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Sample records for 5-substituted five-membered oxocarbenium

  1. Effect of Conformational Rigidity on the Stereoselectivity of Nucleophilic Additions to Five-membered Ring Bicyclic Oxocarbenium Ion Intermediates

    PubMed Central

    Lavinda, O.; Tran, Vi Tuong

    2014-01-01

    Nucleophilic substitution reactions of five-membered ring acetals bearing fused rings reveal that subtle changes in the structure of the fused ring can exert dramatic influences on selectivity. If the fused ring did not constrain the five-membered ring undergoing substitution, selectivity was comparable to what was observed for an unconstrained system (≥92% diastereoselectivity, favoring the product of inside attack on the oxocarbenium ion). If the ring were more constrained by including at least one oxygen atom in the ring, selectivity dropped considerably (to 60% diastereoselectivity in one case). Transition states of the nucleophilic addition of allyltrimethylsilane to selected oxocarbenium ions were calculated using DFT methods. These computational models reproduced the correlation between additional conformational rigidity and selectivity. PMID:25087588

  2. Graphene Layer Growth: Collision of Migrating Five-MemberRings

    SciTech Connect

    Whitesides, Russell; Kollias, Alexander C.; Domin, Dominik; Lester Jr., William A.; Frenklach, Michael

    2005-12-02

    A reaction pathway is explored in which two cyclopenta groups combine on the zigzag edge of a graphene layer. The process is initiated by H addition to a five-membered ring, followed by opening of that ring and the formation of a six-membered ring adjacent to another five-membered ring. The elementary steps of the migration pathway are analyzed using density functional theory to examine the region of the potential energy surface associated with the pathway. The calculations are performed on a substrate modeled by the zigzag edge of tetracene. Based on the obtained energetics, the dynamics of the system are analyzed by solving the energy transfer master equations. The results indicate energetic and reaction-rate similarity between the cyclopenta combination and migration reactions. Also examined in the present study are desorption rates of migrating cyclopenta rings which are found to be comparable to cyclopenta ring migration.

  3. Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

    PubMed Central

    Liu, Jixin; Dasgupta, Srimoyee

    2015-01-01

    Summary The development of enantioselective, copper-catalyzed alkynylations of cyclic iminium and oxocarbenium ions is reviewed. The use of chiral copper-based catalysts has enabled high yields and enantioselectivites in the formation of nitrogen- and oxygen-containing heterocycles with α-stereogenic centers. This review highlights both the accomplishments and the future work needed in this important area. PMID:26877791

  4. Enantioselective Copper(I)-Catalyzed Alkynylation of Oxocarbenium Ions to Set Diaryl Tetrasubstituted Stereocenters.

    PubMed

    Dasgupta, Srimoyee; Rivas, Thomas; Watson, Mary P

    2015-11-16

    An enantioselective, copper(I)-catalyzed addition of terminal alkynes to isochroman ketals to set diaryl, tetrasubstituted stereocenters has been developed. The success of this reaction relies on identification of a Cu/PyBox catalyst capable of distinguishing the faces of the diaryl-substituted oxocarbenium ion. This challenging transformation enables efficient conversion of readily available, racemic ketals into high-value enantioenriched isochroman products with fully substituted stereogenic centers. High yields and enantiomeric excesses are observed for various isochroman ketals and an array of alkynes. PMID:26403641

  5. Synthesis of carbocyclic nucleoside analogs with five-membered heterocyclic nucleobases

    PubMed Central

    Cho, Jong hyun; Coats, Steven J.; Schinazi, Raymond F.

    2015-01-01

    New carbocyclic nucleoside analogs with five-membered heterocyclic nucleobases were synthesized and evaluated as potential anti-HIV and anti-HCV agents. Among the synthesized carbocyclic nucleoside analogs, the pyrazole amide 15f exhibited modest selective anti-HIV-1 activity (EC50 = 24 µM). PMID:26028788

  6. Cascade Synthesis of Five-Membered Lactones using Biomass-Derived Sugars as Carbon Nucleophiles.

    PubMed

    Yamaguchi, Sho; Matsuo, Takeaki; Motokura, Ken; Miyaji, Akimitsu; Baba, Toshihide

    2016-06-01

    We report the cascade synthesis of five-membered lactones from a biomass-derived triose sugar, 1,3-dihydroxyacetone, and various aldehydes. This achievement provides a new synthetic strategy to generate a wide range of valuable compounds from a single biomass-derived sugar. Among several examined Lewis acid catalysts, homogeneous tin chloride catalysts exhibited the best performance to form carbon-carbon bonds. The scope and limitations of the synthesis of five-membered lactones using aldehyde compounds are investigated. The cascade reaction led to high product selectivity as well as diastereoselectivity, and the mechanism leading to the diastereoselectivity was discussed based on isomerization experiments and density functional theory (DFT) calculations. The present results are expected to support new approaches for the efficient utilization of biomass-derived sugars. PMID:27061111

  7. Diels-Alder reactions of five-membered heterocycles containing one heteroatom

    PubMed Central

    Ding, Xiaoyuan; Nguyen, Son T.; Williams, John D.; Peet, Norton P.

    2015-01-01

    Diels-Alder reactions of five-membered heterocycles containing one heteroatom with an N-arylmaleimide were studied. Cycloaddition of 2,5-dimethylfuran (4) with 2-(4-methylphenyl)maleimide (3) in toluene at 60 °C gave bicyclic adduct 5. Cycloadditions of 3 with 2,5-dimethylthiophene (11) and 1,2,5-trimethylpyrrole (14) were also studied. Interestingly, the bicyclic compound 5 cleanly rearranged, with loss of water, when treated with p-toluenesulfonic acid in toluene at 80 °C to give 4,7-dimethyl-2-p-tolylisoindoline-1,3-dione (6). PMID:25838605

  8. Five-membered metallacycles of titanium and zirconium--attractive compounds for organometallic chemistry and catalysis.

    PubMed

    Rosenthal, Uwe; Burlakov, Vladimir V; Bach, Marc A; Beweries, Torsten

    2007-05-01

    In these days a renaissance of metallacycles as an increasingly important class of organometallic compounds for synthetic and catalytic applications is evident, making such very attractive for a plethora of investigations. Titanocene and zirconocene bis(trimethylsilyl)acetylene complexes, regarded as three-membered metallacycles (1-metallacyclopropenes), present a rich chemistry towards unsaturated molecules. By elimination of the alkyne these complexes form by reaction with unsaturated compounds five-membered titana- and zirconacycles, all of which are relevant to stoichiometric and catalytic C-C coupling and cleavage reactions of unsaturated molecules. PMID:17471397

  9. A novel secondary structure based on fused five-membered rings motif

    PubMed Central

    Dhar, Jesmita; Kishore, Raghuvansh; Chakrabarti, Pinak

    2016-01-01

    An analysis of protein structures indicates the existence of a novel, fused five-membered rings motif, comprising of two residues (i and i + 1), stabilized by interresidue Ni+1–H∙∙∙Ni and intraresidue Ni+1–H∙∙∙O=Ci+1 hydrogen bonds. Fused-rings geometry is the common thread running through many commonly occurring motifs, such as β-turn, β-bulge, Asx-turn, Ser/Thr-turn, Schellman motif, and points to its structural robustness. A location close to the beginning of a β-strand is rather common for the motif. Devoid of side chain, Gly seems to be a key player in this motif, occurring at i, for which the backbone torsion angles cluster at ~(−90°, −10°) and (70°, 20°). The fused-rings structures, distant from each other in sequence, can hydrogen bond with each other, and the two segments aligned to each other in a parallel fashion, give rise to a novel secondary structure, topi, which is quite common in proteins, distinct from two major secondary structures, α-helix and β-sheet. Majority of the peptide segments making topi are identified as aggregation-prone and the residues tend to be conserved among homologous proteins. PMID:27511362

  10. Idiopathic avascular necrosis of the femoral heads in five members of a Moroccan family.

    PubMed

    Sekkat, Jihane; Rachidi, Ouafaa; Janani, Saadia; Mkinsi, Ouafaa

    2012-10-01

    Avascular necrosis (AVN) is idiopathic in about 40% of cases. The pathophysiology of avascular necrosis remains incompletely elucidated. Here, we report a case that underlines the role for inherited factors in AVN of the femoral heads. Idiopathic AVN of the femoral heads occurred in five members of the same family (a woman, her two paternal aunts, her male paternal cousin and her female paternal cousin) at a mean age of 42.4 years (range, 33-58 years). Standard pelvic radiographs showed Arlet and Ficat stage 4 AVN in three patients and stage 3 in two patients. None of the patients had a history of glucocorticoid therapy, alcohol abuse, or trauma. All five patients underwent investigations for a cause, including blood cell counts, a lipid profile, coagulation tests, testing for antinuclear antibodies, hemoglobin electrophoresis, ultrasonography of the abdomen, and standard radiographs of the long limb bones. The results were normal or negative, ruling out known hereditary causes of AVN such as sickle cell anemia and Gaucher disease. Many cases of familial AVN of the femoral head have been described in patients with sickle cell anemia or Gaucher disease. However, only five families with idiopathic familial AVN of the femoral heads have been reported (three in the US and two in Taiwan). All the patients in these families had isolated bilateral AVN of the femoral heads without AVN at other sites. PMID:23041471

  11. Stabilization of anti-aromatic and strained five-membered rings with a transition metal

    NASA Astrophysics Data System (ADS)

    Zhu, Congqing; Li, Shunhua; Luo, Ming; Zhou, Xiaoxi; Niu, Yufen; Lin, Minglian; Zhu, Jun; Cao, Zexing; Lu, Xin; Wen, Tingbin; Xie, Zhaoxiong; Schleyer, Paul V. R.; Xia, Haiping

    2013-08-01

    Anti-aromatic compounds, as well as small cyclic alkynes or carbynes, are particularly challenging synthetic goals. The combination of their destabilizing features hinders attempts to prepare molecules such as pentalyne, an 8π-electron anti-aromatic bicycle with extremely high ring strain. Here we describe the facile synthesis of osmapentalyne derivatives that are thermally viable, despite containing the smallest angles observed so far at a carbyne carbon. The compounds are characterized using X-ray crystallography, and their computed energies and magnetic properties reveal aromatic character. Hence, the incorporation of the osmium centre not only reduces the ring strain of the parent pentalyne, but also converts its Hückel anti-aromaticity into Craig-type Möbius aromaticity in the metallapentalynes. The concept of aromaticity is thus extended to five-membered rings containing a metal-carbon triple bond. Moreover, these metal-aromatic compounds exhibit unusual optical effects such as near-infrared photoluminescence with particularly large Stokes shifts, long lifetimes and aggregation enhancement.

  12. Five Members of a Novel Ca2+-binding Protein (CABP) Subfamily with Similarity to Calmodulin*

    PubMed Central

    Haeseleer, Françoise; Sokal, Izabela; Verlinde, Christophe L. M. J.; Erdjument-Bromage, Hediye; Tempst, Paul; Pronin, Alexey N.; Benovic, Jeffrey L.; Fariss, Robert N.; Palczewski, Krzysztof

    2006-01-01

    Five members of a novel Ca2+-binding protein subfamily (CaBP), with 46–58% sequence similarity to calmodulin (CaM), were identified in the vertebrate retina. Important differences between these Ca2+-binding proteins and CaM include alterations within their second EF-hand loop that render these motifs inactive in Ca2+ coordination and the fact that their central α-helixes are extended by one α-helical turn. CaBP1 and CaBP2 contain a consensus sequence for N-terminal myristoylation, similar to members of the recoverin subfamily and are fatty acid acylated in vitro. The patterns of expression differ for each of the various members. Expression of CaBP5, for example, is restricted to retinal rod and cone bipolar cells. In contrast, CaBP1 has a more widespread pattern of expression. In the brain, CaBP1 is found in the cerebral cortex and hippocampus, and in the retina this protein is found in cone bipolar and amacrine cells. CaBP1 and CaBP2 are expressed as multiple, alternatively spliced variants, and in heterologous expression systems these forms show different patterns of subcellular localization. In reconstitution assays, CaBPs are able to substitute functionally for CaM. These data suggest that these novel CaBPs are an important component of Ca2+-mediated cellular signal transduction in the central nervous system where they may augment or substitute for CaM. PMID:10625670

  13. Five-membered cyclic metal carbyne: synthesis of osmapentalynes by the reactions of osmapentalene with allene, alkyne, and alkene.

    PubMed

    Zhu, Congqing; Yang, Yuhui; Wu, Jingjing; Luo, Ming; Fan, Jinglan; Zhu, Jun; Xia, Haiping

    2015-06-01

    The synthesis of small cyclic metal carbynes is challenging due to the large angle strain associated with the highly distorted nonlinear triple bonds. Herein, we report a general route for the synthesis of five-membered cyclic metal carbyne complexes, osmapentalynes, by the reactions of an osmapentalene derivative with allene, alkyne, and alkene. Experimental observations and theoretical calculations document the aromaticity in the fused five-membered rings of osmapentalynes. The realization of transforming osmapentalene to osmapentalyne through this general route would not only allow further exploration of metallapentalyne chemistry but also show promising applications of this novel aromatic system with broad absorption band and high molar absorption coefficient. PMID:25917530

  14. Conformational Transformation of Five-Membered Rings: the Gas Phase Structure of 2-METHYLTETRAHYDROFURAN

    NASA Astrophysics Data System (ADS)

    Van, Vinh; Nguyen, Ha Vinh Lam; Stahl, Wolfgang

    2015-06-01

    2-Methyltetrahydrofuran (2-MeTHF) is a promising environmentally friendly solvent and biofuel component which is derived from renewable resources. Following the principles of Green Chemistry, 2-MeTHF has been evaluated in various fields like organometallics, metathesis, and biosynthesis on the way to more eco-friendly syntheses. Cyclopentane as the prototype of five-membered rings is well-known to exist as twist or envelope structures. However, the conformational analysis of its heterocyclic derivative 2-methyl-tetrahydrothiophene (MTTP) yielded two stable twist conformers and two envelope transition states. Here, we report on the heavy atom r_s structure of the oxygen-analog of MTTP, 2-MeTHF, studied by a combination of molecular beam Fourier transform microwave spectroscopy and quantum chemistry. One conformer of 2-MeTHF was observed and highly accurate molecular parameters were determined using the XIAM program. In addition, all 13C-isotopologues were assigned in natural abundance of 1%. A structural determination based on the r_s positions of all carbon atoms was achieved via Kraitchman's equations. The methyl group in 2-MeTHF undergoes internal rotation and causes A-E splittings of the rotational lines. The barrier was calculated to be 1142 wn at the MP2/6-311++G(d,p) level of theory, which is rather high. Accordingly, narrow A-E splittings could be observed for only a few transitions. However, the barrier height could be fitted while the angles between the internal rotor axis and the principal axes of inertia were taken from the experimental geometry. V. Pace, P. Hoyos, L. Castoldi, P. Domínguez de María, A. R. Alcántara, ChemSusChem 5 (2012), 1369-1379. a) D. F. Aycock, Org. Process Res. Dev. 11 (2007),156-159. b) M. Smoleń, M. Kȩdziorek, K. Grela, Catal. Commun. 44 (2014), 80-84. V. Van, C. Dindic, H.V.L. Nguyen, W. Stahl, ChemPhysChem 16 (2015), 291-294. H. Hartwig, H. Dreizler, Z. Naturforsch. A 51 (1996), 923-932. J. Kraitchman, Am. J. Phys. 21

  15. Soyasaponin Bh, a Triterpene Saponin Containing a Unique Hemiacetal-Functional Five-Membered Ring from Glycine max (Soybeans)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybeans (Glycine max L. Merill) and soy-based food products are major dietary sources of saponins. An oleanane triterpenoid saponin, soyasaponin Bh (1) containing a unique five-membered ring with a hemiacetal functionality together with seven known saponins were isolated from soybeans. Their struct...

  16. Hydride, hydrogen atom, proton, and electron transfer driving forces of various five-membered heterocyclic organic hydrides and their reaction intermediates in acetonitrile.

    PubMed

    Zhu, Xiao-Qing; Zhang, Ming-Tian; Yu, Ao; Wang, Chun-Hua; Cheng, Jin-Pei

    2008-02-27

    The enthalpy changes of 47 five-membered heterocyclic compounds (ZH) [33 substituted 2,3-dihydro-2-phenylbenzo[d]imidazoles (1H-5H), 9 substituted 2,3-dihydro-2-phenylbenzo[d]thiazoles (6H), and 5 substituted 2,3-dihydro-2-phenylbenzo[d]oxazoles (7H)] as a class of very important organic hydride donors to release hydride anion were determined by using titration calorimetry. The result shows that the enthalpy change scale of the 47 ZH in acetonitrile ranges from 49.0 to 93.4 kcal/mol. Such a long energy scale evidently shows that the 47 ZH can construct a large and useful library of organic hydride donors, which can provide various organic hydride donors that the hydride-releasing enthalpies are known. The enthalpy changes of the 47 ZH to release hydrogen atom and the 47 ZH+* to release proton and hydrogen atom were also evaluated by using relative thermodynamic cycles according to Hess' law. The results show: (1) the enthalpy change scale of the 47 ZH to release hydrogen atom covers a range from 71.8 to 91.4 kcal/mol, indicating that the 47 ZH all should be weak hydrogen atom donors. (2) The enthalpy change scales of the 47 ZH+* to release proton and to release hydrogen atom range from 17.5 to 25.7 and from 27.2 to 52.4 kcal/mol, respectively, implying that the proton-donating abilities of ZH+* are generally quite larger than the corresponding hydrogen atom-donating abilities. The standard redox potentials of the 47 ZH and the 47 corresponding salts (Z+) were measured by using cyclic voltammetry (CV) and Osteryoung square wave voltammetry (OSWV), the results display that the standard oxidation potential scale of ZH ranges from -0.254 to -0.002 V for 1H-5H and from 0.310 to 0.638 V for 6H-7H, implying that 1H-5H should be strong one-electron reducing agents and 6H-7H should be weak one-electron reducing agents; the standard reduction potential scale of Z+ ranges from -1.832 to -2.200 V for 1+-5+ and from -1.052 to -1.483V for 6+-7+, meaning that 1+-5+ belong to very

  17. Synthesis of five-membered cyclic ethers by reaction of 1,4-diols with dimethyl carbonate.

    PubMed

    Aricò, Fabio; Tundo, Pietro; Maranzana, Andrea; Tonachini, Glauco

    2012-08-01

    The reaction of 1,4-diols with dimethyl carbonate in the presence of a base led to selective and high-yielding syntheses of related five-membered cyclic ethers. This synthetic pathway has the potential for a wide range of applications. Distinctive cyclic ethers and industrially relevant compounds were synthesized in quantitative yield. The reaction mechanism for the cyclization was investigated. Notably, the chirality of the starting material was maintained. DFT calculations indicated that the formation of five-membered cyclic ethers was energetically the most favorable pathway. Typically, the selectivity exhibited by these systems could be rationalized on the basis of hard-soft acid-base theory. Such principles were applicable as far as computed energy barriers were concerned, but in practice cyclization reactions were shown to be entropically driven. PMID:22730182

  18. A new cascade reaction: concurrent construction of six and five membered rings leading to novel fused quinazolinones.

    PubMed

    Kumar, K Siva; Kumar, P Mahesh; Rao, V Sreenivasa; Jafar, Ahamed A; Meda, Chandana Lakshmi T; Kapavarapu, R; Parsa, Kishore V L; Pal, Manojit

    2012-04-21

    A one-pot cascade reaction has been developed leading to the concurrent construction of six and five membered fused N-heterocyclic rings of indazolo[3,2-b]quinazolinones. The methodology involved the reaction of isatoic anhydride, a hydrazine and o-iodo benzaldehyde in the presence of Pd(PPh(3))(4) and BINAP in MeCN. The mechanism of this cascade reaction is discussed. A variety of indazolo[3,2-b]quinazolinone derivatives were prepared by using this methodology in good yields, some of which were tested for their PDE4 inhibitory properties in vitro. The dose response and docking study performed using a representative compound is presented. PMID:22402867

  19. New series of aromatic/ five-membered heteroaromatic butanesulfonyl hydrazones as potent biological agents: Synthesis, physicochemical and electronic properties

    NASA Astrophysics Data System (ADS)

    Hamurcu, Fatma; Mamaş, Serhat; Ozdemir, Ummuhan Ozmen; Gündüzalp, Ayla Balaban; Senturk, Ozan Sanlı

    2016-08-01

    The aromatic/five-membered heteroaromatic butanesulfonylhydrazone derivatives; 5-bromosalicylaldehydebutanesulfonylhydrazone(1), 2-hydroxy-1-naphthaldehydebutane sulfonylhydrazone(2), indole-3-carboxaldehydebutanesulfonylhydrazone (3), 2-acetylfuran- carboxyaldehydebutanesulfonylhydrazone(4), 2-acetylthiophenecarboxyaldehydebutane- sulfonylhydrazone(5) and 2-acetyl-5-chlorothiophenecarboxyaldehydebutanesulfonyl hydrazone (6) were synthesized by the reaction of butane sulfonic acid hydrazide with aldehydes/ketones and characterized by using elemental analysis, 1H NMR, 13C NMR and FT-IR technique. Their geometric parameters and electronic properties consist of global reactivity descriptors were also determined by theoretical methods. The electrochemical behavior of the butanesulfonylhydrazones were investigated by using cyclic voltammetry (CV), controlled potential electrolysis and chronoamperometry (CA) techniques. The number of electrons transferred (n), diffusion coefficient (D) and standard heterogeneous rate constants (ks) were determined by electrochemical methods.

  20. Ab initio investigation of the structure and nonlinear optical properties of five-membered heterocycles containing sulfur

    NASA Astrophysics Data System (ADS)

    Spassova, Milena; Enchev, Venelin

    2004-03-01

    An ab initio HF and MP2 study of the static (hyper)polarizabilities of 2,4-substituted imidazoles and thiazoles is presented. The comparison of the two types of five-membered heterocycles suggests, that the exocyclic heteroatoms have much more influence upon the calculated hyperpolarizabilities, than the ring heteroatoms. It has been found, that adding diffuse functions to the 6-31G** basis set and inclusion of the electron correlation result in drastic changes in the second hyperpolarizability. The changes are more pronounced for the structures with larger number of sulfur atoms. A HF/6-31G** investigation of a push-pull system, in which thiorhodanine has been chosen as acceptor fragment shows an enhancement of the molecular polarizabilities with respect to the corresponding typical donor-acceptor NH 2/NO 2 polyene.

  1. Two-dimensional character of internal rotation of furfural and other five-member heterocyclic aromatic aldehydes.

    PubMed

    Bataev, Vadim A; Pupyshev, Vladimir I; Godunov, Igor A

    2016-05-15

    The features of nuclear motion corresponding to the rotation of the formyl group (CHO) are studied for the molecules of furfural and some other five-member heterocyclic aromatic aldehydes by the use of MP2/6-311G** quantum chemical approximation. It is demonstrated that the traditional one-dimensional models of internal rotation for the molecules studied have only limited applicability. The reason is the strong kinematic interaction of the rotation of the CHO group and out-of-plane CHO deformation that is realized for the molecules under consideration. The computational procedure based on the two-dimensional approximation is considered for low lying vibrational states as more adequate to the problem. PMID:26971025

  2. Two-dimensional character of internal rotation of furfural and other five-member heterocyclic aromatic aldehydes

    NASA Astrophysics Data System (ADS)

    Bataev, Vadim A.; Pupyshev, Vladimir I.; Godunov, Igor A.

    2016-05-01

    The features of nuclear motion corresponding to the rotation of the formyl group (CHO) are studied for the molecules of furfural and some other five-member heterocyclic aromatic aldehydes by the use of MP2/6-311G** quantum chemical approximation. It is demonstrated that the traditional one-dimensional models of internal rotation for the molecules studied have only limited applicability. The reason is the strong kinematic interaction of the rotation of the CHO group and out-of-plane CHO deformation that is realized for the molecules under consideration. The computational procedure based on the two-dimensional approximation is considered for low lying vibrational states as more adequate to the problem.

  3. Effect of five-membered ring and heteroatom substitution on charge transport properties of perylene discotic derivatives: A theoretical approach.

    PubMed

    Navarro, Amparo; Fernández-Liencres, M Paz; Peña-Ruiz, Tomás; García, Gregorio; Granadino-Roldán, José M; Fernández-Gómez, Manuel

    2016-08-01

    Density functional theory calculations were carried out to investigate the evolvement of charge transport properties of a set of new discotic systems as a function of ring and heteroatom (B, Si, S, and Se) substitution on the basic structure of perylene. The replacement of six-membered rings by five-membered rings in the reference compound has shown a prominent effect on the electron reorganization energy that decreases ∼0.2 eV from perylene to the new carbon five-membered ring derivative. Heteroatom substitution with boron also revealed to lower the LUMO energy level and increase the electron affinity, therefore lowering the electron injection barrier compared to perylene. Since the rate of the charge transfer between two molecules in columnar discotic systems is strongly dependent on the orientation of the stacked cores, the total energy and transfer integral of a dimer as a disc is rotated with respect to the other along the stacking axis have been predicted. Aimed at obtaining a more realistic approach to the bulk structure, the molecular geometry of clusters made up of five discs was fully optimized, and charge transfer rate and mobilities were estimated for charge transport along a one dimensional pathway. Heteroatom substitution with selenium yields electron transfer integral values ∼0.3 eV with a relative disc orientation of 25°, which is the preferred angle according to the dimer energy profile. All the results indicate that the tetraselenium-substituted derivative, not synthetized so far, could be a promising candidate among those studied in this work for the fabrication of n-type semiconductors based on columnar discotic liquid crystals materials. PMID:27497578

  4. Effect of five-membered ring and heteroatom substitution on charge transport properties of perylene discotic derivatives: A theoretical approach

    NASA Astrophysics Data System (ADS)

    Navarro, Amparo; Fernández-Liencres, M. Paz; Peña-Ruiz, Tomás; García, Gregorio; Granadino-Roldán, José M.; Fernández-Gómez, Manuel

    2016-08-01

    Density functional theory calculations were carried out to investigate the evolvement of charge transport properties of a set of new discotic systems as a function of ring and heteroatom (B, Si, S, and Se) substitution on the basic structure of perylene. The replacement of six-membered rings by five-membered rings in the reference compound has shown a prominent effect on the electron reorganization energy that decreases ˜0.2 eV from perylene to the new carbon five-membered ring derivative. Heteroatom substitution with boron also revealed to lower the LUMO energy level and increase the electron affinity, therefore lowering the electron injection barrier compared to perylene. Since the rate of the charge transfer between two molecules in columnar discotic systems is strongly dependent on the orientation of the stacked cores, the total energy and transfer integral of a dimer as a disc is rotated with respect to the other along the stacking axis have been predicted. Aimed at obtaining a more realistic approach to the bulk structure, the molecular geometry of clusters made up of five discs was fully optimized, and charge transfer rate and mobilities were estimated for charge transport along a one dimensional pathway. Heteroatom substitution with selenium yields electron transfer integral values ˜0.3 eV with a relative disc orientation of 25°, which is the preferred angle according to the dimer energy profile. All the results indicate that the tetraselenium-substituted derivative, not synthetized so far, could be a promising candidate among those studied in this work for the fabrication of n-type semiconductors based on columnar discotic liquid crystals materials.

  5. 2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties.

    PubMed

    Sayapin, Yury A; Tupaeva, Inna O; Kolodina, Alexandra A; Gusakov, Eugeny A; Komissarov, Vitaly N; Dorogan, Igor V; Makarova, Nadezhda I; Metelitsa, Anatoly V; Tkachev, Valery V; Aldoshin, Sergey M; Minkin, Vladimir I

    2015-01-01

    A series of derivatives of 2-hetaryl-1,3-tropolone (β-tropolone) was prepared by the acid-catalyzed reaction of 2-methylbenzoxazoles, 2-methylbenzothiazoles and 2,3,3-trimethylindoline with 3,4,5,6-tetrachloro-1,2-benzoquinone. The molecular structures of the three representative compounds were determined by X-ray crystallography. In crystal and (as shown by the DFT PBE0/6-311+G** calculations) in solution, 2-hetaryl-4,5,6,7-tetrachloro- and 2-hetaryl-5,6,7-trichloro-1,3-tropolones exist in the NH-tautomeric form with a strong resonance-assisted intramolecular N-H···O hydrogen bond. The mechanism of the formation of 1,3-tropolones in the reaction of methylene-active five-membered heterocycles with o-chloranil in acetic acid solution has been studied using density functional theory (DFT) methods. The reaction of 2-(2-benzoxa(thia)zolyl)-5,6,7-trichloro(4,5,6,7-tetrachloro)-1,3-tropolones with alcohols leads to the contraction of the seven-membered tropone ring with the formation of 2-(2-benzoxa(thia)zolyl)-6-alkoxycarbonylphenols. The molecular structure of 2-(2-ethoxycarbonyl-6-hydroxy-3,4,5-trichlorophenyl)benzoxazole has been determined by X-ray diffraction. 2-(2-Benzoxa(thia)zolyl)-6-alkoxycarbonylphenols display intense green fluorescence with anomalous Stokes shifts caused by the excited state intramolecular proton transfer (ESIPT) effects. PMID:26664640

  6. 2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties

    PubMed Central

    Sayapin, Yury A; Tupaeva, Inna O; Kolodina, Alexandra A; Gusakov, Eugeny A; Komissarov, Vitaly N; Makarova, Nadezhda I; Metelitsa, Anatoly V; Tkachev, Valery V; Aldoshin, Sergey M; Minkin, Vladimir I

    2015-01-01

    Summary A series of derivatives of 2-hetaryl-1,3-tropolone (β-tropolone) was prepared by the acid-catalyzed reaction of 2-methylbenzoxazoles, 2-methylbenzothiazoles and 2,3,3-trimethylindoline with 3,4,5,6-tetrachloro-1,2-benzoquinone. The molecular structures of the three representative compounds were determined by X-ray crystallography. In crystal and (as shown by the DFT PBE0/6-311+G** calculations) in solution, 2-hetaryl-4,5,6,7-tetrachloro- and 2-hetaryl-5,6,7-trichloro-1,3-tropolones exist in the NH-tautomeric form with a strong resonance-assisted intramolecular N–H···O hydrogen bond. The mechanism of the formation of 1,3-tropolones in the reaction of methylene-active five-membered heterocycles with o-chloranil in acetic acid solution has been studied using density functional theory (DFT) methods. The reaction of 2-(2-benzoxa(thia)zolyl)-5,6,7-trichloro(4,5,6,7-tetrachloro)-1,3-tropolones with alcohols leads to the contraction of the seven-membered tropone ring with the formation of 2-(2-benzoxa(thia)zolyl)-6-alkoxycarbonylphenols. The molecular structure of 2-(2-ethoxycarbonyl-6-hydroxy-3,4,5-trichlorophenyl)benzoxazole has been determined by X-ray diffraction. 2-(2-Benzoxa(thia)zolyl)-6-alkoxycarbonylphenols display intense green fluorescence with anomalous Stokes shifts caused by the excited state intramolecular proton transfer (ESIPT) effects. PMID:26664640

  7. Schleyer hyperconjugative aromaticity and Diels-Alder reactivity of 5-substituted cyclopentadienes.

    PubMed

    Levandowski, Brian J; Zou, Lufeng; Houk, K N

    2016-01-01

    Schleyer's discovery of hyperconjugative aromaticity and antiaromaticity in 5-substituted cyclopentadienes further expanded our understanding of the pervasive influence of aromaticity. Acceptors induce antiaromatic character by Schleyer's negative hyperconjugative aromaticity, and donors have the opposite effect. We computationally explored the Diels-Alder reactivity of 5-substituted cyclopentadienes with ethylene and maleic anhydride. The predicted billionfold difference in the computed gas phase rate constants at room temperature for the Diels-Alder reactions of 5-substituted cyclopentadienes with ethylene or maleic anhydride results from differences in the transition state distortion energies, which are directly related to the hyperconjugative aromaticity of these molecules. PMID:26444427

  8. Molecular basis for the affinity and specificity in the binding of five-membered iminocyclitols with glycosidases: an experimental and theoretical synergy.

    PubMed

    Shandilya, Ashutosh; Ganesan, Muthupandian; Parveen, Firdaus; Ramesh, Namakkal G; Jayaram, B

    2016-06-24

    An unusual substituent dictated complementarity in the inhibition of amino-modified five-membered iminocyclitols toward various glycosidases was reported by us. These intriguing results encouraged us to seek a molecular level explanation for the observation that may facilitate the design of specific iminocyclitol inhibitors against glycosidases of choice. We present here a detailed theoretical account that is substantiated with some new experimental investigations on the molecular origins of the differential affinities of iminocyclitols with various glycosidases. The studies involve docking/scoring, molecular dynamics simulations followed by syntheses of a few novel five-membered iminocyclitols and their in vitro binding assays. Directional hydrogen bonds and snug fit of the ligands are implicated as contributory to the observed selectivities. The observed synergy between the computations and experiment is likely to spur further research in the design of novel iminocyclitols with specific inhibitory activities. PMID:27085905

  9. Competition between the hydrolysis and deamination of cytidine and its 5-substituted derivatives in aqueous acid.

    PubMed Central

    Lönnberg, H; Käppi, R

    1985-01-01

    The monocations of a few 5-substituted cytidines have been shown to undergo competitive deamination to the corresponding uridines and hydrolysis to 5-substituted cytosines and D-ribose. The first-order rate constants measured at different temperatures indicate that the proportion of the hydrolysis is considerably increased with the increasing temperature. Electron-withdrawal by a polar substituent at C5 appears to facilitate the hydrolysis to a larger extent that the deamination. The ionic strength has practically no influence on the rate of either reaction. PMID:4000961

  10. A user-friendly Matlab program and GUI for the pseudorotation analysis of saturated five-membered ring systems based on scalar coupling constants

    PubMed Central

    Hendrickx, Pieter MS; Martins, José C

    2008-01-01

    Background The advent of combinatorial chemistry has revived the interest in five-membered heterocyclic rings as scaffolds in pharmaceutical research. They are also the target of modifications in nucleic acid chemistry. Hence, the characterization of their conformational features is of considerable interest. This can be accomplished from the analysis of the 3JHH scalar coupling constants. Results A freely available program including an easy-to-use graphical user interface (GUI) has been developed for the calculation of five-membered ring conformations from scalar coupling constant data. A variety of operational modes and parameterizations can be selected by the user, and the coupling constants and electronegativity parameters can be defined interactively. Furthermore, the possibility of generating high-quality graphical output of the conformational space accessible to the molecule under study facilitates the interpretation of the results. These features are illustrated via the conformational analysis of two 4'-thio-2'-deoxynucleoside analogs. Results are discussed and compared with those obtained using the original PSEUROT program. Conclusion A user-friendly Matlab interface has been developed and tested. This should considerably improve the accessibility of this kind of calculations to the chemical community. PMID:18950513

  11. Local aromaticity in naphtho-annelated fluoranthenes: can the five-membered rings be more aromatic than the six-membered rings?

    PubMed

    Radenković, Slavko; Tošović, Jelena; Đurđević Nikolić, Jelena

    2015-05-21

    All Kekulé-structure-based theories predict that the central five-membered ring in fluoranthene and naphtho-annelated fluoranthenes is nonaromatic. In the present work, a detailed study of the local aromaticity in a series of naphtho-annelated fluoranthene derivatives was performed by means of the following aromaticity indices: the energy effect (ef), bond resonance energy (BRE), multicenter delocalization indices (MCI), harmonic oscillator model of aromaticity (HOMA) index, nucleus-independent chemical shifts (NICS), and ring current maps. It was found that, according to the ef, BRE, MCI, and HOMA values, the pentagonal rings in some naphtho-annelated fluoranthenes can be even more aromatic than some hexagonal rings in the respective molecules. The magnetic indices do not support the results obtained by the energetic, electron delocalization, and geometrical aromaticity indices. PMID:25915757

  12. Synthesis of chiral five-membered carbocyclic ring amino acids with an acetal moiety and helical conformations of its homo-chiral homopeptides.

    PubMed

    Koba, Yurie; Hirata, Yoko; Ueda, Atsushi; Oba, Makoto; Doi, Mitsunobu; Demizu, Yosuke; Kurihara, Masaaki; Tanaka, Masakazu

    2016-11-01

    Chiral five-membered carbocyclic ring amino acids bearing various diol acetal moieties were synthesized starting from l-malic acid, and homo-chiral homopeptides composed of cyclic amino acid (S)-Ac5 c(3EG) bearing an ethylene glycol acetal, up to an octapeptide, were prepared. A conformational analysis revealed that (S)-Ac5 c(3EG) homopeptides formed helical structures. (S)-Ac5 c(3EG) homopeptides, up to hexapeptides, formed helical structures without controlling the helical screw direction, while (S)-Ac5 c(3EG) hepta- and octapeptides formed helical structures with a preference for the left-handed (M) helical-screw direction. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 555-562, 2016. PMID:26566886

  13. [Synthesis of 2-methyl-5-substituted phenoxy-primaquine and antimalarials activity].

    PubMed

    Zhong, B H; Deng, R X; Zhong, J X; Wang, J

    1990-01-01

    In searching for efficient, safe and radically curative agent and causal prophylactics for malaria, seven 2-methyl-5-substituted phenoxy-6-methoxy-8-(1-methyl-4-aminobutylamino)-quinolines (II1-7) were synthesized and their antimalarial activities were compared with the corresponding 4-methyl substituted derivatives of primaquine. The starting material, 2-nitro-4-methoxy-5-bromo-acetanilide (III), was prepared from p-methoxy aniline through acetylation, bromination and nitration. III was then condensed with substituted phenols in the presence of potassium carbonate. The condensed products were subsequently hydrolyzed with dilute alcoholic hydrochloric acid to yield 2-nitro-4-methoxy-5-substituted phenoxy-aniline (V) which underwent Skraup's reaction with 2-butenal to provide the key intermediates 2-methyl-5-substituted phenoxy-6-methoxy-8-nitroquinolines (VI). These 8-nitroquinoline derivatives were reduced to 8-aminoquinoline derivatives (VII). The latter were condensed with 4-bromo-1-phthalimido-pentane and then hydrolyzed with hydrazine hydrate, the final products were obtained as oxalate or succinate. The structure of the target compounds and unknown intermediates were confirmed by elementary and spectral analysis. Primary biological evaluation showed that all compounds II1-7 were much less active than the 4-methyl substituted derivatives and slightly less active than primaquine in both causal prophylactic test against Plasmodium yoelii and suppressive antimalarial test against P. berhei. PMID:2239331

  14. Design, Synthesis and Bioactivity of N-Glycosyl-N′-(5-substituted phenyl-2-furoyl) Hydrazide Derivatives

    PubMed Central

    Cui, Zining; Su, Hang; Jiang, Jiazhen; Yang, Xinling; Nishida, Yoshihiro

    2014-01-01

    Condensation products of 5-substituted phenyl-2-furoyl hydrazide with different monosaccharides d-glucose, d-galactose,d-mannose, d-fucose and d-arabinose were prepared. The anomerization and cyclic-acyclic isomers were investigated by 1H NMR spectroscopy. The results showed that, except for the d-glucose derivatives, which were in the presence of β-anomeric forms, all derivatives were in an acyclic Schiff base form. Their antifungal and antitumor activities were studied. The bioassay results indicated that some title compounds showed superior effects over the commercial positive controls. PMID:24756095

  15. Theoretical studies on tautomerism and IR spectra of C-5 substituted imidazoles

    NASA Astrophysics Data System (ADS)

    Kurzepa, Mal̷gorzata; Dobrowolski, Jan Cz; Mazurek, Aleksander P.

    2001-05-01

    Total energy, Gibbs free energy, the highest π and σ electronic states, and IR spectra were calculated for twelve C-5 substituted imidazoles at the MP2/6-311++G ∗∗ level. The COOH and BH 2 groups stabilize strongly the N 1-H tautomer, the F and OH groups stabilize strongly the N 3-H tautomer, whereas the NH 2 and NO 2 groups favours the N 3-H tautomer with a similar, medium strength. The calculated IR spectra of the imidazoles studied reveal differences between the two tautomers, but they do not follow the order of derivatives emerging from the energetics.

  16. 5-Substituted 3-chlorokenpaullone derivatives are potent inhibitors of Trypanosoma brucei bloodstream forms.

    PubMed

    Orban, Oliver C F; Korn, Ricarda S; Benítez, Diego; Medeiros, Andrea; Preu, Lutz; Loaëc, Nadège; Meijer, Laurent; Koch, Oliver; Comini, Marcelo A; Kunick, Conrad

    2016-08-15

    Trypanothione synthetase is an essential enzyme for kinetoplastid parasites which cause highly disabling and fatal diseases in humans and animals. Inspired by the observation that N(5)-substituted paullones inhibit the trypanothione synthetase from the related parasite Leishmania infantum, we designed and synthesized a series of new derivatives. Although none of the new compounds displayed strong inhibition of Trypanosoma brucei trypanothione synthetase, several of them caused a remarkable growth inhibition of cultivated Trypanosoma brucei bloodstream forms. The most potent congener 3a showed antitrypanosomal activity in double digit nanomolar concentrations and a selectivity index of three orders of magnitude versus murine macrophage cells. PMID:27349574

  17. Transferable potentials for phase equilibria. 9. Explicit hydrogen description of benzene and five-membered and six-membered heterocyclic aromatic compounds.

    PubMed

    Rai, Neeraj; Siepmann, J Ilja

    2007-09-13

    The explicit hydrogen version of the transferable potentials for phase equilibria (TraPPE-EH) force field is extended to benzene, pyridine, pyrimidine, pyrazine, pyridazine, thiophene, furan, pyrrole, thiazole, oxazole, isoxazole, imidazole, and pyrazole. While the Lennard-Jones parameters for carbon, hydrogen (two types), nitrogen (two types), oxygen, and sulfur are transferable for all 13 compounds, the partial charges are specific for each compound. The benzene dimer energies for sandwich, T-shape, and parallel-displaced configurations obtained for the TraPPE-EH force field compare favorably with high-level electronic structure calculations. Gibbs ensemble Monte Carlo simulations were carried out to compute the single-component vapor-liquid equilibria for benzene, pyridine, three diazenes, and eight five-membered heterocycles. The agreement with experimental data is excellent with the liquid densities and vapor pressures reproduced within 1 and 5%, respectively. The critical temperatures and normal boiling points are predicted with mean deviations of 0.8 and 1.6%, respectively. PMID:17713943

  18. Cytogenetic and symbiont analysis of five members of the B. dorsalis complex (Diptera, Tephritidae): no evidence of chromosomal or symbiont-based speciation events.

    PubMed

    Augustinos, Antonios A; Drosopoulou, Elena; Gariou-Papalexiou, Aggeliki; Asimakis, Elias D; Cáceres, Carlos; Tsiamis, George; Bourtzis, Kostas; Penelope Mavragani-Tsipidou; Zacharopoulou, Antigone

    2015-01-01

    The Bactrocera dorsalis species complex, currently comprising about 90 entities has received much attention. During the last decades, considerable effort has been devoted to delimiting the species of the complex. This information is of great importance for agriculture and world trade, since the complex harbours several pest species of major economic importance and other species that could evolve into global threats. Speciation in Diptera is usually accompanied by chromosomal rearrangements, particularly inversions that are assumed to reduce/eliminate gene flow. Other candidates currently receiving much attention regarding their possible involvement in speciation are reproductive symbionts, such as Wolbachia, Spiroplasma, Arsenophonus, Rickettsia and Cardinium. Such symbionts tend to spread quickly through natural populations and can cause a variety of phenotypes that promote pre-mating and/or post-mating isolation and, in addition, can affect the biology, physiology, ecology and evolution of their insect hosts in various ways. Considering all these aspects, we present: (a) a summary of the recently gained knowledge on the cytogenetics of five members of the Bactrocera dorsalis complex, namely Bactrocera dorsalis s.s., Bactrocera invadens, Bactrocera philippinensis, Bactrocera papayae and Bactrocera carambolae, supplemented by additional data from a Bactrocera dorsalis s.s. colony from China, as well as by a cytogenetic comparison between the dorsalis complex and the genetically close species, Bactrocera tryoni, and, (b) a reproductive symbiont screening of 18 different colonized populations of these five taxa. Our analysis did not reveal any chromosomal rearrangements that could differentiate among them. Moreover, screening for reproductive symbionts was negative for all colonies derived from different geographic origins and/or hosts. There are many different factors that can lead to speciation, and our data do not support chromosomal and/or symbiotic

  19. Cytogenetic and symbiont analysis of five members of the B. dorsalis complex (Diptera, Tephritidae): no evidence of chromosomal or symbiont-based speciation events

    PubMed Central

    Augustinos, Antonios A.; Drosopoulou, Elena; Gariou-Papalexiou, Aggeliki; Asimakis, Elias D.; Cáceres, Carlos; Tsiamis, George; Bourtzis, Kostas; Penelope Mavragani-Tsipidou; Zacharopoulou, Antigone

    2015-01-01

    Abstract The Bactrocera dorsalis species complex, currently comprising about 90 entities has received much attention. During the last decades, considerable effort has been devoted to delimiting the species of the complex. This information is of great importance for agriculture and world trade, since the complex harbours several pest species of major economic importance and other species that could evolve into global threats. Speciation in Diptera is usually accompanied by chromosomal rearrangements, particularly inversions that are assumed to reduce/eliminate gene flow. Other candidates currently receiving much attention regarding their possible involvement in speciation are reproductive symbionts, such as Wolbachia, Spiroplasma, Arsenophonus, Rickettsia and Cardinium. Such symbionts tend to spread quickly through natural populations and can cause a variety of phenotypes that promote pre-mating and/or post-mating isolation and, in addition, can affect the biology, physiology, ecology and evolution of their insect hosts in various ways. Considering all these aspects, we present: (a) a summary of the recently gained knowledge on the cytogenetics of five members of the Bactrocera dorsalis complex, namely Bactrocera dorsalis s.s., Bactrocera invadens, Bactrocera philippinensis, Bactrocera papayae and Bactrocera carambolae, supplemented by additional data from a Bactrocera dorsalis s.s. colony from China, as well as by a cytogenetic comparison between the dorsalis complex and the genetically close species, Bactrocera tryoni, and, (b) a reproductive symbiont screening of 18 different colonized populations of these five taxa. Our analysis did not reveal any chromosomal rearrangements that could differentiate among them. Moreover, screening for reproductive symbionts was negative for all colonies derived from different geographic origins and/or hosts. There are many different factors that can lead to speciation, and our data do not support chromosomal and/or symbiotic

  20. Electrophilic 5-Substituted Uracils as Potential Radiosensitizers: A Density Functional Theory Study.

    PubMed

    Makurat, Samanta; Chomicz-Mańka, Lidia; Rak, Janusz

    2016-08-18

    Although 5-bromo-2'-deoxyuridine (5BrdU) possesses significant radiosensitizing power in vitro, clinical studies do not confirm any advantages of radiotherapy employing 5BrdU. This situation calls for a continuous search for efficient radiosensitizers. Using the proposed mechanism of radiosensitization by 5BrdU, we propose a series of 5-substituted uracils, XYU, that should undergo efficient dissociative electron attachment. The DFT-calculated thermodynamic and kinetic data concerning the XYU degradations induced by electron addition suggests that some of the scrutinized derivatives have much better characteristics than 5BrdU itself. Synthesis of these promising candidates for radiosensitizers, followed by studies of their radiosensitizing properties in DNA context, and ultimately in cancer cells, are further steps to confirm their potential applicability in anticancer treatment. PMID:27156191

  1. Synthesis and Bioactivity of 5-Substituted-2-furoyl Diacylhydazide Derivatives with Aliphatic Chain

    PubMed Central

    Cui, Zining; Li, Xinghai; Tian, Fang; Yan, Xiaojing

    2014-01-01

    A series of 5-substituted-2-furoyl diacylhydazide derivatives with aliphatic chain were designed and synthesized. Their structures were characterized by IR, 1H NMR, elemental analysis, and X-ray single crystal diffraction. The anti-tumor bioassay revealed that some title compounds exhibited promising activity against the selected cancer cell lines, especially against the human promyelocytic leukemic cells (HL-60). Their fungicidal tests indicated that most of the title compounds showed significant anti-fungal activity. The preliminary structure-activity relationship showed that the aliphatic chain length and differences in the R2 group had obvious effects on the anti-tumor and anti-fungal activities. The bioassay results demonstrated that the title compounds hold great promise as novel lead compounds for further drug discovery. PMID:24853128

  2. Synthesis and biological evaluation of C(5)-substituted derivatives of leukotriene biosynthesis inhibitor BRP-7.

    PubMed

    Levent, Serkan; Gerstmeier, Jana; Olgaç, Abdurrahman; Nikels, Felix; Garscha, Ulrike; Carotti, Andrea; Macchiarulo, Antonio; Werz, Oliver; Banoglu, Erden; Çalışkan, Burcu

    2016-10-21

    Pharmacological intervention with 5-lipoxygenase (5-LO) pathway leading to suppression of leukotriene (LT) biosynthesis is a clinically validated strategy for treatment of respiratory and cardiovascular diseases such as asthma and atherosclerosis. Here we describe the synthesis of a series of C(5)-substituted analogues of the previously described 5-LO-activating protein (FLAP) inhibitor BRP-7 (IC50 = 0.31 μM) to explore the effects of substitution at the C(5)-benzimidazole (BI) ring as a strategy to increase the potency against FLAP-mediated 5-LO product formation. Incorporation of polar substituents on the C(5) position of the BI core, exemplified by compound 11 with a C(5)-nitrile substituent, significantly enhances the potency for suppression of 5-LO product synthesis in human neutrophils (IC50 = 0.07 μM) and monocytes (IC50 = 0.026 μM). PMID:27423639

  3. [Characterization of peroxidase-catalyzed oxidation of chromogenic substrates by tetrazole and its 5-substituted derivatives].

    PubMed

    Karaseva, E I; Gaponik, P N; Metelitsa, D I

    2005-01-01

    Peroxidase-catalyzed oxidation of 2,2-azino-di(3-ethyl-benzthiazolydine-6-sulfonic acid) (ABTS) and 3,3',5,5'-tetramethylbenzidine (TMB) is activated by tetrazole and its 5-substituted derivatives--5-amino-(AmT), 5-methyl- (MeT), 5-phenyl- (PhT), and 5-CF3- (CF3-T) tetrazoles. In phosphate-citrate or phosphate buffer (pH 6.4 or 7.2; 20 degrees C), the activating effect of tetrazoles on TMB and ABTS oxidation decreased in the series AmT > MeT > T > PhT > CF3-T and T > AmT > MeT > PhT, respectively. The (coefficient) degree of activation (alpha), expressed in M(-1), determined for both substrates and all activators, depended on substrate type, buffer nature, and pH (it increased as pH increased from 6.4 to 7.2). For TMB oxidation, good correlation between lgalpha and the Hammet constants sigma(meta) for m-substituents in the benzene series NH2, CH3, C6H5, and CF3 was found. It is suggested that AmT, MeT, and T can be used as activators of peroxidase-catalyzed oxidation of TMB and ABTS, as well as in designing peroxidase-based biosensors. PMID:15859456

  4. Prebiotic synthesis of 5-substituted uracils: a bridge between the RNA world and the DNA-protein world

    NASA Technical Reports Server (NTRS)

    Robertson, M. P.; Miller, S. L.

    1995-01-01

    Under prebiotic conditions, formaldehyde adds to uracil at the C-5 position to produce 5-hydroxymethyluracil with favorable rates and equilibria. Hydroxymethyluracil adds a variety of nucleophiles, such as ammonia, glycine, guanidine, hydrogen sulfide, hydrogen cyanide, imidazole, indole, and phenol, to give 5-substituted uracils with the side chains of most of the 20 amino acids in proteins. These reactions are sufficiently robust that, if uracil had been present on the primitive Earth, then these substituted uracils would also have been present. The ribozymes of the RNA world would have included many of the functional groups found in proteins today, and their catalytic activities may have been considerably greater than presently assumed.

  5. Prebiotic Synthesis of 5-Substituted Uracils: A Bridge Between the RNA World and the DNA-Protein World

    NASA Astrophysics Data System (ADS)

    Robertson, Michael P.; Miller, Stanley L.

    1995-05-01

    Under prebiotic conditions, formaldehyde adds to uracil at the C-5 position to produce 5-hydroxymethyluracil with favorable rates and equilibria. Hydroxymethyluracil adds a variety of nucleophiles, such as ammonia, glycine, guanidine, hydrogen sulfide, hydrogen cyanide, imidazole, indole, and phenol, to give 5-substituted uracils with the side chains of most of the 20 amino acids in proteins. These reactions are sufficiently robust that, if uracil had been present on the primitive Earth, then these substituted uracils would also have been present. The ribozymes of the RNA world would have included many of the functional groups found in proteins today, and their catalytic activities may have been considerably greater than presently assumed.

  6. Prebiotic synthesis of 5-substituted uracils: a bridge between the RNA world and the DNA-protein world.

    PubMed

    Robertson, M P; Miller, S L

    1995-05-01

    Under prebiotic conditions, formaldehyde adds to uracil at the C-5 position to produce 5-hydroxymethyluracil with favorable rates and equilibria. Hydroxymethyluracil adds a variety of nucleophiles, such as ammonia, glycine, guanidine, hydrogen sulfide, hydrogen cyanide, imidazole, indole, and phenol, to give 5-substituted uracils with the side chains of most of the 20 amino acids in proteins. These reactions are sufficiently robust that, if uracil had been present on the primitive Earth, then these substituted uracils would also have been present. The ribozymes of the RNA world would have included many of the functional groups found in proteins today, and their catalytic activities may have been considerably greater than presently assumed. PMID:7732378

  7. Receptor binding profiles and quantitative structure-affinity relationships of some 5-substituted-N,N-diallyltryptamines.

    PubMed

    Cozzi, Nicholas V; Daley, Paul F

    2016-02-01

    N,N-Diallyltryptamine (DALT) and 5-methoxy-N,N-diallyltryptamine (5-MeO-DALT) are two tryptamines synthesized and tested by Alexander Shulgin. In self-experiments, 5-MeO-DALT was reported to be psychoactive in the 12-20mg range, while the unsubstituted compound DALT had few discernible effects in the 42-80 mg range. Recently, 5-MeO-DALT has been used in nonmedical settings for its psychoactive effects, but these effects have been poorly characterized and little is known of its pharmacological properties. We extended the work of Shulgin by synthesizing additional 5-substituted-DALTs. We then compared them to DALT and 5-MeO-DALT for their binding affinities at 45 cloned receptors and transporter proteins. Based on in vitro binding affinity, we identified 27 potential receptor targets for the 5-substituted-DALT compounds. Five of the DALT compounds had affinity in the 10-80 nM range for serotonin 5-HT1A and 5-HT2B receptors, while the affinity of DALT itself at 5-HT1A receptors was slightly lower at 100 nM. Among the 5-HT2 subtypes, the weakest affinity was at 5-HT2A receptors, spanning 250-730 nM. Five of the DALT compounds had affinity in the 50-400 nM range for serotonin 5-HT1D, 5-HT6, and 5-HT7 receptors; again, it was the unsubstituted DALT that had the weakest affinity at all three subtypes. The test drugs had even weaker affinity for 5-HT1B, 5-HT1E, and 5-HT5A subtypes and little or no affinity for the 5-HT3 subtype. These compounds also had generally nanomolar affinities for adrenergic α2A, α2B, and α2C receptors, sigma receptors σ1 and σ2, histamine H1 receptors, and norepinephrine and serotonin uptake transporters. They also bound to other targets in the nanomolar-to-low micromolar range. Based on these binding results, it is likely that multiple serotonin receptors, as well as several nonserotonergic sites are important for the psychoactive effects of DALT drugs. To learn whether any quantitative structure-affinity relationships existed, we evaluated

  8. Theoretical studies of the structure, stability, and detonation properties of vicinal-tetrazine 1,3-dioxide annulated with a five-membered heterocycle. 2. Annulation with a pyrazole ring.

    PubMed

    Wang, Tianyi; Zheng, Chunmei; Gong, Xuedong; Xia, Mingzhu

    2015-10-01

    1,2,3,4-Tetrazine (vicinal-tetrazine) high-energy-density compounds (HEDCs) are receiving increasing attention due to their promise as explosives. We have performed a series of studies of vicinal-tetrazine 1,3-dioxides annulated with a range of five-membered heterocycles, considering their potential as high-energy, low-sensitivity explosives. In the present work, 12 pyrazolo-1,2,3,4-tetrazine 1,3-dioxides (pyrazolo-TDOs), P1-P12, were studied theoretically. Their geometrical structures in the gas phase were studied at the B3LYP/6-311++G(d,p) level of density functional theory (DFT). Their gas-phase enthalpies of formation were calculated by the homodesmotic reaction method. Their enthalpies of sublimation and solid phase enthalpies of formation were also predicted. Their detonation properties were estimated with the Kamlet-Jacobs equations, based on their predicted densities and enthalpies of formation in the solid state. Their bond dissociation activation energies (BDAEs) and the available free space in the lattice of each compound were calculated to evaluate their stabilities. P1, P4, and P11 were found to achieve the energy level of RDX and have acceptable stabilities, and are therefore considered to be the three most promising pyrazolo-TDOs for use as high-energy, low-sensitivity explosives. We believe that further studies, both experimental and theoretical, of these three targets would be worthwhile. PMID:26404478

  9. Theoretical studies of the structure, stability, and detonation properties of vicinal-tetrazine 1,3-dioxide annulated with a five-membered heterocycle. 1. Annulation with a triazole ring.

    PubMed

    Wang, Tianyi; Zheng, Chunmei; Liu, Yan; Gong, Xuedong; Xia, Mingzhu

    2015-08-01

    1,2,3,4-Tetrazine (vicinal-tetrazine) high-energy-density compounds (HEDCs) are receiving increasing attention due to their promise as explosives. We have performed a series of studies of vicinal-tetrazine 1,3-dioxides annulated with a range of five-membered heterocycles, considering their potential as high-energy, low-sensitivity explosives. In the present work, twelve 1,2,3-triazol-1,2,3,4-tetrazine 1,3-dioxides (TTDOs; T1-T12) were studied theoretically. Their geometric structures in the gas phase were studied at the B3LYP/6-311++G(d,p) level of density functional theory (DFT). Their gas-phase enthalpies of formation were calculated by the homodesmotic reaction method. Their enthalpies of sublimation and solid-phase enthalpies of formation were also predicted. Their detonation properties were estimated with the Kamlet-Jacobs equations, based on their predicted densities and enthalpies of formation in the solid state. Their bond dissociation activation energies (BDAEs) and the available free space in the lattice of each compound were calculated to evaluate their stabilities. T2, T5, and T11 were found to have higher energies than RDX and acceptable stabilities, and are therefore considered to be the three most promising TTDOs for use as high-energy, low-sensitivity explosives. We believe that further studies, both experimental and theoretical, of these three targets would be worthwhile. PMID:26194022

  10. An insight into the aromaticity of fullerene anions: experimental evidence for diamagnetic ring currents in the five-membered rings of C(60)(6-) and C(70)(6-).

    PubMed

    Sternfeld, Tamar; Thilgen, Carlo; Hoffman, Roy E; Del Rosario Colorado Heras, María; Diederich, François; Wudl, Fred; Scott, Lawrence T; Mack, James; Rabinovitz, Mordecai

    2002-05-22

    Reduction of the two "closed" [6,6] methanofullerenes, [6,6]C(61)H(2) (1) and [6,6]C(71)H(2) (5), to the corresponding hexaanions with lithium metal causes the bridgehead-bridgehead bonds to open, at least partially, and this change gives rise to diamagnetic ring currents in the resulting homoconjugated six-membered rings (6-MRs). These new ring currents shield the overlying hydrogen atoms on the methylene bridge and induce upfield shifts of 1.60 and 0.11 ppm in their (1)H NMR resonances, respectively. Analogous reduction of the already "open" [5,6]methanofullerenes, [5,6]C(61)H(2) (2) and [5,6]C(71)H(2) (3 and 4), only slightly enhances the shielding of the hydrogen atoms over the homoconjugated 6-MRs (upfield shifts of 0.13, 0.68, and 0.14 ppm, respectively) but leads to exceptionally strong diamagnetic ring currents in the homoconjugated five- membered rings (5-MRs), as evidenced by dramatic shielding of the hydrogen atoms situated over them (upfield shift of 5.01, 6.78, and 1.63 ppm, respectively). The strongest shielding is seen for the hydrogen atom sitting over the 5-MR at the pole of C(71)H(2)(6)(-) (delta = -0.255 ppm) indicating that the excess charge density is concentrated at the poles. PMID:12010047

  11. 5'-Substituted Amiloride Derivatives as Allosteric Modulators Binding in the Sodium Ion Pocket of the Adenosine A2A Receptor.

    PubMed

    Massink, Arnault; Louvel, Julien; Adlere, Ilze; van Veen, Corine; Huisman, Berend J H; Dijksteel, Gabrielle S; Guo, Dong; Lenselink, Eelke B; Buckley, Benjamin J; Matthews, Hayden; Ranson, Marie; Kelso, Michael; IJzerman, Adriaan P

    2016-05-26

    The sodium ion site is an allosteric site conserved among many G protein-coupled receptors (GPCRs). Amiloride 1 and 5-(N,N-hexamethylene)amiloride 2 (HMA) supposedly bind in this sodium ion site and can influence orthosteric ligand binding. The availability of a high-resolution X-ray crystal structure of the human adenosine A2A receptor (hA2AAR), in which the allosteric sodium ion site was elucidated, makes it an appropriate model receptor for investigating the allosteric site. In this study, we report the synthesis and evaluation of novel 5'-substituted amiloride derivatives as hA2AAR allosteric antagonists. The potency of the amiloride derivatives was assessed by their ability to displace orthosteric radioligand [(3)H]4-(2-((7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a]-[1,3,5]triazin-5-yl)amino)ethyl)phenol ([(3)H]ZM-241,385) from both the wild-type and sodium ion site W246A mutant hA2AAR. 4-Ethoxyphenethyl-substituted amiloride 12l was found to be more potent than both amiloride and HMA, and the shift in potency between the wild-type and mutated receptor confirmed its likely binding to the sodium ion site. PMID:27124340

  12. Growth of epitaxial orthorhombic YO{sub 1.5}-substituted HfO{sub 2} thin film

    SciTech Connect

    Shimizu, Takao; Katayama, Kiliha; Kiguchi, Takanori; Akama, Akihiro; Konno, Toyohiko J.; Funakubo, Hiroshi

    2015-07-20

    YO{sub 1.5}-substituted HfO{sub 2} thin films with various substitution amounts were grown on (100) YSZ substrates by the pulsed laser deposition method directly from the vapor phase. The epitaxial growth of film with different YO{sub 1.5} amounts was confirmed by the X-ray diffraction method. Wide-area reciprocal lattice mapping measurements were performed to clarify the crystal symmetry of films. The formed phases changed from low-symmetry monoclinic baddeleyite to high-symmetry tetragonal/cubic fluorite phases through an orthorhombic phase as the YO{sub 1.5} amount increased from 0 to 0.15. The additional annular bright-field scanning transmission electron microscopy indicates that the orthorhombic phase has polar structure. This means that the direct growth by vapor is of polar orthorhombic HfO{sub 2}-based film. Moreover, high-temperature X-ray diffraction measurements showed that the film with a YO{sub 1.5} amount of 0.07 with orthorhombic structure at room temperature only exhibited a structural phase transition to tetragonal phase above 450 °C. This temperature is much higher than the reported maximum temperature of 200 °C to obtain ferroelectricity as well as the expected temperature for real device application. The growth of epitaxial orthorhombic HfO{sub 2}-based film helps clarify the nature of ferroelectricity in HfO{sub 2}-based films (186 words/200 words)

  13. Design and synthesis of 5-(substituted benzylidene)thiazolidine-2,4-dione derivatives as novel tyrosinase inhibitors.

