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Sample records for poly heterocyclic molecules

  1. Organic heterocyclic molecules become superalkalis.

    PubMed

    Reddy, G Naaresh; Giri, Santanab

    2016-09-21

    An organic molecule which behaves like a superalkali has been designed from an aromatic heterocyclic molecule, pyrrole. Using first-principles calculation and a systematic two-step approach, we can have superalkali molecules with a low ionization energy, even lower than that of Cs. Couple cluster (CCSD) calculation reveals that a new heterocycle, C3N2(CH3)5 derived from a well-known aromatic heterocycle, pyrrole (C4H5N) has an ionization energy close to 3.0 eV. A molecular dynamics calculation on C3N2(CH3)5 reveals that the structure is dynamically stable. PMID:27530344

  2. Dissociative Ionization of Aromatic and Heterocyclic Molecules

    NASA Technical Reports Server (NTRS)

    Huo, Winifred M.

    2003-01-01

    Space radiation poses a major health hazard to humans in space flight. The high-energy charged particles in space radiation ranging from protons to high atomic number, high-energy (HZE) particles, and the secondary species they produce, attack DNA, cells, and tissues. Of the potential hazards, long-term health effects such as carcinogenesis are likely linked to the DNA lesions caused by secondary electrons in the 1 - 30 eV range. Dissociative ionization (DI) is one of the electron collision processes that can damage the DNA, either directly by causing a DNA lesion, or indirectly by producing radicals and cations that attack the DNA. To understand this process, we have developed a theoretical model for DI. Our model makes use of the fact that electron motion is much faster than nuclear motion and assumes DI proceeds through a two-step process. The first step is electron-impact ionization resulting in a particular state of the molecular ion in the geometry of the neutral molecule. In the second step the ion undergoes unimolecular dissociation. Thus the DI cross section sigma(sup DI)(sub a) for channel a is given by sigma(sup DI)(sub a) = sigma(sup I)(sub a) P(sub D) with sigma(sup I)(sub a) the ionization cross section of channel a and P(sub D) the dissociation probability. This model has been applied to study the DI of H2O, NH3, and CH4, with results in good agreement with experiment. The ionization cross section sigma(sup I)(sub a) was calculated using the improved binary encounter-dipole model and the unimolecular dissociation probability P(sub D) obtained by following the minimum energy path determined by the gradients and Hessians of the electronic energy with respect to the nuclear coordinates of the ion. This model is used to study the DI from the low-lying channels of benzene and pyridine to understand the different product formation in aromatic and heterocyclic molecules. DI study of the DNA base thymine is underway. Solvent effects will also be discussed.

  3. Chemistry and adhesive properties of poly(arylene ether)s containing heterocyclic units

    NASA Technical Reports Server (NTRS)

    Connell, John W.

    1991-01-01

    Novel poly(arylene ether)s containing heterocyclic units were prepared, characterized, and evaluated as adhesives and composite matrices. The polymers were prepared by reacting a heterocyclic bisphenol with an activated aromatic dihalide in a polar aprotic solvent, using potassium carbonate. The polymerizations were generally carried out in N,N-dimethylacetamide at 155 C. In some cases, where the polymers were semicrystalline, higher temperatures and thus higher boiling solvents were necessary to keep the polymers in solution. Heterocyclic rings incorporated into the poly(arylene ether) backbone include phenylquinoxaline, phenylimidazole, benzimidazole, benzoxazole, 1,3,4-oxadiazole, and 1,2,4-triazole. The polymers were characterized by differential scanning calorimetry, solution viscosity, X-ray diffraction, thin film, and adhesive and (in some cases) composite properties. The glass transition temperatures, crystalline melt temperature, solubility, and mechanical properties varied depending upon the heterocyclic ring. The chemistry and properties of these materials are discussed.

  4. Bifunctional-Phosphine-Catalyzed Sequential Annulations of Allenoates and Ketimines: Construction of Functionalized Poly-heterocycle Rings.

    PubMed

    Li, Erqing; Jin, Hongxing; Jia, Penghao; Dong, Xuelin; Huang, You

    2016-09-12

    A highly stereoselective sequential annulation reaction between γ-substituted allenoates and ketimines was reported. By using bifunctional N-acyl aminophosphine catalysts, poly-heterocycle rings were obtained with high stereocontrol in good to excellent yields. The desired products have four contiguous stereogenic centers (one quaternary and three tertiary carbon centers), and only one isomer was obtained in all reactions. PMID:27529614

  5. N-Heterocyclic molecule-capped gold nanoparticles as effective antibiotics against multi-drug resistant bacteria

    NASA Astrophysics Data System (ADS)

    Feng, Yan; Chen, Wenwen; Jia, Yuexiao; Tian, Yue; Zhao, Yuyun; Long, Fei; Rui, Yukui; Jiang, Xingyu

    2016-07-01

    We demonstrate that N-heterocyclic molecule-capped gold nanoparticles (Au NPs) have broad-spectrum antibacterial activity. Optimized antibacterial activity can be achieved by using different initial molar ratios (1 : 1 and 10 : 1) of N-heterocyclic prodrugs and the precursor of Au NPs (HAuCl4). This work opens up new avenues for antibiotics based on Au NPs.We demonstrate that N-heterocyclic molecule-capped gold nanoparticles (Au NPs) have broad-spectrum antibacterial activity. Optimized antibacterial activity can be achieved by using different initial molar ratios (1 : 1 and 10 : 1) of N-heterocyclic prodrugs and the precursor of Au NPs (HAuCl4). This work opens up new avenues for antibiotics based on Au NPs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr03317b

  6. N-Heterocyclic molecule-capped gold nanoparticles as effective antibiotics against multi-drug resistant bacteria.

    PubMed

    Feng, Yan; Chen, Wenwen; Jia, Yuexiao; Tian, Yue; Zhao, Yuyun; Long, Fei; Rui, Yukui; Jiang, Xingyu

    2016-07-21

    We demonstrate that N-heterocyclic molecule-capped gold nanoparticles (Au NPs) have broad-spectrum antibacterial activity. Optimized antibacterial activity can be achieved by using different initial molar ratios (1 : 1 and 10 : 1) of N-heterocyclic prodrugs and the precursor of Au NPs (HAuCl4). This work opens up new avenues for antibiotics based on Au NPs. PMID:27355451

  7. Pulse gas chromatographic study of adsorption of substituted aromatics and heterocyclic molecules on MIL-47 at zero coverage.

    PubMed

    Duerinck, Tim; Couck, Sarah; Vermoortele, Frederik; De Vos, Dirk E; Baron, Gino V; Denayer, Joeri F M

    2012-10-01

    The low coverage adsorptive properties of the MIL-47 metal organic framework toward aromatic and heterocyclic molecules are reported in this paper. The effect of molecular functionality and size on Henry adsorption constants and adsorption enthalpies of alkyl and heteroatom functionalized benzene derivates and heterocyclic molecules was studied using pulse gas chromatography. By means of statistical analysis, experimental data was analyzed and modeled using principal component analysis and partial least-squares regression. Structure-property relationships were established, revealing and confirming several trends. Among the molecular properties governing the adsorption process, vapor pressure, mean polarizability, and dipole moment play a determining role. PMID:22958218

  8. Equilibrium structures of heterocyclic molecules with large principal axis rotations upon isotopic substitution.

    PubMed

    Demaison, Jean; Császár, Attila G; Margulès, Laurent D; Rudolph, Heinz Dieter

    2011-12-01

    Equilibrium structures, r(e), of the heterocyclic molecules oxirane, furazan, furan, ethylene ozonide, and 1,3,4-oxadiazole have been determined using three different, somewhat complementary techniques: a completely experimental technique (r(m)), a semiexperimental technique (r(e)(SE), whereby equilibrium rotational constants are derived from experimental effective ground-state rotational constants and corrections based principally on an ab initio cubic force field), and an ab initio technique (r(e)(BO), whereby geometry optimizations are usually performed at the coupled cluster level of theory including single and double excitations augmented by a perturbational estimate of the effects of connected triple excitations [CCSD(T)] using quadruple-ζ Gaussian basis sets). All these molecules are asymmetric tops with the moment of inertia I(c) much larger than the other two moments of inertia, I(a) and I(b). Molecules of this shape experience a large rotation of the principal axis system upon certain isotopic substitutions. For such isotopologues it is difficult to obtain a good structural fit to the semiexperimental moments of inertia I(a) and I(b), which may significantly reduce the accuracy of the r(e)(SE) structural parameters. The origin of this difficulty is explained. For the heavy-atom skeleton of these molecules it was possible to determine a rather accurate empirical mass-dependent structure without a priori knowledge of the equilibrium structure. PMID:22032750

