), of which (±)-cyclomorusin (1/2), a pair of enantiomers, and 14-methoxy-dihydromorusin (3) are the new ones. Subsequent structural modification of the selected components by methylation, esterification, hydrogenation, and oxidative cyclization led to 14 more derivatives (19-32). The small library was screened for its inhibition against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among them, nine compounds (1-5, 8, 10, 16, and 17) exhibited remarkable activities with IC 50 values ranging from 0.0054 to 0.40 μM, being more active than the positive control rolipram (IC 50  = 0.62 μM). (+)-Cyclomorusin (1), the most active natural PDE4 inhibitor reported so far, also showed a high selectivity across other PDE members with the selective fold greater than 55. The SAR study revealed that the presence of prenyls at C-3 and/or C-8, 2H-pyran ring D, and the phenolic hydroxyl groups were important to the activity, which was further supported by the recognition mechanism study of the inhibitors with PDE4 by using molecular modeling. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

CJ-13610, an orally active inhibitor of 5-lipoxygenase is efficacious in preclinical models of pain.

PubMed

Cortes-Burgos, Luz A; Zweifel, Ben S; Settle, Steven L; Pufahl, Robert A; Anderson, Gary D; Hardy, Medora M; Weir, Dana E; Hu, George; Happa, Fernando A; Stewart, Zachary; Muthian, Shanmugam; Graneto, Matthew J; Masferrer, Jaime L

2009-09-01

Zileuton, a redox and iron chelator 5-lipoxygenase (5-LOX) inhibitor and, leukotriene receptor antagonists are presently used clinically in the long term treatment of asthma. Recent data implicate 5-LOX pathway in pain signaling. We report 5-LOX expression in the central nervous system (CNS) and analyze the pain efficacy of a new class of non redox, non iron chelating 5-LOX inhibitor. CJ-13610, 4-(3-(4-(2-methyl-1H-imidazol-1-yl) phenylthio) phenyl)-tetrahydro-2H-pyran-4-carboxamide, demonstrated antihyperalgesic activity in inflammatory pain models including the acute carrageenan model and the chronic inflammatory model using complete Freund's adjuvant. Following complete Freund's adjuvant stimulus leukotrieneB(4) concentration in the brain was elevated (9+/-1 ng/g, mean+/-S.E.M.) by about 3 times that of the control group (3+/-0.11, mean+/-S.E.M.). Hyperalgesia and leukotrieneB(4) concentration were both reversed following CJ-13610 treatment. Furthermore, we demonstrate CJ-13610 efficacy against osteoarthritis like pain using the rat medial meniscal transection model. CJ-13610 at oral doses of 0.6, 2 and 6 mg/kg/day reversed two modalities of pain in this model; tactile allodynia and weight bearing differential. Taken together, these data suggest that 5-LOX pathway and the leukotriene products are important mediators of pain.

Determination of captopril in biological samples by high-performance liquid chromatography with ThioGlo 3 derivatization.

PubMed

Aykin, N; Neal, R; Yusof, M; Ercal, N

2001-11-01

Captopril, a well-known angiotensin converting enzyme (ACE) inhibitor, is widely used for treatment of arterial hypertension. Recent studies suggest that it may also act as a scavenger of free radicals because of its thiol group. Therefore, the present study describes a rapid, sensitive and relatively simple method for the detection of captopril in biological tissues with reverse-phase HPLC. Captopril was first derivatized with ThioGlo 3 [3H-Naphto[2,1-b]pyran,9-acetoxy-2-(4-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)phenyl-3-oxo-)]. It was then detected by fluorescence-HPLC using an Astec C(18) column as the stationary phase and a water:acetonitrile:acetic acid:phosphoric acid mixture (50:50; 1 mL/L acids) as the mobile phase (excitation wavelength, 365 nm; emission wavelength, 445 nm). The calibration curve for captopril was linear over a range of 10-2500 nM and the coefficient of variation acquired for the within- and between-run precision for captopril was 0.5 and 3.8%, respectively. The detection limit of captopril with this method was found to be 200 fmol/20 microL injection volume. Its relative recovery from biological samples was determined to the range from 93.3 to 105.3%. Based on these results, we believe that our method is advantageous for captopril determination. Copyright 2001 John Wiley & Sons, Ltd.

Identification of prenylated pterocarpans and other isoflavonoids in Rhizopus spp. elicited soya bean seedlings by electrospray ionisation mass spectrometry.

PubMed

Simons, Rudy; Vincken, Jean-Paul; Bohin, Maxime C; Kuijpers, Tomas F M; Verbruggen, Marian A; Gruppen, Harry

2011-01-15

Phytoalexins from soya are mainly characterised as prenylated pterocarpans, the glyceollins. Extracts of non-soaked and soaked soya beans, as well as that of soya seedlings, grown in the presence of Rhizopus microsporus var. oryzae, were screened for the presence of prenylated flavonoids with a liquid chromatography/mass spectrometry (LC/MS)-based screening method. The glyceollins I-III and glyceollidins I-II, belonging to the isoflavonoid subclass of the pterocarpans, were tentatively assigned. The formation of these prenylated pterocarpans was accompanied by that of other prenylated isoflavonoids of the subclasses of the isoflavones and the coumestans. It was estimated that approx. 40% of the total isoflavonoid content in Rhizopus-challenged soya bean seedlings were prenylated pterocarpans, whereas 7% comprised prenylated isoflavones and prenylated coumestans. The site of prenylation (A-ring or B-ring) of the prenylated isoflavones was tentatively annotated using positive-ion mode MS by comparing the (1,3) A(+) retro-Diels-Alder (RDA) fragments of prenylated and non-prenylated isoflavones. Furthermore, the fragmentation pathways of the five pterocarpans in negative-ion (NI) mode were proposed, which involved the cleavage of the C-ring and/or D-ring. The absence of the ring-closed prenyl (pyran or furan) gave exclusively -H(2) O(x,y) RDA fragments, whereas its presence gave predominantly the common RDA fragments. Copyright © 2010 John Wiley & Sons, Ltd.

Volatile Compounds in Honey: A Review on Their Involvement in Aroma, Botanical Origin Determination and Potential Biomedical Activities

PubMed Central

Manyi-Loh, Christy E.; Ndip, Roland N.; Clarke, Anna M.

2011-01-01

Volatile organic compounds (VOCs) in honey are obtained from diverse biosynthetic pathways and extracted by using various methods associated with varying degrees of selectivity and effectiveness. These compounds are grouped into chemical categories such as aldehyde, ketone, acid, alcohol, hydrocarbon, norisoprenoids, terpenes and benzene compounds and their derivatives, furan and pyran derivatives. They represent a fingerprint of a specific honey and therefore could be used to differentiate between monofloral honeys from different floral sources, thus providing valuable information concerning the honey’s botanical and geographical origin. However, only plant derived compounds and their metabolites (terpenes, norisoprenoids and benzene compounds and their derivatives) must be employed to discriminate among floral origins of honey. Notwithstanding, many authors have reported different floral markers for honey of the same floral origin, consequently sensory analysis, in conjunction with analysis of VOCs could help to clear this ambiguity. Furthermore, VOCs influence honey’s aroma described as sweet, citrus, floral, almond, rancid, etc. Clearly, the contribution of a volatile compound to honey aroma is determined by its odor activity value. Elucidation of the aroma compounds along with floral origins of a particular honey can help to standardize its quality and avoid fraudulent labeling of the product. Although only present in low concentrations, VOCS could contribute to biomedical activities of honey, especially the antioxidant effect due to their natural radical scavenging potential. PMID:22272147

Cytotoxic and Antifungal Constituents Isolated from the Metabolites of Endophytic Fungus DO14 from Dendrobium officinale.

PubMed

Wu, Ling-Shang; Jia, Min; Chen, Ling; Zhu, Bo; Dong, Hong-Xiu; Si, Jin-Ping; Peng, Wei; Han, Ting

2015-12-22

Two novel cytotoxic and antifungal constituents, (4S,6S)-6-[(1S,2R)-1, 2-dihydroxybutyl]-4-hydroxy-4-methoxytetrahydro-2H-pyran-2-one (1), (6S,2E)-6-hydroxy-3-methoxy-5-oxodec-2-enoic acid (2), together with three known compounds, LL-P880γ (3), LL-P880α (4), and Ergosta-5,7,22-trien-3b-ol (5) were isolated from the metabolites of endophytic fungi from Dendrobium officinale. The chemical structures were determined based on spectroscopic methods. All the isolated compounds 1-5 were evaluated by cytotoxicity and antifungal effects. Our present results indicated that compounds 1-4 showed notable anti-fungal activities (minimal inhibitory concentration (MIC) ≤ 50 μg/mL) for all the tested pathogens including Candida albicans, Cryptococcus neoformans, Trichophyton rubrum, Aspergillus fumigatus. In addition, compounds 1-4 possessed notable cytotoxcities against human cancer cell lines of HL-60 cells with the IC50 values of below 100 μM. Besides, compounds 1, 2, 4 and 5 showed strong cytotoxities on the LOVO cell line with the IC50 values were lower than 100 μM. In conclusion, our study suggested that endophytic fungi of D. officinale are great potential resources to discover novel agents for preventing or treating pathogens and tumors.

2-[(4-Chloro­phen­yl)selan­yl]-3,4-di­hydro-2H-benzo[h]chromene-5,6-dione: crystal structure and Hirshfeld analysis

PubMed Central

Prado, Karinne E.; Name, Luccas L.; Jotani, Mukesh M.

2017-01-01

The title organoselenium compound, C19H13ClO3Se {systematic name: 2-[(4-chloro­phen­yl)selan­yl]-2H,3H,4H,5H,6H-naphtho­[1,2-b]pyran-5,6-dione}, has the substituted 2-pyranyl ring in a half-chair conformation with the methyl­ene-C atom bound to the methine-C atom being the flap atom. The dihedral angle between the two aromatic regions of the mol­ecule is 9.96 (9)° and indicates a step-like conformation. An intra­molecular Se⋯O inter­action of 2.8122 (13) Å is noted. In the crystal, π–π contacts between naphthyl rings [inter-centroid distance = 3.7213 (12) Å] and between naphthyl and chloro­benzene rings [inter-centroid distance = 3.7715 (13) Å], along with C—Cl⋯π(chloro­benzene) contacts, lead to supra­molecular layers parallel to the ab plane, which are connected into a three-dimensional architecture via methyl­ene-C—H⋯O(carbon­yl) inter­actions. The contributions of these and other weak contacts to the Hirshfeld surface is described. PMID:28638659

Total Synthesis of Biselyngbyolide B and Its C21-C22 Z-Isomer.

PubMed

Kämmler, Lena; Maier, Martin E

2018-04-20

Investigations toward the synthesis of the 18-membered macrolactone biselyngbyolide B (2) from a C1-C13 and a C14-C23 fragment are described. As a key reaction in the synthesis of the C1-C13 fragment, we used an asymmetric propargylation of chiral vinylketene silyl N, O-acetal 12. Access to a C14-C23 fragment featuring a skipped diene and a sensitive allyl alcohol function was initially attempted via reductive fragmentation of a pyran template. However, this ring opening on iodide 32 with t-BuLi led to dienynol 33 with a 21 Z double bond. With a silyl protecting group at 3-OH and by implementing an intramolecular Stille coupling for macrolactonization, the 21 Z-isomer of biselyngbyolide B (47) was obtained. For preparation of a C14-C23 fragment with the 21 E-configuration, a cross-coupling of vinylstannane 48 with 4-bromocrotonate (49) set the configuration of the two double bonds. Biselyngbyolide B (2) was then accessed by an intramolecular Heck coupling. In preliminary biological cytotoxicity assays, 2 turned out to be active, whereas the 21 Z-isomer 47 was much less active. The 3-OMEM analogue 40 was devoid of activity. These results support the notion that the side chain with the correct configuration is relevant for binding to the Ca 2+ -ATPase and the biological activity.

Development of a see-through hollow cathode discharge lamp for (Li/Ne) optogalvanic studies

NASA Astrophysics Data System (ADS)

Saini, V. K.; Kumar, P.; Sarangpani, K. K.; Dixit, S. K.; Nakhe, S. V.

2017-09-01

Development of a demountable and see-through hollow cathode (HC) discharge lamp suitable for optogalvanic (OG) spectroscopy is described. The design of the HC lamp is simple, compact, and inexpensive. Lithium, investigated rarely by the OG method, is selected for cathode material as its isotopes are important for nuclear industry. The HC lamp is characterized electrically and optically for discharge oscillations free OG effect. Strong OG signals of lithium as well as neon (as buffer gas) are produced precisely upon copper vapor laser pumped tunable dye laser irradiation. The HC lamp is capable of generating a clean OG resonance spectrum in the available dye laser wavelength scanning range (627.5-676 nm) obtained with 4-(Dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran dye. About 28 resonant OG lines are explicitly observed. Majority of them have been identified using j-l coupling scheme and assigned to the well-known neon transitions. One line that corresponds to wavelength near about 670.80 nm is assigned to lithium and resolved for its fine (2S1/2 → 2P1/2, 3/2) transitions. These OG transitions allow 0.33 cm-1 accuracy and can be used to supplement the OG transition data available from other sources to calibrate the wavelength of a scanning dye laser with precision at atomic levels.

Development of a see-through hollow cathode discharge lamp for (Li/Ne) optogalvanic studies.

PubMed

Saini, V K; Kumar, P; Sarangpani, K K; Dixit, S K; Nakhe, S V

2017-09-01

Development of a demountable and see-through hollow cathode (HC) discharge lamp suitable for optogalvanic (OG) spectroscopy is described. The design of the HC lamp is simple, compact, and inexpensive. Lithium, investigated rarely by the OG method, is selected for cathode material as its isotopes are important for nuclear industry. The HC lamp is characterized electrically and optically for discharge oscillations free OG effect. Strong OG signals of lithium as well as neon (as buffer gas) are produced precisely upon copper vapor laser pumped tunable dye laser irradiation. The HC lamp is capable of generating a clean OG resonance spectrum in the available dye laser wavelength scanning range (627.5-676 nm) obtained with 4-(Dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran dye. About 28 resonant OG lines are explicitly observed. Majority of them have been identified using j-l coupling scheme and assigned to the well-known neon transitions. One line that corresponds to wavelength near about 670.80 nm is assigned to lithium and resolved for its fine ( 2 S 1/2 → 2 P 1/2, 3/2 ) transitions. These OG transitions allow 0.33 cm -1 accuracy and can be used to supplement the OG transition data available from other sources to calibrate the wavelength of a scanning dye laser with precision at atomic levels.

Tunable Two-color Luminescence and Host-guest Energy Transfer of Fluorescent Chromophores Encapsulated in Metal-Organic Frameworks

NASA Astrophysics Data System (ADS)

Yan, Dongpeng; Tang, Yanqun; Lin, Heyang; Wang, Dan

2014-03-01

Co-assembly of chromophore guests with host matrices can afford materials which have photofunctionalities different from those of individual components. Compared with clay and zeolite materials, the use of metal-organic frameworks (MOFs) as a host structure for fabricating luminescent host-guest materials is still at an early stage. Herein, we report the incorporation of a laser dye, 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCM), into stilbene-based and naphthalene-based MOF systems. The resulting materials exhibit blue/red two-color emission, and the intensity ratio of blue to red fluorescence varies in different planes within the MOF crystal as detected by 3D confocal fluorescence microscopy. The observed changes in ratiometric fluorescence suggest the occurrence of energy transfer from MOF host to DCM molecules, which can be further confirmed by periodic density functional theoretical (DFT) calculations. Moreover, selective changes in luminescence behavior are observed on treating the guest@MOF samples with volatile organic compounds (methanol, acetone and toluene), indicating that these host-guest systems have potential applications as fluorescence sensors. It can be expected that by rational selection of MOF hosts and guest chromophores with suitable emissive colors and energy levels, a wide variety of multi-color luminescent and energy-transfer systems can readily be prepared in a similar manner.

Nickel-catalyzed cycloadditions of unsaturated hydrocarbons, aldehydes, and ketones.

PubMed

Tekavec, Thomas N; Louie, Janis

2008-04-04

The nickel-catalyzed cycloaddition of unsaturated hydrocarbons and carbonyls is reported. Diynes and enynes were used as coupling partners. Carbonyl substrates include both aldehdyes and ketones. Reactions of diynes and aldehydes afforded the [3,3] electrocyclic ring-opened tautomers, rather than pyrans, in high yields. The cycloaddition reaction of enynes and aldehydes afforded two distinct products. A new carbon-carbon bond is formed, prior to a competitive beta-hydrogen elimination of a nickel alkoxide, between the carbonyl carbon and either one of the carbons of the olefin or the alkyne. The steric hindrance of the enyne greatly affected the chemoselectivity of the cycloaddition of enynes and aldehydes. In some cases, dihydropyran was also formed. The scope of the cycloaddition reaction was expanded to include the coupling of enynes and ketones. No beta-hydrogen elimination was observed in cycloaddition reaction of enynes and ketones. Instead, C-O bond-forming reductive elimination occurred exclusively to afford dihydropyrans in excellent yields. In all cases, complete chemoselectivity was observed; only dihydropyrans where the carbonyl carbon forms a carbon-carbon bond with a carbon of the olefin, rather than of the alkyne, were observed. All cycloaddition reactions occur at room temperature and employ nickel catalysts bearing the hindered 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) or its saturated analogue, 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazolin-2-ylidene (SIPr).

Nickel-Catalyzed Cycloadditions of Unsaturated Hydrocarbons, Aldehydes, and Ketones

PubMed Central

Tekavec, Thomas N.