    PubMed

    Ha, Young Mi; Park, Yun Jung; Kim, Jin-Ah; Park, Daeui; Park, Ji Young; Lee, Hye Jin; Lee, Ji Yeon; Moon, Hyung Ryong; Chung, Hae Young

    2012-03-01

    In continuing our search for novel tyrosinase inhibitors, a series of 5-(substituted benzylidene)thiazolidine-2,4-diones were rationally designed and synthesized, and their inhibitory effects on mushroom tyrosinase activity were evaluated. Twelve target compounds 2a-2l were designed and synthesized based on the structural characteristics of N-phenylthiourea, a tyrosinase inhibitor, and tyrosine and L-DOPA, the natural substrates of tyrosinase. Among them, (Z)-5-(4-hydroxybenzylidene)thiazolidine-2,4-dione (2a) and (Z)-5-(3-hydroxy-4-methoxybenzylidene)thiazolidine-2,4-dione (2f) exhibited much higher tyrosinase inhibitory activities, with IC(50) values of 13.36 and 9.87 μM, respectively, than kojic acid (IC(50) = 24.72 μM). Kinetic analysis of tyrosinase inhibition revealed that 2a and 2f are competitive inhibitors of mushroom tyrosinase. In addition, through prediction of the potato catechol oxidase tertiary structure and simulation of docking with compounds 2a and 2f using DOCK6, we found that these inhibitors likely bind to the active site of the enzyme. Docking simulation results suggested that 2a and 2f have high binding affinities with potato catechol oxidase. In addition, compounds 2a and 2f effectively inhibited tyrosinase activity and reduced melanin levels in B16 cells treated with α-melanocyte-stimulating hormone (α-MSH). These data strongly suggest that compounds 2a and 2f suppress the production of melanin via the inhibition of tyrosinase activity. PMID:22301213

  14. Aromaticity effects on the profiles of the lowest triplet-state potential-energy surfaces for rotation about the C=C bonds of olefins with five-membered ring substituents: an example of the impact of Baird's rule.

    PubMed

    Zhu, Jun; Fogarty, Heather A; Möllerstedt, Helene; Brink, Maria; Ottosson, Henrik

    2013-08-01

    A density functional theory study on olefins with five-membered monocyclic 4n and 4n+2 π-electron substituents (C4H3X; X=CH(+), SiH(+), BH, AlH, CH2, SiH2, O, S, NH, and CH(-)) was performed to assess the connection between the degree of substituent (anti)aromaticity and the profile of the lowest triplet-state (T1) potential-energy surface (PES) for twisting about olefinic C=C bonds. It exploited both Hückel's rule on aromaticity in the closed-shell singlet ground state (S0) and Baird's rule on aromaticity in the lowest ππ* excited triplet state. The compounds CH2=CH(C4H3X) were categorized as set A and set B olefins depending on which carbon atom (C2 or C3) of the C4H3X ring is bonded to the olefin. The degree of substituent (anti)aromaticity goes from strongly S0 -antiaromatic/T1 -aromatic (C5H4 (+)) to strongly S0 -aromatic/T1- antiaromatic (C5H4(-)). Our hypothesis is that the shapes of the T1 PESs, as given by the energy differences between planar and perpendicularly twisted olefin structures in T1 [ΔE(T1)], smoothly follow the changes in substituent (anti)aromaticity. Indeed, correlations between ΔE(T1) and the (anti)aromaticity changes of the C4 H3 X groups, as measured by the zz-tensor component of the nucleus-independent chemical shift ΔNICS(T1;1)zz , are found both for sets A and B separately (linear fits; r(2) =0.949 and 0.851, respectively) and for the two sets combined (linear fit; r(2) =0.851). For sets A and B combined, strong correlations are also found between ΔE(T1) and the degree of S0 (anti)aromaticity as determined by NICS(S0,1)zz (sigmoidal fit; r(2) =0.963), as well as between the T1 energies of the planar olefins and NICS(S0,1)zz (linear fit; r(2) =0.939). Thus, careful tuning of substituent (anti)aromaticity allows for design of small olefins with T1 PESs suitable for adiabatic Z/E photoisomerization. PMID:23794153

  15. Planar B3S2H3(-) and B3S2H3 clusters with a five-membered B3S2 ring: boron-sulfur hydride analogues of cyclopentadiene.

    PubMed

    Li, Da-Zhi; Li, Rui; Zhang, Li-Juan; Ou, Ting; Zhai, Hua-Jin

    2016-08-21

    Boron clusters can serve as inorganic analogues of hydrocarbons or polycyclic aromatic hydrocarbons (PAHs). We present herein, based upon global searches and electronic structural calculations at the B3LYP and CCSD(T) levels, the global-minimum structures of two boron-sulfur hydride clusters: C2v B3S2H3(-) (1, (2)B1) and C2v B3S2H3 (2, (1)A1). Both species are perfectly planar and feature a five-membered B3S2 ring as the structural core, with three H atoms attached terminally to the B sites. Chemical bonding analysis shows that C2v B3S2H3(-) (1) has a delocalized 5π system within a heteroatomic B3S2 ring, analogous to the π bonding in cyclopentadiene, D5h C5H5. The corresponding closed-shell C2v B3S2H3(2-) (3, (1)A1) dianion is only a local minimum. At the single-point CCSD(T) level, it is 5.7 kcal mol(-1) above the chain-like C1 ((1)A) open structure. This situation is in contrast to the cyclopentadienyl anion, C5H5(-), a prototypical aromatic hydrocarbon with a π sextet. The C2v B3S2H3 (2) neutral cluster is readily obtained upon removal of one π electron from C2v B3S2H3(-) (1). The anion photoelectron spectrum of C2v B3S2H3(-) (1) and the infrared absorption spectrum of C2v B3S2H3 (2) are predicted. The C2v B3S2H3(-) (1) species can be stabilized in sandwich-type C2h [(B3S2H3)2Fe](2-) and salt C2h [(B3S2H3)2Fe]Li2 complexes. An intriguing difference is observed between the pattern of π sextet in C2v B3S2H3(2-) (3) dianion and that in cyclopentadienyl anion. The present work also sheds light on the mechanism of structural evolution in the B3S2H3(0/-/2-) series with charge states. PMID:27424889

  16. Design and synthesis of novel 5-substituted acyclic pyrimidine nucleosides as potent and selective inhibitors of hepatitis B virus.

    PubMed

    Kumar, Rakesh; Nath, Mahendra; Tyrrell, D Lorne J

    2002-05-01

    A novel class of 5-substituted acyclic pyrimidine nucleosides, 1-[(2-hydroxyethoxy)methyl]-5-(1-azidovinyl)uracil (9a), 1-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl]-5-(1-azidovinyl)uracil (9b), and 1-[4-hydroxy-3-(hydroxymethyl)-1-butyl]-5-(1-azidovinyl)uracil (9c), were synthesized by regiospecific addition of bromine azide to the 5-vinyl substituent of the respective 5-vinyluracils (2a-c) followed by treatment of the obtained 5-(1-azido-2-bromoethyl) compounds (3a-c) with t-BuOK, to affect the base-catalyzed elimination of HBr. Thermal decomposition of 9b and 9c at 110 degrees C in dioxane yielded corresponding 5-[2-(1-azirinyl)]uracil analogues (10b,c). The 5-(1-azidovinyl)uracil derivatives 9a-c were found to exhibit potent and selective in vitro anti-HBV activity against duck hepatitis B virus (DHBV) infected primary duck hepatocytes at low concentrations (EC(50) = 0.01-0.1 microg/mL range). The most active anti-DHBV agent (9c), possessing a [4-hydroxy-3-(hydroxymethyl)-1-butyl] substituent at N-1, exhibited an activity (EC(50) of 0.01-0.05 microg/mL) comparable to that of reference compound (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3-TC) (EC(50) = 0.01-0.05 microg/mL). In contrast, related 5-[2-(1-azirinyl)]uracil analogues (10b,c) were devoid of anti-DHBV activity, indicating that an acyclic side chain at C-5 position of the pyrimidine ring is essential for anti-HBV activity. The pyrimidine nucleosides (9a-c, 10b,c) exhibited no cytotoxic activity against a panel of 60 human cancer cell lines. All of the compounds investigated did not show any detectable toxicity to several stationary and proliferating host cell lines or to mitogen stimulated proliferating human T lymphocytes, up to the highest concentration tested. PMID:11985471

  17. Synthesis of 5-substituted 1H-tetrazoles by the copper-catalyzed [3+2] cycloaddition of nitriles and trimethylsilyl azide.

    PubMed

    Jin, Tienan; Kitahara, Fukuzou; Kamijo, Shin; Yamamoto, Yoshinori

    2008-09-01

    The copper-catalyzed [3+2] cycloaddition between various nitriles and trimethylsilyl azide in DMF/MeOH produced the corresponding 5-substituted 1H-tetrazoles in good to high yields. It was proposed that the reaction proceeds through the formation in situ of a copper azide species and subsequent [3+2] cycloaddition with the nitriles. Furthermore, we found that a copper and triethylamine combined catalyst also promoted the cycloaddition of nitriles and trimethylsilyl azide to afford the 5-substituted 1H-tetrazoles at relatively low reaction temperatures. The copper azide species would be formed by reaction of the copper catalyst with Et(3)NHN(3) generated in situ. PMID:18561350

  18. Stereoselective amine-thiourea-catalysed sulfa-Michael/nitroaldol cascade approach to 3,4,5-substituted tetrahydrothiophenes bearing a quaternary stereocenter

    PubMed Central

    Meninno, Sara; Volpe, Chiara; Della Sala, Giorgio; Capobianco, Amedeo

    2016-01-01

    Summary An investigation on the stereoselective cascade sulfa-Michael/aldol reaction of nitroalkenes and commercially available 1,4-dithiane-2,5-diol to 3,4,5-substituted tetrahydrothiophenes, bearing a quaternary stereocenter, is presented. A secondary amine thiourea derived from (R,R)-1,2-diphenylethylamine was found to be the most effective catalyst when using trans-β-methyl-β-nitrostyrenes affording the heterocyclic products in good yields and moderate stereoselectivities. PMID:27340455

  19. The 5-substituted piperazine as a novel secondary pharmacophore greatly improving the physical properties of urea-based inhibitors of soluble epoxide hydrolase.

    PubMed

    Li, Hui-Yuan; Jin, Yi; Morisseau, Christophe; Hammock, Bruce D; Long, Ya-Qiu

    2006-10-01

    The inhibition of the mammalian soluble epoxide hydrolase (sEH) is a promising new therapy in the treatment of hypertention and inflammation. The problems of limited water solubility and high melting points commonly displayed by the active 1,3-disubstituted ureas prevent the further development of potent urea-based sEH inhibitors. Therefore, a new class of potent inhibitors of sEH were designed and synthesized by the introduction of a polar constrained piperazino group in the right side of adasmantyl urea to increase the water solubility. A facile and general synthesis was established to prepare a series of 1-adamantan-1-yl-3-(2-piperazin-2-yl-ethyl)-ureas (1a-d) with various 5-substitutions on the 2-piperazino ring, which will advance the SAR study by the efficient making of structurally diverse analogs. The effect of the 5-substitution on the activity and the water solubility was examined. The best potency was exhibited by the 5-benzyl-substituted-piperazine-containing urea with an IC50 value of 1.37 microM against human sEH and good water solubility (S=7.46 mg/mL) and low melting point, in which the 5-substituted piperazine serves as a favorable secondary pharmacophore and a water-solubility enhancing group. Our present work provides a promising new template for the design of orally available therapeutic agents for the disorders that can be addressed by changing the in vivo concentration of the chemical mediators that contain an epoxide. PMID:16784862

  20. Synthesis of functionalized 5-substituted thiazolidine-2-thiones via adscititious xanthate-promoted radical cyclization of allyl(alkyl/aryl)dithiocarbamates.

    PubMed

    Gao, Simiao; Zhang, Yu; Dong, Jun; Chen, Ning; Xu, Jiaxi

    2016-01-21

    Functionalized 5-substituted thiazolidine-2-thiones were synthesized efficiently from alkyl allyl(alkyl/aryl)-dithiocarbamates via radical cyclization with the corresponding S-alkyl O-ethyl xanthates as the adscititious radical precursors. The application of the adscititious radical precursors improves not only the yields, but also the efficiency in the radical cyclization reaction significantly. The current adscititious radical precursor method provides a new strategy for the achievement and improvement of some radical reactions which are hardly or difficultly realized by the traditional direct methods. PMID:26626401

  1. Synthesis and antibacterial activity of pyridinium-tailored 2,5-substituted-1,3,4-oxadiazole thioether/sulfoxide/sulfone derivatives.

    PubMed

    Wang, Pei-Yi; Zhou, Lei; Zhou, Jian; Wu, Zhi-Bing; Xue, Wei; Song, Bao-An; Yang, Song

    2016-02-15

    By introducing the pyridinium group into 2,5-substituted-1,3,4-oxadiazole, a series of pyridinium-tailored 2,5-substituted-1,3,4-oxadiazole thioether/sulfoxide/sulfone derivatives were obtained, and their antibacterial activities were evaluated via turbidimeter test in vitro. The bioassays reveal that most of the target compounds exhibit better inhibition activities against pathogen Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri than positive controls bismerthiazol (CK1) or thiodiazole copper (CK2). Among them, I-8, I-10, I-12, II-10, II-12, III-10, and III-12 exert excellent inhibition activities against the three pathogenic bacteria with the half-maximal effective concentration (EC50) values ranging from 0.54 to 12.14 μg/mL. Our results demonstrate that pyridinium-tailored 1,3,4-oxadiazole thioether/sulfoxide/sulfone derivatives can serve as potential alternative bactericides for the management of plant bacterial diseases. PMID:26810264

  2. Synthesis and antimicrobial evaluation of L-phenylalanine-derived C5-substituted rhodanine and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone.

    PubMed

    Jin, Xin; Zheng, Chang-Ji; Song, Ming-Xia; Wu, Yan; Sun, Liang-Peng; Li, Yin-Jing; Yu, Li-Jun; Piao, Hu-Ri

    2012-10-01

    Four novel series of compounds, including the l-phenylalanine-derived C5-substituted rhodanine (6a-q, 7a-j) and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone (9a-e, 11a-e) have been designed, synthesized, characterized, and evaluated for their antibacterial activity. Some of these compounds showed significant antibacterial activity against Gram-positive bacterias, especially against the strains of multidrug-resistant clinical isolates, among which compounds 6c-e, 6g, 6i, 6j and 6q exhibiting high levels of antimicrobial activity against Staphylococcus aureus RN4220 with minimum inhibitory concentration (MIC) values of 2 μg/mL. Compound 6q showed the most potent activity of all of the compounds against all of the test multidrug-resistant clinical isolates tested. Unfortunately, however, none of the compounds were active against Gram-negative bacteria at 64 μg/mL. PMID:22982124

  3. Synthesis and biological activities of novel 5-substituted-1,3,4-oxadiazole Mannich bases and bis-Mannich bases as ketol-acid reductoisomerase inhibitors.

    PubMed

    Zhang, Yan; Liu, Xing-Hai; Zhan, Yi-Zhou; Zhang, Li-Yuan; Li, Zheng-Ming; Li, Yong-Hong; Zhang, Xiao; Wang, Bao-Lei

    2016-10-01

    A series of novel 5-substituted-1,3,4-oxadiazole Mannich bases and bis-Mannich bases have been conveniently synthesized in good yields. Their structures were characterized by IR, (1)H NMR, (13)C NMR and elemental analysis. The preliminary bioassay results indicated that some of the compounds showed promising in vitro fungicidal activities towards several test plant fungi; some of them exhibited significant herbicidal activities against Brassica campestris and excellent in vitro inhibitory activities against rice ketol-acid reductoisomerase (KARI). Among 14 novel compounds, 8c, 8d and 8m showed potent KARI inhibitory activities with Ki value of (0.96±0.42), (3.86±0.49) and (3.10±0.71) μmol/L, respectively, and were comparable with IpOHA. These compounds could be novel KARI inhibitors for further investigation. The density functional theory (DFT) calculations and molecular docking were carried out to study the structure-activity relationship (SAR) of the active inhibitors in this Letter. PMID:27575481

  4. Synthesis, spectral and antimicrobial activity of Zn(II) complexes with Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole and benzaldehyde/2-hydroxyacetophenone/indoline-2,3-dione

    NASA Astrophysics Data System (ADS)

    Singh, Ajay K.; Pandey, O. P.; Sengupta, S. K.

    2013-09-01

    Zn(II) complexes have been synthesized by reacting zinc acetate with Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole and 2-hydroxyacetophenone/benzaldehyde/indoline-2,3-dione. All these complexes are soluble in DMF and DMSO; low molar conductance values indicate that they are non electrolytes. Elemental analyses suggest that the complexes have 1:2 metal to ligands stoichiometry of the types [ZnL2(H2O)2](L = monoanionic Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole and 2-hydroxyacetophenone/indoline-2,3-dione) [ZnL2‧(OOCCH3)2(H2O)2](L‧ = neutral Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole and benzaldehyde), and they were characterized by IR, 1H NMR, and 13C NMR. Particle sizes of synthesized compounds were measured with dynamic light scattering (DLS) analyser which indicates that particle diameter are of the range ca. 100-200 nm. All these Schiff bases and their complexes have also been screened for their antibacterial (Bacillus subtilis (B. subtilis), Escherichia coli (E. coli) and antifungal activities (Colletotrichum falcatum (C. falcatum), Aspergillus niger (A. niger), Fusarium oxysporium (F. oxysporium) Curvularia pallescence (C. pallescence). The antimicrobial activities have shown that upon complexation the activity increases.

  5. High-level ab initio predictions for the ionization energies and heats of formation of five-membered-ring molecules: thiophene, furan, pyrrole, 1,3-cyclopentadiene, and borole, C4H4X/C4H4X+ (X = S, O, NH, CH2, and BH).

    PubMed

    Lo, Po-Kam; Lau, Kai-Chung

    2011-02-10

    The ionization energies (IEs) and heats of formation (ΔH°(f0)/ΔH°(f298)) for thiophene (C(4)H(4)S), furan (C(4)H(4)O), pyrrole (C(4)H(4)NH), 1,3-cyclopentadiene (C(4)H(4)CH(2)), and borole (C(4)H(4)BH) have been calculated by the wave function-based ab initio CCSD(T)/CBS approach, which involves the approximation to the complete basis set (CBS) limit at the coupled-cluster level with single and double excitations plus a quasi-perturbative triple excitation [CCSD(T)]. Where appropriate, the zero-point vibrational energy correction (ZPVE), the core-valence electronic correction (CV), and the scalar relativistic effect (SR) are included in these calculations. The respective CCSD(T)/CBS predictions for C(4)H(4)S, C(4)H(4)O, C(4)H(4)NH, and C(4)H(4)CH(2), being 8.888, 8.897, 8.222, and 8.582 eV, are in excellent agreement with the experimental values obtained from previous photoelectron and photoion measurements. The ΔH°(f0)/ΔH°(f298) values for the aforementioned molecules and their corresponding cations have also been predicted by the CCSD(T)/CBS method, and the results are compared with the available experimental data. The comparisons between the CCSD(T)/CBS predictions and the experimental values for C(4)H(4)S, C(4)H(4)O, C(4)H(4)NH, and C(4)H(4)CH(2) suggest that the CCSD(T)/CBS procedure is capable of predicting reliable IE values for five-membered-ring molecules with an uncertainty of ±13 meV. In view of the excellent agreements between the CCSD(T)/CBS predictions and the experimental values for C(4)H(4)S, C(4)H(4)O, C(4)H(4)NH, and C(4)H(4)CH(2), the similar CCSD(T)/CBS IE and ΔH°(f0)/ΔH°(f298) predictions for C(4)H(4)BH, whose thermochemical data are not readily available due to its reactive nature, should constitute a reliable data set. The CCSD(T)/CBS IE(C(4)H(4)BH) value is 8.868 eV, and ΔH°(f0)/ΔH°(f298) values for C(4)H(4)BH and C(4)H(4)BH(+) are 269.5/258.6 and 1125.1/1114.6 kJ/mol, respectively. The highest occupied molecular orbitals

  6. Three-component synthesis of C2F5-substituted pyrazoles from C2F5CH2NH2·HCl, NaNO2 and electron-deficient alkynes

    PubMed Central

    2015-01-01

    Summary A one-pot reaction between C2F5CH2NH2·HCl, NaNO2 and electron-deficient alkynes gives C2F5-substituted pyrazoles in excellent yields. The transformation smoothly proceeds in dichloromethane/water, tolerates the presence of air, and requires no purification of products by column chromatography. Mechanistically, C2F5CH2NH2·HCl and NaNO2 react first in water to generate C2F5CHN2, that participates in a [3 + 2] cycloaddition with electron-deficient alkynes in dichloromethane. PMID:25670987

  7. I2 mediated synthesis of 5-substituted-3-methyl/benzyl-1,3,4-oxadiazol-2(3H)-ones via sequential condensation/oxidative cyclization and rearrangement.

    PubMed

    Patel, Shyam Sunder; Chandna, Nisha; Kumar, Shreemoyee; Jain, Nidhi

    2016-06-15

    A simple and efficient iodine-assisted protocol for the synthesis of 5-substituted-3-methyl/benzyl-1,3,4-oxadiazol-2(3H)-ones has been developed. The reaction involves a sequential condensation followed by tandem oxidative cyclization and rearrangement of readily available methyl/benzyl carbazates and aldehydes as starting substrates. The presence of iodine and base promotes intramolecular C-O bond formation, followed by Chapman-like rearrangement at 90 °C of the methyl/benzyl group in the hydrazone intermediate formed during the condensation step. This transition-metal-free approach has been adopted to generate a variety of oxadiazolones under mild conditions in good to excellent yields. PMID:26853373

  8. Novel 5-Hydroxy, 5-Substituted Benzenesulfonamide Pyrimidine-2,4,6-Triones Attenuate Lipopolysaccharide-Induced Acute Lung Injury via Inhibition of the Gelatinases, MMP-2 and MMP-9.

    PubMed

    He, Wei; Jiang, Jie; Yu, Ze-Qian; Zhou, Jia-Hua

    2016-08-01

    Preclinical Research A novel series of ten 5-hydroxy, 5-substituted benzene sulfonamide pyrimidine-2,4,6-triones were synthesized and their structures ascertained using (1) H-NMR, (13) C-NMR, mass and elemental analysis. These compounds were subsequently tested for inhibition of MMP-2 and MMP-9 where most exhibited activity with compound 5i being the most potent against MMP-2 and MMP-9 with IC50 values of 2.35 nM and 8.24 nM, respectively. Compound 5i was further analyzed in a mouse LPS-induced acute lung injury model where it had protective activity. Histochemical studies indicated that 5i improved the vascular integrity of the lung. Drug Dev Res 77 : 251-257, 2016. © 2016 Wiley Periodicals, Inc. PMID:27455162

  9. Synthesis and biological activity of novel series of 4-methoxy, and 4,9-dimethoxy-5-substituted furo[2,3-g]-1,2,3-benzoxathiazine-7,7-dioxide derivatives

    PubMed Central

    El-Sawy, Eslam R.; Ebaid, Manal S.; Abo-Salem, Heba M.; El-Hallouty, Salwa; Kassem, Emad M.; Mandour, Adel H.

    2013-01-01

    A novel series of 4-methoxy, and 4,9-dimethoxy-5-substituted furo[2,3-g]-1,2,3-benzoxathiazine-7,7-dioxide derivatives 3a,b, 10a–g and 11a–g were prepared in good yields via the reaction of 4-methoxy (1a) and 4,7-dimethoxy-5-acetyl-6-hydroxybenzofurans (1b) and their α,β-unsaturated keto derivatives 6a–g and 7a–g with chlorosulfonyl isocyanate (CSI). On the other hand, N-chlorosulfonyl carbamate derivatives 4a,b, 12a,b and 13a,b were prepared and allowed to react with piperidine to give the corresponding N-piperidinosulfonyl carbamate derivatives 5a,b, 14a,b and 15a,b, respectively. Sixteen new target compounds 3a,b, 10a–g, and 11a–g were tested for their DPPH radical-scavenging, and in vitro antiproliferative activity against A-549, MCF7 and HCT-116 cancer cell lines. Compounds 10a, 11c, 11e, and 11g showed moderate DPPH radical-scavenging activity compared to ascorbic acid at 100 μg/mL. 4,9-Dimethoxy-5-substituted styrylfuro[3,2-g]-1,2,3-benzoxathiazine-7,7-dioxides 11a, 11b, and 11c were found to be highly active against A-549 and HCT-116 cancer cell lines with IC50 values ranging from 0.02 to 0.08 μmol/mL compared to doxorubicin with IC50 = 0.04 and 0.06 μmol/mL, respectively. PMID:25685501

  10. Novel 5-Substituted Pyrrolo[2,3-d]pyrimidines as Dual Inhibitors of Glycinamide Ribonucleotide Formyltransferase and 5-Aminoimidazole-4-carboxamide Ribonucleotide Formyltransferase and as Potential Antitumor Agents

    PubMed Central

    Wang, Yiqiang; Mitchell-Ryan, Shermaine; Raghavan, Sudhir; George, Christina; Orr, Steven; Hou, Zhanjun; Matherly, Larry H.; Gangjee, Aleem

    2016-01-01

    A new series of 5-substituted thiopheneyl pyrrolo[2,3-d]pyrimidines 6–11 with varying chain lengths (n = 1–6) were designed and synthesized as hybrids of the clinically used anticancer drug pemetrexed (PMX) and our 6-substituted thiopheneyl pyrrolo[2,3-d]pyrimidines 2c and 2d with folate receptor (FR) α and proton-coupled folate transporter (PCFT) uptake specificity over the reduced folate carrier (RFC) and inhibition of de novo purine nucleotide biosynthesis at glycinamide ribonucleotide formyltransferase (GARFTase). Compounds 6–11 inhibited KB human tumor cells in the order 9 = 10 > 8 > 7 > 6 = 11. Compounds 8–10 were variously transported by FRα, PCFT, and RFC and, unlike PMX, inhibited de novo purine nucleotide rather than thymidylate biosynthesis. The antiproliferative effects of 8 and 9 appeared to be due to their dual inhibitions of both GARFTase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase. Our studies identify a unique structure–activity relationship for transport and dual target inhibition. PMID:25602637

  11. Synthesis, chemical reactivity, and antileukemic activity of 5-substituted 6,7-bis(hydroxymethyl)pyrrolo[1,2-c]thiazole biscarbamates and the corresponding sulfoxides and sulfones.

    PubMed

    Anderson, W K; Mach, R H

    1987-11-01

    A series of bis(N-methylcarbamate) and bis[N-(2-propyl)carbamate] derivatives of 5-substituted 6,7-bis(hydroxy-methyl)pyrrolo[1,2-c]thiazoles was prepared. The compounds were tested for activity in vivo against P388 lymphocytic leukemia, and the chemical reactivities of the compounds were compared by using the model nucleophile 4-(4-nitrobenzyl)pyridine (NBP). The 5-(3,4-dichlorophenyl)-substituted biscarbamates 6b, 8b, and 12b were inactive and unreactive toward NBP. The 5-methyl-substituted biscarbamates 6a, 7a, 8a, 9a, 12a, and 13a were all active against murine P388 lymphocytic leukemia. The chemical reactivities of the active compounds depended on the oxidation state of the sulfur. The reactivity toward NBP followed the order S greater than SO much greater than SO2. The sulfones 12a and 13a are the most active compounds in this series, and their lack of reactivity toward NBP led to the suggestion that 12a and 13a are activated in vivo. PMID:3669018

  12. Synthesis of classical, four-carbon bridged 5-substituted furo[2,3-d]pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates1

    PubMed Central

    Gangjee, Aleem; Zeng, Yibin; McGuire, John J.; Kisliuk, Roy L.

    2008-01-01

    We report, for the first time, the biological activities of four carbon atom bridged classical antifolates on dihydrofolate reductase (DHFR), thymidylate synthase (TS) and folylpolyglutamate synthetase (FPGS) as well as on antitumor activity. Extension of the bridge homologation studies of classical two-carbon bridged antifolates, a 5-substituted 2,4-diaminofuro[2,3-d]pyrimidine (1) and a 6-subsituted 2-amino-4-oxopyrrolo[2,3-d]pyrimidine (2) afforded two, four-carbon bridged antifolates, analogues 5 and 6, with enhanced FPGS substrate activity and inhibitory activity against tumor cells in culture (EC50 values of ≤ 10−7 M) compared with the two-carbon bridged analogues. These results support our original hypothesis that the distance and orientation of the side chain para-aminobenzoyl-L-glutamate moiety with respect to the pyrimidine ring is a crucial determinant of biological activity. In addition, this study demonstrates that, for classical antifolates that are substrates for FPGS, poor inhibitory activity against isolated target enzymes is not necessarily a predictor of a lack of antitumor activity. PMID:16078850

  13. General and modular synthesis of isomeric 5-substituted pyridin-2-yl and 6-substituted pyridin-3-yl C-ribonucleosides bearing diverse alkyl, aryl, hetaryl, amino, carbamoyl, and hydroxy groups.

    PubMed

    Štefko, Martin; Slavětínská, Lenka; Klepetářová, Blanka; Hocek, Michal

    2011-08-19

    A general modular and practical methodology for preparation of diverse 5-substituted pyridin-2-yl and 6-substituted pyridin-3-yl C-ribonucleosides was developed. Regioselective lithiation of 2,5-dibromopyridine proceeded at position 5 or 2 depending on the solvent, and the resulting bromopyridyl lithium species underwent additions to TBS-protected ribonolactone and follow-up transformations to corresponding acetylated hemiketal intermediates 7 and 10 that were diastereoselectively reduced to give either 5-bromopyridin-2-yl or 6-bromopyridin-3-yl silyl-protected C-ribonucleosides 8 or 11 in 68% and 77% overall yields as pure β-anomers. These bromopyridyl C-nucleoside intermediates were then subjected to a series of palladium-catalyzed cross-coupling reactions, aminations, aminocarbonylations, and hydroxylations to give a series of protected 1β-(5-alkyl-, 5-aryl-, 5-amino-, 5-carbamoyl-, and 5-hydroxypyridin-2-yl)-C-ribonucleosides 13a-i and β-(6-alkyl-, 6-aryl-, 6-amino-, 6-carbamoyl-, and 6-hydroxypyridin-3-yl)-C-ribonucleosides 15a-i. Deprotection of silylated nucleosides by Et(3)N·3HF, TBAF, or TFA gave a series of free C-nucleosides 14a-i and 16a-i. PMID:21739971

  14. Novel 5-substituted pyrrolo[2,3-d]pyrimidines as dual inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase and as potential antitumor agents.

    PubMed

    Wang, Yiqiang; Mitchell-Ryan, Shermaine; Raghavan, Sudhir; George, Christina; Orr, Steven; Hou, Zhanjun; Matherly, Larry H; Gangjee, Aleem

    2015-02-12

    A new series of 5-substituted thiopheneyl pyrrolo[2,3-d]pyrimidines 6-11 with varying chain lengths (n = 1-6) were designed and synthesized as hybrids of the clinically used anticancer drug pemetrexed (PMX) and our 6-substituted thiopheneyl pyrrolo[2,3-d]pyrimidines 2c and 2d with folate receptor (FR) α and proton-coupled folate transporter (PCFT) uptake specificity over the reduced folate carrier (RFC) and inhibition of de novo purine nucleotide biosynthesis at glycinamide ribonucleotide formyltransferase (GARFTase). Compounds 6-11 inhibited KB human tumor cells in the order 9 = 10 > 8 > 7 > 6 = 11. Compounds 8-10 were variously transported by FRα, PCFT, and RFC and, unlike PMX, inhibited de novo purine nucleotide rather than thymidylate biosynthesis. The antiproliferative effects of 8 and 9 appeared to be due to their dual inhibitions of both GARFTase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase. Our studies identify a unique structure-activity relationship for transport and dual target inhibition. PMID:25602637

  15. Novel 5-Substituted 2-(Aylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides: Synthesis, Molecular Structure, Anticancer Activity, Apoptosis-Inducing Activity and Metabolic Stability.

    PubMed

    Żołnowska, Beata; Sławiński, Jarosław; Pogorzelska, Aneta; Szafrański, Krzysztof; Kawiak, Anna; Stasiłojć, Grzegorz; Belka, Mariusz; Ulenberg, Szymon; Bączek, Tomasz; Chojnacki, Jarosław

    2016-01-01

    A series of novel 5-substituted 2-(arylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl) benzenesulfonamide derivatives 27-60 have been synthesized by the reaction of aminoguanidines with an appropriate phenylglyoxal hydrate in glacial acetic acid. A majority of the compounds showed cytotoxic activity toward the human cancer cell lines HCT-116, HeLa and MCF-7, with IC50 values below 100 μM. It was found that for the analogues 36-38 the naphthyl moiety contributed significantly to the anticancer activity. Cytometric analysis of translocation of phosphatidylserine as well as mitochondrial membrane potential and cell cycle revealed that the most active compounds 37 (HCT-116 and HeLa) and 46 (MCF-7) inhibited the proliferation of cells by increasing the number of apoptotic cells. Apoptotic-like, dose dependent changes in morphology of cell lines were also noticed after treatment with 37 and 46. Moreover, triazines 37 and 46 induced caspase activity in the HCT-116, HeLa and MCF-7 cell lines. Selected compounds were tested for metabolic stability in the presence of pooled human liver microsomes and NADPH, both R² and Ar = 4-CF₃-C₆H₄ moiety in 2-(R²-methylthio)-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides simultaneously increased metabolic stability. The results pointed to 37 as a hit compound with a good cytotoxicity against HCT-116 (IC50 = 36 μM), HeLa (IC50 = 34 μM) cell lines, apoptosis-inducing activity and moderate metabolic stability. PMID:27338337

  16. Palladium Catalyzed Cross-Coupling of Five-Membered Heterocyclic Silanolates

    PubMed Central

    Denmark, Scott E.; Baird, John D.; Regens, Christopher S.

    2009-01-01

    The preparation of π-rich 2-aryl heterocycles by palladium-catalyzed cross-coupling of sodium heteroarylsilanolates with aryl iodides, bromides and chlorides is described. The cross-coupling process was developed through extensive optimization of the follow key variables: (1) identification of stable, isolable alkali metal silanolates, (2) identification of conditions for preformation and isolation of silanolate salts, (3) judicious choice in the palladium catalyst/ligand combination, and (4) selection of the protecting group on the nitrogen of indole. It was found that the alkali metal silanolates, either isolated or formed in situ, offered a significant rate enhancement and broader substrate scope over the use of silanols activated by Brønsted bases such as NaOt-Bu. In addition, the optimized conditions for the cross-coupling of 2-indolylsilanolates were readily applied to the cross-coupling of 2-pyrrolyl-, 2-furyl-, and 2-thienylsilanolates. PMID:18205384

  17. Amino acids and peptides activate at least five members of the human bitter taste receptor family.

    PubMed

    Kohl, Susann; Behrens, Maik; Dunkel, Andreas; Hofmann, Thomas; Meyerhof, Wolfgang

    2013-01-01

    Amino acids and peptides represent important flavor molecules eliciting various taste sensations. Here, we present a comprehensive assessment of the interaction of various peptides and all proteinogenic amino acids with the 25 human TAS2Rs expressed in cell lines. L-Phenylalanine and L-tryptophan activate TAS2R1 and TAS2R4, respectively, whereas TAS2R4 and TAS2R39 responded to D-tryptophan. Structure-function analysis uncovered the basis for the lack of stereoselectivity of TAS2R4. The same three TAS2Rs or subsets thereof were also sensitive to various dipeptides containing L-tryptophan, L-phenylalanine, or L-leucine and to Trp-Trp-Trp, whereas Leu-Leu-Leu specifically activated TAS2R4. Trp-Trp-Trp also activated TAS2R46 and TAS2R14. Two key bitter peptides from Gouda cheese, namely, Tyr-Pro-Phe-Pro-Gly-Pro-Ile-His-Asn-Ser and Leu-Val-Tyr-Pro-Phe-Pro-Gly-Pro-Ile-His-Asn, both activated TAS2R1 and TAS2R39. Thus, the data demonstrate that the bitterness of amino acids and peptides is not mediated by specifically tuned TAS2Rs but rather is brought about by an unexpectedly complex pattern of sensitive TAS2Rs. PMID:23214402

  18. Synthesis and evaluation of antimicrobial and anticonvulsant activities of some new 3-[2- (5-aryl-1,3,4-oxadiazol-2-yl/4-carbethoxymethylthiazol-2-yl) imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-ones and investigation of their structure-activity relationships.

    PubMed

    Altintaş, Handan; Ateş, Oznur; Uyde-Doğan, B Sönmez; Alp, F Ilkay; Kaleli, Deniz; Ozdemir, Osman; Birteksöz, Seher; Otük, Gülten; Atana, Dilek; Uzun, Meltem

    2006-01-01

    In the present study, 20 new compounds having 3-[2-(5-aryl-1,3,4-oxadiazol-2-yl) imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-one (I-XII) and 3-[2-(4-carbethoxymethylthiazol-2-yl)imino-4-thiazoldinon-5-ylidenel-5-substituted/nonsubstituted IH-indole-2-one (XIII-XX) systems were synthesized. The structures were confirmed by spectral methods (UV, IR, 1H-NMR, 13C-NMR, 13C-DEPT (135), electron impact mass spectrometry) and elemental analysis. All compounds were tested for in vitro antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis ATCC 14153, Candida albicans ATCC 10231, Microsporum gypseum (NCPF-580), Microsporum canis, Trichophyton mentagrophytes and Trichophyton rubrum and some of them were found to be active. Especially, compound I was more active than cefuroxime sodium (CAS 56238-63-2) which was used as a standard, and the activity of compound XII was close to that of cefuroxime sodium against Staphylococcus epidermidis ATCC 12228. Primary screening for antituberculous activity was conducted at 6.25 microg/ml against Mycobacterium tuberculosis H37Rv in BACTEC 12B medium using the BACTEC 460 radiometric system. The anticonvulsant activities of selected prototoype compounds (I, IV-VI, VIII, XI, XIII, XVI-XVIII) administered at doses of 50-200 mg/kg (i.p.) were evaluated using the pentetrazol test (PTZ) in mice. PMID:16618017

  19. Diastereoselective synthesis of tetrahydrofurans via mead reductive cyclization of keto-beta-lactones derived from the tandem Mukaiyama aldol lactonization (TMAL) process.

    PubMed

    Mitchell, T Andrew; Romo, Daniel

    2007-11-23

    The development of a diastereoselective, three-step strategy for the construction of substituted tetrahydrofurans from alkenyl aldehydes based on the tandem Mukaiyama aldol-lactonization process and Mead reductive cyclization of keto beta-lactones is reported. Stereochemical outcomes of the TMAL process are consistent with models established for Lewis acid-mediated additions to alpha-benzyloxy and beta-silyloxy aldehydes while reductions of the five-membered oxocarbenium ions are consistent with Woerpel's models. Further rationalization for observed high diastereoselectivity in reductions of alpha-silyloxy 5-membered oxocarbenium ions based on stereoelectronic effects are posited. A diagnostic trend for coupling constants of gamma-benzyloxy beta-lactones was observed that should enable assignment of the relative configuration of these systems. PMID:17973527

  20. Diastereoselective Synthesis of Tetrahydrofurans via Mead Reductive Cyclization of Keto-β-Lactones Derived from the Tandem Mukaiyama Aldol Lactonization (TMAL) Process

    PubMed Central

    Mitchell, T. Andrew; Romo, Daniel

    2008-01-01

    The development of a diastereoselective, three-step strategy for the construction of substituted tetrahydrofurans from alkenyl aldehydes based on the tandem Mukaiyama aldol-lactonization process and Mead reductive cyclization of keto β-lactones is reported. Stereochemical outcomes of the TMAL process are consistent with models established for Lewis acid-mediated additions to α-benzyloxy and β-silyloxy aldehydes while reductions of the five-membered oxocarbenium ions are consistent with Woerpel’s models. Further rationalization for observed high diastereoselectivity in reductions of α-silyloxy 5-membered oxocarbenium ions based on stereoelectronic effects are posited. A diagnostic trend for coupling constants of γ-benzyloxy β-lactones was observed that should enable assignment of the relative configuration of these systems. PMID:17973527

  1. Preferential selection of isomer binding from chiral mixtures: alternate binding modes observed for the E and Z isomers of a series of 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines as ternary complexes with NADPH and human dihydrofolate reductase

    SciTech Connect

    Cody, Vivian; Piraino, Jennifer; Pace, Jim; Li, Wei; Gangjee, Aleem

    2010-12-01

    The structures of six chirally mixed E/Z-isomers of 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines reveals only one isomer is bound in the active site of human DHFR. The configuration of all but one C9-analogue is observed as the E-isomer. The crystal structures of six human dihydrofolate reductase (hDHFR) ternary complexes with NADPH and a series of mixed E/Z isomers of 5-substituted 5-[2-(2-methoxyphenyl)-prop-1-en-1-yl]furo[2,3-d]pyrimidine-2,4-diamines substituted at the C9 position with propyl, isopropyl, cyclopropyl, butyl, isobutyl and sec-butyl (E2–E7, Z3) were determined and the results were compared with the resolved E and Z isomers of the C9-methyl parent compound. The configuration of all of the inhibitors, save one, was observed as the E isomer, in which the binding of the furopyrimidine ring is flipped such that the 4-amino group binds in the 4-oxo site of folate. The Z3 isomer of the C9-isopropyl analog has the normal 2,4-diaminopyrimidine ring binding geometry, with the furo oxygen near Glu30 and the 4-amino group interacting near the cofactor nicotinamide ring. Electron-density maps for these structures revealed the binding of only one isomer to hDHFR, despite the fact that chiral mixtures (E:Z ratios of 2:1, 3:1 and 3:2) of the inhibitors were incubated with hDHFR prior to crystallization. Superposition of the hDHFR complexes with E2 and Z3 shows that the 2′-methoxyphenyl ring of E2 is perpendicular to that of Z3. The most potent inhibitor in this series is the isopropyl analog Z3 and the least potent is the isobutyl analog E6, consistent with data that show that the Z isomer makes the most favorable interactions with the active-site residues. The isobutyl moiety of E6 is observed in two orientations and the resultant steric crowding of the E6 analog is consistent with its weaker activity. The alternative binding modes observed for the furopyrimidine ring in these E/Z isomers suggest that new templates can be designed to probe these binding

  2. Synthesis and Antimicrobial Activity of 2-[2-(2,6-dichloro phenyl)amino]benzyl-3-(5-substituted phenyl-4,5-dihydro-1H-pyrazol-3-yl-amino)-6,8-dibromoquinazolin-4(3H)ones.

    PubMed

    Patel, Nb; Patel, Jc; Barat, Gg

    2010-04-01

    A series of 2-[2-(2,6-dichlorophenyl)amino]benzyl-3-(5-substituted phenyl-4,5-dihydro-1H-pyrazol-3-yl-amino)-6,8-dibromoquinazolin-4(3H) ones 6a-m have been synthesized by the reaction of 2-[2-(2,6-dichlorophenyl)amino]benzyl-3-substituted phenylacrylamido-6,8-dibromoquinazolin-4(3H) ones 5a-m with hydrazine hydrate in the presence of glacial acetic acid. The chalcones 5a-m were prepared by the condensation of 2-[2-(2,6-dichlorophenyl)amino]benzyl-3-acetamido-6,8-dibromoquinazolin-4(3H)one 4 with different substituted aromatic aldehyde. The benzoxazinone 2 was synthesized from 2-[2-(2,6-dichlorophenyl)amino]phenyl acetyl chloride 1 on treatment with 3,5-dibromoanthranilic acid in pyridine, which on reaction with hydrazine hydrate and then on acetylation reaction yielded 4. The structures of these compounds have been elucidated by elemental analyses, IR, and NMR spectral data. The title compounds pyrazolyl-quinazolin-4(3H)ones 6a-m were evaluated for their antibacterial and antifungal activities in vitro. PMID:21264122

  3. Discovery of 5-substituted pyrrolo[2,3-d]pyrimidine antifolates as dual acting inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase in de novo purine nucleotide biosynthesis: implications of inhibiting 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase to AMPK activation and anti-tumor activity

    PubMed Central

    Raghavan, Sudhir; Ravindra, Manasa Punaha; Hales, Eric; Orr, Steven; Cherian, Christina; Hou, Zhanjun

    2014-01-01

    We synthesized 5-substituted pyrrolo[2,3-d]pyrimidine antifolates (compounds 5–10) with 1 to 6 bridge carbons and a benozyl ring in the side chain as antitumor agents. Compound 8 with a 4-carbon bridge was the most active analog and potently inhibited proliferation of folate receptor (FR) α-expressing Chinese hamster ovary and KB human tumor cells. Growth inhibition was reversed completely or in part by excess folic acid, indicating that FRα is involved in cellular uptake, and resulted in S-phase accumulation and apoptosis. Anti-proliferative effects of compound 8 toward KB cells were protected by excess adenosine but not thymidine, establishing de novo purine nucleotide biosynthesis as the targeted pathway. However, 5-aminoimidazole-4-carboxamide (AICA) protection was incomplete, suggesting inhibition of both AICA ribonucleotide formyltransferase (AICARFTase) and glycinamide ribonucleotide formyltransferase (GARFTase). Inhibition of GARFTase and AICARFTase by compound 8 was confirmed by cellular metabolic assays and resulted in ATP pool depletion. To our knowledge, this is the first example of an antifolate that acts as a dual inhibitor of GARFTase and AICARFTase as its principal mechanism of action. PMID:24256410

  4. A mechanistic study of the addition of alcohol to a five-membered ring silene via a photochemical reaction.

    PubMed

    Su, Ming-Der

    2016-03-21

    The mechanism for the photochemical rearrangement of a cyclic divinyldisilane (1-Si) in its first excited state ((1)π → (1)π*) is determined using the CAS/6-311G(d) and MP2-CAS/6-311++G(3df,3pd) levels of theory. The photoproduct, a cyclic silene, reacts with various alcohols to yield a mixture of cis- and trans- adducts. The two reaction pathways are denoted as the cis- addition path (path A) and the trans-addition path (path B). These model studies demonstrate that conical intersections play a crucial role in the photo-rearrangements of cyclic divinyldisilanes. The theoretical evidence also demonstrates that the addition of alcohol to a cyclic divinyldisilane follows the reaction path: cyclic divinyldisilane → Franck-Condon region → conical intersection → photoproduct (cyclic silene) → local intermediate (with alcohol) → transition state → cis- or trans-adduct. The theoretical studies demonstrate that the steric effects as well as the concentrations of CH3OH must have a dominant role in determining the yields of the final adducts by stereochemistry. The same mechanism for the carbon derivative (1-C) is also considered in this work. However, the theoretical results indicate that 1-C does not undergo a methanol addition reaction via the photochemical reaction pathway, since its energy of conical intersection (S1/S0-CI-C) is more than that of its FC (FC-C). The reason for these phenomena could be that the atomic radius of carbon is much smaller than that of silicon (77 and 117 pm, respectively). As a result, the conformation for 1-C is more sterically congested than that for 1-Si, along the 1,3-silyl-migration pathway. PMID:26928893

  5. Five-membered heterocycles. Part I. Application of the HOMA index to 1,2,4-trizoles

    NASA Astrophysics Data System (ADS)

    Mrozek, A.; Karolak-Wojciechowska, J.; Amiel, P.; Barbe, J.

    2000-06-01

    Aromaticity of the heterorings containing nitrogen, sulphur, and/or oxygen was studied on the basis of crystallographic data (CSD). The HOMA index, quantitative estimation of heteroring aromaticity, was calculated for pyrroles, thiophenes, furanes, pyrazoles, oksazoles, and imidazoles. For triazoles, used as a training set of molecules, correlation between heteroring aromaticity and number of substituents was indicated. At the same time, molecular structure of 3-amino-5-[2'-diethylamino)ethylthio]-1,2,4-triazole hydrochloride was determined as a reference compound using X-ray crystallography.

  6. Five-membered heterocycles. Part III. Aromaticity of 1,3-imidazole in 5+ n hetero-bicyclic molecules

    NASA Astrophysics Data System (ADS)

    Mrozek, Agnieszka; Karolak-Wojciechowska, Janina; Kieć-Kononowicz, Katarzyna

    2003-08-01

    The aromaticity (in the form of HOMA index) of 1,3-imidazole ring and its bicyclic derivatives was studied on the basis of statistical data from Cambridge Structural Database and X-ray investigations performed by authors. As a starting point, aromaticity of the 1,3-imidazoles with exocyclic X substituent at C2 (XN, O or S) was calculated. Subsequently, the HOMA index was calculated for various 5+ n bicyclic skeletons with N, O, and S as endocyclic heteroatoms in the second ring. For the isolated 1,3-imidazole ring, aromaticity depends on exocyclic substituent at C2 and decreases in sequence N, S, O. For bicyclic derivatives it was found that both rings are aromatic and coplanar in very few molecules (17% of investigated ones), and positive charge—located on endocyclic heteroatom—increases the aromaticity. For remaining compounds, presence of sp 3 carbons excludes possibility of aromatic ring existence.

  7. Chemiluminescence detection of five-membered heteroaromatic compounds using electrogenerated tris(2,2'-bipyridine)-ruthenium(III).

    PubMed

    Kodamatani, Hitoshi; Komatsu, Yu; Yamazaki, Shigeo; Saito, Keiitsu

    2007-04-01

    Heteroaromatic compounds, such as 2,5-dimethylthiophene, 2,5-dimethylpyrrole, and 2,5-dimethylfuran, were found to act as reducing agents for the tris(2,2'-bipyridine)ruthenium(III), Ru(bpy)3(3+), chemiluminescent reaction. In order to characterize the chemiluminescent reaction of Ru(bpy)3(3+) with heteroaromatic compounds, we have investigated various mono-, di-, and tri-heteroaromatic compounds. The pi-electron density and stability of aromatic rings influence the chemiluminescent efficiency of the reaction. Above all, 2,5-dimethylthiophene produced strong chemiluminescence under acidic conditions. In addition, we confirmed that the rate of the chemiluminescent reaction of Ru(bpy)3(3+) with 2,5-dimethylthiophene is very fast. PMID:17420543

  8. Phylogenetic and ecological patterns in nighttime transpiration among five members of the genus Rubus co-occurring in western Oregon

    PubMed Central

    McNellis, Brandon; Howard, Ava R

    2015-01-01

    Nighttime transpiration is a substantial portion of ecosystem water budgets, but few studies compare water use of closely related co-occurring species in a phylogenetic context. Nighttime transpiration can range up to 69% of daytime rates and vary between species, ecosystem, and functional type. We examined leaf-level daytime and nighttime gas exchange of five species of the genus Rubus co-occurring in the Pacific Northwest of western North America in a greenhouse common garden. Contrary to expectations, nighttime transpiration was not correlated to daytime water use. Nighttime transpiration showed pronounced phylogenetic signals, but the proportion of variation explained by different phylogenetic groupings varied across datasets. Leaf osmotic water potential, water potential at turgor loss point, stomatal size, and specific leaf area were correlated with phylogeny but did not readily explain variation in nighttime transpiration. Patterns in interspecific variation as well as a disconnect between rates of daytime and nighttime transpiration suggest that variation in nighttime water use may be at least partly driven by genetic factors independent of those that control daytime water use. Future work with co-occurring congeneric systems is needed to establish the generality of these results and may help determine the mechanism driving interspecific variation in nighttime water use. PMID:26380686

  9. Stabilities and structures in cluster ions of five-membered heterocyclic compounds containing O, N, and S atoms

    SciTech Connect

    Hiraoka, K.; Takimoto, H.; Yamabe, S.

    1987-11-25

    Clustering and hydration reactions of protonated and radical cations of heterocyclic compounds, e.g., furan, tetrahydrofuran, pyrrole, pyrrolidine, thiophene, and tetrahydrothiophene, have been studied using a pulsed electron beam mass spectrometer. The bond energies of proton-held dimer cations for furan, pyrrole, and thiophene are much smaller than those for tetrahydrofuran, pyrrolidine, and tetrahydrothiophene, respectively. This result suggests that not the heteroatoms but the ..cap alpha.. carbon atoms are protonated for furan, pyrrole, and thiophene. The hydrogen-bond site for the protonated furan and thiophene is calculated to be the unprotonated ..cap alpha.. hydrogen (C-H/sub ..cap alpha../ adjacent to the heteroatom) which is the most acidic one. On the other hand, the N-H hydrogen is the best hydrogen-bond site for the protonated pyrrole. It was found that the radical-cations dimers have greater bond energies than the proton-held dimer cations for furan and thiophene. This suggests that the bonds of the former have more covalent nature. Some unique reactions of C/sub 4/H/sub 4/O/sup .+/ and C/sub 4/H/sub 5/O/sup +/ with a furan molecule were observed. With an increase of temperature, the ions with m/z which are the same as those for (C/sub 4/H/sub 4/O)/sub 2//sup .+/ and H/sup +/(C/sub 4/H/sub 4/O)/sub 2/ are found to be formed at the expense of C/sup 4/H/sub 4/O/sup .+/ and C/sub 4/H/sub 5/O/sup +/ ions, respectively. It is suggested that the reactions observed are Diels-Alder type condensation reactions.

  10. Hyperresistance to 4-nitroquinoline 1-oxide cytotoxicity and reduced DNA damage formation in dermal fibroblast strains derived from five members of a cancer-prone family.

    PubMed Central

    Mirzayans, R.; Sabour, M.; Rauth, A. M.; Paterson, M. C.

    1993-01-01

    Dermal fibroblasts cultured from members of a family presenting multiple polyps and sarcomas were compared with fibroblast strains from unrelated healthy donors for sensitivity to killing by four genotoxic agents. Cells from the sister of the male proband (strain 3437T), mother (strain 3703T), two of his paternal aunts (3701T and 3704T) and one paternal uncle (3702T) displayed marked resistance (1.8 to 4.3 times greater than the normal mean) to 4-nitroquinoline 1-oxide (4NQO), a procarcinogen whose DNA-damaging properties encompass those of both far (254 nm) ultraviolet (UV) light and ionising radiation. These same 4NQO-resistant cells, however, responded normally to reproductive inactivation by UV light, 60Co gamma radiation or the alkylating agent methylnitrosourea, signifying that the abnormal resistance of these cells to 4NQO is not associated with aberrant DNA metabolism. In keeping with this conclusion, exposure to a given dose of 4NQO produced decreased amounts of DNA damage and stimulated lower levels of repair DNA synthesis in all five 4NQO-resistant strains than in normal controls. Moreover, exogenous radiolabelled 4NQO accumulated to a lesser extent in the 4NQO-resistant than in the normal fibroblasts. Cell sonicates of strains 3437T, 3701T and 3702T exhibited reduced capacities (40-60% of normal) to catalise the conversion of 4NQO to the proximate carcinogen 4-hydroxyaminoquinoline 1-oxide. However, the 4NQO-resistant strains 3703T and 3704T carried out 4NQO bioreduction at normal rates. Our data therefore indicate that enhanced resistance to 4NQO cytotoxicity in 3437T, 3701T and 3702T is a consequence of anomalies in both intracellular accumulation and enzymatic reduction of 4NQO, whereas 4NQO resistance in 3703T and 3704T appears to result solely from reduced intracellular drug accumulation. PMID:8217598

  11. The oxytocin/vasopressin receptor family has at least five members in the gnathostome lineage, inclucing two distinct V2 subtypes.

    PubMed

    Ocampo Daza, Daniel; Lewicka, Michalina; Larhammar, Dan

    2012-01-01

    The vertebrate oxytocin and vasopressin receptors form a family of G-protein-coupled receptors (GPCRs) that mediate a large variety of functions, including social behavior and the regulation of blood pressure, water balance and reproduction. In mammals four family members have been identified, three of which respond to vasopressin (VP) named V1A, V1B and V2, and one of which is activated by oxytocin (OT), called the OT receptor. Four receptors have been identified in chicken as well, but these have received different names. Until recently only V1-type receptors have been described in several species of teleost fishes. We have identified family members in several gnathostome genomes and performed phylogenetic analyses to classify OT/VP-receptors across species and determine orthology relationships. Our phylogenetic tree identifies five distinct ancestral gnathostome receptor subtypes in the OT/VP receptor family: V1A, V1B, V2A, V2B and OT receptors. The existence of distinct V2A and V2B receptors has not been previously recognized. We have found these two subtypes in all examined teleost genomes as well as in available frog and lizard genomes and conclude that the V2A-type is orthologous to mammalian V2 receptors whereas the V2B-type is orthologous to avian V2 receptors. Some teleost fishes have acquired additional and more recent gene duplicates with up to eight receptor family members. Thus, this analysis reveals an unprecedented complexity in the gnathostome repertoire of OT/VP receptors, opening interesting research avenues regarding functions such as regulation of water balance, reproduction and behavior, particularly in reptiles, amphibians, teleost fishes and cartilaginous fishes. PMID:22057000

  12. Quantum-chemical investigation of the mutual influences between structural fragments in oxo derivatives of five-membered saturated heterocycles in the ground and reactive states

    SciTech Connect

    Tupitsyn, I.F.; Kane, A.A.; Shibaev, A. Yu.

    1985-07-01

    The purpose of this work was to study the possibilities of the application of the semiempirical SCF MO LCAO method in the CNDO/2 and MINDO/3 variants to discovering laws between the sequences of variation of calculated characteristics which are dependent mainly on the electronic structure of methylene or carbonyl groups and the chemical shifts in /sup 13/C and /sup 1/H NMR spectra, the frequencies of stretching vibrations in the IR spectra, and the constants of the kinetic CH acidity of a large group of oxo derivatives of saturated heterocycles. Besides the local electron density, comparable contributions are made to the value of the chemical shift of a carbon atom directly attached to a cyclic atom by the diamagnetic component of the shielding and the effect of the intramolecular electric field of the lone pairs.

  13. Microsynteny and phylogenetic analysis of tandemly organised miRNA families across five members of Brassicaceae reveals complex retention and loss history.

    PubMed

    Rathore, Priyanka; Geeta, R; Das, Sandip

    2016-06-01

    Plant genomes are characterized by the presence of large miRNA gene families which are few in number. The expansion of miRNA families is thought to be driven by gene and genome duplication. Some members of these miRNA gene families are tandemly arranged and their analysis is of interest because such organisation may indicate origin through tandem duplication and also to investigate whether some such tandem clusters have similar expression patterns, and whether these are regulated through a common set of cis-regulatory elements (eg. promoters and enhancers). As a first step, we undertake a comprehensive study using micro-synteny analyses of tandemly organised miRNA families across the Brassicaceae spanning an evolutionary time scale of ca. 45 million years, among Arabidopsis, Capsella, Brassica and Thellungiella species, to address the following questions: Are most miRNA gene families present as tandem clusters? To what extent are these tandem patterns retained? To what extent can family sizes be ascribed to genome duplication? Our analysis of thirteen tandemly organised miRNA families revealed that synteny is largely conserved among Arabidopsis thaliana, A. lyrata and Capsella rubella, which form a clade spanning approximately between 6.2-9.8 my (Acarkan et al., 2000) [1]. On the other hand, comparison of sequences from these species with Brassica rapa, B. oleracea and Thellungiella halophila, which form a separate clade spanning 31 my (Franzke et al., 2011)[2] reveals many differences. The latter clade reveals several paralogous duplications that probably resulted from whole genome duplication, as well as disrupted synteny. Phylogenetic analyses of precursor sequences generally support the history inferred from synteny analysis. Synteny and phylogenetic analysis of six members of the tandemly organised miR169 family suggest that the Brassicaceae ancestral state consisted of a "dimer as a unit" which may have undergone direct local duplication to retain the transcriptional orientation followed by lineage specific changes. MiR169, to the best of our knowledge, is one of the largest tandemly organised miRNA gene family across plant kingdom and further analysis should reveal the generality of this pattern of evolution. The conserved organisation of miR395A-B-C and miR395 D-E-F as two clusters on same chromosome/scaffold across A. thaliana, B. rapa and salsuginea demonstrates retention of the large chromosomal segment across the two lineages. MiRNA family miR845 was detected only in Arabidopsis species and Thellungiella indicating a complex loss and retention history. MiR447A-B family was only found in A. thaliana indicating that it is a species-specific gene family of recent origin. PMID:27095398

  14. Discovery of 3,5-substituted 6-azaindazoles as potent pan-Pim inhibitors.

    PubMed

    Hu, Huiyong; Wang, Xiaojing; Chan, Grace Ka Yan; Chang, Jae H; Do, Steven; Drummond, Jake; Ebens, Allen; Lee, Wendy; Ly, Justin; Lyssikatos, Joseph P; Murray, Jeremy; Moffat, John G; Chao, Qi; Tsui, Vickie; Wallweber, Heidi; Kolesnikov, Aleksandr

    2015-11-15

    Pim kinase inhibitors are promising cancer therapeutics. Pim-2, among the three Pim isoforms, plays a critical role in multiple myeloma yet inhibition of Pim-2 is challenging due to its high affinity for ATP. A co-crystal structure of a screening hit 1 bound to Pim-1 kinase revealed the key binding interactions of its indazole core within the ATP binding site. Screening of analogous core fragments afforded 1H-pyrazolo[3,4-c]pyridine (6-azaindazole) as a core for the development of pan-Pim inhibitors. Fragment and structure based drug design led to identification of the series with picomolar biochemical potency against all three Pim isoforms. Desirable cellular potency was also achieved. PMID:26459208

  15. Enantioselective synthesis and antioxidant activity of 3,4,5-substituted piperidine derivatives.

    PubMed

    Kim, Jin Ho; Shyam, Pranab K; Kim, Mi Jeong; Lee, Hwa-Jung; Lee, Jeong Tae; Jang, Hye-Young

    2016-07-01

    In this study, 3,4,5-trisubstituted piperidines were synthesized enantioselectively, and their antioxidant activity was evaluated. The 3,4,5-trisubstituted piperidines containing TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) and a spatially proximal hydroxy group showed good antioxidant activity. Some of these compounds showed IC50 values in a nanomolar range, comparable to that of TEMPO. Probably the TEMPO generated from the homolysis of the CON bond of 3,4,5-trisubstituted piperidines functions as a radical-scavenging entity, and the hydroxy group of piperidines has a synergistic effect to the antioxidant activity. PMID:27177825

  16. Synthesis of divinyl derivatives of 5-substituted 1,2,4-triazole-3-thiones

    SciTech Connect

    Trzhtsinskaya, B.V.; Rudakova, E.V.; Afonin, A.V.; Pertsikov, B.Z.; Mansurov, Yu.A.; Aksenov, V.P.

    1987-01-20

    The authors have previously described the synthesis of two divinyl derivatives of unsubstituted triazolethione. In order to expand the range of such compounds, they studied the reaction of 5-methyl- (I), 5-phenyl- (II), and 5-..cap alpha..-furyl-1,2,4-triazole-3-thione (III) with acetylene. Triazoles (I) and (III) in the presence of alkali add one acetylene molecule. An increase in the reaction time yields the product of the addition of two acetylene molecules to (I) in yields up to 50%. The substitution of the alkaline catalyst by CuCl facilitates the formation of divinyl derivatives. However, the use of CuCl in this case led to a decrease in the yield of the desired product. N-Vinyl-3-vinylthio-5-methyl-1,2,4-triazoles were obtained in yields up to 64% in the presence of cadmium acetate. On the other hand, the use of CuCl as the catalyst facilitates the synthesis of N-vinyl-3-vinylthio-5-phenyl- and N-vinyl-3-vinylthio-5-..cap alpha..-furyl-1,2,4-triazoles.