  9. Gas phase reactions of CH(3)(+) with a series of homo- and heterocyclic molecules.

    PubMed

    Fondren, L Dalila; Adams, Nigel G; Stavish, Leah

    2009-01-22

    In gas phase ion chemistry, the growth of larger molecules is known to occur through association of ions and neutrals. Where the ion attaches to the neutral is important because it can influence the possibility of additional associations, effectively enabling or terminating further molecular growth. This was investigated by using a Selected Ion Flow Tube (SIFT) at 300 K to study the reactions of CH(3)(+) with the following series of single-ring homocyclic and heterocyclic molecules: benzene (C(6)H(6)), cyclohexane (C(6)H(12)), pyridine (C(5)H(5)N), pyrimidine (C(4)H(4)N(2)), piperidine (C(5)H(11)N), 1,4-dioxane (C(4)H(8)O(2)), furan (C(4)H(4)O), pyrrole (C(4)H(5)N), and pyrrolidine (C(4)H(9)N). Most of the reactions, except for 1,4-dioxane, pyrrole, and pyrrolidine, proceed at the gas kinetic rate. In the ion product distributions, charge transfer, hydride ion abstraction, proton transfer, fragmentation, and association were observed. In particular, proton transfer is seen to be small in all cases even though these channels are energetically favorable. Association is appreciable when the molecules are aromatic (except for furan) and nonexistent when there are no pi electrons in the ring. CH(3)(+) ions are an important intermediate in molecular synthesis in interstellar clouds and in the Titan ionosphere and ring molecules have also been detected in these media. The significance of the studied reactions to these media is discussed. PMID:19090756

  10. The Depolymerization of Poly(Ethylene Terephthalate) (PET) Using N-Heterocyclic Carbenes from Ionic Liquids

    ERIC Educational Resources Information Center

    Kamber, Nahrain E.; Tsujii, Yasuhito; Keets, Kate; Waymouth, Robert M.; Pratt, Russell C.; Nyce, Gregory W.; Hedrick, James L.

    2010-01-01

    The depolymerization of the plastic polyethylene terephthalate (PET or PETE) is described in this laboratory procedure. The transesterification reaction used to depolymerize PET employs a highly efficient N-heterocyclic carbene catalyst derived from a commercially available imidazolium ionic liquid. N-heterocyclic carbenes are potent nucleophilic…

  11. Inhibition of p-nitrophenol hydroxylase in rat liver microsomes by small aromatic and heterocyclic molecules.

    PubMed

    Hargreaves, M B; Jones, B C; Smith, D A; Gescher, A

    1994-01-01

    The cytochrome P450 isoenzyme P4502E1 is constitutively expressed in human liver and catalyzes the oxidation of many known or suspected carcinogens of low molecular weight. In this structure-metabolism study, the role that heteroatoms in heterocyclic compounds play in determining their affinity for P4502E1 was investigated. The ability of 16 six-membered and 10 five-membered compounds to inhibit the hydroxylation of p-nitrophenol, which is specifically catalyzed by P4502E1, was studied in suspensions of microsomes from rat livers in which P4502E1 had been induced by inclusion of acetone in the drinking water. Apparent Ki values were extrapolated from kinetic models of Dixon or Cornish-Bowden plots for enzyme inhibition. Enzyme inhibition was generally of the non-or uncompetitive type. Pyridine was the most potent and benzene one of the least potent inhibitors, with Ki values of 0.4 microM and 8,400 microM, respectively. Pyridazine was less inhibitory than 1,3,5-triazine, which inhibited P4502E1 to a lesser degree than pyrazine and pyrimidine. Among the unsubstituted unsaturated five-membered ring molecules, pyrrole was a better inhibitor than furan or thiophene. 4-Methylimidazole was a much stronger inhibitor than imidazole or 1-and 2-methylimidazole. The ability of compounds to inhibit P4502E1 seems to depend in the main on the presence of a nitrogen atom in the molecule and on the ability of the nitrogen lone pair of electrons to ligand to the heme. PMID:7835233

  12. Toward fully nonempirical simulations of optical band shapes of molecules in solution: a case study of heterocyclic ketoimine difluoroborates.

    PubMed

    Zaleśny, Robert; Murugan, N Arul; Gel'mukhanov, Faris; Rinkevicius, Zilvinas; Ośmiałowski, Borys; Bartkowiak, Wojciech; Ågren, Hans

    2015-05-28

    This study demonstrates that a hybrid density functional theory/molecular mechanics approach can be successfully combined with time-dependent wavepacket approach to predict the shape of optical bands for molecules in solutions, including vibrational fine structure. A key step in this treatment is the estimation of the inhomogeneous broadening based on the hybrid approach, where the polarization between solute and atomically decomposed solvent is taken into account in a self-consistent manner. The potential of this approach is shown by predicting optical absorption bands for three heterocyclic ketoimine difluoroborates in solution. PMID:25418554

  13. Direct estimate of the internal π-donation to the carbene centre within N-heterocyclic carbenes and related molecules

    PubMed Central

    Andrada, Diego M; Holzmann, Nicole; Hamadi, Thomas

    2015-01-01

    Summary Fifteen cyclic and acylic carbenes have been calculated with density functional theory at the BP86/def2-TZVPP level. The strength of the internal X→p(π) π-donation of heteroatoms and carbon which are bonded to the C(II) atom is estimated with the help of NBO calculations and with an energy decomposition analysis. The investigated molecules include N-heterocyclic carbenes (NHCs), the cyclic alkyl(amino)carbene (cAAC), mesoionic carbenes and ylide-stabilized carbenes. The bonding analysis suggests that the carbene centre in cAAC and in diamidocarbene have the weakest X→p(π) π-donation while mesoionic carbenes possess the strongest π-donation. PMID:26877795

  14. Laboratory Studies of Stabilities of Heterocyclic Aromatic Molecules: Suggested Gas Phase Ion-Molecule Routes to Production in Interstellar Gas Clouds

    NASA Astrophysics Data System (ADS)

    Adams, N. G.; Fondren, L. D.; McLain, J. L.; Jackson, D. M.

    Several ring compounds have been detected in interstellar gas clouds, ISC, including the aromatic, benzene. Polycyclic aromatic hydrocarbons, PAH's, have been implicated as carriers of diffuse interstellar bands (DIB's) and unidentified infrared (UIR) bands. Heterocyclic aromatic rings of intermediate size containing nitrogen, possibly PreLife molecules, were included in early searches but were not detected and a recent search for Pyrimidine was unsuccessful. Our laboratory investigations of routes to such molecules could establish their existence in ISC and suggest conditions under which their concentrations would be maximized thus aiding the searches. The stability of such ring compounds (C_5H_5N, C_4H_4N_2, C_5H_{11}N and C_4H_8O_2) has been tested in the laboratory using charge transfer excitation in ion-molecule reactions. The fragmentation paths, including production of C_4H_4^+, C_3H_3N^+ and HCN, suggest reverse routes to the parent molecules, which are presently under laboratory investigation as production sources.

  15. Laboratory Studies of Stabilities of Heterocyclic Aromatic Molecules: Suggested Gas Phase Ion-Molecule Routes to Production in Interstellar Gas Clouds

    NASA Technical Reports Server (NTRS)

    Adams, Nigel G.; Fondren, L. Dalila; McLain, Jason L.; Jackson, Doug M.

    2006-01-01

    Several ring compounds have been detected in interstellar gas clouds, ISC, including the aromatic, benzene. Polycyclic aromatic hydrocarbons, PAHs, have been implicated as carriers of diffuse interstellar bands (DIBs) and unidentified infrared (UIR) bands. Heterocyclic aromatic rings of intermediate size containing nitrogen, possibly PreLife molecules, were included in early searches but were not detected and a recent search for Pyrimidine was unsuccessful. Our laboratory investigations of routes to such molecules could establish their existence in ISC and suggest conditions under which their concentrations would be maximized thus aiding the searches. The stability of such ring compounds (C5H5N, C4H4N2, C5H11N and C4H8O2) has been tested in the laboratory using charge transfer excitation in ion-molecule reactions. The fragmentation paths, including production of C4H4(+), C3H3N(+) and HCN, suggest reverse routes to the parent molecules, which are presently under laboratory investigation as production sources.

