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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. 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

  8. 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

  9. 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

  10. 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

  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. 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.

  19. 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.

  20. 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

  1. 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

  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. 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.

  15. 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

  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. 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

  1. 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

  2. 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

  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. 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

  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. 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

  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. 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

  13. 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

  14. 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

  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. 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

  17. 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

  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. 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

  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. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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.

  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. 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.

  16. 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

  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 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  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. 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

  14. 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.

  15. 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

  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. 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

  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. 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

  20. 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

  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. 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…

  15. 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;...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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…

  5. 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...

  6. 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…

  7. 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...

  8. 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-...

  9. 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

  10. 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

  11. 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…

  12. 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

  13. 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…

  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. 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…

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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…

  12. 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)

  13. 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…

  14. 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. ...

  15. 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.

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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

  1. 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…

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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…

  9. 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

  10. 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.

  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. 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

  18. 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

  19. 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

  20. 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

  1. 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

  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. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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

  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. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. (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

  13. (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

  14. 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

  15. (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

  16. 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

  17. 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

  18. 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

  19. "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

  20. 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

  1. (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

  2. 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).

  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. 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

  8. 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

  9. 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.

  10. 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