  17. Scaffold hopping towards potent and selective JAK3 inhibitors: discovery of novel C-5 substituted pyrrolopyrazines.

    PubMed

    de Vicente, Javier; Lemoine, Remy; Bartlett, Mark; Hermann, Johannes C; Hekmat-Nejad, Mohammad; Henningsen, Robert; Jin, Sue; Kuglstatter, Andreas; Li, Hongju; Lovey, Allen J; Menke, John; Niu, Linghao; Patel, Vaishali; Petersen, Ann; Setti, Lina; Shao, Ada; Tivitmahaisoon, Parcharee; Vu, Minh Diem; Soth, Michael

    2014-11-01

    The discovery of a novel series of pyrrolopyrazines as JAK inhibitors with comparable enzyme and cellular activity to tofacitinib is described. The series was identified using a scaffold hopping approach aided by structure based drug design using principles of intramolecular hydrogen bonding for conformational restriction and targeting specific pockets for modulating kinase activity. PMID:25262541

  18. Synthesis, cytostatic activity and ADME properties of C-5 substituted and N-acyclic pyrimidine derivatives.

    PubMed

    Kraljević, Tatjana Gazivoda; Klika, Mateja; Kralj, Marijeta; Martin-Kleiner, Irena; Jurmanović, Stella; Milić, Astrid; Padovan, Jasna; Raić-Malić, Silvana

    2012-01-01

    The synthesis of the novel 5-alkyl pyrimidine derivatives, 5,6-dihydrofuro[2,3-d]pyrimidines and 5-alkyl N-methoxymethyl pyrimidine derivatives and evaluation of their cytostatic activities are described. The mechanism of antiproliferative effect of 5-(2-chloroethyl)-substituted pyrimidine 3 that exerted the pronounced cytostatic activity was studied in further details on colon carcinoma (HCT116) cells. The cell cycle perturbation analysis demonstrated severe DNA damage (G2/M arrest) pointing to a potential DNA alkylating ability of 3. Preliminary ADME data of 3 and its 6-methylated structural congener (6-Me-3) showed their high permeability and good metabolic stability. PMID:22130132

  19. Synthesis of 5-Substituted Derivatives of Isophthalic Acid as Non-Polymeric Amphiphilic Coating for Metal Oxide Nanoparticles

    PubMed Central

    Nilov, Denis; Kucheryavy, Pavel; Walker, Verina; Kidd, Clayton; Kolesnichenko, Vladimir L.; Goloverda, Galina Z.

    2014-01-01

    In the course of development of novel capping ligands with variable steric factor, which will be used as an organic coating for metal oxide nanoparticles, a base-catalyzed nucleophilic oxirane ring-opening addition reaction between dimethyl 5-hydroxyisophthalate and allyl glycidyl ether was studied. The allyl-terminated 1-1, 1-2 and 1-3 adducts and dihydroxylated derivative of the 1-1 adduct, 5-diglyceroxy isophthalic acid, were synthesized. The latter binds to the surface of 5 nm γ-Fe2O3 nanoparticles in reaction with their surfactant-free diethylene glycol colloids. PMID:25152545

  20. Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF5-substituted phenylboronic esters and iodobenzenes.

    PubMed

    Iakobson, George; Du, Junyi; Slawin, Alexandra M Z; Beier, Petr

    2015-01-01

    Pyridine promotes dediazoniation of aryldiazonium tetrafluoroborates. The formed aryl radicals were trapped with B2pin2, iodine, or tetrahydrofuran to afford boronic esters, iodobenzenes and benzenes, respectively. The application to the synthesis of (pentafluorosulfanyl)phenylboronic esters, iodo(pentafluorosulfanyl)benzenes and (pentafluorosulfanyl)benzene is shown. PMID:26425206

  1. Synthesis and Anticancer Activity of N-Aryl-5-substituted-1,3,4-oxadiazol-2-amine Analogues

    PubMed Central

    Ahsan, Mohamed Jawed; Sharma, Jyotika; Singh, Monika; Jadav, Surender Singh; Yasmin, Sabina

    2014-01-01

    In continuance of our search for anticancer agents, we report herein the synthesis and anticancer activity of some novel oxadiazole analogues. The compounds were screened for anticancer activity as per National Cancer Institute (NCI US) protocol on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancers cell lines. N-(2,4-Dimethylphenyl)-5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-amine (4s) showed maximum activity with mean growth percent (GP) of 62.61 and was found to be the most sensitive on MDA-MB-435 (melanoma), K-562 (leukemia), T-47D (breast cancer), and HCT-15 (colon cancer) cell lines with GP of 15.43, 18.22, 34.27, and 39.77, respectively. Maximum GP was observed on MDA-MB-435 (melanoma) cell line (GP = 6.82) by compound N-(2,4-dimethylphenyl)-5-(4-hydroxyphenyl)-1,3,4-oxadiazol-2-amine (4u). PMID:24977160

  2. Computer-aided identification of novel 3,5-substituted rhodanine derivatives with activity against Staphylococcus aureus DNA gyrase.

    PubMed

    Werner, Malela M; Li, Zhiyu; Zauhar, Randy J

    2014-04-01

    Methicillin resistant Staphylococcus aureus (MRSA) is among the major drug resistant bacteria that persist in both the community and clinical settings due to resistance to commonly used antimicrobials. This continues to fuel the need for novel compounds that are active against this organism. For this purpose we have targeted the type IIA bacterial topoisomerase, DNA gyrase, an essential enzyme involved in bacterial replication, through the ATP-dependent supercoiling of DNA. The virtual screening tool Shape Signatures was applied to screen a large database for agents with shape similar to Novobiocin, a known gyrase B inhibitor. The binding energetics of the top hits from this initial screen were further validated by molecular docking. Compounds with the highest score on available crystal structure of homologous DNA gyrase from Thermus thermophilus were selected. From this initial set of compounds, several rhodanine-substituted derivatives had the highest antimicrobial activity against S. aureus, as determined by minimal inhibitory concentration assays, with Novobiocin as the positive control. Further activity validation of the rhodanine compounds through biochemical assays confirmed their inhibition of both the supercoiling and the ATPase activity of DNA gyrase. Subsequent docking and molecular dynamics on the crystal structure of DNA gyrase from S. aureus when it became available, provides further rationalization of the observed biochemical activity and understanding of the receptor-ligand interactions. A regression model for MIC prediction against S. aureus is generated based on the current molecules studied as well as other rhodanines derivatives found in the literature. PMID:24629449

  3. 4,5-Substituted 3-Isoxazolols with Insecticidal Activity Act as Competitive Antagonists of Housefly GABA Receptors.

    PubMed

    Liu, Genyan; Ozoe, Fumiyo; Furuta, Kenjiro; Ozoe, Yoshihisa

    2015-07-22

    The insect GABA receptor (GABAR), which is composed of five RDL subunits, represents an important target for insecticides. A series of 4,5-disubstituted 3-isoxazolols, including muscimol analogues, were synthesized and examined for their activities against four splice variants (ac, ad, bc, and bd) of housefly GABARs expressed in Xenopus oocytes. Muscimol was a more potent agonist than GABA in all four splice variants, whereas synthesized analogues did not exhibit agonism but rather antagonism in housefly GABARs. The introduction of bicyclic aromatic groups at the 4-position of muscimol and the simultaneous replacement of the aminomethyl group with a carbamoyl group at the 5-position to afford six 4-aryl-5-carbamoyl-3-isoxazolols resulted in compounds that exhibited significantly enhanced antagonism with IC50 values in the low micromolar range in the ac variant. The inhibition of GABA-induced currents by 100 μM analogues was approximately 1.5-4-fold greater in the ac and bc variants than in the ad and bd variants. 4-(3-Biphenylyl)-5-carbamoyl-3-isoxazolol displayed competitive antagonism, with IC50 values of 30, 34, 107, and 96 μM in the ac, bc, ad, and bd variants, respectively, and exhibited moderate insecticidal activity against houseflies, with an LD50 value of 5.6 nmol/fly. These findings suggest that these 3-isoxazolol analogues are novel lead compounds for the design and development of insecticides that target the orthosteric site of housefly GABARs. PMID:26120732

  4. Unusual behavior in the reactivity of 5-substituted-1H-tetrazoles in a resistively heated microreactor

    PubMed Central

    Gutmann, Bernhard; Glasnov, Toma N; Razzaq, Tahseen; Goessler, Walter; Roberge, Dominique M

    2011-01-01

    Summary The decomposition of 5-benzhydryl-1H-tetrazole in an N-methyl-2-pyrrolidone/acetic acid/water mixture was investigated under a variety of high-temperature reaction conditions. Employing a sealed Pyrex glass vial and batch microwave conditions at 240 °C, the tetrazole is comparatively stable and complete decomposition to diphenylmethane requires more than 8 h. Similar kinetic data were obtained in conductively heated flow devices with either stainless steel or Hastelloy coils in the same temperature region. In contrast, in a flow instrument that utilizes direct electric resistance heating of the reactor coil, tetrazole decomposition was dramatically accelerated with rate constants increased by two orders of magnitude. When 5-benzhydryl-1H-tetrazole was exposed to 220 °C in this type of flow reactor, decomposition to diphenylmethane was complete within 10 min. The mechanism and kinetic parameters of tetrazole decomposition under a variety of reaction conditions were investigated. A number of possible explanations for these highly unusual rate accelerations are presented. In addition, general aspects of reactor degradation, corrosion and contamination effects of importance to continuous flow chemistry are discussed. PMID:21647324

  5. Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF5-substituted phenylboronic esters and iodobenzenes

    PubMed Central

    Iakobson, George; Du, Junyi; Slawin, Alexandra M Z

    2015-01-01

    Summary Pyridine promotes dediazoniation of aryldiazonium tetrafluoroborates. The formed aryl radicals were trapped with B2pin2, iodine, or tetrahydrofuran to afford boronic esters, iodobenzenes and benzenes, respectively. The application to the synthesis of (pentafluorosulfanyl)phenylboronic esters, iodo(pentafluorosulfanyl)benzenes and (pentafluorosulfanyl)benzene is shown. PMID:26425206

  6. Synthesis and biological investigations of 5-substituted pyrimidine nucleosides coupled to a dihydropyridine/pyridinium salt redox chemical delivery system.

    PubMed

    Kumar, R; Wang, L; Wiebe, L I; Knaus, E E

    2001-11-01

    The syntheses, antiviral activities, and partition coefficients (P) of 3'-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-coupled nucleosides are described. These novel compounds were designed in an effort to enhance the lipophilicity, and thereby the delivery to the CNS, without compromising the anti-HSV-1 activity of the parental nucleosides. We have previously reported the synthesis of 3'-O-(1-methyl-1,4-dihydropyridyl-3- carbonyl) analogs of 5-iodo-(5), 5-vinyl-(6), and (E)-5-(2-iodovinyl)-2'-deoxyuridines (7). We now report the synthesis of 5-iodo-3'-O-(1-methyl-1,4-dihydropyridyl-3- carbonyl)-5'-O-acetyl-2'-deoxyuridine (15) and 3'-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2'-deoxyuridine (17). Quarternization of the 3'-O-(3-pyridylcarbonyl) compounds (10,12) using iodomethane afforded the corresponding 1-methyl pyridinium salts (13,14) which were reduced with sodium dithionite to yield the corresponding 3'-O-1-methyl-1,4-dihydropyridyl-3-carbonyl compounds (15,16). The deprotection of 3'-O-(1-methyl-1,4-dihydropyridyl- 3-carbonyl)-5'-O-t-butyldimethylsilyl-2'-deoxyuridine (16) with Bu4N+F- afforded 3'-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2'-deoxyuridine (17). Compounds 5-7 and 15 were evaluated for their antiviral activity in vitro against HSV-1, HSV-2, HCMV, and VZV, and were found to retain anti-HSV-1, HSV-2 and VZV activity as compared to their parental nucleosides (1-3). In addition, the cellular toxicity of 3'-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-coupled compounds (5-7 and 15) was found to be lower than the parent nucleosides. The lipophilicity of compounds (5-7,15,17) are enhanced substantially, compared to the parent nucleosides, as indicated by an increase in corresponding P values (1-octanol-water) upon replacement of the C-3' hydroxyl by 1-methyl-1,4-dihydropyridyl-3-carbonyl moiety. PMID:11822172

  7. Novel 5-substituted-2-anilinoquinolines with 3-(morpholino or 4-methylpiperazin-1-yl)propoxy moiety as broad spectrum antiproliferative agents: Synthesis, cell based assays and kinase screening.

    PubMed

    El-Damasy, Ashraf Kareem; Cho, Nam-Chul; Pae, Ae Nim; Kim, Eunice Eunkyeong; Keum, Gyochang

    2016-07-15

    A series of new 2-anilinoquinolines possessing 3-(morpholino or 4-methylpiperazin-1-yl)propoxy moiety at C5 of quinoline has been designed and synthesized as potential anticancer agents. Their antiproliferative activities were evaluated against a panel of 60 cancer cell lines at NCI and compared with gefitinib as a reference compound. Most of the tested compounds displayed potent and broad spectrum antiproliferative activities. Compounds 7d, 7f and 7g showed strong inhibitory and lethal effects at 10μM concentration. Moreover, they manifested superior potencies and efficacies than gefitinib across the most tested cell lines. Compound 7d, with 4-chloro-3-trifluoromethylphenyl group, proved to be the most potent and efficacious derivative in this series, with mean GI50 and TGI values of 1.62μM and 3.47μM, respectively. Kinase screening of 7d against a panel of 47 oncogenic kinases revealed its selective inhibitory effect (96% inhibition) towards TrkA kinase. Furthermore, the most potent compounds showed low cytotoxic effects against HFF-1 normal cell line. PMID:27241691

  8. Synthesis, Physicochemical Properties, and Hydrogen Bonding of 4(5)-Substituted 1-H-Imidazole-2-carboxamide, A Potential Universal Reader for DNA Sequencing by Recognition Tunneling

    PubMed Central

    Liang, Feng; Li, Shengqing

    2012-01-01

    We have developed a chemical reagent that recognizes all naturally occurring DNA bases, a so called universal reader, for DNA sequencing by recognition tunnelling in nanopores.[1] The primary requirements for this type of molecules are the ability to form non-covalent complexes with individual DNA bases and to generate recognizable electronic signatures under an electrical bias. 1-H-imidazole-2-carboxamide was designed as such a recognition moiety to interact with the DNA bases through hydrogen bonding. In the present study, we first furnished a synthetic route to 1-H-imidazole-2-carboxamide containing a short ω-functionalized alkyl chain at its 4(5) position for its attachment to metal and carbon electrodes. The acid dissociation constants of the imidazole-2-carboxamide were then determined by UV spectroscopy. The data show that the 1-H-imidazole-2-carboxamide exists in a neutral form between pH 6–10. Density functional theory (DFT) and NMR studies indicate that the imidazole ring exists in prototropic tautomers. We propose an intramolecular mechanism for tautomerization of 1-H-imidazole-2-carboxamide. In addition, the imidazole-2-carboxamide can self-associate to form hydrogen bonded dimers. NMR titration found that naturally occurring nucleosides interacted with 1-H-imidazole-2-carboxamide through hydrogen bonding in a tendency of dG>dC≫dT> dA. These studies are indispensable to assisting us in understanding the molecular recognition that takes place in the nanopore where routinely used analytical tools such as NMR and FTIR cannot be conveniently applied. PMID:22461259

  9. Synthesis, preclinical evaluation and antidepressant activity of 5-substituted phenyl-3-(thiophen-2-yl)-4, 5-dihydro-1H-pyrazole-1-carbothioamides

    PubMed Central

    Mathew, Bijo; Suresh, Jerad; Anbazhagan, S.

    2014-01-01

    A series of phenyl-3-(thiophen-2-yl)-4, 5-dihydro-1H-pyrazole-1-carbothioamides (TTa-TTg) were synthesized by the ring closure reaction of phenyl-1-(thiophen-2-yl) prop-2-en-1-ones with thiosemicarbazide in alcoholic basic medium. All the final derivatives were evaluated for their antidepressant and neurotoxicity screening. The structures of the compounds were characterized by IR, 1H NMR, 13C NMR, Mass and elemental analyses. Preclinical evaluation of the compounds were ascertained by in silico toxicity, blood-brain barrier and human oral absorption prediction. In this series, 5-(4-hydroxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1 carbothioamide (TTg) reduced immobility time 61.17 and 62.05 % in both force swimming and tail suspension test respectively at 10 mg/kg dose level when compared to the standard Imipramine without influencing the baseline locomotion. Moreover it was observed that the titled scaffold possessing electron withdrawing chlorine atom in the 4th position of aromatic ring of the scaffold also showed good the antidepressant activity. In conclusion, the behavioural investigation revealed that thiophene based pyrazolines having a carbothioamide tail unit in the N1 position may be therapeutically useful as potential antidepressant medications. PMID:26417270

  10. Triazolines 26: 1-Aryl-5-amido-1,2,3-triazolines, a new group of triazoline anticonvulsants. Effect of 5-substitution on anticonvulsant activity.

    PubMed

    Kadaba, P K

    1996-01-01

    Studies in our laboratories have led to the discovery of the delta 2-1,2,3-triazolines as a unique family of anticonvulsant agents hitherto unknown. The anticonvulsant activity of 1,5-diaryl- and 1-aryl-5-pyridyltriazolines was previously reported; this paper describes the evaluation of two series of 1-aryl-5-amido-1,2,3-triazolines, A and B, where the 5-amido groups are (2-oxo-1-pyrrolidino)- (1-8) and (N-methyl-N-acetamido)- (9-15), respectively. The 1-aryl-5-(2-oxo-1-pyrrolidino)-1,2,3-triazolines of the A series, which are uniquely substituted with the pyrrolidinone lactam ring, a cyclic gamma-aminobutyric acid (GABA) structure, seem to function by enhancing inhibitory GABAergic mechanisms. Radioligand binding studies for the two most active triazolines 2 and 7, indicate that both compounds strongly inhibit the specific binding of [3H]GABA to GABAB receptor sites, with Ki = 1.7 and 0.91 microM respectively. The anticonvulsant activity among the various groups of triazolines studied so far appears to be dependent on the 5-substituent groups: 4-pyridyl- > 2-oxo-1-pyrrolidino- > N-methyl-N-acetamido- > 3-pyridyl > or = aryl approximately 2-pyridyl > 2-quinolyl. PMID:8881374

  11. Copper(II) complexes of N-(2-{[(2E)-2-(2-Hydroxy-(5-substituted)-benzylidene)-hydrazino]carbonyl}phenyl)benzamide ligands and heterocyclic coligands

    NASA Astrophysics Data System (ADS)

    Chavan, S. S.; Sawant, V. A.; Jadhav, A. N.

    2014-01-01

    Some copper(II) complexes of the type [Cu(L1-3)(phen]ṡCH2Cl2 (1a-3a) and [Cu(L1-3) (bipy)]ṡCH2Cl2 (1b-3b) (where L1 = N-(2-{[(2E)-2-(2-Hydroxy-benzylidene)-hydrazino]carbonyl}phenyl)benzamide, L2 = N-(2-{[(2E)-2-(2-Hydroxy-(5-bromo)-benzylidene)-hydrazino]carbonyl}phenyl)benzamide, L3 = N-(2-{[(2E)-2-(2-Hydroxy-(5-methoxy)-benzylidene)-hydrazino]carbonyl}phenyl)benzamide; phen = 1,10-phenanthroline, bipy = 2,2‧-bipyridine) have been prepared and characterized on the basis of elemental analyses, IR, UV-Vis and EPR spectral studies. IR spectra indicate that the ligand L1-3 exists in the keto form in the solid state, while at the time of complexation, it tautomerises into enol form. The single crystal X-ray diffraction study of the representative complex [Cu(L1) (phen)]ṡCH2Cl2 (1a) reveals the distorted square pyramidal geometry around copper(II). Crystal data of (1a): space group = P21/n, a = 11.5691(16) Å, b = 11.0885(15) Å, c = 24.890(4) Å, V = 3166.2(8) Å3, Z = 4. The electrochemical behavior of all the complexes indicate that the phen complexes appears at more positive potential as compared to those for bipy complexes, as a consequence of its stronger π acidic character. All the complexes exhibit blue-green emission as a result of the fluorescence from the intra-ligand (π → π∗) emission excited state.

  12. C-C Bond Formation: Synthesis of C5 Substituted Pyrimidine and C8 Substituted Purine Nucleosides Using Water Soluble Pd-imidate Complex.

    PubMed

    Gayakhe, Vijay; Ardhapure, Ajaykumar V; Kapdi, Anant R; Sanghvi, Yogesh S; Serrano, Jose Luis; Schulzke, Carola

    2016-01-01

    The synthesis of a highly efficient, water soluble [Pd(Sacc)2 (TPA)2 ] complex for C-C bond formation is described. Additionally, application of the [Pd(Sacc)2 (TPA)2 ] complex for Suzuki-Miyaura arylation of all four nucleosides (5-iodo-2'-deoxyuridine [5-IdU], 5-iodo-2'-deoxycytidine [5-IdC], 8-bromo-2'-deoxyadenosine, and 8-bromo-2'-deoxyguanosine) with various aryl/heteroaryl boronic acids in plain water under milder conditions is demonstrated. © 2016 by John Wiley & Sons, Inc. PMID:27248782

  13. Synthesis and anti-inflammatory activity of 1-acetyl-5-substituted aryl-3-(beta-aminonaphthyl)-2-pyrazolines and beta-(substituted aminoethyl) amidonaphthalenes.

    PubMed

    Bansal, E; Srivastava, V K; Kumar, A

    2001-01-01

    The title compounds were prepared by reaction of beta-acetylamino-naphthalene with different aromatic aldehydes followed by cyclisation with hydrazine hydrate and with different primary or secondary amines (Mannich's reaction), respectively. The structures of new compounds were confirmed by 1H-NMR and IR spectral data. Anti-inflammatory and ulcerogenic activities in vivo were evaluated and compared with the standard drugs, phenylbutazone and indomethacin. Some compounds of the series exhibited promising anti-inflammatory activity with a lower ulcerogenic liability than the standard drugs. PMID:11231052

  14. Structure-Activity Relationships in a Novel Series of 7-Substituted-Aryl Quinolines and 5-Substituted-Aryl Benzothiazoles at the Metabotropic Glutamate Receptor Subtype 5

    PubMed Central

    Zhang, Peng; Zou, Mu-Fa; Rodriguez, Alice L.; Conn, P. Jeffrey; Newman, Amy Hauck

    2010-01-01

    The metabotropic glutamate receptor subtype 5 (mGluR5) has been implicated in numerous neuropsychiatric disorders including addiction. We have discovered that the rigid diaryl alkyne template, derived from the potent and selective noncompetitive mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP), can serve to guide the design of novel quinoline analogues and pharmacophore optimization has resulted in potent mGluR5 noncompetitive antagonists (EC50 range 60–100 nM) in the quinoline series. PMID:20382541

  15. Synthesis and Antibacterial Evaluation of (S,Z)-4-methyl-2-(4-oxo-5-((5-substituted phenylfuran-2-yl) methylene)-2-thioxothiazolidin-3-yl)Pentanoic Acids

    PubMed Central

    Song, Ming-Xia; Deng, Xian-Qing; Wei, Zhi-Yu; Zheng, Chang-Ji; Wu, Yan; An, Chang-Shan; Piao, Hu-Ri

    2015-01-01

    The microbial resistance has become a global hazard with the irrational use of antibiotics. Infection of drug-resistant bacteria seriously threatens human health. Currently, there is an urgent need for the development of novel antimicrobial agents with new mechanisms and lower levels of toxicity. In this paper, a series of (S,Z)-4-methyl-2-(4-oxo-5-((5-substitutedphenylfuran-2-yl) methylene)-2-thioxothiazolidin-3-yl)pentanoic acids via a Knoevenagel condensation were synthesized and evaluated for their antibacterial activity in-vitro. The synthesized compounds were characterized by IR, 1H NMR and MS. The antibacterial test in-vitro showed that all of the synthesized compounds had good antibacterial activity against several Gram-positive bacteria (including multidrug-resistant clinical isolates) with minimum inhibitory concentration (MIC) values in the range of 2–4 µg/mL. Especially compounds 4c, 4d, 4e and 4f were the most potent, with MIC values of 2 µg/mL against four multidrug-resistant Gram-positive bacterial strains. PMID:25561915

  16. Discovery of 3-(5'-Substituted)-Benzimidazole-5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors: Design, Synthesis, and Biological Evaluation.

    PubMed

    Yan, Wei; Wang, Xinyi; Dai, Yang; Zhao, Bin; Yang, Xinying; Fan, Jun; Gao, Yinglei; Meng, Fanwang; Wang, Yuming; Luo, Cheng; Ai, Jing; Geng, Meiyu; Duan, Wenhu

    2016-07-28

    Fibroblast growth factor receptor (FGFR) represents an attractive oncology target for cancer therapy in view of its critical role in promoting cancer formation and progression, as well as causing resistance to approved therapies. In this article, we describe the identification of the potent pan-FGFR inhibitor (R)-21c (FGFR1-4 IC50 values of 0.9, 2.0, 2.0, and 6.1 nM, respectively). Compound (R)-21c exhibited excellent in vitro inhibitory activity against a panel of FGFR-amplified cell lines. Western blot analysis demonstrated that (R)-21c suppressed FGF/FGFR and downstream signaling pathways at nanomolar concentrations. Moreover, (R)-21c provided nearly complete inhibition of tumor growth (96.9% TGI) in NCI-H1581 (FGFR1-amplified) xenograft mice model at the dose of 10 mg/kg/qd via oral administration. PMID:27348537

  17. Hit Optimization of 5-Substituted-N-(piperidin-4-ylmethyl)-1H-indazole-3-carboxamides: Potent Glycogen Synthase Kinase-3 (GSK-3) Inhibitors with in Vivo Activity in Model of Mood Disorders.

    PubMed

    Furlotti, Guido; Alisi, Maria Alessandra; Cazzolla, Nicola; Dragone, Patrizia; Durando, Lucia; Magarò, Gabriele; Mancini, Francesca; Mangano, Giorgina; Ombrato, Rosella; Vitiello, Marco; Armirotti, Andrea; Capurro, Valeria; Lanfranco, Massimiliano; Ottonello, Giuliana; Summa, Maria; Reggiani, Angelo

    2015-11-25

    Novel treatments for bipolar disorder with improved efficacy and broader spectrum of activity are urgently needed. Glycogen synthase kinase 3β (GSK-3β) has been suggested to be a key player in the pathophysiology of bipolar disorder. A series of novel GSK-3β inhibitors having the common N-[(1-alkylpiperidin-4-yl)methyl]-1H-indazole-3-carboxamide scaffold were prepared taking advantage of an X-ray cocrystal structure of compound 5 with GSK-3β. We probed different substitutions at the indazole 5-position and at the piperidine-nitrogen to obtain potent ATP-competitive GSK-3β inhibitors with good cell activity. Among the compounds assessed in the in vivo PK experiments, 14i showed, after i.p. dosing, encouraging plasma PK profile and brain exposure, as well as efficacy in a mouse model of mania. Compound 14i was selected for further in vitro/in vivo pharmacological evaluation, in order to elucidate the use of ATP-competitive GSK-3β inhibitors as new tools in the development of new treatments for mood disorders. PMID:26486317

  18. Reactivity of damaged pyrimidines: formation of a Schiff base intermediate at the glycosidic bond of saturated dihydrouridine.

    PubMed

    Jian, Yajun; Lin, Gengjie; Chomicz, Lidia; Li, Lei

    2015-03-11

    DNA glycosylases catalyze the first step of the base excision repair (BER) pathway. The chemistry used by these enzymes for deglycosylation has been largely considered as the chemistry of the oxocarbenium ion, e.g., direct rupture of the C1'-N1 bond resulting in an oxocarbenium ion intermediate. Here we present mechanistic studies revealing the 2'-deoxyribose isomerization and subsequent deglycosylation processes in two pyrimidine lesions: 5,6-dihydro-2'-deoxyuridine (dHdU) and 5,6-dihydrothymidine (dHT), formed via ionizing radiation damage to 2'-deoxycytidine and thymidine, respectively, under anoxic conditions. Acid or heat treatment of these two lesions leads to the production of two pairs of C1' epimers containing a pyranose and a furanose, respectively, indicating that both lesions favor the rupture of the C1'-O4' bond, resulting in a Schiff base intermediate at the N-glycosidic bond. Such a Schiff base intermediate was trapped and characterized by either Pd-catalyzed hydrogenation or thiol-mediated addition reaction. In contrast, in undamaged 2'-deoxyuridine and thymidine, reactions at elevated temperatures lead to the release of nucleobases most likely via the traditional oxocarbenium ion pathway. DFT calculations further support the experimental findings, suggesting that the oxocarbenium ion intermediate is responsible for the deglycosylation process if the integrity of the pyrimidine ring is maintained, while the Schiff base intermediate is preferred if the C5═C6 bond is saturated. Currently, the oxocarbenium ion pathway is indicated to be solely responsible for the deglycosylation in BER enzymes, however our results suggest an alternative Schiff base mechanism which may be responsible for the repair of saturated pyrimidine damages. PMID:25671389

  19. Conformational properties of 1,4- and 1,5-substituted 1,2,3-triazole amino acids – building units for peptidic foldamers† †Electronic supplementary information (ESI) available: Tables on the RHF/3-21G conformers, NMR spectra and analysis. See DOI: 10.1039/c4ob02359e Click here for additional data file.

    PubMed Central

    2015-01-01

    Peptidic foldamers have recently emerged as a novel class of artificial oligomers with properties and structural diversity similar to that of natural peptides, but possessing additional interesting features granting them great potential for applications in fields from nanotechnology to pharmaceuticals. Among these, foldamers containing 1,4- and 1,5-substitued triazole amino acids are easily prepared via the Cu- and Ru-catalyzed click reactions and may offer increased side chain variation, but their structural capabilities have not yet been widely explored. We here describe a systematic analysis of the conformational space of the two most important basic units, the 1,4-substitued (4Tzl) and the 1,5-substitued (5Tzl) 1,2,3-triazole amino acids, using quantum chemical calculations and NMR spectroscopy. Possible conformations of the two triazoles were scanned and their potential minima were located using several theoretical approaches (B3LYP/6-311++G(2d,2p), ωB97X-D/6-311++G(2d,2p), M06-2X/6-311++G(2d,2p) and MP2/6-311++G(2d,2p)) in different solvents. BOC-protected versions of 4Tzl and 5Tzl were also prepared via one step transformations and analyzed by 2D NOESY NMR. Theoretical results show 9 conformers for 5Tzl derivatives with relative energies lying close to each other, which may lead to a great structural diversity. NMR analysis also indicates that conformers preferring turn, helix and zig-zag secondary structures may coexist in solution. In contrast, 4Tzl has a much lower number of conformers, only 4, and these lack strong intraresidual interactions. This is again supported by NMR suggesting the presence of both extended and bent conformers. The structural information provided on these building units could be employed in future design of triazole foldamers. PMID:25605623

  20. Coordination polymers of 5-substituted isophthalic acid† †Electronic supplementary information (ESI) available. CCDC 1417516–1417520 contain the supplementary crystallographic data for this paper. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ce02091c Click here for additional data file. Click here for additional data file.

    PubMed Central

    Morris, Samuel A.; Slawin, Alexandra M. Z.; Teat, Simon J.; Morris, Russell E.

    2016-01-01

    The synthesis and characterisation of five coordination polymers – Ni2(mip)2(H2O)8·2H2O (1), Zn6(mip)5(OH)2(H2O)4·7.4H2O (2), Zn6(mip)5(OH)2(H2O)2·4H2O (3), Mn(HMeOip)2 (4), and Mn3(tbip)2(Htbip)2(EtOH)2 (5) – are reported. Preliminary nitric oxide release data on compounds 2 and 3 are also given. PMID:27019640

  1. A Propos of Glycosyl Cations and the Mechanism of Chemical Glycosylation; the Current State of the Art

    PubMed Central

    Bohé, Luis

    2014-01-01

    An overview of recent advances in glycosylation with particular emphasis on mechanism is presented. The mounting evidence for both the existence of glycosyl oxocarbenium ions as fleeting intermediates in some reactions, and the crucial role of the associated in counter ion in others is discussed. The extremes of the SN1 and SN2 manifolds for the glycosylation reaction are bridged by a continuum of mechanisms in which it appears likely that most examples are located. PMID:25108484

  2. Transition-Metal-Free Cross-Coupling of Indium Organometallics with Chromene and Isochroman Acetals Mediated by BF3·OEt2.

    PubMed

    Gil-Negrete, José M; Pérez Sestelo, José; Sarandeses, Luis A

    2016-09-01

    A transition-metal-free coupling of triorganoindium reagents with benzopyranyl acetals mediated by a Lewis acid has been developed. The reaction of R3In with chromene and isochroman acetals in the presence of BF3·OEt2 afforded 2-substituted chromenes and 1-substituted isochromans, respectively, in good yields. The reactions proceed with a variety of triorganoindium reagents (aryl, heteroaryl, alkynyl, alkenyl, alkyl) using only 50 mol % of the organometallic, thus demonstrating the efficiency of these species. Preliminary mechanistic studies indicate the formation of an oxocarbenium ion intermediate in the presence of the Lewis acid. PMID:27530143

  3. The role of enzyme distortion in the single displacement mechanism of family 19 chitinases

    PubMed Central

    Brameld, Ken A.; Goddard, William A.

    1998-01-01

    By using molecular dynamics simulations, we have examined the binding of a hexaNAG substrate and two potential hydrolysis intermediates (an oxazoline ion and an oxocarbenium ion) to a family 19 barley chitinase. We find the hexaNAG substrate binds with all sugars in a chair conformation, unlike the family 18 chitinase which causes substrate distortion. Glu 67 is in a position to protonate the anomeric oxygen linking sugar residues D and E whereas Asn 199 serves to hydrogen bond with the C2′ N-acetyl group of sugar D, thus preventing the formation of an oxazoline ion intermediate. In addition, Glu 89 is part of a flexible loop region allowing a conformational change to occur within the active site to bring the oxocarbenium ion intermediate and Glu 89 closer by 4–5 Å. A hydrolysis product with inversion of the anomeric configuration occurs because of nucleophilic attack by a water molecule that is coordinated by Glu 89 and Ser 120. Issues important for the design of inhibitors specific to family 19 chitinases over family 18 chitinases also are discussed. PMID:9539727

  4. Synthesis of new ent-labdane diterpene derivatives from andrographolide and evaluation on cytotoxic activities.

    PubMed

    Luo, Yan; Wang, Ke; Zhang, Meng-han; Zhang, Da-yong; Wu, Yang-chang; Wu, Xiao-ming; Hua, Wei-yi

    2015-06-01

    There are many reports for andrographolide modification regarding antitumor effects. Transformation of the five-membered lactone ring to furan aromatic ring still results in compounds with good cytotoxicity. To determine further the importance of the five-membered lactone ring and to obtain better lead compounds, we transformed the five-membered lactone ring in andrographolide. New types of ent-labdane diterpene derivatives were made, whose cytotoxic activities were measured in vitro. Preliminary SAR was summarized and two compounds, 7 and 26, with good cytotoxic activity were obtained, which have the potential to be developed into new antitumor drugs. PMID:25913115

  5. Photo-alteration of hydantoins against UV light and its relevance to prebiotic chemistry

    NASA Astrophysics Data System (ADS)

    Sarker, Palash K.; Takahashi, Jun-ichi; Obayashi, Yumiko; Kaneko, Takeo; Kobayashi, Kensei

    2013-06-01

    Aqueous solutions of 5-substituted hydantoins were irradiated with ultraviolet (UV) light, to investigate their structural stability against UV radiation as well as the possible photolysis products. The photolysis products were identified and the degree of photolysis was measured using reversed-phase and ion-exchange high-performance liquid chromatography. Hydantoin (2,4-imidazolidinedione) was dominantly detected as a photolysis product of 5-substituted hydantoins. With hydrolysis of UV-irradiated 5-substituted hydantoins, glycine and alanine were dominantly detected. These experimental results are important for the prebiotic photochemistry of 5-substituted hydantoins in the formation of hydantoin since they have been detected in Solar System materials.

  6. An aromatic ion platform for enantioselective Brønsted acid catalysis.

    PubMed

    Gheewala, Chirag D; Collins, Bridget E; Lambert, Tristan H

    2016-02-26

    Chiral acid catalysts are useful for the synthesis of enantioenriched small molecules, but the standard catalysts require laborious and expensive preparations. Here, we describe a chiral Brønsted acid prepared in one step from naturally occurring (-)-menthol and readily available 1,2,3,4,5-pentacarbomethoxycyclopentadiene. Aromatic stabilization serves as a key contributing factor to the potent acidity of the resulting compound, which is shown to catalyze both Mukaiyama-Mannich and oxocarbenium aldol reactions with high efficiency and enantioselectivity. Catalyst loadings as low as 0.01 mole percent and preparative scalability (25 grams) are demonstrated. Alternative amide catalysts are also shown to be promising platforms. In addition to proton catalysis, a chiral anion pathway is demonstrated to be viable with this catalyst system. PMID:26917768

  7. Structural basis of actin recognition and arginine ADP-ribosylation by Clostridium perfringens ι-toxin

    PubMed Central

    Tsuge, Hideaki; Nagahama, Masahiro; Oda, Masataka; Iwamoto, Shinobu; Utsunomiya, Hiroko; Marquez, Victor E.; Katunuma, Nobuhiko; Nishizawa, Mugio; Sakurai, Jun

    2008-01-01

    The ADP-ribosylating toxins (ADPRTs) produced by pathogenic bacteria modify intracellular protein and affect eukaryotic cell function. Actin-specific ADPRTs (including Clostridium perfringens ι-toxin and Clostridium botulinum C2 toxin) ADP-ribosylate G-actin at Arg-177, leading to disorganization of the cytoskeleton and cell death. Although the structures of many actin-specific ADPRTs are available, the mechanisms underlying actin recognition and selective ADP-ribosylation of Arg-177 remain unknown. Here we report the crystal structure of actin-Ia in complex with the nonhydrolyzable NAD analog βTAD at 2.8 Å resolution. The structure indicates that Ia recognizes actin via five loops around NAD: loop I (Tyr-60–Tyr-62 in the N domain), loop II (active-site loop), loop III, loop IV (PN loop), and loop V (ADP-ribosylating turn–turn loop). We used site-directed mutagenesis to confirm that loop I on the N domain and loop II are essential for the ADP-ribosyltransferase activity. Furthermore, we revealed that Glu-378 on the EXE loop is in close proximity to Arg-177 in actin, and we proposed that the ADP-ribosylation of Arg-177 proceeds by an SN1 reaction via first an oxocarbenium ion intermediate and second a cationic intermediate by alleviating the strained conformation of the first oxocarbenium ion. Our results suggest a common reaction mechanism for ADPRTs. Moreover, the structure might be of use in rational drug design to block toxin-substrate recognition. PMID:18490658

  8. (Phen­yl)(3-phenyl­sulfonyl-1,2-dihydro­pyrrolo­[1,2-a]quinoxalin-1-yl)methanone

    PubMed Central

    Dürüst, Yaşar; Sağırlı, Akın; Fronczek, Frank R.

    2011-01-01

    In the title mol­ecule, C24H18N2O3S, the 13-atom ring system comprising the quinoxaline and fused five-membered ring exhibits an r.m.s. deviation from coplanarity of 0.039 Å, with a maximum deviation of 0.0710 (10) Å for the PhCO-bearing C atom of the five-membered ring. The 10-membered C8N2 quinoxaline ring system has an r.m.s. deviation from coplanarity of 0.022 Å, with a maximum deviation of 0.0403 (9) Å for the C atom involved in the C=C bond in the five-membered ring. The three atoms of the five-membered ring fused to the quinoxaline ring system show deviations of up to 0.118 (2) Å for the PhCO-bearing C atom. C—N bond distances in the quinoxaline ring system of the title mol­ecule deviate from those in unsubstituted quinoxaline. In particular, the two C—N distances to the N atom involved in the five-membered ring are essentially equal, with values of 1.3786 (17) and 1.3773 (16) Å, unlike the difference of nearly 0.06 Å in quinoxaline. PMID:22219900

  9. Crystal structure of 3-meth­oxy­carbonyl-2-(4-meth­oxy­phen­yl)-8-oxo-1-aza­spiro[4.5]deca-1,6,9-trien-1-ium-1-olate

    PubMed Central

    Martins, Lucimara Julio; Simoni, Deborah de Alencar; Aparicio, Ricardo; Coelho, Fernando

    2014-01-01

    The title compound, C18H17NO5, was prepared by a synthetic strategy based on the Heck reaction from Morita–Baylis–Hillman adducts. The five-membered ring adopts a slightly twisted conformation on the Ca—Cm (a = aromatic and m = methyl­ene) bond. The dihedral angle between the five-membered ring and the spiro aromatic ring is 89.35 (7)°; that between the five-membered ring and the 4-meth­oxy­benzene ring is 4.65 (7)°. Two short intra­molecular C—H⋯O contacts occur. In the crystal, mol­ecules are linked by C—H⋯O hydrogen bonds to generate a three-dimensional network. PMID:25484828

  10. 2-Methyl-6-(4,4,10,13,14-penta­methyl-3-oxo-2,3,4,5,6,7,10,11,12,13,14,15,16,17-tetra­deca­hydro-1H-cyclo­penta­[a]phenanthren-17-yl)hept-2-enoic acid

    PubMed Central

    Arfan, Mohammad; Rauf, Abdur; Tahir, M. Nawaz; Ali, Mumtaz; Uddin, Ghias

    2011-01-01

    In the title compound, C30H46O3, an isolation product of Pistacia integerima Stewart, the five-membered ring is nearly in the envelope form. A 6-carb­oxy­hept-5-en-2-yl group is attached to the five-membered ring. An S(6) ring motif is formed due to intra­molecular C—H⋯O hydrogen bonding. In the crystal, inter­molecular O—H⋯O hydrogen bonds form carboxyl­ate dimers with R 2 2(8) ring motifs. PMID:21522454

  11. Chemical abundances of A-type dwarfs in the young open cluster M6

    NASA Astrophysics Data System (ADS)

    Kílíçoǧlu, T.; Monier, R.; Fossati, L.

    2011-12-01

    Elemental abundance analysis of five members in the open cluster M6 (age ˜90 myr) were performed using FLAMES-GIRAFFE spectrograph mounted on 8-meter class VLT telescopes. The abundances of 14 chemical elements were derived. Johnson and Geneva photometric systems, hydrogen line profile fittings, and ionization equilibrium were used to derive the atmospheric parameters of the stars. Synthetic spectra were compared to the observed spectra to derive chemical abundances. The abundance analysis of these five members shows that these stars have an enhancement (or solar composition) of metals in general, with some exceptions. C, O, Ca, Sc, Ni, Y, and Ba exhibit the largest star-to-star abundance variations.

  12. Trimethyl-3-meth­oxy-4-oxo-5-triphenyl­phospho­ranyl­idene­cyclo­pent-1-ene-1,2,3-tricarboxyl­ate

    PubMed Central

    Krawczyk, Krzysztof K.; Wojtasiewicz, Krystyna; Maurin, Jan K.; Gronowska, Ewa; Czarnocki, Zbigniew

    2010-01-01

    The title compound, C30H27O8P (2), was formed as one of two products {(1) [Krawczyk et al. (2010 ▶). Acta Cryst. E66 (cv2752)] and (2)} in the reaction of dimethyl acetyl­enedicarboxyl­ate with triphenyl­phosphine. The mol­ecule of (2) consists of a five-membered carbocyclic ring. The P atom is a part of a triphenylphosphoranylidene substituent. In contrast to (1), the five-membered ring of (2) is planar, the r.m.s. deviation being only 0.009 (2) Å. PMID:21588989

  13. ANAEROBIC BIODEGRADATION OF NITROGEN-SUBSTITUTED AND SULFONATED BENZENE AQUIFER CONTAMINANTS (JOURNAL)

    EPA Science Inventory

    A literature survey of ground water contaminants indicated that aquifers are repositories for hazardous wastes, including N- and 5-substituted benzene derivatives. We therefore examined the susceptibility of several anilines, benzamides, benenesulfonic acids and benenesulfonamide...

  14. THE FAD2 GENE FAMILY OF SOYBEAN:INSIGHTS INTO THE STRUCTURAL AND FUNCTIONAL DIVERGENCE OF A PALEOPOLYPLOID GENOME

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The omega-6 fatty acid desaturase (FAD2) gene family in soybean consists of at least five members in four regions of the genome. These desaturases are responsible for the conversion of oleic acid to linoleic acid. Bacterial artificial chromosomes (BACs) corresponding to these loci were sequenced to ...

  15. Columbia (STS-65) landing

    NASA Technical Reports Server (NTRS)

    1994-01-01

    Space Shuttle Columbia (STS-62) comes to a graceful halt with the help of a parachute after a 14-day mission. The five member crew performed materials processing experiments on the United States Microgravity Payload 2 (USMP-2), and also conducted experiments designed to enable or extend space flight technology aboard the Office of Aeornautics and Space Technology 2 payload (OAST-2).

  16. How to Add Philosophy Dimensions in Your Basic International Business Course

    ERIC Educational Resources Information Center

    Thanopoulos, John

    2010-01-01

    This article aims to assist professors in introducing concepts of self, philosophy, religions, the universe, existential dilemmas, etc., in their basic international business classes. Using active learning and five-member student teams, a student organized and administered conference adds a very useful dimension of knowledge sacrificing only one…

  17. Relieving DELLA Repression of Stem Elongation and Flowering, Evidence for a Proteolysis Independent Mechanism for GA signaling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    GA stimulates germination, stem elongation, and flowering by lifting DELLA protein repression of these responses via both proteolysis dependent and independent pathways. There are five members of the DELLA protein family in Arabidopsis with partially overlapping functions. GA biosynthesis lifts DELL...

  18. 10 CFR 13.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... COMMISSION PROGRAM FRAUD CIVIL REMEDIES § 13.2 Definitions. As used in this part: ALJ means an Administrative... to 5 U.S.C. 3344. Authority means the Nuclear Regulatory Commission. Authority head means the Commission of five members or a quorum thereof sitting as a body, as provided by section 201 of the...

  19. A Secret Support Network

    ERIC Educational Resources Information Center

    Wasley, Paula

    2007-01-01

    This article describes Hanover College's Early Alert Team, an early-alert program that seeks to identify students' academic, social, or personal troubles as soon as they surface. The team's five members gather information about students from all corners of the campus and then devise strategies to help them. The early-alert system has not only…

  20. Portraiture as Pedagogy: Learning Research through the Exploration of Context and Methodology

    ERIC Educational Resources Information Center

    Gaztambide-Fernandez, Ruben; Cairns, Kate; Kawashima, Yuko; Menna, Lydia; VanderDussen, Elena

    2011-01-01

    In this reflective essay, five members of a research team involving graduate students and a faculty member offer individual "studies" of specific moments in the field in which lessons about methodology, the research context, and the researcher herself/himself crystallized. The article highlights the pedagogical possibilities of portraiture for…

  1. 12 CFR 905.10 - Board of Directors.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Board of Directors. 905.10 Section 905.10 Banks... DESCRIPTION OF ORGANIZATION AND FUNCTIONS General Organization § 905.10 Board of Directors. (a) Board of Directors—(1) General. The Bank Act vests management of the Finance Board in a five-member Board...

  2. Gold Sulfinyl Mesoionic Carbenes: Synthesis, Structure, and Catalytic Activity.

    PubMed

    Frutos, María; Avello, Marta G; Viso, Alma; Fernández de la Pradilla, Roberto; de la Torre, María C; Sierra, Miguel A; Gornitzka, Heinz; Hemmert, Catherine

    2016-08-01

    Gold mesoionic carbenes having a chiral sulfoxide group attached to the C4 position of the five membered ring have been prepared and tested as catalysts in the cycloisomerization of enynes. These new catalysts are very efficient, with the sulfoxide moiety playing a key role in their activity and the N1-substituent in control of the regioselectivity of these processes. PMID:27403763

  3. Exploring the Cautionary Attitude toward Wikipedia in Higher Education: Implications for Higher Education Institutions

    ERIC Educational Resources Information Center

    Bayliss, Gemma

    2013-01-01

    This article presents the research findings of a small-scale study which aimed to explore the cautionary attitude toward the use of Wikipedia in the process of learning. A qualitative case study approach was taken, using literature review, institutional documentation, and semi-structured interviews with five members of academic teaching staff from…

  4. Synthesis and characterization of estolide esters containing epoxy and cyclic carbonate groups

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The unsaturated sites in oleic 2-ethylhexyl estolide esters (containing 35% monoenic fatty acids) were converted into epoxide and five-membered cyclic carbonate groups and the products characterized by Fourier transform infrared spectra (FTIR), 1H-, and 13C-nuclear magnetic resonance (NMR) spectrosc...

  5. Using WRF for Regional Climate Modeling: An Emphasis on the Southeast U.S. for Future Air Quality

    EPA Science Inventory

    This presentation describes preliminary analysis of a five-member regional climate ensemble (developed by AMAD and its contractors, including UNC) to determine if there is any consensus on projected changes to the placement of the North Atlantic Subtropical High (NASH, or Bermuda...

  6. phyA dominates in transduction of red-light signals to rapidly responding genes at the initiation of Arabidopsis seedling de-etiolation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Contrary to expectations based on the visible phenotypic behavior of seedlings undergoing de-etiolation in response to continuous red light (Rc), previous gene expression profiling showed that one or more of the five-membered phytochrome (phy) family of Arabidopsis, other than phyB, is predominantly...

  7. Evaluation of the Albuquerque Indian School Motivational Environment Program.

    ERIC Educational Resources Information Center

    Hiat, Albert B.; And Others

    In order to evaluate the impact of a token economy behavior modification program implemented from 1970-71 in the Albuquerque Indian School (AIS), a secondary institution, a five-member evaluation team assessed standardized test results, behavioral data, and student and staff attitudes. A battery of tests (Tennessee Self-Concept Scale, SRA…

  8. 21 CFR 19.10 - Food and Drug Administration Conflict of Interest Review Board.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Food and Drug Administration Conflict of Interest... and Drug Administration Conflict of Interest Review Board. (a) The Commissioner shall establish a permanent five-member Conflict of Interest Review Board, which shall review and make recommendations to...

  9. Remembering Nancy. 25 Members of the Montessori Community Share Their Reflections on the Death of the AMS Founder.

    ERIC Educational Resources Information Center

    Turner, Joy; And Others

    1995-01-01

    Twenty-five members of the Montessori community share their memories of Dr. Nancy McCormick Rambusch, charismatic founder of the American Montessori movement, early childhood professional, and innovative educator, who died of pancreatic cancer on October 27, 1994. Rambusch's work of 40 years now flowers as an institutionalized educational program…

  10. 12 CFR 905.10 - Board of Directors.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Board of Directors. 905.10 Section 905.10 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS... Directors—(1) General. The Bank Act vests management of the Finance Board in a five-member Board...

  11. 78 FR 65728 - Medley Capital Corporation, et al.; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-01

    ... meaning of section 2(a)(19) of the Act (the ``Independent Directors''). Each of Andrew Fentress, Brooke...'') currently consists of five members, three of whom are Independent Directors. Two of the Principals, Brook... condition will ensure that the Independent Directors will act independently in evaluating the Co-...

  12. Current Updates on Oxazolidinone and Its Significance

    PubMed Central

    Pandit, Neha; Singla, Rajeev K.; Shrivastava, Birendra

    2012-01-01

    Oxazolidinone is a five-member heterocyclic ring exhibiting potential medicinal properties with preferential antibacterial activity. Scientists reported various synthetic procedures for this heterocyclic structure. Current review articles tried to cover each and every potential aspect of oxazolidinone like synthetic routes, pharmacological mechanism of action, medicinal properties, and current research activities. PMID:25954524

  13. Recent Pharmacological Developments on Rhodanines and 2,4-Thiazolidinediones

    PubMed Central

    Bhatti, Ravinder Singh; Shah, Sakshi; Suresh; Krishan, Pawan; Sandhu, Jagir S.

    2013-01-01

    Thiazolidines are five-member heterocyclic having sulfur, nitrogen, and oxygen atoms in their ring structure and exhibiting potent as well as wide range of pharmacological activities. In this minireview, recent updates on synthesis and pharmacological evaluations of molecules based on 2,4-thiazolidine and rhodanine are discussed. PMID:25379289

  14. Speech Writing--A Major Public Relations Activity?

    ERIC Educational Resources Information Center

    Baskin, Otis

    The magnitude and importance of nonpolitical speech ghostwriting as a public relations activity was investigated. Corporate public relations departments and public relations counseling firms with more than five members that are listed in the directory of the Public Relations Society of America received a questionnaire asking seven questions about…

  15. Synthesis and electronic properties of polycyclic aromatic hydrocarbons doped with phosphorus and sulfur.

    PubMed

    Delaunay, W; Szűcs, R; Pascal, S; Mocanu, A; Bouit, P-A; Nyulászi, L; Hissler, M

    2016-02-01

    In this work, we report on the synthesis of polyaromatic hydrocarbons containing phosphole and thiophene rings at the edge. The ring-closure reactions have been investigated by theoretical calculations. The optical and electrochemical properties and density functional theory calculations showed that the properties depend on the relative position of these five membered rings in the PAH structure. PMID:26646633

  16. Institutional Self Study in Support of Reaffirmation of Accreditation.

    ERIC Educational Resources Information Center

    El Camino Coll., Torrance, CA.

    El Camino College, California, is a public two-year college in the South Bay area of Los Angeles County. The El Camino College District encompasses 5 high school districts, 12 elementary school districts and nine cities, with a population of almost 1 million. The district is governed by a five-member Board of Trustees, each representing one of the…

  17. 14 CFR 1230.107 - IRB membership.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true IRB membership. 1230.107 Section 1230.107 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION PROTECTION OF HUMAN SUBJECTS § 1230.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of...

  18. 5-Bromo-1H-pyrrolo-[2,3-b]pyridine.

    PubMed

    Starha, Pavel; Trávníček, Zdeněk

    2013-03-01

    In the title compound, C7H5BrN2, fused six-membered pyridine and five-membered pyrrole rings form the essentially planar aza-indole skeleton (r.m.s. deviation = 0.017 Å). In the crystal, pairs of N-H⋯N hydrogen bonds connect the mol-ecules into inversion dimers. PMID:23476567

  19. Attitudes to Agricultural Policy and Farming Futures in the Context of the 2003 CAP Reform: A Comparison of Farmers in Selected Established and New Member States

    ERIC Educational Resources Information Center

    Gorton, Matthew; Douarin, Elodie; Davidova, Sophia; Latruffe, Laure

    2008-01-01

    Farmers' attitudes, to agricultural production, diversification and policy support, and behavioural intentions in five Member States of the EU (France, Lithuania, Slovakia, Sweden, England) are analysed comparatively. Groups of farmers with similarly held attitudes are identified using cluster analysis to investigate whether differences in…

  20. Acrylamide encephaloneuropathy due to well water pollution.

    PubMed Central

    Igisu, H; Goto, I; Kawamura, Y; Kato, M; Izumi, K

    1975-01-01

    All five members of a family developed subacutely mental confusion and/or truncal ataxia. Symptoms and signs of polyneuropathy were seen later. The well water in the patients' home contained 400 ppm acrylamide. The present cases are unique in that they are cases of acrylamide poisoning induced by oral intake and percutaneous penetration, and that central nervous system symptoms were prominent. PMID:168322

  1. 49 CFR 802.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Other Regulations Relating to Transportation (Continued) NATIONAL TRANSPORTATION SAFETY BOARD RULES... the five Members of the National Transportation Safety Board, or a quorum thereof; Individual means a... Transportation Safety Board (NTSB) means the agency set up under the Independent Safety Board Act of 1974;...

  2. 17 CFR 200.10 - The Commission.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... President pursuant to the provisions of section 3 of Reorganization Plan No. 10 of 1950 (3 CFR, 1949-1953... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false The Commission. 200.10 Section... The Commission. The Commission is composed of five members, not more than three of whom may be...

  3. 17 CFR 200.10 - The Commission.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... President pursuant to the provisions of section 3 of Reorganization Plan No. 10 of 1950 (3 CFR, 1949-1953... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false The Commission. 200.10 Section... The Commission. The Commission is composed of five members, not more than three of whom may be...

  4. 17 CFR 200.10 - The Commission.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... President pursuant to the provisions of section 3 of Reorganization Plan No. 10 of 1950 (3 CFR, 1949-1953... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false The Commission. 200.10 Section... The Commission. The Commission is composed of five members, not more than three of whom may be...

  5. 17 CFR 200.10 - The Commission.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... President pursuant to the provisions of section 3 of Reorganization Plan No. 10 of 1950 (3 CFR, 1949-1953... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false The Commission. 200.10 Section... The Commission. The Commission is composed of five members, not more than three of whom may be...

  6. 17 CFR 200.10 - The Commission.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... President pursuant to the provisions of section 3 of Reorganization Plan No. 10 of 1950 (3 CFR, 1949-1953... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false The Commission. 200.10 Section... The Commission. The Commission is composed of five members, not more than three of whom may be...

  7. 7 CFR 1215.21 - Establishment and membership.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Popcorn Board § 1215.21 Establishment and membership. (a) There is hereby established a Popcorn Board of five members. The number...

  8. 7 CFR 1215.21 - Establishment and membership.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Popcorn Board § 1215.21 Establishment and membership. (a) There is hereby established a Popcorn Board of five members. The number...

  9. 7 CFR 1215.21 - Establishment and membership.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Popcorn Board § 1215.21 Establishment and membership. (a) There is hereby established a Popcorn Board of five members. The number...

  10. 7 CFR 1215.21 - Establishment and membership.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Popcorn Board § 1215.21 Establishment and membership. (a) There is hereby established a Popcorn Board of five members. The number...

  11. Alameda Unified School District, 2009-2011. Alameda Case Study

    ERIC Educational Resources Information Center

    Pivot Learning Partners, 2011

    2011-01-01

    When the five-member Board of the Alameda Unified School District selected Kirsten Vital as the new superintendent in 2009, they chose someone from outside their tight-knit community. Board Trustee Margie Sherratt thought Vital was chosen to "get us moving," to be a change agent on closing the achievement gap. Vital, in her initial conversations…

  12. 32 CFR 865.107 - DRB composition and meeting location.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 6 2012-07-01 2012-07-01 false DRB composition and meeting location. 865.107 Section 865.107 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE... composition and meeting location. (a) The DRB consists of five members, with the senior line officer acting...

  13. 32 CFR 865.107 - DRB composition and meeting location.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false DRB composition and meeting location. 865.107 Section 865.107 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE... composition and meeting location. (a) The DRB consists of five members, with the senior line officer acting...

  14. 32 CFR 865.107 - DRB composition and meeting location.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 6 2014-07-01 2014-07-01 false DRB composition and meeting location. 865.107 Section 865.107 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE... composition and meeting location. (a) The DRB consists of five members, with the senior line officer acting...

  15. 32 CFR 865.107 - DRB composition and meeting location.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 6 2011-07-01 2011-07-01 false DRB composition and meeting location. 865.107 Section 865.107 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE... composition and meeting location. (a) The DRB consists of five members, with the senior line officer acting...

  16. 32 CFR 865.107 - DRB composition and meeting location.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false DRB composition and meeting location. 865.107 Section 865.107 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE... composition and meeting location. (a) The DRB consists of five members, with the senior line officer acting...

  17. An Assessment of the Basic Curriculum Guide for Teaching Vocational Agriculture in Texas.

    ERIC Educational Resources Information Center

    Brown, Herman D.

    The major purpose of this study was to revise the basic production agriculture curriculum guide used by vocational agrculture teachers in Texas. A twenty-five member advisory committee for curriculum revision conducted the following activities: (1) obtained thirty-one curriculum guides for a technical agriculture program, (2) surveyed vocational…

  18. 78 FR 18625 - Call for Nominations for the California Desert District Advisory Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-27

    ... Bureau of Land Management Call for Nominations for the California Desert District Advisory Council AGENCY...) California Desert District is soliciting nominations from the public for five members to serve 3-year terms on its Desert District Advisory Council. Council members provide advice and recommendations to...

  19. The Curriculum Development Project for the Medical Laboratory Technology Program at Miami-Dade Junior College, Miami, Florida. Final Report.

    ERIC Educational Resources Information Center

    Miami-Dade Junior Coll., FL. Div. of Allied Health Studies.

    During Phase I of an Allied Health Professions Basic Improvement Grant, a five-member committee developed a curriculum for a medical laboratory technology program at Miami-Dade Junior College by: (1) defining competencies which differentiate a certified laboratory assistant from a medical laboratory technician, (2) translating expected laboratory…

  20. Single kernel method for detection of 2-acetyl-1-pyrroline in aromatic rice germplasm using SPME-GC/MS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    INTRODUCTION Aromatic rice or fragrant rice, (Oryza sativa L.), has a strong popcorn-like aroma due to the presence of a five-membered N-heterocyclic ring compound known as 2-acetyl-1-pyrroline (2-AP). To date, existing methods for detecting this compound in rice require the use of several kernels. ...

  1. Ligand iron catalysts for selective hydrogenation

    DOEpatents

    Casey, Charles P.; Guan, Hairong

    2010-11-16

    Disclosed are iron ligand catalysts for selective hydrogenation of aldehydes, ketones and imines. A catalyst such as dicarbonyl iron hydride hydroxycyclopentadiene) complex uses the OH on the five member ring and hydrogen linked to the iron to facilitate hydrogenation reactions, particularly in the presence of hydrogen gas.

  2. Causality: School Libraries and Student Success (CLASS). White Paper

    ERIC Educational Resources Information Center

    American Association of School Librarians, 2014

    2014-01-01

    On April 11 and 12, 2014, the American Association of School Librarians (AASL) held "Causality: School Libraries and Student Success" (CLASS), an IMLS-funded national forum. Dr. Thomas Cook, one of the most influential methodologists in education research, and a five member panel of expert scholars and practitioners led 50 established…

  3. Igniting Diversity: Actionable Methods and Ideas for Advancing Diversity in LIS Education in the US

    ERIC Educational Resources Information Center

    Lee, Shari A.; Chancellor, Renate; Chu, Clara M.; Rodriguez-Mori, Howard; Roy, Loriene

    2015-01-01

    The Association for Library and Information Science Education (ALISE) appointed a five-member Taskforce in 2011 to pursue the development of an ALISE Statement on Diversity. Two years later, the ALISE membership voted unanimously to adopt the statement. In an effort to move the statement from mere words on paper, the Taskforce provided actionable…

  4. 10 CFR 1.11 - The Commission.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Headquarters § 1.11 The Commission. (a) The Nuclear Regulatory Commission, composed of five members, one of whom is designated by the... of the licensing and regulatory process, as mandated by the Atomic Energy Act of 1954, as...

  5. 10 CFR 1.11 - The Commission.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Headquarters § 1.11 The Commission. (a) The Nuclear Regulatory Commission, composed of five members, one of whom is designated by the... of the licensing and regulatory process, as mandated by the Atomic Energy Act of 1954, as...

  6. 10 CFR 1.11 - The Commission.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Headquarters § 1.11 The Commission. (a) The Nuclear Regulatory Commission, composed of five members, one of whom is designated by the... of the licensing and regulatory process, as mandated by the Atomic Energy Act of 1954, as...

  7. 10 CFR 1.11 - The Commission.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Headquarters § 1.11 The Commission. (a) The Nuclear Regulatory Commission, composed of five members, one of whom is designated by the... of the licensing and regulatory process, as mandated by the Atomic Energy Act of 1954, as...

  8. 10 CFR 1.11 - The Commission.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Headquarters § 1.11 The Commission. (a) The Nuclear Regulatory Commission, composed of five members, one of whom is designated by the... of the licensing and regulatory process, as mandated by the Atomic Energy Act of 1954, as...

  9. A Delicate Balance: Scientific Communication vs. National Security.

    ERIC Educational Resources Information Center

    Wallerstein, Mitchel B., Ed.; Gould, Stephen B., Ed.