  16. Caveats for poly(methimazolyl)borate chemistry: the novel inorganic heterocycles [H2C(mt)2BR2]Cl (mt = methimazolyl; BR2 = BH2, BH(mt), 9-BBN).

    PubMed

    Crossley, Ian R; Hill, Anthony F; Humphrey, Elizabeth R; Smith, Matthew K; Tshabang, Never; Willis, Anthony C

    2004-08-21

    Whilst frequently used for reactions of poly(methimazolyl)borates, dichloromethane is not an innocent solvent, but rather slowly forms heterocyclic salts [H(2)C(mt)(2)BR(2)]Cl, three examples of which (BR(2) = BH(2), BH(mt), 9-borabicyclononyl) have been structurally characterised to confirm the unprecedented B(NCS)(2)C connectivity. PMID:15306929

  17. Synthesis of Previously Inaccessible Borylated Heterocycle Motifs Using Novel Boron-Containing Amphoteric Molecules.

    PubMed

    Trinchera, Piera; Corless, Victoria B; Yudin, Andrei K

    2015-07-27

    The photoredox-organocatalyzed α-alkylation of the α-MIDA boryl aldehyde with a range of α-bromoketones resulted in the first examples of boron-containing 1,4-dicarbonyl compounds. These novel trifunctional amphoteric molecules, which bear an additional, strategically placed electrophilic site compared to the starting amphoteric α-boryl aldehyde, were subjected to double-condensation reactions in the presence of various nucleophiles. As a result, a variety of synthetically challenging 3-borylated pyrroles and furans and 4-borylated pyridazines were generated. The borylated regioisomers accessible with this condensation-based strategy are distinctly different from those arising from the well-known lithiation and C-H activation processes. PMID:26110917

  18. A heterocyclic molecule kartogenin induces collagen synthesis of human dermal fibroblasts by activating the smad4/smad5 pathway.

    PubMed

    Wang, Jing; Zhou, Jia; Zhang, Ning; Zhang, Xiaoling; Li, Qingfeng

    2014-07-18

    Declined production of collagen by fibroblasts is one of the major causes of aging appearance. However, only few of compounds found in cosmetic products are able to directly increase collagen synthesis. A novel small heterocyclic compound called kartogenin (KGN) was found to stimulate collagen synthesis of mesenchymal stem cells (MSCs). So, we hypothesized and tested that if KGN could be applied to stimulate the collagen synthesis of fibroblasts. Human dermal fibroblasts in vitro were treated with various concentrations of KGN, with dimethyl sulfoxide (DMSO) serving as the negative control. Real-time reverse-transcription polymerase chain reaction, Western blot, and immunofluorescence analyses were performed to examine the expression of collagen and transforming growth factor beta (TGF-β) signaling pathway. The production of collagen was also tested in vivo by Masson's trichrome stain and immunohistochemistry in the dermis of mice administrated with KGN. Results showed that without obvious influence on fibroblasts' apoptosis and viability, KGN stimulated type-I collagen synthesis of fibroblasts at the mRNA and protein levels in a time-dependent manner, but KGN did not induce expression of α-skeletal muscle actin (α-sma) or matrix metallopeptidase1 (MMP1), MMP9 in vitro. Smad4/smad5 of the TGF-β signaling pathway was activated by KGN while MAPK signaling pathway remained unchanged. KGN also increased type-I collagen synthesis in the dermis of BALB/C mice. Our results indicated that KGN promoted the type-I collagen synthesis of dermal fibroblasts in vitro and in the dermis of mice through activation of the smad4/smad5 pathway. This molecule could be used in wound healing, tissue engineering of fibroblasts, or aesthetic and reconstructive procedures. PMID:24928394

  19. Understanding the relationships between molecule structure and imprinting effect of two acetyl-nitrogen heterocyclic compounds.

    PubMed

    Wang, Jian; Dong, Xiao; Xue, Min; Dong, Xuemin; Xu, Zhibin; Meng, Zihui; Luo, Jun

    2016-06-01

    The molecularly imprinted polymers (MIPs) for two structural analogs, 1,3,5-triacetyl-1,3,5-triazacyclohexane (TRAT) and 1,3,5,7-tetraacetyl-1,3,5,7-tetraazacyclooctane (TAT), have been synthesized respectively under the same conditions. The TAT-MIP showed excellent imprinting effect, whereas the TRAT-MIP did not. To understand the different imprinting effects of the MIPs prepared from these two templates, the geometric structures and energetic properties of complexes formed around TAT and TRAT were studied computationally. The results indicate that in liquid phase, for the complexes formed with TAT and its nearest neighbor molecules, the magnitude of the binding energy increases with the number of surrounding TAT, methacrylic acid, and acetonitrile (ACT), whereas for the cases of TRAT, the magnitude of the binding energy increases with the number of surrounding TRAT and trimethylolpropane trimethacrylate. The studied systems form stronger and thus more stable networks encapsulating TAT than with TRAT. ACT may also play an important role in the polymerization phase in stabilizing the shapes of the cavities that TATs reside in. We propose these as the major factors that affect the different imprinting effects of the two MIPs. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26787468

  20. Stabilities of nitrogen containing heterocyclic radicals and geometrical influences on non-radiative processes in organic molecules

    NASA Technical Reports Server (NTRS)

    Evleth, E. M.

    1972-01-01

    Stabilities of nitrogen containing heterocyclic radicals were studied to detect radicals of the type R-N-R, and to theoretically rationalize their electronic structure. The computation of simple potential energy surfaces for ground and excited states is discussed along with the photophysical properties of indolizine. Methods of calculation and problems associated with the calculations are presented. Results, tables, diagrams, discussions, and references are included.

  1. Syntheses, characterizations and photoluminescent properties of two novel coordination polymers constructed by poly-carboxylate and N-heterocyclic ligands

    NASA Astrophysics Data System (ADS)

    Yan, Li; Li, Chuanbi; Wang, Yifei

    2013-03-01

    Two novel coordination compounds constructed from aromatic acid and N-heterocyclic ligands, namely, [Mn(dipt)2(n-BDC)]n (1) [dipt = 2-(2,4-dichlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline, n-BDC = 5-nitrobenzene-1,3-dioic acid] and [Cu2(bip)2(m-BDC)2(H2O)3]ṡ2H2O (2) [bip = 2-(4-bromophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline, m-BDC = isophthalic acid] have been synthesized by hydrothermal reaction: compounds 1 and 2 were characterized by elemental analysis, infrared spectrum (IR), single crystal X-ray diffraction and thermogravimetric analysis (TGA). In 1, n-BDC anions link the adjacent Mn(II) centers to generate a one-dimensional (1D) zigzag chain. Furthermore, unprecedented intersections of C-H⋯O bonds lead 1D chain into 2D sheet supra-molecular architecture. Differed from 1, 2 exhibits 0D structure, and displays a 2D topology via strong H-bond and π-π stacking interactions. TG analysis shows clear courses of weight loss, which corresponds to the decomposition of different ligands. The structure-related solid-state fluorescence spectra of compounds 1 and 2 have been determined, and the result displays that compounds 1 and 2 are potential luminescent material.

  2. Visualizing and quantifying protein polySUMOylation at the single-molecule level.

    PubMed

    Yang, Yong; Zhang, Chun-yang

    2014-01-21

    Protein polySUMOylation, the attachment of small ubiquitin-like modifier (SUMO) chains to the target protein, is associated with a variety of physiological processes. However, the analysis of protein polySUMOylation is often complicated by the heterogeneity of SUMO-target conjugates. Here, we develop a new strategy to visualize and quantify polySUMOylation at the single-molecule level by integrating the tetracysteine (TC) tag labeling technology and total internal reflection fluorescence (TIRF)-based single-molecule imaging. As a proof-of-concept, we employ the human SUMO-2 as the model. The addition of TC tag to SUMO-2 can specifically translate the SUMO-mediated modification into visible fluorescence signal without disturbing the function of SUMO-2. The SUMO monomers display homogeneous fluorescence spots at the single-molecule level, whereas the mixed SUMO chains exhibit nonuniform fluorescence spots with a wide range of intensities. Analysis of the number and the brightness of fluorescence spots enable quantitative measurement of the polySUMOylation degree inside the cells under different physiological conditions. Due to the frequent occurrence of posttranslational modification by polymeric chains in cells, this single-molecule strategy has the potential to be broadly applied for studying protein posttranslational modification in normal cellular physiology and disease etiology. PMID:24383460

  3. 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.