2014-01-01

The nickel-catalyzed cycloaddition of unsaturated hydrocarbons and carbonyls is reported. Diynes and enynes were used as coupling partners. Carbonyl substrates include both aldehdyes and ketones. Reactions of diynes and aldehydes afforded the [3, 3] electrocyclic ring-opened tautomers, rather than pyrans, in high yields. The cycloaddition reaction of enynes and aldehydes afforded two distinct products. A new carbon–carbon bond is formed, prior to a competitive β-hydrogen elimination of a nickel alkoxide, between the carbonyl carbon and either one of the carbons of the olefin or the alkyne. The steric hindrance of the enyne greatly affected the chemoselectivity of the cycloaddition of enynes and aldehydes. In some cases, dihydropyran was also formed. The scope of the cycloaddition reaction was expanded to include the coupling of enynes and ketones. No β-hydrogen elimination was observed in cycloaddition reaction of enynes and ketones. Instead, C–O bond-forming reductive elimination occurred exclusively to afford dihydropyrans in excellent yields. In all cases, complete chemoselectivity was observed; only dihydropyrans where the carbonyl carbon forms a carbon–carbon bond with a carbon of the olefin, rather than of the alkyne, were observed. All cycloaddition reactions occur at room temperature and employ nickel catalysts bearing the hindered 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) or its saturated analogue, 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazolin-2-ylidene (SIPr). PMID:18318544

Three VO2+ complexes of the pyridoxal-derived Schiff bases: Synthesis, experimental and theoretical characterizations, and catalytic activity in a cyclocondensation reaction

NASA Astrophysics Data System (ADS)

Jafari-Moghaddam, Faezeh; Beyramabadi, S. Ali; Khashi, Maryam; Morsali, Ali

2018-02-01

Three oxovanadium(IV) complexes of the pyridoxal Schiff bases have been newly synthesized and characterized. The used Schiff bases were N,N‧-dipyridoxyl(ethylenediamine), N,N‧-dipyridoxyl(1,3-propanediamine) and N,N‧-dipyridoxyl(1,2-benzenediamine). Also, the optimized geometry, assignment of the IR bands and the Natural Bond Orbital (NBO) analysis of the complexes have been computed using the density functional theory (DFT) methods. Dianionic form of the Schiff bases (L2-) acts as a tetradentate N2O2 ligand. The coordinating atoms of the Schiff base are the phenolate oxygens and imine nitrogens, which occupy four base positions of the square-pyramidal geometry of the complexes. The oxo ligand occupies the apical position of the [VO(L)] complexes. In the optimized geometry of the complexes, the coordinated Schiff bases have more planar structure than their free form. Due to the high-energy gaps, all of the complexes are predicted to be stable. Good agreement between the experimental values and the DFT-computed results supports suitability of the optimized geometries for the complexes. The investigated complexes show high catalytic activities in synthesis of the tetrahydrobenzo[b]pyrans through a three-component cyclocondensation reaction of dimedone, malononitrile and some aromatic aldehydes. The complexes catalyzed the reaction in solvent free conditions and the catalysts were found to be reusable.

Extraction and identification of bioactive components in Sida cordata (Burm.f.) using gas chromatography-mass spectrometry.

PubMed

Ganesh, Mani; Mohankumar, Murugan

2017-09-01

Sida cordata (Burm.f.) is a pineal tropical plant in the family Malvaceae that is found throughout India and used to treat various diseases and ailments in many complementary and alternative medicine systems. This study identified the bioactive components present in whole-plant ethanol extracts of S . cordata using gas chromatography-mass spectrometry (GC-MS). Based on their retention times (RT) and mass-to-charge ratios (m/z), 29 bioactive compounds were identified: nonanoic acid, vitamin D 3 , 3-trifluroacetoxypentadecane, α-d-glucopyranoside, O-α-d-glucopyranosyl-(1.fwdarw.3)-α-d-fructofuranosyl,3,7,11,15-tetramethyl-2-hexadecan-1-ol, octadecanoic acid, ethyl ester, phytol, 9,12-octadecadienoic acid, methyl ester (E,E), 9,12,15-octadecadienoic acid, methyl ester (Z,Z,Z), oleic acid, 1,2-15,16-diepoxyhexadecane, 3-hexadecyloxycarbonyl-5-(2-hydroxyethyl)-4-methylimidazolium ion, methoxyacetic acid, 4-tetradecyl ester, 1,2-benzenedicarboxylic acid, mono (2-ethylhexyl) ester, 1-iodo-2-methylundecane, dodecane, 2,6,10-trimethyl-, 2-piperidinone-N-[4-bromo-n-butyl]-, squalene, octadecane-1-(ethenyloxy)-, Z,Z-2,5-pentadecadien-1-ol, 1-hexadecanol, 2-methyl-, spiro[androst-5ene-17,1'-cyclobutan]-2'-one-3-hydroxy-, (3a,17a)-, diethylene glycol monododecyl ether, vitamin E, cholestan-3-ol, 2-methylene-, (3a,5a)-, 2H-pyran, 2-(7-heptadecynyloxy)tetrahydro-, and cis -Z-α-bisabolene epoxide. The presence of various bioactive compounds justifies the use of this plant for treating various ailments by traditional practitioners.

Efficient protocol for isolation and purification of different soyasaponins from soy hypocotyls.

PubMed

Zhao, Dayun; Yan, Mingxia; Huang, Yuai; Sun, Xiangjun

2012-12-01

Soyasaponins are naturally occurring triterpenoid glycosides associated with many biological activities. The aim of the present study was to develop an effective method for isolation and purification of differently glycosylated, acetylated, and 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP)-conjugated soyasaponins from soy hypocotyls. Both gel filtration using Sephadex LH-20 chromatography (Amersham Pharmacia Biotech AB; elution phase: methanol, flow rate: 3.0 mL/min, sample loading: 60 mg) and high-speed countercurrent chromatography (stationary phase: n-butanol-acetic acid (5.0%, v/v), mobile phase: water flow rate: 3.0 mL/min, sample loading: 100 mg) could effectively fractionate isoflavones and soyasaponins from the crude extract with yield of soyasaponin complexes 20.5 mg and 22.3 mg, respectively. After fractionation, the soyasaponin complexes could be purified further using preparative HPLC to separate individuals. A total of nine soyasaponins, triacetyl soyasaponin Ab (yield 1.55%, HPLC purity >98%), Aa (2.68%, >99%), Ab (18.53%, >98%), Ae (0.85%, >98%), Ba (0.63%, >91%), Af (1.12%, >85%), Bb (3.45%, >98%) and Be (0.59%, >76.8%) were obtained. DDMP-conjugated groups, αg (2.06%, >85%), βg (7.59%, >85%), and γg (0.29%, >85%) that were very labile even in mild conditions, were also collected. The method described here can be used as an effective protocol to separate different soyasaponins occurring in the original sample. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization of Chemical Compounds with Antioxidant and Cytotoxic Activities in Bougainvillea x buttiana Holttum and Standl, (var. Rose) Extracts

PubMed Central

Abarca-Vargas, Rodolfo; Peña Malacara, Carlos F.; Petricevich, Vera L.

2016-01-01

Bougainvillea is widely used in traditional Mexican medicine to treat several diseases. This study was designed to characterize the chemical constituents of B. x buttiana extracts with antioxidant and cytotoxic activities using different solvents. The extraction solvents used were as follows: distilled water (dH2O), methanol (MeOH), acetone (DMK), ethanol (EtOH), ethyl acetate (EtOAc), dichloromethane (DCM), and hexane (Hex) (100%) at an extraction temperature of 26 °C. Analysis of bioactive compounds present in the B. x buttiana extracts included the application of common phytochemical screening assays, GC-MS analysis, and cytotoxicity and antioxidant assays. The results show that the highest extraction yield was observed with water and methanol. The maximum total phenolic content amount and highest antioxidant potential were obtained when extraction with methanol was used. With the exceptions of water and ethanol extractions, all other extracts showed cytotoxicity ranging between 31% and 50%. The prevailing compounds in water, methanol, ethanol, and acetone solvents were as follows: 4H-pyran-4-one, 2,3-dihydro-3, 5-dihydroxy-6-methyl (2), 2-propenoic acid, 3-(2-hydrophenyl)-(E)- (3), and 3-O-methyl-d-glucose (6). By contrast, the major components in the experiments using solvents such as EtOH, DMK, EtOAc, DCM, and Hex were n-hexadecanoic acid (8), 9,12-octadecadienoic acid (Z,Z) (12); 9-octadecenoic acid (E)- (13), and stigmasta-5,22-dien-3-ol (28). PMID:27918436

White-light-emitting organic electroluminescent devices based on interlayer sequential energy transfer

NASA Astrophysics Data System (ADS)

Deshpande, R. S.; Bulović, V.; Forrest, S. R.

1999-08-01

We demonstrate efficient, molecular organic white-light-emitting devices using vacuum-deposited thin films of red luminescent [2-methyl-6-[2-(2,3,6,7-tetrahydro-1H, 5H-benzo [ij] quinolizin-9-yl) ethenyl]-4H-pyran-4-ylidene] propane-dinitrile (DCM2), doped into blue-emitting 4, 4' bis [N-1-napthyl-N-phenyl-amino]biphenyl (α-NPD), and green-emitting tris-(8-hydroxyquinolinato) aluminum(III) (AlQ3). The luminescent layers are separated by a hole-blocking layer of 2,9-dimethyl, 4,7-diphenyl, 1,10-phenanthroline (BCP), whose thickness is on the order of a typical Förster transfer radius of 30-40 Å. Excitons formed on α-NPD sequentially transfer their energy via a Förster mechanism to AlQ3 across the BCP layer, and from AlQ3 to DCM2. This interlayer sequential energy transfer results in partial excitation of all three molecular species, thereby producing white light emission. The thickness of the blocking layer and the concentration of DCM2 in α-NPD permit the tuning of the device spectrum to achieve a balanced white emission with Commission Internationale d'Eclairage chromaticity coordinates of (0.33, 0.33). The spectrum is largely insensitive to the drive current, and the devices have a maximum luminance of 13 500 cd/m2. At a luminance of 100 cd/m2, the quantum and power efficiencies are 0.5% and 0.35 lm/W, respectively.

Accumulation of True Single Strand Breaks and AP sites in Base Excision Repair Deficient Cells

PubMed Central

Luke, April M.; Chastain, Paul D.; Pachkowski, Brian F.; Afonin, Valeriy; Takeda, Shunichi; Kaufman, David G.; Swenberg, James A.; Nakamura, Jun

2010-01-01

Single strand breaks (SSBs) are one of the most frequent DNA lesions caused by endogenous and exogenous agents. The most utilized alkaline-based assays for SSB detection frequently give false positive results due to the presence of alkali-labile sites that are converted to SSBs. Methoxyamine, an acidic O-hydroxylamine, has been utilized to measure DNA damage in cells. However, the neutralization of methoxyamine is required prior to usage. Here we developed a convenient, specific SSB assay using alkaline gel electrophoresis (AGE) coupled with a neutral O-hydroxylamine, O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (OTX). OTX stabilizes abasic sites (AP sites) to prevent their alkaline incision while still allowing for strong alkaline DNA denaturation. DNA from DT40 and isogenic polymerase β null cells exposed to methyl methanesulfonate were applied to the OTX-coupled AGE (OTX-AGE) assay. Time-dependent increases in SSBs were detected in each cell line with more extensive SSB formation in the null cells. These findings were supported by an assay that indirectly detects SSBs through measuring NAD(P)H depletion. An ARP-slot blot assay demonstrated a significant time-dependent increase in AP sites in both cell lines by 1 mM MMS compared to control. Furthermore, the Pol β-null cells displayed greater AP site formation than the parental DT40 cells. OTX use represents a facile approach for assessing SSB formation, whose benefits can also be applied to other established SSB assays. PMID:20851134

Thermogenesis, Flowering and the Association with Variation in Floral Odour Attractants in Magnolia sprengeri (Magnoliaceae)

PubMed Central

Wang, Ruohan; Xu, Sai; Liu, Xiangyu; Zhang, Yiyuan; Wang, Jianzhong; Zhang, Zhixiang

2014-01-01

Magnolia sprengeri Pamp. is an ornamentally and ecologically important tree that blooms at cold temperatures in early spring. In this study, thermogenesis and variation in the chemical compounds of floral odours and insect visitation in relation to flowering cycles were studied to increase our understanding of the role of floral thermogenesis in the pollination biology of M. sprengeri. There were five distinct floral stages across the floral cycle of this species: pre-pistillate, pistillate, pre-staminate, staminate and post-staminate. Floral thermogenesis during anthesis and consisted of two distinct peaks: one at the pistillate stage and the other at the staminate stage. Insects of five families visited M. sprengeri during the floral cycle, and sap beetles (Epuraea sp., Nitidulidae) were determined to be the most effective pollinators, whereas bees (Apis cerana, Apidae) were considered to be occasional pollinators. A strong fragrance was released during thermogenesis, consisting of 18 chemical compounds. Although the relative proportions of these compounds varied at different floral stages across anthesis, linalool, 1-iodo-2-methylundecane and 2,2,6-trimethyl-6-vinyltetrahydro-2H-pyran-3-ol were dominant. Importantly, we found that the floral blends released during the pistillate and staminate stages were very similar, and coincided with flower visitation by sap beetles and the two thermogenic episodes. Based on these results, we propose that odour acts as a signal for a reward (pollen) and that an odour mimicry of staminate-stage flowers occurs during the pistillate stage. PMID:24922537

Cochliotoxin, a Dihydropyranopyran-4,5-dione, and Its Analogues Produced by Cochliobolus australiensis Display Phytotoxic Activity against Buffelgrass (Cenchrus ciliaris).

PubMed

Masi, Marco; Meyer, Susan; Clement, Suzette; Cimmino, Alessio; Cristofaro, Massimo; Evidente, Antonio

2017-05-26

Buffelgrass (Pennisetum ciliare or Cenchrus ciliaris) is a perennial grass that has become highly invasive in the Sonoran Desert of southern Arizona. In the search for novel control strategies against this weed, strains of the foliar fungal pathogen Cochliobolus australiensis from buffelgrass have been screened for their ability to produce phytotoxic metabolites that could potentially be used as natural herbicides in an integrated pest management strategy. A new phytotoxin, named cochliotoxin, was isolated from liquid culture of this fungus together with radicinin, radicinol, and their 3-epimers. Cochliotoxin was characterized, essentially by spectroscopic methods, as 3-hydroxy-2-methyl-7-(3-methyloxiranyl)-2,3-dihydropyrano[4,3-b]pyran-4,5-dione. Its relative stereochemistry was assigned by 1 H NMR techniques, while the absolute configuration (2S,3S) was determined applying the advanced Mosher's method by esterification of its hydroxy group at C-3. When bioassayed in a buffelgrass coleoptile elongation test and by leaf puncture bioassay against the host weed and two nontarget grasses, cochliotoxin showed strong phytotoxicity. In the same tests, radicinin and 3-epi-radicinin also showed phytotoxic activity, while radicinol and 3-epi-radicinol were largely inactive. All five compounds were more active in leaf puncture bioassays on buffelgrass than on the nontarget grass tanglehead (Heteropogon contortus), while the nontarget grass Arizona cottontop (Digitaria californica) was more sensitive to radicinin and 3-epi-radicinin. Cochliotoxin at low concentration was significantly more active on buffelgrass than on either native grass, but the difference was small.

Synthesis, spectroscopic characterization and crystallographic behavior of a biologically relevant novel indole-fused heterocyclic compound - Experimental and theoretical (DFT) studies

NASA Astrophysics Data System (ADS)

Sharma, Sakshi; Brahmachari, Goutam; Banerjee, Bubun; Nurjamal, Khondekar; Kumar, Abhishek; Srivastava, Ambrish Kumar; Misra, Neeraj; Pandey, Sarvesh Kumar; Rajnikant; Gupta, Vivek K.

2016-08-01

The present communication deals with the eco-friendly synthesis, spectral properties and X-ray crystal structure of an indole derivative - Ethyl 2'-amino-3'-cyano-6'-methyl-5-nitro-2-oxospiro [indoline-3,4'-pyran]-5'-carboxylate. The title compound was synthesized in 87% yield. The crystal structure of the molecule is stabilized by intermolecular Nsbnd H … N, Nsbnd H … O and Csbnd H … π interactions. The molecule is organized in the crystal lattice forming sheet like structure. To interpret the experimental data, ab initio computations of the vibrational frequencies were carried out using the Gaussian 09 program followed by the full optimizations done using Density Functional Theory (DFT) at B3LYP/6-31 + G(d,p) level. The combined use of experiments and computations allowed a firm assignment of the majority of observed bands for the compound. The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) with frontier orbital gap were presented. The electronic and charge transfer properties have been explained on the basis of highest occupied molecular orbitals (HOMOs), lowest unoccupied molecular orbitals (LUMOs) and density of states (DOS). From the optimized geometry of the molecule, molecular electrostatic potential (MEP) distribution, frontier molecular orbitals (FMOs) of the title compound have been calculated in the ground state theoretically. The theoretical results showed good agreement with the experimental values. First hyperpolarizability values have been calculated to describe the nonlinear optical (NLO) property of the synthesized compound.

Stimulation of secretion by the T84 colonic epithelial cell line with dietary flavonols.

PubMed

Nguyen, T D; Canada, A T; Heintz, G G; Gettys, T W; Cohn, J A

1991-06-15

Flavonols are dietary compounds widely distributed in plants and characterized by a 2-phenyl-benzo(alpha)pyrane nucleus possessing hydroxyl and ketone groups at positions 3 and 4, respectively. Kaempferol, quercetin, and myricetin are flavonols that are further mono-, di-, or trihydroxylated on the phenyl ring, respectively. To test whether these ingested flavonols might exert a direct secretory effect on intestinal epithelial cells, monolayers of the T84 colonocyte cell line were mounted in Ussing chambers and examined for ion transport response. Twenty minutes after addition of 100 microM quercetin to either the serosal or mucosal side, the short-circuit current change was maximal at 16.6 microA/cm2. Kaempferol was less potent than quercetin, while myricetin and glycosylated quercetin (rutin) did not induce secretion. The secretion induced by quercetin did not seem to be mediated by the reactive oxygen species generated by quercetin through auto-oxidation and/or redox cycling (superoxide, hydrogen peroxide, and the hydroxyl radical) because it was neither enhanced by iron, nor inhibited by desferroxamine B or catalase (alone or in combination with superoxide dismutase). Like vasoactive intestinal peptide, quercetin induced a secretory response that was inhibited by barium chloride and bumetanide, and which exhibited synergism with carbachol. Quercetin also stimulated a modest increase in intracellular cAMP levels and the phosphorylation of endogenous protein substrates for cAMP-dependent protein kinase. Thus, quercetin is a potent stimulus of colonocyte secretion that resembles secretagogues which act via a cAMP-mediated signaling pathway.