    1987-01-01

    Provides the statements of the representatives of five member countries of the Coordinating Committee on Multilateral Export Control (CoCom) regarding the dissemination of government-sponsored research. Includes textual statements from representatives of the United Kingdom, France, the Federal Republic of Germany, Japan, and the United States. (TW)

  10. Mechanistic insights into the gold(I)-catalyzed activation of glycosyl ortho-alkynylbenzoates for glycosidation.

    PubMed

    Tang, Yu; Li, Jiakun; Zhu, Yugen; Li, Yao; Yu, Biao

    2013-12-11

    Anomerization, which involves cleavage and formation of the anomeric C-O bond, is of fundamental importance in the carbohydrate chemistry. Herein, the unexpected gold(I)-catalyzed anomerization of glycosyl ortho-alkynylbenzoates has been studied in detail. Especially, crossover experiments in the presence of an exogenous isochromen-4-yl gold(I) complex confirm that the anomerization proceeds via the exocleavage mechanism, involving (surprisingly) the addition of the isochromen-4-yl gold(I) complex onto a sugar oxocarbenium (or dioxolenium) and an elimination of LAu(+) from the vinyl gold(I) complex. The inhibitory effect of the exogenous isochromen-4-yl gold(I) complex when in stoichiometric amount on the anomerization has guided us to disclose an isochromen-4-yl gem-gold(I) complex, which is inactive in catalysis but in equilibrium with the monogold(I) complex and the LAu(+) catalyst. The proposed key intermediate in the anomerization, a transient glycosyloxypyrylium species, is successfully trapped via a cycloaddition reaction with n-butyl vinyl ether as a dienophile. SN2-like substitution of the initially formed glycosyloxypyrylium intermediate has then been achieved to a large extent via charging with acceptors in an excess amount to lead to the corresponding glycosides in a stereoselective manner. PMID:24252170

  11. Structure and Cell Wall Cleavage by Modular Lytic Transglycosylase MltC of Escherichia coli

    PubMed Central

    2015-01-01

    The lytic transglycosylases are essential bacterial enzymes that catalyze the nonhydrolytic cleavage of the glycan strands of the bacterial cell wall. We describe here the structural and catalytic properties of MltC, one of the seven lytic transglycosylases found in the genome of the Gram-negative bacterium Escherichia coli. The 2.3 Å resolution X-ray structure of a soluble construct of MltC shows a unique, compared to known lytic transglycosylase structures, two-domain structure characterized by an expansive active site of 53 Å length extending through an interface between the domains. The structures of three complexes of MltC with cell wall analogues suggest the positioning of the peptidoglycan in the active site both as a substrate and as a product. One complex is suggested to correspond to an intermediate in the course of sequential and exolytic cleavage of the peptidoglycan. Moreover, MltC partitioned its reactive oxocarbenium-like intermediate between trapping by the C6-hydroxyl of the muramyl moiety (lytic transglycosylase activity, the major path) and by water (muramidase activity). Genomic analysis identifies the presence of an MltC homologue in no less than 791 bacterial genomes. While the role of MltC in cell wall assembly and maturation remains uncertain, we propose a functional role for this enzyme as befits the uniqueness of its two-domain structure. PMID:24988330

  12. C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands.

    PubMed

    Del Fueyo, M Celeste; Dansey, M Virginia; Paolo, Luciano S; Pecci, Adalí; Veleiro, Adriana S; Burton, Gerardo

    2016-08-01

    The DAF-12 receptor in nematodes and the Liver X Receptor (LXR) in mammals are structurally related transcription factors that play key roles in determining the life span of the organism. Both types of receptors are activated by oxysterols, cholesterol metabolites with oxidized side chains. Restricting the movement of the oxysterol side chain to certain orientations may have profound effects in the activity profile, however this has not been explored so far. In a first attempt to obtain analogues of natural ligands of DAF-12 and LXR with restricted side chain mobility we introduced a 16,22-oxygen bridge in 26-hydroxycholesterol, a cholestenoic acid and a dafachronic acid (5-7). Diosgenin was used as starting material, the key step to obtain the 16,22 epoxy functionality was the one pot formation and reduction of a cyclic hemiketal via the oxocarbenium ion using sodium cyanoborohydride. All new compounds were characterized by NMR and mass spectrometry and assayed as ceDAF-12 or LXR ligands in transactivation cell-based assays. The dafachronic acid analogue 7 behaved as a ceDAF-12 agonist. PMID:27235856

  13. Dissecting the Mechanisms of a Class of Chemical Glycosylation Using Primary 13C Kinetic Isotope Effects

    PubMed Central

    Huang, Min; Garrett, Graham E.; Birlirakis, Nicolas; Bohé, Luis

    2012-01-01

    Although arguably the most important reaction in glycoscience, chemical glycosylations are among the least well understood of organic chemical reactions resulting in an unnecessarily high degree of empiricism and a brake on rational development in this critical area. To address this problem primary 13C kinetic isotope effects now have been determined for the formation of β- and α-manno- and glucopyranosides by a natural abundance NMR method. In contrast to the common current assumption, for three of the four cases studied the experimental values concur with those computed for associative displacement of the intermediate covalent glycosyl trifluoromethanesulfonates. For the formation of the α-mannopyranosides the experimentally determined KIE differs significantly from that computed for an associative displacement, which is strongly suggestive of a dissociative mechanism that approaches the intermediacy of a glycosyl oxocarbenium ion. The application of comparable experiments to other glycosylation systems should shed further light on their glycosylation mechanisms and thus assist in the design of better reactions conditions with improved stereoselectivity. PMID:22824899

  14. UDP-(5F)-GlcNAc acts as a slow-binding inhibitor of MshA, a retaining glycosyltransferase.

    PubMed

    Frantom, Patrick A; Coward, James K; Blanchard, John S

    2010-05-19

    Glycosyltransferase enzymes play important roles in numerous cellular pathways. Despite their participation in many therapeutically relevant pathways, there is a paucity of information on how to effectively inhibit this class of enzymes. Here we report that UDP-(5F)-GlcNAc acts as a slow-binding, competitive inhibitor of the retaining glycosyltransferase MshA from Corynebacterium glutamicum (K(i) approximately 1.6 muM). The kinetic data are consistent with a single-step inhibition mechanism whose equilibration is slow relative to catalysis. We believe that this is the first slow-onset inhibitor to be reported for the glycosyltransferase family of enzymes. The potent inhibition of the enzyme by the fluoro-substituted substrate is consistent with the involvement of an oxocarbenium transition-state structure, which has been previously proposed for this family of enzymes. Additionally, although several members of the GT-B enzyme family, including MshA, have been shown to undergo a conformational change upon UDP-GlcNAc binding, the kinetic data are inconsistent with a two-step inhibition mechanism. This suggests that there may be other conformations of the enzyme that are useful for the design of inhibitors against the large family of GT-B glycosyltransferase enzymes. PMID:20411981

  15. Synthesis of the C-glycoside of α-D-mannose-(1 → 6)-d-myo-inositol†

    PubMed Central

    Hans, Sunej; Altiti, Ahmad; Mootoo, David R.

    2015-01-01

    The dimannosylatedinositol pseudotrisaccharide phospholipid of the lipoarabinomannan (LAM) component of the mycobacterial cell wall has attracted interest as a therapeutic target because of its uniqueness to mycobacteria, its assembly at an early stage in LAM biosynthesis and the immunological activity of oligosaccharides containing this subunit. Accordingly, analogues of this pseudotrisaccharide, α-d-mannose-(1 → 2)-α-d-mannose-(1 → 6)-d-myo-inositol are of interest as mechanistic probes and drug leads. C-glycosides are of special interest because of their hydrolytic stability and conformational differences compared to O-glycosides. Herein, as a prelude to C-glycoside analogues of this pseudotrisaccharide, we describe the synthesis of the C-glycoside of α-D-mannose-(1 → 6)-d-myo-inositol. The synthetic strategy centers on the elaboration of a C1-linked glycal-inositol, the glycone segment of which is assembled via an oxocarbenium ion cyclization on a thioacetal-enol ether precursor that originates from “glycone” and “aglycone” components. PMID:24057020

  16. Structure of the catalytic core module of the Chaetomium thermophilum family GH6 cellobiohydrolase Cel6A.

    PubMed

    Thompson, Andrew J; Heu, Tia; Shaghasi, Tarana; Benyamino, Romil; Jones, Aubrey; Friis, Esben P; Wilson, Keith S; Davies, Gideon J

    2012-08-01

    Cellulases, including cellobiohydrolases and endoglucanases, are important enzymes involved in the breakdown of the polysaccharide cellulose. These catalysts have found widescale industrial applications, particularly in the paper and textile industries, and are now finding use in `second-generation' conversion of biomass to biofuels. Despite this considerable biotechnological application, and undoubted future potential, uncertainty remains as to the exact reaction mechanism of the inverting cellulases found in the GH6 family of carbohydrate-active enzymes. In order to gain additional understanding as to how these societally beneficial biocatalysts function, the crystal structure of a GH6 cellobiohydrolase from Chaetomium thermophilum, CtCel6A, has been solved. This structure reveals a distorted α/β-barrel fold comprising a buried tunnel-like active site quite typical of Cel6A enzymes. Analysis of an enzyme-product complex (cellobiose in the -3 and -2 subsites and cellotetraose in subsites +1 to +4) supports the hypothesis that this group of enzymes act via an atypical single-displacement mechanism. Of particular note in this analysis is an active-centre metal ion, Li(+), the position of which matches the position of the positively charged anomeric carbon of the oxocarbenium-ion-like transition state. PMID:22868752

  17. Theoretical study of enzymatic catalysis explains why the trapped covalent intermediate in the E303C mutant of glycosyltransferase GTB was not detected in the wild-type enzyme.

    PubMed

    Bobovská, Adela; Tvaroška, Igor; Kóňa, Juraj

    2015-01-01

    Hybrid quantum mechanics/molecular mechanics calculations were used to study the catalytic mechanism of the retaining human α-(1,3)-galactosyltransferase (GTBWT) and its E303C mutant (GTBE303C). Both backside (via covalent glycosyl-enzyme intermediate, CGEI) and frontside SNi-like mechanisms (via oxocarbenium-ion intermediate, OCII) were investigated. The calculations suggest that both mechanisms are feasible in the enzymatic catalysis. The nucleophilic attack of the acceptor substrate to the anomeric carbon of OCII is the rate-determining step with an overall reaction barrier (ΔE(‡) = 19.5 kcal mol(-1)) in agreement with an experimental rate constant (kcat = 5.1 s(-1)). A calculated α-secondary kinetic isotope effect (α-KIE) of 1.27 (GTBWT) and 1.26 (GTBE303C) predicts dissociative character of the transition state in agreement with experimentally measured α-KIE of other retaining glycosyltransferases. Remarkably, stable CGEI in GTBE303C compared with its counterpart in GTBWT may explain why the CGEI has been detected by mass spectrometry only in GTBE303C ( Soya N, Fang Y, Palcic MM, Klassen JS. 2011. Trapping and characterization of covalent intermediates of mutant retaining glycosyltransferases. Glycobiology, 21: 547-552). PMID:25138306

  18. Dissecting the mechanisms of a class of chemical glycosylation using primary 13C kinetic isotope effects

    NASA Astrophysics Data System (ADS)

    Huang, Min; Garrett, Graham E.; Birlirakis, Nicolas; Bohé, Luis; Pratt, Derek A.; Crich, David

    2012-08-01

    Although arguably the most important reaction in glycoscience, chemical glycosylations are among the least well understood of organic chemical reactions, resulting in an unnecessarily high degree of empiricism and a brake on rational development in this critical area. To address this problem, primary 13C kinetic isotope effects have now been determined for the formation of β- and α-manno- and glucopyranosides using a natural abundance NMR method. In contrast to the common current assumption, for three of the four cases studied the experimental and computed values are indicative of associative displacement of the intermediate covalent glycosyl trifluoromethanesulfonates. For the formation of the α-mannopyranosides, the experimentally determined KIE differs significantly from that computed for an associative displacement, which is strongly suggestive of a dissociative mechanism that approaches the intermediacy of a glycosyl oxocarbenium ion. The application of analogous experiments to other glycosylation systems should shed further light on their mechanisms and thus assist in the design of better reactions conditions with improved stereoselectivity.

  19. Catalytic mechanism and novel receptor binding sites of human parainfluenza virus type 3 hemagglutinin-neuraminidase (hPIV3 HN).

    PubMed

    Streltsov, Victor A; Pilling, Pat; Barrett, Susan; McKimm-Breschkin, Jennifer L

    2015-11-01

    The human parainfluenza virus type 3 (hPIV3) hemagglutinin-neuraminidase (HN) has opposing functions of binding sialic acid receptors and cleaving them, facilitating virus release. The crystal structure of hPIV3 HN complexed with the substrate analogue difluorosialic acid (DFSA) revealed that catalysis by HN involves the formation of a covalently linked sialosyl-enzyme intermediate which was trapped along with a transition-state analogue resembling an oxocarbenium ion. This mechanism of enzyme catalysis was also confirmed in the crystal structure of the influenza N9 neuraminidase complexed with DFSA. Additionally, novel secondary receptor binding sites were identified in the hPIV3 HN-DFSA complex including one near the catalytic cavity which upon binding DFSA imposes subtle changes and may help the HN balance the opposing functions. Multiple receptor binding sites may increase avidity to facilitate cell binding and fusion promotion. The secondary receptor binding sites in the paramyxoviruses are so far unique to each virus type. PMID:26364554

  20. An allolactose trapped at the lacZ β-galactosidase active site with its galactosyl moiety in a (4)H3 conformation provides insights into the formation, conformation, and stabilization of the transition state.

    PubMed

    Wheatley, Robert W; Huber, Reuben E

    2015-12-01

    When lactose was incubated with G794A-β-galactosidase (a variant with a "closed" active site loop that binds transition state analogs well) an allolactose was trapped with its Gal moiety in a (4)H3 conformation, similar to the oxocarbenium ion-like conformation expected of the transition state. The numerous interactions formed between the (4)H3 structure and β-galactosidase indicate that this structure is representative of the transition state. This conformation is also very similar to that of d-galactono-1,5-lactone, a good transition state analog. Evidence indicates that substrates take up the (4)H3 conformation during migration from the shallow to the deep mode. Steric forces utilizing His418 and other residues are important for positioning the O1 leaving group into a quasi-axial position. An electrostatic interaction between the O5 of the distorted Gal and Tyr503 as well as C-H-π bonds with Trp568 are also significant. Computational studies of the energy of sugar ring distortion show that the β-galactosidase reaction itinerary is driven by energetic considerations in utilization of a (4)H3 transition state with a novel (4)C1-(4)H3-(4)C1 conformation itinerary. To our knowledge, this is the first X-ray crystallographic structural demonstration that the transition state of a natural substrate of a glycosidase has a (4)H3 conformation. PMID:26291713

  1. Structure and cell wall cleavage by modular lytic transglycosylase MltC of Escherichia coli.

    PubMed

    Artola-Recolons, Cecilia; Lee, Mijoon; Bernardo-García, Noelia; Blázquez, Blas; Hesek, Dusan; Bartual, Sergio G; Mahasenan, Kiran V; Lastochkin, Elena; Pi, Hualiang; Boggess, Bill; Meindl, Kathrin; Usón, Isabel; Fisher, Jed F; Mobashery, Shahriar; Hermoso, Juan A

    2014-09-19

    The lytic transglycosylases are essential bacterial enzymes that catalyze the nonhydrolytic cleavage of the glycan strands of the bacterial cell wall. We describe here the structural and catalytic properties of MltC, one of the seven lytic transglycosylases found in the genome of the Gram-negative bacterium Escherichia coli. The 2.3 Å resolution X-ray structure of a soluble construct of MltC shows a unique, compared to known lytic transglycosylase structures, two-domain structure characterized by an expansive active site of 53 Å length extending through an interface between the domains. The structures of three complexes of MltC with cell wall analogues suggest the positioning of the peptidoglycan in the active site both as a substrate and as a product. One complex is suggested to correspond to an intermediate in the course of sequential and exolytic cleavage of the peptidoglycan. Moreover, MltC partitioned its reactive oxocarbenium-like intermediate between trapping by the C6-hydroxyl of the muramyl moiety (lytic transglycosylase activity, the major path) and by water (muramidase activity). Genomic analysis identifies the presence of an MltC homologue in no less than 791 bacterial genomes. While the role of MltC in cell wall assembly and maturation remains uncertain, we propose a functional role for this enzyme as befits the uniqueness of its two-domain structure. PMID:24988330

  2. Iminosugars as potential inhibitors of glycogenolysis: structural insights into the molecular basis of glycogen phosphorylase inhibition.

    PubMed

    Oikonomakos, Nikos G; Tiraidis, Costas; Leonidas, Demetres D; Zographos, Spyros E; Kristiansen, Marit; Jessen, Claus U; Nørskov-Lauritsen, Leif; Agius, Loranne

    2006-09-21

    Iminosugars DAB (5), isofagomine (9), and several N-substituted derivatives have been identified as potent inhibitors of liver glycogen phosphorylase a (IC(50) = 0.4-1.2 microM) and of basal and glucagon-stimulated glycogenolysis (IC(50) = 1-3 microM). The X-ray structures of 5, 9, and its N-3-phenylpropyl analogue 8 in complex with rabbit muscle glycogen phosphorylase (GPb) shows that iminosugars bind tightly at the catalytic site in the presence of the substrate phosphate and induce conformational changes that characterize the R-state conformation of the enzyme. Charged nitrogen N1 is within hydrogen-bonding distance with the carbonyl oxygen of His377 (5) and in ionic contact with the substrate phosphate oxygen (8 and 9). Our findings suggest that the inhibitors function as oxocarbenium ion transition-state analogues. The conformational change to the R state provides an explanation for previous findings that 5, unlike inhibitors that favor the T state, promotes phosphorylation of GPb in hepatocytes with sequential inactivation of glycogen synthase. PMID:16970395

  3. Importance of a Fluorine Substituent for the Preparation of meta- and para-Pentafluoro-λ(6) -sulfanyl-Substituted Pyridines.

    PubMed

    Kosobokov, Mikhail; Cui, Benqiang; Balia, Andrii; Matsuzaki, Kohei; Tokunaga, Etsuko; Saito, Norimichi; Shibata, Norio

    2016-08-26

    Although there are ways to synthesize ortho-pentafluoro-λ(6) -sulfanyl (SF5 ) pyridines, meta- and para-SF5 -substituted pyridines are rare. We disclose herein a general route for their synthesis. The fundamental synthetic approach is the same as reported methods for ortho-SF5 -substituted pyridines and SF5 -substituted arenes, that is, oxidative chlorotetrafluorination of the corresponding disulfides to give pyridylsulfur chlorotetrafluorides (SF4 Cl-pyridines), followed by chloride/fluoride exchange with fluorides. However, the trick in this case is the presence on the pyridine ring of at least one fluorine atom, which is essential for the successful transformation of the disulfides into m-and p-SF5 -pyridines. After enabling the synthesis of an SF5 -substituted pyridine, ortho-F groups can be efficiently substituted by C, N, S, and O nucleophiles through an SN Ar pathway. This methodology provides access to a variety of previously unavailable SF5 -substituted pyridine building blocks. PMID:27485809

  4. Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes

    PubMed Central

    Vida, Norbert; Václavík, Jiří

    2016-01-01

    Summary Oxidation of 3- and 4-pentafluorosulfanyl-substituted anisoles and phenols with hydrogen peroxide and sulfuric acid provided a mixture of SF5-substituted muconolactone, maleic, and succinic acids. A plausible mechanism for the formation of the aliphatic SF5 compounds was presented and their chemical reactivity was investigated. SF5-substituted para-benzoquinone was synthesized; its oxidation led to an improved yield of 2-(pentafluorosulfanyl)maleic acid. The reaction of SF5-substituted maleic anhydride and para-benzoquinone with cyclopentadiene afforded the Diels–Alder adducts. Decomposition of 3-(pentafluorosulfanyl)muconolactone in acidic, neutral and basic aqueous media was investigated and the decarboxylation of 2-(pentafluorosulfanyl)maleic acid provided 3-(pentafluorosulfanyl)acrylic acid. PMID:26877813

  5. Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes.

    PubMed

    Vida, Norbert; Václavík, Jiří; Beier, Petr

    2016-01-01

    Oxidation of 3- and 4-pentafluorosulfanyl-substituted anisoles and phenols with hydrogen peroxide and sulfuric acid provided a mixture of SF5-substituted muconolactone, maleic, and succinic acids. A plausible mechanism for the formation of the aliphatic SF5 compounds was presented and their chemical reactivity was investigated. SF5-substituted para-benzoquinone was synthesized; its oxidation led to an improved yield of 2-(pentafluorosulfanyl)maleic acid. The reaction of SF5-substituted maleic anhydride and para-benzoquinone with cyclopentadiene afforded the Diels-Alder adducts. Decomposition of 3-(pentafluorosulfanyl)muconolactone in acidic, neutral and basic aqueous media was investigated and the decarboxylation of 2-(pentafluorosulfanyl)maleic acid provided 3-(pentafluorosulfanyl)acrylic acid. PMID:26877813

  6. Enantio- and periselective nitroalkene Diels-Alder reactions catalyzed by helical-chiral hydrogen bond donor catalysts.

    PubMed

    Peng, Zhili; Narcis, Maurice J; Takenaka, Norito

    2013-01-01

    Helical-chiral double hydrogen bond donor catalysts promote the nitroalkene Diels-Alder reaction in an enantio- and periselective manner. This represents the first asymmetric catalytic nitroalkene Diels-Alder reaction via LUMO-lowering catalysis. To gain an insight into this new process, the substrate scope of our catalyst was investigated by exploiting readily available 5-substituted pentamethylcyclopentadienes. The catalyst was found to tolerate dienes with different steric demands as well as dienes substituted with heteroatoms. The synthetic utility of 5-substituted pentamethylcyclopentadienes is rather limited, and thus we have developed a three-step route to 1,4,5,5-tetrasubstituted cyclopentadienes from commercially available ketones. PMID:23966083

  7. Density-functional investigation of the geometric and electronic structure of ethylene oxide adsorbed on Si(100)

    NASA Astrophysics Data System (ADS)

    Wang, Lu; Li, Qing-Fang; Yang, Cui-Hong; Wei, Yue-Ling; Zhu, Xing-Feng; Rao, Wei-Feng

    2016-05-01

    The geometric and electronic structures of the ethylene oxide (EO) molecule adsorbed on Si(100)-(2 × 1) surface were investigated by using the density-functional theory calculations. All possible adsorbed structures were considered and it was found that only four adsorption structures are stable. The calculations of the formation energy revealed the most stable conformation and demonstrated that the nature of Si-O bond significantly affects the stability of adsorption systems. The analysis of corresponding electronic structures showed that two adsorbed structures are still semiconductor compounds but the other two are not. In particular, the EO after adsorbing was found to be connected via a ring-opening reaction where the molecule forms a five-membered ring together with the surface of dimer silicon atoms, and the produced five-membered ring is almost perpendicular to the silicon surface.

  8. Synthesis and characterization of the three dicyclopentapyrenes

    SciTech Connect

    Scott, L.T.; Necula, A.

    1996-01-12

    Polycyclic aromatic hydrocarbons containing fully unsaturated five-membered rings as integral components of their trigonal carbon networks (CP-PAHs) have attracted considerable attention recently in a variety of scientific circles. Some of these novel nonalternant hydrocarbons exhibit unusual photophysical behavior, e.g., anomalous fluorescence, and/or pronounced biological activity, acute cyctotoxicity. Many have been identified or are believed to be formed as products of incomplete combustion, either in flames or in cigarette smoke, and a few have been produced by flash pyrolyses of other hydrocarbons. Five-membered rings fully encircled by benzene rings impart a curvature to the trigonal carbon network that gives rise to the bowl-shaped geometry of corannulene and to the closed polyhedral surfaces of the fullerenes. Herein, the authors report the syntheses and a preliminary spectroscopic examination of the three isomeric dicyclopentapyrenes.

  9. Crystal structure of {3-[3,5-bis­(2,6-di­methyl­phen­yl)-1,2-phenyl­ene]-1-(2,6,2′′,6′′-tetra­methyl-1,1′:3′,1′′-ter­phen­yl-5′-yl)imidazol-2-yl­idene}chlorido­(η6-p-cymene)ruthenium(II) benzene disolvate

    PubMed Central

    Sase, Shohei; Ikehara, Yuriko; Goto, Kei

    2014-01-01

    The title compound, [Ru(C47H43N2)Cl(C10H14)]·2C6H6, crystallized with two independent mol­ecules of benzene. One of the N-aryl moieties of the N-heterocyclic carbene (NHC) ligand underwent cyclo­metallation to form a five-membered ruthenacycle. The complex has a three-legged piano-stool structure with two C atoms incorporated in the five-membered ruthenacycle and a Cl atom as legs. The ruthenacycle is essentially coplanar with the imidazole ring of the NHC ligand, making a dihedral angle of 0.85 (8)°. PMID:25553006

  10. Menshutkin reaction between DABCO and benzyfluoride/fluorodiphenylmethane: a mechanistic study.

    PubMed

    Singh, Amritpal; Goel, Neetu

    2014-06-01

    The microcosmic mechanism of the Menshutkin reaction between DABCO and benzyl fluoride/fluorodiphenylmethane has been investigated in both the gas and solvent phase by performing DFT calculations at B3LYP/6-31G(d,p) level of theory. The Gibbs free energy profiles to reach the possible transition states, i.e., five-membered ring transition state and SN2 transition state show that the reaction between DABCO and benzyl fluoride proceeds through SN2 transition state in accordance with previously reported studies, while the reaction between DABCO and fluorodiphenylmethane proceeds through five-membered ring transition state contrary to earlier literature. The role of solvent has been elucidated by reoptimizing the structures using SMD model of solvation. Hydrogen bonding and steric hinderance have been identified as the key factors in guiding the reaction pathway of commercially important Menshutkin reaction. PMID:24827613

  11. An alternative approach to PEPPSI catalysts: from palladium isonitriles to highly active unsymmetrically substituted PEPPSI catalysts.

    PubMed

    Zeiler, Anna; Rudolph, Matthias; Rominger, Frank; Hashmi, A Stephen K

    2015-07-27

    A series of new pyridine-enhanced precatalyst preparation, stabilization, and initiation (PEPPSI)-type complexes bearing different types of carbene ligands was prepared by the modular and convergent template synthesis strategy. Nitrogen acyclic carbenes, saturated and unsaturated five-membered NHC, saturated six-membered NHCs, and five-membered N-heterocyclic oxo-carbene (NHOC) ligands on palladium were prepared this way. These new organometallic compounds then were tested in Suzuki and Negishi cross-coupling reactions by using substrates with one or two substituents in ortho-position of the new CC bond being formed. Both aryl chlorides and bromides were tested as coupling partners. In some cases, the new ligands gave results similar to Organ's successful IPr-based and IPent-based PEPPSI derivatives, with aryl bromides 0.05 mol % catalyst load still gave satisfactory results, with aryl chlorides 0.5 mol % were needed. PMID:26096141

  12. Crystal structure of N′-[(E)-(1S,3R)-(3-isopropyl-1-methyl-2-oxo­cyclo­pent­yl)methyl­idene]-4-methyl­benzene­sulfono­hydrazide

    PubMed Central

    Tymann, David; Dragon, Dina Christina; Golz, Christopher; Preut, Hans; Strohmann, Carsten; Hiersemann, Martin

    2015-01-01

    The title compound, C17H24N2O3S, was synthesized in order to determine the relative configuration of the corresponding β-keto aldehyde. In the U-shaped mol­ecule, the five-membered ring approximates an envelope, with the methyl­ene C atom adjacent to the quaternary C atom being the flap, and the methyl and isopropyl substituents lying to the same side of the ring. The dihedral angles between the four nearly coplanar atoms of the five-membered ring and the flap and the aromatic ring are 35.74 (15) and 55.72 (9)°, respectively. The bond angles around the S atom are in the range from 103.26 (12) to 120.65 (14)°. In the crystal, mol­ecules are linked via N—H⋯O hydrogen bonds, forming a chain along the a axis. PMID:26870519

  13. Crystal structure of (E)-N′-{[(1R,3R)-3-isopropyl-1-methyl-2-oxo­cyclo­pent­yl]methyl­idene}-4-methyl­benzene­sulfono­hydrazide

    PubMed Central

    Tymann, David; Dragon, Dina Christina; Golz, Christopher; Preut, Hans; Strohmann, Carsten; Hiersemann, Martin

    2015-01-01

    The title compound, C17H24N2O3S, was synthesized in order to determine the relative configuration of the corresponding β-keto aldehyde. In the U-shaped mol­ecule, the five-membered ring approximates an envelope with the methyl­ene atom adjacent to the quaternary C atom being the flap. The dihedral angles between the four nearly coplanar atoms of the five-membered ring and the flap and the aromatic ring are 38.8 (4) and 22.9 (2)°, respectively. The bond angles around the S atom are in the range 104.11 (16)–119.95 (16)°. In the crystal, mol­ecules are linked via N—H⋯O by hydrogen bonds, forming a chain along the a-axis direction. PMID:25878892

  14. Synthesis of Naphthylpyridines from Unsymmetrical Naphthylheptadiynes and the Configurational Stability of the Biaryl Axis.

    PubMed

    Fischer, Fabian; Siegle, Alexander F; Checinski, Marek; Fischer, Christine; Kral, Karolin; Thede, Richard; Trapp, Oliver; Hapke, Marko

    2016-04-15

    A series of different unsymmetrically substituted naphthyl-based diynes were synthesized. These substrates formed the foundation for the assembly of novel biaryls containing pyridine moieties with differently substituted five-membered rings in the backbone of the newly formed heterobiaryl system. The key step for their efficient construction was the photo- and cobalt-catalyzed [2 + 2 + 2] cycloaddition reaction between the corresponding naphthyldiyne and aceto- or benzonitrile. The heterobiaryl products have been isolated and investigated with respect to the configurational stability of their biaryl axis using dynamic chiral HPLC; subtle effects of the substitution pattern on the stability of the axis were observed. For several compounds the activation barriers (ΔG(‡)) of racemization were determined. Suitable substitution of the five-membered ring backbone exemplarily allowed the Co-catalyzed enantioselective cyclization to yield the enantiomerically enriched heterobiaryl. PMID:26999378

  15. Functionalization, cyclization and antiviral activity of A-secotriterpenoids.

    PubMed

    Grishko, Victoria V; Galaiko, Natalia V; Tolmacheva, Irina A; Kucherov, Igor I; Eremin, Vladimir F; Boreko, Eugene I; Savinova, Olga V; Slepukhin, Pavel A

    2014-08-18

    Triterpene derivatives with an α,β-alkenenitrile moiety in the five-membered ring A have been synthesized by nitrile anion cyclizations of 1-cyano-2,3-secotriterpenoids. Oxime-containing precursors, 2,3-secointermediates and five-membered ring A products of cyclizations were screened for in vitro antiviral activity against enveloped viruses - influenza A virus and human immunodeficiency virus type I (HIV-1). Lupane ketoxime and the 2,3-secolupane C-3 aldoxime which possess antiviral activities against both influenza A virus (EC50 12.9-18.2 μM) and HIV-1 (EC50 0.06 μM) were the most promising compounds. PMID:24997292

  16. Tetra­methyl 1,1,2-triphenyl-2H-1λ5-phosphole-2,3,4,5-tetra­carboxyl­ate

    PubMed Central

    Krawczyk, Krzysztof K.; Wojtasiewicz, Krystyna; Maurin, Jan K.; Gronowska, Ewa; Czarnocki, Zbigniew

    2010-01-01

    The title compound, C30H27O8P (1), was formed as one of two products {(1) and (2) [Krawczyk et al. (2010 ▶). Acta Cryst. E66 (cv2753)]} in the reaction of dimethyl acetyl­enedicarboxyl­ate with triphenyl­phosphine. The mol­ecule of (1) consists of a five-membered ring, in which the P atom is incorporated. One of the phenyl groups of the triphenyl­phosphine migrated to a vicinal C atom during the reaction. The five-membered ring of (1) is corrugated [r.m.s. deviation = 0.0719 (8) Å], whereas that in compound (2) is planar, the r.m.s. deviation being only 0.009 (2) Å. PMID:21588988

  17. Ethyl 3-hydr­oxy-13-methyl-4′-phenyl-2′-(3,4,5-trimethoxy­phen­yl)-6,7,8,9,11,12,13,14,15,16-deca­hydro­spiro­[cyclo­penta­[a]phenanthrene-16,3′-pyrrolidine]-5′-carboxyl­ate

    PubMed Central

    Kamala, E. Theboral Sugi; Murugan, R.; Nirmala, S.; Sudha, L.; Narayanan, S. Sriman

    2008-01-01

    In the title compound, C39H45NO7,the pyrrolidine ring is connected to an estrone group, a trimeth­oxy benzene and a phenyl ring. The pyrrolidine ring exhibits a twist conformation and the other five-membered ring an envelope conformation. Mol­ecules are linked by N—H⋯O hydrogen bonds, C—H⋯π inter­actions and C—H⋯O hydrogen bonds. PMID:21581075

  18. Isolation of a Cyclic (Alkyl)(amino)germylene.

    PubMed

    Wang, Liliang; Lim, Yi Shan; Li, Yongxin; Ganguly, Rakesh; Kinjo, Rei

    2016-01-01

    A 1,4-addition of a dichlorogermylene dioxane complex with α,β-unsaturated imine 1 gave a dichlorogermane derivative 2 bearing a GeC₃N five-membered ring skeleton. By reducing 2 with KC₈, cyclic (alkyl)(amino)germylene 3 was synthesized and fully characterized. Germylene 3 readily reacted with TEMPO, N₂O and S₈, producing the 1:2 adduct 4, the oxo-bridged dimer 5 and the sulfido-bridged dimer 6, respectively. PMID:27483223

  19. NAD metabolism in Vibrio cholerae.

    PubMed Central

    Foster, J W; Brestel, C

    1982-01-01

    Extracts of Vibrio cholerae were assayed for various enzymatic activities associated with pyridine nucleotide cycle metabolism. The activities measured include NAD glycohydrolase, nicotinamide deamidase, nicotinamide mononucleotide deamidase, and nicotinic acid phosphoribosyltransferase. The results obtained demonstrate the existence in V. cholerae of the five-membered pyridine nucleotide cycle and the potential for a four-membered pyridine nucleotide cycle. The data presented also suggest that most of the NAD glycohydrolase in V. cholerae extracts is not directly related to cholera toxin. PMID:6119307

  20. Synthesis of pyridazinones through the copper(I)-catalyzed multicomponent reaction of aldehydes, hydrazines, and alkynylesters.

    PubMed

    Mantovani, Anderson C; Goulart, Tales A C; Back, Davi F; Zeni, Gilson

    2014-09-22

    The copper-catalyzed multicomponent cyclization reaction, which combined aldehydes, hydrazines, and alkynylesters, was applied in the synthesis of pyridazinones. The reaction was regioselective and gave only six-membered pyridazinones in the complete absence of five-membered pyrazoles or a regioisomeric mixture. During this investigation, the use of 2-halobenzaldehyde as the starting material, under identical reaction conditions, gave 6-(2-ethoxyphenyl)pyridazinones after sequential Michael addition/1,2-addition/Ullmann cross-coupling reactions. PMID:25124722

  1. STS 51-L crewmembers briefed during training session

    NASA Technical Reports Server (NTRS)

    1986-01-01

    Five members of the STS 51-L crew and a backup crewmember are briefed during a training session in JSC's Shuttle mockup and integration laboratory. From left to right are Astronauts Ellison S. Onizuka, mission specialist; Ronald E. McNair, mission specialist; Gregory Jarvis, Hughes payload specialist; Judith A. Resnik, mission specialist; Sharon Christa McAuliffe, citizen observer/payload specialist representing the Teacher in Space project. Barbara R. Morgan, backup to McAuliffe, is in the right foreground.

  2. Tandem Rh(III)-Catalyzed C-H Amination/Annulation Reactions: Synthesis of Indoloquinoline Derivatives in Water.

    PubMed

    Shi, Liangliang; Wang, Baiquan

    2016-06-17

    An efficient Rh(III)-catalyzed synthetic method for indoloquinoline derivatives from readily available indoles and isoxazoles was developed. This annulation procedure undergoes tandem C-H activation, cyclization, and condensation steps. In this domino cyclization reaction, water is an efficient solvent. A catalytically competent five-membered rhodacycle has been isolated and characterized, thus revealing a key intermediate in the catalytic cycle. PMID:27266834

  3. 4-(2,4,6-Trimethyl-benz-yl)-1,3-thia-zol-2-amine.

    PubMed

    Maharramov, Abel M; Khalilov, Ali N; Gurbanov, Atash V; Allahverdiyev, Mirze A; Ng, Seik Weng

    2011-01-01

    The methyl-ene C atom in the title compound, C(13)H(16)N(2)S, is connected to a five-membered thia-zole ring and a mesityl substituent. The rings are aligned at 75.4 (1)°. The amino substitutent inter-acts with the ring N atom of an adjacent mol-ecule by an inter-molecular N-H⋯N hydrogen bond, generating a helical chain running along the b axis. PMID:21522463

  4. Expedient Access to 2,3-Dihydropyridines from Unsaturated Oximes by Rh(III)-Catalyzed C-H Activation.

    PubMed

    Romanov-Michailidis, Fedor; Sedillo, Kassandra F; Neely, Jamie M; Rovis, Tomislav

    2015-07-22

    α,β-Unsaturated oxime pivalates are proposed to undergo reversible C(sp(2))-H insertion with cationic Rh(III) complexes to furnish five-membered metallacycles. In the presence of 1,1-disubstituted olefins, these species participate in irreversible migratory insertion to give, after reductive elimination, 2,3-dihydropyridine products in good yields. Catalytic hydrogenation can then be used to convert these molecules into piperidines, which are important structural components of numerous pharmaceuticals. PMID:26154248

  5. Landing of the Shuttle Atlantis and the end of the STS 51-J mission

    NASA Technical Reports Server (NTRS)

    1985-01-01

    George W.S. Abbey, bottom right, greets the five members of the STS 51-J crew as they egress the Atlantis following its landing. Astronauts Karol J. Bobko, crew commander, shakes hands with Abbey at bottom of stairs. He is followed by (bottom to top) Astronauts Ronald J. Grabe, pilot; David C. Hilmers and Robert L. Stewart, both mission specialists; and USAF Maj. William A. Pailes, payload specialist.

  6. NFAT Gene Family in Inflammation and Cancer

    PubMed Central

    Pan, M.-G.; Xiong, Y.; Chen, F.

    2013-01-01

    Calcineurin-NFAT signaling is critical for numerous aspects of vertebrate function during and after embryonic development. Initially discovered in T cells, the NFAT gene family, consisting of five members, regulates immune system, inflammatory response, angiogenesis, cardiac valve formation, myocardial development, axonal guidance, skeletal muscle development, bone homeostasis, development and metastasis of cancer, and many other biological processes. In this review we will focus on the NFAT literature relevant to the two closely related pathological systems: inflammation and cancer. PMID:22950383

  7. Two equivalent methyl internal rotations in 2,5-dimethylthiophene investigated by microwave spectroscopy.

    PubMed

    Van, Vinh; Stahl, Wolfgang; Nguyen, Ha Vinh Lam

    2015-12-28

    The microwave spectrum of 2,5-dimethylthiophene, a sulfur-containing five-membered ring with two conjugated double bonds, was recorded in the frequency range from 2 to 40 GHz using molecular beam Fourier transform technique. Highly accurate molecular parameters were determined. A labeling scheme for the group G36 written as the semi-direct product (C(I)(3) × C(I)(3)) ⋊ C(2v) was introduced. PMID:26444182

  8. An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

    PubMed Central

    2011-01-01

    Summary This review presents a comprehensive overview on selected synthetic routes towards commercial drug compounds as published in both journal and patent literature. Owing to the vast number of potential structures, we have concentrated only on those drugs containing five-membered heterocycles and focused principally on the assembly of the heterocyclic core. In order to target the most representative chemical entities the examples discussed have been selected from the top 200 best selling drugs of recent years. PMID:21647262

  9. "Conformational lock"via unusual intramolecular C-FO[double bond, length as m-dash]C and C-HCl-C parallel dipoles observed in in situ cryocrystallized liquids.

    PubMed

    Dey, Dhananjay; Bhandary, Subhrajyoti; Sirohiwal, Abhishek; Hathwar, Venkatesha R; Chopra, Deepak

    2016-06-01

    We report an unusual intramolecular C-FO[double bond, length as m-dash]C and C-HCl-C parallel dipole-dipole alignment which "locks" the molecular conformation of cryocrystallized liquids towards planarity where the diatropic ring current establishes the existence of aromaticity in the five-membered ring associated with FO contact. Topological analysis establishes the bonding interaction between [F, O] and [H, Cl]. PMID:27149236

  10. Synthesis, Crystal Analyses, Physical Properties, and Electroluminescent Behavior of Unsymmetrical Heterotwistacenes.

    PubMed

    Lv, Bo; Xiao, Jinchong; Zhou, Jian; Zhang, Xi; Duan, Jingdan; Su, Wenming; Zhao, Jianwen

    2016-07-27

    Four novel unsymmetrical heteroacenes containing five-membered heterocycles (OPyN, TPyN, TPyC, TPyO) have been synthesized and characterized. The formed molecules exhibited twisted structures, determined by crystal analysis and showed blue/green fluorescence in dichloromethane and in thin film. Compounds OPyN and TPyN were selectively used as active ingredients, and the fabricated devices displayed promising electroluminescent performance. PMID:27383556

  11. (2S*,3S*,3aS*,6S*,7aR*)-3-Hy­droxy-2-[(2R*,3S*)-3-isopropyl­oxiran-2-yl]-3,6-dimethyl-3,3a,5,6,7,7a-hexa­hydro-1-benzofuran-4(2H)-one

    PubMed Central

    Ding, Mingruo; Zhang, Qiaoyin; Chen, Lei; Huang, Nianyu; Wang, Junzhi

    2012-01-01

    In the title compound, C15H24O4, the six-membered ring shows a distorted chair conformation and the five-membered ring adopts an envelope conformation with the C atom bearing the methyl and OH groups as the flap. In the crystal, O—H⋯O hydrogen bonds link the mol­ecules into chains running along the a-axis direction. PMID:23125734

  12. 5-Bromo-1H-pyrrolo­[2,3-b]pyridine

    PubMed Central

    Štarha, Pavel; Trávníček, Zdeněk

    2013-01-01

    In the title compound, C7H5BrN2, fused six-membered pyridine and five-membered pyrrole rings form the essentially planar aza­indole skeleton (r.m.s. deviation = 0.017 Å). In the crystal, pairs of N—H⋯N hydrogen bonds connect the mol­ecules into inversion dimers. PMID:23476567

  13. Three STS 26 astronauts training in the Crew Compartment trainer

    NASA Technical Reports Server (NTRS)

    1986-01-01

    Three astronauts named in January 1987 as part of a five-member crew for NASA's first flight since the Challenger accident are shown in a photo session of July 1986. Left to right are Astronauts John M. (Mike) Lounge, Richard O. Covey and David C. Hilmers. Lounge and Hilmers will serve as Mission specialists for the STS 26 flight and Covey will serve as pilot. The three are on the middeck of JSC's one-G Crew Compartment Trainer (CCT).

  14. (2Z,3Z)-Quinoxaline-2,3(1H,4H)-dione dioxime

    PubMed Central

    Kakanejadifard, Ali; Amani, Vahid

    2008-01-01

    The asymmetric unit of the title compound, C8H8N4O2, contains one half-mol­ecule; a twofold rotation axis bisects the molecule. An intra­molecular N—H⋯O hydrogen bond results in the formation of a five-membered ring, which displays an envelope conformation. In the crystal structure, inter­molecular O—H⋯N hydrogen bonds link the mol­ecules. PMID:21203220

  15. (2Z,3Z)-Quinoxaline-2,3(1H,4H)-dione dioxime.

    PubMed

    Kakanejadifard, Ali; Amani, Vahid

    2008-01-01

    The asymmetric unit of the title compound, C(8)H(8)N(4)O(2), contains one half-mol-ecule; a twofold rotation axis bisects the molecule. An intra-molecular N-H⋯O hydrogen bond results in the formation of a five-membered ring, which displays an envelope conformation. In the crystal structure, inter-molecular O-H⋯N hydrogen bonds link the mol-ecules. PMID:21203220

  16. endo-3,3-Dimethyl-4-oxobicyclo-[3.1.0]hexan-2-yl methane-sulfonate.

    PubMed

    Kremer, Adrian; Norberg, Bernadette; Krief, Alain; Wouters, Johan

    2010-01-01

    The relative configuration of the endo isomer of the title compound, C(9)H(14)O(4)S, has been established and the conformation of the diastereoisomer is discussed. The five-membered ring adopts an envelope conformation. The conformation of the methane-sulfonate substituent is stabilized by inter-molecular C-H⋯O hydrogen bonds. The crystal packing results in alternating layers of polar methane-sulfonates and stacked bicyclo-hexa-nyl rings parallel to ab. PMID:21580752

  17. (1S,5R)-1-(3,4-Dichloro-phen-yl)-3-oxa-bicyclo-[3.1.0]hexan-2-one.

    PubMed

    Görbitz, Carl Henrik; Hansen, Tore; Vestli, Kristian

    2009-01-01

    The absolute structure has been determined by X-ray analysis for the title compound, C(11)H(8)Cl(2)O(2). The five-membered ring of the mol-ecule is best described as a flattened envelope conformation with the methyl-ene C atom located 0.208 (2) Å below the plane formed by the other four atoms. A weak intermolecular C-H⋯O hydrogen bond is present in the crystal structure. PMID:21582428

  18. Search for aromatic anions in the P2E3(-) (E = N, P, As, Sb, Bi) series.

    PubMed

    Nizovtsev, Anton S

    2016-06-28

    We report a systematic computational study focused on the global minimum and low-lying isomer search for the P2E3(-) (E = N, P, As, Sb, Bi) series of anions. We found nine planar five-membered rings and proved their aromatic character by various quantum chemical techniques. The possible use of two different P2N3(-) aromatic anions as ligands in a number of sandwich complexes was also studied. PMID:27250818

  19. A new class of simplified phorbol ester analogues: synthesis and binding to PKC and eta PKC-C1B (eta PKC-CRD2).

    PubMed

    Wender, P A; Kirschberg, T A; Williams, P D; Bastiaans, H M; Irie, K

    1999-10-01

    [formula: see text] A unique class of simplified phorbol ester analogues is described for the first time. A highly efficient retro-annelation sequence was developed in order to remove the five-membered ring from the phorbol diterpene core, allowing access to BCD ring analogues of the phorbol esters. The binding of these analogues to protein kinase C (PKC) and the truncated peptide eta PKC-C1B (eta PKC-CRD2) is also reported. PMID:10825954

  20. Synthesis and Structural Reassignment of Plakinidone.

    PubMed

    Xu, Ze-Jun; Tan, Dong-Xing; Wu, Yikang

    2015-10-16

    In connection with its first synthesis, plakinidone was structurally revised to a five-membered lactone. The key evidence for the previous assignment of this natural product as a perlactone was proven to be a misinterpretation of the MS data because of unawareness of a facile air oxidation. The synthetic samples also allowed for detection of differences in (13)C NMR for diastereomers of remote stereogenic centers, along with the influence of the air oxidation on the optical rotation. PMID:26434640

  1. 10-Formyl-2,4,6,8,12-penta­nitro-2,4,6,8,10,12-hexa­azatetra­cyclo­[5.5.0.03,11.05,9]dodeca­ne

    PubMed Central

    Jin, Shaohua; Chen, Shusen; Chen, Huaxiong; Li, Lijie; Shi, Yanshan

    2009-01-01

    The title compound, C7H7N11O11 (PNMFIW), is a caged heterocycle substituted with five nitro and one formyl groups. It is related to the hexa­azaisowurtzitane family of high-density high-energy polycyclic cage compounds. Four nitro groups are appended to the four N atoms of the two five-membered rings, while a nitro group and a formyl are attached to the two N atoms of the six-membered ring. PMID:21578838

  2. Combining silver catalysis and organocatalysis: a sequential Michael addition/hydroalkoxylation one-pot approach to annulated coumarins.

    PubMed

    Hack, Daniel; Chauhan, Pankaj; Deckers, Kristina; Hermann, Gary N; Mertens, Lucas; Raabe, Gerhard; Enders, Dieter

    2014-10-01

    A highly stereoselective one-pot procedure for the synthesis of five-membered annulated hydroxycoumarins has been developed. By merging primary amine catalysis with silver catalysis, a series of functionalized coumarin derivatives were obtained in good yields (up to 91%) and good to excellent enantioselectivities (up to 99% ee) via a Michael addition/hydroalkoxylation reaction. Depending on the substituents on the enynone, the synthesis of annulated six-membered rings is also feasible. PMID:25250728

  3. Crystal structure of histone demethylase LSD1 and tranylcypromine at 2.25 A

    SciTech Connect

    Mimasu, Shinya; Sengoku, Toru; Fukuzawa, Seketsu; Umehara, Takashi; Yokoyama, Shigeyuki

    2008-02-01

    Transcriptional activity and chromatin structure accessibility are correlated with the methylation of specific histone residues. Lysine-specific demethylase 1 (LSD1) is the first discovered histone demethylase, which demethylates Lys4 or Lys9 of histone H3, using FAD. Among the known monoamine oxidase inhibitors, tranylcypromine (Parnate) showed the most potent inhibitory effect on LSD1. Recently, the crystal structure of LSD1 and tranylcypromine was solved at 2.75 A, revealing a five-membered ring fused to the flavin of LSD1. In this study, we refined the crystal structure of the LSD1-tranylcypromine complex to 2.25 A. The five-membered ring model did not fit completely with the electron density, giving R{sub work}/R{sub free} values of 0.226/0.254. On the other hand, the N(5) adduct gave the lowest R{sub work}/R{sub free} values of 0.218/0.248, among the tested models. These results imply that the LSD1-tranylcypromine complex is not completely composed of the five-membered adduct, but partially contains an intermediate, such as the N(5) adduct.

  4. 9α-Hy-droxy-12-{[4-(4-hy-droxy-phen-yl)piperazin-1-yl]meth-yl}-4,8-dimethyl-3,14-dioxatri-cyclo-[9.3.0.0(2,4)]tetra-dec-7-en-13-one.

    PubMed

    Loubidi, Mohamed; Benharref, Ahmed; El Ammari, Lahcen; Saadi, Mohamed; Berraho, Moha

    2014-05-01

    The title compound, C25H34N2O5, was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methylen-3, 14-dioxa-tri-cyclo-[9.3.0.0(2,4)]tetra-dec-7-en-13-one), which in turn was isolated from the chloro-form extract of the aerial parts of Anvillea radiata. The mol-ecule comprises a ten-membered ring fused to a five-membered ring with an additional ep-oxy ring system fused to the ten-membered ring. The five-membered ring also carries a 4-hy-droxy-phenyl-piperazin-1-ylmethyl substituent. The ten-membered ring adopts an approximate chair-chair conformation, while the piperazine ring displays a chair conformation and the five-membered ring shows an envelope conformation with the C atom closest to the hy-droxy group forming the flap. Two C atoms in the phenyl ring and the O atom of the hydroxyl group are disordered over two sites, with an occupancy ratio of 0.53 (5):0.47 (5). An intra-molecular O-H⋯N hydrogen-bond stabilizes the mol-ecular conformation. In the crystal, C-H⋯O hydrogen bonds link the mol-ecules into zigzag chains running along the a-axis direction. PMID:24860343

  5. 3-{2-[(3-Phenyl­quinoxalin-2-yl)­oxy]ethyl}-1,3-oxazolidin-2-one

    PubMed Central

    Daouda, Ballo; Brelot, Lydia; Doumbia, Mouhamadou Lamine; Essassi, El Mokhtar; Ng, Seik Weng

    2011-01-01

    The asymmetric unit of the title compound, C19H17N3O3, consists of two independent mol­ecules that are disposed about a pseudo-centre of inversion. The plane of the phenyl substituent is twisted by 38.1 (1)° [43.6 (1)° in the second mol­ecule] out of the plane of the quinoxaline ring system. The five-membered ring of the substituent at the 2-position adopts an envelope conformation; the 5-CH2 atom representing the flap lies out of the plane defined by the other four atoms [deviation 0.264 (7) Å in the first mol­ecule and 0.291 (6) Å in the second]. The dihedral angle between the five-membered ring and the 4-phenyl ring is 84.9 (1)° while that between the five-membered ring and the 5-phenyl ring is 65.6 (1)°. PMID:21754531

  6. Hydrogen bonding in the mechanism of GDP-mannose mannosyl hydrolase

    NASA Astrophysics Data System (ADS)

    Mildvan, A. S.; Xia, Z.; Azurmendi, H. F.; Legler, P. M.; Balfour, M. R.; Lairson, L. L.; Withers, S. G.; Gabelli, S. B.; Bianchet, M. A.; Amzel, L. M.

    2006-06-01

    GDP-mannose mannosyl hydrolase (GDPMH) from E. coli catalyzes the hydrolysis of GDP-α- D-sugars to GDP and β- D-sugars by nucleophilic substitution with inversion at the anomeric C1 of the sugar, with general base catalysis by His-124. The 1.3 Å X-ray structure of the GDPMH-Mg 2+-GDP complex was used to model the complete substrate, GDP-mannose into the active site. The substrate is linked to the enzyme by 12 hydrogen bonds, as well as by the essential Mg 2+. In addition, His-124 was found to participate in a hydrogen bonded triad: His-124-NδH⋯Tyr-127-OH⋯Pro-120(C dbnd6 O). The contributions of these hydrogen bonds to substrate binding and to catalysis were investigated by site-directed mutagenesis. The hydrogen bonded triad detected in the X-ray structure was found to contribute little to catalysis since the Y127F mutation of the central residue shows only 2-fold decreases in both kcat and Km. The GDP leaving group is activated by the essential Mg 2+ which contributes at least 10 5-fold to kcat, and by nine hydrogen bonds, including those from Tyr-103, Arg-37, Arg-52, and Arg-65 (via an intervening water), each of which contribute factors to kcat ranging from 24- to 309-fold. Both Arg-37 and Tyr-103 bind the β-phosphate of the leaving GDP and are only 5.0 Å apart. Accordingly, the R37Q/Y103F double mutant shows partially additive effects of the two single mutants on kcat, indicating cooperativity of Arg-37 and Tyr-103 in promoting catalysis. The extensive activation of the GDP leaving group suggests a mechanism with dissociative character with a cationic oxocarbenium-like transition state and a half-chair conformation of the sugar ring, as found with glycosidase enzymes. Accordingly, Asp-22 which contributes 10 2.1- to 10 2.6-fold to kcat, is positioned to both stabilize a developing cationic center at C1 and to accept a hydrogen bond from the C2-OH of the mannosyl group, and His-88, which contributes 10 2.3-fold to kcat, is positioned to accept

  7. Crystal structures of Mycobacterium tuberculosis GlgE and complexes with non-covalent inhibitors

    PubMed Central

    Lindenberger, Jared J.; Kumar Veleti, Sri; Wilson, Brittney N.; Sucheck, Steven J.; Ronning, Donald R.

    2015-01-01

    GlgE is a bacterial maltosyltransferase that catalyzes the elongation of a cytosolic, branched α-glucan. In Mycobacterium tuberculosis (M. tb), inactivation of GlgE (Mtb GlgE) results in the rapid death of the organism due to a toxic accumulation of the maltosyl donor, maltose-1-phosphate (M1P), suggesting that GlgE is an intriguing target for inhibitor design. In this study, the crystal structures of the Mtb GlgE in a binary complex with maltose and a ternary complex with maltose and a maltosyl-acceptor molecule, maltohexaose, were solved to 3.3 Å and 4.0 Å, respectively. The maltohexaose structure reveals a dominant site for α-glucan binding. To obtain more detailed interactions between first generation, non-covalent inhibitors and GlgE, a variant Streptomyces coelicolor GlgEI (Sco GlgEI-V279S) was made to better emulate the Mtb GlgE M1P binding site. The structure of Sco GlgEI-V279S complexed with α-maltose-C-phosphonate (MCP), a non-hydrolyzable substrate analogue, was solved to 1.9 Å resolution, and the structure of Sco GlgEI-V279S complexed with 2,5-dideoxy-3-O-α-D-glucopyranosyl-2,5-imino-D-mannitol (DDGIM), an oxocarbenium mimic, was solved to 2.5 Å resolution. These structures detail important interactions that contribute to the inhibitory activity of these compounds, and provide information on future designs that may be exploited to improve upon these first generation GlgE inhibitors. PMID:26245983

  8. LacZ β-galactosidase: structure and function of an enzyme of historical and molecular biological importance.

    PubMed

    Juers, Douglas H; Matthews, Brian W; Huber, Reuben E

    2012-12-01

    This review provides an overview of the structure, function, and catalytic mechanism of lacZ β-galactosidase. The protein played a central role in Jacob and Monod's development of the operon model for the regulation of gene expression. Determination of the crystal structure made it possible to understand why deletion of certain residues toward the amino-terminus not only caused the full enzyme tetramer to dissociate into dimers but also abolished activity. It was also possible to rationalize α-complementation, in which addition to the inactive dimers of peptides containing the "missing" N-terminal residues restored catalytic activity. The enzyme is well known to signal its presence by hydrolyzing X-gal to produce a blue product. That this reaction takes place in crystals of the protein confirms that the X-ray structure represents an active conformation. Individual tetramers of β-galactosidase have been measured to catalyze 38,500 ± 900 reactions per minute. Extensive kinetic, biochemical, mutagenic, and crystallographic analyses have made it possible to develop a presumed mechanism of action. Substrate initially binds near the top of the active site but then moves deeper for reaction. The first catalytic step (called galactosylation) is a nucleophilic displacement by Glu537 to form a covalent bond with galactose. This is initiated by proton donation by Glu461. The second displacement (degalactosylation) by water or an acceptor is initiated by proton abstraction by Glu461. Both of these displacements occur via planar oxocarbenium ion-like transition states. The acceptor reaction with glucose is important for the formation of allolactose, the natural inducer of the lac operon. PMID:23011886

  9. Distortional binding of transition state analogs to human purine nucleoside phosphorylase probed by magic angle spinning solid-state NMR.

    PubMed

    Vetticatt, Mathew J; Itin, Boris; Evans, Gary B; Schramm, Vern L

    2013-10-01

    Transition state analogs mimic the geometry and electronics of the transition state of enzymatic reactions. These molecules bind to the active site of the enzyme much tighter than substrate and are powerful noncovalent inhibitors. Immucillin-H (ImmH) and 4'-deaza-1'-aza-2'-deoxy-9-methylene Immucillin-H (DADMe-ImmH) are picomolar inhibitors of human purine nucleoside phosphorylase (hPNP). Although both molecules are electronically similar to the oxocarbenium-like dissociative hPNP transition state, DADMe-ImmH is more potent than ImmH. DADMe-ImmH captures more of the transition state binding energy by virtue of being a closer geometric match to the hPNP transition state than ImmH. A consequence of these similarities is that the active site of hPNP exerts greater distortional forces on ImmH than on DADMe-ImmH to "achieve" the hPNP transition state geometry. By using magic angle spinning solid-state NMR to investigate stable isotope-labeled ImmH and DADMe-ImmH, we have explored the difference in distortional binding of these two inhibitors to hPNP. High-precision determinations of internuclear distances from NMR recoupling techniques, rotational echo double resonance, and rotational resonance, have provided unprecedented atomistic insight into the geometric changes that occur upon binding of transition state analogs. We conclude that hPNP stabilizes conformations of these chemically distinct analogs having distances between the cation and leaving groups resembling those of the known transition state. PMID:24043827

  10. Theoretical Analysis of Kinetic Isotope Effects on Proton Transfer Reactions between Substituted α-Methoxystyrenes and Substituted Acetic Acids

    PubMed Central

    Wong, Kin Yiu; Richard, John P.; Gao, Jiali

    2009-01-01

    Primary kinetic isotope effects (KIEs) on a series of carboxylic acid-catalyzed protonation reactions of aryl-substituted α-methoxystyrenes (X-1) to form oxocarbenium ions have been computed using the Kleinert variational second-order perturbation theory (KP2) in the framework of Feynman path integrals (PI) along with the potential energy surface obtained at the B3LYP/6-31+G(d,p) level. Good agreement with the experimental data was obtained, demonstrating that this novel computational approach for computing KIEs of organic reactions is a viable alternative to the traditional method employing Bigeleisen equation and harmonic vibrational frequencies. Although tunneling makes relative small contributions to the lowering of the free energy barriers for the carboxylic acid catalyzed protonation reaction, it is necessary to include tunneling contributions to obtain quantitative estimates of the KIEs. Consideration of anharmonicity can further improve the calculated KIEs for the protonation of substituted α-methoxystyrenes by chloroacetic acid, but for the reactions of the parent and 4-NO2 substituted α-methoxystyrene with substituted carboxylic acids, the correction of anharmonicity overestimates the computed KIEs for strong acid catalysts. In agreement with experimental findings, the largest KIEs are found in nearly ergoneutral reactions, ΔGo ≈ 0, where the transition structures are nearly symmetric and the reaction barriers are relatively low. Furthermore, the optimized transition structures are strongly dependent on the free energy for the formation of the carbocation intermediate, i.e., the driving force ΔGo, along with a good correlation of Hammond shift in the transition state structure. PMID:19754046

  11. Transition State Structure and Inhibition of Rv0091, a 5'-Deoxyadenosine/5'-methylthioadenosine Nucleosidase from Mycobacterium tuberculosis.

    PubMed

    Namanja-Magliano, Hilda A; Stratton, Christopher F; Schramm, Vern L

    2016-06-17

    5'-Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) is a bacterial enzyme that catalyzes the hydrolysis of the N-ribosidic bond in 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH). MTAN activity has been linked to quorum sensing pathways, polyamine biosynthesis, and adenine salvage. Previously, the coding sequence of Rv0091 was annotated as a putative MTAN in Mycobacterium tuberculosis. Rv0091 was expressed in Escherichia coli, purified to homogeneity, and shown to be a homodimer, consistent with MTANs from other microorganisms. Substrate specificity for Rv0091 gave a preference for 5'-deoxyadenosine relative to MTA or SAH. Intrinsic kinetic isotope effects (KIEs) for the hydrolysis of [1'-(3)H], [1'-(14)C], [5'-(3)H2], [9-(15)N], and [7-(15)N]MTA were determined to be 1.207, 1.038, 0.998, 1.021, and 0.998, respectively. A model for the transition state structure of Rv0091 was determined by matching KIE values predicted via quantum chemical calculations to the intrinsic KIEs. The transition state shows a substantial loss of C1'-N9 bond order, well-developed oxocarbenium character of the ribosyl ring, and weak participation of the water nucleophile. Electrostatic potential surface maps for the Rv0091 transition state structure show similarity to DADMe-immucillin transition state analogues. DADMe-immucillin transition state analogues showed strong inhibition of Rv0091, with the most potent inhibitor (5'-hexylthio-DADMe-immucillinA) displaying a Ki value of 87 pM. PMID:27019223

  12. Is aspartate 52 essential for catalysis by chicken egg white lysozyme? The role of natural substrate-assisted hydrolysis

    SciTech Connect

    Matsumura, Ichiro; Kirsch, J.F.