  4. Smart magnetic poly(N-isopropylacrylamide) to control the release of bio-active molecules.

    PubMed

    Dionigi, Chiara; Lungaro, Lisa; Goranov, Vitaly; Riminucci, Alberto; Piñeiro-Redondo, Yolanda; Bañobre-López, Manuel; Rivas, José; Dediu, Valentin

    2014-10-01

    Thermo switchable magnetic hydrogels undoubtedly have a great potential for medical applications since they can behave as smart carriers able to transport bioactive molecules to a chosen part of the body and release them on demand via magneto-thermal activation. We report on the ability to modify the lower critical solution temperature (LCST) of poly(N-isopropylacrylamide) (PNIPAM) on demand from 32 °C to LCST ≥ 37 °C. This was achieved by the absorption of controlled amounts of magnetite nanoparticles on the polymer chains. We show, through the effect on cell viability, that the resulting magnetic PNIPAM is able to trap and to release bio-active molecules, such as cell growth factors. The activities of the released bio molecule are tested on human umbilical vein endothelial cells culture. We demonstrate that the LCST of the magnetic PNIPAM can be reached remotely via inductive heating with an alternating magnetic field. This approach on magnetic PNIPAM clearly supports appealing applications in safe biomedicine. PMID:24477874

  5. Single molecule force spectroscopy by AFM indicates helical structure of poly(ethylene-glycol) in water

    NASA Astrophysics Data System (ADS)

    Oesterhelt, F.; Rief, M.; Gaub, H. E.

    1999-03-01

    We elongated individual poly(ethylene-glycol) (PEG) molecules tethered at one end to an AFM cantilever. We observed the resistive force as a function of elongation in different solvents. In all cases the molecular response was found to be fully reversible and thus in thermodynamic equilibrium. In hexadecane the stretched PEG acts like an ideal entropy spring and can be well described as a freely jointed chain. In water we observed marked deviations in the transition region from entropic to enthalpic elasticity, indicating the deformation of a supra-structure within the polymer. An analysis based on elastically coupled Markovian two-level systems agrees well with recent ab initio calculations predicting that PEG in water forms a non-planar supra-structure which is stabilized by water bridges. We obtained a binding free energy of 3.0+/-0.3 kT.

  6. Complete free energy landscape and statistical thermodynamics of single poly(ethylene glycol) molecules

    NASA Astrophysics Data System (ADS)

    Staple, Douglas; Hanke, Felix; Kreuzer, Hans Jürgen

    2007-03-01

    In this paper, we revisit the statistical mechanics of poly(ethylene glycol) with the intention to check ad hoc approximations made in previous works, namely to keep all C O bonds along the chain in the trans configuration. The theory developed here includes all the bonds on an equal footing. Starting with density functional theory calculations for the ethylene glycol monomer, dimer and trimer one can determine all the energetic and geometric parameters needed for a rotationally isomeric state model with interactions between nearest neighbour monomers included. The properties of short molecules are presented in detail, including the force-extension curves, end-to-end distributions, and also a discussion of the local helix properties. Finally, we use the transfer matrix method for long chains of 200 ethylene glycol monomers, i.e. 600 bonds. The agreement with the experimental force-extension curve is excellent.

  7. Conformational study of a single molecule of poly para phenylene ethynylenes in dilute solutions

    NASA Astrophysics Data System (ADS)

    Maskey, Sabina; Pierce, Flint; Perahia, Dvora; Grest, Gary S.

    2011-06-01

    The conformation of single molecules of dialkyl poly para phenylene ethynylenes (PPEs), electro-active polymers, is studied in solutions using molecular dynamics simulations. The conformation of conjugated polymers affects their electro-optical properties and therefore is critical to their current and potential uses, though only limited theoretical knowledge is available regarding the factors that control their configuration. The present study investigates the affects of molecular parameters including molecular weight of the polymer and chemical structure of the side chains of PPEs in different solvents on the conformation of the polymers. The PPEs are modeled atomistically where the solvents are modeled both implicitly and explicitly. The study finds that PPEs assume extended configuration which is affected by the length of the polymer backbone and the nature and length of substituting side chains. While the polymer remains extended, local dynamics is retained and no long range correlations are observed within the backbone. The results are compared with scattering experiments.

  8. Delivery of large molecules via poly(butyl cyanoacrylate) nanoparticles into the injured rat brain

    NASA Astrophysics Data System (ADS)

    Lin, Yong; Pan, Yaohua; Shi, Yinfeng; Huang, Xianjian; Jia, Nengqin; Jiang, Ji-yao

    2012-04-01

    Poly(n-butyl-2-cyanoacrylate) (PBCA) nanoparticles have been successfully applied to deliver small-molecule drugs to the central nervous system (CNS). However, it is unclear whether PBCA nanoparticles can be used as the delivery system for large molecules to potentially treat traumatic brain injury (TBI). In this study, we tested the capacity of PBCA nanoparticles in passing through the blood-brain barrier (BBB) and transporting large molecules into normal and injured brains in the rat. We first synthesized PBCA nanoparticles by dispersion polymerization and then loaded the particles with either horseradish peroxidase (HRP, 44 kDa) or enhanced green fluorescent protein (EGFP, 29 kDa), which were further coated with polysorbate 80. Next, the polysorbate 80-coated HRP or EGFP-loaded PBCA nanoparticles were intravenously injected into the normal and brain-injured rats. We found that, at 45 min after injection, PBCA nanoparticle-delivered HRP or EGFP was hardly detected in the normal brains of the rats, but a small amount of EGFP carried by PBCA nanoparticles was noted in the normal brains 48 h after administration, which was further confirmed by immunolocalization with anti-EGFP antibodies. In contrast, at 4 h after TBI with a circulation time of 45 min, although the penetration of HRP or EGFP alone was hampered by the BBB, the PBCA nanoparticle-delivered HRP or EGFP was widely distributed near injured sites. Together, our findings provide histological evidence that PBCA nanoparticles can be used as an efficient delivery system for large molecules to overcome the barrier in the brain with TBI.

  9. Cross-Linking Poly(lactic acid) Film Surface by Neutral Hyperthermal Hydrogen Molecule Bombardment.

    PubMed

    Du, Wangli; Shao, Hong; He, Zhoukun; Tang, Changyu; Liu, Yu; Shen, Tao; Zhu, Yan; Lau, Woon-ming; Hui, David

    2015-12-16

    Constructing a dense cross-linking layer on a polymer film surface is a good way to improve the water resistance of poly(lactic acid) (PLA). However, conventional plasma treatments have failed to achieve the aim as a result of the unavoidable surface damage arising from the charged species caused by the uncontrolled high energy coming from colliding ions and electrons. In this work, we report a modified plasma method called hyperthermal hydrogen-induced cross-linking (HHIC) technology to construct a dense cross-linking layer on PLA film surfaces. This method produces energy-controlled neutral hyperthermal hydrogen, which selectively cleaves C-H bonds by molecule collision from the PLA film without breaking other bonds (e.g., C-C bonds in the polymer backbone), and results in subsequent cross-linking of the carbon radicals generated from the organic molecules. The formation of a dense cross-linking layer can serve as a barrier layer to significantly improve both the hydrophobicity and water vapor barrier property of the PLA film. Because of the advantage of selective cleavage of C-H bonds by HHIC treatment, the original physical properties (e.g., mechanical strength and light transmittance) of the PLA films are well-preserved. PMID:26594874

  10. Homogeneously aligned liquid crystal molecules on reformed poly(methyl methacrylate) via ion-beam irradiation

    NASA Astrophysics Data System (ADS)

    Jeong, Hae-Chang; Park, Hong-Gyu; Lee, Ju Hwan; Jang, Sang Bok; Oh, Byeong-Yun; Han, Jeong-Min; Seo, Dae-Shik

    2016-04-01

    We demonstrated uniform LC alignment using IB-irradiated poly(methyl methacrylate) (PMMA) as an alignment layer. We confirmed the topographical changes on PMMA caused by IB irradiation. Moreover, the wettability and chemical modification of the PMMA surface were investigated as functions of incidence angle. The results show that PMMA irradiated with IB at an incidence angle of 30° had a higher molecular polarity than PMMA irradiated with IB at other incidence angles, resulting in strong van der Waals interactions between the surface and LC molecules. The LC cells containing PMMA irradiated with IB at an incidence angle of 30° exhibited good thermal stability (180°) compared with LC cells containing conventional rubbing PI (150°). In addition, LC molecules on PMMA irradiated with IB at an incidence angle of 30° were observed to switch faster than those on conventional rubbing PI. Therefore, PMMA irradiated with IB under the optimal conditions may allow for PMMA to be applied in advanced LC devices as an alternative alignment layer.