Deoxyarbutin Possesses a Potent Skin-Lightening Capacity with No Discernible Cytotoxicity against Melanosomes.

PubMed

Miao, Fang; Shi, Ying; Fan, Zhi-Feng; Jiang, Shan; Xu, Shi-Zheng; Lei, Tie-Chi

2016-01-01

Safe and effective ingredients capable of removing undesired hyperpigmentation from facial skin are urgently needed for both pharmaceutical and cosmetic purposes. Deoxyarbutin (4-[(tetrahydro-2H-pyran-2-yl) oxy] phenol, D-Arb) is a glucoside derivative of hydroquinone. Here, we investigated the toxicity and efficacy of D-Arb at the sub-cellular level (directly on melanosomes) and skin pigmentation using in vivo and in vitro models to compare with its parent compound hydroquinone (1,4-benzenediol, HQ). At first, we examined the ultrastructural changes of melanosomes in hyperpigmented guinea pig skin induced by 308-nm monochromatic excimer lightand/or treated with HQ and D-Arb using transmission electron microscopy. The results showed that prominent changes in the melanosomal membrane, such as bulb-like structure and even complete rupture of the outer membranes, were found in the skin after topical application of 5% HQ for 10 days. These changes were barely observed in the skin treated with D-Arb. To further clarify whether membrane toxicity of HQ was a direct result of the compound treatment, we also examinedultrastructural changes of individual melanosomes purified from MNT1 human melanoma cells. Similar observations were obtained from the naked melanosome model in vitro. Finally, we determined the effects of melanosomal fractions exposed to HQ or D-Arb on hydroxyl radical generation in the Fenton reaction utilizing an electron spin resonance assay. D-Arb-treated melanosomesexhibit a moderate hydroxyl radical-scavenging activity, whereas HQ-treated melanosomessignificantly generate more hydroxyl free radicals. This study suggests that D-Arb possesses a potent ability in skin lightening and antioxidation with less melanosome cytotoxicity.

Synthesis of erbium,ytterbium-doped hexagonal phase sodium yttrium fluoride nanoparticles and application to ligand exchange and energy transfer studies

NASA Astrophysics Data System (ADS)

Goel, Vishya

Nanoparticles containing rare earth ions have the ability to absorb and convert infrared light into visible light. The purpose of this work is to synthesize rare earth ion-doped NaYF4 nanoparticles in their most efficient form, the hexagonal phase. These nanoparticles are then used in ligand exchange and energy transfer studies. The synthesis procedure produces gram scale quantities of nanoparticles. Such a scale is important for reproducibility and application of these materials. Oleylamine-capped NaYF4 nanoparticles were synthesized and were doped with 2 % Er3+ and 20 % Yb3+ using a thermal decomposition method. The procedure was optimized in terms of precursor concentration and injection rate. The samples were characterized using photoluminescence spectroscopy, transmission electron microscopy, and X-ray diffraction. Photoluminescence spectra were collected using infrared excitation (980 nm). Control of the temperature and injection resulted in 15 nm (diameter) hexagonal phase NaYF4:Er3+,Yb3+ nanoparticles capped with oleylamine. The nanoparticles exhibited bright emission in the red (640 nm) and green (540 nm) portions of the visible spectrum. The surface of the nanoparticles was modified with decanoic acid, dodecanedioic acid, or dodecane sulfonic acid using a ligand exchange reaction. Energy transfer was studied from the oleylamine-capped nanoparticles to the fluorophores Nile Red, 4-(dicyanomethylene)-2-t-butyl-6(1,1,7,7-tetramethyljulolidyl-9-enyl)-4H-pyran, and poly(2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylene vinylene). Successful surface ligand exchange was achieved and the preliminary exploration of upconverting nanoparticles as an energy transfer donor was performed.

Investigation of Exciton Recombination Zone in Quantum Dot Light-Emitting Diodes Using a Fluorescent Probe.

PubMed

Huang, Xiaoyu; Zhang, Heng; Xu, Dingxin; Wen, Feng; Chen, Shuming

2017-08-23

Exciton recombination zone, where the photons are generated, can greatly affect the performance, such as the efficiency and color purity, of the quantum dot (QD) light-emitting diodes (QLEDs). To probe the exciton recombination zone, 4-(dicyanomethylene)-2-t-butyl-6(1,1,7,7-tetramethyljulolidyl-9-enyl)-4H-pyran (DCJTB) is doped into the charge transport layer as a fluorescent sensor; by monitoring the Förster resonant energy transfer (FRET) between QD and DCJTB, the location of the recombination zone can be determined. It is found that the electron transport layer (ETL) has a great impact on the recombination zone. For example, in QLEDs with ZnMgO ETL, the recombination zone is near the interface of the QD/hole transport layer (HTL) and is shifted to the interface of the QD/ETL as the driving voltage is increased, whereas in devices with 1,3,5-tris(2-N-phenylbenzimidazolyl) benzene (TPBi) ETL, the recombination zone is close to the interface of the QD/ETL and moved to the interface of the QD/HTL with the increase in the driving voltage. Our results can also clarify the light emission mechanism in QLEDs. In devices with ZnMgO ETL, the emission is dominated by the direct charge recombination, whereas in devices with TPBi ETL, the emission is contributed by both FRET and direct charge recombination. Our studies suggest that fluorescent probe can be a powerful tool for investigating the exciton recombination zone, light emission mechanism, and other fundamental processes in QLEDs.

Pyranopterin Coordination Controls Molybdenum Electrochemistry in Escherichia coli Nitrate Reductase*

PubMed Central

Wu, Sheng-Yi; Rothery, Richard A.; Weiner, Joel H.

2015-01-01

We test the hypothesis that pyranopterin (PPT) coordination plays a critical role in defining molybdenum active site redox chemistry and reactivity in the mononuclear molybdoenzymes. The molybdenum atom of Escherichia coli nitrate reductase A (NarGHI) is coordinated by two PPT-dithiolene chelates that are defined as proximal and distal based on their proximity to a [4Fe-4S] cluster known as FS0. We examined variants of two sets of residues involved in PPT coordination: (i) those interacting directly or indirectly with the pyran oxygen of the bicyclic distal PPT (NarG-Ser719, NarG-His1163, and NarG-His1184); and (ii) those involved in bridging the two PPTs and stabilizing the oxidation state of the proximal PPT (NarG-His1092 and NarG-His1098). A S719A variant has essentially no effect on the overall Mo(VI/IV) reduction potential, whereas the H1163A and H1184A variants elicit large effects (ΔEm values of −88 and −36 mV, respectively). Ala variants of His1092 and His1098 also elicit large ΔEm values of −143 and −101 mV, respectively. An Arg variant of His1092 elicits a small ΔEm of +18 mV on the Mo(VI/IV) reduction potential. There is a linear correlation between the molybdenum Em value and both enzyme activity and the ability to support anaerobic respiratory growth on nitrate. These data support a non-innocent role for the PPT moieties in controlling active site metal redox chemistry and catalysis. PMID:26297003

α-Farnesene and ocimene induce metabolite changes by volatile signaling in neighboring tea (Camellia sinensis) plants.

PubMed

Zeng, Lanting; Liao, Yinyin; Li, Jianlong; Zhou, Ying; Tang, Jinchi; Dong, Fang; Yang, Ziyin

2017-11-01

Herbivore-induced plant volatiles (HIPVs) act as direct defenses against herbivores and as indirect defenses by attracting herbivore enemies. However, the involvement of HIPVs in within-plant or plant-to-plant signaling is not fully clarified. Furthermore, in contrast to model plants, HIPV signaling roles in crops have hardly been reported. Here, we investigated HIPVs emitted from tea (Camellia sinensis) plants, an important crop used for beverages, and their involvement in tea plant-to-plant signaling. To ensure uniform and sufficient exposure to HIPVs, jasmonic acid combined with mechanical damage (JAMD) was used to simulate herbivore attacks. Metabonomics techniques based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry and gas chromatography-mass spectrometry were employed to determine metabolite changes in undamaged tea plants exposed to JAMD-stimulated volatiles. JAMD-stimulated volatiles mainly enhanced the amounts of 1-O-galloyl-6-O-luteoyl-α-d-glucose, assamicain C, 2,3,4,5-tetrahydroxy-6-oxohexyl gallate, quercetagitrin, 2-(2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)-4,5-dihydroxy-6-(hydroxymethyl)-tetrahydro-2H-pyran-3-yl, 3,4-dimethoxybenzoate, 1,3,4,5,6,7-hexahydroxyheptan-2-one, and methyl gallate in neighboring undamaged tea leaves. Furthermore, α-farnesene and β-ocimene, which were produced after JAMD treatments, were identified as two main JAMD-stimulated volatiles altering metabolite profiles of the neighboring undamaged tea leaves. This research advances our understanding of the ecological functions of HIPVs and can be used to develop crop biological control agents against pest insects in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

[Multiplayer white organic light-emitting diodes with different order and thickness of emission layers].

PubMed

Xu, Wei; Lu, Fu-Han; Cao, Jin; Zhu, Wen-Qing; Jiang, Xue-Yin; Zhang, Zhi-Lin; Xu, Shao-Hong

2008-02-01

In multilayer OLED devices, the order and thickness of the emission layers have great effect on their spectrum. Based on the three basic colours of red, blue and green, a series of white organic light-emitting diodes(WOLEDS)with the structure of ITO/CuPc(12 nm)/NPB(50 nm)/EML/LiF(1 nm)/Al(100 nm) and a variety of emission layer's orders and thicknesses were fabricated. The blue emission material: 2-t-butyl-9,10-di-(2-naphthyl)anthracene (TBADN) doped with p-bis(p-N, N-diphenyl-amono-styryl)benzene(DSA-Ph), the green emission material: tris-[8-hydroxyquinoline]aluminum(Alq3) doped with C545, and the red emission material: tris-[8-hydroxyquinoline]aluminum( Alq3) doped with 4-(dicyanomethylene)-2-t-butyl-6-(1, 1, 7, 7-tetramethyljulolidyl-9-enyl)-4H-pyran (DCJTB) were used. By adjusting the order and thickness of each emission layer in the RBG structure, we got a white OLED with current efficiency of 5.60 cd x A(-1) and Commission Internationale De L'Eclairage (CIE) coordinates of (0. 34, 0.34) at 200 mA x cm(-2). Its maximum luminance reached 20 700 cd x m(-2) at current density of 400 mA x cm(-2). The results were analyzed on the basis of the theory of excitons' generation and diffusion. According to the theory, an equation was set up which relates EL spectra to the luminance efficiency, the thickness of each layer and the exciton diffusion length. In addition, in RBG structure with different thickness of red layer, the ratio of th e spectral intensity of red to that of blue was calculated. It was found that the experimental results are in agreement with the theoretical values.

High color rendering index white organic light-emitting diode using levofloxacin as blue emitter

NASA Astrophysics Data System (ADS)

Miao, Yan-Qin; Gao, Zhi-Xiang; Zhang, Ai-Qin; Li, Yuan-Hao; Wang, Hua; Jia, Hu-Sheng; Liu, Xu-Guang; Tsuboi, Taijuf

2015-05-01

Levofloxacin (LOFX), which is well-known as an antibiotic medicament, was shown to be useful as a 452-nm blue emitter for white organic light-emitting diodes (OLEDs). In this paper, the fabricated white OLED contains a 452-nm blue emitting layer (thickness of 30 nm) with 1 wt% LOFX doped in CBP (4,4’-bis(carbazol-9-yl)biphenyl) host and a 584-nm orange emitting layer (thickness of 10 nm) with 0.8 wt% DCJTB (4-(dicyanomethylene)-2-tert-butyl-6-(1,1,7,7-tetramethyljulolidin-4-yl-vinyl)-4H-pyran) doped in CBP, which are separated by a 20-nm-thick buffer layer of TPBi (2,2’,2”-(benzene-1,3,5-triyl)-tri(1-phenyl-1H-benzimidazole). A high color rendering index (CRI) of 84.5 and CIE chromaticity coordinates of (0.33, 0.32), which is close to ideal white emission CIE (0.333, 0.333), are obtained at a bias voltage of 14 V. Taking into account that LOFX is less expensive and the synthesis and purification technologies of LOFX are mature, these results indicate that blue fluorescence emitting LOFX is useful for applications to white OLEDs although the maximum current efficiency and luminance are not high. The present paper is expected to become a milestone to using medical drug materials for OLEDs. Project supported by the Program for New Century Excellent Talents in University of Ministry of Education of China (Grant No. NCET-13-0927), the International Science & Technology Cooperation Program of China (Grant No. 2012DFR50460), the National Natural Science Foundation of China (Grant Nos. 21101111 and 61274056), and the Shanxi Provincial Key Innovative Research Team in Science and Technology, China (Grant No. 2012041011).

Transcriptome analysis of germinating maize kernels exposed to smoke-water and the active compound KAR1.

PubMed

Soós, Vilmos; Sebestyén, Endre; Juhász, Angéla; Light, Marnie E; Kohout, Ladislav; Szalai, Gabriella; Tandori, Júlia; Van Staden, Johannes; Balázs, Ervin

2010-11-02

Smoke released from burning vegetation functions as an important environmental signal promoting the germination of many plant species following a fire. It not only promotes the germination of species from fire-prone habitats, but several species from non-fire-prone areas also respond, including some crops. The germination stimulatory activity can largely be attributed to the presence of a highly active butenolide compound, 3-methyl-2H-furo[2,3-c]pyran-2-one (referred to as karrikin 1 or KAR1), that has previously been isolated from plant-derived smoke. Several hypotheses have arisen regarding the molecular background of smoke and KAR1 action. In this paper we demonstrate that although smoke-water and KAR1 treatment of maize kernels result in a similar physiological response, the gene expression and the protein ubiquitination patterns are quite different. Treatment with smoke-water enhanced the ubiquitination of proteins and activated protein-degradation-related genes. This effect was completely absent from KAR1-treated kernels, in which a specific aquaporin gene was distinctly upregulated. Our findings indicate that the array of bioactive compounds present in smoke-water form an environmental signal that may act together in germination stimulation. It is highly possible that the smoke/KAR1 'signal' is perceived by a receptor that is shared with the signal transduction system implied in perceiving environmental cues (especially stresses and light), or some kind of specialized receptor exists in fire-prone plant species which diverged from a more general one present in a common ancestor, and also found in non fire-prone plants allowing for a somewhat weaker but still significant response. Besides their obvious use in agricultural practices, smoke and KAR1 can be used in studies to gain further insight into the transcriptional changes during germination.

Karrikins discovered in smoke trigger Arabidopsis seed germination by a mechanism requiring gibberellic acid synthesis and light.

PubMed

Nelson, David C; Riseborough, Julie-Anne; Flematti, Gavin R; Stevens, Jason; Ghisalberti, Emilio L; Dixon, Kingsley W; Smith, Steven M

2009-02-01

Discovery of the primary seed germination stimulant in smoke, 3-methyl-2H-furo[2,3-c]pyran-2-one (KAR1), has resulted in identification of a family of structurally related plant growth regulators, karrikins. KAR1 acts as a key germination trigger for many species from fire-prone, Mediterranean climates, but a molecular mechanism for this response remains unknown. We demonstrate that Arabidopsis (Arabidopsis thaliana), an ephemeral of the temperate northern hemisphere that has never, to our knowledge, been reported to be responsive to fire or smoke, rapidly and sensitively perceives karrikins. Thus, these signaling molecules may have greater significance among angiosperms than previously realized. Karrikins can trigger germination of primary dormant Arabidopsis seeds far more effectively than known phytohormones or the structurally related strigolactone GR-24. Natural variation and depth of seed dormancy affect the degree of KAR1 stimulation. Analysis of phytohormone mutant germination reveals suppression of KAR1 responses by abscisic acid and a requirement for gibberellin (GA) synthesis. The reduced germination of sleepy1 mutants is partially recovered by KAR1, which suggests that germination enhancement by karrikin is only partly DELLA dependent. While KAR1 has little effect on sensitivity to exogenous GA, it enhances expression of the GA biosynthetic genes GA3ox1 and GA3ox2 during seed imbibition. Neither abscisic acid nor GA levels in seed are appreciably affected by KAR1 treatment prior to radicle emergence, despite marked differences in germination outcome. KAR1 stimulation of Arabidopsis germination is light-dependent and reversible by far-red exposure, although limited induction of GA3ox1 still occurs in the dark. The observed requirements for light and GA biosynthesis provide the first insights into the karrikin mode of action.