    1996-02-13

    The chicken and goose egg white lysozymes (ChEWL and GoEWL) are homologues, but differ in substrate specificity. ChEWL catalyzes the hydrolysis of the glycosidic bonds of bacterial peptidoglycans and chitin-derived substrates, while GoEWL is specific for bacterial peptidoglycans. The active-site aspartate 52 residue of ChEWL, which is postulated to stabilize the oxocarbenium ion intermediate, has no counterpart in GoEWL. The substrate specificity of the D52A ChEWL mutant was compared with those of wild-type ChEWL and GoEWL. D52A ChEWL retains approximately 4% of the wild-type catalytic activity in reactions with three different bacterial cell suspensions. Asp52 therefore is not essential to the catalytic mechanism, accounting for only a 2 kcal/mol decrease in AG. The function of Asp52 in D52A ChEWL- and GoEWL-catalyzed cleavage of (carboxymethyl)chitin may be partially fulfilled by an appropriately positioned carboxyl group on the substrate (substrate-assisted catalysis). D52A ChEWL and GoEWL, unlike wild-type ChEWL, exhibit biphasic kinetics in the clearing of Micrococcus luteus cell suspensions, suggesting preferences for subsets of the linkages in the M. luteus peptidoglycan. These subsets do not exist in the peptidoglycans of Escherichia coli or Sarcina lutea, since neither D52A ChEWL nor GoEWL exhibits initial bursts in reactions with suspensions of these bacteria. We propose that substrate-assisted catalysis occurs in reactions of D52A ChEWL and GoEWL with M. luteus peptidoglycans, with the glycine carboxyl group of uncross-linked peptides attached to N-acetylmuramic acid partially substituting the function of the missing Asp52. 52 refs., 6 figs., 1 tab.

  13. Stepwise Catalytic Mechanism via Short-Lived Intermediate Inferred from Combined QM/MM MERP and PES Calculations on Retaining Glycosyltransferase ppGalNAcT2

    PubMed Central

    Trnka, Tomáš; Kozmon, Stanislav; Tvaroška, Igor; Koča, Jaroslav

    2015-01-01

    The glycosylation of cell surface proteins plays a crucial role in a multitude of biological processes, such as cell adhesion and recognition. To understand the process of protein glycosylation, the reaction mechanisms of the participating enzymes need to be known. However, the reaction mechanism of retaining glycosyltransferases has not yet been sufficiently explained. Here we investigated the catalytic mechanism of human isoform 2 of the retaining glycosyltransferase polypeptide UDP-GalNAc transferase by coupling two different QM/MM-based approaches, namely a potential energy surface scan in two distance difference dimensions and a minimum energy reaction path optimisation using the Nudged Elastic Band method. Potential energy scan studies often suffer from inadequate sampling of reactive processes due to a predefined scan coordinate system. At the same time, path optimisation methods enable the sampling of a virtually unlimited number of dimensions, but their results cannot be unambiguously interpreted without knowledge of the potential energy surface. By combining these methods, we have been able to eliminate the most significant sources of potential errors inherent to each of these approaches. The structural model is based on the crystal structure of human isoform 2. In the QM/MM method, the QM region consists of 275 atoms, the remaining 5776 atoms were in the MM region. We found that ppGalNAcT2 catalyzes a same-face nucleophilic substitution with internal return (SNi). The optimized transition state for the reaction is 13.8 kcal/mol higher in energy than the reactant while the energy of the product complex is 6.7 kcal/mol lower. During the process of nucleophilic attack, a proton is synchronously transferred to the leaving phosphate. The presence of a short-lived metastable oxocarbenium intermediate is likely, as indicated by the reaction energy profiles obtained using high-level density functionals. PMID:25849117

  14. Crystal structures of Mycobacterium tuberculosis GlgE and complexes with non-covalent inhibitors.

    PubMed

    Lindenberger, Jared J; Veleti, Sri Kumar; Wilson, Brittney N; Sucheck, Steven J; Ronning, Donald R

    2015-01-01

    GlgE is a bacterial maltosyltransferase that catalyzes the elongation of a cytosolic, branched α-glucan. In Mycobacterium tuberculosis (M. tb), inactivation of GlgE (Mtb GlgE) results in the rapid death of the organism due to a toxic accumulation of the maltosyl donor, maltose-1-phosphate (M1P), suggesting that GlgE is an intriguing target for inhibitor design. In this study, the crystal structures of the Mtb GlgE in a binary complex with maltose and a ternary complex with maltose and a maltosyl-acceptor molecule, maltohexaose, were solved to 3.3 Å and 4.0 Å, respectively. The maltohexaose structure reveals a dominant site for α-glucan binding. To obtain more detailed interactions between first generation, non-covalent inhibitors and GlgE, a variant Streptomyces coelicolor GlgEI (Sco GlgEI-V279S) was made to better emulate the Mtb GlgE M1P binding site. The structure of Sco GlgEI-V279S complexed with α-maltose-C-phosphonate (MCP), a non-hydrolyzable substrate analogue, was solved to 1.9 Å resolution, and the structure of Sco GlgEI-V279S complexed with 2,5-dideoxy-3-O-α-D-glucopyranosyl-2,5-imino-D-mannitol (DDGIM), an oxocarbenium mimic, was solved to 2.5 Å resolution. These structures detail important interactions that contribute to the inhibitory activity of these compounds, and provide information on future designs that may be exploited to improve upon these first generation GlgE inhibitors. PMID:26245983

  15. Silent information regulator 2 family of NAD- dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose.

    PubMed

    Tanner, K G; Landry, J; Sternglanz, R; Denu, J M

    2000-12-19

    Conflicting reports have suggested that the silent information regulator 2 (SIR2) protein family employs NAD(+) to ADP-ribosylate histones [Tanny, J. C., Dowd, G. J., Huang, J., Hilz, H. & Moazed, D. (1999) Cell 99, 735-745; Frye, R. A. (1999) Biochem. Biophys. Res. Commun. 260, 273-279], deacetylate histones [Landry, J., Sutton, A., Tafrov, S. T., Heller, R. C., Stebbins, J., Pillus, L. & Sternglanz, R. (2000) Proc. Natl. Acad. Sci. USA 97, 5807-5811; Smith, J. S., Brachmann, C. B., Celic, I., Kenna, M. A., Muhammad, S., Starai, V. J., Avalos, J. L., Escalante-Semerena, J. C., Grubmeyer, C., Wolberger, C. & Boeke, J. D. (2000) Proc. Natl. Acad. Sci. USA 97, 6658-6663], or both [Imai, S., Armstrong, C. M., Kaeberlein, M. & Guarente, L. (2000) Nature (London) 403, 795-800]. Uncovering the true enzymatic function of SIR2 is critical to the basic understanding of its cellular function. Therefore, we set out to authenticate the reaction products and to determine the intrinsic catalytic mechanism. We provide direct evidence that the efficient histone/protein deacetylase reaction is tightly coupled to the formation of a previously unidentified acetyl-ADP-ribose product (1-O-acetyl-ADP ribose). One molecule of NAD(+) and one molecule of acetyl-lysine are readily catalyzed to one molecule of deacetylated lysine, nicotinamide, and 1-O-acetyl-ADP-ribose. A unique reaction mechanism involving the attack of enzyme-bound acetate or the direct attack of acetyl-lysine on an oxocarbenium ADP-ribose intermediate is proposed. We suggest that the reported histone/protein ADP-ribosyltransferase activity is a low-efficiency side reaction that can be explained through the partial uncoupling of the intrinsic deacetylation and acetate transfer to ADP-ribose. PMID:11106374

  16. Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles.

    PubMed

    Boschelli, Diane H; Wu, Biqi; Ye, Fei; Wang, Yan; Golas, Jennifer M; Lucas, Judy; Boschelli, Frank

    2006-12-28

    Compound 1 (SKI-606, bosutinib), a 7-alkoxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-3-quinolinecarbonitrile, is a potent inhibitor of Src kinase activity. We previously reported that analogs of 1 with thiophene groups at C-7 retained the Src activity of the parent compound. The corresponding C-7 furan analogs were prepared and it was found that the 3,5-substituted furan analog had increased activity compared to that of the 2,5-substituted furan isomer. Addition of a methoxy group at C-6 decreased the Src inhibitory activity of the C-7 2,5-substituted furan analog but increased the activity of the C-7 3,5-substituted furan isomer. This compound, 10, was a more potent Src inhibitor than 1 in both enzymatic and cell-based assays. The kinase selectivity profile of 10 was similar to that of 1, with 10 also inhibiting the activity of Abl and Lck. When tested in a solid tumor xenograft model, 10 had comparable oral activity to that of 1. PMID:17181170

  17. Enantio- and periselective nitroalkene Diels-Alder reaction.

    PubMed

    Narcis, Maurice J; Sprague, Daniel J; Captain, Burjor; Takenaka, Norito

    2012-12-14

    The periselective Diels-Alder reaction of 5-substituted pentamethylcyclopentadienes and nitroethylene has been realized by helical-chiral hydrogen bond donor catalysts. To our knowledge, this represents the first asymmetric catalytic nitroalkene Diels-Alder reaction via activation of nitroalkene, and thus establishes its proof-of-principle. PMID:23104427

  18. Synthesis and biological evaluation of the first pentafluorosulfanyl analogs of mefloquine†

    PubMed Central

    Mo, Tingting; Geib, Steven J.; Caridha, Diana; Dow, Geoffrey S.; Gerena, Lucia; Roncal, Norma; Milner, Erin E.

    2010-01-01

    Two novel SF5 analogs of the antimalarial agent mefloquine were synthesized in 5 steps and 10–23% overall yields and found to have improved activity and selectivity against malaria parasites. This work also represents the first report of SF5-substituted quinolines. PMID:19795052

  19. Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins

    PubMed Central

    Roy, Joyeeta; Mal, Tanushree; Jana, Supriti

    2016-01-01

    Summary Dibromobenzoisofuranone 12, synthesized in six steps, was regiospecifically annulated with 5-substituted cyclohexenones 13/36 in the presence of LiOt-Bu to give brominated anthraquinones 14/38 in good yields. Darzens condensation of 30 was shown to give chain-elongated anthraquinone 32. Alkaline hydrolysis of 38 furnished 39 representing desulfoproisocrinin F. PMID:27340445

  20. Quantitative autoradiographic mapping of focal herpes simplex virus encephalitis using a radiolabeled antiviral drug

    SciTech Connect

    Price, R.

    1984-12-18

    A method of mapping herpes simplex viral infection comprising administering a radiolabeled antiviral active 5-substituted 1-(2'-deoxy-2'-substituted-D-arabinofuranosyl) pyrimidine nucleoside to the infected subject, and scanning the area in which the infection is to be mapped for the radiolabel.

  1. 17α-Acet­oxy-11β-hy­droxy-6α-methyl­pregn-4-ene-3,20-dione

    PubMed Central

    Yousuf, Sammer; Bano, Saira; Choudhary, M. Iqbal

    2012-01-01

    The title compound, C24H34O5, a fungal-transformed metabolite of the injecta­ble contraceptive medroxyprogesterone acetate, consists of four fused rings (A, B, C and D; steroid labelling). Ring A exists in a half-chair conformation while trans-fused rings B and C adopt chair conformations. The five-membered ring D adopts an envelope conformation with the C atom bound to the methyl group at the flap. In the crystal, adjacent mol­ecules are linked by O—H⋯O and C—H⋯O hydrogen bonds, forming infinite chains along the a axis. PMID:22807835

  2. Crystal structure of N-[(E)-(1,3-benzodioxol-5-yl)-methyl-idene]-4-chloro-aniline.

    PubMed

    García-Merinos, J Pablo; López, Yliana; González-Campos, J Betzabe; Aviña-Verduzco, Judit A; Del Río, Rosa E; Santillan, Rosa

    2014-11-01

    In the title compound, C14H10ClNO2, obtained by the condensation of 4-chloro-aniline and piperonal, the five-membered ring is almost planar (r.m.s. deviation = 0.023 Å) and the dihedral angle between the aromatic rings is 43.22 (14)°. In the crystal, a short O⋯Cl contact of 3.173 (2) Å is observed. The mol-ecules are arranged into corrugated (010) layers. PMID:25484825

  3. Selective Monoarylation of Primary Amines Using the Pd-PEPPSI-IPent(Cl) Precatalyst.

    PubMed

    Sharif, Sepideh; Rucker, Richard P; Chandrasoma, Nalin; Mitchell, David; Rodriguez, Michael J; Froese, Robert D J; Organ, Michael G

    2015-08-10

    A single set of reaction conditions for the palladium-catalyzed amination of a wide variety of (hetero)aryl halides using primary alkyl amines has been developed. By combining the exceptionally high reactivity of the Pd-PEPPSI-IPent(Cl) catalyst (PEPPSI=pyridine enhanced precatalyst preparation, stabilization, and initiation) with the soluble and nonaggressive sodium salt of BHT (BHT=2,6-di-tert-butyl-hydroxytoluene), both six- and five-membered (hetero)aryl halides undergo efficient and selective amination. PMID:26097000

  4. Regioselective Synthesis of N-Heteroaromatic Trifluoromethoxy Compounds by Direct O-CF3 Bond Formation.

    PubMed

    Liang, Apeng; Han, Shuaijun; Liu, Zhenwei; Wang, Liang; Li, Jingya; Zou, Dapeng; Wu, Yangjie; Wu, Yusheng

    2016-04-01

    The first one-step method for the synthesis of ortho-N-heteroaromatic trifluoromethoxy derivatives by site-specific O-CF3 bond formation using hydroxylated N-heterocycles and Togni's reagent is described. The approach enables the unprecedented syntheses of a wide range of six or five-membered N-heteroaromatic trifluoromethoxy compounds containing one or two heteroatoms from most commonly used hydroxylated N-heterocycles. Notable advantages of this method include its simplicity and mild conditions, avoidance of the need for metals or toxic reagents, and compatibility with a variety of functional groups. Furthermore, this method is especially suitable for the larger scale application. PMID:26791812

  5. Photoswitching Behavior of a Cyclohexene-Bridged versus a Cyclopentene-Bridged Dithienylethene System.

    PubMed

    Steenbock, Torben; Escribano, Alejandra; Heck, Jürgen; Herrmann, Carmen

    2015-05-18

    Photoswitching is an intriguing way of incorporating functionality into molecules or their subunits. Dithienylethene switches are particularly promising, but have so far mostly been studied with five-membered ring (cyclopentenyl) backbones. We aim at comparing the switching properties of backbones with five and six carbon atoms in the ring. A major advantage is that cyclohexenyl rings offer new options for chiral functionalization. A slight change in the reaction conditions of a McMurry ring closure reaction leads to the formation of dithienyl derivatives with a cyclohexene backbone in reasonable yield. Density functional theory calculations were carried out, demonstrating the similarity of both compounds. Experimental results confirm the theoretical outcomes. PMID:25704168

  6. Synthesis of new pyrazolyl-1,3-diazabicyclo[3.1.0]hexe-3-ene derivatives

    NASA Astrophysics Data System (ADS)

    Kiyani, Hamzeh; Albooyeh, Fereshteh; Fallahnezhad, Saied

    2015-07-01

    A series of new of photochromic 1,3-diazabicyclo[3.1.0]hex-3-ene derivatives based on the skeleton of five-membered pyrazole moiety have been synthesized and characterized by spectral techniques, as well as their photochromic properties were examined under UV light irradiation in various solutions. All these newly synthesized compounds showed good photochromic properties in the both solution and solid states. The UV-Visible spectral analysis of the corresponding pyrazolyl bicyclic aziridines established structure-photochromic behavior relationships.

  7. Ethyl 4-{[3-(adamantan-1-yl)-4-phenyl-5-sulfanyl­idene-4,5-dihydro-1H-1,2,4-triazol-1-yl]meth­yl}piperazine-1-carboxyl­ate

    PubMed Central

    Al-Abdullah, Ebtehal S.; Asiri, Hanadi H.; El-Emam, Ali A.; Ng, Seik Weng

    2012-01-01

    The title mol­ecule, C26H35N5O2S, displays a chair-shaped piperazine ring, as well as a planar triazole ring whose phenyl substituent is perpendicular to the mean plane of the five-membered ring [dihedral angle = 90.00 (13)°]. The methyl­ene substituent on the piperazine ring occupies an equatorial site. Weak inter­molecular C—H⋯O hydrogen bonding is present in the crystal structure. The crystal studied was a non-merohedral twin, with a 33.9 (3)% minor component. PMID:22347127

  8. 3-(Adamantan-1-yl)-1-[(4-benzyl­piperazin-1-yl)meth­yl]-4-phenyl-1H-1,2,4-triazole-5(4H)-thione

    PubMed Central

    Al-Abdullah, Ebtehal S.; Asiri, Hanadi H.; El-Emam, Ali; Ng, Seik Weng

    2012-01-01

    The title mol­ecule, C30H37N5S, displays a chair-shaped piperazine ring, as well as an approximately planar triazole ring [maximum deviation = 0.002 (2) Å] whose phenyl substituent is nearly perpendicular to the mean plane of the five-membered ring [dihedral angle = 80.4 (1)°]. The substit­uents on the piperazine ring occupy equatorial sites. Weak inter­molecular C—H⋯S hydrogen bonding is present in the crystal structure. PMID:22346973

  9. 3-(Adamantan-1-yl)-4-phenyl-1-[(4-phenyl­piperazin-1-yl)meth­yl]-1H-1,2,4-triazole-5(4H)-thione

    PubMed Central

    Al-Abdullah, Ebtehal S.; Asiri, Hanadi H.; El-Emam, Ali; Ng, Seik Weng

    2012-01-01

    The title mol­ecule, C29H35N5S, displays a chair-shaped piperazine ring, as well as an approximately planar triazole ring (r.m.s. deviation = 0.001 Å) whose phenyl substituent is nearly perpendicular to the mean plane of the five-membered ring [dihedral angle = 88.9 (1)°]. The substituents on the piperazine ring occupy equatorial sites. In the crystal, the adamantyl cage is disordered over two sets of sites with a major component of 67.8 (5)%. Weak inter­molecular C—H⋯S hydrogen bonding is present in the crystal. PMID:22346974

  10. Design, synthesis, and evaluation of conformationally restricted acetanilides as potent and selective β3 adrenergic receptor agonists for the treatment of overactive bladder.

    PubMed

    Moyes, Christopher R; Berger, Richard; Goble, Stephen D; Harper, Bart; Shen, Dong-Ming; Wang, Liping; Bansal, Alka; Brown, Patricia N; Chen, Airu S; Dingley, Karen H; Di Salvo, Jerry; Fitzmaurice, Aileen; Gichuru, Loise N; Hurley, Amanda L; Jochnowitz, Nina; Miller, Randall R; Mistry, Shruty; Nagabukuro, Hiroshi; Salituro, Gino M; Sanfiz, Anthony; Stevenson, Andra S; Villa, Katherine; Zamlynny, Beata; Struthers, Mary; Weber, Ann E; Edmondson, Scott D

    2014-02-27

    A series of conformationally restricted acetanilides were synthesized and evaluated as β3-adrenergic receptor agonists (β3-AR) for the treatment of overactive bladder (OAB). Optimization studies identified a five-membered ring as the preferred conformational lock of the acetanilide. Further optimization of both the aromatic and thiazole regions led to compounds such as 19 and 29, which have a good balance of potency and selectivity. These compounds have significantly reduced intrinsic clearance compared to our initial series of pyridylethanolamine β3-AR agonists and thus have improved unbound drug exposures. Both analogues demonstrated dose dependent β3-AR mediated responses in a rat bladder hyperactivity model. PMID:24437735

  11. Drugs derived from cannabinoids. 4. Effect of alkyl substitution in sulfur and carbocyclic analogs.

    PubMed

    Razdan, R K; Handrick, G R; Dalzell, H C; Howes, J F; Winn, M; Plotnikoff, N P; Dodge, P W; Dren, A T

    1976-04-01

    Various CNS-active cannabinoids in which the alicyclic ring was thiopheno, cyclopenteno, or cyclohexeno with the alkyl substituent in various positions (structural types 1-6) were synthesized by procedures described previously. These compounds were compared in selected pharmacological tests in mice, rats, dogs, and cats. The results suggested that methyl substitution in the close proximity of the phenolic hydroxyl group strongly influenced the activity of some cannabinoids, particularly of those which had a planar five-membered alicyclic ring rather than a six-membered ring. PMID:944269

  12. Noncovalent Substrate-Directed Enantioselective Heck Reactions: Synthesis of S- and P-Stereogenic Heterocycles.

    PubMed

    de Azambuja, Francisco; Carmona, Rafaela C; Chorro, Tomaz H D; Heerdt, Gabriel; Correia, Carlos Roque D

    2016-08-01

    S- and P-Stereogenic heterocycles were synthesized by a remarkably simple enantioselective Heck desymmetrization reaction based on the unprecedented noncovalent directing effect of S=O and P=O functionalities. Selected prochiral symmetric substrates were efficiently arylated using the recently disclosed chiral PyraBOx ligand under mild and open-flask reaction conditions. Several five-membered aryl- sulfones, sulfoxides, and phosphine oxides were synthesized in good to excellent yields, in good to high diastereoselectivity, and enantiomeric ratios up to 98:2. Theoretical calculations also support the noncovalent directing effect of the S=O and P=O functionalities during the arylation process. PMID:27273079

  13. 1β,15α-Dihy­droxy-16α,17-ep­oxy­pregn-4-ene-3,20-dione

    PubMed Central

    Shen, Yan-Bing; Wang, Yi-Bo; Luo, Jian-Mei; Wang, Min

    2013-01-01

    The title mol­ecule, C21H28O5, is composed of three six-membered rings (A/B/C) and a five-membered ring (D). Ring A adopts a 1α-sofa conformation, while rings B and C adopt chair conformations. Cyclo­pentane ring D adopts a 14α-envelope conformation. In the crystal, O—H⋯O hydrogen bonds lead to the formation of ribbons running along the a axis. The structure is further consolidated by C—H⋯O inter­actions, which link the molecules head-to-tail into ribbons along the a axis. PMID:23476615

  14. Isolation and structure elucidation of a novel product of the acidic degradation of cefaclor.

    PubMed

    Baertschi, S W; Dorman, D E; Occolowitz, J L; Spangle, L A; Collins, M W; Wildfeuer, M E; Lorenz, L J

    1993-06-01

    The acidic aqueous degradation of cefaclor, an orally administered cephalosporin antibiotic, has been investigated. The most prominent peak in the high-performance liquid chromatography profile of a degraded solution of cefaclor was isolated by preparative high-performance liquid chromatography. Mechanistically, the formation of this degradent from cefaclor involves a condensation of two cefaclor degradation products in which both products have undergone contraction from a six-membered cephem ring to a five-membered thiazole ring, presumably via a common episulfonium ion intermediate. PMID:8331538

  15. Catalytic Intramolecular Ketone Alkylation with Olefins by Dual Activation.

    PubMed

    Lim, Hee Nam; Dong, Guangbin

    2015-12-01

    Two complementary methods for catalytic intramolecular ketone alkylation reactions with unactivated olefins, resulting in Conia-ene-type reactions, are reported. The transformations are enabled by dual activation of both the ketone and the olefin and are atom-economical as stoichiometric oxidants or reductants are not required. Assisted by Kool's aniline catalyst, the reaction conditions can be both pH- and redox-neutral. A broad range of functional groups are thus tolerated. Whereas the rhodium catalysts are effective for the formation of five-membered rings, a ruthenium-based system that affords the six-membered ring products was also developed. PMID:26486569

  16. Post-transcriptional regulation of ethylene perception and signaling in Arabidopsis

    SciTech Connect

    Schaller, George Eric

    2014-03-19

    The simple gas ethylene functions as an endogenous regulator of plant growth and development, and modulates such energy relevant processes as photosynthesis and biomass accumulation. Ethylene is perceived in the plant Arabidopsis by a five-member family of receptors related to bacterial histidine kinases. Our data support a general model in which the receptors exist as parts of larger protein complexes. Our goals have been to (1) characterize physical interactions among members of the signaling complex; (2) the role of histidine-kinase transphosphorylation in signaling by the complex; and (3) the role of a novel family of proteins that regulate signal output by the receptors.

  17. Vaccines against 'the other' Ebolavirus species.

    PubMed

    Kozak, Robert A; Kobinger, Gary P

    2016-09-01

    The Ebolavirus genus includes five member species, all of which pose a threat to global public health. These viruses cause fatal hemorrhagic fever in humans and nonhuman primates, and are considered category A pathogens due to the risk of their use as a bioweapon. The potential for an outbreak, either as a result of a natural emergence, deliberate release, or imported case underscores the need for protective vaccines. Recent progress in advancing vaccines for use against the strain of Zaire ebolavirus (EBOV) responsible for the West African Ebola outbreak offers reasons for optimism against EBOV, and demonstrates that protection against other Ebolavirus species is achievable. PMID:27010528

  18. The effect of biothiol on UV irradiated alpha-lipoic acid.

    PubMed

    Wada, Naoki; Wakami, Hirotaka; Konishi, Tetsuya; Matsugo, Seiichi

    2008-01-01

    alpha-Lipoic acid (LA) and its reduced form dihydrolipoic acid (DHLA) are well known as strong antioxidants. LA has the characteristic distorted five membered 1,2-dithiolane ring, which is quite vulnerable to UV irradiation. The UV induced decomposition of LA and the effect of the following addition of biothiols to the photoirradiated solution of LA were investigated by UV-vis spectrometry and (1)H NMR spectral analysis. The mechanism of UV irradiated LA decomposition was proposed based on the results obtained from NMR and GPC measurements. PMID:19850983

  19. (E)-1-[(1,3-Dioxan-4-yl)meth-yl]-2-(nitro-methyl-idene)imidazolidine.

    PubMed

    Tian, Zhongzhen; Dong, Haijun; Li, Dongmei; Wang, Gaolei

    2010-01-01

    In the title compound, C(9)H(15)N(3)O(4), the 1,3-dioxane ring displays a chair conformation and the five-membered ring is close to planar (r.m.s. deviation = 0.054 Å). An intra-molecular N-H⋯O hydrogen bond to one of the nitro-group O atoms generates an S(6) ring. In the crystal, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into C(6) chains propagating in [010] and a C-H⋯O link also occurs. PMID:21588701

  20. Rhodium-Catalyzed Intramolecular C-H Silylation by Silacyclobutanes.

    PubMed

    Zhang, Qing-Wei; An, Kun; Liu, Li-Chuan; Guo, Shuangxi; Jiang, Chenran; Guo, Huifang; He, Wei

    2016-05-17

    Silacyclobutane was discovered to be an efficient C-H bond silylation reagent. Under the catalysis of Rh(I) /TMS-segphos, silacyclobutane undergoes sequential C-Si/C-H bond activations, affording a series of π-conjugated siloles in high yields and regioselectivities. The catalytic cycle was proposed to involve a rarely documented endocyclic β-hydride elimination of five-membered metallacycles, which after reductive elimination gave rise to a Si-Rh(I) species that is capable of C-H activation. PMID:27073004

  1. Temperature-controlled redox-neutral ruthenium(ii)-catalyzed regioselective allylation of benzamides with allylic acetates.

    PubMed

    Manikandan, Rajendran; Jeganmohan, Masilamani

    2016-08-10

    Substituted aromatic amides reacted efficiently with allylic acetates in the presence of a cationic ruthenium complex in ClCH2CH2Cl at room temperature providing ortho allylated benzamides in a highly regioselective manner without any oxidant and base. The whole catalytic reaction occurred in a Ru(ii) oxidation state and thus the oxidation step is avoided. By tuning the reaction temperature, ortho allyl and vinyl benzamides were prepared exclusively. Later, ortho allyl and vinylated benzamides were converted into biologically useful six- and five-membered benzolactones in the presence of HCl. PMID:27456467

  2. Ruthenium-Catalyzed Hydroalkynylative Cyclization of 1,6-Enynes Induced by Substituent Effects.

    PubMed

    Liu, Rui; Ni, Zhenjie; Giordano, Laurent; Tenaglia, Alphonse

    2016-08-19

    The ruthenium-catalyzed 1,6-enyne cyclization in the presence of bulky substituted terminal alkyne proceeds smoothly at room temperature to afford highly substituted five-membered cyclic compounds featuring a 1,5-enyne motif. Deuterium-labeling experiments showed that the key ruthenacyclopentene intermediate undergoes cleavage of metal-carbon bonds through the metal-assisted σ-bond metathesis reaction, thus leading to the formation of C(sp(2))-H and C(sp(3))-C(sp) bonds. PMID:27504966

  3. Theoretical study on the catalytic reactivity of N-hydroxyphthalimide tuned by different heterocyclic substitutions on its phenyl ring for aerobic oxidation

    NASA Astrophysics Data System (ADS)

    Chen, Kexian; Xie, Haiying; Jiang, Kezhi; Mao, Jianyong

    2016-07-01

    The structure-reactivity relationship of new hydroxyimide organocatalysts based on the heterocyclic replacements of the phenyl ring of N-hydroxyphthalimide (NHPI) has been theoretically investigated to gain a mature understanding of this particular catalysis for aerobic oxidation. We find that the reactivity of catalysts with the common five-member aromatic rings is lower than that of NHPI. The catalyst with the recyclable structure of imidazolium ionic liquid may serve as a novel model catalyst for further improvements due to its reactivity comparable to that of NHPI. The catalytic reactivity of multi-nitroxyl catalysts is theoretically more fascinating than that of the highly efficient N,N-dihydroxypyromellitimide.

  4. LC-UV-Guided Isolation and Structure Determination of Lancolide E: A Nortriterpenoid with a Tetracyclo[5.4.0.0(2,4).0(3,7)]undecane-Bridged System from a "Talented" Schisandra Plant.

    PubMed

    Shi, Yi-Ming; Cai, Song-Liang; Li, Xiao-Nian; Liu, Miao; Shang, Shan-Zhai; Du, Xue; Xiao, Wei-Lie; Pu, Jian-Xin; Sun, Han-Dong

    2016-01-01

    Lancolide E (1) featuring a complex tetracyclo[5.4.0.0(2,4).0(3,7)]undecane-bridged system that is constructed by an eight-, a three-, and two five-membered carbon rings in a sterically congested region was obtained in trace amounts from a "talented" schinortriterpenoid producer Schisandra lancifolia. Its structure was fully characterized by combining 2D NMR spectroscopy, theoretical calculations, and X-ray diffraction analysis. The biogenetic pathway of 1 was proposed to involve a Prins cyclization. PMID:26673855

  5. The human growth hormone gene is regulated by a multicomponent locus control region

    SciTech Connect

    Jones, B.; Cooke, N.E.; Liebhaber, S.A.; Monks, B.R.

    1995-12-01

    This article describes research involving the five-member human growth hormone (hGH)/chorionic somatomammotropin (hCS) gene cluster and its expression in the placenta. The results indicate that interactions among multiple elements are required to restrict hGH transcription to the pituitary and generate appropriate levels of expression in the mouse genome. In addition, the results suggest a role for shared and unique regulatory sequences in locus control region-mediated expression of the hGH/hCS gene cluster in the pituitary and possibly the placenta. 67 refs., 9 figs.

  6. Crystal structure of 16-hy­droxy-4,4,10,13,14-penta­methyl-17-(6-methyl­hept-5-en-2-yl)-4,5,6,9,10,11,12,13,14,15,16,17-dodeca­hydro-1H-cyclo­penta­[a]phenanthren-3(2H)-one

    PubMed Central

    Ge, Jun-Jun; Chen, Pian; Ye, Xiao-Xia

    2015-01-01

    The title compound, C30H48O2, contains a fused four-ring triterpenoid system. In the mol­ecule, the two cyclo­hexane rings adopt a chair conformation and a twist boat conformation, respectively, the central cyclo­hexene ring adopts a half-chair conformation whereas the five membered ring adopts an envelope conformation. In the crystal, O—H⋯O hydrogen bonds between the hy­droxy and carbonyl groups of adjacent mol­ecules link the mol­ecules into supra­molecular chains propagating along the b-axis direction. PMID:26279910

  7. Instrumental analysis for differentiation of beers and evaluation of beer ageing

    NASA Astrophysics Data System (ADS)

    Dreve, Simina; Voica, Cezara; Dragan, Felicia; Georgiu, Monica

    2013-11-01

    A representative selection of 5 different beers commercially available were measured spectrophotometrically in UV-Vis spectral region and by fluorescence spectroscopy, in order to determine qualitative differentiation due to the mainly iso-R-acids (with a five member ring) originating from R-acids present in hops. Minerals and trace elements analysis were also performed by ICP-MS method. The determination of the bitter organic acids in beers and of the content in metallic ions can be used as indicators for differentiation of beers and evaluation of beer ageing.

  8. 4-(2,4,6-Trimethyl­benz­yl)-1,3-thia­zol-2-amine

    PubMed Central

    Maharramov, Abel M.; Khalilov, Ali N.; Gurbanov, Atash V.; Allahverdiyev, Mirze A.; Ng, Seik Weng

    2011-01-01

    The methyl­ene C atom in the title compound, C13H16N2S, is connected to a five-membered thia­zole ring and a mesityl substituent. The rings are aligned at 75.4 (1)°. The amino substitutent inter­acts with the ring N atom of an adjacent mol­ecule by an inter­molecular N—H⋯N hydrogen bond, generating a helical chain running along the b axis. PMID:21522463

  9. Hybrid [5]Radialenes with Bispyrroloheteroles: New Electron-Donating Units.

    PubMed

    Higashino, Tomohiro; Imahori, Hiroshi

    2015-09-14

    Bispyrroloheteroles have been synthesized to address their intrinsic structural, optical, and electrochemical properties. The X-ray crystal structures and calculated natural bond orbital (NBO) bond orders unambiguously demonstrated the existence of a two pyrrole-fused five-membered ring with short exocyclic C-C double bonds and long endocyclic C-C single bonds, supporting that the bispyrroloheteroles are rare examples of structurally characterized hybrid [5]radialenes. The bispyrroloheteroles were found to act as an electron-donating unit, which would be fascinating for the rational design of new charge-transporting and donor-acceptor photovoltaic materials as well as versatile charge-transfer complexes. PMID:26242481

  10. Pulsed-field gel electrophoresis for epidemiologic studies of Campylobacter hyointestinalis isolates.

    PubMed Central

    Salama, S M; Tabor, H; Richter, M; Taylor, D E

    1992-01-01

    Campylobacter hyointestinalis was isolated from five members of the same family who had previously consumed raw milk. Pulsed-field gel electrophoresis of genomic DNAs from the five strains, after digestion with restriction endonuclease SalI, revealed that three strains had identical genome patterns and therefore appeared to be related, whereas the other two had completely different genome patterns and appeared to be unrelated. We report here for the first time the isolation of C. hyointestinalis from family members who had consumed raw milk. Our study also demonstrates the usefulness of pulsed-field gel electrophoresis for epidemiologic studies of this unusual campylobacter. Images PMID:1500503

  11. Mechanistic Considerations in the Synthesis of 2-Aryl-Indole Analogues under Bischler-Mohlau Conditions

    PubMed Central

    MacDonough, Matthew T.; Shi, Zhe; Pinney, Kevin G.

    2015-01-01

    Mechanistic insight into the pathway of the Bischler-Mohlau indole formation reaction is provided by isotopic labeling utilizing judicious incorporation of a 13C atom within the α-bromoacetophenone analogue reactant. The resulting rearranged 2-aryl indole, isolated as the major product, located the 13C isotope label at the methine carbon of the fused five-membered heterocyclic ring, which suggested that the mechanistic pathway of cyclization, in this specific example, required two equivalents of the aniline analogue reactant partner and proceeded through an imine intermediate rather than by direct formation of the corresponding 3-aryl indole accompanied by a concomitant 1,2-aryl shift rearrangement. PMID:26973358

  12. Cp*Rh(III)-Catalyzed Cross-Coupling of Alkyltrifluoroborate with α-Diazomalonates for C(sp(3))-C(sp(3)) Bond Formation.

    PubMed

    Lu, Yin-Suo; Yu, Wing-Yiu

    2016-03-18

    A Cp*Rh(III)-catalyzed cross-coupling of alkyltrifluoroborate with α-diazomalonates was developed; the C(sp(3))-C(sp(3)) bond coupled products were formed in up to 97% yields. The reaction tolerates some useful functional groups, including ketone, ester, amide, ether, sulfonyl, and thiophene. Electrospray ionization mass spectrometry (ESI-MS) analysis revealed the formation of a distinct molecular species corresponding to σ-alkylrhodium(III) complexes. The successful diazo coupling reaction may be attributed to coordination of the amide group that promotes stability of the alkylrhodium(III) complex through the formation of a five-membered metallacycle. PMID:26926387

  13. Crystal structure of 3,4'-diphenyl-3'-p-tolyl-4'H-spiro-[indan-2,5'-[1,2]oxazol]-1-one.

    PubMed

    Mahfoud, Asmae; Al Houari, Ghali; El Yazidi, Mohamed; Saadi, Mohamed; El Ammari, Lahcen

    2015-11-01

    In the title compound, C30H23NO2, the five-membered rings are both in envelope conformations with the same spiro C atom as the flap. The benzene ring and the two phenyl rings are inclined to the mean plane of the indene ring system by 83.98 (8), 81.46 (8) and 72.31 (7)°. In the crystal, mol-ecules are linked by pairs of C-H⋯O hydrogen bonds into inversion dimers. The dimers are further connected by C-H⋯N inter-actions, forming layers parallel to (10-1). PMID:26594573

  14. Impact of metal-alkoxide functionalized linkers on H2 binding: A density functional study

    NASA Astrophysics Data System (ADS)

    Banu, Tahamida; Ghosh, Avik; Das, Abhijit K.

    2016-08-01

    The effect of metal-alkoxide functionalization of different organic linkers on the H2 binding is investigated employing DFT approach. While analyzing the H2 binding interaction of magnesium-alkoxide modified benzene, naphthalene, anthracene and pyrene linkers, we find their comparable affinity toward H2 molecules. Six-member alkoxide ring containing naphthalene and pyrene systems interact with the H2 molecules in a comparatively better way than their five-member analogues. AIM, NBO and LMO-EDA analyses have been performed to comprehend the bonding nature between Mg center and the H2 molecules. Polarization along with the charge transfer interactions play significant role in stabilizing the systems.

  15. Crystal structure of 2-ethyl-4-methyl-1-(2-oxido-3,4-dioxo-cyclo-but-1-en-1-yl)-1H-imidazol-3-ium.

    PubMed

    Korkmaz, Ufuk; Bulut, Iclal; Bulut, Ahmet

    2016-07-01

    In the title inner salt molecule, C10H10N2O3, the four-membered cyclobutene ring is twisted by 7.1 (2)° with respect to the five-membered imidazole ring. The crystal packing exhibits an R 2 (2)(9) hydrogen-bonding ring motif through N-H⋯O and C-H⋯O inter-actions. The potential non-linear optical properties were studied by a computational ab initio calculations performed at the DFT/B3LYP/6-31++G(d,p) level of theory. PMID:27555949

  16. Squaramide-Catalyzed Synthesis of Enantioenriched Spirocyclic Oxindoles via Ketimine Intermediates with Multiple Active Sites.

    PubMed

    Sun, Qiang-Sheng; Zhu, Hua; Chen, Yong-Jian; Yang, Xiao-Di; Sun, Xing-Wen; Lin, Guo-Qiang

    2015-11-01

    A new method for the construction of five-membered spirocyclic oxindoles is based on a Michael-Mannich cascade reaction of a ketimine intermediated catalyzed by a bifunctional quinine-derived squaramide. The desired products were obtained in excellent yields (up to 94%) and stereoselectivities (up to >20:1 d.r., >99% ee). A scaled-up variant also proceeded smoothly showing that the one-pot reaction might find application in the synthesis of bioactive-compound libraries. PMID:26337819

  17. Crystal structure of 2-ethyl-4-methyl-1-(2-oxido-3,4-dioxo­cyclo­but-1-en-1-yl)-1H-imidazol-3-ium

    PubMed Central

    Korkmaz, Ufuk; Bulut, Iclal; Bulut, Ahmet

    2016-01-01

    In the title inner salt molecule, C10H10N2O3, the four-membered cyclobutene ring is twisted by 7.1 (2)° with respect to the five-membered imidazole ring. The crystal packing exhibits an R 2 2(9) hydrogen-bonding ring motif through N—H⋯O and C—H⋯O inter­actions. The potential non-linear optical properties were studied by a computational ab initio calculations performed at the DFT/B3LYP/6–31++G(d,p) level of theory. PMID:27555949

  18. Kinetic Stability of Non-IPR Fullerene Molecular Ions.

    PubMed

    Aihara, Jun-ichi; Nakagami, Yuto; Sekine, Rika

    2015-06-18

    Many fullerenes that violate the isolated pentagon rule (IPR) form stable metallofullerenes. In general, a fullerene cage is kinetically stabilized by acquiring a given number of electrons. Kinetic stability of negatively charged non-IPR fullerenes, including the recently isolated endohedral metallofullerene with a heptagonal face, was rationalized in terms of bond resonance energy (BRE). Interestingly, molecular anions of conventional fullerenes found in most isolated metallofullerenes are kinetically stable with large positive BREs for all CC bonds. As we pointed out in 1993, the IPR does not apply to charged fullerenes because π-bonds shared by two five-membered rings are aromatized to varying extents. PMID:26020361

  19. Crystal structure of 2-hy­droxy-2-(2-oxo­cyclo­hept­yl)-2,3-di­hydro-1H-indene-1,3-dione

    PubMed Central

    Ahamed, P. Kaleel; Srinivasan, N.; Ranjith Kumar, R.; Krishnakumar, R. V.

    2015-01-01

    In the title compound, C16H16O4, the five-membered ring of the indene-1,3-dione unit adopts a twist conformation, whereas the seven-membered ring adopts a twist–chair conformation. In the crystal, mol­ecules are linked by O—H⋯O hydrogen bonds, weak C—H⋯O hydrogen bonds and π–π stacking [centroid-to-centroid distance = 3.7373 (8) Å] into a three-dimensional supra­molecular architecture. PMID:26594439

  20. Crystal structure of 4-{[(cyano­imino)(methyl­sulfanyl)meth­yl]amino}-1,5-dimethyl-2-phenyl-2,3-di­hydro-1H-pyrazol-3-one

    PubMed Central

    Elgemeie, Galal H.; Abouzeid, Mamdouh; Jones, Peter G.

    2015-01-01

    In the title compound, C14H15N5OS, the tautomer present in the solid state is that in which the immediately exocyclic N atom bears the H atom. The central five-membered ring is almost planar (r.m.s. deviation = 0.025 Å), but both its N atoms are significantly pyramidalized. A classical hydrogen bond from the N—H group to the cyanide N atom forms inversion-symmetric dimers, which are further linked by C—H⋯O inter­actions. PMID:25705464

  1. 2-tert-Butyl-1-(4-nitro­amino-1,2,5-oxadiazol-3-yl)diazene 1-oxide

    PubMed Central

    Li, Xiang-Zhi; Wang, Bo-Zhou; Fan, Xue-Zhong; Ng, Seik Weng

    2012-01-01

    In the title compound, C6H10N6O4, the nitro­amine –NHNO2 substituent and the C–N=N(→ O) unit of the other substituent of the oxadiazole ring are nearly coplanar with the five-membered ring [dihedral angles = 5.7 (1) and 3.0 (1)°]. The amino group of the –NHNO2 substituent is a hydrogen-bond donor to the two-coordinate N atom of the C—N=N(→ O) unit. PMID:22798842

  2. (E,E)-1-(2-Hydroxy­imino-1-phenyl­ethyl­idene)semicarbazide monohydrate

    PubMed Central

    Öztürk, Aslı; Babahan, İlknur; Sarıkavaklı, Nursabah; Hökelek, Tuncer

    2009-01-01

    In the title compound, C9H10N4O2·H2O, the oxime unit has an E configuration, and an intra­molecular N—H⋯N hydrogen bond results in the formation of a planar five-membered ring, which is oriented with respect to the aromatic ring at a dihedral angle of 74.82 (17)°. In the crystal structure, inter­molecular O—H⋯O and N—H⋯O hydrogen bonds link the mol­ecules and R 2 2(8) ring motifs are apparent. PMID:21583876

  3. endo-3,3-Dimethyl-4-oxobicyclo­[3.1.0]hexan-2-yl methane­sulfonate

    PubMed Central

    Kremer, Adrian; Norberg, Bernadette; Krief, Alain; Wouters, Johan

    2010-01-01

    The relative configuration of the endo isomer of the title compound, C9H14O4S, has been established and the conformation of the diastereoisomer is discussed. The five-membered ring adopts an envelope conformation. The conformation of the methane­sulfonate substituent is stabilized by inter­molecular C—H⋯O hydrogen bonds. The crystal packing results in alternating layers of polar methane­sulfonates and stacked bicyclo­hexa­nyl rings parallel to ab. PMID:21580752

  4. (1S,5R)-1-(3,4-Dichloro­phen­yl)-3-oxa­bicyclo­[3.1.0]hexan-2-one

    PubMed Central

    Görbitz, Carl Henrik; Hansen, Tore; Vestli, Kristian

    2009-01-01

    The absolute structure has been determined by X-ray analysis for the title compound, C11H8Cl2O2. The five-membered ring of the mol­ecule is best described as a flattened envelope conformation with the methyl­ene C atom located 0.208 (2) Å below the plane formed by the other four atoms. A weak intermolecular C—H⋯O hydrogen bond is present in the crystal structure PMID:21582428

  5. Chlorido(1-cyclo­pentyl­idene-4-ethyl­thio­semicarbazidato-κ2 N 1,S)diphenyl­tin(IV)

    PubMed Central

    Venkatraman, Ramaiyer; Sitole, Lungile; Fronczek, Frank R.

    2009-01-01

    The Sn atom in the title compound, [Sn(C6H5)2(C8H14N3S)Cl], is penta­coordinated with a trigonal-bipyramidal coordination geometry. The 1-cyclo­pentyl­idene-4-ethyl­thio­semicarbazidate (cpetsc) ligand coordinates through the S atom and the N atom bonds to the cyclo­pentyl group, forming a five-membered ring with the Sn center. The chloride ligand and the coordinated N atom are in axial positions. In the crystal structure, inter­molecular N—H⋯Cl hydrogen bonds form chains along [101]. PMID:21578665

  6. An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

    PubMed Central

    2013-01-01

    Summary This review which is the second in this series summarises the most common synthetic routes as applied to the preparation of many modern pharmaceutical compounds categorised as containing a six-membered heterocyclic ring. The reported examples are based on the top retailing drug molecules combining synthetic information from both scientific journals and the wider patent literature. It is hoped that this compilation, in combination with the previously published review on five-membered rings, will form a comprehensive foundation and reference source for individuals interested in medicinal, synthetic and preparative chemistry. PMID:24204439

  7. Use of a New Spirophosphine to Achieve Catalytic Enantioselective [4+1] Annulations of Amines with Allenes to Generate Dihydropyrroles

    PubMed Central

    Kramer, Søren; Fu, Gregory C.

    2015-01-01

    Due in part to the common occurrence of five-membered nitrogen heterocycles in bioactive molecules, the discovery of methods for the enantioselective synthesis of such structures is a useful endeavor. Building on a single example by Tong of a phosphine-catalyzed [4+1] annulation of an amine with an allene that furnished an achiral dihydropyrrole in 22% yield, we have developed, with the aid of a new chiral spirophosphine catalyst, a method with increased utility, specifically, improved yield, enhanced scope (the use of γ-substituted allenes), and good ee. The enantioenriched dihydropyrrole products can be transformed into other interesting families of compounds with very good stereoselectivity. PMID:25780940

  8. Low catalyst loadings in olefin metathesis: synthesis of nitrogen heterocycles by ring-closing metathesis.

    PubMed

    Kuhn, Kevin M; Champagne, Timothy M; Hong, Soon Hyeok; Wei, Wen-Hao; Nickel, Andrew; Lee, Choon Woo; Virgil, Scott C; Grubbs, Robert H; Pederson, Richard L

    2010-03-01

    A series of ruthenium catalysts have been screened under ring-closing metathesis (RCM) conditions to produce five-, six-, and seven-membered carbamate-protected cyclic amines. Many of these catalysts demonstrated excellent RCM activity and yields with as low as 500 ppm catalyst loadings. RCM of the five-membered carbamate series could be run neat, the six-membered carbamate series could be run at 1.0 M, and the seven-membered carbamate series worked best at 0.2-0.05 M. PMID:20141172

  9. Microwave and Quantum Chemical Study of the Hydrazino Group as Proton Donor in Intramolecular Hydrogen Bonding of (2-Fluoroethyl)hydrazine (FCH2CH2NHNH2).

    PubMed

    Møllendal, Harald; Samdal, Svein; Guillemin, Jean-Claude

    2015-09-01

    The microwave spectrum of (2-fluoroethyl)hydrazine (FCH2CH2NHNH2) was studied in the 11-123 GHz spectral region to investigate the ability of the hydrazino group to form intramolecular hydrogen bonds acting as a proton donor. This group can participate both in five-member and in six-member internal hydrogen bonds with the fluorine atom. The spectra of four conformers were assigned, and the rotational and centrifugal distortion constants of these rotameric forms were determined. Two of these conformers have five-member intramolecular hydrogen bonds, while the two other forms are without this interaction. The internal hydrogen bonds in the two hydrogen-bonded forms are assumed to be mainly electrostatic in origin because the N-H and C-F bonds are nearly parallel and the associated bond moments are antiparallel. This is the first example of a gas-phase study of a hydrazine where the hydrazino functional group acts as a proton donor in weak intramolecular hydrogen bonds. Extensive quantum chemical calculations at the B3LYP/cc-pVTZ, MP2/cc-pVTZ, and CCSD/cc-pVQZ levels of theory accompanied and guided the experimental work. These calculations predict the existence of no less than 18 conformers, spanning a CCSD internal energy range of 15.4 kJ/mol. Intramolecular hydrogen bonds are predicted to be present in seven of these conformers. Three of these forms have six-member hydrogen bonds, while four have five-member hydrogen bonds. The three lowest-energy conformers have five-member internal hydrogen bonds. The spectrum of the conformer with the lowest energy was not assigned because it has a very small dipole moment. The CCSD relative energies of the two hydrogen-bonded rotamers whose spectra were assigned are 1.04 and 1.62 kJ/mol, respectively, whereas the relative energies of the two conformers with assigned spectra and no hydrogen bonds have relative energies of 6.46 and 4.89 kJ/mol. PMID:26258892

  10. Dichlorido(6-methyl-2,2′-bipyridine-κ2 N,N′)zinc(II)

    PubMed Central

    Ahmadi, Roya; Kalateh, Khadijeh; Ebadi, Amin; Amani, Vahid; Khavasi, Hamid Reza

    2008-01-01

    In the mol­ecule of the title compound, [ZnCl2(C11H10N2)], the ZnII atom is four-coordinated in a distorted tetra­hedral configuration by two N atoms from the 6-methyl-2,2′-bipyridine ligand and by two Cl atoms. There are π–π contacts between the pyridine ring and the five-membered ring, and also between the pyridine rings, [centroid–centroid distances = 3.685 (3) and 3.757 (3) Å, respectively]. PMID:21201019

  11. Crystal structure of 1,2,3,5-di-O-methyl­ene-α-d-xylo­furan­ose

    PubMed Central

    Tiritiris, Ioannis; Tussetschläger, Stefan; Kantlehner, Willi

    2015-01-01

    The title compound, C7H10O5, was synthesized by reaction of d-xylose with paraformaldehyde. In the crystal, the central part of the mol­ecule consists of a five-membered C4O ring with an envelope conformation, with the methine C atom adjacent to the O atom being the flap. The protected O atoms of both cyclic acetal groups are oriented so that the four chiral C atoms of the furan­ose part show an R configuration. C—H⋯O hydrogen bonds are present between adjacent mol­ecules, generating a three-dimensional network. PMID:26594582

  12. QSAR studies on benzodiazepine receptor binding of purines and amino acid derivatives.

    PubMed

    Saha, R N; Meera, J; Agrawal, N; Gupta, S P

    1991-01-01

    Quantitative structure-activity relationship (QSAR) studies are reported on the benzodiazepine receptor binding of a series of substituted 9-benzyl-6-dimethylamino-9H-purines and N-(indol-3-ylglyoxylyl)amino acid derivatives. The nitrogen of the five membered heterocyclic ring and the polar substituent in the aromatic ring, present in both series of compounds, form important centres in the binding interaction. We conclude that the receptor must possess a strong nucleophilic centre and a polar site, and that a hydrophobic pocket exists to accommodate hydrophobic moieties. PMID:1654919

  13. Spatial organization and conformational peculiarities of the callatostatin family of neuropeptides.

    PubMed

    Alieva, I N; Velieva, L I; Alie, D I; Godjaev, N M

    2002-08-01

    The structures and conformational peculiarities of five members of the callatostatin family of neuropeptides, i.e. Leu- and Met-callatostatins, ranging in size from 8 to 16 amino acid residues have been investigated by a theoretical conformational analysis method. A comparative analysis of the conformational flexibilities of Met-callatostatin with those of the hydroxylated analogues, [Hyp2]- and [Hyp3]-Met-callatostatin has been carried out. Helically packed C-terminal pentapeptide in the structure of all investigated Leu-callatostatins are shown to be possible. The reason for the great number low-energy conformers for the callatostatin N-terminus is discussed. PMID:12212802

  14. Mechanism for chelated sulfate formation from SO2 and bis (triphenylphosphine) platinum

    NASA Technical Reports Server (NTRS)

    Mehandru, S. P.; Anderson, A. B.

    1985-01-01

    Structure and energy surface calculations using the atom superposition and electron delocalization molecular orbital theory show that the first step in the reaction between SO2 and the dioxygen complex (PPh3)2PtO2 is the coordination of SO2 with one oxygen atom of the complex, followed by metal-oxygen bond breaking and reorientation, leading to a five-membered cyclic structure. This then rearranges to form the bidentate coordinated sulfate. Alternative pathways are considered and are found to be less favorable.

  15. [2+2+1] cyclization of allenes.

    PubMed

    Kitagaki, S; Inagaki, F; Mukai, C

    2014-05-01

    The [2+2+1] cyclization of an alkyne, an alkene and carbon monoxide, i.e., the Pauson-Khand reaction, is one of the most powerful tools for constructing a five-membered ring. In place of the alkene or alkyne part, the use of an allene functionality has proven to make this reaction more valuable for organic synthesis. This review focuses on the origin and progress of the allenic [2+2+1] cyclocarbonylation, including the chirality transfer of the allene and its synthetic applications. PMID:24514744

  16. An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles.

    PubMed

    Baumann, Marcus; Baxendale, Ian R

    2013-01-01

    This review which is the second in this series summarises the most common synthetic routes as applied to the preparation of many modern pharmaceutical compounds categorised as containing a six-membered heterocyclic ring. The reported examples are based on the top retailing drug molecules combining synthetic information from both scientific journals and the wider patent literature. It is hoped that this compilation, in combination with the previously published review on five-membered rings, will form a comprehensive foundation and reference source for individuals interested in medicinal, synthetic and preparative chemistry. PMID:24204439

  17. Biodegradation and dissolution of polyaromatic hydrocarbons by Stenotrophomonas sp.

    PubMed

    Tiwari, Bhagyashree; Manickam, N; Kumari, Smita; Tiwari, Akhilesh

    2016-09-01

    The aim of this work was to study the biodegradation capabilities of a locally isolated bacterium, Stenotrophomonas sp. strain IITR87 to degrade the polycyclic aromatic hydrocarbons and also check the preferential biodegradation of polycyclic aromatic hydrocarbons (PAHs). From preferential substrate degradation studies, it was found that Stenotrophomonas sp. strain IITR87 first utilized phenanthrene (three membered ring), followed by pyrene (four membered ring), then benzo[α]pyrene (five membered ring). Dissolution study of PAHs with surfactants, rhamnolipid and tritonX-100 showed that the dissolution of PAHs increased in the presence of surfactants. PMID:27342606

  18. Theoretical study of amino derivatives and anticancer platinum drug grafted on various carbon nanostructures.

    PubMed

    Kraszewski, S; Duverger, E; Ramseyer, C; Picaud, F

    2013-11-01

    Density functional theory calculations with van der Waals approximation have been conducted to analyze the functionalization of various carbon-based nanostructures (fullerene, metallic, and semi-conducting nanotubes) with amino derivative groups. The results obtained with azomethine, show the formation of a five membered ring on fullerenes, and on nanotubes consistent with experimental observations. The attachment of an azomethine plus subsequent drug like a Pt(IV) complex does not perturb the cycloaddition process. Moreover, all theoretical results show that the length of different amino derivatives with subsequent Pt(IV) complex does not affect the complexed therapeutic agent when it is attached onto these carbon-based nanostructures. PMID:24206319

  19. Method for controlling clathrate hydrates in fluid systems

    DOEpatents

    Sloan, Jr., Earle D.

    1995-01-01

    Discussed is a process for preventing clathrate hydrate masses from impeding the flow of fluid in a fluid system. An additive is contacted with clathrate hydrate masses in the system to prevent those clathrate hydrate masses from impeding fluid flow. The process is particularly useful in the natural gas and petroleum production, transportation and processing industry where gas hydrate formation can cause serious problems. Additives preferably contain one or more five member and/or six member cyclic chemical groupings. Additives include poly(N-vinyl-2-pyrrolidone) and hydroxyethylcellulose, either in combination or alone.

  20. Quaternary anticholinesterase therapeutics. Annual report, 22 July 1986-21 July 1987

    SciTech Connect

    Harris, R.N.; Koolpe, G.A.; Lovejoy, S.M.; Kelson, A.B.; Vu, H.M.

    1988-04-01

    Ninety-five new imidazolium, pyridinium, and 1,2,4-triazolium salts were prepared, characterized, and submitted to WRAIR for in-vivo evaluation as antidotes against the nerve agent soman. Many of the salts were evaluated at the U.S. Army Institute of Chemical Defense (ICD) in the mouse as treatment therapeutics for organophosphonate nerve agent intoxication. Of the effective type I compounds, those that provided the greatest protective ability incorporated side chains functionalized with nitro, sulfone, and amino groups. In an effort to prepare type I and II compounds that have the potential to reactivate aged, inhibited acetylcholinesterase by means of a chelated metal ion, several new phosphatase simulant ligands were prepared and characterized. Unfortunately, the ligands could not be induced to form stable metal complexes. Finally, a methodology for preparing 4(5)-substituted imidazoles was established and subsequently applied to the preparation of several new 4(5)-substituted type I salts.

  1. Atroposelective formation of dibenz[c,e]azepines via intramolecular direct arylation with centre-axis chirality transfer.

    PubMed

    Cheetham, Caroline A; Massey, Richard S; Pira, Silvain L; Pritchard, Robin G; Wallace, Timothy W

    2011-03-21

    5-Substituted 6,7-dihydrodibenz[c,e]azepines, a class of secondary amine incorporating a centre-axis chirality relay, are accessible from 1-substituted N-(2-bromobenzyl)-1-phenylmethanamines via N-acylation and ring-closing intramolecular direct arylation. The ring closure proceeds with high atropodiastereoselectivity due to strain effects that are induced by trigonalisation of the nitrogen atom, as predicted using molecular mechanics calculations. PMID:21267501

  2. Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064

    SciTech Connect

    Bass, Jonathan Y.; Caldwell, Richard D.; Caravella, Justin A.; Chen, Lihong; Creech, Katrina L.; Deaton, David N.; Madauss, Kevin P.; Marr, Harry B.; McFadyen, Robert B.; Miller, Aaron B.; Parks, Derek J.; Todd, Dan; Williams, Shawn P.; Wisely, G. Bruce

    2010-09-27

    Starting from the known FXR agonist GW 4064 1a, a series of alternately 3,5-substituted isoxazoles was prepared. Several of these analogs were potent full FXR agonists. A subset of this series, with a tether between the isoxazole ring and the 3-position aryl substituent, were equipotent FXR agonists to GW 4064 1a, with the 2,6-dimethyl phenol analog 1t having greater FRET FXR potency than GW 4064 1a.

  3. The Ugi reaction in the generation of new nucleosides as potential antiviral and antileishmanial agents.

    PubMed

    Fan, Xuesen; Zhang, Xinying; Bories, Christian; Loiseau, Philippe M; Torrence, Paul F

    2007-04-01

    5-Formyl-2'-deoxyuridine-3',5'-diacetate was converted to a small library of 5-substituted pyrimidine nucleoside N-acylamino acid amides by means of a Ugi multicomponent reaction. The reaction allowed introduction of various substituents at the acyl moiety, at the amino acid alpha-amide group, and at the amino acid carboxyl function. Evaluation of these novel 5-substituted nucleosides against vaccinia virus and cowpox virus provided one compound with discernable activity against cowpox virus but five- to eightfold less active than the Cidofovir standard. More promising activity was seen for the inhibition of Leishmania donovani promastigotes. Several synthetic products showed antileishmanial activity in the 10(-5)M range. When compared to earlier studies demonstrating anti-orthopoxviral and antileishmanial activity of 5-substituted pyrimidine nucleosides, these results imply that the 5-(N-acylamino acid amide)-derivatized pyrimidine nucleosides may possess more steric bulk, greater hydrophobicity, and more flexibility than is compatible with these particular biological activities. PMID:16996561

  4. Synthesis of Phthalocyanines with a Pentafluorosulfanyl Substituent at Peripheral Positions.

    PubMed

    Iida, Norihito; Tanaka, Kenta; Tokunaga, Etsuko; Mori, Satoru; Saito, Norimichi; Shibata, Norio

    2015-12-01

    The pentafluorosulfanyl (SF5) group is more electronegative, lipophilic and sterically bulky relative to the well-explored trifluoromethyl (CF3) group. As such, the SF5 group could offer access to pharmaceuticals, agrochemicals and optoelectronic materials with novel properties. Here, the first synthesis of phthalocyanines (Pcs), a class of compounds used as dyes and with potential as photodynamic therapeutics, with a SF5 group directly attached on their peripheral positions is disclosed. The key for this work is the preparation of a series of SF5-containing phthalonitriles, which was beautifully regio-controlled by a stepwise cyanation via ortho-lithiation/iodination from commercially available pentafluorosulfanyl arenes. The macrocyclization of the SF5-containing phthalonitriles to SF5-substituted Pcs required harsh conditions with the exception of the synthesis of β-SF5-substituted Pc. The regiospecificity of the newly developed SF5-substituted Pcs observed by UV/Vis spectra and fluorescence quantum yields depend on the peripheral positon of the SF5 group. PMID:27308194

  5. Structural Snapshots of Beta- 1,4Galactosyltransferase-l Along the Kinetic Pathway

    SciTech Connect

    Ramakrishnan,B.; Ramasamy, V.; Qasba, P.

    2006-01-01

    During the catalytic cycle of {beta}1,4-galactosyltransferase-1 (Gal-T1), upon the binding of Mn{sup 2+} followed by UDP-Gal, two flexible loops, a long and a short loop, change their conformation from open to closed. We have determined the crystal structures of a human M340H-Gal-T1 mutant in the open conformation (apo-enzyme), its Mn{sup 2+} and Mn{sup 2+}-UDP-Gal-bound complexes, and of a pentenary complex of bovine Gal-T1-Mn{sup 2+}-UDP-GalNAc-Glc-{alpha}-lactalbumin. These studies show that during the conformational changes in Gal-T1, the coordination of Mn{sup 2+} undergoes significant changes. It loses a coordination bond with a water molecule bound in the open conformation of Gal-T1 while forming a new coordination bond with another water molecule in the closed conformation, creating an active ground-state structure that facilitates enzyme catalysis. In the crystal structure of the pentenary complex, the N-acetylglucosamine (GlcNAc) moiety is found cleaved from UDP-GalNAc and is placed 2.7 {angstrom} away from the O4 oxygen atom of the acceptor Glc molecule, yet to form the product. The anomeric C1 atom of the cleaved GalNAc moiety has only two covalent bonds with its non-hydrogen atoms (O5 and C2 atoms), similar to either an oxocarbenium ion or N-acetylgalactal form, which are crystallographically indistinguishable at the present resolution. The structure also shows that the newly formed, metal-coordinating water molecule forms a hydrogen bond with the {beta}-phosphate group of the cleaved UDP moiety. This hydrogen bond formation results in the rotation of the {beta}-phosphate group of UDP away from the cleaved GalNAc moiety, thereby preventing the re-formation of the UDP-sugar during catalysis. Therefore, this water molecule plays an important role during catalysis in ensuring that the catalytic reaction proceeds in a forward direction.