  11. (211)At-labeled and biotinylated effector molecules for pretargeted radioimmunotherapy using poly-L- and poly-D-Lysine as multicarriers.

    PubMed

    Lindegren, Sture; Karlsson, Börje; Jacobsson, Lars; Andersson, Håkan; Hultborn, Ragnar; Skarnemark, Gunnar

    2003-09-01

    Poly-L- and poly-D-lysine were evaluated as carriers of astatine and biotin for prospective use as effector molecules in pretargeted radioimmunotherapy of micrometastases. The precursor polylysine was derivatized in a three-step, single-pot procedure, including biotinylation with biotin amidocaproic N-hydroxysuccinimide, astatination via the intermediate reagent N-succinimidyl 3-(trimethylstannyl)benzoate, and, finally, charge modification using succinic anhydride. The chemistry was shown to be very facile, with a biotinylation efficiency of 75 +/- 5%, and overall radiochemical yields in the range of 50-70%. After charge modification, no amines could be detected in the final product. The biotin function was unaffected by the chemistry and the radiation, as confirmed by almost complete binding of the effector molecule to avidin beads using a convenient filter tube assay. The effector molecules were evaluated in tumor-free female nude mice with regard to whole-body retention and tissue distribution after i.p. administration. The distribution of the L-isomer effector molecule showed rapid whole-body clearance with low uptake in all tissues, whereas the D-isoform showed whole-body clearance related to uptake in the kidneys. Both D-isomer and L-isomer showed faster blood clearance and generally lower tissue uptakes than labeled antibodies. The normal tissue distribution after the peritoneal administration implies that pretargeting using L-structure polylysine as the effector molecule may give a higher therapeutic index than that achieved in conventional radioimmunotherapy. PMID:14506185

  12. Proton-bound dimers of nitrogen heterocyclic molecules: Substituent effects on the structures and binding energies of homodimers of diazine, triazine, and fluoropyridine

    SciTech Connect

    Attah, Isaac K.; Platt, Sean P.; Meot-Ner, Michael; El-Shall, M. S.; Aziz, Saadullah G.; Alyoubi, Abdulrahman O.

    2014-03-21

    The bonding energies of proton-bound homodimers BH{sup +}B were measured by ion mobility equilibrium studies and calculated at the DFT B3LYP/6-311++G{sup **} level, for a series of nitrogen heterocyclic molecules (B) with electron-withdrawing in-ring N and on-ring F substituents. The binding energies (ΔH°{sub dissoc}) of the proton-bound dimers (BH{sup +}B) vary significantly, from 29.7 to 18.1 kcal/mol, decreasing linearly with decreasing the proton affinity of the monomer (B). This trend differs significantly from the constant binding energies of most homodimers of other organic nitrogen and oxygen bases. The experimentally measured ΔH°{sub dissoc} for (1,3-diazine){sub 2}H{sup +}, i.e., (pyrimidine){sub 2}H{sup +} and (3-F-pyridine){sub 2}H{sup +} are 22.7 and 23.0 kcal/mol, respectively. The measured ΔH°{sub dissoc} for the pyrimidine{sup ·+}(3-F-pyridine) radical cation dimer (19.2 kcal/mol) is signifcantly lower than that of the proton-bound homodimers of pyrimidine and 3-F-pyridine, reflecting the stronger interaction in the ionic H-bond of the protonated dimers. The calculated binding energies for (1,2-diazine){sub 2}H{sup +}, (pyridine){sub 2}H{sup +}, (2-F-pyridine){sub 2}H{sup +}, (3-F-pyridine){sub 2}H{sup +}, (2,6-di-F-pyridine){sub 2}H{sup +}, (4-F-pyridine){sub 2}H{sup +}, (1,3-diazine){sub 2}H{sup +}, (1,4-diazine){sub 2}H{sup +}, (1,3,5-triazine){sub 2}H{sup +}, and (pentafluoropyridine){sub 2}H{sup +} are 29.7, 24.9, 24.8, 23.3, 23.2, 23.0, 22.4, 21.9, 19.3, and 18.1 kcal/mol, respectively. The electron-withdrawing substituents form internal dipoles whose electrostatic interactions contribute to both the decreased proton affinities of (B) and the decreased binding energies of the protonated dimers BH{sup +}B. The bonding energies also vary with rotation about the hydrogen bond, and they decrease in rotamers where the internal dipoles of the components are aligned efficiently for inter-ring repulsion. For compounds substituted at the 3 or 4

  13. Proton-bound dimers of nitrogen heterocyclic molecules: Substituent effects on the structures and binding energies of homodimers of diazine, triazine, and fluoropyridine

    NASA Astrophysics Data System (ADS)

    Attah, Isaac K.; Platt, Sean P.; Meot-Ner Mautner, Michael; El-Shall, M. S.; Aziz, Saadullah G.; Alyoubi, Abdulrahman O.

    2014-03-01

    The bonding energies of proton-bound homodimers BH+B were measured by ion mobility equilibrium studies and calculated at the DFT B3LYP/6-311++G** level, for a series of nitrogen heterocyclic molecules (B) with electron-withdrawing in-ring N and on-ring F substituents. The binding energies (ΔH°dissoc) of the proton-bound dimers (BH+B) vary significantly, from 29.7 to 18.1 kcal/mol, decreasing linearly with decreasing the proton affinity of the monomer (B). This trend differs significantly from the constant binding energies of most homodimers of other organic nitrogen and oxygen bases. The experimentally measured ΔH°dissoc for (1,3-diazine)2H+, i.e., (pyrimidine)2H+ and (3-F-pyridine)2H+ are 22.7 and 23.0 kcal/mol, respectively. The measured ΔH°dissoc for the pyrimidine.+(3-F-pyridine) radical cation dimer (19.2 kcal/mol) is signifcantly lower than that of the proton-bound homodimers of pyrimidine and 3-F-pyridine, reflecting the stronger interaction in the ionic H-bond of the protonated dimers. The calculated binding energies for (1,2-diazine)2H+, (pyridine)2H+, (2-F-pyridine)2H+, (3-F-pyridine)2H+, (2,6-di-F-pyridine)2H+, (4-F-pyridine)2H+, (1,3-diazine)2H+, (1,4-diazine)2H+, (1,3,5-triazine)2H+, and (pentafluoropyridine)2H+ are 29.7, 24.9, 24.8, 23.3, 23.2, 23.0, 22.4, 21.9, 19.3, and 18.1 kcal/mol, respectively. The electron-withdrawing substituents form internal dipoles whose electrostatic interactions contribute to both the decreased proton affinities of (B) and the decreased binding energies of the protonated dimers BH+B. The bonding energies also vary with rotation about the hydrogen bond, and they decrease in rotamers where the internal dipoles of the components are aligned efficiently for inter-ring repulsion. For compounds substituted at the 3 or 4 (meta or para) positions, the lowest energy rotamers are T-shaped with the planes of the two rings rotated by 90° about the hydrogen bond, while the planar rotamers are weakened by repulsion between the