Gibepyrone Biosynthesis in the Rice Pathogen Fusarium fujikuroi Is Facilitated by a Small Polyketide Synthase Gene Cluster*

PubMed Central

Janevska, Slavica; Arndt, Birgit; Niehaus, Eva-Maria; Burkhardt, Immo; Rösler, Sarah M.; Brock, Nelson L.; Humpf, Hans-Ulrich; Dickschat, Jeroen S.; Tudzynski, Bettina

2016-01-01

The 2H-pyran-2-one gibepyrone A and its oxidized derivatives gibepyrones B–F have been isolated from the rice pathogenic fungus Fusarium fujikuroi already more than 20 years ago. However, these products have not been linked to the respective biosynthetic genes, and therefore, their biosynthesis has not yet been analyzed on a molecular level. Feeding experiments with isotopically labeled precursors clearly supported a polyketide origin for the formal monoterpenoid gibepyrone A, whereas the terpenoid pathway could be excluded. Targeted gene deletion verified that the F. fujikuroi polyketide synthase PKS13, designated Gpy1, is responsible for gibepyrone A biosynthesis. Next to Gpy1, the ATP-binding cassette transporter Gpy2 is encoded by the gibepyrone gene cluster. Gpy2 was shown to have only a minor impact on the actual efflux of gibepyrone A out of the cell. Instead, we obtained evidence that Gpy2 is involved in gene regulation as it represses GPY1 gene expression. Thus, GPY1 was up-regulated and gibepyrone A production was enhanced both extra- and intracellularly in Δgpy2 mutants. Furthermore, expression of GPY genes is strictly repressed by members of the fungus-specific velvet complex, Vel1, Vel2, and Lae1, whereas Sge1, a major regulator of secondary metabolism in F. fujikuroi, affects gibepyrone biosynthesis in a positive manner. The gibepyrone A derivatives gibepyrones B and D were shown to be produced by cluster-independent P450 monooxygenases, probably to protect the fungus from the toxic product. In contrast, the formation of gibepyrones E and F from gibepyrone A is a spontaneous process and independent of enzymatic activity. PMID:27856636

Genotoxicity of waterpipe smoke in buccal cells and peripheral blood leukocytes as determined by comet assay.

PubMed

Al-Amrah, Hadba Jar-Allah; Aboznada, Osama Abdullah; Alam, Mohammad Zubair; ElAssouli, M-Zaki Mustafa; Mujallid, Mohammad Ibrahim; ElAssouli, Sufian Mohamad

2014-12-01

Waterpipe smoke causes DNA damage in peripheral blood leukocytes and in buccal cells of smokers. To determine the exposure effect of waterpipe smoke on buccal cells and peripheral blood leukocytes in regard to DNA damage using comet assay. The waterpipe smoke condensates were analyzed by gas chromatography-mass spectrometry (GC-MS). The study was performed on 20 waterpipe smokers. To perform comet assay on bucaal cells of smokers, 10 µl of cell suspension was mixed with 85 µl of pre-warmed 1% low melting agarose, applied to comet slide and electrophoresed. To analyze the effect of smoke condensate in vitro, 1 ml of peripheral blood was mixed with 10 µl of smoke condensate and subjected for comet assay. The GC-MS analysis revealed the presence of 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4on, nicotine, hydroxymethyl furancarboxaldehyde and 3-ethoxy-4-hydroxybenzaldehyde in the smoke condensates. Waterpipe smoking caused DNA damage in vivo in buccal cells of smokers. The tail moment and tail length in buccal cells of smokers were 186 ± 26 and 456 ± 71, respectively, which are higher than control. The jurak and moassel smoke condensates were found to cause DNA damage in peripheral blood leukocytes. The moassel smoke condensate was more damaging. There is wide misconception that waterpipe smoking is not as harmful as cigarette smoking. This study demonstrated that waterpipe smoke induced DNA damage in exposed cells. Waterpipe smokes cause DNA damage in buccal cells. The smoke condensate of both jurak and moassel caused comet formation suggesting DNA damage in peripheral blood leukocytes.

Exploring the Saccharomyces cerevisiae Volatile Metabolome: Indigenous versus Commercial Strains

PubMed Central

Alves, Zélia; Melo, André; Figueiredo, Ana Raquel; Coimbra, Manuel A.; Gomes, Ana C.; Rocha, Sílvia M.

2015-01-01

Winemaking is a highly industrialized process and a number of commercial Saccharomyces cerevisiae strains are used around the world, neglecting the diversity of native yeast strains that are responsible for the production of wines peculiar flavours. The aim of this study was to in-depth establish the S. cerevisiae volatile metabolome and to assess inter-strains variability. To fulfill this objective, two indigenous strains (BT2652 and BT2453 isolated from spontaneous fermentation of grapes collected in Bairrada Appellation, Portugal) and two commercial strains (CSc1 and CSc2) S. cerevisiae were analysed using a methodology based on advanced multidimensional gas chromatography (HS-SPME/GC×GC-ToFMS) tandem with multivariate analysis. A total of 257 volatile metabolites were identified, distributed over the chemical families of acetals, acids, alcohols, aldehydes, ketones, terpenic compounds, esters, ethers, furan-type compounds, hydrocarbons, pyrans, pyrazines and S-compounds. Some of these families are related with metabolic pathways of amino acid, carbohydrate and fatty acid metabolism as well as mono and sesquiterpenic biosynthesis. Principal Component Analysis (PCA) was used with a dataset comprising all variables (257 volatile components), and a distinction was observed between commercial and indigenous strains, which suggests inter-strains variability. In a second step, a subset containing esters and terpenic compounds (C10 and C15), metabolites of particular relevance to wine aroma, was also analysed using PCA. The terpenic and ester profiles express the strains variability and their potential contribution to the wine aromas, specially the BT2453, which produced the higher terpenic content. This research contributes to understand the metabolic diversity of indigenous wine microflora versus commercial strains and achieved knowledge that may be further exploited to produce wines with peculiar aroma properties. PMID:26600152

UHPLC-MS Metabolome Fingerprinting: The Isolation of Main Compounds and Antioxidant Activity of the Andean Species Tetraglochin ameghinoi (Speg.) Speg.

PubMed

Luna, Lorena; Simirgiotis, Mario J; Lima, Beatriz; Bórquez, Jorge; Feresin, Gabriela E; Tapia, Alejandro

2018-03-29

The seriated extracts of petroleum ether (PE-E), dichloromethane (DCM-E) and methanol extracts (MeOH-E) from the aerial parts of the native South American plant Tetraglochin ameghinoi (Rosaceae), were evaluated regarding their antioxidant and antibacterial activities. The antioxidant properties were evaluated by free radical scavenging methods (DPPH and TEAC), ferric-reducing antioxidant power (FRAP) and lipoperoxidation in erythrocytes (LP), while the antibacterial activity was performed against Gram-positive and Gram-negative bacteria according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The chemical and biological analyses of this plant are very important since this bush is currently used in traditional medicine as a cholagogue and digestive. The polar MeOH-E showed the highest antioxidant activities (17.70 µg/mL in the DPPH assay, 381.43 ± 22.38 mM TE/g extract in the FRAP assay, 387.76 ± 91.93 mg TE/g extract in the TEAC assay and 93.23 + 6.77% in the LP assay) and it was selected for chromatographic isolation of its components. These components were found to be four acetophenones, including the new phloracetophenone glucoside: 4',6',-dihydroxy-2'- O -(6″-acetyl)- β -d-glucopyranosylacetophenone or IUPAC name: (6-(2-acetyl-3,5-dihydroxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)methyl acetate, whose structure was elucidated by NMR and MS methods. In addition, twenty-six compounds, including five of these acetophenone derivatives, two sugars, six flavonoids, eleven phenolic acids and two triterpenes, were identified based on UHPLC-OT-MS and PDA analysis on the MeOH-E. The results support the medicinal use of the plant.

Deoxyarbutin Possesses a Potent Skin-Lightening Capacity with No Discernible Cytotoxicity against Melanosomes

PubMed Central

Fan, Zhi-Feng; Jiang, Shan; Xu, Shi-Zheng; Lei, Tie-Chi

2016-01-01

Safe and effective ingredients capable of removing undesired hyperpigmentation from facial skin are urgently needed for both pharmaceutical and cosmetic purposes. Deoxyarbutin (4-[(tetrahydro-2H-pyran-2-yl) oxy] phenol, D-Arb) is a glucoside derivative of hydroquinone. Here, we investigated the toxicity and efficacy of D-Arb at the sub-cellular level (directly on melanosomes) and skin pigmentation using in vivo and in vitro models to compare with its parent compound hydroquinone (1,4-benzenediol, HQ). At first, we examined the ultrastructural changes of melanosomes in hyperpigmented guinea pig skin induced by 308-nm monochromatic excimer lightand/or treated with HQ and D-Arb using transmission electron microscopy. The results showed that prominent changes in the melanosomal membrane, such as bulb-like structure and even complete rupture of the outer membranes, were found in the skin after topical application of 5% HQ for 10 days. These changes were barely observed in the skin treated with D-Arb. To further clarify whether membrane toxicity of HQ was a direct result of the compound treatment, we also examinedultrastructural changes of individual melanosomes purified from MNT1 human melanoma cells. Similar observations were obtained from the naked melanosome model in vitro. Finally, we determined the effects of melanosomal fractions exposed to HQ or D-Arb on hydroxyl radical generation in the Fenton reaction utilizing an electron spin resonance assay. D-Arb-treated melanosomesexhibit a moderate hydroxyl radical-scavenging activity, whereas HQ-treated melanosomessignificantly generate more hydroxyl free radicals. This study suggests that D-Arb possesses a potent ability in skin lightening and antioxidation with less melanosome cytotoxicity. PMID:27776184

Density functional theory and RRKM calculations of decompositions of the metastable E-2,4-pentadienal molecular ions.

PubMed

Solano Espinoza, Eduardo A; Vallejo Narváez, Wilmer E

2010-07-01

The potential energy profiles for the fragmentations that lead to [C(5)H(5)O](+) and [C(4)H(6)](+*) ions from the molecular ions [C(5)H(6)O](+*) of E-2,4-pentadienal were obtained from calculations at the UB3LYP/6-311G + + (3df,3pd)//UB3LYP/6-31G(d,p) level of theory. Kinetic barriers and harmonic frequencies obtained by the density functional method were then employed in Rice-Ramsperger-Kassel-Marcus calculations of individual rate coefficients for a large number of reaction steps. The pre-equilibrium and rate-controlling step approximations were applied to different regions of the complex potential energy surface, allowing the overall rate of decomposition to be calculated and discriminated between three rival pathways: C-H bond cleavage, decarbonylation and cyclization. These processes should have to compete for an equilibrated mixture of four conformers of the E-2,4-pentadienal ions. The direct dissociation, however, can only become important in the high-energy regime. In contrast, loss of CO and cyclization are observable processes in the metastable kinetic window. The former involves a slow 1,2-hydrogen shift from the carbonyl group that is immediately followed by the formation of an ion-neutral complex which, in turn, decomposes rapidly to the s-trans-1,3-butadiene ion [C(4)H(6)](+*). The predominating metastable channel is the second one, that is, a multi-step ring closure which starts with a rate-limiting cis-trans isomerization. This process yields a mixture of interconverting pyran ions that dissociates to the pyrylium ions [C(5)H(5)O](+). These results can be used to rationalize the CID mass spectrum of E-2,4-pentadienal in a low-energy regime. 2010 John Wiley & Sons, Ltd.

Pyranopterin Coordination Controls Molybdenum Electrochemistry in Escherichia coli Nitrate Reductase.

PubMed

Wu, Sheng-Yi; Rothery, Richard A; Weiner, Joel H

2015-10-09

We test the hypothesis that pyranopterin (PPT) coordination plays a critical role in defining molybdenum active site redox chemistry and reactivity in the mononuclear molybdoenzymes. The molybdenum atom of Escherichia coli nitrate reductase A (NarGHI) is coordinated by two PPT-dithiolene chelates that are defined as proximal and distal based on their proximity to a [4Fe-4S] cluster known as FS0. We examined variants of two sets of residues involved in PPT coordination: (i) those interacting directly or indirectly with the pyran oxygen of the bicyclic distal PPT (NarG-Ser(719), NarG-His(1163), and NarG-His(1184)); and (ii) those involved in bridging the two PPTs and stabilizing the oxidation state of the proximal PPT (NarG-His(1092) and NarG-His(1098)). A S719A variant has essentially no effect on the overall Mo(VI/IV) reduction potential, whereas the H1163A and H1184A variants elicit large effects (ΔEm values of -88 and -36 mV, respectively). Ala variants of His(1092) and His(1098) also elicit large ΔEm values of -143 and -101 mV, respectively. An Arg variant of His(1092) elicits a small ΔEm of +18 mV on the Mo(VI/IV) reduction potential. There is a linear correlation between the molybdenum Em value and both enzyme activity and the ability to support anaerobic respiratory growth on nitrate. These data support a non-innocent role for the PPT moieties in controlling active site metal redox chemistry and catalysis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Structural insights, protein-ligand interactions and spectroscopic characterization of isoformononetin

NASA Astrophysics Data System (ADS)

Srivastava, Anubha; Singh, Harshita; Mishra, Rashmi; Dev, Kapil; Tandon, Poonam; Maurya, Rakesh

2017-04-01

Isoformononetin, a methoxylated isoflavone present in medicinal plants, has non-estrogenic bone forming effect via differential mitogen-activated protein kinase (MAPK) signaling. Spectroscopic (FT-Raman, FT-IR, UV-vis and NMR spectra) and quantum chemical calculations using density functional theory (DFT) and 6-311++G(d,p) as a large basis set have been employed to study the structural and electronic properties of isoformononetin. A detailed conformational analysis is performed to determine the stability among conformers and the various possibilities of intramolecular hydrogen bonding formation. Molecular docking studies with different protein kinases were performed on isoformononetin and previously studied isoflavonoid, formononetin in order to understand their inhibitory nature and the effect of functional groups on osteogenic or osteoporosis associated proteins. It is found that the oxygen atoms of methoxy, hydroxyl groups attached to phenyl rings R1, R3 and carbonyl group attached to pyran ring R2, play a major role in binding with the protein kinases that is responsible for the osteoporosis; however, no hydrophobic interactions are observed between rings of ligand and protein. The electronic properties such as HOMO and LUMO energies were determined by time-dependent TD-DFT which predict that conformer II is a little bit more stable and chemically low reactive than conformer I of isoformononetin. To estimate the structure-activity relationship, the molecular electrostatic potential (MEP) surface map, and reactivity descriptors are calculated from the optimized geometry of the molecule. From these results, it is also found that isoformononetin is kinetically more stable, less toxic, weak electrophile and chemically less reactive than formononetin. The atoms in molecules and natural bond orbital analysis are applied for the detailed analysis of intra and intermolecular hydrogen bonding interactions.

Maillard reaction of lactose and fluoxetine hydrochloride, a secondary amine.

PubMed

Wirth, D D; Baertschi, S W; Johnson, R A; Maple, S R; Miller, M S; Hallenbeck, D K; Gregg, S M

1998-01-01

Analysis of commercially available generic formulations of fluoxetine HCl revealed the presence of lactose as the most common excipient. We show that such formulations are inherently less stable than formulations with starch as the diluent due to the Maillard reaction between the drug, a secondary amine hydrochloride, and lactose. The Amadori rearrangement product was isolated and characterized; the characterization was aided by reduction with sodium borohydride and subsequent characterization of this reduced adduct. The lactose-fluoxetine HCl reaction was examined in aqueous ethanol and in the solid state, in which factors such as water content, lubricant concentration, and temperature were found to influence the degradation. N-Formylfluoxetine was identified as a major product of this Maillard reaction and it is proposed that N-formyl compounds be used as markers for this drug-excipient interaction since they are easy to prepare synthetically. Many characteristic volatile products of the Maillard reaction have been identified by GC/MS, including furaldehyde, maltol, and 2,3-dihydro-3,5-dihydroxy-6-methyl-4 H-pyran-4-one. Close similarity between the degradation products of simple mixtures and formulated generic products was found; however, at least one product decomposed at a rate nearly 10 times that predicted from the simple models. Maillard products have also been identified in unstressed capsules. The main conclusion is that drugs which are secondary amines (not just primary amines as sometimes reported) undergo the Maillard reaction with lactose under pharmaceutically relevant conditions. This finding should be considered during the selection of excipients and stability protocols for drugs which are secondary amines or their salts, just as it currently is for primary amines.

HARNESSING THE CHEMISTRY OF CO2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Louie, Janis

2010-05-11

Our research program is broadly focused on activating CO{sub 2} through the use of organic and organometallic based catalysts. Some of our methods have centered on annulation reactions of unsaturated hydrocarbons (and carbonyl substrates) to provide a diverse array of carbocycles and heterocycles. We use a combination of catalyst discovery and optimization in conjunction with classical physical organic chemistry to elucidate the key mechanistic features of the cycloaddition reactions such that the next big advances in catalyst development can be made. Key to all of our cycloaddition reactions is the use of a sterically hindered, electron donating N heterocyclic carbenemore » (NHC) ligand, namely IPr (or SIPr), in conjunction with a low valent nickel pre-catalyst. The efficacy of this ligand is two-fold: (1) the high {delta}-donating ability of the NHC increases the nucleophilicity of the metal center which thereby facilitates interaction with the electrophilic carbonyl and (2) the steric hindrance prevents an otherwise competitive side reaction involving only the alkyne substrate. Such a system has allowed for the facile cycloaddition to prepare highly functionalized pyrones, pyridones, pyrans, as well as novel carbocycles. Importantly, all reactions proceed under extremely mild conditions (room temperature, atmospheric pressures, and short reaction times), require only catalytic amounts of Ni/NHC and readily available starting materials, and afford annulated products in excellent yields. Our current focus revolves around understanding the fundamental processes that govern these cycloadditions such that the next big advance in the cyclization chemistry of CO{sub 2} can be made. Concurrent to our annulation chemistry is our investigation of the potential for imidazolylidenes to function as thermally-actuated CO{sub 2} sequestering and delivery agents.« less

Autophagy and Apoptosis in Hepatocellular Carcinoma Induced by EF25-(GSH)2: A Novel Curcumin Analog

PubMed Central

Zhou, Tao; Ye, Lili; Bai, Yu; Sun, Aiming; Cox, Bryan; Liu, Dahai; Li, Yong; Liotta, Dennis; Snyder, James P.; Fu, Haian; Huang, Bei

2014-01-01

Curcumin, a spice component as well as a traditional Asian medicine, has been reported to inhibit proliferation of a variety of cancer cells but is limited in application due to its low potency and bioavailability. Here, we have assessed the therapeutic effects of a novel and water soluble curcumin analog, 3,5-bis(2-hydroxybenzylidene)tetrahydro-4H-pyran-4-one glutathione conjugate [EF25-(GSH)2], on hepatoma cells. Using the MTT and colony formation assays, we determined that EF25-(GSH)2 drastically inhibits the proliferation of hepatoma cell line HepG2 with minimal cytotoxicity for the immortalized human hepatic cell line HL-7702. Significantly, EF25-(GSH)2 suppressed growth of HepG2 xenografts in mice with no observed toxicity to the animals. Mechanistic investigation revealed that EF25-(GSH)2 induces autophagy by means of a biphasic mechanism. Low concentrations (<5 µmol/L) induced autophagy with reversible and moderate cytoplasmic vacuolization, while high concentrations (>10 µmol/L) triggered an arrested autophagy process with irreversible and extensive cytoplasmic vacuolization. Prolonged treatment with EF25-(GSH)2 induced cell death through both an apoptosis-dependent and a non-apoptotic mechanism. Chloroquine, a late stage inhibitor of autophagy which promoted cytoplasmic vacuolization, led to significantly enhanced apoptosis and cytotoxicity when combined with EF25-(GSH)2. Taken together, these data imply a fail-safe mechanism regulated by autophagy in the action of EF25-(GSH)2, suggesting the therapeutic potential of the novel curcumin analog against hepatocellular carcinoma (HCC), while offering a novel and effective combination strategy with chloroquine for the treatment of patients with HCC. PMID:25268357

Infrared matrix-isolation and theoretical studies of the reactions of ferrocene with ozone.