  6. From formamide to purine: an energetically viable mechanistic reaction pathway.

    PubMed

    Wang, Jing; Gu, Jiande; Nguyen, Minh Tho; Springsteen, Greg; Leszczynski, Jerzy

    2013-02-28

    A step-by-step mechanistic pathway following the transformation of formamide to purine through a five-membered ring intermediate has been explored by density functional theory computations. The highlight of the mechanistic route detailed here is that the proposed pathway represents the simplest reaction pathway. All necessary reactants are generated from a single starting compound, formamide, through energetically viable reactions. Several important reaction steps are involved in this mechanistic route: formylation-dehydration, Leuckart reduction, five- and six-membered ring-closure, and deamination. On the basis of the study of noncatalytic pathways, catalytic water has been found to provide energetically viable step-by-step mechanistic pathways. Among these reaction steps, five-member ring-closure is the rate-determining step. The energy barrier (ca. 42 kcal/mol) of this rate-control step is somewhat lower than the rate-determining step (ca. 44 kcal/mol) for a pyrimidine-based pathway reported previously. The mechanistic pathway reported herein is less energetically demanding than for previously proposed routes to adenine. PMID:23347082

  7. X-ray and DFT Study of Glaucocalyxin A Compound with Cytotoxic Activity

    NASA Astrophysics Data System (ADS)

    Wang, Fu-dong; Wang, Tao; Wu, An-an; Ding, Lan; Wang, Han-qing

    2009-06-01

    The title compound glaucocalyxin A (1) (7α, 14β-dihydroxy-ent-kaur-16-en-3,15-dione) isolated from the leaves of isodon excisoides was characterized by IR, 1H NMR, 13C NMR, 1H-1H COSY, HMQC, HMBC, and EIMS, and its crystal structure was determined by single-crystal X-ray diffraction. The X-ray crystal structure revealed that the molecular backbone of the chosen crystal is a tetracyclic system, including three six-membered rings and a five-membered ring, and the three six-membered rings are in a chair-like conformation. The five-membered ring adopts a twisted envelope-like conformation, and its geometrical parameters were compared with theoretical calculations at the B3LYP and HF level of theory. The molecules form extensive networks through the intra- and intermolecular hydrogen bonds. The experimental NMR data were interpreted with the aid of magnetic shielding constant calculations, by means of the GIAO (gauge-lncluding atomic orbitals) method. Calculated and experimental results were compared with a satisfactory level of agreement. Molecular electrostatic potential map was used in an attempt to identify key features of the diterpenoid glaucocalyxin A that is necessary for its activity. Calculations of molecular electrostatic potential and stabilization energies suggest that the protonation of glaucocalyxin A will be able to occur on carbonyl oxygen atoms.

  8. Crystal structure of methyl 2-(2H-1,3-benzodioxol-5-yl)-7,9-di­bromo-8-oxo-1-oxa­spiro­[4.5]deca-2,6,9-triene-3-car­boxyl­ate

    PubMed Central

    Martins, Lucimara Julio; Simoni, Deborah de Alencar; Aparicio, Ricardo; Coelho, Fernando

    2014-01-01

    The title compound, C18H12Br2O6, was synthesized from Morita–Baylis–Hillman adducts. It incorporates the bromin­ated spiro-hexa­dienone moiety typically exhibited by compounds of this class that exhibit biological activity. Both the brominated cyclo­hexa­dienone and the central five-membered rings are nearly planar (r.m.s. deviations of 0.044 and 0.016 Å, respectively), being almost perpendicularly oriented [inter­planar angle = 89.47 (5)°]. With respect to the central five-membered ring, the brominated cyclo­hexa­dienone ring, the benzodioxol ring and the carboxyl­ate fragment make C—O—C—C, O—C—C—C and C—C—C—O dihedral angles of −122.11 (8), −27.20 (11) and −8.40 (12)°, respectively. An intra­molecular C—H⋯O hydrogen bond occurs. In the crystal, mol­ecules are linked by non-classical C—H⋯O and C—H⋯Br hydrogen bonds resulting in a molecular packing in which the brominated rings are in a head-to-head orientation, forming well marked planes parallel to the b axis. PMID:25553042

  9. Crystal structure of methyl (3RS,4SR,4aRS,11aRS,11bSR)-5-oxo-3,4,4a,5,7,8,9,10,11,11a-deca­hydro-3,11b-ep­oxy­azepino[2,1-a]iso­indole-4-carboxyl­ate

    PubMed Central

    Toze, Flavien A. A.; Poplevin, Dmitry S.; Zubkov, Fedor I.; Nikitina, Eugeniya V.; Porras, Ciara; Khrustalev, Victor N.

    2015-01-01

    The title compound, C15H19NO4, is the a product of the esterification of the corresponding carbonic acid with methanol. The mol­ecule comprises a fused tetra­cyclic system containing three five-membered rings (2-pyrrolidinone, tetra­hydro­furan and di­hydro­furan) and one seven-membered ring (azepane). The five-membered rings have the usual envelope conformations, with the quaternary C atom being the flap atom for the 2-pyrrolidinone ring, and the ether O atom being the common flap atom for the remaining rings. The seven-membered azepane ring adopts a chair conformation with the methine and middle methyl­ene C atoms lying above and below the mean plane defined by the remaining five atoms. The carboxyl­ate substituent is rotated by 77.56 (5)° with respect to the base plane of the tetra­hydro­furan ring. In the crystal, the mol­ecules are bound by weak C—H⋯O hydrogen-bonding inter­actions into puckered layers parallel to (001). PMID:26594446

  10. Antifungal Activity of Fused Mannich Ketones Triggers an Oxidative Stress Response and Is Cap1-Dependent in Candida albicans

    PubMed Central

    Rossignol, Tristan; Kocsis, Béla; Bouquet, Orsolya; Kustos, Ildikó; Kilár, Ferenc; Nyul, Adrien; Jakus, Péter B.; Rajbhandari, Kshitij; Prókai, László; d’Enfert, Christophe; Lóránd, Tamás

    2013-01-01

    We investigated the antifungal activity of fused Mannich ketone (FMK) congeners and two of their aminoalcohol derivatives. In particular, FMKs with five-membered saturated rings were shown to have minimum inhibitory concentration (MIC90s) ranging from 0.8 to 6 µg/mL toward C. albicans and the closely related C. parapsilosis and C. krusei while having reduced efficacy toward C. glabrata and almost no efficacy against Aspergillus sp. Transcript profiling of C. albicans cells exposed for 30 or 60 min to 2-(morpholinomethyl)-1-indanone, a representative FMK with a five-membered saturated ring, revealed a transcriptional response typical of oxidative stress and similar to that of a C. albicans Cap1 transcriptional activator. Consistently, C. albicans lacking the CAP1 gene was hypersensitive to this FMK, while C. albicans strains overexpressing CAP1 had decreased sensitivity to 2-(morpholinomethyl)-1-indanone. Quantitative structure–activity relationship studies revealed a correlation of antifungal potency and the energy of the lowest unoccupied molecular orbital of FMKs and unsaturated Mannich ketones thereby implicating redox cycling-mediated oxidative stress as a mechanism of action. This conclusion was further supported by the loss of antifungal activity upon conversion of representative FMKs to aminoalcohols that were unable to participate in redox cycles. PMID:23646117

  11. Resonance Raman spectra of. cap alpha. -copper phthalocyanine

    SciTech Connect

    Bovill, A.J.; McConnell, A.A.; Nimmo, J.A.; Smith, W.E.

    1986-02-13

    Raman spectra of ..cap alpha..-copper phthalocyanine (..cap alpha..-CuPc) were recorded at room temperature and at 10 K with excitation wavelengths between 457 and 714 nm. Resonance enhancement was greatest for modes for which the largest displacements were on either the inner five-membered ring of the isoindole groups or the inner macrocycle and consequently assignment of the bands to modes of the entire molecule was possible by comparison with nickel octaethylporphyrin. Four out of five bands resonant in the Q band region and preresonant near the B band absorption region are totally symmetric modes. B band preresonance occurs more strongly with high-frequency modes. At low temperatures, multimode interactions are reduced and profiles were obtained which can be compared with solution profiles of porphyrins. Both Q/sub x/ and Q/sub y/ 0-0 scattering can be identified and a helper mode is evident. A term enhancement predominates, with B/sub 1g/ and B/sub 2g/ modes enhanced because of a Jahn-Teller distortion of the excited state. The resonance studies, together with electronic absorption spectra and published theoretical studies, confirm that the Q band in ..cap alpha..-CuPc is largely due to an allowed ..pi..-..pi..* transition associated mainly with the macrocycle and inner five-membered rings of the isoindole groups. 25 references, 5 figures, 2 tables.

  12. Ring Enlargement of Three-Membered Boron Heterocycles upon Reaction with Organic π Systems: Implications for the Trapping of Borylenes.

    PubMed

    Krasowska, Małgorzata; Bettinger, Holger F

    2016-07-18

    New low-energy pathways for the reaction between substituted boriranes and borirenes with unsaturated hydrocarbons (ethyne or ethene) were discovered using density functional and coupled cluster theory. The interaction between the π bond of the hydrocarbon and the empty p orbital of the boron center leads to ring expansion of the three-membered to a five-membered boron heterocycle. The reactions are strongly exothermic and have low or even no barriers. They involve intermediates with a pentacoordinate boron center with two hydrocarbon molecules coordinating to boron akin to metal-olefin complexes. These borylene complexes are shallow minima on the potential energy surfaces. But significantly higher barriers for ring formation are computed for 1,5-cyclooctadiene and dibenzocyclooctatetraene complexes of borylenes, making these complexes likely detectable under appropriate experimental conditions. Our computational findings have implications for the interpretation of trapping experiments of thermally generated small borylenes with excess of small π systems. Because of very low barriers for reactions of three-membered boron heterocycles with π systems and the at least locally large excess of the latter under such conditions, formation of five-membered boron heterocycles should be considered. PMID:27305278

  13. Sulfone-Containing Methacrylate Homopolymers: Wetting and Thermal Properties.

    PubMed

    Fujii, Shota; McCarthy, Thomas J

    2016-01-26

    Although the sulfonyl functional group has a large dipole moment and compounds containing them (sulfones) have correspondingly high dielectric constants, this chemical structure has been neglected for use as a functional group to render surfaces hydrophilic. We have prepared three methacrylate polymers containing side chains capped with sulfolane, methylsulfone, and ethylsulfone functionality. The sulfolane-containing polymer exhibits an unusually high glass transition temperature (Tg = 188°C) for a methacrylate polymer and slightly different thermal degradation behavior than the other two sulfone-containing polymers, likely due to the bulky structure of the sulfolane group in the polymer side chain. At macroscopic polymer film/water interfaces, the sulfone-containing side chains exposed to the interface impart hydrophilic properties as assessed by contact angle analysis. The hydrophilicities of sulfolane and methylsulfone surfaces are similar, and greater than the ethylsulfone surface. Although the chemical compositions of the sulfolane and ethylsulfone polymers are almost identical, the five-membered ring structure of sulfolane allows the sulfonyl moiety to be exposed at the interface in a manner similar to that of the methylsulfone polymer. The sulfonyl group at the ethylsulfone polymer/water interface is slightly masked by the ethyl group. Interestingly, the sulfolane surface displays a higher affinity to methylene iodide and n-hexadecane probe fluids compared to the other sulfone surfaces, suggesting that the five-membered ring structure of the sulfolane moiety can orient in a manner that shelters the sulfonyl group at hydrophobic interfaces. PMID:26716766

  14. Synthesis and X-ray crystal and solution structures of 2,5-anhydro-3,4-O-(1,2-ethanediyl)-D-mannitol: a locked 4T3 furanose conformer.

    PubMed

    Voll, R J; Fronczek, F R; Vargas, D; Younathan, E S

    1992-06-16

    2,5-Anhydro-3,4-O-(1,2-ethanediyl)-D-mannitol (1) was prepared from 2,5-anhydro-D-mannitol (2) in three steps. The fused ring system was introduced by a phase-transfer alkylation using 1,2-dibromoethane. Its conformation in solution was determined by NMR studies at 500 MHz. Variable-temperature studies showed no lineshape change from 25 to 80 degrees in D2O. The data indicate that the five-membered ring is locked by the trans-fused six-membered 1,4-dioxane ring into a twist 4T3 conformation. A single-crystal X-ray study was carried out. The crystals are orthorhombic, C222(1), a = 4.7252 (6), b = 14.0364 (12), c = 13.268 (2) A, Z = 4, with R = 0.032 for 894 observations. The molecule lies upon a crystallographic two-fold axis, and thus the five-membered ring exists in a perfect 4T3 conformation with a pseudorotation angle of 0 degree and amplitude of 47.2 degrees, in agreement with the NMR results. We have shown earlier that, among twenty possible conformers, phosphofructokinase acts specifically on the 4T3 conformer of the beta anomer of D-fructose 6-phosphate. PMID:1394297

  15. Biotransformation of natural compounds: unexpected thio conjugation of Sch-642305 with 3-mercaptolactate catalyzed by Aspergillus niger ATCC 16404 cells.

    PubMed

    Adelin, Emilie; Martin, Marie-Thérèse; Bricot, Marie-Françoise; Cortial, Sylvie; Retailleau, Pascal; Ouazzani, Jamal

    2012-12-01

    Sch-642305 is produced by the endophytic fungi Phomopsis sp. CMU-LMA and exhibits both antimicrobial and cytotoxic activities. The incubation of Sch-642305 with Aspergillus niger ATCC 16404 resting cells leads to two unexpected thio conjugates. Compound (1) is formed by the addition of the cysteine metabolite 3-mercaptolactate to the double bond of Sch-642305. Compound (1) undergoes an intramolecular rearrangement to give compound (2), which contains two rings: a five-membered hydroxylactone ring and a five-membered thiophene ring. The absolute configuration of compound (1) is similar to that of the parent compound, but the configuration of the mercaptolactate side-chain was not determined. The absolute configuration of compound (2) was deduced from the crystal structure and confirmed by the anomal effect of the sulfur atom. To the best of our knowledge, this is the first time such a conjugation rearrangement reactions were observed. The biological significance and the reaction mechanisms are discussed. Compound (1) exhibits a weak antimicrobial activity against Gram-positive bacteria, whereas derivatives (1) and (2) showed an IC₅₀ of 1 and 1.2 μM, respectively, against colonic epithelial cancer cells. PMID:22975164

  16. Modeling the local structure and energetics of protozeolitic nanoclusters in hydrothermally stable aluminosilicate mesostructures.

    PubMed

    Li, Hong; Mahanti, S D; Pinnavaia, Thomas J

    2005-02-24

    The density functional theory (DFT) method is used to investigate the structure and bonding of silica and aluminosilicate nanoclusters containing five- and six-membered oxygen rings. The clusters, which are derived from the BEA zeolite structure, are considered as models of the protozeolitic clusters that are incorporated into the pore walls of steam stable aluminosilicate mesostructures assembled from zeolite seeds. Two locally different Brønsted acid sites in the aluminosilicate structure are identified for the adsorption of a water molecule. The sterically more open acid site is favored for water binding. The stability of the aluminosilicate structure in the presence of H2O molecule is studied by breaking an Al-O bond and inserting a water molecule into the five-membered ring structure. We find that an excitation energy at least 18 times larger than the room-temperature thermal energy is needed to break the stable five-membered ring structure, implying a high hydrothermal stability and acidity for this aluminosilicate structure. PMID:16851274

  17. Crystal structure of methyl (3RS,4SR,4aRS,11aRS,11bSR)-5-oxo-3,4,4a,5,7,8,9,10,11,11a-deca-hydro-3,11b-ep-oxy-azepino[2,1-a]iso-indole-4-carboxyl-ate.

    PubMed

    Toze, Flavien A A; Poplevin, Dmitry S; Zubkov, Fedor I; Nikitina, Eugeniya V; Porras, Ciara; Khrustalev, Victor N

    2015-10-01

    The title compound, C15H19NO4, is the a product of the esterification of the corresponding carbonic acid with methanol. The mol-ecule comprises a fused tetra-cyclic system containing three five-membered rings (2-pyrrolidinone, tetra-hydro-furan and di-hydro-furan) and one seven-membered ring (azepane). The five-membered rings have the usual envelope conformations, with the quaternary C atom being the flap atom for the 2-pyrrolidinone ring, and the ether O atom being the common flap atom for the remaining rings. The seven-membered azepane ring adopts a chair conformation with the methine and middle methyl-ene C atoms lying above and below the mean plane defined by the remaining five atoms. The carboxyl-ate substituent is rotated by 77.56 (5)° with respect to the base plane of the tetra-hydro-furan ring. In the crystal, the mol-ecules are bound by weak C-H⋯O hydrogen-bonding inter-actions into puckered layers parallel to (001). PMID:26594446

  18. Electrochemical Behavior of meso-Substituted Porphyrins: The Role of Cation Radicals to the Half-Wave Oxidation Potential Splitting.

    PubMed

    Tran, Thai T H; Chang, Yan-Ru; Hoang, Tuan K A; Kuo, Ming-Yu; Su, Yuhlong O

    2016-07-21

    In this study, the electrochemical behavior of free base and zinc meso-substituted porphyrins is examined by cyclic voltammetry (CV) and density functional theory (DFT). The results show that the half-wave oxidation potential splitting of the two oxidation states (ΔE= second E1/2 - first E1/2) of tetraphenylporphyrin (H2TPP) and its zinc complex (ZnTPP) are higher than those of porphyrins and their zinc complexes with meso-substituted five-membered heterocylic rings. The ΔE values follow the trend of TPP > T(3'-thienyl)P > T(3'-furyl)P > T(2'-thienyl)P for both meso-porphyrins and their respective zinc complexes. By employing DFT calculations, we have found that the trend of ΔE values is consistent with that of highest spin density (HSD) distribution and HOMO-LUMO energy gaps of cationic radicals as well as the π-conjugation between central porphyrin and meso-substituted rings. Also, they exhibit the better resonance between the porphyrin ring with meso-substituted rings as moving from porphyrins and their zinc complexes with phenyl rings to five-membered heterocyclic rings. A good agreement between calculated and experimental results indicates that cationic radicals, especially their spin density distribution, do play an important role in half-wave oxidation potential splitting of meso-porphyrins and their zinc complexes. PMID:27379447

  19. Crystal structure of N-de­acetyl­lappa­coni­tine

    PubMed Central

    Shi, Xin-Wei; Lu, Qiang-Qiang; Zhou, Jun-Hui; Cui, Xin-Ai

    2015-01-01

    The title compound, C30H42N2O7 [systematic name: (1S,4S,5S,7S,8S,9S,10S,11S,13R,14S,16S,17R)-20-ethyl-4,8,9-trihy­droxy-1,14,16-tri­meth­oxy­aconitan-4-yl 2-amino­benzoate], isolated from roots of Aconitum sinomontanum Nakai, is a typical aconitane-type C19-diterpenoid alkaloid, which crystallizes with two independent mol­ecules in the asymmetric unit. The conformations of the two independent mol­ecules are closely similar. Each mol­ecule comprises four six-membered rings (A, B, D and E) including one six-membered N-containing heterocyclic ring (E), and two five-membered rings (C and F). Rings A, B and E adopt chair conformations, while ring D displays a boat conformation. Five-membered rings C and F exhibit envelope conformations. IntramolecularN—H⋯O hydrogen bonds between the amino group and carbonyl O atom help to stabilize molecular structure. In the crystal, O—H⋯O hydrogen bonds link the mol­ecules into zigzag chains propagating in [010]. PMID:26396805

  20. Novel Nanostructured Materials for Hydrogen Storage

    NASA Astrophysics Data System (ADS)

    Dillon, Anne

    2005-03-01

    The United States Department of Energy's (DOE's) Office of Energy Efficiency and Renewable Energy and the Office of Basic Sciences have concluded that hydrogen storage is a cornerstone technology for implementing a hydrogen energy economy. However, significant scientific advancement is still required if a viable on-board storage technology is to be developed. For example, an adsorption process for on-board vehicular storage will require a hydrogen binding energy between ˜20-60 kJ/mol to allow for near-room temperature operation at reasonable pressures. Typically, non-dissociative physisorption due purely to van der Waals forces involves a binding energy of only ˜ 4 kJ/mol, whereas a chemical bond is ˜ 400 kJ/mol. The desired binding energy range for vehicular hydrogen storage therefore dictates that molecular H2 be stabilized in an unusual manor. Hydrogen adsorption has been observed with a binding energy of ˜ 50 kJ /mol on carbon multi-wall nanotubes (MWNTs) containing iron nanoparticles at their tips. However, hydrogen adsorption at near ambient conditions is neither anticipated nor observed on either purified MWNTs or iron nanoparticles by themselves. Recent theoretical studies have shown that an iron adatom forms a complex with a C36 fullerene and shares charge with four carbon atoms of a bent five-membered ring in the C36 molecule. Three H2 ligands then also coordinate with the iron forming a stable 18-electron organo-metallic complex. Here the binding energy of the molecular hydrogen ligands is ˜ 43 kJ /mol. It is believed that a similar interaction may be occurring for MWNTs containing iron nanoparticles. However, a more optimized material must be produced in order to increase the hydrogen capacity. Iron has also been predicted to complex with all twelve of the five-membered rings in C60 with a binding energy of ˜42 kJ/mol and an H2 capacity of 4.9 wt.%. Further, Scandium has been shown to complex with the twelve five-membered rings in C60 with a

  1. Correlation of exchange bias with magneto-structural effects across the compensation temperature of Co(Cr1-xFex)2O4 (x = 0.05 and 0.075)

    NASA Astrophysics Data System (ADS)

    Kumar, Ram; Padam, R.; Rayaprol, S.; Siruguri, Vasudeva; Pal, D.

    2016-03-01

    A small amount of Fe (5% and 7.5%) substitution in the Cr-site of the multiferroic compound CoCr2O4 leads to a magnetization reversal. In these compounds, we report a sign change in the exchange bias across the compensation temperature, accompanied by a non-monotonic change in the local moments across the compensation temperature. Such non-monotonic change in the magnetic moments is triggered by a similar change in the lattice structure. We relate here the sign change of exchange bias with that of the crystalline energy of the lattice and the Zeeman energy term arising from the anti-site disorder.

  2. Sequential Regioselective C-H Functionalization of Thiophenes.

    PubMed

    Daniels, Matthew H; Armand, Jeremy R; Tan, Kian L

    2016-07-15

    Herein, the sequential functionalization of 5-membered ring heterocycles is disclosed. By employing a pH sensitive directing group both directed and nondirected C-H activation pathways are available, providing access to 2,3,4- and 2,4,5-substituted thiophenes. The C-H arylation was performed in water, and using a surfactant greatly improved the yield and mass recovery. The use of a directing group with an on/off switch offers a potentially powerful means of generating diversity around medicinally relevant cores. PMID:27388746

  3. Synthesis of furans and pyrroles via migratory and double migratory cycloisomerization reactions of homopropargylic aldehydes and imines

    PubMed Central

    Shiroodi, Roohollah Kazem; Vera, Claudia I. Rivera; Dudnik, Alexander S.; Gevorgyan, Vladimir

    2015-01-01

    A novel gold-catalyzed divergent sysnthesis of furans and pyrroles employing readily available homopropargylic aldehydes and imines have been developed. The regiochemical outcome of this reaction is dependent on the substituent on the terminal alkyne of substrate. Thus, substrates possessing alkyl and aryl substituent at the alkyne moiety produce 2,3,5-substituted furans and pyrroles via a migratory cycloisomerizaton reaction. Whereas, their silicon analogues are capable to undergo a double migratory process leading to 2,3,4-substituted heterocycles. PMID:26185336

  4. Formation of 1,4- and 1,5-regioisomers of triazolines in reactions of 2-ethoxyethyl azide with monosubstituted ethylenes

    SciTech Connect

    Lanovaya, G.A.; Mishchenko, V.F.; Korniets, E.D.

    1987-12-01

    The structural specificity of the reactions of 2-ethoxyethyl azide with alkenes RCH=CH/sub 2/ (R = CH/sub 2/C/sub 6/H/sub 5/, CH/sub 2/OC/sub 6/H/sub 13/, CH(OC/sub 2/H/sub 5/)/sub 2/, C/sub 6/H/sub 5/) was studied. The formation of 1,4- and 1,5-substituted triazolines and the high stabilities of the latter were demonstrated by PMR spectroscopy, data from gas-liquid chromatography (GLC), and the kinetics of thermolysis.

  5. Canthin-4-ones as Novel Antibacterial Agents.

    PubMed

    Tremmel, Tim; Puzik, Andreas; Gehring, André P; Bracher, Franz

    2016-09-01

    Based on the chemotype of canthin-4-one alkaloids with moderate antimicrobial activity, a collection of variously substituted canthin-4-ones and desaza analogs were synthesized. Key steps in the syntheses were regioselective halogenations of (desaza) canthin-4-one, followed by Pd-catalyzed cross-coupling reactions. The in vitro screening for antimicrobial activity revealed that two 5-substituted canthin-4-ones (3-pyridyl, 2-bromophenyl) exhibit significant activity against Streptococcus entericus, coupled with high selectivity and the lack of cytotoxicity against mammalian cells. The intact canthin-4-one ring system was demonstrated to be essential for antibacterial activity. PMID:27503113

  6. Pd-Catalyzed sequential β-C(sp(3))-H arylation and intramolecular amination of δ-C(sp(2))-H bonds for synthesis of quinolinones via an N,O-bidentate directing group.

    PubMed

    Guan, Mingyu; Pang, Yubo; Zhang, Jingyu; Zhao, Yingsheng

    2016-05-19

    The pharmacological importance of 2-quinolinone derivatives is well known. Herein, we developed an effective protocol for the synthesis of 2-quinolinone derivatives by palladium-catalyzed sequential β-C(sp(3))-H arylation and selective intramolecular C(sp(2))-H/N-H amination starting with aryl iodides and carboxylic acids. A novel directing group, glycine dimethylamide, was used in the synthesis. We synthesized various quinolinone derivatives, including 5-substituted quinolinones, which are difficult to obtain using the traditional pathway. The directing group could be easily removed and could be readily transformed into other useful functional groups. PMID:27161570

  7. Mechanistic possibilities in prebiotic thiophosphate chemistry

    NASA Technical Reports Server (NTRS)

    Kapovits, I.; Nagyvary, J.

    1978-01-01

    The two types of thiophosphate reactivities were studied in a system that involves reactions of 5'-substituted adenosine derivatives. In this system, both nucleophilic displacement on carbon and P-S cleavage are possible. The products and possible mechanisms of cyclization experiments involving different leaving groups are reported. The data indicate superior reactivity of the 3'-OH of the ribonucleoside, although in most other systems the 2'-OH is found to show superior reactivity. It is suggested that thiophosphates might play a role in prebiotic activation and phosphorylation reactions.

  8. Antimalarial and antimicrobial activities of 8-Aminoquinoline-Uracils metal complexes

    PubMed Central

    Phopin, Kamonrat; Sinthupoom, Nujarin; Treeratanapiboon, Lertyot; Kunwittaya, Sarun; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong

    2016-01-01

    8-Aminoquinoline (8AQ) derivatives have been reported to have antimalarial, anticancer, and antioxidant activities. This study investigated the potency of 8AQ-5-substituted (iodo and nitro) uracils metal (Mn, Cu, Ni) complexes (1-6) as antimalarial and antimicrobial agents. Interestingly, all of these metal complexes (1-6) showed fair antimalarial activities. Moreover, Cu complexes 2 (8AQ-Cu-5Iu) and 5 (8AQ-Cu-5Nu) exerted antimicrobial activities against Gram-negative bacteria including P. shigelloides and S. dysenteriae. The results reveal application of 8AQ and its metal complexes as potential compounds to be further developed as novel antimalarial and antibacterial agents. PMID:27103894

  9. 1,3-Bis(pyridin-2-yl)-1H-benzimidazol-3-ium tetra­fluoridoborate

    PubMed Central

    Grieco, Gabriele; Blacque, Olivier; Berke, Heinz

    2011-01-01

    The asymmetric unit of the title compound, C17H13N4 +·BF4 −, contains one half of the benzimidazolium cation and one half of the tetra­fluoridoborate anion, with crystallographic mirror planes bis­ecting the mol­ecules. One F atom of the tetra­fluoridoborate is equally disordered about a crystallographic mirror plane. In the crystal, C—H⋯F inter­actions link the cations and anions into layers parallel to (100). The crystal packing is further stabilized by F⋯π contacts involving the tetra­fluoridoborate anions and the five-membered rings [F⋯centroid = 2.811 (2) Å]. PMID:22091091

  10. The miR-302/367 cluster: a comprehensive update on its evolution and functions.

    PubMed

    Gao, Zeqian; Zhu, Xueliang; Dou, Yongxi

    2015-12-01

    microRNAs are a subclass of small non-coding RNAs that fine-tune the regulation of gene expression at the post-transcriptional level. The miR-302/367 cluster, generally consisting of five members, miR-367, miR-302d, miR-302a, miR-302c and miR-302b, is ubiquitously distributed in vertebrates and occupies an intragenic cluster located in the gene La-related protein 7 (LARP7). The cluster was demonstrated to play an important role in diverse biological processes, such as the pluripotency of human embryonic stem cells (hESCs), self-renewal and reprogramming. This paper provides an overview of the mir-302/367 cluster, discusses our current understanding of the cluster's evolutionary history and transcriptional regulation and reviews the literature surrounding the cluster's roles in cell cycle regulation, epigenetic regulation and different cellular signalling pathways. PMID:26631377

  11. Redetermined structure of oxaline: absolute configuration using Cu Kα radiation

    PubMed Central

    Qu, Peng; Wu, Zhi-Yong; Zhu, Wei-Ming

    2012-01-01

    In the title compound, C24H25N5O4, the stereogenic C atom bonded to three N atoms and one C atom has an S configuration and its directly bonded neighbour has an R configuration. An intra­molecular N—H⋯O hydrogen bond supports the near coplanarity of the two C3N2-five-membered rings [dihedral angle = 5.64 (10)°]. In the crystal, mol­ecules are linked by N—H⋯N hydrogen bonds, forming a C(8) chain propagating in [001]. The chains are connected by C—H⋯O inter­actions, generating a three-dimensional network. The previous study [Nagel et al. (1974 ▶). Chem. Commun. pp. 1021–1022] did not establish the absolute structure and no atomic coordinates were published or deposited. PMID:22719429

  12. Geometric and electronic structures of one-dimensionally polymerized coronene molecules

    NASA Astrophysics Data System (ADS)

    Narita, Kohei; Okada, Susumu

    2016-06-01

    On the basis of density functional theory, we studied the energetics, geometries, and electronic structures of dicoronylene molecules (coronene dimers) and one-dimensionally polymerized coronene molecules. Our calculations showed that the relative stability of the coronene dimers and polymers strongly depends on the mutual arrangement of molecules with respect to the polymer or dimer directions: the coronene dimer and the polymer with six-membered rings in the intermolecular bonds are the most stable structures among the three possible intermolecular arrangements. The dimer possesses a large energy gap between the highest occupied and lowest unoccupied states, which is narrower than that of the isolated coronene. The polymers are semiconductors with a moderate direct band gap and a large indirect gap for the polymers with six- and four-membered rings and that with five-membered rings, respectively, indicating the possibility of the electronic structure control of polymers via the intermolecular arrangement.

  13. The miR-302/367 cluster: a comprehensive update on its evolution and functions

    PubMed Central

    Gao, Zeqian; Zhu, Xueliang; Dou, Yongxi

    2015-01-01

    microRNAs are a subclass of small non-coding RNAs that fine-tune the regulation of gene expression at the post-transcriptional level. The miR-302/367 cluster, generally consisting of five members, miR-367, miR-302d, miR-302a, miR-302c and miR-302b, is ubiquitously distributed in vertebrates and occupies an intragenic cluster located in the gene La-related protein 7 (LARP7). The cluster was demonstrated to play an important role in diverse biological processes, such as the pluripotency of human embryonic stem cells (hESCs), self-renewal and reprogramming. This paper provides an overview of the mir-302/367 cluster, discusses our current understanding of the cluster's evolutionary history and transcriptional regulation and reviews the literature surrounding the cluster's roles in cell cycle regulation, epigenetic regulation and different cellular signalling pathways. PMID:26631377

  14. Non-proliferation treaty at 25

    SciTech Connect

    Cooper, M.H.

    1995-01-27

    In April, negotiators from more than 160 countries will meet in New York to decide the fate of the 25-year-old Nuclear Non-Proliferation Treaty (NPT). Under the agreement`s unusual terms, signatories must decide whether to extend it indefinitely, extend it for a specified period or abandon it. Supporters of a permanent NPT, including the United States, warn that instability in the post-Cold War era makes it all the more necessary to prevent rogue nations or terrorists from acquiring nuclear weapons. Critics, especially countries without nuclear weapons, say the treaty unfairly guarantees military superiority to the NPT`s five-member {open_quotes}nuclear club.{close_quotes} They also charge the nuclear powers, especially the United States and Russia, with not living up to the treaty`s requirement that they vigorously seek to halt the arms race and eliminate nuclear weapons.

  15. 2-Hy­droxy-16-[(E)-4-methyl­benzyl­idene]-13-(4-methyl­phen­yl)-12-phenyl-1,11-diaza­penta­cyclo­[12.3.1.02,10.03,8.010,14]octa­deca-3(8),4,6-triene-9,15-dione

    PubMed Central

    Kumar, Raju Suresh; Osman, Hasnah; Abdul Rahim, Aisyah Saad; Goh, Jia Hao; Fun, Hoong-Kun

    2010-01-01

    In the title compound, C37H32N2O3, an intra­molecular O—H⋯N hydrogen bond generates a five-membered ring, producing an S(5) motif. The piperidone ring adopts a half-chair conformation. The two fused pyrrolidine rings have similar envelope conformations. The interplanar angles between the benzene rings A/B and C/D are 75.68 (7) and 30.22 (6)°, respectively. In the crystal structure, adjacent mol­ecules are inter­connected into chains propagating along the [010] direction via inter­molecular C—H⋯O hydrogen bonds. Further stabilization is provided by weak C—H⋯π inter­actions. PMID:21588384

  16. Microtubule-binding protein doublecortin-like kinase 1 (DCLK1) guides kinesin-3-mediated cargo transport to dendrites.

    PubMed

    Lipka, Joanna; Kapitein, Lukas C; Jaworski, Jacek; Hoogenraad, Casper C

    2016-02-01

    In neurons, the polarized distribution of vesicles and other cellular materials is established through molecular motors that steer selective transport between axons and dendrites. It is currently unclear whether interactions between kinesin motors and microtubule-binding proteins can steer polarized transport. By screening all 45 kinesin family members, we systematically addressed which kinesin motors can translocate cargo in living cells and drive polarized transport in hippocampal neurons. While the majority of kinesin motors transport cargo selectively into axons, we identified five members of the kinesin-3 (KIF1) and kinesin-4 (KIF21) subfamily that can also target dendrites. We found that microtubule-binding protein doublecortin-like kinase 1 (DCLK1) labels a subset of dendritic microtubules and is required for KIF1-dependent dense-core vesicles (DCVs) trafficking into dendrites and dendrite development. Our study demonstrates that microtubule-binding proteins can provide local signals for specific kinesin motors to drive polarized cargo transport. PMID:26758546

  17. Thermochromism in nickel(II) complexes: thermal, solid state 1H NMR and single crystal X-ray analysis of bis-( N, N-dimethyl-1,2-ethanediamine) nickel(II) perchlorate

    NASA Astrophysics Data System (ADS)

    Koner, Subratanath; Tsutake, Masaru; Nagasawa, Isoroku; Ikeda, Ryuichi; Saha, Pratap K.; Mukherjee, Alok K.; Banerjee, Surajit

    2002-08-01

    The complex bis-( N, N-dimethyl-1,2-ethanediamine) nickel(II) perchlorate undergoes a first-order thermochromic phase transition at ca. 476 K, changing its color from orange to red. The room temperature X-ray crystal structure determination showed that the nickel ion possesses a square-planar geometry with two five membered chelate rings, in the δλ conformation, forming the NiN 4 chromophore. The broad-line 1H NMR indicates the onset of a dynamic disorder of diamine chelate rings at the phase transition temperature region, while T1 measurement of 1H affords the activation energy of the puckering metal chelate rings to be 26 kJ mol -1. The electronic spectrum revealed that a weakening of ligand field around the nickel is associated with the phase transition.

  18. [2-(1-{2-[Aza­nid­yl(ethyl­sulfan­yl)methyl­idene-κN]hydrazin-1-yl­idene-κN 1}eth­yl)phenolato-κO](pyridine-κN)nickel(II)

    PubMed Central

    Takjoo, Reza; Ng, Seik Weng; Tiekink, Edward R. T.

    2012-01-01

    The NiII atom in the title complex, [Ni(C11H13N3OS)(C5H5N)], exists within a square-planar N3O donor set provided by N,N′,O atoms of the dianionic tridentate ligand and a pyridine N atom. The maximum deviation from the ideal geometry is seen in the N—Ni—N five-membered chelate bite angle of 83.28 (12)°. The pyridine mol­ecule forms a dihedral angle of 44.43 (6)° with the N3O donor set. Supra­molecular stacks along the a axis mediated by alternating π–π inter­actions between the pyridine and five- [centroid–centroid distance = 3.4784 (16) Å] and six-membered [3.4633 (17) Å] chelate rings, feature in the crystal packing. PMID:22807749

  19. Expression of the human growth hormone variant gene in cultured fibroblasts and transgenic mice

    SciTech Connect

    Selden, R.F.; Wagner, T.E.; Blethen, S.; Yun, J.S.; Rowe, M.E.; Goodman, H.M. )

    1988-11-01

    The nucleotide sequence of the human growth hormone variant gene, one of the five members of the growth hormone gene family, predicts that it encodes a growth hormone-like protein. As a first step in determining whether this gene is functional in humans, the authors have expressed a mouse methallothionein I/human growth hormone variant fusion gene in mouse L cells and in transgenic mice. The growth hormone variant protein expressed in transiently transfected L cells is distinct from growth hormone itself with respect to reactivity with anti-growth hormone monoclonal antibodies, behavior during column chromatography, and isoelectric point. Transgenic mice expressing the growth hormone variant protein are 1.4- to 1.9-fold larger than nontransgenic controls, suggesting that the protein has growth-promoting properties.

  20. 6,8-Dihy­droxy-8a-methyl-3,5-dimethyl­idenedeca­hydro­naphtho­[2,3-b]furan-2(3H)-one

    PubMed Central

    Liu, Ting-ting; Wu, Hai-Bo; Wang, Wen-Shu

    2012-01-01

    The title compound, C15H20O4, is a eudesmanolide isolated from the Chinese medicinal plant Carpesium tris­te Maxim. The mol­ecule contains three rings, viz. two fused six-membered rings in chair conformations and a five-membered ring in a flattened envelope conformation. In the crystal, two hy­droxy groups are involved in the formation of intra- and inter­molecular O—H⋯O hydrogen bonds. The H atoms in these groups are split, with site-occupation factors of 0.5. The inter­molecular hydrogen bonds link mol­ecules into chains propagating in [010]. PMID:23284548

  1. Cloning and identification of the human LPAAT-zeta gene, a novel member of the lysophosphatidic acid acyltransferase family.

    PubMed

    Li, Dan; Yu, Long; Wu, Hai; Shan, Yuxi; Guo, Jinhu; Dang, Yongjun; Wei, Youheng; Zhao, Shouyuan

    2003-01-01

    Lysophosphatidic acid (LPA) is a naturally occurring component of phospholipid and plays a critical role in the regulation of many physiological and pathophysiological processes including cell growth, survival, and pro-angiogenesis. LPA is converted to phosphatidic acid by the action of lysophosphatidic acid acyltransferase (LPAAT). Five members of the LPAAT gene family have been detected in humans to date. Here, we report the identification of a novel LPAAT member, which is designated as LPAAT-zeta. LPAAT-zeta was predicted to encode a protein consisting of 456 amino acid residues with a signal peptide sequence and the acyltransferase domain. Northern blot analysis showed that LPAAT-zeta was ubiquitously expressed in all 16 human tissues examined, with levels in the skeletal muscle, heart, and testis being relatively high and in the lung being relatively low. The human LPAAT-zeta gene consisted of 13 exons and is positioned at chromosome 8p11.21. PMID:12938015

  2. Hydrindacene-based acetylenic macrocycles with horizontally and vertically ordered functionality arrays.

    PubMed

    Kawai, Hidetoshi; Utamura, Tatsuya; Motoi, Erina; Takahashi, Tomoko; Sugino, Hiroyoshi; Tamura, Manabu; Ohkita, Masakazu; Fujiwara, Kenshu; Saito, Takao; Tsuji, Takashi; Suzuki, Takanori

    2013-04-01

    The macrocyclization of 2,6-diethynyl hydrindacenes (1) with functional groups at mutually perpendicular positions results in the formation of novel macrocycles which, as a result of the hindered rotation of the hydrindacene units, possess directionally persistent peripheral functionalities. The two hydrindacene units in the dimer macrocycle (2) have been shown to interact electronically through their respective butadiyne moieties, whereas the trimer macrocycle (3) demonstrates a moderate degree of geometrical flexibility as a result of the five-membered hydrindacene rings. In addition, these trimer macrocycles contain a central cavity suitably sized for the inclusion of various solvent molecules. These new macrocycles can be further modified by introducing π-conjugated side groups, such as styryl and thienyl groups, as well as by attaching a variety of peripheral ester groups. PMID:23401349

  3. A general access to organogold(iii) complexes by oxidative addition of diazonium salts.

    PubMed

    Huang, Long; Rominger, Frank; Rudolph, Matthias; Hashmi, A Stephen K

    2016-05-11

    At room temperature under mild photochemical conditions, namely irradiation with a simple blue light LED, gold(i) chloro complexes of both phosphane and carbene ligands in combination with aryldiazonium salts afford arylgold(iii) complexes. With chelating P,N-ligands cationic six- or five-membered chelate complexes were isolated in the form of salts with weakly coordinating counter anions that were brought in from the diazonium salt. With monodentate P ligands or N-heterocyclic carbene ligands and diazonium chlorides neutral arylgold(iii) dichloro complexes were obtained. The coordination geometry was determined by X-ray crystal structure analyses of representative compounds, a cis arrangement of the aryl and the phosphane ligand at the square planar gold(iii) center is observed. PMID:27094217

  4. Reduction Mechanism of Fluoroethylene Carbonate for Stable Solid–Electrolyte Interphase Film on Silicon Anode

    SciTech Connect

    Chen, Xilin; Li, Xiaolin; Mei, Donghai; Feng, Ju; Hu, Mary Y.; Hu, Jian Z.; Engelhard, Mark H.; Zheng, Jianming; Xu, Wu; Xiao, Jie; Liu, Jun; Zhang, Jiguang

    2014-02-01

    Fluoroethylene Carbonate (FEC) is an effective electrolyte additive which can significantly improve the cyclability of Si and other anode materials. However, the fundamental mechanism on this improvement is still not well understood. Based on the results obtained from 6Li Nuclear Magnetic Resonance and X-ray Photoelectron Scanning study, we propose a molecular level mechanism on how FEC affects the formation of solid electrolyte interphase (SEI) film: 1) FEC is reduced through the opening of the five member ring leading to the formation of lithium poly (vinyl carbonate), LiF and some dimmers; 2) The high tensile strength of the FEC-derived lithium poly (vinyl carbonate) enhances the stability of the SEI film. This mechanism has been verified by the results of electrochemical tests.

  5. Synthesis and structural investigation of internally coordinated alpha-amidoboronic acids.

    PubMed

    Lai, Jack H; Liu, Yuxin; Wu, Wengen; Zhou, Yuhong; Maw, Hlaing H; Bachovchin, William W; Bhat, Krishna L; Bock, Charles W

    2006-01-20

    [structure: see text] Six new N-acyl-boroGly derivatives, along with their N-acyl-boroSar analogues, have been synthesized by modification of conventional procedures. Structural characterization of these alpha-amidoboronic acids was accomplished by extensive use of 11B and 1H NMR spectroscopy. These compounds were prepared to determine the extent of intramolecular B-O dative bond formation within the context of a five-membered (:O=C-N-C-B) ring motif. It is shown that the formation of such dative bonds depends on the nature of the substituents at both the acyl carbon and the nitrogen atoms. Computational evidence from second-order Møller-Plesset perturbation theory is provided in support of these findings. PMID:16408958

  6. Arctic science input wanted

    NASA Astrophysics Data System (ADS)

    The Arctic Research and Policy Act (Eos, June 26, 1984, p. 412) was signed into law by President Ronald Reagan this past July. One of its objectives is to develop a 5-year research plan for the Arctic. A request for input to this plan is being issued this week to nearly 500 people in science, engineering, and industry.To promote Arctic research and to recommend research policy in the Arctic, the new law establishes a five-member Arctic Research Commission, to be appointed by the President, and establishes an Interagency Arctic Research Policy Committee, to be composed of representatives from nearly a dozen agencies having interests in the region. The commission will make policy recommendations, and the interagency committee will implement those recommendations. The National Science Foundation (NSF) has been designated as the lead agency of the interagency committee.

  7. Electron-Deficient Tetrabenzo-Fused Pyracylene and Conversions into Curved and Planar π-Systems Having Distinct Emission Behaviors.

    PubMed

    Chaolumen; Murata, Michihisa; Sugano, Yasunori; Wakamiya, Atsushi; Murata, Yasujiro

    2015-08-01

    Polycyclic aromatic compounds containing fully unsaturated five-membered ring(s) have been intensively studied because of their unique properties, which include high electron affinity and reactivity. Reported herein is an efficient route for the synthesis of tetrabenzo-fused pyracylene, which comprises pyracylene and tetracene segments, using intramolecular oxidative C-H coupling. It was shown to possess high electron affinity and was found to undergo addition reactions with n-butyllithium or benzyne. These reactions led to either a 1,4-addition compound or triptycene-type adduct with a curved or planar π-system, respectively. Although these compounds exhibited similar sky-blue emissions in a dilute solution, the emission band of the 1,4-addition compound was significantly red-shifted in the solid state and exhibited intense yellow emission attributable to the excimer, while the triptycene-type adduct retained the intense blue color emission in the solid state. PMID:26088048

  8. Chemical speciation and bioavailability of Cu(II). Study of the ionic copper(II) and bis(glycinate)-copper(II) accumulation by Lemna species

    SciTech Connect

    Benda, F.; Kouba, J. )

    1991-03-01

    In this paper, the authors examined the accumulation of copper(II) in, and its toxic effect on, duckweed, a plant which exhibits extremely high concentration factors. The effect of copper(II) was investigated by adding it to the minimal medium in two forms: CuSO{sub 4} and (Cu(Gly){sub 2}). The neutral (2:1) tetracoordinated bis(glycinate)-copper(II) complex is constituted by two five-membered rings bonded to the central copper atom with the cis configuration. This complex was chosen to model the function of a neutral species (eliminating the charge effect) involving a nontoxic ligand, for which - in contrast to the hydrated Cu{sup 2+} species - direct permeation through the cell wall is conceivable.

  9. The first stable lower fullerene: C36

    NASA Astrophysics Data System (ADS)

    Piskoti, C.; Zettl, A.

    1998-08-01

    A new pure carbon material, presumably composed of thirty six carbon atom molecules, has been synthesized and isolated in milligram quantities. It appears as though these molecules have a closed cage structure making them the smallest member of a new class of molecules known as fullerenes, most notably of which is the soccer ball shaped C60. However, unlike other known fullerenes, any closed, fullerene-like C36 cage will necessarily contain fused pentagon rings. Therefore, this molecule apparently violates the isolated pentagon rule, a criterion which requires isolated pentagons for stability in fullerene molecules. Striking parallels between this problem and the synthesis of other fused five member fused ring systems will be discussed. Also, it will be shown that certain biological structures known as clathrin behave in a manner which gives excellent predictions about fullerenes and nanotubes. These predictions help to explain the presence of abundant quantities of C36 in arced graphite soot.

  10. A Cucurbituril Derivative That Exhibits Cation-Modulated Self-Assembly.

    PubMed

    Ustrnul, Lukas; Babiak, Michal; Kulhanek, Petr; Sindelar, Vladimir

    2016-07-15

    Cucurbiturils are the most potent artificial receptors known for many organic molecules in water. However, little is known about their supramolecular chemistry in organic solvents. Here we present a new cucurbituril derivative, 1, and investigate its supramolecular properties in methanol. The macrocycle resembles a five-membered cucurbituril in which four glycoluril units are replaced with propanediurea. Macrocycle 1 can bind to one cation such as potassium or anilinium via each of its opposed portals. The stability of these complexes in methanol at nanomolar concentrations exceeds that of complexes between metal cations and crown ethers. Moreover, macrocycle 1 forms a self-assembled tetrameric aggregate in the solid state and in methanol. The tetramer is stabilized by the addition of up to 1 equiv of a cation but is fully disassembled in the presence of 2 equiv of the cation. Cations can thus be used to tune the aggregation of 1 in solution. PMID:27308961

  11. Atomic Structure of Graphene Subnanometer Pores.

    PubMed

    Robertson, Alex W; Lee, Gun-Do; He, Kuang; Gong, Chuncheng; Chen, Qu; Yoon, Euijoon; Kirkland, Angus I; Warner, Jamie H

    2015-12-22

    The atomic structure of subnanometer pores in graphene, of interest due to graphene's potential as a desalination and gas filtration membrane, is demonstrated by atomic resolution aberration corrected transmission electron microscopy. High temperatures of 500 °C and over are used to prevent self-healing of the pores, permitting the successful imaging of open pore geometries consisting of between -4 to -13 atoms, all exhibiting subnanometer diameters. Picometer resolution bond length measurements are used to confirm reconstruction of five-membered ring projections that often decorate the pore perimeter, knowledge which is used to explore the viability of completely self-passivated subnanometer pore structures; bonding configurations where the pore would not require external passivation by, for example, hydrogen to be chemically inert. PMID:26524121

  12. Conformational studies of DL-lactaldehyde by 1H-NMR, Raman and i.r. spectroscopy

    NASA Astrophysics Data System (ADS)

    Takahashi, Hiroaki; Kobayashi, Yoko; Kaneko, Norio

    1H-NMR, Raman and i.r. spectra of DL-lactaldehyde reveal that this compound crystallizes in three different crystal forms. All of them consist of hemiacetal dimers having the same 1,4-dioxane ring skeleton but with different configurations (e,e), (e,a) and (a,a) with respect to the two OH groups attached to the ring (e and a denote equatorial and axial, respectively). In addition to these three species, the monomer and at least one five-membered ring dimer, though both in negligibly small amount, exist in equilibrium solution. The most easily obtainable species in the crystalline state has the centrosymmetric configuration (a,a) which is least populated in solution. The existence of the crystal form which consists of non-centrosymmetric dimers having the (e,a) configuration is in contrast to simple carbohydrates such as glycolaldehyde, glyceraldehyde and 1,3-dihydroxyacetone which crystallize only as centrosymmetric dimers.

  13. Crystal structure of 5''-(4-chloro-benzyl-idene)-4'-(4-chloro-phen-yl)-1'-methyltri-spiro[acenapthylene-1,2'-pyrrolidine-3',1''-cyclo-hexane-3'',2'''-[1,3]dioxane]-2(1H),6''-dione.

    PubMed

    Chandralekha, Kuppan; Gavaskar, Deivasigamani; Sureshbabu, Adukamparai Rajukrishnan; Lakshmi, Srinivasakannan

    2015-11-01

    In the title compound, C36H29Cl2NO4, two spiro links connect the methyl-substituted pyrrolidine ring to the ace-naphthyl-ene and cyclo-hexa-none rings. The cyclo-hexa-none ring is further connected to the dioxalane ring by a third spiro junction. The five-membered ring of the ace-naphthylen-1-one ring system adopts a flattened envelope conformation, with the ketonic C atom as the flap, whereas the dioxalane and pyrrolidine rings each have a twist conformation. The cyclo-hexenone ring assumes a boat conformation. An intra-molecular C-H⋯O hydrogen-bond inter-action is present. In the crystal, mol-ecules are linked by non-classical C-H⋯O hydrogen bonds, forming chains extending parallel to the a axis. PMID:26594541

  14. Crystal structure of 5′′-(4-chloro­benzyl­idene)-4′-(4-chloro­phen­yl)-1′-methyltri­spiro[acenapthylene-1,2′-pyrrolidine-3′,1′′-cyclo­hexane-3′′,2′′′-[1,3]dioxane]-2(1H),6′′-dione

    PubMed Central

    Chandralekha, Kuppan; Gavaskar, Deivasigamani; Sureshbabu, Adukamparai Rajukrishnan; Lakshmi, Srinivasakannan

    2015-01-01

    In the title compound, C36H29Cl2NO4, two spiro links connect the methyl-substituted pyrrolidine ring to the ace­naphthyl­ene and cyclo­hexa­none rings. The cyclo­hexa­none ring is further connected to the dioxalane ring by a third spiro junction. The five-membered ring of the ace­naphthylen-1-one ring system adopts a flattened envelope conformation, with the ketonic C atom as the flap, whereas the dioxalane and pyrrolidine rings each have a twist conformation. The cyclo­hexenone ring assumes a boat conformation. An intra­molecular C—H⋯O hydrogen-bond inter­action is present. In the crystal, mol­ecules are linked by non-classical C—H⋯O hydrogen bonds, forming chains extending parallel to the a axis. PMID:26594541

  15. Crystal structure of 5''-benzyl-idene-1'-methyl-4'-phenyl-tri-spiro-[ace-naphthyl-ene-1,2'-pyrrolidine-3',1''-cyclo-hexane-3'',2'''-[1,3]dioxane]-2,6''-dione.

    PubMed

    Chandralekha, Kuppan; Gavaskar, Deivasigamani; Sureshbabu, Adukamparai Rajukrishnan; Lakshmi, Srinivasakannan

    2016-03-01

    In the title compound, C36H31NO4, two spiro links connect the methyl-substituted pyrrolidine ring to the ace-naphthyl-ene and cyclo-hexa-none rings. The cyclo-hexa-none ring is further connected to the dioxalane ring by a third spiro junction. The five-membered ring of the ace-naphthylen-1-one ring system adopts a flattened envelope conformation with the ketonic C atom as flap, whereas the dioxalane and pyrrolidine rings each have a twist conformation. The cyclo-hexa-none ring assumes a boat conformation. Three intra-molecular C-H⋯O hydrogen bonds involving both ketonic O atoms as acceptors are present. In the crystal, C-H⋯O hydrogen bonds connect centrosymmetrically related mol-ecule into chains parallel to the b axis, forming rings of R 2 (2)(10)and R 2 (2)(8) graph-set motifs. PMID:27006814

  16. Crystal structure of (+)-N-[(1R,5S,6S,9S)-5-hydroxy-methyl-3,3,9-trimethyl-8-oxo-2,4,7-trioxabi-cyclo-[4.3.0]nonan-9-yl]acetamide.

    PubMed

    Oishi, Takeshi; Tsuzaki, Shun; Sugai, Tomoya; Sato, Takaaki; Chida, Noritaka

    2016-05-01

    In the title compound, C12H19NO6, the six-membered 1,3-dioxane ring adopts a chair-like conformation. The seat of this chair, containing two O atoms, is essentially planar, with a maximum deviation of 0.0021 (12) Å. The five-membered oxolane ring cis-fused to the 1,3-dioxane ring adopts an envelope form. The bridgehead C atom at the flap, which is bonded to the tetra-substituted C atom of the oxolane ring, deviates from the mean plane of other ring atoms by 0.539 (4) Å. In the crystal, classical O-H⋯O and N-H⋯O hydrogen bonds link the mol-ecules into a sheet structure enclosing an R 4 (4)(24) graph-set motif. Weak inter-molecular C-H⋯O inter-actions support the sheet formation. PMID:27308035

  17. (E)-17β,19-Epoxy-methano-17,23,24-tridemethyl-4-nor-5β,18α-olean-3-one oxime.

    PubMed

    Froelich, Anna; Kazakova, Oxana B; Tolstikov, Genrikh; Gzella, Andrzej K

    2009-01-01

    In the penta-cyclic triterpenoide skeleton of the title mol-ecule, C(27)H(43)NO(2) [systematic name: (3E,3aS,5aR,5bR,7aR,11R,11aR,11bR,13aR,13bR)-5a,5b,10,10,13b-penta-methyl-icosa-hydro-1H-11,7a-(epoxy-methano)cyclo-penta-[a]chrysen-3-one oxime], the five-membered ring A has an envelope conformation, while the six-membered rings B-E adopt chair conformations. Rings A and B are cis-fused. The hydroximino group has an E configuration. Strong inter-molecular O-H⋯O hydrogen bonds link the mol-ecules into helical chains. PMID:21583127

  18. (E)-17β,19-Epoxy­methano-17,23,24-tridemethyl-4-nor-5β,18α-olean-3-one oxime

    PubMed Central

    Froelich, Anna; Kazakova, Oxana B.; Tolstikov, Genrikh; Gzella, Andrzej K.

    2009-01-01

    In the penta­cyclic triterpenoide skeleton of the title mol­ecule, C27H43NO2 [systematic name: (3E,3aS,5aR,5bR,7aR,11R,11aR,11bR,13aR,13bR)-5a,5b,10,10,13b-penta­methyl­icosa­hydro-1H-11,7a-(epoxy­methano)cyclo­penta­[a]chrysen-3-one oxime], the five-membered ring A has an envelope conformation, while the six-membered rings B–E adopt chair conformations. Rings A and B are cis-fused. The hydroximino group has an E configuration. Strong inter­molecular O—H⋯O hydrogen bonds link the mol­ecules into helical chains. PMID:21583127

  19. Synthesis of Thienamycin methyl ester from 2-deoxy-D-ribose via Kinugasa reaction.

    PubMed

    Soluch, Magdalena; Grzeszczyk, Barbara; Staszewska-Krajewska, Olga; Chmielewski, Marek; Furman, Bartłomiej

    2016-03-01

    A novel synthesis of thienamycin is described. The crucial step of the synthesis is based on Cu(I)-mediated Kinugasa cycloaddition/rearrangement cascade reaction between terminal acetylene derived from D-lactic acid and suitable, partially protected, five-membered cyclic nitrone obtained from 2-deoxy-D-ribose. The reaction was performed in the presence of tetramethylguanidine as a base to provide 5,6-trans substituted carbapenam as the main product. Thus obtained carbapenam 11 with (5R,6S) configuration at the azetidinone ring was subsequently subjected to oxidation/deprotection/oxidation reaction sequence to afford the β-keto ester 20, which was directly transformed into N,O-protected methyl ester of thienamycin. PMID:26506859

  20. Crystal structure of 2-(1,3-dioxoindan-2-yl)iso­quinoline-1,3,4-trione

    PubMed Central

    Ghalib, Raza Murad; Chidan Kumar, C. S.; Hashim, Rokiah; Sulaiman, Othman; Fun, Hoong-Kun

    2015-01-01

    In the title iso­quinoline-1,3,4-trione derivative, C18H9NO5, the five-membered ring of the indane fragment adopts an envelope conformation with the nitro­gen-substituted C atom being the flap. The planes of the indane benzene ring and the iso­quinoline-1,3,4-trione ring make a dihedral angle of 82.06 (6)°. In the crystal, mol­ecules are linked into chains extending along the bc plane via C—H⋯O hydrogen-bonding inter­actions, enclosing R 2 2(8) and R 2 2(10) loops. The chains are further connected by π–π stacking inter­ations, with centroid-to-centroid distances of 3.9050 (7) Å, forming layers parallel to the b axis. PMID:25705509

  1. Design, Synthesis and Evaluation of Dibenzo[c,h][1,6]naphthyridines as Topoisomerase I Inhibitors and Potential Anticancer Agents

    PubMed Central

    Kiselev, Evgeny; Dexheimer, Thomas; Pommier, Yves; Cushman, Mark

    2010-01-01

    Indenoisoquinoline topoisomerase I (Top1) inhibitors are a novel class of anticancer agents. Modifications of the indenoisoquinoline A, B and D rings have been extensively studied in order to optimize Top1 inhibitory activity and cytotoxicity. To improve understanding of the forces that stabilize drug-Top1-DNA ternary complexes, the five-membered cyclopentadienone C-ring of the indenoisoquinoline system was replaced by six-membered nitrogen heterocyclic rings, resulting in dibenzo[c,h][1,6]naphthyridines that were synthesized by a novel route and tested for Top1 inhibition. This resulted in several compounds that have unique DNA cleavage site selectivities and potent antitumor activities in a number of cancer cell lines. PMID:21090809

  2. Rhodnius barretti, a new species of Triatominae (Hemiptera: Reduviidae) from western Amazonia

    PubMed Central

    Abad-Franch, Fernando; Pavan, Márcio G; Jaramillo-O, Nicolás; Palomeque, Francisco S; Dale, Carolina; Chaverra, Duverney; Monteiro, Fernando A

    2013-01-01

    Rhodnius barretti , a new triatomine species, is described based on adult specimens collected in rainforest environments within the Napo ecoregion of western Amazonia (Colombia and Ecuador). R. barretti resembles Rhodnius robustus s.l. , but mitochondrial cytochrome b gene sequences reveal that it is a strongly divergent member of the “robustus lineage”, i.e., basal to the clade encompassing Rhodnius nasutus , Rhodnius neglectus , Rhodnius prolixus and five members of the R. robustus species complex. Morphometric analyses also reveal consistent divergence from R. robustus s.l. , including head and, as previously shown, wing shape and the length ratios of some anatomical structures. R. barretti occurs, often at high densities, in Attalea butyracea and Oenocarpus bataua palms. It is strikingly aggressive and adults may invade houses flying from peridomestic palms. R. barretti must therefore be regarded as a potential Trypanosoma cruzi vector in the Napo ecoregion, where Chagas disease is endemic. PMID:24473808

  3. STS-26 Preflight Press Briefing: Crew Escape/Crew Equipment. Part 4 of 9

    NASA Technical Reports Server (NTRS)

    1988-01-01

    This NASA KSC video release presents part of a press conference held prior to Discovery flight STS-26, the first shuttle mission flown following the 51-L Challenger accident. The five member panel present individual viewgraph discussions followed by a question and answer period for the benefit of scientific journalists. William A. Chandler (Asst. to the Dir. of Engineering and the NSTS program) gives a brief overview of the crew escape system followed by Steven Nagel's (Astronaut) presentation on crew equipment. Robert Rice (Crew Escape System Manager) describes the flight test program and the innovative pyrotechnics system test program. Tim Pelischek (Pole Design Team) gives an assessment of the critical design review and Ricardo Machin reviews aerodynamic flight tests performed at Texas A&M and California. The second part of the video includes Robert Crippen's (Deputy Dir. of Operations, Kennedy Space Center) overview of NASA Management, the organizational changes and actions taken to meet the Roger's Commission recommendations.

  4. Hypochlorous acid reacts with the N-terminal methionines of proteins to give dehydromethionine, a potential biomarker for neutrophil-induced oxidative stress.

    PubMed

    Beal, Jennifer L; Foster, Steven B; Ashby, Michael T

    2009-11-24

    Electrophilic halogenating agents, including hypohalous acids and haloamines, oxidize free methionine and the N-terminal methionines of peptides and proteins (e.g., Met-1 of anti-inflammatory peptide 1 and ubiquitin) to produce dehydromethionine (a five-membered isothiazolidinium heterocycle). Amide derivatives of methionine are oxidized to the corresponding sulfoxide derivatives under the same reaction conditions (e.g., Met-3 of anti-inflammatory peptide 1). Other biological oxidants, including hydrogen peroxide and peroxynitrite, also produce only the corresponding sulfoxides. Hypothiocyanite does not react with methionine residues. We suggest that dehydromethionine may be a useful biomarker for the myeloperoxidase-induced oxidative stress associated with many inflammatory diseases. PMID:19839600

  5. Pre-Study Walkthrough with a Commercial Pilot for a Preliminary Single Pilot Operations Experiment

    NASA Technical Reports Server (NTRS)

    O'Connor-Dreher, Ryan; Roberts, Z.; Ziccardi, J.; Vu, K-P. L.; Strybel, T.; Koteskey, Robert William; Lachter, Joel B.; Vi Dao, Quang; Johnson, Walter W.; Battiste, V.