  14. Poly(ortho ester) nanoparticle-based targeted intraocular therapy for controlled release of hydrophilic molecules.

    PubMed

    Palamoor, Mallika; Jablonski, Monica M

    2013-02-01

    Development of an efficient intraocular drug delivery nanosystem remains the most difficult challenge to attain a prolonged therapeutic effect at the site of drug action. The purpose of this work was to develop a biodegradable, long-term sustained release, and biocompatible nanoparticulate system to treat various intraocular diseases. To attain the objectives, poly(ortho ester) (POE), a hydrophobic, surface erodible, and nontoxic polymer, was selected for fabrication of nanoparticles for the first time using a double emulsion solvent evaporation method. The influence of POE molecular weight on particle size, polydispersity index, zeta potential, drug content, in vitro release, degradation, in vitro cytotoxicity, and cell uptake studies was investigated. Drug-loaded nanoparticles had a spherical shape with an average particle diameter from 241 to 298 nm and zeta potential values from -8 to -11 mV. Encapsulation efficiency ranged between 21 and 63%, depending on the type of the water-soluble molecule used. Approximately 20-30% of the loaded drug was released over a period of 14 weeks. The drug release and degradation profiles of nanoparticles followed perfect zero-order kinetics confirming the POE-surface erosion mechanism. In vitro cytotoxicity and cell uptake studies revealed the cyto-compatible nature and nonendocytic behavior of POE nanoparticles. Collectively, POE nanoparticles are a very promising vehicle for sustained delivery of therapeutics to the back of the eye. PMID:23256649

  15. Dielectric dependence of single-molecule photoluminescence intermittency: nile red in poly(vinylidene fluoride).

    PubMed

    Hess, Chelsea M; Riley, Erin A; Reid, Philip J

    2014-07-24

    The dependence of single-molecule photoluminescence intermittency (PI) or "blinking" on the local dielectric constant (ε) is examined for nile red (NR) in thin films of poly(vinylidene fluoride) (PVDF). In previous studies, variation of the local dielectric constant was accomplished by studying luminophores in chemically and structurally different hosts. In contrast, the NR/PVDF guest-host pair allows for the investigation of PI as a function of ε while keeping the chemical composition of both the luminophore and host unchanged. The solvatochromic properties of NR are used to measure the local ε, while fluctuations in NR emission intensity over time provide a measure of the PI. PVDF is an ideal host for this study because it provides submicron-sized dielectric domains that vary from nonpolar (ε ≈ 2) to very polar (ε ≈ 70). The results presented here demonstrate that the local dielectric environment can have a pronounced effect on PI. We find that the NR emissive events increase 5-fold with an increase in ε from 2.2 to 74. A complex dependence on ε is also observed for NR nonemissive event durations, initially increasing as ε increases from 2.2 to 3.4 but decreasing in duration with further increase in ε. The variation in emissive event durations with ε is reproduced using a photoinduced electron-transfer model involving electron transfer from NR to PVDF. In addition, an increase in NR photostability with an increase in ε is observed, suggesting that the dielectric environment plays an important role in defining the photostability of NR in PVDF. PMID:24995904

  16. Design, diversity-oriented synthesis and structure activity relationship studies of quinolinyl heterocycles as antimycobacterial agents.

    PubMed

    Rachakonda, Venkatesham; Alla, Manjula; Kotipalli, Sudha Sravanti; Ummani, Ramesh

    2013-01-01

    The current study reports design and diversity oriented synthesis of novel bis heterocycles with a common 2-methyl, C-4 unsubstituted quinoline moiety as the central key heterocycle. Employing reagent based skeletal diversity approach; a facile synthesis of bis heterocycles with different heterocyclic rings at C-3 position of the quinoline moiety has been accomplished. A broad range of heterocyclic frameworks thus obtained were evaluated for their antimycobacterial activity. The active scaffolds were further explored by a parallel library generation in order to establish SAR. Further, low cytotoxicity against A549 cell line enhances the potential of the synthesized molecules as promising antimycobacterial agents. PMID:24189497

  17. Alkali-Metal-Mediated Magnesiations of an N-Heterocyclic Carbene: Normal, Abnormal, and "Paranormal" Reactivity in a Single Tritopic Molecule.

    PubMed

    Martínez-Martínez, Antonio J; Fuentes, M Ángeles; Hernán-Gómez, Alberto; Hevia, Eva; Kennedy, Alan R; Mulvey, Robert E; O'Hara, Charles T

    2015-11-16

    Herein the sodium alkylmagnesium amide [Na4Mg2(TMP)6(nBu)2] (TMP=2,2,6,6-tetramethylpiperidide), a template base as its deprotonating action is dictated primarily by its 12 atom ring structure, is studied with the common N-heterocyclic carbene (NHC) IPr [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]. Remarkably, magnesiation of IPr occurs at the para-position of an aryl substituent, sodiation occurs at the abnormal C4 position, and a dative bond occurs between normal C2 and sodium, all within a 20 atom ring structure accommodating two IPr(2-). Studies with different K/Mg and Na/Mg bimetallic bases led to two other magnesiated NHC structures containing two or three IPr(-) monoanions bound to Mg through abnormal C4 sites. Synergistic in that magnesiation can only work through alkali-metal mediation, these reactions add magnesium to the small cartel of metals capable of directly metalating a NHC. PMID:26417985

  18. Pincer-CNC mononuclear, dinuclear and heterodinuclear Au(iii) and Pt(ii) complexes supported by mono- and poly-N-heterocyclic carbenes: synthesis and photophysical properties.

    PubMed

    Gonell, S; Poyatos, M; Peris, E

    2016-04-01

    A family of cyclometallated Au(iii) and Pt(ii) complexes containing a CNC-pincer ligand (CNC = 2,6-diphenylpyridine) supported by pyrene-based mono- or bis-NHC ligands have been synthesized and characterized, together with the preparation of a Pt-Au hetero-dimetallic complex based on a Y-shaped tris-NHC ligand. The photophysical properties of all the new species and of two related Ru(ii)-arene complexes were studied and compared. Whereas the pyrene-based complexes only exhibit emission in solution, those containing the Y-shaped tris-NHC ligand are only luminescent when dispersed in poly(methyl methacrylate) (PMMA). In particular, the pyrene-based complexes were found to be emissive in the range of 373-440 nm, with quantum yields ranging from 3.1 to 6.3%, and their emission spectra were found to be almost superimposable, pointing to the fluorescent pyrene-centered nature of the emission. This observation suggests that the emission properties of the pyrene fragment may be combined with some of the numerous applications of NHCs as supporting ligands allowing, for instance, the design of biological luminescent agents. PMID:26911885

  19. The Domino Way to Heterocycles

    PubMed Central

    Padwa, Albert; Bur, Scott K.

    2007-01-01

    Sequential transformations enable the facile synthesis of complex target molecules from simple building blocks in a single preparative step. Their value is amplified if they also create multiple stereogenic centers. In the ongoing search for new domino processes, emphasis is usually placed on sequential reactions which occur cleanly and without forming by-products. As a prerequisite for an ideally proceeding one-pot sequential transformation, the reactivity pattern of all participating components has to be such that each building block gets involved in a reaction only when it is supposed to do so. The development of sequences that combine transformations of fundamentally different mechanisms broadens the scope of such procedures in synthetic chemistry. This mini review contains a representative sampling from the last 15 years on the kinds of reactions that have been sequenced into cascades to produce heterocyclic molecules. PMID:17940591

  20. The conversion of allenes to strained three-membered heterocycles.

    PubMed

    Adams, C S; Weatherly, C D; Burke, E G; Schomaker, J M

    2014-05-01

    This article reviews methods for converting allenes to strained, three-membered methylene heterocycles, and also covers the reactivity of these products. Specifically, the synthesis and reactivity of methylene aziridines, allene oxides/spirodiepoxides, methylene silacyclopropanes, methylene phosphiranes, and methylene thiiranes are described, including applications to the synthesis of complex molecules. Due to the primary focus on heterocyclic motifs, the all-carbon analogue of these species (methylene cyclopropane) is only briefly discussed. PMID:24647416

  1. Stretching of single poly-ubiquitin molecules revisited: Dynamic disorder in the non-exponential unfolding kinetics

    NASA Astrophysics Data System (ADS)

    Zheng, Yue; Bian, Yukun; Zhao, Nanrong; Hou, Zhonghuai

    2014-03-01

    A theoretical framework based on a generalized Langevin equation (GLE) with fractional Gaussian noise (fGn) and a power-law memory kernel is presented to describe the non-exponential kinetics of the unfolding of a single poly-ubiquitin molecule under a constant force [T.-L. Kuo, S. Garcia-Manyes, J. Li, I. Barel, H. Lu, B. J. Berne, M. Urbakh, J. Klafter, and J. M. Fernández, Proc. Natl. Acad. Sci. U.S.A. 107, 11336 (2010)]. Such a GLE-fGn strategy is made on the basis that the pulling coordinate variable x undergoes subdiffusion, usually resulting from conformational fluctuations, over a one-dimensional force-modified free-energy surface U(x, F). By using the Kramers' rate theory, we have obtained analytical formulae for the time-dependent rate coefficient k(t, F), the survival probability S(t, F) as well as the waiting time distribution function f(t, F) as functions of time t and force F. We find that our results can fit the experimental data of f(t, F) perfectly in the whole time range with a power-law exponent γ = 1/2, the characteristic of typical anomalous subdiffusion. In addition, the fitting of the survival probabilities for different forces facilitates us to reach rather reasonable estimations for intrinsic properties of the system, such as the free-energy barrier and the distance between the native conformation and the transition state conformation along the reaction coordinate, which are in good agreements with molecular dynamics simulations in the literatures. Although static disorder has been implicated in the original work of Kuo et al., our work suggests a sound and plausible alternative interpretation for the non-exponential kinetics in the stretching of poly-ubiquitin molecules, associated with dynamic disorder.