PubMed

Kugel, Roger W; Pinelo, Laura F; Ault, Bruce S

2015-03-19

The reactions between ferrocene (Cp2Fe) (2a) and ozone (O3) were studied using low-temperature matrix-isolation techniques coupled with theoretical density functional theory (DFT) calculations. Co-deposition of Ar/Cp2Fe and Ar/O3 gas mixtures onto a cryogenically cooled CsI window produced a dark-green charge-transfer complex, Cp2Fe-O3, that photodecomposed upon red (λ ≥ 600 nm) and infrared (λ ≥ 1000 nm) irradiation but was stable to green or blue irradiation. Products of photodecomposition were characterized by FT-IR, oxygen-18 labeling, and DFT calculations using the B3LYP functionals and the 6-311G++(d,2p) basis set. Likely, photochemical products included four structures having the molecular formula C10H10FeO, identified by DFT calculations based on their calculated infrared spectra and (18)O isotope shifts. Each of these calculated molecules had one intact and fully coordinated η(5)-C5H5 cyclopentadienyl (Cp) ring and (1) an η(5)-C5H5O cyclic ether (pyran ring) (2b), (2) an η(4)-C5H5O linear aldehyde (2c), (3) a bidentate cyclic aldehyde with a seven-membered ring including the iron atom (2d), or (4) an Fe-O bond and an η(2)-C5H5 (Cp) ring (2e). No conclusive evidence for a gas-phase thermal reaction between ferrocene and ozone was observed under the conditions of these experiments. However, strong evidence for a surface-catalyzed thermal reaction was observed in merged-jet experiments wherein the gases were premixed before deposition. Surface-catalyzed ferrocene-ozone reaction products included a thin film of Fe2O3 observed on the walls of the merged tube as well as cyclopentadiene (C5H6), cyclopentadienone (C5H4O), and further oxidation products observed in the matrix. Possible mechanisms for both the photochemical and the thermal reactions are discussed.

A Novel trans-1-(9-Anthryl)-2-phenylethene Derivative Containing a Phenanthroimidazole Unit for Application in Organic Light-Emitting Diodes.

PubMed

Zhou, Nonglin; Wang, Shirong; Xiao, Yin; Li, Xianggao

2018-01-04

Aryl-substituted phenanthroimidazoles (PIs) have attracted tremendous attention in the field of organic light-emitting diodes (OLEDs), because they are simple to synthesize and have excellent thermal properties, high photoluminescence quantum yields (PLQYs), and bipolar properties. Herein, a novel blue-green emitting material, (E)-2-{4'-[2-(anthracen-9-yl)vinyl]-[1,1'-biphenyl]-4-yl}-1-phenyl-1H-phenanthro[9,10-d]imidazole (APE-PPI), containing a t-APE [1-(9-anthryl)-2-phenylethene] core and a PI moiety was designed and synthesized. Owing to the PI skeleton, APE-PPI possesses high thermal stability and a high PLQY, and the compound exhibits bipolar transporting characteristics, which were identified by single-carrier devices. Nondoped blue-green OLEDs with APE-PPI as the emitting layer show emission at λ=508 nm, a full width at half maximum of 82 nm, a maximum brightness of 9042 cd m -2 , a maximum current efficiency of 2.14 cd A -1 , and Commission Internationale de L'Eclairage (CIE) coordinates of (0.26, 0.55). Furthermore, a white OLED (WOLED) was fabricated by employing APE-PPI as the blue-green emitting layer and 4-(dicyanomethylene)-2-tert-butyl-6-(1,1,7,7-tetramethyljulolidin-4-yl-vinyl)-4H-pyran (DCJTB) doped in tris-(8-hydroxyquinolinato)aluminum (Alq 3 ) as the red-green emitting layer. This WOLED exhibited a maximum brightness of 10029 cd m -2 , a maximum current efficiency of 16.05 cd A -1 , CIE coordinates of (0.47, 0.47), and a color rendering index (CRI) of 85. The high performance of APE-PPI-based devices suggests that the t-APE and PI combination can potentially be used to synthesize efficient electroluminescent materials for WOLEDs. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Karrikins Discovered in Smoke Trigger Arabidopsis Seed Germination by a Mechanism Requiring Gibberellic Acid Synthesis and Light1[W][OA

PubMed Central

Nelson, David C.; Riseborough, Julie-Anne; Flematti, Gavin R.; Stevens, Jason; Ghisalberti, Emilio L.; Dixon, Kingsley W.; Smith, Steven M.

2009-01-01

Discovery of the primary seed germination stimulant in smoke, 3-methyl-2H-furo[2,3-c]pyran-2-one (KAR1), has resulted in identification of a family of structurally related plant growth regulators, karrikins. KAR1 acts as a key germination trigger for many species from fire-prone, Mediterranean climates, but a molecular mechanism for this response remains unknown. We demonstrate that Arabidopsis (Arabidopsis thaliana), an ephemeral of the temperate northern hemisphere that has never, to our knowledge, been reported to be responsive to fire or smoke, rapidly and sensitively perceives karrikins. Thus, these signaling molecules may have greater significance among angiosperms than previously realized. Karrikins can trigger germination of primary dormant Arabidopsis seeds far more effectively than known phytohormones or the structurally related strigolactone GR-24. Natural variation and depth of seed dormancy affect the degree of KAR1 stimulation. Analysis of phytohormone mutant germination reveals suppression of KAR1 responses by abscisic acid and a requirement for gibberellin (GA) synthesis. The reduced germination of sleepy1 mutants is partially recovered by KAR1, which suggests that germination enhancement by karrikin is only partly DELLA dependent. While KAR1 has little effect on sensitivity to exogenous GA, it enhances expression of the GA biosynthetic genes GA3ox1 and GA3ox2 during seed imbibition. Neither abscisic acid nor GA levels in seed are appreciably affected by KAR1 treatment prior to radicle emergence, despite marked differences in germination outcome. KAR1 stimulation of Arabidopsis germination is light-dependent and reversible by far-red exposure, although limited induction of GA3ox1 still occurs in the dark. The observed requirements for light and GA biosynthesis provide the first insights into the karrikin mode of action. PMID:19074625

Transcriptome analysis of germinating maize kernels exposed to smoke-water and the active compound KAR1

PubMed Central

2010-01-01

Background Smoke released from burning vegetation functions as an important environmental signal promoting the germination of many plant species following a fire. It not only promotes the germination of species from fire-prone habitats, but several species from non-fire-prone areas also respond, including some crops. The germination stimulatory activity can largely be attributed to the presence of a highly active butenolide compound, 3-methyl-2H-furo[2,3-c]pyran-2-one (referred to as karrikin 1 or KAR1), that has previously been isolated from plant-derived smoke. Several hypotheses have arisen regarding the molecular background of smoke and KAR1 action. Results In this paper we demonstrate that although smoke-water and KAR1 treatment of maize kernels result in a similar physiological response, the gene expression and the protein ubiquitination patterns are quite different. Treatment with smoke-water enhanced the ubiquitination of proteins and activated protein-degradation-related genes. This effect was completely absent from KAR1-treated kernels, in which a specific aquaporin gene was distinctly upregulated. Conclusions Our findings indicate that the array of bioactive compounds present in smoke-water form an environmental signal that may act together in germination stimulation. It is highly possible that the smoke/KAR1 'signal' is perceived by a receptor that is shared with the signal transduction system implied in perceiving environmental cues (especially stresses and light), or some kind of specialized receptor exists in fire-prone plant species which diverged from a more general one present in a common ancestor, and also found in non fire-prone plants allowing for a somewhat weaker but still significant response. Besides their obvious use in agricultural practices, smoke and KAR1 can be used in studies to gain further insight into the transcriptional changes during germination. PMID:21044315

A fluorescence correlation spectroscopy study of the diffusion of an organic dye in the gel phase and fluid phase of a single lipid vesicle.

PubMed

Ghosh, Subhadip; Adhikari, Aniruddha; Sen Mojumdar, Supratik; Bhattacharyya, Kankan

2010-05-06

The mobility of the organic dye DCM (4-dicyanomethylene-2-methyl-6-p-dimethyl aminostyryl-4H-pyran) in the gel and fluid phases of a lipid vesicle is studied by fluorescence correlation spectroscopy (FCS). Using FCS, translational diffusion of DCM is determined in the gel phase and fluid phase of a single lipid vesicle adhered to a glass surface. The size of a lipid vesicle (average diameter approximately 100 nm) is smaller than the diffraction limited spot size (approximately 250 nm) of the microscope. Thus, the vesicle is confined within the laser focus. Three lipid vesicles (1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)) having different gel transition temperatures (-1, 23, and 41 degrees C, respectively) were studied. The diffusion coefficient of the dye DCM in bulk water is approximately 300 microm(2)/s. In the lipid vesicle, the average D(t) decreases markedly to approximately 5 microm(2)/s (approximately 60 times) in the gel phase (for DPPC at 20 degrees C) and 40 microm(2)/s ( approximately 8 times) in the fluid phase (for DLPC at 20 degrees C). This clearly demonstrates higher mobility in the fluid phase compared with the gel phase of a lipid. It is observed that the D(t) values vary from lipid to lipid and there is a distribution of D(t) values. The diffusion of the hydrophobic dye DCM (D(t) approximately 5 microm(2)/s) in the DPPC vesicle is found to be 8 times smaller than that of a hydrophilic anioinic dye C343 (D(t) approximately 40 microm(2)/s). This is attributed to different locations of the hydrophobic (DCM) and hydrophilic (C343) dyes.

Detection of fluorescent organic nanoparticles by confocal laser endomicroscopy in a rat model of Barrett’s esophageal adenocarcinoma

PubMed Central

Dassie, Elisa; Arcidiacono, Diletta; Wasiak, Iga; Damiano, Nunzio; Dall’Olmo, Luigi; Giacometti, Cinzia; Facchin, Sonia; Cassaro, Mauro; Guido, Ennio; De Lazzari, Franca; Marin, Oriano; Ciach, Tomasz; Fery-Forgues, Suzanne; Alberti, Alfredo; Battaglia, Giorgio; Realdon, Stefano

2015-01-01

For many years, novel strategies for cancer detection and treatment using nanoparticles (NPs) have been developed. Esophageal adenocarcinoma is the sixth leading cause of cancer-related deaths in Western countries, and despite recent advances in early detection and treatment, its prognosis is still very poor. This study investigated the use of fluorescent organic NPs as potential diagnostic tool in an experimental in vivo model of Barrett’s esophageal adenocarcinoma. NPs were made of modified polysaccharides loaded with [4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran] (DCM), a well-known fluorescent dye. The NP periphery might or might not be decorated with ASYNYDA peptide that has an affinity for esophageal cancer cells. Non-operated and operated rats in which gastroesophageal reflux was surgically induced received both types of NPs (NP-DCM and NP-DCM-ASYNYDA) by intravenous route. Localization of mucosal NPs was assessed in vivo by confocal laser endomicroscopy, a technique which enables a “real time” and in situ visualization of the tissue at a cellular level. After injection of NP-DCM and NP-DCM-ASYNYDA, fluorescence was observed in rats affected by esophageal cancer, whereas no signal was observed in control non-operated rats, or in rats with simple esophagitis or Barrett’s esophagus mucosa. Fluorescence was observable in vivo 30 minutes after the administration of NPs. Interestingly, NP-DCM-ASYNYDA induced strong fluorescence intensity 24 hours after administration. These observations suggested that NPs could reach the tumor cells, likely by enhanced permeability and retention effect, and the peptide ASYNYDA gave them high specificity for esophageal cancer cells. Thus, the combination of NP platform and confocal laser endomicroscopy could play an important role for highlighting esophageal cancer conditions. This result supports the potential of this strategy as a targeted carrier for photoactive and bioactive molecules in esophageal cancer diagnosis and treatment. PMID:26586943

Cytotoxicity of lapachol metabolites produced by probiotics.

PubMed

Oliveira Silva, E; Cruz de Carvalho, T; Parshikov, I A; Alves dos Santos, R; Silva Emery, F; Jacometti Cardoso Furtado, N A

2014-07-01

Probiotics are currently added to a variety of functional foods to provide health benefits to the host and are commonly used by patients with gastrointestinal complaints or diseases. The therapeutic effects of lapachol continue to inspire studies to obtain derivatives with improved bioactivity and lower unwanted effects. Therefore, the general goal of this study was to show that probiotics are able to convert lapachol and are important to assess the effects of bacterial metabolism on drug performance and toxicity. The microbial transformations of lapachol were carried out by Bifidobacterium sp. and Lactobacillus acidophilus and different metabolites were produced in mixed and isolated cultures. The cytotoxic activities against breast cancer and normal fibroblast cell lines of the isolated metabolites (4α-hydroxy-2,2-dimethyl-5-oxo-2,3,4,4α,5,9β-hexahydroindeno[1,2-β]pyran-9β-carboxilic acid, a new metabolite produced by mixed culture and dehydro-α-lapachone produced by isolated cultures) were assessed and compared with those of lapachol. The new metabolite displayed a lower activity against a breast cancer cell line (IC50 = 532.7 μmol l(-1) ) than lapachol (IC50 = 72.3 μmol l(-1) ), while dehydro-α-lapachone (IC50 = 10.4 μmol l(-1) ) displayed a higher activity than lapachol. The present study is the first to demonstrate that probiotics are capable of converting lapachol into the most effective cytotoxic compound against a breast cancer cell line. Probiotics have been used in dairy products to promote human health and have the ability to metabolize drugs and other xenobiotics. Naphthoquinones, such as lapachol, are considered privileged scaffolds due to their high propensity to interact with biological targets. The present study is the first to demonstrate that probiotics are capable of converting lapachol into the most effective cytotoxic compound against a breast cancer cell line. The developed approach highlights the importance of probiotics to assess the effects of bacterial metabolism on drug performance and toxicity. © 2014 The Society for Applied Microbiology.

In vitro-in vivo correlation and translation to the clinical outcome for CJ-13,610, a novel inhibitor of 5-lipoxygenase.

PubMed

Matthew Hutzler, J; Linder, Collette D; Melton, Roger J; Vincent, John; Daniels, J Scott

2010-07-01

The metabolism of the 5-lipoxygenase inhibitor, 4-(3-(4-(2-methyl-1H-imidazol-1-yl)phenylthio)phenyl)-tetrahydro-2H-pyran-4-carboxamide (CJ-13,610), was investigated in liver microsomes from human and preclinical species in an effort to compare metabolite profiles and evaluate the in vitro-in vivo correlation for metabolic clearance. Overall, the metabolite profile of CJ-13,610 was comparable across the species tested with multiple oxidative metabolites observed, including sulfoxidation. The sulfoxidation kinetics characterized in rat, dog, and human liver microsomes (HLM) indicated a low apparent Michaelis-Menten constant (K(m, app)) of 4 to 5 microM. Results from cDNA-expressed cytochrome P450 (P450) studies indicated that the metabolism in HLM was primarily mediated by CYP3A4 and 3A5. A subsequent in vitro study using ketoconazole as an inhibitor of CJ-13,610 sulfoxidation corroborated the CYP3A4/5-mediated pathway (IC(50) = 7 nM). Assessment of multiple methods for predicting the human pharmacokinetic profile observed with CJ-13,610 after a 30-mg single oral dose indicated that clearance scaled from human liver microsomes yielded a better prediction when coupled with a Vd(ss) term that was scaled from dog [area under the concentration-time curve (AUC) and half-life within 1.3-fold of actual] versus a Vd(ss) term obtained from rat. Single-species allometric scaling of clearance and Vd(ss) from dog pharmacokinetic studies was equally predictive, whereas scaling from rat resulted in underpredictions of both AUC and maximal concentration (C(max)). Results from these studies support the strategy of predicting human pharmacokinetics using human liver microsomal intrinsic clearance data. More importantly, results from the present investigation enabled the selection of alternative drug candidates from the chemical series via in vitro screening, while subsequently eliminating costly routine preclinical in vivo studies.