    2013-01-01

    The number of crew members in commercial flights has decreased to two members, down from the five-member crew required 50 years ago. One question of interest is whether the crew should be reduced to one pilot. In order to determine the critical factors involved in safely transitioning to a single pilot, research must examine whether any performance deficits arise with the loss of a crew member. With a concrete understanding of the cognitive and behavioral role of a co-pilot, aeronautical technologies and procedures can be developed that make up for the removal of the second aircrew member. The current project describes a pre-study walkthrough process that can be used to help in the development of scenarios for testing future concepts and technologies for single pilot operations. Qualitative information regarding the tasks performed by the pilots can be extracted with this technique and adapted for future investigations of single pilot operations.

  6. Skill improvement of dynamical seasonal Arctic sea ice forecasts

    NASA Astrophysics Data System (ADS)

    Krikken, Folmer; Schmeits, Maurice; Vlot, Willem; Guemas, Virginie; Hazeleger, Wilco

    2016-05-01

    We explore the error and improve the skill of the outcome from dynamical seasonal Arctic sea ice reforecasts using different bias correction and ensemble calibration methods. These reforecasts consist of a five-member ensemble from 1979 to 2012 using the general circulation model EC-Earth. The raw model reforecasts show large biases in Arctic sea ice area, mainly due to a differently simulated seasonal cycle and long term trend compared to observations. This translates very quickly (1-3 months) into large biases. We find that (heteroscedastic) extended logistic regressions are viable ensemble calibration methods, as the forecast skill is improved compared to standard bias correction methods. Analysis of regional skill of Arctic sea ice shows that the Northeast Passage and the Kara and Barents Sea are most predictable. These results show the importance of reducing model error and the potential for ensemble calibration in improving skill of seasonal forecasts of Arctic sea ice.

  7. Exome sequencing identified new mutations in a Marfan syndrome family

    PubMed Central

    2014-01-01

    Marfan syndrome is a common autosomal dominant hereditary connective tissue disorder. There is no cure for Marfan syndrome currently. Next-generation sequencing (NGS) technology is efficient to identify genetic lesions at the exome level. Here we carried out exome sequencing of two Marfan syndrome patients. Further Sanger sequencing validation in other five members from the same family was also implemented to confirm new variants which may contribute to the pathogenesis of the disease. Two new variants, including one nonsense SNP in the Marfan syndrome gene FBN1 and one missense mutation in exon 15 of LRP1, which may be related to the phenotype of the patients were identified. The exome sequencing analysis provides us a new insight into the molecular events governing pathogenesis of Marfan syndrome. Virtual slide http://www.diagnosticpathology.diagnomx.eu/vs/1229110069114125. PMID:24484584

  8. Crystal structure of ethyl N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-di­hydro-1H-pyrazol-4-yl)carbamate

    PubMed Central

    Danish, Muhammad; Tahir, Muhammad Nawaz; Anwar, Uzma; Raza, Muhammad Asam

    2015-01-01

    In the title compound, C14H17N3O3, the dihedral angle between the benzene ring and the five-membered di­hydro­pyrazole ring is 52.26 (9)°. The ethyl ester group is approximately planar (r.m.s. deviation 0.0568 Å) and subtends an angle 67.73 (8)° to the pyrazole ring. In the crystal, molecules are linked by pairs of N—H⋯O hydrogen bonds, forming inversion dimers with an R 2 2(10) ring motif. Weaker C—H⋯O contacts link these dimers into a three-dimensional network of mol­ecules stacked along the a-axis direction. Offset π–π stacking inter­actions between the benzene rings [centroid-to-centroid distance = 3.8832 (12) Å] further stabilize the crystal packing. PMID:26029449

  9. Crystal structure of sepaconitine, a C19-diterpenoid alkaloid from the roots of Aconitum sinomontanum Nakai

    PubMed Central

    Shi, Xin-Wei; Lu, Qiang-Qiang; Zhou, Jun-Hui; Cui, Xin-Ai

    2015-01-01

    The title compound [systematic name: [(1α,14α,16β)-20-ethyl-8,9,10-trihy­droxy-1,14,16-tri­meth­oxy­aconitan-4-yl 2-amino­benzoate], C30H42N2O8, a natural C19-diterpenoid alkaloid, possesses an aconitane carbon skeleton with four six-membered rings and two five-membered rings. The fused ring system contains two chair, one boat, one twist-boat and two envelope conformations. Intra­molecular N—H⋯O hydrogen bonds are observed between the amino and carbonyl groups. The mol­ecules are linked together via O—H⋯O hydrogen bonds, forming a three-dimensional framework. PMID:26396791

  10. Activation of protein kinase Ceta triggers cortical granule exocytosis in Xenopus oocytes.

    PubMed

    Gundersen, Cameron B; Kohan, Sirus A; Chen, Qian; Iagnemma, Joseph; Umbach, Joy A

    2002-03-15

    Previous work has shown that phorbol esters or diacylglycerol trigger cortical granule exocytosis in Xenopus oocytes. We sought to identify the isoform(s) of protein kinase C (PKC) that mediate(s) this regulated secretory event. Because this process is initiated by lipid activators of PKC but is independent of calcium ions, we focused on the family of novel (calcium-independent) PKCs. Pharmacological investigations using Gö6976 and Gö6983 tended to exclude PKCdelta, epsilon and mu as secretory triggers. Subcellular fractionation and immunoblot data revealed that these oocytes expressed all five members of the novel PKC family, but it was only PKCeta that colocalized with cortical granules. Finally, expression of wild type or constitutively active forms of PKCdelta and eta strongly supported the conclusion that it is PKCeta that initiates cortical granule exocytosis in these cells. These observations represent an important step in identifying the mechanism of secretory triggering in this system. PMID:11884530

  11. Coordination Chemistry of Disilylated Germylenes with Group 4 Metallocenes

    PubMed Central

    2013-01-01

    Reaction of the PEt3 adduct of a disilylated five-membered cyclic germylene with group 4 metallocene dichlorides in the presence of magnesium led to the formation of the respective germylene metallocene phosphine complexes of titanium, zirconium, and hafnium. Attempts to react the related NHC adduct of a disilylated four-membered cyclic germylene under the same conditions with Cp2TiCl2 did not give the expected germylene NHC titanocene complex. This complex was, however, obtained in the reaction of Cp2Ti(btmsa) with the NHC germylene adduct. A computational analysis of the structure of the group 4 metallocene germylene complexes revealed the multiple-bond character of the M–Ge(II) linkage, which can be rationalized with the classical σ-donor/π-acceptor interaction. The strength of the M–Ge(II) bond increases descending group 4. PMID:23874053

  12. STS-70 Mission Commander Henricks inspects tire

    NASA Technical Reports Server (NTRS)

    1995-01-01

    STS-70 Mission Commander Terence 'Tom' Henricks inspects the nose wheel landing gear tires of the Space Shuttle Orbiter Discovery along with Mission Specialist Mary Ellen Weber after the spaceplane touched down on KSC's Runway 33 to successfully conclude the nearly nine-day space flight. Main gear touchdown was unofficially listed at 8:02 a.m. EDT on July 22, 1995 on the second landing attempt after the first opportunity was waved off. The orbiter was originally scheduled to land on the 21st, but fog and low visibility at the Shuttle Landing Facility led to the one-day extension. This was the 24th landing at KSC and the 70th Space Shuttle mission. During the space flight, the five-member crew deployed the NASA Tracking and Data Relay Satellite-G (TDRS- G). The other crew members were Pilot Kevin R. Kregel and Mission Specialists Nancy Jane Currie and Donald A. Thomas.

  13. Photoelectron spectroscopic and computational study of the PtMgH3,5(-) cluster anions.

    PubMed

    Zhang, Xinxing; Ganteför, Gerd; Alexandrova, Anastassia N; Bowen, Kit

    2016-07-28

    The two cluster anions, PtMgH3(-) and PtMgH5(-), were studied by photoelectron spectroscopy and theoretical calculations. Experimentally-determined electron affinity (EA) and vertical detachment energy (VDE) values were compared with those predicted by our computations; excellent agreement was found. The calculated structures of PtMgH3(-) and PtMgH3 both exhibit η2-bonded H2 moieties. Activation of these H2 moieties is implied by the elongation of their bond lengths relative to the bond length of free H2. The calculated structures of PtMgH5(-) and PtMgH5 both exhibit all-hydrogen, five-member, σ-aromatic rings. These attributes are responsible for this anion's special stability. PMID:27373793

  14. Structures and the Hydrogen Bonding Abilities of Estrogens Studied by Supersonic Jet/laser Spectroscopy

    NASA Astrophysics Data System (ADS)

    Morishima, Fumiya; Inokuchi, Yoshiya; Ebata, Takayuki

    2013-06-01

    Estrone, estradiol, estriol are known as endogenous estrogen which have the same steroidal frame with different substituent, leading to difference of physiological activity upon the formation of hydrogen bond with estrogen receptor. In the present study, structures of estrogens and their hydrated clusters in a supersonic jet have been studied by various laser spectroscopic techniques and density functional theory calculation to study how the difference of substituents affects their hydrogen bonding ability. Infrared spectra in the OH stretching region indicate a formation of intramolecular hydrogen-bond in estriol, which may lead to weaker physiological activity among the three estrogens. We also measured electronic and infrared spectra of 1:1 hydrated clusters of estrogen. The results show a switch of stable hydration site from the phenolic OH group to the five member ring by substituting one more OH group.

  15. DFT STUDY OF HYDROGEN STORAGE ON Li- AND Na-DOPED C59B HETEROFULLERENE

    NASA Astrophysics Data System (ADS)

    Zahedi, Ehsan; Mozaffari, Majid

    2014-05-01

    Effect of light alkali metal (Li and Na) decorated on the C59B heterofullerene for hydrogen storage is considered using DFT-MPW1PW91 method. Results show that Li and Na atoms strongly prefer to adsorb on top of five-member and six-member ring where a carbon atom is replaced by a boron atom. Significant charge transfer from the alkali metal to the C59B compensates for the electron deficiency of C59B and makes the latter aromatic in nature. Corrected binding energies of hydrogen molecule on the alkali-doped C59B using counterpoise method, structural properties and NBO analysis indicate that first hydrogen molecule is adsorbed physically and does not support minimal conditions of DOE requirement. Finally, positive values of binding energies for the adsorption of a second hydrogen molecule show that alkali doped C59B are capable of storing a maximum of one hydrogen molecule.

  16. [Acidites et complexes des acides (alkyl-et aminoalkyl-) phosphoniques--III Alkylphosphonates substitues de calcium(II) et cuivre(II)].

    PubMed

    Wozniak, M; Nowogrocki, G

    1979-05-01

    The stability constants of some phosphoric acids RPO(3)H(2) [R = CH(3), C(2)H(5), ClCH(2), Cl(2)CH, Cl(3)C, BrCH(2), Br(2)CH, BrCH(2)CH(2), ICH(2), HOCH(2), (CH(3))(3)N + CH2] and their complexes RPO(3)Ca, RPO(3)Cu, RPO(3)Cu(OH)(-) have been determined by multiparametric refinement of potentiometric titration data obtained at 25 degrees , in a 0.1M potassium nitrate medium. Linear relationships are obtained between stability and acidity constants. Formation of five-membered rings stabilize the hydroxymethylphosphonates. Conversely, cation repulsion by the permanent positive charge reduces the stabilities of complexes with trimethylammoniummethylphosphonic acid. PMID:18962453

  17. Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP.

    PubMed

    Maita, Nobuo; Okada, Kengo; Hatakeyama, Kazuyuki; Hakoshima, Toshio

    2002-02-01

    In the presence of phenylalanine, GTP cyclohydrolase I feedback regulatory protein (GFRP) forms a stimulatory 360-kDa complex with GTP cyclohydrolase I (GTPCHI), which is the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin. The crystal structure of the stimulatory complex reveals that the GTPCHI decamer is sandwiched by two GFRP homopentamers. Each GFRP pentamer forms a symmetrical five-membered ring similar to beta-propeller. Five phenylalanine molecules are buried inside each interface between GFRP and GTPCHI, thus enhancing the binding of these proteins. The complex structure suggests that phenylalanine-induced GTPCHI x GFRP complex formation enhances GTPCHI activity by locking the enzyme in the active state. PMID:11818540

  18. Insights into the cycloaddition reaction mechanism between ketenimine and unsaturated hydrocarbon: A theoretical study

    NASA Astrophysics Data System (ADS)

    He, Wenxing; Zhang, Hong; Wang, Nana; Tan, Xiaojun; Wang, Weihua; Li, Ping

    2016-05-01

    The cycloaddition reaction mechanisms between interstellar molecule ketenimine and unsaturated hydrocarbon (ethyne and ethylene) have been systematically investigated employing the second-order Møller-Plesset perturbation theory (MP2) method. Geometry optimizations and vibrational analyses have been performed for the stationary points on the potential energy surfaces of the system. The calculated results show that it can be produced the five-membered cyclic carbene intermediates through pericyclic reaction processes between ketenimine and ethyne (or ethylene). For the reaction between ketenimine and ethyne, through the following H-transferred processes, carbene intermediate can be isomerized to the pyrrole compounds. For the reaction between ketenimine and ethylene, carbene intermediate can be isomerized to the pyrroline compounds. The present study is helpful to understand the reactivity of nitrogenous cumulene ketenimine and the formation of prebiotic species in interstellar space.

  19. X-ray, conformation and electronic structures of 1-nitropyrrolidine

    NASA Astrophysics Data System (ADS)

    Gajda, Katarzyna; Ejsmont, Krzysztof; Daszkiewicz, Zdzisław; Gianopoulos, Christopher G.; Zarychta, Bartosz

    2016-03-01

    The chemistry of pyrrolidine compounds has drawn much attention because of their biological activities. The crystal and molecular structure of 1-nitropyrrolidine (C4H8NNO2) at 150K, along with calculated structures (DFT and MP2), are reported herein. In the solid-state, the asymmetric part of the unit cell is composed of one quartermolecule at the position of two perpendicular mirror planes and the five-membered ring is disordered over a mirror plane, revealing the twisted conformation. Both geometries suggest slight sp3 hybridization of the amine nitrogen atom. The non-planar geometry suggests the lack of conjugation of the amine nitrogen lone pair with the nitro group, however the N-N bond distance indicates oppositely.

  20. 3-(2-Amino-1,3-thia­zol-4-yl)-6-bromo-2H-chromen-2-one

    PubMed Central

    Chopra, Deepak; Choudhury, A. R.; Venugopala, K. N.; Govender, Thavendran; Kruger, Hendrik G.; Maguire, Glenn E. M.; Guru Row, T. N.

    2009-01-01

    The mol­ecule of the title compound, C12H7BrN2O2S, is essentially planar with a maximum deviation of 0.234 (3) Å from the mean plane through all non-H atoms. The dihedral angle between the coumarin ring plane and that of the five-membered thia­zole ring is 12.9 (1)°. In the crystal, strong N—H⋯O, N—H⋯N and weak but highly directional C—H⋯O hydrogen bonds provide the links between the mol­ecules. In addition, C—H⋯π and π–π inter­actions [centroid–centroid distances = 3.950 (3)–4.024 (3) Å] provide additional stability to the inter­layer regions in the lattice. PMID:21578780

  1. Cyclic Amine/Borane Lewis Pairs by the Reaction of N,N-Diallylaniline with Lancaster's H2 B-C6 F5 Reagent.

    PubMed

    Wang, Tongdao; Liu, Lei; Grimme, Stefan; Daniliuc, Constantin G; Kehr, Gerald; Erker, Gerhard

    2016-05-01

    Twofold hydroboration of N,N-diallylaniline with the C6 F5 BH2 ⋅SMe2 reagent gave the respective hetero-bicyclo[3.3.0]octane and hetero-methylbicyclo[3.2.0]heptane compounds 4 and 5 as the major products, both showing strong internal N-B amine Lewis base/borane Lewis acid adduct formation. A DFT analysis indicated their formation (and that of a small amount of several isomeric five-membered heterocyclic products) under thermodynamic control. Compound 5 underwent fragmentation with propene liberation to form compound 7 with a formal N=B bond at 100 °C. This product was also obtained from the isomer 4 at much higher temperature (300 °C). PMID:27010508

  2. New Approaches to Edge-Doping Graphene Nanoribbons

    NASA Astrophysics Data System (ADS)

    Rizzo, Daniel J.; Marangoni, Tomas; Cao, Ting; Nguyen, Giang D.; Tsai, Hsin-Zon; Omrani, Arash A.; Bronner, Christopher; Joshi, Trinity; Rodgers, Griffin F.; Choi, Won-Woo; Cloke, Ryan R.; Louie, Steven G.; Fischer, Felix R.; Crommie, Michael F.; Crommie Team; Fischer Team; Louie Team

    Graphene nanoribbons (GNRs) are narrow semiconducting strips of graphene that exhibit novel electronic and magnetic properties. New bottom-up fabrication techniques enable atomic-scale precision in GNR synthesis. The use of these techniques to reliably tune the position and size of GNR band gaps is an important challenge that also has relevance for the question of whether GNRs are viable for future nanotechnologies. We have used scanning tunneling microscopy (STM) and scanning tunneling spectroscopy (STS) to investigate how the geometry of heteroatom incorporation alters the electronic structure of bottom-up fabricated chevron-type GNRs. We find that the addition of nitrogen into the GNR edge via a five-membered ring yields a reduced band gap compared to the behavior of pristine, undoped chevron GNRs. Performed STM, STS, and nc-AFM measurements.

  3. U.S. Lab module given name in ceremony

    NASA Technical Reports Server (NTRS)

    1998-01-01

    In the Space Station Processing Facility, Center Director Roy Bridges (left), , Program Manager of the International Space Station (ISS) Randy Brinkley (second from left) and (right) STS- 98 Commander Ken Cockrell applaud the unveiling of the name Destiny given the U.S. Lab module. The lab, which is behind them on a workstand, is scheduled to be launched on Space Shuttle Endeavour in early 2000. It will become the centerpiece of scientific research on the ISS. Cockrell is part of the five- member crew expected to be aboard. The Shuttle will spend six days docked to the station while the laboratory is attached and three space walks are conducted to complete its assembly. The laboratory will be launched with five equipment racks aboard, which will provide essential functions for station systems, including high data-rate communications, and maintain the station's orientation using control gyroscopes launched earlier. Additional equipment and research racks will be installed in the laboratory on subsequent Shuttle flights.

  4. U.S. Lab module given name in ceremony

    NASA Technical Reports Server (NTRS)

    1998-01-01

    In the Space Station Processing Facility, STS-98 crew members Pilot Mark Polansky, Mission Specialist Marsha Ivins and Commander Ken Cockrell pose underneath the banner revealing the name Destiny given to the U.S. Lab module. They are part of the five-member crew scheduled to carry the lab into space aboard Space Shuttle Endeavour early in the year 2000 where it will become the centerpiece of scientific research on the International Space Station. The Shuttle will spend six days docked to the station while the laboratory is attached and three space walks are conducted to complete its assembly. The laboratory will be launched with five equipment racks aboard, which will provide essential functions for station systems, including high data-rate communications, and maintain the station's orientation using control gyroscopes launched earlier. Additional equipment and research racks will be installed in the laboratory on subsequent Shuttle flights.

  5. (1'S,12'R,13'S,17'S)-15',15'-Dimethyl-1,2-dihydro-11',14',16',18'-tetra-oxa-7'-aza-spiro-[indole-3,8'-penta-cyclo-[10.6.0.0(2,9).0(3,7).0(13,17)]octa-deca-ne]-2,10'-dione.

    PubMed

    Sabari, V; Ponnusamy, R; Prasanna, R; Raghunathan, R; Aravindhan, S

    2013-04-01

    In the title compound, C22H24N2O6, the indole ring has a twist conformation and the tetra-hydro-2H-pyran-2-one ring a half-chair conformation. One of the pyrrolidine rings adopts an envelope conformation on the N atom, while the other has a twist conformation; the 'butterfly' angle between their mean planes is 62.98 (11)°. The dioxolane ring adopts a twist conformation and the tetra-hydro-furan ring has an envelope conformation on the C atom in the fused tetra-hydro-2H-pyran-2-one ring adjacent to the O atom of the tetra-hydro-furan ring. The 'butterfly' angle between the mean planes of these two five-membered rings is 69.14 (10)°. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds, forming chains along the a axis. PMID:23634025

  6. Excited-state dynamics of oxazole: A combined electronic structure calculations and dynamic simulations study

    NASA Astrophysics Data System (ADS)

    Cao, Jun; Xie, Zhi-Zhong; Yu, Xiaodong

    2016-08-01

    In the present work, the combined electronic structure calculations and surface hopping simulations have been performed to investigate the excited-state decay of the parent oxazole in the gas phase. Our calculations show that the S2 state decay of oxazole is an ultrafast process characterized by the ring-opening and ring-closure of the five-membered oxazole ring, in which the triplet contribution is minor. The ring-opening involves the Osbnd C bond cleavage affording the nitrile ylide and airine intermediates, while the ring-closure gives rise to a bicyclic species through a 2sbnd 5 bond formation. The azirine and bicyclic intermediates in the S0 state are very likely involved in the phototranspositions of oxazoles. This is different from the previous mechanism in which these intermediates in the T1 state have been proposed for these phototranspositions.

  7. EPR study of radical reactions of C 60 dimer connected by a silicon bridge and single bond (C 60SiPh 2C 60)

    NASA Astrophysics Data System (ADS)

    Tumanskii, B. L.; Kalina, O. G.; Sokolov, V. I.; Chistyakov, A. L.; Stankevich, I. V.; Han, A.; Murata, Y.; Komatsu, K.

    2004-09-01

    Radical reactions of C 60 dimer connected by a silicon bridge and single bond (C 60SiPh 2C 60) were studied by EPR-spectroscopy. Attack of phosphoryl radicals or 2,2,6,6-tetramethylpiperidine- N-oxyl on the silicon atom leads to radical substitution of the fullerene and formation of a new fullerenyl radical, the structure of the former being confirmed by quantum-chemical calculations (DFT). The formation of only one type of spin-adduct on addition of phosphoryl radicals to the fullerene core is associated with small distortion of the fullerene cage in C 60SiPh 2C 60. Geometry of fullerene core in dimer differs only slightly from C 60 owing probably to flexibility of Si-C and C-C bonds which share a five-membered ring.

  8. Recent advances in isoxazole chemistry

    NASA Astrophysics Data System (ADS)

    Galenko, A. V.; Khlebnikov, A. F.; Novikov, M. S.; Pakalnis, V. V.; Rostovskii, N. V.

    2015-04-01

    The preparation methods and reactions of isoxazoles are described and systematized on the basis of analysis of the literature published from 2005 to present. In the discussion of synthesis, major attention is focused on the most efficient approaches: condensation of hydroxylamine with 1,3-dielectrophiles and reactions of nitrile oxides with alkenes and alkynes. Five-membered ring opening reactions leading to acyclic functionalized or other heterocyclic compounds are considered. The transformations of isoxazole derivatives that occur without ring cleavage to form fused heterocyclic systems, as well as reactions that lead to the introduction of C-substituents into isoxazoles, are considered. Data on the biological activity of some isoxazole derivatives are reported. The bibliography includes 439 references.

  9. Extended Simulations of Graphene Growth with Updated Rate Coefficients

    SciTech Connect

    Whitesides, R; You, X; Frenklach, M

    2010-03-18

    New simulations of graphene growth in flame environments are presented. The simulations employ a kinetic Monte Carlo (KMC) algorithm coupled to molecular mechanics (MM) geometry optimization to track individual graphenic species as they evolve. Focus is given to incorporation of five-member rings and resulting curvature and edge defects. The model code has been re-written to be more computationally efficient enabling a larger set of simulations to be run, decreasing stochastic fluctuations in the averaged results. The model also includes updated rate coefficients for graphene edge reactions recently published in the literature. The new simulations are compared to results from the previous model as well as to hydrogen to carbon ratios recorded in experiment and calculated with alternate models.

  10. Fluorescent aromatic sensors and their methods of use

    NASA Technical Reports Server (NTRS)

    Meador, Michael A. (Inventor); Tyson, Daniel S. (Inventor); Ilan, Ulvi F. (Inventor)

    2012-01-01

    Aromatic molecules that can be used as sensors are described. The aromatic sensors include a polycyclic aromatic hydrocarbon core with a five-membered imide rings fused to the core and at least two pendant aryl groups. The aromatic sensor molecules can detect target analytes or molecular strain as a result of changes in their fluorescence, in many cases with on-off behavior. Aromatic molecules that fluoresce at various frequencies can be prepared by altering the structure of the aromatic core or the substituents attached to it. The aromatic molecules can be used as sensors for various applications such as, for example, the detection of dangerous chemicals, biomedical diagnosis, and the detection of damage or strain in composite materials. Methods of preparing aromatic sensor molecules are also described.

  11. Tuning the Nucleophilicity in Cyclopropenylidenes

    PubMed Central

    Schoeller, Wolfgang W.; Frey, Guido D.; Bertrand, Guy

    2008-01-01

    Cyclopropenylidenes are Hückel aromatic π-systems in which one of the ring atoms is a carbene center. Quantum chemical calculations at density functional level, supplemented by coupled-cluster calculations, indicate that these species have a sizeable energy separation between the lowest energy singlet and triplet states. Amino groups considerably increase the energy difference between these two states, while electron-withdrawing substituents decrease it. The 1.1-dimerization products of cyclopropenylidenes, namely triafulvalenes, are investigated. The calculations show that, without steric hindrance and considerable electronic stabilization, cyclopropenylidenes are kinetically not stable and dimerize. Different substituents (alkyl, silyl, terphenyl, amino, and posphaneiminato) were probed to tune the energy levelling of the frontier orbitals in cyclopropenylidenes. Accordingly, it is predicted that by a suitable choice of substituents at the olefinic positions, cyclopropenylidenes can be more nucleophilic than their five-membered ring congeners, namely imidazol-2-ylidenes. PMID:18404754

  12. Arabinoamidine synthesis and its inhibition toward β-glucosidase (sweet almonds) in comparison to a library of galactonoamidines.

    PubMed

    Pickens, Jessica B; Striegler, Susanne; Fan, Qiu-Hua

    2016-08-15

    Aiming at the development of potent inhibitors of β-glucosidases, a small library of galactonoamidines and one arabinoamidine derived in analogy were studied as inhibitors of sweet almond β-glucosidase. The five-membered glycon in arabinoamidine was shown to interact with the proton donor in the active site of the retaining enzyme, but not with the nucleophile. By contrast, the corresponding galactonoamidine with a six-membered glycon and identical aglycon interacts with both hydrolysis-promoting amino acids in the active site and inhibits the enzymatic hydrolysis of β-glucosides in the low nanomolar concentration range. While both inhibitors are competitive, their inhibition ability is more than 37,000-fold different. PMID:27298003

  13. Fullerenes in Allende Meteorite

    NASA Technical Reports Server (NTRS)

    Becker, L.; Bada, J. L.; Winans, R. E.; Bunch, T. E.

    1994-01-01

    The detection of fullerenes in deposits from meteor impacts has led to renewed interest in the possibility that fullerenes are present in meteorites. Although fullerenes have not previously been detected in the Murchison and Allende meteorites, the Allende meteorite is known to contain several well-ordered graphite particles which are remarkably similar in size and appearance to the fullerene-related structures carbon onions and nanotubes. We report that fullerenes are in fact present in trace amounts in the Allende meteorite. In addition to fullerenes, we detected many polycyclic aromatic hydrocarbons (PAHs) in the Allende meteorite, consistent with previous reports. In particular, we detected benzofluoranthene and corannulene (C20H10), five-membered ring structures which have been proposed as precursors to the formation of fullerene synthesis, perhaps within circumstellar envelopes or other sites in the interstellar medium.

  14. Petroleum and petroleum/coal blends as feedstocks in laboratory-scale and pilot-scale cokers to obtain carbons of potentially high value

    NASA Astrophysics Data System (ADS)

    Escallon, Maria M.

    2008-12-01

    The main goal of this research is to understand how the chemical composition of the feedstock and reactor design affects the quality of the coke toward the formation of a needle (premium) coke. Although a lot of information has been published related to the production of the premium coke, via mesophase formation, some contradictory results have been reported because the conclusions are reached based on chemical composition of the feedstock alone or reactor design alone. A raw decant oil, EI-107, was hydrotreated to different levels giving origin to six derivatives. Based on greater differences in chemical composition between the hydrotreated decant oils and the raw decant oil, and the sample quantity, three out of six derivatives were selected to continue with the carbonization process. It was found that the quality of the coke obtained through the pyrolysis of the four decant oils using the reactor operated at atmospheric pressure and 465°C (LSCopen) is related to the chemical composition of the decant oil. The coke that displays the lowest coke quality is EI-135, which is explained by the presence of five-membered rings and biphenyls in the decant oil that are detrimental to the mesophase formation due to the loss of planarity and free rotation. Even though this decant oil has alkylbenzenes which improve the mesophase formation, it appears that the amount of these compounds is not enough to compensate the negative effect that five-membered rings and biphenyls exert on the mesophase. The next best coke in quality is EI-107. While its feedstock (EI-107) has the lowest amount of alkylbenzenes and naphthenic compounds, the decant oil EI-107 displays little or no presence of five-membered rings and biphenyls making its quality higher than coke EI-135. The cokes EI-134 and EI-138 display, respectively, the highest coke quality among the four cokes tested. Their feedstocks have the highest amount of alkylbenzenes and naphthenic compounds but an intermediate content of

  15. Crystal structure of methyl 3-(3-fluoro-phen-yl)-1-methyl-1,3a,4,9b-tetra-hydro-3H-thio-chromeno[4,3-c]isoxazole-3a-carboxyl-ate.

    PubMed

    Savithri, M P; Suresh, M; Raghunathan, R; Vimala, G; SubbiahPandi, A

    2015-08-01

    In the title compound, C19H18FNO3S, the five-membered oxazolidine ring adopts an envelope conformation with the methine C atom of the fused bond as the flap. Its mean plane is oriented at a dihedral angle of 50.38 (1)° with respect to the fluoro-phenyl ring. The six-membered thio-pyran ring has a half-chair conformation and its mean plane is almost coplanar with the fused benzene ring, making a dihedral angle of 4.94 (10)°. The two aromatic rings are inclined to one another by 85.96 (11)°, and the mean planes of the oxazolidine and thio-pyran rings are inclined to one another by 57.64 (12)°. In the crystal, mol-ecules are linked by C-H⋯π inter-actions, forming a three-dimensional structure. PMID:26396818

  16. Conversion of unsaturated alcohols into functionalized tetrahydrofurans and tetrahydropyrans via nitrile oxide dipolar cycloadditions

    SciTech Connect

    Hassner, A.; Murthy, K.S.K. ); Padwa, A.; Dean, D.C.; Schoffstall, A.M. ); Chiacchio, U. )

    1989-10-27

    The intramolecular nitrile oxide cycloaddition (INOC) of a series of unsaturated oximino ethers has been investigated. The synthesis of the olefinic nitrile oxides involves treating an unsaturated alcohol with a {alpha}-bromoalkanal O-(trimethylsilyl)oxime in the presence of fluoride ion followed by subsequent sodium hypochlorite oxidation. The nitrile oxides were not isolated but spontaneously underwent intramolecular cycloaddition to give fused five- and six-membered ring ethers. The preferred stereoisomer in the formation of the five-membered ring ethers is trans, whereas in the six-membered ring ethers the cis isomer predominates. MM2 calculations help rationalize the observed stereoselectivity. The ratio of diastereomeric products from the INOC reaction appears to correlate with product stabilities. Simple heating of some of the oximino ethers led to intramolecular cycloaddition. The ring closure apparently proceeds subsequent to a tautomeric equilibration of the oxime with a transient nitrone which is trapped by the neighboring {pi}-bond.

  17. Synthesis of Diverse Nitrogen-Enriched Heterocyclic Scaffolds Using a Suite of Tunable One-Pot Multicomponent Reactions

    PubMed Central

    2015-01-01

    Five elegant and switchable three-component reactions which enable access to a new series of nitrogen-containing heterocycles are reported. A novel one-step addition of an isocyanide to a hydrazine derived Schiff base affords unique six-membered pyridotriazine scaffolds (A and E). With slight modification of reaction conditions and replacement of the nucleophilic isocyanide moiety with different electrophiles (i.e., isocyanates, isothiocyanates, cyclic anhydrides, and acyl chlorides) five-membered triazolopyridine scaffolds (B, D, F, G) are generated in a single step. Furthermore, the use of phenyl hydrazine enables access to dihydroindazole-carboxamides, devoid of a bridge-head nitrogen (C). All protocols are robust and tolerate a diverse collection of reactants, and as such, it is expected that the new scaffolds and associated chemistry will garner high interest from medicinal chemists involved in either file enhancement or specific target-related drug discovery campaigns. PMID:24788091

  18. Palladium-Catalyzed Trimethylenemethane Cycloaddition of Olefins Activated by the σ-Electron-Withdrawing Trifluoromethyl Group.

    PubMed

    Trost, Barry M; Debien, Laurent

    2015-09-16

    α-Trifluoromethyl-styrenes, trifluoromethyl-enynes, and dienes undergo palladium-catalyzed trimethylenemethane cycloadditions under mild reaction conditions. The trifluoromethyl group serves as a unique σ-electron-withdrawing group for the activation of the olefin toward the cycloaddition. This method allows for the formation of exomethylene cyclopentanes bearing a quaternary center substituted by the trifluoromethyl group, compounds of interest for the pharmaceutical, agrochemical, and materials industries. In the diene series, the cycloaddition operates in a [3 + 4] and/or [3 + 2] manner to give rise to seven- and/or five-membered rings. This transformation greatly improves the scope of the TMM cycloaddition technology and provides invaluable insights into the reaction mechanism. PMID:26291872

  19. Task 11 final report

    SciTech Connect

    Bolton, P.

    2000-10-01

    Under this task, RAE personnel were on call to accompany members of the Concerned Citizens for Nuclear Safety (CCNS) if and when they exercised the option to borrow radiac instruments from the Laboratory and survey areas they thought might be contaminated by the Lab. Five members of the RAE team were given refresher training on the latest Lab owned instruments and on Lab procedures for using them and reporting results. On one occasion, a RAE team member accompanied LANL personnel when they did a survey of a house trailer which the owner claimed may have been contaminated. No contamination was found at the site. No requests were received to accompany CCNS members. The original task completion date of September 30, 1998 was extended to June 21, 1999. No requests were received to accompany CCNS members during this timeframe either. The task was terminated as it was determined there was no longer a need.

  20. Synthesis, molecular spectroscopy and thermal analysis of some cefepime complexes

    NASA Astrophysics Data System (ADS)

    Masoud, Mamdouh S.; Ali, Alaa E.; Ghareeb, Doaa A.; Nasr, Nessma M.

    2016-03-01

    The metal complexes of cefepime with Cr (III), Mn (II), Fe (III), Co (II), Cu (II), Zn (II), Cd (II), Hg (II) and mixed metals (Fe, Ni) or (Cu, Fe) were synthesized, the suggested structures of the complexes are based on the results of the elemental analysis, infrared, UV-visible, mass and HNMR spectra, effective magnetic moment as well as the thermal analysis (DTA, TGA & DSC) and characterized by energy dispersive x-ray (EDX) and scanning electron microscopy (SEM). The results obtained suggested that cefepime reacted with metal ions as bidentate ligand through the nitrogen of the β-lactone thiozolidine ring and carboxylate ion forming a five membered ring. The kinetic thermodynamic parameters were estimated from the DTA curves.

  1. Regioselective synthesis of dihydrothiophene and thiopyran frameworks via catalyst-controlled intramolecular Cγ/Cδ-S fusion of α-allyl-β'-oxodithioesters.

    PubMed

    Chowdhury, Sushobhan; Chanda, Tanmoy; Koley, Suvajit; Anand, Namrata; Singh, Maya Shankar

    2014-11-01

    A highly efficient and atom-economic dual reaction manifold has been developed to synthesize 4H-thiopyran and 4,5-dihydrothiophene frameworks via regioselective intramolecular C-S fusion of α-allyl-β'-oxodithioesters. The ring size of the sulfur-heterocycles has been efficiently tuned by the use of two different catalytic systems. Palladium activates the Cδ-H of the allyl termini and facilitates the intramolecular Cδ-S coupling to furnish six-membered thiopyran skeletons exclusively. Conversely, the allylic double bond of the same substrate has been activated by BF3·Et2O to promote the Cγ-S cyclization leading to the formation of a five-membered dihydrothiophene nucleus. PMID:25343754

  2. Synthesis and antiproliferative evaluation of 3,5-disubstituted 1,2,4-triazoles containing flurophenyl and trifluoromethanephenyl moieties.

    PubMed

    Wang, Li-Ya; Tseng, Wen-Che; Wu, Tian-Shung; Kaneko, Kimiyoshi; Takayama, Hiroyuki; Kimura, Masayuki; Yang, Wen-Chin; Wu, Jin Bin; Juang, Shin-Hun; Wong, Fung Fuh

    2011-09-15

    An efficient 1,3-dipolar cycloaddition method was performed for the synthesis of a series of monofluoro- and trifluoromethane-3,5-disubstituted 1,2,4-triazoles. This efficient cycloaddition method was to react hydrazonoyl hydrochlorides with a series of aldehydes in the presence of NEt(3) as catalytic basic agent to provide the corresponding product in 28-94%. Their growth inhibitory results against cancer cells indicated that some of the fluorine- and trifluoromethane-containing compounds could effectively inhibit the growth of NCI-H226 and T-cell leukemia (Jurkat) cells. Among the compounds, trifluoromethane-containing 1,2,4-triazoles possessed the five-membered ring groups on the C-5 position of the triazolic ring, including cyclopentyl, 3-furyl, 3-thienyl, and 2-pyrrolyl, possessed the significant inhibitory activity for NCI-H226 cancer cells. PMID:21802949

  3. Uranium pyrophosphate / methylenediphosphonate polyoxometalate cage clusters

    SciTech Connect

    Ling, Jie; Qiu, Jie; Sigmon, Ginger E.; Ward, Matt; Szymanowski, Jennifer E.S.; Burns, Peter C

    2010-09-29

    Despite potential applications in advanced nuclear energy systems, nanoscale control of uranium materials is in its infancy. In its hexavalent state, U occurs as (UO{sub 2}){sup 2+} uranyl ions that are coordinated by various ligands to give square, pentagonal, or hexagonal bipyramids. Creation and design of nanostructured uranyl materials requires interruption of the tendency of uranyl bipyramids to share equatorial edges to form infinite sheets that occur in extended structures. Where a bidentate peroxide group bridges uranyl bipyramids, the configuration is inherently bent, fostering formation of cage clusters. Here the bent configurations of four- and five-membered rings of uranyl peroxide hexagonal bipyramids are bridged by pyrophosphate or methylenediphosphonate, creating eight chemically complex cage clusters with specific topologies. Chemical complexity in such clusters provides opportunities for the tuning of cage sizes, pore sizes, and properties such as aqueous solubility. Several of these are topological derivatives of simpler clusters that contain only uranyl bipyramids, whereas others exhibit new topologies.

  4. Indolizinones as synthetic scaffolds: fundamental reactivity and the relay of stereochemical information†

    PubMed Central

    Hardin Narayan, Alison R.

    2012-01-01

    Indolizinones are under-explored N-heterocycles that react with exquisite chemo- and stereoselectivity. An exploration of the fundamental reactivity of these azabicycles demonstrates the potential to relay stereochemical information from the ring-fusion to newly formed stereocenters on the bicyclic core. The indolizinone diene undergoes selective hydrogenation and readily participates in Diels–Alder cycloadditions as well as ene reactions. The vinylogous amide embedded in the five-membered ring is resistant to reaction when the diene is in place. However, removal of the diene allows for diastereoselective hydrogenation of, and 1,4-additions to, the vinylogous amide. These fundamental reactions with indolizinones have provided a structurally diverse array of products that hold promise in the context of natural product synthesis. PMID:22072189

  5. CENDI - A strategic interagency alliance in the 1990s

    NASA Technical Reports Server (NTRS)

    Caponio, Joseph; Buffum, Elizabeth; Cotter, Gladys; Smith, Kent; Molholm, Kurt

    1991-01-01

    The goals, functions, and accomplishments of the CENDI Group, a government interagency cooperative organization formed to improve federal research and development productivity and R&D information management systems through information exchange, are briefly reviewed. The five member agencies are the Departments of Commerce, Energy, Defense, and Health and Human Services, and NASA. CENDI provides a means for its members to share technologies, resources, ideas, information, management activities, and standards. The top priorities of CENDI are: work with R&D managers to improve productivity; provide technical data and information to all users; improve the effectiveness and efficiency of all CENDI agency operations; and familiarize R&D managers and policy makers with the value of STI.

  6. The therapeutic voyage of pyrazole and its analogs: A review.

    PubMed

    Khan, Mohemmed Faraz; Alam, Mohammad Mumtaz; Verma, Garima; Akhtar, Wasim; Akhter, Mymoona; Shaquiquzzaman, Mohammad

    2016-09-14

    Pyrazole, a five membered heteroaromatic ring with two nitrogen atoms is of immense significance. Presence of this nucleus in the pharmacological agents of diverse therapeutic categories viz. antianxiety, anti-inflammatory, antipsychotic, anticancer, antiobesity, analgesic, antipyretic etc. has made it an indispensable anchor for design and development of new pharmacological agents. Owing to the development of novel and new pyrazole based therapeutic agents at a faster pace, there is a need to couple the latest information with previously available information to understand status of this moiety in medicinal chemistry research. The review herein highlights the therapeutic worth of pyrazole derivatives. Several therapeutically active pyrazole based derivatives developed by numerous scientists across the globe are reported here. PMID:27191614

  7. Crystal structure of (±)-(7RS,8SR)-7-methyl-1,4-dioxa-spiro-[4.5]decane-7,8-diol.

    PubMed

    Oishi, Takeshi; Yamamoto, Hiroaki; Sugai, Tomoya; Fukaya, Keisuke; Yamaguchi, Yu; Watanabe, Ami; Sato, Takaaki; Chida, Noritaka

    2015-10-01

    In the title compound, C9H16O4, the five-membered dioxolane ring adopts a twist conformation; two adjacent C atoms deviate alternately from the mean plane of other atoms by -0.297 (4) and 0.288 (4) Å. The spiro-fused cyclo-hexane ring shows a chair form. The hy-droxy group substituted in an axial position makes an intra-molecular O-H⋯O hydrogen bond with one of the O atoms in the cyclic ether, forming an S(6) ring motif. In the crystal, the O-H⋯O hydrogen bond involving the equatorial hy-droxy group connects the mol-ecules into a zigzag chain with a C(5) motif running along the c axis. PMID:26594401

  8. SHANNON LUCID, FLANKED BY CENTER DIRECTOR HONEYCUTT AND PILOT WILCUTT, AT THE SKID STRIP AT CCAS

    NASA Technical Reports Server (NTRS)

    1996-01-01

    At the Skid Strip on Cape Canaveral Air Station, U.S. astronaut Shannon W. Lucid gets a personal escort from KSC Director Jay Honeycutt (left) and STS-79 Pilot Terrence W. Wilcutt as she prepares to return to Johnson Space Center in Houston. A special ceremony awaits Lucid and the other five members of the STS-79 flight crew to commemorate Lucid's record-setting stay aboard the Russian Space Station Mir. Lucid embarked to Mir on March 22 and returned to Earth yesterday, Sept. 26, aboard the orbiter Atlantis with the crew of Space Shuttle Mission STS-79. Her 188 days on-orbit represent a U.S. human spaceflight record as well as the longest stay in space by a woman.

  9. X(1812) in the quarkonia-glueball-hybrid mixing scheme

    SciTech Connect

    He Xiaogang

    2006-06-01

    Recently a J{sup PC}=0{sup ++} [X(1812)] state with a mass near the threshold of {omega} and {phi} has been observed by the BES collaboration in J/{psi}{yields}{gamma}{omega}{phi} decay. It has been suggested that it is a I{sup G}=0{sup +} state. If it is true, this state fits in a mixing scheme based on quarkonia, glueball, and hybrid (QGH) very nicely where five physical states are predicted. Together with the known f{sub 0}(1370), f{sub 0}(1500), f{sub 0}(1710), and f{sub 0}(1790) states, X(1812) completes the five members in this family. Using known experimental data on these particles, we determine the ranges of the mixing parameters and predict decay properties for X(1812). We also discuss some features which may be able to distinguish between four-quark and hybrid mixing schemes.

  10. 6-(3,5-Dimeth-oxy-benzyl-amino)-9-(oxan-2-yl)-9H-purine.

    PubMed

    Starha, Pavel; Popa, Igor; Dvořák, Zdeněk; Trávníček, Zdeněk

    2013-04-01

    The mol-ecule of the title compound, C19H23N5O3, contains six-membered pyrimidine and five-membered imidazole rings merged into the essentially planar purine skeleton (r.m.s. deviation = 0.01 Å). In the crystal, pairs of N-H⋯N hydrogen bonds link mol-ecules into inversion dimers. The dimers are linked via C-H⋯O hydrogen bonds, forming double-stranded chains propagating along [001]. These chains are linked via C-H⋯π and parallel slipped π-π inter-actions [centroid-centroid distance = 3.467 (1) Å; slippage 0.519 Å], forming a three-dimensional network. PMID:23634074

  11. 6-(3,5-Dimeth­oxy­benzyl­amino)-9-(oxan-2-yl)-9H-purine

    PubMed Central

    Štarha, Pavel; Popa, Igor; Dvořák, Zdeněk; Trávníček, Zdeněk

    2013-01-01

    The mol­ecule of the title compound, C19H23N5O3, contains six-membered pyrimidine and five-membered imidazole rings merged into the essentially planar purine skeleton (r.m.s. deviation = 0.01 Å). In the crystal, pairs of N—H⋯N hydrogen bonds link mol­ecules into inversion dimers. The dimers are linked via C—H⋯O hydrogen bonds, forming double-stranded chains propagating along [001]. These chains are linked via C—H⋯π and parallel slipped π–π inter­actions [centroid–centroid distance = 3.467 (1) Å; slippage 0.519 Å], forming a three-dimensional network. PMID:23634074

  12. 2-Acetamido-N-benzyl-1,4-imino-1,2,4-tride­oxy-l-xylitol (N-benzyl-l-XYLNAc)

    PubMed Central

    Jenkinson, Sarah. F.; Crabtree, Elizabeth. V.; Glawar, Andreas. F. G.; Butters, Terry D.; Fleet, George. W. J.; Watkin, David. J.

    2010-01-01

    X-ray crystallography defines the relative configuration at the three-stereogenic centres in the title compound N-benzyl-l-XYLNAc, C14H20N2O3. The five-membered pyrrolidine ring adopts an envelope conformation with the N atom lying out of the plane of the other four atoms. In the crystal structure, inter­molecular O—H⋯O, N—H⋯O and O—H⋯N hydrogen bonds link the mol­ecules into chains along [100]. The carbonyl group O atom acts as an acceptor for a bifurcated hydrogen bond. The absolute configuration is determined by the use of l-glucuronolactone as the starting material for the synthesis. PMID:21579195

  13. 2,2,2-Trifluoro-1-[3-(2,2,2-trifluoro­acet­yl)azulen-1-yl]ethanone

    PubMed Central

    Förster, Sebastian; Eissmann, Frank; Seichter, Wilhelm; Weber, Edwin

    2011-01-01

    There are two mol­ecules in the asymmetric unit of the title compound, C14H6F6O2, in which the azulene systems possess an almost planar geometry with maximum deviations of 0.0438 (15) and 0.0396 (14) Å. Besides intra- and inter­molecular C—H⋯O and C—H⋯F inter­actions, the structure displays three F⋯F contacts [2.793 (2), 2.8820 (17) and 2.9181 (16) Å]. Furthermore, a characteristic azulene π-stacking is observed with an alternating sequence of electron-rich five-membered rings and electron-deficient seven-membered rings [centroid–centroid distances = 3.5413 (12), 3.6847 (12), 3.5790 (12) and 3.7718 (12) Å]. PMID:21754800

  14. Gulosibacter molinativorax ON4T Molinate Hydrolase, a Novel Cobalt-Dependent Amidohydrolase ▿ ‡

    PubMed Central

    Duarte, Márcia; Ferreira-da-Silva, Frederico; Lünsdorf, Heinrich; Junca, Howard; Gales, Luís; Pieper, Dietmar H.; Nunes, Olga C.

    2011-01-01

    A new pathway of molinate mineralization has recently been described. Among the five members of the mixed culture able to promote such a process, Gulosibacter molinativorax ON4T has been observed to promote the initial breakdown of the herbicide into ethanethiol and azepane-1-carboxylate. In the current study, the gene encoding the enzyme responsible for molinate hydrolysis was identified and heterologously expressed, and the resultant active protein was purified and characterized. Nucleotide sequence analysis revealed that the gene encodes a 465-amino-acid protein of the metal-dependent hydrolase A subfamily of the amidohydrolase superfamily with a predicted molecular mass of 50.9 kDa. Molinate hydrolase shares the highest amino acid sequence identity (48 to 50%) with phenylurea hydrolases of Arthrobacter globiformis and Mycobacterium brisbanense. However, in contrast to previously described members of the metal-dependent hydrolase A subfamily, molinate hydrolase contains cobalt as the only active-site metal. PMID:21840982

  15. Some higher N-substituted 1,3-thiazolidine-2,4-diones and 5,5-diphenylhydantoins, their synthesis and corrosion preventive properties in mineral oil medium

    NASA Astrophysics Data System (ADS)

    Öztürk, Serkan; Yıldırım, Ayhan; Çetin, Mehmet

    2013-01-01

    Some five membered heterocyclic compounds were synthesized by the reaction of 2,4-thiazolidinedione or 5,5-diphenylhydantoin potassium salts with 2-chloro-N-alkylacetamides and alkyl-2-chloroacetates. The structure confirmations of the synthesized compounds were performed by FT-IR, 1H NMR, 13C NMR spectra. The inhibitory effectiveness of the compounds were evaluated against the corrosion of steel strip immersed in water containing paraffin based mineral oil medium in accordance to standard test method. Surface characterization studies of the metal coupons used were performed by SEM analysis and also by the contact angle measurements using the Sessile-Drop method. In addition the 3D image of the metal surface was obtained using optical profilometer. The test results and surface characterization studies showed that all synthesized compounds are excellent corrosion inhibitors in such a water in oil emulsion system.

  16. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Missouri. Preliminary background report

    SciTech Connect

    Feurer, D A; Weaver, C L; Gallagher, K C; Hejna, D; Rielley, K J

    1980-01-01

    The authority to regulate public utilities in Missouri is vested in the Public Service Commission. The Commission is composed of five members who are appointed by the governor with the advice and consent of the senate. Commissioners are appointed for a term of six years. Commissioners must be free from any employment or pecuniary interests incompatible with the duties of the Commission. The Commission is charged with the general supervision of public utilities. The Public Service Commission Law passed in 1913, makes no provision for the regulation of public utilities by municipalities. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  17. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Connecticut. Preliminary background report

    SciTech Connect

    Feurer, D.A.; Weaver, C.L.; Gallagher, K.C.; Hejna, D.; Rielley, K.J.

    1980-01-01

    The Connecticut statutes expressly provide for the regulation of public utilities. As of January 1, 1979, responsibility for the regulation of utilities is vested in the Public Utilities Control Authority (PUCA). Formerly such authority was exercised by the Public Utilities Commission which has been abolished and replaced by the PUCA. The Public Utilities Act provides that the PUCA is to consist of five members appointed by the governor with the advice and consent of both houses of the general assembly. It should be noted that statutory references to the Public Utilities Commission are deemed to mean the Public Utilities Control Authority. The statute gives only a minor role to local government in regulating public utilities. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  18. Liftoff of Space Shuttle Endeavour on mission STS-97

    NASA Technical Reports Server (NTRS)

    2000-01-01

    As Space Shuttle Endeavour rockets off Launch Pad 39B, spewing clouds of smoke and steam, a majestic heron soars over the nearby water and Endeavour'''s reflection. Liftoff occurred on time at 10:06:01 p.m. EST. The Shuttle and its five-member crew will deliver U.S. solar arrays to the International Space Station and be the first Shuttle crew to visit the Station'''s first resident crew. The 11-day mission includes three spacewalks. This marks the 101st mission in Space Shuttle history and the 25th night launch. Endeavour is expected to land Dec. 11 at 6:19 p.m. EST.

  19. Ethyl 1′′-benzyl-1′-methyl-2′′-oxodi­spiro­[indeno­[1,2-b]quinoxaline-11,3′-pyrrolidine-2′,3′′-indoline]-4′-carboxyl­ate

    PubMed Central

    Kannan, Piskala Subburaman; Lanka, Srinu; Thennarasu, Sathiah; Govindan, Elumalai; SubbiahPandi, Arunachalathevar

    2013-01-01

    In the title compound, C36H30N4O3, the quinoxaline–indene system is roughly planar, with a maximum deviation from the mean plane of 0.218 Å for the C atom shared with the central pyrrolidine ring. This latter ring forms dihedral angles of 84.54 (7) and 83.91 (8)° with the quinoxaline–indene system and the indole ring, respectively. The central pyrrolidine ring has an envelope conformation with the N atom as the flap, while the pyrrolidine and five-membered rings of the indole group adopt twisted conformation and envelope (with the C atom bearing the quinoxaline–indene system as the flap) conformations, respectively. In the crystal, mol­ecules are linked via weak C—H⋯N hydrogen bonds, forming a chain running along [100]. PMID:23795014

  20. Dichloro[(1E,1'E)-1,1'-(pyridine-2,6-diyl)diethanone bis(O-methyloxime)-kappa(3)N(1),N(2),N(6)]copper(II).

    PubMed

    Ozdemir, Namik; Dinçer, Muharrem; Dayan, Osman; Cetinkaya, Bekir

    2006-07-01

    In the title compound, [CuCl(2)(C(11)H(15)N(3)O(2))], the Cu(II) ion is five-coordinated in a strongly distorted trigonal-bipyramidal arrangement, with the two methyloxime N atoms located in the apical positions, and the pyridine N and the Cl atoms located in the basal plane. The two axial Cu-N distances are almost equal (mean 2.098 A) and are substantially longer than the equatorial Cu-N bond [1.9757 (15) A]. It is observed that the N(oxime)-M-N(pyridine) bond angle for five-membered chelate rings of 2,6-diacetylpyridine dioxime complexes is inversely related to the magnitude of the M-N(pyridine) bond. The structure is stabilized by intra- and intermolecular C-H...Cl hydrogen bonds which involve the methyl H atoms, except for one of the two acetylmethyl groups. PMID:16823201

  1. Stevioside methanol tetra-solvate.

    PubMed

    Wu, Yunshan; Rodenburg, Douglas L; Ibrahim, Mohamed A; McChesney, James D; Avery, Mitchell A

    2013-03-01

    Stevioside is a naturally occurring diterpenoid glycoside in Stevia rebaudiana Bertoni. The title compound, C38H60O18·4CH3OH, crystallized as its methanol tetrasolvate. Stevioside consists of an aglycone steviol (a tetra-cyclic diterpene in which the four-fused-ring system consists of three six-membered rings and one five-membered ring) and a sugar part (three glucose units). A weak intra-molecular O-H⋯O hydrogen bond occurs. In the crystal, the methanol mol-ecules participate in a two-dimensional hydrogen-bonded network parallel to b axis with the sugars and together they form a hydrophilic tunnel which encloses the lipophilic part of the molecule. PMID:23476589

  2. Advances in synthetic approach to and antifungal activity of triazoles

    PubMed Central

    Kumar, Nitin; Drabu, Sushma; Sharma, Pramod Kumar

    2011-01-01

    Summary Several five membered ring systems, e.g., triazole, oxadiazole dithiazole and thiadiazole with three heteroatoms at symmetrical or asymmetrical positions have been studied because of their interesting pharmacological properties. In this article our emphasis is on synthetic development and pharmacological activity of the triazole moiety which exhibit a broad spectrum of pharmacological activity such as antifungal, antibacterial, anti-inflammatory and anticancer etc. Triazoles have increased our ability to treat many fungal infections, for example, candidiasis, cryptococcal meningitis, aspergillosis etc. However, mortality due to these infections even with antifungal therapy is still unacceptably high. Therefore, the development of new antifungal agents targeting specific fungal structures or functions is being actively pursued. Rapid developments in molecular mycology have led to a concentrated search for more target antifungals. Although we are entering a new era of antifungal therapy in which we will continue to be challenged by systemic fungal diseases, the options for treatment will have greatly expanded. PMID:21804864

  3. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Florida. Preliminary background report

    SciTech Connect

    Feurer, D A; Weaver, C L; Gallagher, K C; Hejna, D; Rielley, K J

    1980-01-01

    The authority to regulate public utilities is vested generally in the Florida Public Service Commission. The Commission is comprised of five members appointed by the governor with the approval of the senate. The governor must choose his appointees from a list of persons recommended by the nine-person Florida Public Service Commission Nominating Council. Commissioners serve either three- or four-year terms. They must be free from any employment or pecuniary interests in any utility subject to the jurisdiction of the Commission. Within the purview of its powers, the authority of the Commission supersedes that of local governments. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  4. Taking professional learning to isolated schools: perceptions of providers and principals, and lessons for effective professional learning

    NASA Astrophysics Data System (ADS)

    Beswick, Kim; Jones, Tammy

    2011-06-01

    This article describes the implementation and outcomes, as perceived by the professional learning providers and school principals, of a professional learning (PL) model devised in response to recognition that models of PL that are effective in urban settings are not effective in rural and remote areas. Rather than expecting the teachers to travel to an urban venue, the project used a five member team to provide 11 person-days of mathematics PL to a relatively remote cluster of schools over the course of one school week. The model was designed to meet the specific needs of teachers and schools in the cluster and to establish relationships that would form the basis of ongoing contacts. Data demonstrating the effectiveness of the model as well as the difficulties encountered, particularly by the PL providers, are presented and discussed. In addition, the importance of relationships between PL providers and teachers, and the value of grounding PL in a theory of learning are highlighted.

  5. Stabilizing Pentacene By Cyclopentannulation.

    PubMed

    Bheemireddy, Sambasiva R; Ubaldo, Pamela C; Rose, Peter W; Finke, Aaron D; Zhuang, Junpeng; Wang, Lichang; Plunkett, Kyle N

    2015-12-21

    A new class of stabilized pentacene derivatives with externally fused five-membered rings are prepared by means of a key palladium-catalyzed cyclopentannulation step. The target compounds are synthesized by chemical manipulation of a partially saturated 6,13-dibromopentacene precursor that can be fully aromatized in a final step through a DDQ-mediated dehydrogenation reaction (DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone). The new 1,2,8,9-tetraaryldicyclopenta[fg,qr]pentacene derivatives have narrow energy gaps of circa 1.2 eV and behave as strong electron acceptors with lowest unoccupied molecular orbital energies between -3.81 and -3.90 eV. Photodegradation studies reveal the new compounds are more photostable than 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-pentacene). PMID:26768696

  6. New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones

    PubMed Central

    Georgescu, Emilian; Nicolescu, Alina; Georgescu, Florentina; Teodorescu, Florina; Marinescu, Daniela; Macsim, Ana-Maria

    2014-01-01

    Summary The one-pot three-component reactions of 1-substituted benzimidazoles with ethyl bromoacetate and electron-deficient alkynes, in 1,2-epoxybutane, gave a variety of pyrrolo[1,2-a]quinoxalin-4-ones and pyrrolo[1,2-a]benzimidazoles. The influence of experimental conditions on the course of reaction was investigated. A novel synthetic pathway starting from benzimidazoles unsubstituted at the five membered ring, alkyl bromoacetates and non-symmetrical electron-deficient alkynes in the molar ratio of 1:2:1, in 1,2-epoxybutane at reflux temperature, led directly to pyrrolo[1,2-a]quinoxalin-4-ones in fair yield by an one-pot three-component reaction. PMID:25383108

  7. (3-Chloro­phen­yl){2-eth­oxy-5-[(Z)-hydroxy(phen­yl)methyl­idene]cyclo­penta-1,3-dien-1-yl}methanone

    PubMed Central

    Tinţaş, Mihaela-Liliana; Varga, Richard A.; Grosu, Ion; Bogdan, Elena

    2012-01-01

    The title compound, C21H17ClO3, which crystallizes as one of two possible oxo/hy­droxy-fulvene prototropic tautomers, possesses a strong intra­molecular O—H⋯O hydrogen bond that closes a seven-membered ring. The dihedral angles between the central five-membered ring and two pendant rings are 55.05 (9) and 44.51 (10)°. The crystal packing is characterized by weak inter­molecular C—H⋯O inter­actions between an H atom of the oxymethyl­ene unit and the carbonyl group of an adjacent mol­ecule, resulting in formation of chains of mol­ecules along the a axis. PMID:22346947

  8. Clicking the Arsenic-Carbon Triple Bond: An Entry into a New Class of Arsenic Heterocycles.

    PubMed

    Pfeifer, Gregor; Papke, Martin; Frost, Daniel; Sklorz, Julian A W; Habicht, Marija; Müller, Christian

    2016-09-19

    Arsaalkynes can undergo regioselective and quantitative [3+2] cycloaddition reactions with organic azides to give hitherto unknown 3H-1,2,3,4-triazaarsole derivatives. The reaction product was obtained as a white, air- and moisture-stable solid, and the presence of a planar, five-membered arsenic heterocycle was unambiguously verified by means of X-ray crystallography. DFT calculations gave insight into the electronic structure of these novel compounds compared to tetrazoles and triazaphospholes. The coordination chemistry towards Re(I) was investigated and compared with the structurally related phosphorus-containing ligand. These preliminary investigations pave the way for a new class of arsenic heterocycles and fill the gap between the azaarsoles already known. PMID:27460759

  9. HRMS studies on the fragmentation pathways of metallapentalyne

    NASA Astrophysics Data System (ADS)

    Lin, Zhiwei; Zhu, Congqing; Xia, Haiping

    2015-02-01

    The electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) using collision-induced dissociation (CID) method was applied to investigate the characteristic fragment ions of metalla-aromatic complexes for the first time. The fragmentation process of osmapentalyne, which contained metal-carbon triple bond in a five-membered ring, was discussed in detail. The ESI FT-ICR MS CID experimental results at high resolution mass spectra (HRMS) demonstrated the elemental composition of fragment ions unambiguously, thus a reasonable fragmentation pathway of osmapentalyne was proposed. In addition, the characteristic fragment ions have been investigated, which were specific and useful for the identification of some osmapentalynes complexes. These characteristic fragmentation pathways were helpful to analyze and interpret the stability and property of the parent ion. Also, this method could be used for the characterization of other organometallic complexes, especially containing characteristic isotopic peaks.