  2. Heterocyclic anions of astrobiological interest

    SciTech Connect

    Cole, Callie A.; Demarais, Nicholas J.; Bierbaum, Veronica M.; Yang, Zhibo; Snow, Theodore P. E-mail: Nicholas.Demarais@colorado.edu E-mail: Zhibo.Yang@ou.edu

    2013-12-20

    As more complex organic molecules are detected in the interstellar medium, the importance of heterocyclic molecules to astrobiology and the origin of life has become evident. 2-Aminothiazole and 2-aminooxazole have recently been suggested as important nucleotide precursors, highlighting azoles as potential prebiotic molecules. This study explores the gas-phase chemistry of three deprotonated azoles: oxazole, thiazole, and isothiazole. For the first time, their gas-phase acidities are experimentally determined with bracketing and H/D exchange techniques, and their reactivity is characterized with several detected interstellar neutral molecules (N{sub 2}O, O{sub 2}, CO, OCS, CO{sub 2}, and SO{sub 2}) and other reactive species (CS{sub 2}, CH{sub 3}Cl, (CH{sub 3}){sub 3}CCl, and (CH{sub 3}){sub 3}CBr). Rate constants and branching fractions for these reactions are experimentally measured using a modified commercial ion trap mass spectrometer whose kinetic data are in good accord with those of a flowing afterglow apparatus reported here. Last, we have examined the fragmentation patterns of these deprotonated azoles to elucidate their destruction mechanisms in high-energy environments. All experimental data are supported and complemented by electronic structure calculations at the B3LYP/6-311++G(d,p) and MP2(full)/aug-cc-pVDZ levels of theory.

  3. Heterocyclic Anions of Astrobiological Interest

    NASA Astrophysics Data System (ADS)

    Cole, Callie A.; Demarais, Nicholas J.; Yang, Zhibo; Snow, Theodore P.; Bierbaum, Veronica M.

    2013-12-01

    As more complex organic molecules are detected in the interstellar medium, the importance of heterocyclic molecules to astrobiology and the origin of life has become evident. 2-Aminothiazole and 2-aminooxazole have recently been suggested as important nucleotide precursors, highlighting azoles as potential prebiotic molecules. This study explores the gas-phase chemistry of three deprotonated azoles: oxazole, thiazole, and isothiazole. For the first time, their gas-phase acidities are experimentally determined with bracketing and H/D exchange techniques, and their reactivity is characterized with several detected interstellar neutral molecules (N2O, O2, CO, OCS, CO2, and SO2) and other reactive species (CS2, CH3Cl, (CH3)3CCl, and (CH3)3CBr). Rate constants and branching fractions for these reactions are experimentally measured using a modified commercial ion trap mass spectrometer whose kinetic data are in good accord with those of a flowing afterglow apparatus reported here. Last, we have examined the fragmentation patterns of these deprotonated azoles to elucidate their destruction mechanisms in high-energy environments. All experimental data are supported and complemented by electronic structure calculations at the B3LYP/6-311++G(d,p) and MP2(full)/aug-cc-pVDZ levels of theory.

  4. Nanopore detachment kinetics of poly(A) binding proteins from RNA molecules reveals the critical role of C-terminus interactions.

    PubMed

    Lin, Jianxun; Fabian, Marc; Sonenberg, Nahum; Meller, Amit

    2012-03-21

    The ubiquitous and abundant cytoplasmic poly(A) binding protein (PABP) is a highly conserved multifunctional protein, many copies of which bind to the poly(A) tail of eukaryotic mRNAs to promote translation initiation. The N-terminus of PABP is responsible for the high binding specificity and affinity to poly(A), whereas the C-terminus is known to stimulate PABP multimerization on poly(A). Here, we use single-molecule nanopore force spectroscopy to directly measure interactions between poly(A) and PABPs. Both electrical and biochemical results show that the C-C domain interaction between two consecutive PABPs promotes cooperative binding. Up to now, investigators have not been able to probe the detailed polarity configuration (i.e., the internal arrangement of two PABPs on a poly(A) streak in which the C-termini face toward or away from each other). Our nanopore force spectroscopy system is able to distinguish the cooperative binding conformation from the noncooperative one. The ∼50% cooperative binding conformation of wild-type PABPs indicates that the C-C domain interaction doubles the cooperative binding probability. Moreover, the longer dissociation time of a cooperatively bound poly(A)/PABP complex as compared with a noncooperatively bound one indicates that the cooperative mode is the most stable conformation for PABPs binding onto the poly(A). However, ∼50% of the poly(A)/PABP complexes exhibit a noncooperative binding conformation, which is in line with previous studies showing that the PABP C-terminal domain also interacts with additional protein cofactors. PMID:22455926

  5. Pyrimidine-fused heterocycle derivatives as a novel class of inhibitors for α-glucosidase.

    PubMed

    Yousefi, Reza; Alavian-Mehr, Mohammad-Mehdi; Mokhtari, Fatemeh; Panahi, Farhad; Mehraban, Mohammad H; Khalafi-Nezhad, Ali

    2013-12-01

    The needs for diverse inhibitors of α-glucosidase (α-Gls) encouraged us to synthesize five different poly-hydroxy functionalized pyrimidine-fused heterocyclic (PHPFH) molecules, having either aliphatic or aromatic side chains (C1-C5) and their inhibitory activities were examined spectroscopically against yeast and mouse intestinal α-Gls. The results revealed that aromatic substitution of the synthetic compounds has significant impact on their inhibitory properties. Moreover C3 with the substituted moiety as 4-(4-aminophenylsulfonyl) phenyl (4-APSP) revealed strong inhibitory activity with non-competitive and competitive inhibition modes against yeast and mouse α-Gls, respectively. Furthermore, in the presence of increasing concentration of C3, both Trp and 1-anilinonaphthalene-8-sulfonic acid (ANS) fluorescence intensities of yeast α-Gls were gradually decreased, suggesting that C3 binding induced significant structural alteration which was accompanied with the reduction of hydrophobic surfaces. Also, the interaction between yeast α-Gls and C3 was proved to be spontaneous and driven mainly by hydrophobic forces. Overall, this study suggests that aromatic substitution on pyrimidine-fused heterocyclic (PFH) scaffold may represent a novel class of promising inhibitors of α-Gls. PMID:23043430

  6. Hierarchical Nanostructures of Bent-Core Molecules Blended With Poly(styrene-b-4-vinylpyridine) Block Copolymer

    SciTech Connect

    Tenneti,K.; Chen, X.; Li, C.; Wan, X.; Fan, X.; Zhou, Q.; Rong, L.; Hsiao, B.