Combined optical gain and degradation measurements in DCM2 doped Tris-(8-hydroxyquinoline)aluminum thin-films

NASA Astrophysics Data System (ADS)

Čehovski, Marko; Döring, Sebastian; Rabe, Torsten; Caspary, Reinhard; Kowalsky, Wolfgang

2016-04-01

Organic laser sources offer the opportunity to integrate flexible and widely tunable lasers in polymer waveguide circuits, e.g. for Lab-on-Foil applications. Therefore, it is necessary to understand gain and degradation processes for long-term operation. In this paper we address the challenge of life-time (degradation) measurements of photoluminescence (PL) and optical gain in thin-film lasers. The well known guest-host system of aluminum-chelate Alq3 (Tris-(8-hydroxyquinoline)aluminum) as host material and the laser dye DCM2 (4-(Dicyanomethylene)-2- methyl-6-julolidyl-9-enyl-4H-pyran) as guest material is employed as laser active material. Sample layers have been built up by co-evaporation in an ultrahigh (UHV) vacuum chamber. 200nm thick films of Alq3:DCM2 with different doping concentrations have been processed onto glass and thermally oxidized silicon substrates. The gain measurements have been performed by the variable stripe length (VSL) method. This measurement technique allows to determine the thin-film waveguide gain and loss, respectively. For the measurements the samples were excited with UV irradiation (ƛ = 355nm) under nitrogen atmosphere by a passively Q-switched laser source. PL degradation measurements with regard to the optical gain have been done at laser threshold (approximately 3 μJ/cm2), five times above laser threshold and 10 times above laser threshold. A t50-PL lifetime of > 107 pulses could be measured at a maximum excitation energy density of 32 μJ/cm2. This allows for a detailed analysis of the gain degradation mechanism and therefore of the stimulated cross section. Depending on the DCM2 doping concentration C the stimulated cross section was reduced by 35 %. Nevertheless, the results emphasizes the necessity of the investigation of degradation processes in organic laser sources for long-term applications.

Aciculatin Inhibits Granulocyte Colony-Stimulating Factor Production by Human Interleukin 1β-Stimulated Fibroblast-Like Synoviocytes

PubMed Central

Shih, Kao-Shang; Wang, Jyh-Horng; Wu, Yi-Wen; Teng, Che-Ming; Chen, Chien-Chih; Yang, Chia-Ron

2012-01-01

The expression of granulocyte colony-stimulating factor (G-CSF), the major regulator of neutrophil maturation, by human fibroblast-like synoviocytes (FLS) can be stimulated by the inflammatory cytokine interleukin-1β (IL-1β). G-CSF is known to contribute to the pathologic processes of destructive arthritis, but the induction mechanism remains unknown. The aims of this study were to identify the signaling pathways involved in IL-1β-stimulated G-CSF production and to determine whether this process was inhibited by aciculatin (8-((2R,4S,5S,6R)-tetrahydro-4,5-dihydroxy-6-methyl-2H-pyran-2-yl)-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one), the major bioactive component of Chrysopogon aciculatus. IL-1β-induced cytokine expression was evaluated by measuring mRNA and protein levels by RT-PCR, ELISA, and Milliplex® assay. Whether aciculatin inhibited IL-1β-stimulated G-CSF expression, and if so, how, were evaluated using western blot assay, an electrophoretic mobility shift assay, and a reporter gene assay. Neutrophil differentiation was determined by Wright-Giemsa staining and flow cytometry. Aciculatin markedly inhibited G-CSF expression induced by IL-1β (10 ng/mL) in a concentration-dependent manner (1–10 µM). In clarifying the mechanisms involved, aciculatin was found to inhibit the IL-1β-induced activation of the IκB kinase (IKK)/IκB/nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways by suppressing the DNA binding activity of the transcription factors NF-κB and activator protein (AP)-1. Furthermore, aciculatin significantly inhibited the G-CSF-mediated phosphorylation of Janus kinase-signal transducer and activator of transcription (JAK-STAT) and Akt and neutrophil differentiation from precursor cells. Our results show that aciculatin inhibits IL-1β-stimulated G-CSF expression and the subsequent neutrophil differentiation, suggesting that it might have therapeutic potential for inflammatory arthritis. PMID:22860122

Materials Design via Optimized Intramolecular Noncovalent Interactions for High-Performance Organic Semiconductors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Xiaojie; Liao, Qiaogan; Manley, Eric F.

2016-03-15

We report the design, synthesis, and implemention in semiconducting polymers of a novel head-to-head linkage containing the TRTOR (3-alkyl-3'-alkoxy-2,2'-bithiophene) donor subunit having a single strategically optimized, planarizing noncovalent S···O interaction. Diverse complementary thermal, optical, electrochemical, X-ray scattering, electrical, photovoltaic, and electron microscopic characterization techniques are applied to establish structure-property correlations in a TRTOR-based polymer series. In comparison to monomers having double S···O interactions, replacing one alkoxy substituent with a less electron-donating alkyl one yields TRTOR-based polymers with significantly depressed (0.2-0.3 eV) HOMOs. Furthermore, the weaker single S···O interaction and greater TRTOR steric encumberance enhances materials processability without sacrificing backbone planarity.more » From another perspective, TRTOR has comparable electronic properties to ring-fused 5Hdithieno[ 3,2-b:2',3'-d]pyran (DTP) subunits, but a centrosymmetric geometry which promotes a more compact and ordered structure than bulkier, axisymmetric DTP. Compared to monosubstituted TTOR (3-alkoxy-2,2'-bithiophene), alkylation at the TRTOR bithiophene 3-position enhances conjugation and polymer crystallinity with contracted π-π stacking. Grazing incidence wide-angle X-ray scattering (GIWAXS) data reveal that the greater steric hindrance and the weaker single S···O interaction are not detrimental to close packing and high crystallinity. As a proof of materials design, copolymerizing TRTOR with phthalimides yields copolymers with promising thin-film transistor mobility as high as 0.42 cm2/(V·s) and 6.3% power conversion efficiency in polymer solar cells, the highest of any phthalimide copolymers reported to date. The depressed TRTOR HOMOs imbue these polymers with substantially increased Ion/Ioff ratios and Voc’s versus analogous subunits with multiple electron donating, planarizing alkoxy substituents. Implementing a head-to-head linkage with an alkyl/alkoxy substitution pattern and a single S···O interaction is a promising strategy for organic electronics materials design.« less

Stimulated emission and optical properties of pyranyliden fragment containing compounds in PVK matrix

NASA Astrophysics Data System (ADS)

Vembris, Aivars; Zarins, Elmars; Kokars, Valdis

2017-10-01

Organic solid state lasers are thoughtfully investigated due to their potential applications in communication, sensors, biomedicine, etc. Low amplified spontaneous emission (ASE) excitation threshold value is essential for further use of the material in devices. Intramolecular interaction limits high molecule density load in the matrix. It is the case of the well-known red light emitting laser dye - 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCM). The lowest ASE threshold value of the mentioned laser dye could be obtained within the concentration range between 2 and 4 wt%. At higher concentration threshold energy drastically increases. In this work optical and ASE properties of three original DCM derivatives in poly(N-vinylcarbazole) (PVK) at various concentrations will be discussed. One of the derivatives is modified DCM dye in which the methyl substituents in the electron donor part have been replaced with bulky trityloxyethyl groups (DWK-1). These sterically significant functional groups do not influence electron transitions in the dye but prevent aggregation of the molecules. The chemical structure of the second investigated compound is similar to DWK-1 where the methyl group is replaced with the tert-butyl substituent (DWK-1TB). The third derivative (DWK-2) consists of two N,N-di(trityloxyethyl)amino electron donor groups. All results were compared with DCM:PVK system. Photoluminescence quantum yield (PLQY) is up to ten times larger for DWK-1TB with respect to DCM systems. Bulky trityloxyethyl groups prevent aggregation of the molecules thus decreasing interaction between dyes and amount of non-radiative decays. The red shift of the photoluminescence and amplified spontaneous emission at higher concentrations were observed due to the solid state solvation effect. The increase of the investigated dye density in the matrix with a smaller reduction in PLQY resulted in low ASE threshold energy. The lowest threshold value was obtained around 21 μJ/cm2 (2.1 kW/cm2) in DWK-1TB:PVK films.

Mononuclear late first row transition metal complexes of ONO donor hydrazone ligand: Synthesis, characterization, crystallographic insight, in vivo and in vitro anti-inflammatory activity

NASA Astrophysics Data System (ADS)

Kendur, Umashri; Chimmalagi, Geeta H.; Patil, Sunil M.; Gudasi, Kalagouda B.; Frampton, Christopher S.; Mangannavar, Chandrashekhar V.; Muchchandi, Iranna S.

2018-02-01

Air and moisture stable coordination compounds of late first row transition metal ions, viz., Co(II), Ni(II), Cu(II) and Zn(II) with a newly designed ligand, (E)-2-amino-N'-(1-(2-hydroxy-6-methyl-4-oxo-4H-pyran-3-yl)ethylidene)benzohydrazide (H2L) were prepared and extensively characterized using various spectro-analytical techniques. The ligand acts both in mono as well as doubly deprotonated manner. The ligand to metal stoichiometry was found to be 1:2 in case of complexes using chloride salts, whereas 1:1 in case of copper (II) complex using its acetate salt. The molecular structures of H2L, nickel and copper complexes were unambiguously determined by single-crystal X-ray diffraction studies reveal that H2L exists in a zwitterionic form while copper complex has copper centre in a distorted square planar environment. On the other hand, cobalt, nickel and zinc complexes display distorted octahedral coordination around the metal ion. In case of [Ni(HL)2].H2O, intramolecular Csbnd H⋯π stacking interaction were observed between the centroid of five membered chelate ring and phenyl proton C5sbnd H5 and intermolecular Csbnd H⋯π stacking interaction between the centroid of phenyl ring, dehydroacetic acid (DHA) ring and phenyl protons. The [Cu(L)DMF] complex is stabilized by intramolecular hydrogen bonding N1H⋯N2 and by intermolecular hydrogen bonding N1H⋯O4. Intermolecular interactions were investigated by Hirshfeld surfaces. Further, H2L and its metal complexes were screened for their in vivo and in vitro anti-inflammatory activities. The activity of the ligand has enhanced on coordination with transition metals. The tested compounds have shown excellent activity, which is almost equipotent to the standard used in the study.

Detection of fluorescent organic nanoparticles by confocal laser endomicroscopy in a rat model of Barrett's esophageal adenocarcinoma.

PubMed

Dassie, Elisa; Arcidiacono, Diletta; Wasiak, Iga; Damiano, Nunzio; Dall'Olmo, Luigi; Giacometti, Cinzia; Facchin, Sonia; Cassaro, Mauro; Guido, Ennio; De Lazzari, Franca; Marin, Oriano; Ciach, Tomasz; Fery-Forgues, Suzanne; Alberti, Alfredo; Battaglia, Giorgio; Realdon, Stefano

2015-01-01

For many years, novel strategies for cancer detection and treatment using nanoparticles (NPs) have been developed. Esophageal adenocarcinoma is the sixth leading cause of cancer-related deaths in Western countries, and despite recent advances in early detection and treatment, its prognosis is still very poor. This study investigated the use of fluorescent organic NPs as potential diagnostic tool in an experimental in vivo model of Barrett's esophageal adenocarcinoma. NPs were made of modified polysaccharides loaded with [4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran] (DCM), a well-known fluorescent dye. The NP periphery might or might not be decorated with ASYNYDA peptide that has an affinity for esophageal cancer cells. Non-operated and operated rats in which gastroesophageal reflux was surgically induced received both types of NPs (NP-DCM and NP-DCM-ASYNYDA) by intravenous route. Localization of mucosal NPs was assessed in vivo by confocal laser endomicroscopy, a technique which enables a "real time" and in situ visualization of the tissue at a cellular level. After injection of NP-DCM and NP-DCM-ASYNYDA, fluorescence was observed in rats affected by esophageal cancer, whereas no signal was observed in control non-operated rats, or in rats with simple esophagitis or Barrett's esophagus mucosa. Fluorescence was observable in vivo 30 minutes after the administration of NPs. Interestingly, NP-DCM-ASYNYDA induced strong fluorescence intensity 24 hours after administration. These observations suggested that NPs could reach the tumor cells, likely by enhanced permeability and retention effect, and the peptide ASYNYDA gave them high specificity for esophageal cancer cells. Thus, the combination of NP platform and confocal laser endomicroscopy could play an important role for highlighting esophageal cancer conditions. This result supports the potential of this strategy as a targeted carrier for photoactive and bioactive molecules in esophageal cancer diagnosis and treatment.

Antinociceptive activity of extracts and secondary metabolites from wild growing and micropropagated plants of Renealmia alpinia

PubMed Central

Gómez-Betancur, Isabel; Cortés, Natalie; Benjumea, Dora; Osorio, Edison; León, Francisco; Cutler, Stephen J.

2015-01-01

Ethnopharmacological relevance Renealmia alpinia is native to the American continent and can be found from Mexico to Brazil, and in the Caribbean islands. It is known as “matandrea” in Colombia, and it has been commonly used in traditional medicine to treat painful diseases and ailments. Based on its traditional uses, it is of interest to evaluate the pharmacologic effects of this plant and its secondary metabolites. Materials and methods Methanol and aqueous extracts of wild and micropropagated R. alpinia (leaves) were obtained and chemically compared by High Performance Thin Layer Chromatography (HPTLC). The antinociceptive activity of these extracts was examined using an in vivo assay (Siegmund test). Additionally, the dichloromethane extract of R. alpinia was fractionated and pure compounds were isolated by chromatographic methods. The structure elucidation of isolated compounds was performed by NMR experiments and spectroscopic techniques and comparison with the literature data. Purified compounds were evaluated for their in vitro binding affinity for opioids and cannabinoids receptors. Results The dichloromethane extract of the plant’s aerial part afforded sinostrobin (1), naringenin 7,4′-dimethyl ether (2), 2′,6′-dihydroxy-4′-methoxychalcone (3), 4-methoxy-6-(2-phenylethenyl)-2H-pyran-2-one (4), naringenin 7-methyl ether (5) and 3,5-heptanediol, 1,7-diphenyl (6), which were isolated using chromatographic methods. Their chemical structures were established by physical and spectroscopic techniques. The antinociceptive effects observed in mice by extracts of wild and micropropagated plants were similar. The compounds isolated from R. alpinia do not show affinity to opioid or cannabinoid receptors. Conclusion Aqueous and methanol extracts of R. alpinia provide antinociceptive and analgesic effects in an in vivo model. These results contribute additional insight as to why this plant is traditionally used for pain management. Also, this is the first comprehensive report of a phytochemical study of R. alpinia. PMID:25686780

An assessment of the genotoxicity and human health risk of topical use of kojic acid [5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one].

PubMed

Nohynek, Gerhard J; Kirkland, David; Marzin, Daniel; Toutain, Herve; Leclerc-Ribaud, Christele; Jinnai, Hiroyuki

2004-01-01

Kojic acid (KA), a natural substance produced by fungi or bacteria, such as Aspergillus, Penicillium or Acetobacter spp, is contained in traditional Japanese fermented foods and is used as a dermatological skin-lightening agent. High concentrations of KA (>or=1000 microg/plate) were mutagenic in S. typhimurium strains TA 98, TA 100, TA 1535, TA102 and E. coli WP2uvrA, but not in TA 1537. An Ames test following the "treat and plate" protocol was negative. A chromosome aberration test in V79 cells following a robust protocol showed only a marginal increase in chromosome aberrations at cytotoxic concentrations after prolonged (>or=18 h) exposure. No genotoxic activity was observed for hprt mutations either in mouse lymphoma or V79 cells, or in in vitro micronucleus tests in human keratinocytes or hepatocytes. All in vivo genotoxicity studies on KA doses were negative, including mouse bone marrow micronucleus tests after single or multiple doses, an in vivo/in vitro unscheduled DNA synthesis (UDS) test, or a study in the liver of the transgenic Muta(TM) Mouse. On the basis of pharmacokinetic studies in rats and in vitro absorption studies in human skin, the systemic exposure of KA in man following its topical application is estimated to be in the range of 0.03-0.06 mg/kg/day. Comparing these values with the NOAEL in oral subchronic animal studies (250 mg/kg/day), the calculated margin of safety would be 4200- to 8900-fold. Comparing human exposure with the doses that were negative for micronuclei, UDS and gene mutations in vivo, the margins of safety are 16000 to 26000-fold. In conclusion, the topical use of KA as a skin lightening agent results in minimal exposure that poses no or negligible risk of genotoxicity or toxicity to the consumer.

Evaluation of TER-SYSTEM resist for 193-nm imaging

NASA Astrophysics Data System (ADS)

Johnson, Donald W.; Egbe, Matthew I.; Chen, Cindy X.; Lin, Lin; Liao, Yihua; Bukasa, Ngalula C.; Suzuki, Yasuhiro

1997-07-01

Exposures leading to 0.18 micrometer or better resolution are now being demanded by IC development. Photolithography using 193 nm exposure tools is the leading technology for the development of these next generation of devices. We are reporting on our development efforts on the TER resist system, which is a single layer resist designed for image evaluation applications at 193 nm exposure wavelengths. The TER-system has been developed to allow equipment manufacturers to evaluate their equipment, to provide R&D lithographers with materials to qualify their 193 nm equipment and to determine process control parameters. The TER-system is a chemically amplified methacrylate resist terpolymer. It is composed of methyl methacrylate (MMA), methacrylic acid (MAA) and an acid labile acrylic ester. We have evaluated different leaving groups as the acid labile component and we report on the initial results of several. We also examined different onium salts as the PAG component. One such example is di(t- butylphenyl)-iodonium p-toluenesulfonate and we report on other examples which were used. We evaluated the thermal stability of the resins and thermal analysis showed they start to decompose at about 125 degrees Celsius when tetrahydropyranyl methacrylate is used. Other more thermally stable systems were also evaluated. Post apply bake (PAB) temperatures of 100 - 125 degrees Celsius were preferably used with the tetrahydropyranyl ester. Other more thermally stable esters, such as tetrahydro-4-methyl-2-oxo-2H-pyran-4-yl methacrylate (mevalonic lactone), ethoxy-ethyl methacrylate and 3-oxo-cyclohexyl methacrylate, also are described. Exposures in the range of 5 - 50 mJ/cm2 were typical and varied depending on the ester, the PAG, and other processing parameters. The acid catalyzed reaction rates after exposure were observed to be rapid. In all cases, post exposure bake (PEB) was typically carried out at 10 degrees Celsius or lower. Initial exposure evaluations at 193 nm and 248 nm show good resolution and image fidelity. The TER-system produced better than 0.225 micrometer resolution using 248 nm exposure equipment (NA equals 0.55) suggesting that better than 0.18 micrometer resolution is possible with 193 nm exposures. Results of resist synthesis, formulation and evaluation are presented.