  10. First Principles Study of NO and NNO Chemisorption on Silicon Carbide Nanotubes and Other Nanotubes.

    PubMed

    Gao, Guohua; Kang, Hong Seok

    2008-10-14

    Using methods based on first principles, we find that NO and NNO molecules can be chemisorbed on silicon carbide nanotubes (SiCNTs) with an appreciable binding energy and that this is not the case for either carbon nanotubes (CNTs) or boron nitride nanotubes (BNNTs). A detailed analysis of the energetics, geometry, and electronic structure of various isomers of the complexes was performed. The adsorption energy (∼-0.7 eV) is larger for the SiCNT-NO complex. The complex exhibits magnetism, and a ferromagnetic coupling of spins is observed when more than one NO molecule is adsorbed. This observation suggests that magnetic properties can be used to sense the amount of NO molecules adsorbed. The SiCNT-NNO complex is a nonmagnetic system in which five-membered rings form at the binding site. PMID:26620175

  11. [4,4′-(Ethane-1,2-diyldinitrilo)­bis­(pent-2-en-2-olato)]copper(II) 0.25-hydrate

    PubMed Central

    Aslam, Muhammad; Anis, Itrat; Afza, Nighat; Hussain, Ajaz; Ahmed, Waseem; Arshad, Muhammad Nadeem

    2012-01-01

    In the title compound, [Cu(C12H18N2O2)]·0.25H2O, the coordination of the O,N,N′,O′-tetra­dentate ligand results in a cis-CuN2O2 square-planar geometry for the metal ion and the presence of two six-membered and one five-membered chelate rings. The complete complex mol­ecule is close to planar (r.m.s. deviation = 0.047 Å). The uncoordinated water mol­ecule (O-atom site symmetry 2) was modelled as half occupied. In the crystal, C—H⋯Ow and Ow—H⋯O (w = water) hydrogen bonds link the components into layers parallel to ab plane. PMID:22590153

  12. Dichlorido(5,5′-dimethyl-2,2′-bipyridine-κ2 N,N′)zinc(II)

    PubMed Central

    Khalighi, Aida; Ahmadi, Roya; Amani, Vahid; Khavasi, Hamid Reza

    2008-01-01

    The asymmetric unit of the title compound, [ZnCl2(C12H12N2)], contains two independent mol­ecules. The ZnII atoms are four-coordinated in distorted tetra­hedral configurations by two N atoms from 5,5′-dimethyl-2,2′-bipyridine and two terminal Cl atoms. In the crystal structure, inter­molecular C—H⋯Cl hydrogen bonds link the mol­ecules. There are C—H⋯π contacts between the methyl groups and the pyridine and five-membered rings containing ZnII atoms; π–π contacts also exist between the pyridine rings [centroid–centroid distances = 3.665 (5) and 3.674 (5) Å]. PMID:21201646

  13. Commission 19: Rotation of the Earth

    NASA Astrophysics Data System (ADS)

    Brzezinski, Aleksander; Ma, Chopo; Dehant, Véronique; Defraigne, Pascale; Dickey, Jean O.; Huang, Cheng-Li; Souchay, Jean; Vondrák, Jan; Charlot, Patrick; Richter, Bernd; Schuh, Harald

    The Commission supports and coordinates scientific investigations in the Earth rotation and related reference frames. Several changes had been introduced to the structure of Commission 19 since the IAU XXVI General Assembly in Prague, 2006. The Organizing Committee of Commission 19 has been substantially reduced. It consists now of six ex-officio members, the Commission president, vice-president, past president and representatives from the International Association of Geodesy (IAG), International Earth Rotation and Reference Systems Service (IERS), International VLBI Service for Geodesy and Astrometry (IVS), and five members at-large who are nominated by the OC, selected by the Commission members and elected by the IAU GA for a maximum of two terms. The modified terms of reference of Commission 19, the list of members and other details can be found at the Commission website .

  14. 5-Chloro-2-methyl-sulfanyl-6-(naphtha-len-1-yl-oxy)-1H-benzimidazole methanol monosolvate.

    PubMed

    Flores-Ramos, Miguel; Castillo, Rafael; Hernández-Campos, Alicia; Flores-Alamo, Marcos

    2014-01-01

    In the title compound, C18H13ClN2OS·CH3OH, the dihedral angle between the benzimidazole group and the naphth-yloxy moiety [82.89 (5)°] very near to orthogonality. The H atom in the five-membered ring is disordered with equal occupancies at the two N atoms and the H atom of the methano-lic hy-droxy group is disordered with equal occupancies over two sites at the O atom. The methanol mol-ecule acts as a hydrogen-bond acceptor for the amino H atom and donates a hydrogen bond to the nonprotonated ring N atom. As a result, chains are formed running along the a axis. PMID:24527009

  15. 5-Chloro-2-methyl­sulfanyl-6-(naphtha­len-1-yl­oxy)-1H-benzimidazole methanol monosolvate

    PubMed Central

    Flores-Ramos, Miguel; Castillo, Rafael; Hernández-Campos, Alicia; Flores-Alamo, Marcos

    2014-01-01

    In the title compound, C18H13ClN2OS·CH3OH, the dihedral angle between the benzimidazole group and the naphth­yloxy moiety [82.89 (5)°] very near to orthogonality. The H atom in the five-membered ring is disordered with equal occupancies at the two N atoms and the H atom of the methano­lic hy­droxy group is disordered with equal occupancies over two sites at the O atom. The methanol mol­ecule acts as a hydrogen-bond acceptor for the amino H atom and donates a hydrogen bond to the nonprotonated ring N atom. As a result, chains are formed running along the a axis. PMID:24527009

  16. Unusual Aggregation-Induced Emission of a Coumarin Derivative as a Result of the Restriction of an Intramolecular Twisting Motion.

    PubMed

    Bu, Fan; Duan, Ruihong; Xie, Yujun; Yi, Yuanping; Peng, Qian; Hu, Rongrong; Qin, Anjun; Zhao, Zujin; Tang, Ben Zhong

    2015-11-23

    Aggregation-induced emission (AIE) is commonly observed for propeller-like luminogens with aromatic rotors and stators. Herein, we report that a coumarin derivative containing a seven-membered aliphatic ring (CD-7) but no rotors showed typical AIE characteristics, whereas its analogue with a five-membered aliphatic ring (CD-5) exhibited an opposite aggregation-caused quenching (ACQ) effect. Experimental and theoretical results revealed that a large aliphatic ring in CD-7 weakens structural rigidity and promotes out-of-plane twisting of the molecular backbone to drastically accelerate nonradiative excited-state decay, thus resulting in poor emission in solution. The restriction of twisting motion in aggregates blocks the nonradiative decay channels and enables CD-7 to fluoresce strongly. The results also show that AIE is a general phenomenon and not peculiar to propeller-like molecules. The AIE and ACQ effects can be switched readily by the modulation of molecular rigidity. PMID:26439884

  17. 6-Nitro-2,3-dihydro-1H-pyrrolo­[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione

    PubMed Central

    Jebani, Abdessamad; Zouihri, Hafid; El Hakmaoui, Ahmed; Lazar, Saïd; Akssira, Mohamed

    2011-01-01

    In the two mol­ecules of the asymmetric unit of the title compound, C12H11N3O4, the seven-membered diazepine ring adopts a boat conformation (with the two phenyl­ene C atoms representing the stern and the methine C atom the prow). The five-membered pyrrole ring, which has an envelope conformation, makes dihedral angles of 60.47 (10) and 54.69 (9)° with the benzene ring of the benzodiazepine unit in the two mol­ecules. In the crystal, inter­molecular N—H⋯O hydrogen bonds and π–π stacking inter­actions [centroid–centroid distance = 3.8023 (7)–3.8946 (7) Å] lead to the formation of a three-dimensional framework. PMID:22091037

  18. Molecular, crystal, and electronic structure of the cobalt(II) complex with 10-(2-benzothiazolylazo)-9-phenanthrol

    SciTech Connect

    Linko, R. V.; Sokol, V. I.; Polyanskaya, N. A.; Ryabov, M. A.; Strashnov, P. V.; Davydov, V. V.; Sergienko, V. S.

    2013-05-15

    The reaction of 10-(2-benzothiazolylazo)-9-phenanthrol (HL) with cobalt(II) acetate gives the coordination compound [CoL{sub 2}] {center_dot} CHCl{sub 3} (I). The molecular and crystal structure of I is determined by X-ray diffraction. The coordination polyhedron of the Co atom in complex I is an octahedron. The anion L acts as a tridentate chelating ligand and is coordinated to the Co atom through the phenanthrenequinone O1 atom and the benzothiazole N1 atom of the moieties L and the N3 atom of the azo group to form two five-membered metallocycles. The molecular and electronic structures of the compounds HL, L, and CoL{sub 2} are studied at the density functional theory level. The results of the quantum-chemical calculations are in good agreement with the values determined by X-ray diffraction.

  19. Cleavage of nicotinamide adenine dinucleotide by the ribosome-inactivating protein from Momordica charantia.

    PubMed

    Vinkovic, M; Dunn, G; Wood, G E; Husain, J; Wood, S P; Gill, R

    2015-09-01

    The interaction of momordin, a type 1 ribosome-inactivating protein from Momordica charantia, with NADP(+) and NADPH has been investigated by X-ray diffraction analysis of complexes generated by co-crystallization and crystal soaking. It is known that the proteins of this family readily cleave the adenine-ribose bond of adenosine and related nucleotides in the crystal, leaving the product, adenine, bound to the enzyme active site. Surprisingly, the nicotinamide-ribose bond of oxidized NADP(+) is cleaved, leaving nicotinamide bound in the active site in the same position but in a slightly different orientation to that of the five-membered ring of adenine. No binding or cleavage of NADPH was observed at pH 7.4 in these experiments. These observations are in accord with current views of the enzyme mechanism and may contribute to ongoing searches for effective inhibitors. PMID:26323301

  20. Crystal structure of bis­(aceto­phenone 4-benzoyl­thio­semicarbazonato-κ2 N 1,S)nickel(II)

    PubMed Central

    Kadir, Faraidoon Karim; Shamsuddin, Mustaffa; Rosli, Mohd Mustaqim

    2016-01-01

    In the asymmetric unit of the title complex, [Ni(C16H14N3OS)2], the nickel ion is tetra­coordinated in a distorted square-planar geometry by two independent mol­ecules of the ligand which act as mononegative bidentate N,S-donors and form two five-membered chelate rings. The ligands are in trans (E) conformations with respect to the C=N bonds. The close approach of hydrogen atoms to the Ni2+ atom suggests anagostic inter­actions (Ni⋯H—C) are present. The crystal structure is built up by a network of two C—H⋯O inter­actions. One of the inter­actions forms inversion dimers and the other links the mol­ecules into infinite chains parallel to [100]. In addition, a weak C—H⋯π inter­action is also present. PMID:27308036

  1. Crystal structure of bis-(aceto-phenone 4-benzoyl-thio-semicarbazonato-κ(2) N (1),S)nickel(II).

    PubMed

    Kadir, Faraidoon Karim; Shamsuddin, Mustaffa; Rosli, Mohd Mustaqim

    2016-05-01

    In the asymmetric unit of the title complex, [Ni(C16H14N3OS)2], the nickel ion is tetra-coordinated in a distorted square-planar geometry by two independent mol-ecules of the ligand which act as mononegative bidentate N,S-donors and form two five-membered chelate rings. The ligands are in trans (E) conformations with respect to the C=N bonds. The close approach of hydrogen atoms to the Ni(2+) atom suggests anagostic inter-actions (Ni⋯H-C) are present. The crystal structure is built up by a network of two C-H⋯O inter-actions. One of the inter-actions forms inversion dimers and the other links the mol-ecules into infinite chains parallel to [100]. In addition, a weak C-H⋯π inter-action is also present. PMID:27308036

  2. Visible-light-induced, Ir-catalyzed reactions of N-methyl-N-((trimethylsilyl)methyl)aniline with cyclic α,β-unsaturated carbonyl compounds

    PubMed Central

    Lenhart, Dominik

    2014-01-01

    Summary N-Methyl-N-((trimethylsilyl)methyl)aniline was employed as reagent in visible-light-induced, iridium-catalyzed addition reactions to cyclic α,β-unsaturated carbonyl compounds. Typical reaction conditions included the use of one equivalent of the reaction substrate, 1.5 equivalents of the aniline and 2.5 mol % (in MeOH) or 1.0 mol % (in CH2Cl2) [Ir(ppy)2(dtbbpy)]BF4 as the catalyst. Two major reaction products were obtained in combined yields of 30–67%. One product resulted from aminomethyl radical addition, the other product was a tricyclic compound, which is likely formed by attack of the intermediately formed α-carbonyl radical at the phenyl ring. For five-membered α,β-unsaturated lactone and lactam substrates, the latter products were the only products isolated. For the six-membered lactones and lactams and for cyclopentenone the simple addition products prevailed. PMID:24778745

  3. Structure, energetics, and bonding of novel potential high energy density materials Rh2(N5)4: A DFT study

    NASA Astrophysics Data System (ADS)

    Tang, Lihong; Bao, Shuangyou; Peng, Jinhui; Li, Kai; Ning, Ping; Guo, Huibin; Zhu, Tingting; Gu, Junjie; Li, Qianshu

    2015-10-01

    Theoretical studies examining a series of binuclear transition metal pentazolides Rh2(N5)4 predict paddle wheel type structures with very short metal-metal distances. Natural bonding orbital analysis indicated that the bonding between the metal atom and the five-membered ring is predominantly ionic for Rh2(N5)4 species, and a high-order metal-metal multiple bonding exists between the two metal atoms. In addition, the presence of the delocalized π orbital plays an important role in the stabilization of Rh2(N5)4. Nucleus independent chemical shift values confirm that the planar N5- exhibits aromaticity. The dissociation energies into mononuclear fragments are predicted for Rh2(N5)4.

  4. Detection of CMY-2 AmpC β-lactamase-producing enterohemorrhagic Escherichia coli O157:H7 from outbreak strains in a nursery school in Japan.

    PubMed

    Kameyama, Mitsuhiro; Yabata, Junko; Nomura, Yasuharu; Tominaga, Kiyoshi

    2015-07-01

    In 2013, an outbreak of enterohemorrhagic Escherichia coli (EHEC) O157:H7 occurred in a nursery school in Japan. The outbreak affected 12 school children and five members of their families. All 17 isolates obtained from these individuals were found to be clonal, as determined by pulsed-field gel electrophoresis analysis and multilocus variable number tandem repeat analysis. The antimicrobial susceptibility profiles of the isolates to 20 drugs were examined, with three isolates showing resistance to the extended-spectrum cephalosporins (ESC) and cephamycin, including cefotaxime, ceftazidime, and cefminox. The resistant isolates carried the blaCMY-2 AmpC β-lactamase gene. It is proposed that the ESC-resistant EHEC O157:H7 isolates might have acquired the resistance plasmid encoding the blaCMY-2 gene during human to human infection in the nursery school. PMID:25835518

  5. A semiempirical study of heterocycle oligomers and polymers in different dielectric media

    SciTech Connect

    Juerimaee, T.; Strandberg, M.; Karelson, M.

    1995-06-15

    Four common five-membered heterocycles-pyrrole, phosphole, thiophene, and furan- and their oligomers with the chain length of 2, 4, 6, and 10 units have been studied quantum chemically using the semiempirical PM3 parameterization. The oligomers of pyrrole and phosphole with the homolytically dissociated N-H bond and P-H bond, respectively, and oligomers of thiophene and furan with one electron removed per monomer unit (4n + 2 {pi}-electron bipolaron systems) have also been studied. The electronic properties of the respective polymers were extrapolated from the oligomer data. Bulk polymer effects on the electronic structure were modeled using the self-consistent reaction field theory in the multicavity approximation (MCa SCRF). 48 refs., 3 figs., 6 tabs.

  6. Extension of N-Heteroacenes through a Four-Membered Ring.

    PubMed

    Yang, Shuaijun; Shan, Bowen; Xu, Xiaomin; Miao, Qian

    2016-05-01

    The synthesis of novel π-extended N-heteroacenes, which have a large tetraazaacene subunit and a quinoxaline subunit connected through a four-membered ring, is reported. They were studied with experimental and computational methods in comparison to the corresponding tetraazaacenes. As found from the DFT calculation, the four-membered ring is a better linker than a five-membered ring or a C-C single bond to extend N-heteroacenes for a new design of n-type semiconductors in terms of the spatial delocalization and energy level of LUMO as well as the reorganization energy. In solution-processed thin film transistors, the π-extended N-heteroacenes are found to function as n-type semiconductors with field effect mobility of up to 0.02 cm(2)  V(-1)  s(-1) under ambient conditions. PMID:27027902

  7. (S)-2-[(2-Hy­droxy­benz­yl)aza­nium­yl]-4-(methyl­sulfan­yl)butano­ate

    PubMed Central

    Brancatelli, Giovanna; Bruno, Giuseppe; Nicoló, Francesco; Canfora, Loredana; Ruisi, Giuseppe

    2011-01-01

    The zwitterionic title compound, C12H17NO3S, is a reduced Schiff base derived from (S)-N-(2-hy­droxy­benzyl­idene)methio­nine. An intra­molecular inter­action between the N—H and carboxyl­ate groups forms a roughly planar (r.m.s. deviation = 0.1405 Å) five-membered ring containing the H(N), N, Cα, C(carboxyl­ate) and O atoms in a penta­gonal conformation. In the crystal, a supra­molecular triangle-shaped motif is generated by mol­ecules held together by O—H⋯O and N—H⋯O hydrogen bonds. PMID:21754759

  8. Reactions of a tungsten-germylyne complex with α,β-unsaturated ketones: complete cleavage of the W≡Ge bond and formation of two types of η3-germoxyallyl tungsten complexes.

    PubMed

    Fukuda, Tetsuya; Hashimoto, Hisako; Tobita, Hiromi

    2014-01-01

    Germylyne complex Cp*(CO)2W≡Ge{C(SiMe3)3} (1) reacted with two molecules of RC(O)CH═CH2 (R = Me, Et) to give η(3)-allyl complexes, in which an oxagermacyclopentene framework was bound to an η(3)-allyl ligand through an oxygen atom. In the reaction with α-Me-substituted MeC(O)C(Me)═CH2, 1 reacted with only one molecule of the substrate to give another type of η(3)-allyl complex, in which a five-membered oxagermacyclopentenyl ring was coordinated to the W center in an η(3) fashion. Both reactions resulted in unprecedented complete cleavage of a W≡Ge triple bond. PMID:24328309

  9. (4-Benzyl-2-oxo-1,3-oxazolidin-5-yl)methyl methane­sulfonate

    PubMed Central

    Cunico, Wilson; Gomes, Claudia R. B.; Tiekink, Edward R. T.; Vellasco Junior, Walcimar T.; Wardell, James L.; Wardell, Solange M. S. V.

    2010-01-01

    The title compound, C12H15NO5S, features an approximately planar five-membered oxazolidin ring (r.m.s. deviation = 0.045 Å) with the peripheral benzyl and methyl methane­sulfonate residues lying to either side of the plane. In the crystal, N—H⋯O hydrogen bonds, involving one of the sulfur-bound oxo groups as acceptor, lead to the formation of supra­molecular chains along the b axis. These chains are reinforced by C—H⋯O contacts with the carbonyl O atom accepting three such inter­actions. The structure was refined as a racemic twin, with the major component being present 89% of the time. PMID:21579707

  10. Florida Governor Jeb Bush and Daniel Goldin in the Firing Room after the STS-97 launch

    NASA Technical Reports Server (NTRS)

    2000-01-01

    In the Firing Room, Launch Control Center, after a successful launch of Space Shuttle Endeavour on mission STS-97, Launch Director Michael Leinbach (with microphone) addresses the launch team. Behind him at right are Florida Governor Jeb Bush and NASA Administrator Daniel Goldin. Liftoff of Endeavour occurred at 10:06:01 p.m. EST. Endeavour and its five-member crew will deliver U.S. solar arrays to the International Space Station and be the first Shuttle crew to visit the Station's first resident crew. The 11-day mission includes three spacewalks. This marks the 101st mission in Space Shuttle history and the 25th night launch. Endeavour is expected to land at KSC Dec. 11 at 6:19 p.m. EST.

  11. VIPs join Florida Governor Jeb Bush in the Firing Room after the STS-97 launch

    NASA Technical Reports Server (NTRS)

    2000-01-01

    In the Firing Room, Launch Control Center, after a successful launch of STS-97, VIPs gather to congratulate the launch team. In the center of the photo is Florida Governor Jeb Bush. On his left is KSC Director of External Relations and Business Development JoAnn H. Morgan; on Bush's right is Joseph Rothenberg, associate administrator, Office of Space Flight; on the far right is Bill Readdy, manager at Johnson Space Center. Liftoff of Endeavour occurred at 10:06:01 p.m. EST. Endeavour and its five-member crew will deliver U.S. solar arrays to the International Space Station and be the first Shuttle crew to visit the Station's first resident crew. The 11-day mission includes three spacewalks. This marks the 101st mission in Space Shuttle history and the 25th night launch. Endeavour is expected to land at KSC Dec. 11 at 6:19 p.m. EST.

  12. Florida Governor Jeb Bush addresses launch team in the Firing Room after the STS-97 launch

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Florida Governor Jeb Bush (with microphone) addresses the launch team in the Firing Room, Launch Control Center, after a successful launch of STS-97. At right is NASA Administrator Daniel Goldin. Liftoff of Space Shuttle Endeavour occurred at 10:06:01 p.m. Endeavour and its five-member crew will deliver U.S. solar arrays to the International Space Station and be the first Shuttle crew to visit the Station's first resident crew. The 11-day mission includes three spacewalks. This marks the 101st mission in Space Shuttle history and the 25th night launch. Endeavour is expected to land at KSC Dec. 11 at 6:19 p.m. EST.

  13. Florida Governor Jeb Bush and Daniel Goldin in the Firing Room after the STS-97 launch

    NASA Technical Reports Server (NTRS)

    2000-01-01

    In the Firing Room, Launch Control Center, after a successful launch of Space Shuttle Endeavour on mission STS-97, Florida Governor Jeb Bush shakes the hand of NASA Administrator Daniel Goldin. Liftoff of Endeavour occurred at 10:06:01 p.m. Endeavour and its five-member crew will deliver U.S. solar arrays to the International Space Station and be the first Shuttle crew to visit the Station's first resident crew. The 11-day mission includes three spacewalks. This marks the 101st mission in Space Shuttle history and the 25th night launch. Endeavour is expected to land at KSC Dec. 11 at 6:19 p.m. EST.

  14. Method for controlling clathrate hydrates in fluid systems

    DOEpatents

    Sloan, Jr., Earle D.

    1995-01-01

    Discussed is a process for preventing clathrate hydrate masses from impeding the flow of fluid in a fluid system. An additive is contacted with clathrate hydrate masses in the system to prevent those clathrate hydrate masses from impeding fluid flow. The process is particularly useful in the natural gas and petroleum production, transportation and processing industry where gas hydrate formation can cause serious problems. Additives preferably contain one or more five member, six member and/or seven member cyclic chemical groupings. Additives include poly(N-vinyl-2-pyrrolidone) and hydroxyethylcellulose, either in combination or alone. Additives can also contain multiple cyclic chemical groupings having different size rings. One such additive is sold under the name Gaffix VC-713.

  15. Method for controlling clathrate hydrates in fluid systems

    DOEpatents

    Sloan, E.D. Jr.

    1995-07-11

    Discussed is a process for preventing clathrate hydrate masses from impeding the flow of fluid in a fluid system. An additive is contacted with clathrate hydrate masses in the system to prevent those clathrate hydrate masses from impeding fluid flow. The process is particularly useful in the natural gas and petroleum production, transportation and processing industry where gas hydrate formation can cause serious problems. Additives preferably contain one or more five member, six member and/or seven member cyclic chemical groupings. Additives include poly(N-vinyl-2-pyrrolidone) and hydroxyethylcellulose, either in combination or alone. Additives can also contain multiple cyclic chemical groupings having different size rings. One such additive is sold under the name Gaffix VC-713.

  16. Analysis of the magnetically induced current density of molecules consisting of annelated aromatic and antiaromatic hydrocarbon rings.

    PubMed

    Sundholm, Dage; Berger, Raphael J F; Fliegl, Heike

    2016-06-21

    Magnetically induced current susceptibilities and current pathways have been calculated for molecules consisting of two pentalene groups annelated with a benzene (1) or naphthalene (2) moiety. Current strength susceptibilities have been obtained by numerically integrating separately the diatropic and paratropic contributions to the current flow passing planes through chosen bonds of the molecules. The current density calculations provide novel and unambiguous current pathways for the unusual molecules with annelated aromatic and antiaromatic hydrocarbon moieties. The calculations show that the benzene and naphthalene moieties annelated with two pentalene units as in molecules 1 and 2, respectively, are unexpectedly antiaromatic sustaining only a local paratropic ring current around the ring, whereas a weak diatropic current flows around the C-H moiety of the benzene ring. For 1 and 2, the individual five-membered rings of the pentalenes are antiaromatic and a slightly weaker semilocal paratropic current flows around the two pentalene rings. Molecules 1 and 2 do not sustain any net global ring current. The naphthalene moiety of the molecule consisting of a naphthalene annelated with two pentalene units (3) does not sustain any strong ring current that is typical for naphthalene. Instead, half of the diatropic current passing the naphthalene moiety forms a zig-zag pattern along the C-C bonds of the naphthalene moiety that are not shared with the pentalene moieties and one third of the current continues around the whole molecule partially cancelling the very strong paratropic semilocal ring current of the pentalenes. For molecule 3, the pentalene moieties and the individual five-membered rings of the pentalenes are more antiaromatic than for 1 and 2. The calculated current patterns elucidate why the compounds with formally [4n + 2] π-electrons have unusual aromatic properties violating the Hückel π-electron count rule. The current density calculations also provide

  17. From formamide to purine: a self-catalyzed reaction pathway provides a feasible mechanism for the entire process.

    PubMed

    Wang, Jing; Gu, Jiande; Nguyen, Minh Tho; Springsteen, Greg; Leszczynski, Jerzy

    2013-08-15

    A formamide self-catalyzed mechanistic pathway that transforms formamide to purine through a five-membered ring intermediate has been explored by density functional theory calculations. The highlight of the mechanistic route detailed here is that the proposed pathway represents the simplest and lowest energy reaction pathway. All necessary reactants, including catalysts, are generated from a single initial compound, formamide. The most catalytically effective form of formamide is found to be the imidic acid isomer. The catalytic effect of formamide has been found to be much more significant than that of water. The self-catalytic mechanism revealed here provides a pathway with the lowest energy barriers among all reaction routes previously published. Several important reaction steps are involved in this mechanistic route: formylation-dehydration, Leuckart reduction, five- and six-member ring-closing, and deamination. Overall, a five-membered ring-closing is the rate-determining step in the present catalytic route, which is consistent with our previous mechanistic investigations. The activation energy of this rate-controlling step (ca. 27 kcal/mol) is significantly lower than the rate-determining step (ca. 34 kcal/mol) in the pathway from 4-aminoimidazole-5-carboxamidine described by Schleyer's group (Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 17272-17277) and in the pyrimidine pathway (ca. 44 kcal/mol) reported by Sponer et al. (J. Phys. Chem. A 2012, 116, 720-726). The self-catalyzed mechanistic pathway reported herein is less energetically demanding than previously proposed routes. PMID:23902343

  18. Ethical considerations related to participation and partnership: an investigation of stakeholders’ perceptions of an action-research project on user fee removal for the poorest in Burkina Faso

    PubMed Central

    2014-01-01

    Background Healthcare user fees present an important barrier for accessing services for the poorest (indigents) in Burkina Faso and selective removal of fees has been incorporated in national healthcare planning. However, establishing fair, effective and sustainable mechanisms for the removal of user fees presents important challenges. A participatory action-research project was conducted in Ouargaye, Burkina Faso, to test mechanisms for identifying those who are indigents, and funding and implementing user fee removal. In this paper, we explore stakeholder perceptions of ethical considerations relating to participation and partnership arising in the action-research. Methods We conducted 39 in-depth interviews to examine ethical issues associated with the action-research. Respondents included 14 individuals identified as indigent through the community selection process, seven members of village selection committees, six local healthcare professionals, five members of the management committees of local health clinics, five members of the research team, and four regional or national policy-makers. Using constant comparative techniques, we carried out an inductive thematic analysis of the collected data. Results The Ouargaye project involved a participatory model, included both implementation and research components, and focused on a vulnerable group within small, rural communities. Stakeholder perceptions and experiences relating to the participatory approach and reliance on multiple partnerships in the project were associated with a range of ethical considerations related to 1) seeking common ground through communication and collaboration, 2) community participation and risk of stigmatization, 3) impacts of local funding of the user fee removal, 4) efforts to promote fairness in the selection of the indigents, and 5) power relations and the development of partnerships. Conclusions This investigation of the Ouargaye project serves to illuminate the distinctive

  19. (S)-N-[(4-{(S)-1-[2-(4-Meth-oxy-benz-amido)-2-methyl-propano-yl]pyrrolidine-2-carboxamido}-3,4,5,6-tetra-hydro-2H-pyran-4-yl)carbon-yl]proline dimethyl sulfoxide monosolvate (4-MeBz-Aib-Pro-Thp-Pro-OH).

    PubMed

    Stoykova, Svetlana A; Linden, Anthony; Heimgartner, Heinz

    2013-03-01

    The asymmetric unit of the title compound, C28H38N4O8·C2H6OS, contains one tetra-peptide and one disordered dimethyl sulfoxide (DMSO) mol-ecule. The central five-membered ring (Pro(2)) of the peptide mol-ecule has a disordered envelope conformation [occupancy ratio 0.879 (2):0.121 (2)] with the envelope flap atom, the central C atom of the three ring methylene groups, lying on alternate sides of the mean ring plane. The terminal five-membered ring (Pro(4)) also adopts an envelope conformation with the C atom of the methylene group closest to the carboxylic acid function as the envelope flap, and the six-membered tetra-hydro-pyrane ring shows a chair conformation. The tetra-peptide exists in a helical conformation, stabilized by an intra-molecular hydrogen bond between the amide N-H group of the heterocyclic α-amino acid Thp and the amide O atom of the 4-meth-oxy-benzoyl group. This inter-action has a graph set motif of S(10) and serves to maintain a fairly rigid β-turn structure. In the crystal, the terminal hy-droxy group forms a hydrogen bond with the amide O atom of Thp of a neighbouring mol-ecule, and the amide N-H group at the opposite end of the mol-ecule forms a hydrogen bond with the amide O atom of Thp of another neighbouring mol-ecule. The combination of both inter-molecular inter-actions links the mol-ecules into an extended three-dimensional framework. PMID:23476594

  20. 3He NMR studies on helium-pyrrole, helium-indole, and helium-carbazole systems: a new tool for following chemistry of heterocyclic compounds.

    PubMed

    Radula-Janik, Klaudia; Kupka, Teobald

    2015-02-01

    The (3)He nuclear magnetic shieldings were calculated for free helium atom and He-pyrrole, He-indole, and He-carbazole complexes. Several levels of theory, including Hartree-Fock (HF), Second-order Møller-Plesset Perturbation Theory (MP2), and Density Functional Theory (DFT) (VSXC, M062X, APFD, BHandHLYP, and mPW1PW91), combined with polarization-consistent pcS-2 and aug-pcS-2 basis sets were employed. Gauge-including atomic orbital (GIAO) calculated (3)He nuclear magnetic shieldings reproduced accurately previously reported theoretical values for helium gas. (3)He nuclear magnetic shieldings and energy changes as result of single helium atom approaching to the five-membered ring of pyrrole, indole, and carbazole were tested. It was observed that (3)He NMR parameters of single helium atom, calculated at various levels of theory (HF, MP2, and DFT) are sensitive to the presence of heteroatomic rings. The helium atom was insensitive to the studied molecules at distances above 5 Å. Our results, obtained with BHandHLYP method, predicted fairly accurately the He-pyrrole plane separation of 3.15 Å (close to 3.24 Å, calculated by MP2) and yielded a sizable (3)He NMR chemical shift (about -1.5 ppm). The changes of calculated nucleus-independent chemical shifts (NICS) with the distance above the rings showed a very similar pattern to helium-3 NMR chemical shift. The ring currents above the five-membered rings were seen by helium magnetic probe to about 5 Å above the ring planes verified by the calculated NICS index. PMID:25228253

  1. Tuning the Electronic Structure of Fe(II) Polypyridines via Donor Atom and Ligand Scaffold Modifications: A Computational Study.

    PubMed

    Bowman, David N; Bondarev, Alexey; Mukherjee, Sriparna; Jakubikova, Elena

    2015-09-01

    Fe(II) polypyridines are an important class of pseudo-octahedral metal complexes known for their potential applications in molecular electronic switches, data storage and display devices, sensors, and dye-sensitized solar cells. Fe(II) polypyridines have a d(6) electronic configuration and pseudo-octahedral geometry and can therefore possess either a high-spin (quintet) or a low-spin (singlet) ground state. In this study, we investigate a series of complexes based on [Fe(tpy)2](2+) (tpy = 2,2';6',2″-terpyridine) and [Fe(dcpp)2](2+) (dcpp = 2,6-bis(2-carboxypyridyl)pyridine). The ligand field strength in these complexes is systematically tuned by replacing the central pyridine with five-membered (N-heterocyclic carbene, pyrrole, furan) or six-membered (aryl, thiazine-1,1-dioxide, 4-pyrone) moieties. To determine the impact of ligand substitutions on the relative energies of metal-centered states, the singlet, triplet, and quintet states of the Fe(II) complexes were optimized in water (PCM) using density functional theory at the B3LYP+D2 level with 6-311G* (nonmetals) and SDD (Fe) basis sets. It was found that the dcpp ligand scaffold allows for a more ideal octahedral coordination environment in comparison to the tpy ligand scaffold. The presence of six-membered central rings also allows for a more ideally octahedral coordination environment relative to five-membered central rings, regardless of the ligand scaffold. We find that the ligand field strength in the Fe(II) polypyridines can be tuned by altering the donor atom identity, with C donor atoms providing the strongest ligand field. PMID:26295275

  2. Photoisomerization of azobenzenes isolated in cryogenic matrices.

    PubMed

    Duarte, Luís; Khriachtchev, Leonid; Fausto, Rui; Reva, Igor

    2016-06-22

    2,2'-Dihydroxyazobenzene (DAB), 2,2'-azotoluene (AT) and azobenzene (AB) were isolated in argon and xenon matrices and their molecular structures and photochemical transformations were characterized by infrared spectroscopy and theoretical calculations. All these compounds can adopt the E and Z isomeric forms around the central CNNC moiety, which can be enriched by several conformational and tautomeric modifications for DAB and AT. A number of DAB and AT isomeric forms were identified for the first time. For DAB, the E azo-enol isomer with two intramolecular six-membered quasi-rings formed via OHN hydrogen bonds was found after deposition. Irradiation with UV light generated a different E azo-enol form with two intramolecular H-bonded five-membered quasi-rings. Phototransformation was shown to be reversible and the forms could be interconverted by irradiation at different wavelengths. The isomerization between these two forms constitutes a direct experimental observation of an E → E isomerization in azobenzene-type molecules. Further irradiation generated a form(s) bearing both OH and NH groups. For AT, two E isomers with the CH3 groups forming five-membered and five/six-membered quasi-rings with the azo group were observed in the as-deposited matrices. Irradiation of AT with UV light generated a Z form that can be converted back to the E form at different irradiation wavelengths. E-AB was deposited in a xenon matrix and both E → Z and Z → E phototransformations were observed (contrary to what was previously reported in an argon matrix where only the Z → E conversion occurred). AB photoisomerization becomes more pronounced at elevated temperatures, thus indicating that the matrix effects responsible for hindering the AB photoisomerization are essentially due to steric restrictions. The different photoisomerization channels observed for these compounds are discussed in terms of a small-amplitude pedal motion. PMID:27279432

  3. Inhibition of p-nitrophenol hydroxylase in rat liver microsomes by small aromatic and heterocyclic molecules.

    PubMed

    Hargreaves, M B; Jones, B C; Smith, D A; Gescher, A

    1994-01-01

    The cytochrome P450 isoenzyme P4502E1 is constitutively expressed in human liver and catalyzes the oxidation of many known or suspected carcinogens of low molecular weight. In this structure-metabolism study, the role that heteroatoms in heterocyclic compounds play in determining their affinity for P4502E1 was investigated. The ability of 16 six-membered and 10 five-membered compounds to inhibit the hydroxylation of p-nitrophenol, which is specifically catalyzed by P4502E1, was studied in suspensions of microsomes from rat livers in which P4502E1 had been induced by inclusion of acetone in the drinking water. Apparent Ki values were extrapolated from kinetic models of Dixon or Cornish-Bowden plots for enzyme inhibition. Enzyme inhibition was generally of the non-or uncompetitive type. Pyridine was the most potent and benzene one of the least potent inhibitors, with Ki values of 0.4 microM and 8,400 microM, respectively. Pyridazine was less inhibitory than 1,3,5-triazine, which inhibited P4502E1 to a lesser degree than pyrazine and pyrimidine. Among the unsubstituted unsaturated five-membered ring molecules, pyrrole was a better inhibitor than furan or thiophene. 4-Methylimidazole was a much stronger inhibitor than imidazole or 1-and 2-methylimidazole. The ability of compounds to inhibit P4502E1 seems to depend in the main on the presence of a nitrogen atom in the molecule and on the ability of the nitrogen lone pair of electrons to ligand to the heme. PMID:7835233

  4. Synthesis of New 3-Heteroarylindoles as Potential Anticancer Agents.

    PubMed

    Abdelhamid, Abdou O; Gomha, Sobhi M; Abdelriheem, Nadia A; Kandeel, Saher M

    2016-01-01

    2-(3-(1H-Indol-3-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-substituted-5-(substituted diazenyl)thiazoles and 2-(1H-indol-3-yl)-9-substituted-4,7-disubstituted pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(7H)-ones were synthesized via reaction of hydrazonoyl halides with each of 3-(1H-indol-2-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide and 7-(1H-indol-3-yl)-2- thioxo-5-substituted-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones, respectively. Also, hydrazonoyl halides were reacted with N'-(1-(1H-indol-3-yl)ethylidene)-2-cyanoacetohydrazide to afford 1,3,4-thiadiazole derivatives. Structures of the new synthesis were elucidated on the basis of elemental analysis, spectral data, and alternative synthetic routes whenever possible. Fifteen of the new compounds have been evaluated for their antitumor activity against the MCF-7 human breast carcinoma cell line. The results indicated that many of the tested compounds showed moderate to high anticancer activity when compared with doxorubicin as a reference drug. PMID:27438822

  5. Approved Antiviral Drugs over the Past 50 Years.

    PubMed

    De Clercq, Erik; Li, Guangdi

    2016-07-01

    Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2'-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2'-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide. PMID:27281742

  6. Synthesis and spectral characterization of Zn(II) microsphere series for antimicrobial application

    NASA Astrophysics Data System (ADS)

    Singh, Ajay K.; Pandey, Sarvesh K.; Pandey, O. P.; Sengupta, S. K.

    2014-09-01

    Microsphere series have been synthesized by reacting zinc(II) acetate dihydrate with Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole/oxadiazole/triazole with salicylaldehyde. Elemental analysis suggests that the complexes have 1:2 and 1:1 stoichiometry of the type [Zn(L)2(H2O)2] and [Zn(L‧)(H2O)2]; LH = Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thia/oxadiazole with salicylaldehyde; L‧H2 = Schiff bases derived from 3-(substituted phenyl)-4-amino-5-hydrazino-1,2,4-triazole and salicylaldehyde and were characterized by elemental analyses, IR, 1H NMR and 13C NMR spectral data. Scanning electron microscopy (SEM) showed that synthesized materials have microsphere like structure and there EDX analysis comparably matches with elemental analysis. For the antimicrobial application Schiff bases and their zinc(II) complexes were screened for four bacteria e.g. Bacillus subtilis, Pseudomonas aeruginosa, Salmonella typhi, Streptococcus pyogenes and four fungi e.g. Cyrtomium falcatum, Aspergillus niger, Fusarium oxysporium and Curvularia pallescence by the reported method. Schiff base and Zn(II) compounds showed significant antimicrobial activities. However, activities increase upon chelation. Thermal analysis (TGA) data of compound (10) showed its stability up to 300 °C.

  7. Identification of pharmacological chaperones for Gaucher disease and characterization of their effects on beta-glucocerebrosidase by hydrogen/deuterium exchange mass spectrometry.

    PubMed

    Tropak, Michael B; Kornhaber, Gregory J; Rigat, Brigitte A; Maegawa, Gustavo H; Buttner, Justin D; Blanchard, Jan E; Murphy, Cecilia; Tuske, Steven J; Coales, Stephen J; Hamuro, Yoshitomo; Brown, Eric D; Mahuran, Don J

    2008-11-01

    Point mutations in beta-glucocerebrosidase (GCase) can result in a deficiency of both GCase activity and protein in lysosomes thereby causing Gaucher Disease (GD). Enzyme inhibitors such as isofagomine, acting as pharmacological chaperones (PCs), increase these levels by binding and stabilizing the native form of the enzyme in the endoplasmic reticulum (ER), and allow increased lysosomal transport of the enzyme. A high-throughput screen of the 50,000-compound Maybridge library identified two, non-carbohydrate-based inhibitory molecules, a 2,4-diamino-5-substituted quinazoline (IC(50) 5 microM) and a 5-substituted pyridinyl-2-furamide (IC(50) 8 microM). They raised the levels of functional GCase 1.5-2.5-fold in N370S or F213I GD fibroblasts. Immunofluorescence confirmed that treated GD fibroblasts had decreased levels of GCase in their ER and increased levels in lysosomes. Changes in protein dynamics, monitored by hydrogen/deuterium-exchange mass spectrometry, identified a domain III active-site loop (residues 243-249) as being significantly stabilized upon binding of isofagomine or either of these two new compounds; this suggests a common mechanism for PC enhancement of intracellular transport. PMID:18972510

  8. Identification of Pharmacological Chaperones for Gaucher Disease and Characterization of Their Effects on β-Glucocerebrosidase by Hydrogen/Deuterium Exchange Mass Spectrometry

    PubMed Central

    Tropak, Michael B.; Kornhaber, Gregory J.; Rigat, Brigitte A.; Maegawa, Gustavo H.; Buttner, Justin D.; Blanchard, Jan E.; Murphy, Cecilia; Tuske, Steven J.; Coales, Stephen J.; Hamuro, Yoshitomo; Brown, Eric D.

    2010-01-01

    Point mutations in β-glucocerebrosidase (GCase) can result in a deficiency of both GCase activity and protein in lysosomes thereby causing Gaucher Disease (GD). Enzyme inhibitors such as isofagomine, acting as pharmacological chaperones (PCs), increase these levels by binding and stabilizing the native form of the enzyme in the endoplasmic reticulum (ER), and allow increased lysosomal transport of the enzyme. A high-throughput screen of the 50 000-compound Maybridge library identified two, non-carbohydrate-based inhibitory molecules, a 2,4-diamino-5-substituted quinazoline (IC50 5 μM) and a 5-substituted pyridinyl-2-furamide (IC50 8 μM). They raised the levels of functional GCase 1.5–2.5-fold in N370S or F213I GD fibroblasts. Immunofluorescence confirmed that treated GD fibroblasts had decreased levels of GCase in their ER and increased levels in lysosomes. Changes in protein dynamics, monitored by hydrogen/deuterium-exchange mass spectrometry, identified a domain III active-site loop (residues 243–249) as being significantly stabilized upon binding of isofagomine or either of these two new compounds; this suggests a common mechanism for PC enhancement of intracellular transport. PMID:18972510

  9. Composition-dependent magnetic properties of melt-spun La or/and Ce substituted nanocomposite NdFeB alloys

    NASA Astrophysics Data System (ADS)

    Hussain, M.; Zhao, L. Z.; Zhang, C.; Jiao, D. L.; Zhong, X. C.; Liu, Z. W.

    2016-02-01

    Aiming at high-performance low-cost NdFeB magnets, the magnetic properties and microstructure for melt spun nanocrystalline (Nd1-xMx)10Fe84B6 (M=La, Ce, or La0.5Ce0.5; x=0-0.7) alloys were investigated. Relatively, LaCe-substituted alloys show high values of the remanent magnetization Mr, the maximum energy product (BH)max and the coercivity Hc, up to 114 emu/g (1.07 T), 147 kJ/m3 and 471 kA/m, respectively, at x=0.1. The unusual increase in coercivity for the alloys with 10% La or 10% La0.5Ce0.5 substitution is possibly attributed to the phase segregation in alloys with certain La or LaCe contents. The reduced Curie temperature and spin-reorientation temperature were obtained for La, Ce or LaCe substituted alloys. Transmission electron microscope analysis has revealed that a fine and uniform distributed grain structure leads to remanence enhancement for La0.5Ce0.5 substituted alloys. The present results indicate that partially substituting Nd by La or/and Ce cannot only effectively reduce the cost of nanocrystalline NdFeB based magnetic powders but also can maintain a relatively good combination of magnetic properties.

  10. Structural characterisation of the polysaccharides from endemic Mongolian desert plants and their effect on the intestinal absorption of ovalbumin.

    PubMed

    Golovchenko, Victoria V; Khramova, Daria S; Shashkov, Alexandre S; Otgonbayar, Dorjgoo; Chimidsogzol, Aria; Ovodov, Yury S

    2012-07-15

    Using successive extractions with water and 0.7% aqueous ammonium oxalate, pectic polysaccharides were isolated from the following plants growing in the arid climate of Mongolia (Gobi): saxaul Haloxylon ammodendron Maxim., rhubarb Rheum nanum Sievers, Nitraria sibirica Pall., Peganum harmala L. and almond Amygdalus mongolica Maxim. The data obtained exhibited the primary synthesis of the cell wall pectic polysaccharides but not the middle lamellae water-soluble pectins in plants growing in the dry climatic zone. Both α-(1→4)-D-galacturonan and α-(1→4)-D-galacturonan, which was substituted with methyl groups, were found to be backbone of pectins. The L-arabinofuranose residues were identified as the main components of ramified regions. The pectins from almond differed from other pectins due to a high arabinose content. The data from NMR spectroscopy and methylation analyses demonstrated that pectic polysaccharides from almond included terminal, (1→5)-, (1→3)-linked and 3,5-substituted L-arabinofuranose residues and a small terminal D-galactopyranose and 2,5- and 2,3,5-substituted L-arabinofuranose residue content. The pectic polysaccharides were found to decrease the absorption of ovalbumin (OVA) in the blood from the gut lumen. The serum OVA level was lower in mice fed with OVA mixed with the pectins compared with the control group, which was administered OVA alone. PMID:22549013

  11. Formation of ternary complexes by coordination of (diethylenetriamine)-platinum(II) to N1 or N7 of the adenine moiety of the antiviral nucleotide analogue 9.

    PubMed

    Kampf, G; Lüth, M S; Kapinos, L E; Müller, J; Holý, A; Lippert, B; Sigel, H

    2001-05-01

    The synthesis of (Dien)Pt(PMEA-N1), where Dien = diethylenetriamine and PMEA2- = dianion of 9-[2-(phosphonomethoxy)ethyl]adenine, is described. The acidity constants of the threefold protonated H3[(Dien)Pt(PMEA-N1)]3+ complex were determined and in part estimated (UV spectrophotometry and potentiometric pH titration): The release of the proton from the (N7)H+ site in H4[(Dien)Pt(PMEA-N1)]3+ occurs with a rather low pKa (= 0.52+/-0.10). The release of the proton from the -P(O)2(OH) group (pKa = 6.69+/-0.03) in H[(Dien)Pt(PMEA-N1)]+ is only slightly affected by the N1-coordinated (Dien)Pt2+ unit. Comparison with the acidic properties of the H[(Dien)Pt(PMEA-N7)]+ species provides evidence that in the (Dien)Pt(PMEA-N7) complex in aqueous solution an intramolecular, outer-sphere macrochelate is formed through hydrogen bonds between the -PO3(2-) residue of PMEA2- and a PtII-coordinated (Dien)NH2 group; its formation degree amounts to about 40%. The stability constants of the M[(Dien)Pt(PMEA-N1)]2+ complexes with M2+ = Mg2+, Ca2+, Ni2+, Cu2+ and Zn2+ were measured by potentiometric pH titrations in aqueous solution at 25 degrees C and I = 0.1 M (NaNO3). Application of previously determined straight-line plots of log K(M(R-PO3))M versus pK(H(R-PO3)H for simple phosph(on)ate ligands. R-PO3(2-), where R represents a non-inhibiting residue without an affinity for metal ions, proves that the primary binding site of (Dien)Pt(PMEA-N1) is the phosphonate group with all metal ions studied; in fact, Mg2+, Ca2+ and Ni2+ coordinate (within the error limits) only to this site. For the Cu[(Dien)Pt(PMEA-N1)]2+ and Zn[(Dien)Pt(PMEA-N1)]2- systems also the formation of five-membered chelates involving the ether oxygen of the -CH2-O-CH2-PO3(2-) residue could be detected; the formation degrees are about 60% and 30%, respectively. The metal-ion-binding properties of the isomeric (Dien)Pt(PMEA-N7) species studied previously differ in so far that the resulting M[(Dien)Pt(PMEA-N7)]2+ complexes

  12. Homolytic Cleavage of Both Heme-Bound Hydrogen Peroxide and Hydrogen Sulfide Leads to the Formation of Sulfheme.

    PubMed

    Arbelo-Lopez, Hector D; Simakov, Nikolay A; Smith, Jeremy C; Lopez-Garriga, Juan; Wymore, Troy

    2016-08-01

    Many heme-containing proteins with a histidine in the distal E7 (HisE7) position can form sulfheme in the presence of hydrogen sulfide (H2S) and a reactive oxygen species such as hydrogen peroxide. For reasons unknown, sulfheme derivatives are formed specifically on solvent-excluded heme pyrrole B. Sulfhemes severely decrease the oxygen-binding affinity in hemoglobin (Hb) and myoglobin (Mb). Here, use of hybrid quantum mechanical/molecular mechanical methods has permitted characterization of the entire process of sulfheme formation in the HisE7 mutant of hemoglobin I (HbI) from Lucina pectinata. This process includes a mechanism for H2S to enter the solvent-excluded active site through a hydrophobic channel to ultimately form a hydrogen bond with H2O2 bound to Fe(III). Proton transfer from H2O2 to His64 to form compound (Cpd) 0, followed by hydrogen transfer from H2S to the Fe(III)-H2O2 complex, results in homolytic cleavage of the O-O and S-H bonds to form a reactive thiyl radical (HS(•)), ferryl heme Cpd II, and a water molecule. Subsequently, the addition of HS(•) to Cpd II, followed by three proton transfer reactions, results in the formation of a three-membered ring ferric sulfheme that avoids migration of the radical to the protein matrix, in contrast to that in other peroxidative reactions. The transformation of this three-membered episulfide ring structure to the five-membered thiochlorin ring structure occurs through a significant potential energy barrier, although both structures are nearly isoenergetic. Both three- and five-membered ring structures reveal longer NB-Fe(III) bonds compared with other pyrrole nitrogen-Fe(III) bonds, which would lead to decreased oxygen binding. Overall, these results are in agreement with a wide range of experimental data and provide fertile ground for further investigations of sulfheme formation in other heme proteins and additional effects of H2S on cell signaling and reactivity. PMID:27357070

  13. Coordination chemistry and hydrolysis of Fe(III) in a peat humic acid studied by X-ray absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Karlsson, Torbjörn; Persson, Per

    2010-01-01

    The speciation of iron (Fe) in soils, sediments and surface waters is highly dependent on chemical interactions with natural organic matter (NOM). However, the molecular structure and hydrolysis of the Fe species formed in association with NOM is still poorly described. In this study extended X-ray absorption fine structure (EXAFS) spectroscopy was used to determine the coordination chemistry and hydrolysis of Fe(III) in solution of a peat humic acid (5010-49,200 μg Fe g -1 dry weight, pH 3.0-7.2). Data were analyzed by both conventional EXAFS data fitting and by wavelet transforms in order to facilitate the identification of the nature of backscattering atoms. Our results show that Fe occurs predominantly in the oxidized form as ferric ions and that the speciation varies with pH and Fe concentration. At low Fe concentrations (5010-9920 μg g -1; pH 3.0-7.2) mononuclear Fe(III)-NOM complexes completely dominates the speciation. The determined bond distances for the Fe(III)-NOM complexes are similar to distances obtained for Fe(III) complexed by desferrioxamine B and oxalate indicating the formation of a five-membered chelate ring structure. At higher Fe concentrations (49,200 μg g -1; pH 4.2-6.9) we detect a mixture of mononuclear Fe(III)-NOM complexes and polymeric Fe(III) (hydr)oxides with an increasing amount of Fe(III) (hydr)oxides at higher pH. However, even at pH 6.9 and a Fe concentration of 49,200 μg g -1 our data indicates that a substantial amount of the total Fe (>50%) is in the form of organic complexes. Thus, in environments with significant amounts of organic matter organic Fe complexes will be of great importance for the geochemistry of Fe. Furthermore, the formation of five-membered chelate ring structures is in line with the strong complexation and limited hydrolytic polymerization of Fe(III) in our samples and also agrees with EXAFS derived structures of Fe(III) in organic soils.

  14. STRUCTURE-BASED PREDICTIVE MODEL FOR COAL CHAR COMBUSTION

    SciTech Connect

    CHRISTOPHER M. HADAD; JOSEPH M. CALO; ROBERT H. ESSENHIGH; ROBERT H. HURT

    1999-01-13

    Significant progress continued to be made during the past reporting quarter on both major technical tasks. During the reporting period at OSU, computational investigations were conducted of addition vs. abstraction reactions of H, O(3 P), and OH with monocyclic aromatic hydrocarbons. The potential energy surface for more than 80 unique reactions of H, O ( 3 P), and OH with aromatic hydrocarbons were determined at the B3LYP/6-31G(d) level of theory. The calculated transition state barriers and reaction free energies indicate that the addition channel is preferred at 298K, but that the abstraction channel becomes dominant at high temperatures. The thermodynamic preference for reactivity with aromatic hydrocarbons increases in the order O(3 P) < H < OH. Abstraction from six-membered aromatic rings is more facile than abstraction from five-membered aromatic rings. However, addition to five-membered rings is thermodynamically more favorable than addition to six-membered rings. The free energies for the abstraction and addition reactions of H, O, and OH with aromatic hydrocarbons and the characteristics of the respective transition states can be used to calculate the reaction rate constants for these important combustion reactions. Experimental work at Brown University on the effect of reaction on the structural evolution of different chars (i.e., phenolic resin char and chars produced from three different coals) have been investigated in a TGA/TPD-MS system. It has been found that samples of different age of these chars appeared to lose their "memory" concerning their initial structures at high burn-offs. During the reporting period, thermal desorption experiments of selected samples were conducted. These spectra show that the population of low temperature oxygen surface complexes, which are primarily responsible for reactivity, are more similar for the high burn-off than for the low burn-off samples of different ages; i.e., the population of active sites are more

  15. 1,2-Disilanediyl Bis(triflate), F(3)CSO(3)-SiH(2)SiH(2)-O(3)SCF(3), as the Key Intermediate for a Facile Preparation of Open-Chain and Cyclic 1,1- and 1,2-Diaminodisilanes.

    PubMed

    Söldner, Marcus; Schier, Annette; Schmidbaur, Hubert

    1997-04-23

    Convenient high-yield syntheses for several open-chain and cyclic diaminodisilanes with fully hydrogenated Si-Si linkages are reported. The key intermediate for the preparation of the title compounds, 1,2-bis(((trifluoromethyl)sulfonyl)oxy)disilane (1), reacts with 2 equiv of diethylamine to afford a mixture of the isomers Et(2)NSiH(2)SiH(2)NEt(2) (2a) and (Et(2)N)(2)SiHSiH(3) (2a'). Isopropylamine and 1 give (i)Pr(2)NSiH(2)SiH(2)N(i)Pr(2) (2b) exclusively. Treatment of 1 with 1 equiv of a primary alkylamine affords 2,3,5,6-tetrasilapiperazines [RNSiH(2)SiH(2)RNSiH(2)SiH(2); R = (i)Pr (3a), (t)Bu (3b), Bzl (3c)] comprising two SiH(2)-SiH(2) linkages. 1,3-Bifunctional bis(isopropylamino)silanes [((i)PrNH)(2)SiR(2); R = Me, Ph] were found to react with 1 to give trisilaimidazolidines [((i)PrN)SiR(2)((i)PrN)SiH(2)SiH(2); R = Me (4a), Ph (4b)] again comprising the N-SiH(2)-SiH(2)-N unit. The crystal structures of N,N'-diisopropyl-2,2-diphenyl-2,4,5-trisilaimidazolidine (4b) and N,N'-di-tert-butyl-2,3,5,6-tetrasilapiperazine (3b) were determined in X-ray diffraction studies; the five-membered ring of 4b is nearly planar with all nitrogen atoms in a planar configuration. The six-membered ring of 3b has a twist conformation, but again with the two nitrogen atoms in a planar configuration. Surprisingly, the treatment of 1 with 1,4-bifunctional N,N'-dialkylethylenediamines [(RNHCH(2)-)(2); R = (i)Pr, (t)Bu] does not give the analogous six-membered-ring compounds but leads selectively to the isomeric five-membered heterocycles [(CH(2)NR)(2)SiHSiH(3); R = (i)Pr (5a), (t)Bu (5b)], which are the products of a Si --> Si hydrogen shift rearrangement. PMID:11669777

  16. Structural and spectroscopic study of reactions between chelating zinc-binding groups and mimics of the matrix metalloproteinase and disintegrin metalloprotease catalytic sites: the coordination chemistry of metalloprotease inhibition.

    PubMed

    He, Hongshan; Puerta, David T; Cohen, Seth M; Rodgers, Kenton R

    2005-10-17

    To understand the coordination chemistry of zinc-binding groups (ZBGs) with catalytic zinc centers in matrix metalloproteinases (MMPs) and disintegrin metalloproteases (ADAMs), we have undertaken a model compound study centered around tris(3,5-methylphenypyrazolyl)hydroboratozinc(II) hydroxide and aqua complexes ([Tp(Ph,Me)ZnOH] and [Tp(Ph,Me)Zn(OH2)]+, respectively, wherein (Tp(Ph,Me))- = hydrotris(3,5-methylphenylpyrazolyl)borate) and the products of their reactions with a class of chelating Schiff's base ligands. The results show that the protic ligands, HL (HL = N-propyl-1-(5-methyl-2-imidazolyl)methanimine (5-Me-4-ImHPr), N-propyl-1-(4-imidazolyl)methanimine (4-ImHPr), and N-propyl-1-(2-imidazolyl)methanimine (2-ImHPr)), react with [Tp(Ph,Me)ZnOH] and give products with the general formula [Tp(Ph,Me)ZnL], whereas reactions with neutral aprotic ligands, L' (L' = N-propyl-1-(1-methyl-2-imidazolyl)methanimine (1-Me-2-ImPr) and N-propyl-1-(2-thiazolyl)methanimine (2-TaPr)), yield the corresponding [Tp(Ph,Me)ZnL]+ complexes. Although the phenol group of N-propyl-1-(2-hydroxyphenyl)methanimine (2-HOPhPr) is protic, this ligand forms a cationic four-coordinate complex containing an intraligand hydrogen bond. The solid-state structures of these complexes were determined by single-crystal X-ray diffraction, and the results showed that the protic ligands form five-membered chelates of the Zn2+ ion. All ligands displace the aqua ligand in [Tp(Ph,Me)Zn(OH2)]+ to yield complexes having 1H NMR spectra consistent with the formation of five membered chelates. The 1H resonance frequencies of the chelating ligands typically shift upfield upon coordination to the zinc center, due to ring current effects from the pendant phenyl groups of the (Tp(Ph,Me))- ligand. Thus, the 1H NMR spectra provide a convenient and sensitive means of tracking the solution reactions by titration. The resulting series of spectra showed that the stabilities of the chelates in solution depend on the

  17. Partial sequencing of Bm86 gene for studying the phylogeny of an Indian isolate of Rhipicephalus (Boophilus) microplus tick.

    PubMed

    Anbarasi, P; Latha, B R; Dhinakar Raj, G; Sreekumar, C; Senthuran, S

    2014-09-01

    Tick gut glycoprotein, designated as Bm86, found on the luminal surface of the plasma membrane of gut epithelial cells of Boophilus microplus, which is a concealed antigen, has been used as vaccine candidate molecule for immunization against ticks. To better understand the molecular diversity of Bm86 gene in ticks, a portion of the cDNA was sequenced from an Indian isolate of B. microplus. Comparison of nucleotide sequence revealed that Indian isolate had 97 % homology (18 polymorphisms) with that of the Australian isolate and 96 % homology (20 polymorphisms) with that of the Cuban vaccine strain. Further, the Indian isolate differed from the Cuban vaccine isolate at 7 amino acid loci, including 5 substitutions (at residues 88, 94, 175, 176 and 177) and 2 deletions (at 183 and 184). However, protein prediction studies did not show any difference in the putative antigenic epitopes of the protein expressed. PMID:25035581

  18. N-alkylated and O-alkylated regioisomers of 5-(hydroxyalkyl)pyrimidines: Synthesis and structural study

    NASA Astrophysics Data System (ADS)

    Meščić, Andrijana; Glavač, Danijel; Osmanović, Amar; Završnik, Davorka; Cetina, Mario; Makuc, Damjan; Plavec, Janez; Ametamey, Simon M.; Raić-Malić, Silvana

    2013-05-01

    Synthesis of novel 5-(2-hydroxyethyl) and 5-(3-hydroxypropyl) acyclic pyrimidine nucleosides is described. Introduction of penciclovir-like side chain in C-5 substituted pyrimidines occurred both at N-1 and O-2 position of pyrimidine moiety that was corroborated by correlation of signals in 2D HMBC spectra. Therefore, alkylation of 5-(acetoxyethyl)-4-methoxypyrimidin-2-one (2a) and 5-(acetoxypropyl)-4-methoxypyrimidin-2-one (2b) afforded mixture of N- and O-acyclic pyrimidine nucleosides in the ratio of 49: 45 (4a: 5a) and 41: 21 (4b: 5b). Structures of 5-(acetoxyalkyl)-4-methoxypyrimidin-2-ones, as the first examples of 4-methoxypyrimidin-2-ones, were unambiguously confirmed by single crystal X-ray diffraction analysis.

  19. Preparation of base-modified nucleosides suitable for non-radioactive label attachment and their incorporation into synthetic oligodeoxyribonucleotides.

    PubMed Central

    Haralambidis, J; Chai, M; Tregear, G W

    1987-01-01

    A very mild and efficient procedure has been developed for the preparation of C-5 substituted deoxyuridines. The substituent carries a masked primary aliphatic amino group. These compounds are readily converted into their phosphoramidites and can be used to prepare oligonucleotides carrying one or more aliphatic amino groups. Fluorescein isothiocyanate coupled to these compounds gives oligonucleotide probes carrying multiple fluorescein labels. These compounds have a free 5'-hydroxy group enabling additional 5'- end radioactive labelling for evaluation of their hybridization characteristics. It was found that oligonucleotides carrying a long (11 atom) linker arm to the fluorescein hybridize more efficiently to mRNA than those carrying a short (4 atom) arm. The long linker arm derivatives are comparable to underivatized oligonucleotides in hybridizing to mRNA. Images PMID:3110740

  20. Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

    PubMed Central

    Chou, Ting-Yi; ALJaroudi, Zainab; Ellis, Bobby D; Cameron, T Stanley

    2014-01-01

    Summary The synthesis of 5-substituted 6,6a-dihydroisoindolo[2,1-a]quinolin-11(5H)-ones via [4 + 2] imino-Diels–Alder cyclization from N-aryl-3-hydroxyisoindolinones and N-vinyl lactams under Lewis acid-catalysed anhydrous conditions is reported. Reactions of N-(2-substituted-aryl)-3-hydroxyisoindolinones with N-vinylpyrrolidone under identical conditions resulted in the formation of 2-(2-substitued-aryl)-3-(2-(2-oxopyrrolidin-1-yl)vinyl)isoindolin-1-one analogues indicating steric hinderance as the cause of deviation. The probable mechanism of the reaction based on the results from X-ray crystallography and molecular modelling is discussed. PMID:24778740