SUPPRESSOR OF MORE AXILLARY GROWTH2 1 Controls Seed Germination and Seedling Development in Arabidopsis1[W][OPEN

PubMed Central

Stanga, John P.; Smith, Steven M.; Briggs, Winslow R.; Nelson, David C.

2013-01-01

Abiotic chemical signals discovered in smoke that are known as karrikins (KARs) and the endogenous hormone strigolactone (SL) control plant growth through a shared MORE AXILLARY GROWTH2 (MAX2)-dependent pathway. A SL biosynthetic pathway and candidate KAR/SL receptors have been characterized, but signaling downstream of MAX2 is poorly defined. A screen for genetic suppressors of the enhanced seed dormancy phenotype of max2 in Arabidopsis (Arabidopsis thaliana) led to identification of a suppressor of max2 1 (smax1) mutant. smax1 restores the seed germination and seedling photomorphogenesis phenotypes of max2 but does not affect the lateral root formation, axillary shoot growth, or senescence phenotypes of max2. Expression of three transcriptional markers of KAR/SL signaling, D14-LIKE2, KAR-UP F-BOX1, and INDOLE-3-ACETIC ACID INDUCIBLE1, is rescued in smax1 max2 seedlings. SMAX1 is a member of an eight-gene family in Arabidopsis that has weak similarity to HEAT SHOCK PROTEIN 101, which encodes a caseinolytic peptidase B chaperonin required for thermotolerance. SMAX1 and the SMAX1-like (SMXL) homologs are differentially expressed in Arabidopsis tissues. SMAX1 transcripts are most abundant in dry seed, consistent with its function in seed germination control. Several SMXL genes are up-regulated in seedlings treated with the synthetic SL GR24. SMAX1 and SMXL2 transcripts are reduced in max2 seedlings, which could indicate negative feedback regulation by KAR/SL signaling. smax1 seed and seedling growth mimics the wild type treated with KAR/SL, but smax1 seedlings are still responsive to 2H-furo[2,3-c]pyran-2-one (KAR2) or GR24. We conclude that SMAX1 is an important component of KAR/SL signaling during seed germination and seedling growth but is not necessary for all MAX2-dependent responses. We hypothesize that one or more SMXL proteins may also act downstream of MAX2 to control the diverse developmental responses to KARs and SLs. PMID:23893171

LX4211 increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium/glucose cotransporter 1 (SGLT1)-mediated absorption of intestinal glucose.

PubMed

Powell, David R; Smith, Melinda; Greer, Jennifer; Harris, Angela; Zhao, Sharon; DaCosta, Christopher; Mseeh, Faika; Shadoan, Melanie K; Sands, Arthur; Zambrowicz, Brian; Ding, Zhi-Ming

2013-05-01

LX4211 [(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol], a dual sodium/glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor, is thought to decrease both renal glucose reabsorption by inhibiting SGLT2 and intestinal glucose absorption by inhibiting SGLT1. In clinical trials in patients with type 2 diabetes mellitus (T2DM), LX4211 treatment improved glycemic control while increasing circulating levels of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). To better understand how LX4211 increases GLP-1 and PYY levels, we challenged SGLT1 knockout (-/-) mice, SGLT2-/- mice, and LX4211-treated mice with oral glucose. LX4211-treated mice and SGLT1-/- mice had increased levels of plasma GLP-1, plasma PYY, and intestinal glucose during the 6 hours after a glucose-containing meal, as reflected by area under the curve (AUC) values, whereas SGLT2-/- mice showed no response. LX4211-treated mice and SGLT1-/- mice also had increased GLP-1 AUC values, decreased glucose-dependent insulinotropic polypeptide (GIP) AUC values, and decreased blood glucose excursions during the 6 hours after a challenge with oral glucose alone. However, GLP-1 and GIP levels were not increased in LX4211-treated mice and were decreased in SGLT1-/- mice, 5 minutes after oral glucose, consistent with studies linking decreased intestinal SGLT1 activity with reduced GLP-1 and GIP levels 5 minutes after oral glucose. These data suggest that LX4211 reduces intestinal glucose absorption by inhibiting SGLT1, resulting in net increases in GLP-1 and PYY release and decreases in GIP release and blood glucose excursions. The ability to inhibit both intestinal SGLT1 and renal SGLT2 provides LX4211 with a novel dual mechanism of action for improving glycemic control in patients with T2DM.

Comparison of germination responses of Anigozanthos flavidus (Haemodoraceae), Gyrostemon racemiger and Gyrostemon ramulosus (Gyrostemonaceae) to smoke-water and the smoke-derived compounds karrikinolide (KAR1) and glyceronitrile

PubMed Central

Downes, Katherine S.; Light, Marnie E.; Pošta, Martin; Kohout, Ladislav; van Staden, Johannes

2013-01-01

Background and Aims A major germination-promoting chemical in smoke-water is 3-methyl-2H-furo[2,3-c]pyran-2-one (karrikinolide, KAR1). However, not all species that germinate in response to smoke-water are responsive to KAR1, such as Tersonia cyathiflora (Gyrostemonaceae). In this study, a test was made of whether two Gyrostemon species (Gyrostemonaceae) that have previously been shown to respond to smoke-water, respond to KAR1. If not, then the smoke-derived chemical that stimulates germination of these species is currently unknown. Recently, glyceronitrile was isolated from smoke-water and promoted the germination of certain Anigozanthos species (Haemodoraceae). Whether this chemical promotes Gyrostemon racemiger germination is also examined. Furthermore, an investigation was carried out into whether these species germinate in response to smoke-water derived from burning cellulose alone. Methods Gyrostemon racemiger and G. ramulosus seeds were buried after collection and retrieved in autumn the following year when dormancy was alleviated and seeds had become responsive to smoke-water. Anigozanthos flavidus seeds were after-ripened at 35 °C to alleviate dormancy. Gyrostemon and Anigozanthos seeds were then tested with ‘Seed Starter’ smoke-water, KAR1, glyceronitrile and cellulose-derived smoke-water. Key Results Although Gyrostemon racemiger, G. ramulosus and A. flavidus were all stimulated to germinate by ‘Seed Starter’ smoke-water, none of these species responded to KAR1. Gyrostemon racemiger germination was not promoted by glyceronitrile. This is in contrast to A. flavidus, where glyceronitrile, at concentrations of 1–500 µm, promoted germination, although seedling growth was inhibited at ≥400 µm. Maximum A. flavidus germination occurred at glyceronitrile concentrations of 25–300 µm. Some Gyrostemon germination was promoted by cellulose-derived smoke-water. Conclusions KAR1 and glyceronitrile, chemicals in smoke-water that are known to stimulate germination in other species, did not promote the germination of G. racemiger. This suggests that other chemical(s) which promote germination are present in smoke, and may be derived from burning cellulose alone. PMID:23299994

Comparison of germination responses of Anigozanthos flavidus (Haemodoraceae), Gyrostemon racemiger and Gyrostemon ramulosus (Gyrostemonaceae) to smoke-water and the smoke-derived compounds karrikinolide (KAR1) and glyceronitrile.

PubMed

Downes, Katherine S; Light, Marnie E; Pošta, Martin; Kohout, Ladislav; van Staden, Johannes

2013-03-01

A major germination-promoting chemical in smoke-water is 3-methyl-2H-furo[2,3-c]pyran-2-one (karrikinolide, KAR(1)). However, not all species that germinate in response to smoke-water are responsive to KAR(1), such as Tersonia cyathiflora (Gyrostemonaceae). In this study, a test was made of whether two Gyrostemon species (Gyrostemonaceae) that have previously been shown to respond to smoke-water, respond to KAR(1). If not, then the smoke-derived chemical that stimulates germination of these species is currently unknown. Recently, glyceronitrile was isolated from smoke-water and promoted the germination of certain Anigozanthos species (Haemodoraceae). Whether this chemical promotes Gyrostemon racemiger germination is also examined. Furthermore, an investigation was carried out into whether these species germinate in response to smoke-water derived from burning cellulose alone. Gyrostemon racemiger and G. ramulosus seeds were buried after collection and retrieved in autumn the following year when dormancy was alleviated and seeds had become responsive to smoke-water. Anigozanthos flavidus seeds were after-ripened at 35 °C to alleviate dormancy. Gyrostemon and Anigozanthos seeds were then tested with 'Seed Starter' smoke-water, KAR(1), glyceronitrile and cellulose-derived smoke-water. Although Gyrostemon racemiger, G. ramulosus and A. flavidus were all stimulated to germinate by 'Seed Starter' smoke-water, none of these species responded to KAR(1). Gyrostemon racemiger germination was not promoted by glyceronitrile. This is in contrast to A. flavidus, where glyceronitrile, at concentrations of 1-500 µm, promoted germination, although seedling growth was inhibited at ≥400 µm. Maximum A. flavidus germination occurred at glyceronitrile concentrations of 25-300 µm. Some Gyrostemon germination was promoted by cellulose-derived smoke-water. KAR(1) and glyceronitrile, chemicals in smoke-water that are known to stimulate germination in other species, did not promote the germination of G. racemiger. This suggests that other chemical(s) which promote germination are present in smoke, and may be derived from burning cellulose alone.

Materials Design via Optimized Intramolecular Noncovalent Interactions for High-Performance Organic Semiconductors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Xiaojie; Liao, Qiaogan; Manley, Eric F.

2016-03-15

We report the design, synthesis, and implemention in semiconducting polymers of a novel head-to-head linkage containing the TRTOR (3-alkyl-3'-alkoxy-2,2'-bithiophene) donor subunit having a single strategically optimized, planarizing noncovalent S···O interaction. Diverse complementary thermal, optical, electrochemical, X-ray scattering, electrical, photovoltaic, and electron microscopic characterization techniques are applied to establish structure–property correlations in a TRTOR-based polymer series. In comparison to monomers having double S···O interactions, replacing one alkoxy substituent with a less electron-donating alkyl one yields TRTOR-based polymers with significantly depressed (0.2–0.3 eV) HOMOs. Furthermore, the weaker single S···O interaction and greater TRTOR steric encumberance enhances materials processability without sacrificing backbone planarity.more » From another perspective, TRTOR has comparable electronic properties to ring-fused 5H-dithieno[3,2-b:2',3'-d]pyran (DTP) subunits, but a centrosymmetric geometry which promotes a more compact and ordered structure than bulkier, axisymmetric DTP. Compared to monosubstituted TTOR (3-alkoxy-2,2'-bithiophene), alkylation at the TRTOR bithiophene 3-position enhances conjugation and polymer crystallinity with contracted π–π stacking. Grazing incidence wide-angle X-ray scattering (GIWAXS) data reveal that the greater steric hindrance and the weaker single S···O interaction are not detrimental to close packing and high crystallinity. As a proof of materials design, copolymerizing TRTOR with phthalimides yields copolymers with promising thin-film transistor mobility as high as 0.42 cm2/(V·s) and 6.3% power conversion efficiency in polymer solar cells, the highest of any phthalimide copolymers reported to date. The depressed TRTOR HOMOs imbue these polymers with substantially increased Ion/Ioff ratios and Voc’s versus analogous subunits with multiple electron donating, planarizing alkoxy substituents. Implementing a head-to-head linkage with an alkyl/alkoxy substitution pattern and a single S···O interaction is a promising strategy for organic electronics materials design.« less

Protective Role of Cannabinoid Receptor 2 Activation in Galactosamine/Lipopolysaccharide-Induced Acute Liver Failure through Regulation of Macrophage Polarization and MicroRNAs

PubMed Central

Tomar, Sunil; E. Zumbrun, Elizabeth; Nagarkatti, Mitzi

2015-01-01

Acute liver failure (ALF) is a potentially life-threatening disorder without any effective treatment strategies. d-Galactosamine (GalN)/lipopolysaccharide (LPS)–induced ALF is a widely used animal model to identify novel hepato-protective agents. In the present study, we investigated the potential of a cannabinoid receptor 2 (CB2) agonist, JWH-133 [(6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran], in the amelioration of GalN/LPS-induced ALF. JWH-133 treatment protected the mice from ALF-associated mortality, mitigated alanine transaminase and proinflammatory cytokines, suppressed histopathological and apoptotic liver damage, and reduced liver infiltration of mononuclear cells (MNCs). Furthermore, JWH-133 pretreatment of M1/M2-polarized macrophages significantly increased the secretion of anti-inflammatory cytokine interleukin-10 (IL-10) in M1 macrophages and potentiated the expression of M2 markers in M2-polarized macrophages. In vivo, JWH-133 treatment also suppressed ALF-triggered expression of M1 markers in liver MNCs, while increasing the expression of M2 markers such as Arg1 and IL-10. microRNA (miR) microarray analysis revealed that JWH-133 treatment altered the expression of only a few miRs in the liver MNCs. Gene ontology analysis of the targets of miRs suggested that Toll-like receptor (TLR) signaling was among the most significantly targeted cellular pathways. Among the altered miRs, miR-145 was found to be the most significantly decreased. This finding correlated with concurrent upregulated expression of its predicted target gene, interleukin-1 receptor–associated kinase 3, a negative regulator of TLR4 signaling. Together, these data are the first to demonstrate that CB2 activation attenuates GalN/LPS-induced ALF by inducing an M1 to M2 shift in macrophages and by regulating the expression of unique miRs that target key molecules involved in the TLR4 pathway. PMID:25749929

Both plants Sebastiania chamaelea from Niger and Chrozophora senegalensis from Senegal used in African traditional medicine in malaria treatment share a same active principle.

PubMed

Garcia-Alvarez, M-C; Moussa, I; Njomnang Soh, P; Nongonierma, R; Abdoulaye, A; Nicolau-Travers, M-L; Fabre, A; Wdzieczak-Bakala, J; Ahond, A; Poupat, C; Ikhiri, K; Benoit-Vical, F

2013-10-07

Based on ethnobotanical data obtained from Nigerien and Senegalese traditional healers, two Euphorbiaceae plants, Sebastiania chamaelea and Chrozophora senegalensis, traditionally used to treat malaria, were selected for further investigations. Plant extracts were prepared with different solvents and tested both in vitro on several strains of Plasmodium falciparum, and in vivo to evaluate their antiplasmodial properties and isolate their active principles. With IC50 values around 6.5µg/ml and no significant cytotoxicity (>50µg/ml), the whole plant aqueous extract from S. chamaelea showed the best in vitro results. In vitro potentiation assays showed strong synergistic activity of S. chamaelea extract with the antiplasmodial drug chloroquine on the chloroquine-resistant P. falciparum strain W2-Indochina. In other respects, the aqueous crude extract of C. senegalensis leaves showed the most significant antiplasmodial activity in vitro (IC50 values less than 2µg/ml). We also demonstrated the prophylactic activity of C. senegalensis in vivo in a murine malaria model. Bioassay-guided fractionation of aqueous extracts of these plants enabled the isolation and identification of ellagic acid (EA, 1) as the main compound responsible for their antiplasmodial activity. Together with EA, other derivatives belonging to different chemical groups were isolated but showed moderate antimalarial activity: gallic acid (2), brevifolin carboxylic acid (3), protocatechuic acid (4), corillagin (5), rutin (6) and 3,4,8,9,10-pentahydroxy-dibenzo(b,d)pyran-6-one (7). The structures were determined by the usual spectroscopic methods and by comparison with published data. Furthermore, we report here the quantification of compound 1 (EA) by RP-HPLC in the dried extracts of these plants, reported for the first time in both these species, and possessing the highest in vitro antiplasmodial activity with IC50 values from 180 to 330nm. These in vitro and in vivo results support the traditional use in Africa of crude extracts of both S. chamaelea and C. senegalensis as an antimalarial treatment and prove the significant antiplasmodial property of EA. © 2013 Elsevier Ireland Ltd. All rights reserved.

Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan.

PubMed

van Erp, Nielka P H; Baker, Sharyn D; Zhao, Ming; Rudek, Michelle A; Guchelaar, Henk-Jan; Nortier, Johan W R; Sparreboom, Alex; Gelderblom, Hans

2005-11-01

Milk thistle (Silybum marianum) is one of the most commonly used herbal therapies, and its principal constituent silybin significantly inhibits cytochrome P450 isoform 3A4 (CYP3A4) and UDP glucuronosyltransferase isoform 1A1 (UGT1A1) in vitro. Here, we investigated whether milk thistle affects the pharmacokinetics of irinotecan, a substrate for CYP3A4 and UGT1A1, in humans. Six cancer patients were treated with irinotecan (dose, 125 mg/m(2)) given as a 90-minute infusion once every week. Four days before the second dose, patients received 200 mg milk thistle, thrice a day, for 14 consecutive days. Pharmacokinetic studies of irinotecan and its metabolites 7-ethyl-10-hydroxycamptothecin (SN-38), 7-ethyl-10-[3,4,5-trihydroxy-pyran-2-carboxylic acid]-camptothecin (SN-38-glucuronide), and 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin were done during the first three irinotecan administrations. Short-term (4 days) or more prolonged intake of milk thistle (12 days) had no significant effect on irinotecan clearance (mean, 31.2 versus 25.4 versus 25.6 L/h; P = 0.16). The area under the curve ratio of SN-38 and irinotecan was slightly decreased by milk thistle (2.58% versus 2.23% versus 2.17%; P = 0.047), whereas the relative extent of glucuronidation of SN-38 was similar (10.8 versus 13.5 versus 13.1; P = 0.64). Likewise, the area under the curve ratio of 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin and irinotecan was unaffected by milk thistle (0.332 versus 0.285 versus 0.337; P = 0.53). The maximum plasma concentrations of silybin ranged between 0.0249 and 0.257 micromol/L. Silybin concentrations after intake of milk thistle are too low to significantly affect the function of CYP3A4 and UGT1A1 in vivo, indicating that milk thistle is unlikely to alter the disposition of anticancer drugs metabolized by these enzymes.

Metabolism and Disposition of a Novel B-Cell Lymphoma-2 Inhibitor Venetoclax in Humans and Characterization of Its Unusual Metabolites.

PubMed

Liu, Hong; Michmerhuizen, Melissa J; Lao, Yanbin; Wan, Katty; Salem, Ahmed Hamed; Sawicki, James; Serby, Michael; Vaidyanathan, Srirajan; Wong, Shekman L; Agarwal, Suresh; Dunbar, Martin; Sydor, Jens; de Morais, Sonia M; Lee, Anthony J

2017-03-01

Venetoclax (ABT-199), a B-cell lymphoma-2 (Bcl-2) protein inhibitor, is currently in clinical development for the treatment of hematologic malignancies. We characterized the absorption, metabolism, and excretion of venetoclax in humans. After a single oral dose of [ 14 C]venetoclax to healthy volunteers, the recovery of total radioactive dose was 100%, with feces being the major route of elimination of the administered dose, whereas urinary excretion was minimal (<0.1%). The extent of absorption was estimated to be at least 65%. Venetoclax was primarily cleared by hepatic metabolism (∼66% of the administered dose). ∼33% of the administered dose was recovered as the parent drug and its nitro reduction metabolite M30 [2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-N-((3-amino-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzamide] (13%) in feces. Biotransformation of venetoclax in humans primarily involves enzymatic oxidation on the dimethyl cyclohexenyl moiety, followed by sulfation and/or nitro reduction. Nitro reduction metabolites were likely formed by gut bacteria. Unchanged venetoclax was the major drug-related material in circulation, representing 72.8% of total plasma radioactivity. M27 (oxidation at the 6 position of cyclohexenyl ring followed by cyclization at the α-carbon of piperazine ring; 4-[(10aR,11aS)-7-(4-chlorophenyl)-9,9-dimethyl-1,3,4,6,8,10,10a,11a-octahydropyrazino[2,1-b][1,3]benzoxazin-2-yl]-N-[3-nitro-4-(tetrahydropyran-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide) was identified as a major metabolite, representing 12% of total drug-related material. M27 was primarily formed by cytochrome P450 isoform 3A4 (CYP3A4). Steady-state plasma concentrations of M27 in human and preclinical species used for safety testing suggested that M27 is a disproportionate human metabolite. M27 is not expected to have clinically relevant on- or off-target pharmacologic activities. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Integrated optical components in thin films of polymers

NASA Technical Reports Server (NTRS)

Sarkisov, Sergey; Abdeldayem, Hossin; Venkateswarlu, Putcha; Teague, Zedric

1995-01-01

The results will be reported on the study of integrated optical components based on nonlinear optical polymeric films. Polymers poly(methyl methacrylate) (PMMA) and polyimide (PI) doped with organic laser dyes 4-dicyanomethylene-2-methyl-6-p dimethylaminostyryl-4H pyran (DCM) and 1, 3, 5, 7, 8 - pentamethyl-2,6 -diethyl-pyrromethene -BF2-complex (Pyrommethene 567, PM-567) were selected as materials for light guiding films. Additionally, UV polymerized polydiacetylene (PDA) on glass substrate was used as a waveguide material. Optical waveguides were fabricated using spin coating of preoxidized silicon wafers (1.5 micrometer silicon oxide layer) with organic dye/polymer solution followed by soft baking. the modes in slab waveguides were studied using prism coupling techniques. Measured values of mode coupling angles in multimode waveguides were used to calculate film thickness and refractive index for different polarizations. Refractive index anisotropy was found in PDA waveguide. The optimal conditions of spin coating for single mode waveguide fabrication were estimated. Propagation losses were measured by collecting the light scattered from the trace of a propagating mode either by scanning photo detector or by CCD camera. Different types of light coupling techniques were used including end-dire coupling, prism and grating coupling. Mechanical printing technique was developed for coupling grating fabrication resulting in gratings with 4% diffraction efficiency. The gratings demonstrated good stability with diffraction efficiency relaxation rate 2.4 dB/hour at a temperature approximately 15-20 C below glass transition point. Dye doped waveguides were transversally pumped with frequency doubled Nd:YAG Q-switched laser producing intensive light emission with apparent 6 kW/sq cm pump threshold and spectrum narrowing near 617 nm peak in the case of DCM doped waveguide. PM-567 doped waveguide pumped with CW Ar(+) laser (514 nm wavelength) far below threshold (0.1 W/sq.cm pump power) demonstrated emission spectrum narrowing near 616 nm peak with 18% power conversion slope efficiency. In this case emission spectrum modification was caused by the enhanced light absorption along the direction of propagating waveguide modes. Changing length, thickness, and other morphlogical waveguide parameters one can modify emission spectrum in predictable direction. The results show that polymeric waveguides, especially based on high temperature polymers such as Pl, can be used to produce a varietiy of active and passive silicon compatible integrated optical components for aerospace applications.

Crystal structure of bis­{μ2-2,2′-[(4,10-dimethyl-1,4,7,10-tetra­aza­cyclo­dodecane-1,7-di­yl)bis(meth­yl­ene)]bis­(4-oxo-4H-pyran-3-olato)}dicobalt­calcium bis­(perchlorate) 1.36-hydrate

PubMed Central

Rossi, Patrizia; Paoli, Paola; Giorgi, Luca; Formica, Mauro; Fusi, Vieri

2017-01-01

The title compound, [CaCo2(C22H30N4O6)2](ClO4)2·1.36H2O or {Ca[Co(H–2 L1)]2}·2ClO4·1.36H2O {where L1 is 4,10-bis­[(3-hy­droxy-4-pyron-2-yl)meth­yl]-1,7-dimethyl-1,4,7,10-tetra­aza­cyclo­dodecane}, is a trinuclear complex whose asymmetric unit comprises a quarter of the {Ca[Co(H–2 L1)]2}2+ trinuclear complex, half of a perchlorate ion and 0.34-water mol­ecules. In the neutral [Co(H–2 L1)] moiety, the cobalt ion is hexa­coordinated in a trigonal–prismatic fashion by the surrounding N4O2 donor set. A Ca2+ cation holds together two neutral [Co(H–2 L1)] moieties and is octa­coordinated in a distorted trigonal–dodeca­hedral fashion by the surrounding O atoms belonging to the deprotonated oxide and carbonyl groups of two [Co(H–2 L1)] units. The coordination of the CoII cation preorganizes L1 and an electron-rich area forms, which is able to host hard metal ions. The comparison between the present structure and the previously published ones suggests a high versatility of this ligand; indeed, hard metal ions with different nature and dimensions lead to complexes having different stoichiometry (mono- and dinuclear monomers and trinuclear dimers) or even a polymeric structure. The heterotrinuclear CoII–CaII–CoII complexes are connected in three dimensions via weak C—H⋯O hydrogen bonds, which are also responsible for the inter­actions with the perchlorate anions and the lattice water mol­ecules. The perchlorate anion is disordered about a twofold rotation axis and was refined giving the two positions a fixed occupancy factor of 0.5. The crystal studied was refined as a two-component inversion twin [BASF parameter = 0.14 (4)]. PMID:29250424

Biodistribution and radiation dosimetry of 18F-CP-18, a potential apoptosis imaging agent, as determined from PET/CT scans in healthy volunteers.

PubMed

Doss, Mohan; Kolb, Hartmuth C; Walsh, Joseph C; Mocharla, Vani; Fan, Hong; Chaudhary, Ashok; Zhu, Zhihong; Alpaugh, R Katherine; Lango, Miriam N; Yu, Jian Q

2013-12-01

(18)F-CP-18, or (18S,21S,24S,27S,30S)-27-(2-carboxyethyl)-21-(carboxymethyl)-30-((2S,3R,4R,5R,6S)-6-((2-(4-(3-F18-fluoropropyl)-1H-1,2,3-triazol-1-yl)acetamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxamido)-24-isopropyl-18-methyl-17,20,23,26,29-pentaoxo-4,7,10,13-tetraoxa-16,19,22,25,28-pentaazadotriacontane-1,32-dioic acid, is being evaluated as a tissue apoptosis marker for PET imaging. The purpose of this study was to determine the biodistribution and estimate the normal-organ radiation-absorbed doses and effective dose from (18)F-CP-18. Successive whole-body PET/CT scans were obtained at approximately 7, 45, 90, 130, and 170 min after intravenous injection of (18)F-CP-18 in 7 healthy human volunteers. Blood samples and urine were collected between the PET/CT scans, and the biostability of (18)F-CP-18 was assessed using high-performance liquid chromatography. The PET scans were analyzed to determine the radiotracer uptake in different organs. OLINDA/EXM software was used to calculate human radiation doses based on the biodistribution of the tracer. (18)F-CP-18 was 54% intact in human blood at 135 min after injection. The tracer cleared rapidly from the blood pool with a half-life of approximately 30 min. Relatively high (18)F-CP-18 uptake was observed in the kidneys and bladder, with diffuse uptake in the liver and heart. The mean standardized uptake values (SUVs) in the bladder, kidneys, heart, and liver at around 50 min after injection were approximately 65, 6, 1.5, and 1.5, respectively. The calculated effective dose was 38 ± 4 μSv/MBq, with the urinary bladder wall having the highest absorbed dose at 536 ± 61 μGy/MBq using a 4.8-h bladder-voiding interval for the male phantom. For a 1-h voiding interval, these doses were reduced to 15 ± 2 μSv/MBq and 142 ± 15 μGy/MBq, respectively. For a typical injected activity of 555 MBq, the effective dose would be 21.1 ± 2.2 mSv for the 4.8-h interval, reduced to 8.3 ± 1.1 mSv for the 1-h interval. (18)F-CP-18 cleared rapidly through the renal system. The urinary bladder wall received the highest radiation dose and was deemed the critical organ. Both the effective dose and the bladder dose can be reduced by frequent voiding. From the radiation dosimetry perspective, the apoptosis imaging agent (18)F-CP-18 is suitable for human use.

Radiotracers For Lipid Signaling Pathways In Biological Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gatley, S. J.

The primary focus of this project continues to be the development of radiotracers and radiotracer methodology for studying physiology and biochemistry. The compounds that have been labeled areacylethanolamines and acylglycerols that are, as classes, represented in both in plants and in animals. In the latter, some of these act as ligands for cannabinoid receptors and they are therefore known as endocannabinoids. Cannabinoid receptors are not found in plant genomes so that plants must contain other receptors and signaling systems that use acylethanolamines. Relatively little work has been done on that issue, though acylethanolamines do modulate plant growth and stress resistance,more » thus possessing obvious relevance to agriculture and energy production. Progress has been described in five peer-reviewed papers and seven meeting abstracts. Preparation of 2-acylglycerol lipid messengers in high purity. A novel enzymatic synthesis was developedthat gave pure 2-acylglycerols free of any rearrrangement to the thermodynamically more stable 1(3)-acylglycerol byproducts. The method utilized 1,3-dibutyryl-2-acylglycerol substrate ethanolysis by a resinimobilized lipase. Thus, pure radiolabeled 2-acylglycerols can now be conveniently prepared just prior to their utilization. These synthetic studies were published in the Journal of Medicinal Chemistry, 2011. Diacylglycerol lipase assay methodology. Diacylglycerol lipases (DAGLs) generate 2- acylglycerols, and are thus potential targets for disease- or growth-modifying agents, by means of reducing formation of 2-acylglycerols. A radioTLC assay of the hydrolysis of radiolabeled diglyceride substrate [1''-carbon-14]2-arachidonoyl-1-stearoyl-sn-glycerol has been implemented, and used to validate a novel, potentially highthroughput fluorescence resonance energy transfer (FRET) based assay. A number of new DAGL inhibitors that have selectivity for DAGLs were synthesized and screened. This work was very recently published in Bioorganic and Medicinal Chemistry Letters.Acylethanolamines. The work initially focused on myristoylethanolamine (MEA) labeled in the acyl moiety with tritium and with carbon-14. Standard coupling conditions were used and gave the desired radiotracers in decent yields. Tritiated product was needed for the search for binding sites of this signaling messenger, and C-14 labeled product for imaging using phosphorimaging screens. Additionally, C-14 MEA was prepared labeled in the ethanolamine moiety. Fluorine-18 labeled acylethanolamines. A multi-step synthesis was performed to obtain unlabeled N-(16- fluorohexadecanoyl)ethanolamide for an HPLC standard via the precursor 16-bromo-N- [2[(tetrahydro-2Hpyran-2-yl)oxy]ethyl]hexadecanoylamide. Near-anhydrous F-18 and the bromo precursor (approximately 2-3 mg) in acetonitrile (0.5 ml) were heated with a PETWave microwave reactor for 10 min at 80 °C. F-18 incorporation was checked using silica-gel TLC (8:92 methanol/chloroform). Deprotection was carried out using TFA. The crude product was purified by semi-preparative ODS HPLC (80:20 AcN/ H2O). The product peak was diluted in water, concentrated on an SPE column, and eluted in 1 mL EtOH. F-18 incorporation to form the THP protected product was >90% with negligible side products observed. Deprotection and HPLC purification proceeded successfully with >99% radiochemical l purity. Brain distribution studies were done in mice. This work was presented at the Society of Nuclear Medicine meeting in June 2012. Subsequent more detailed studies including whole body tissue distribution studies, microPET experiments and radiochromatographic studies were published in ACS Chemical Neurosciences in 2014. Iodine-125 labeled acylethanolamines. The precursor 12-bromo-N-[2[(tetrahydro-2H-pyran-2-yl)oxy]ethyl]dodecanoylamide was prepared and a 1 mg sample was subject to exchange labeling withradioiodide in refluxing acetonitrile for 1 hour. HPLC analysis as above indicated incorporation of about10% of the radioactivity into a compound with the expected retention time of the corresponding iodocompound. Treatment with TFA converted the radioactivity into a compound with the expected retentiontime of 12-iodododenanoyl ethanolamine. Radiotracer studies in plants. One of the aims of this funding was to follow up the studies of Tripathy et al. (Plant Physiol., 2003) who first reported high affinity binding sites for tritiated myristoylethanolamine in plants, and also reported blockage of these sites by the cannabinoid receptor antagonist AM281. Because plant genomes do not contain genes for cannabinoid receptors, this was an intriguing report. I-125 labeled AM281 was therefore prepared, to facilitate identification of binding sites for this compound in Arabodopsis thaliana plants. However, such sites could not be found, the binding studies were repeated in tobacco plants. Again, binding sites for AM281 were not found. Additionally, it has become evident that clear demonstration of binding sites for tritiated MEA is obscured by metabolic incorporation of radioactivity into plant tissues. Studies on this issue are being aggressively pursued. Binding methodologies used in experiments with animal tissues require modification for their optimal use with plant tissues. Detailed studies of [14C]myristoylethanolamine isotopomers and of [14C]arachidonoylethanolamine isotopomers Since the labeled compounds being prepared for experiments with plants may have utility in Nuclear Medicine, studies were conducted with some of these compounds in mice. The brain uptake of C-14 MEA labeled in either acyl or ethanolamine moiety was 3-4 fold higher than uptake of C-14 myristic acid or C-14 ethanolamine. Carrier MEA increased brain uptake. Autoradiographs of MEA showed regionally specific uptake, with somewhat different patterns for acyl and ethanolamine isotopomers. It is hypothesized that these labeled compounds might form the basis of autoradiographic imaging of regional activity of enzymes such as fatty acid amide hydrolase, which may regulate endocannabinoid tone in animals. Early results were presented at the 2011 ICRS meeting, and at the 2012 Society for Neurosciences. Narachidonoylethanolamine is an endocannabinoid signaling messenger in animals and is known as “anandamide”. It is one of several families of signaling molecules derived from arachidonic acid, the principal omega-6 polyunsaturated fatty acids (PUFA’s) in animal species. Other derivatives of arachidonic acid include thromboxanes and prostaglandins. Full details of the studies with the ethanolamide isotopomers were a part of the PhD dissertation of Kun Hu (nee Qian), and were submitted for publication to Nuclear Medicine and Biology in August 2016. Syntheses of [14C]docosahexanoylethanolamine isotopomers and preliminary biological investigations Docosahexaenoic acid (DHA) is the omega-3 PUFA that can be regarded in some respects as the counterpart of arachidonic acid in the omega-6 series. While arachidonic acid is proinflammatory, DHA is anti-inflammatory, and foods high in DHA (or artificially enriched in DHA) are commonly regarded as promoting health. In contrast to the large literature on the Nethanolamide of arachidonic acid (i.e. the endocannabinoid anandamide) as of now (9/25/2016) there are only six papers on the corresponding ethanolamide of DHA, and when our studies under this grant began there were none. Beneficial actions of endogenously produced DHAethanolamine (“synaptamide”) have been indicated, and to help elucidate the possible roles of synaptamide, we have synthesized this molecule for the first time labeled with C-14 in either the ethanolamine moiety or the fatty acid moiety. Studies of the disposition of endogenously administered isotopomers of DHA-ethanolamine are in progress, to complement tissue culture experiments evaluation hypothesized protective effects of this DHA derivative.« less