    2007-01-01

    We report the phase structures observed in blends of poly(styrene-b-4-vinylpyridine) (PS-b-P4VP) block copolymer (BCP) and a bent-core molecule 1-[4'-(3' ',4' ',5' '-tridecyloxybenzoyloxy)phenyleneoxycarbonyl]-3-[(4'-hydroxyphenyl)oxycarbonyl]benzene (BP). Hydrogen bonding between the terminal -OH group of BP and pyridine of P4VP led to the formation of P4VP(BP)n complex, which exhibited liquid crystalline (LC) order. This LC ordering, combined with microphase separation of the BCP, led to the formation of hierarchical nanostructures. The phase structures of the blend samples were investigated as a function of the concentration of BP using small-angle and wide-angle X-ray scattering and transmission electron microscopy techniques. By increasing the BP content, BCP phase morphology transformed from lamellae to cylinders. In the two cases investigated, the P4VP/BP complex formed a bilayer smectic A LC structure within the BCP domains, and these layered structures were oriented perpendicular to the BCP interface. A detailed structural and morphological study will be reported.

  7. Thiadiazole molecules and poly(ethylene glycol)-block-polylactide self-assembled nanoparticles as effective photothermal agents.

    PubMed

    Sun, Tingting; Qi, Ji; Zheng, Min; Xie, Zhigang; Wang, Zhiyuan; Jing, Xiabin

    2015-12-01

    A new photothermal nano-agent was obtained by the coprecipitation of 2,5-Bis(2,5-bis(2-thienyl)-N-dodecyl pyrrole) thieno[3,4-b][1,2,5] thiadiazole (TPT-TT) and a biodegradable amphiphilic block copolymer, methoxypoly(ethylene glycol)2K-block-poly(D,L-lactide)2K (mPEG2K-PDLLA2K). TPT-TT, a donor-acceptor-donor (D-A-D) type small molecule, with bis(2-thienyl)-N-alkylpyrrole (TPT) as the donor and thieno[3,4-b]thiadiazole (TT) as the acceptor was a strong near infrared (NIR) absorber, which could convert the absorbed light energy into heat. The formation of TPT-TT nanoparticles (TPT-NPs), which possessed high stability in water, was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). TPT-NPs showed high photothermal conversion efficiency (32%) and excellent photostability and heating reproducibility. The photostability of TPT-TT NPs was much better than that of indocyanine green (ICG), a federal drug administration (FDA) approved NIR dye. Besides, TPT-TT NPs exhibited significant photothermal therapeutic effect toward human cervical carcinoma (HeLa) and human liver hepatocellular carcinoma (HepG2) cells, while no appreciable dark cytotoxicity was observed. These results highlight the potential of TPT-TT NPs as an effective photothermal agent for cancer therapy. PMID:26398145

  8. Structural and Substituent Group Effects on Multielectron Standard Reduction Potentials of Aromatic N-Heterocycles.

    PubMed

    Groenenboom, Mitchell C; Saravanan, Karthikeyan; Zhu, Yaqun; Carr, Jeffrey M; Marjolin, Aude; Faura, Gabriel G; Yu, Eric C; Dominey, Raymond N; Keith, John A

    2016-09-01

    Aromatic N-heterocycles have been used in electrochemical CO2 reduction, but their precise role is not yet fully understood. We used first-principles quantum chemistry to determine how the molecular sizes and substituent groups of these molecules affect their standard redox potentials involving various proton and electron transfers. We then use that data to generate molecular Pourbaix diagrams to find the electrochemical conditions at which the aromatic N-heterocycle molecules could participate in multiproton and electron shuttling in accordance with the Sabatier principle. While one-electron standard redox potentials for aromatic N-heterocycles can vary significantly with molecule size and the presence of substituent groups, the two-electron and two-proton standard redox potentials depend much less on structural modifications and substituent groups. This indicates that a wide variety of aromatic N-heterocycles can participate in proton, electron, and/or hydride shuttling under suitable electrochemical conditions. PMID:27529793

  9. Connection between the conformation and emission properties of poly[2-methoxy-5-(2'-ethyl-hexyloxy)-1,4-phenylene vinylene] single molecules during thermal annealing

    NASA Astrophysics Data System (ADS)

    Ou, Jiemei; Yang, Yuzhao; Lin, Wensheng; Yuan, Zhongke; Gan, Lin; Lin, Xiaofeng; Chen, Xudong; Chen, Yujie

    2015-03-01

    We investigated the transitions of conformations and their effects on emission properties of poly[2-methoxy-5-(2'-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV) single molecules in PMMA matrix during thermal annealing process. Total internal reflection fluorescence microscopy measurements reveal the transformation from collapsed conformations to extended, highly ordered rod-like structures of MEH-PPV single molecules during thermal annealing. The blue shifts in the ensemble single molecule PL spectra support our hypnosis. The transition occurs as the annealing temperature exceeds 100 °C, implying that an annealing temperature near the glass transition temperature Tg of matrix is ideal for the control and optimization of blend polymer films.

  10. Gold-Catalyzed Synthesis of Heterocycles

    NASA Astrophysics Data System (ADS)

    Arcadi, Antonio

    2014-04-01

    The following sections are included: * Introduction * Synthesis of Heterocycles via Gold-Catalyzed Heteroatom Addition to Unsaturated C-C Bonds * Synthesis of Heterocyclic Derivatives through Gold-Catalyzed Cyclization of Polyunsaturated Compounds * Synthesis of Heterocyclic Compounds via α-Oxo Gold Carbenoid * Synthesis of Heterocyclic Derivatives through Gold-Catalyzed Cycloaddition Reactions * Synthesis of Heterocyclic Derivatives through Gold-Catalyzed Activation of Carbonyl Groups and Alcohols * Synthesis of Heterocyclic Compounds through Gold-Mediated C-H Bond Functionalization * Gold-Catalyzed Domino Cyclization/Oxidative Coupling Reactions * Conclusions * References

  11. 40 CFR 721.4110 - Allyloxysubstituted heterocycle.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Allyloxysubstituted heterocycle. 721... Substances § 721.4110 Allyloxysubstituted heterocycle. (a) Chemical substance and significant new uses... heterocycle (PMN P-93-1471) is subject to reporting under this section for the significant new uses...

  12. Practical and innate C–H functionalization of heterocycles

    PubMed Central

    Fujiwara, Yuta; Dixon, Janice A.; O’Hara, Fionn; Funder, Erik Daa; Dixon, Darryl D.; Rodriguez, Rodrigo A.; Baxter, Ryan D.; Herle, Bart; Sach, Neal; Collins, Michael R.; Ishihara, Yoshihiro; Baran, Phil S.

    2012-01-01

    Nitrogen-rich heterocyclic compounds have had a profound impact on human health, as these chemical motifs are found in a large number of drugs used to combat a broad range of diseases and pathophysiological conditions. Advances in transition metal-mediated cross-coupling have simplified the synthesis of such molecules; however, the development of practical and selective C–H functionalization methods that do not rely upon prefunctionalized starting materials is an underdeveloped area.1–9 Paradoxically, the innate properties of heterocycles that make them so desirable for biological applications render them challenging substrates for direct chemical functionalization, such as limited solubility, functional group incompatibilities, and reagent/catalyst deactivation. Herein we report that zinc sulfinate salts9 can be used to transfer alkyl radicals to heterocycles, allowing for a mild, direct and operationally simple formation of medicinally relevant C–C bonds while reacting in an orthogonal fashion to other innate C–H functionalization methods (Minisci, borono-Minisci, electrophilic aromatic substitution, transition metal-mediated C–H insertion, C–H deprotonation).2–7,9 A toolkit of these reagents was prepared and reacted across a wide range of heterocycles (natural products, drugs, building blocks) without recourse to protecting group chemistry, and can even be employed in a tandem fashion in a single pot in the presence of water and air. PMID:23201691

  13. Nucleobases in Space: Laboratory Studies of Polycyclic Aromatic Nitrogen Heterocycles

    NASA Technical Reports Server (NTRS)

    Elsila, Jamie; Mattioda, Andy; Bernstein, Max; Sandford, Scott; Hudgins, Doug

    2005-01-01

    Polycyclic Aromatic Nitrogen Heterocycles (PANHs) are heterocyclic aromatics Le., PAHs with carbon atoms replaced by a nitrogen atom. These molecules have been detected in meteorite extracts, and in general these nitrogen heterocycles are of astrobiological interest since this class of molecules include nucleobases, basic components of our nucleic acids. These compounds are predicted to be present in the interstellar medium and in Titan tholin, but have received relatively little attention. We will present spectra and reactions of PANHs, frozen in solid H2O at 12 K, conditions germane to astronomical observations. In contrast to simple PAHs, that do not interact strongly with solid H2O, the nitrogen atoms in PANHs are potentially capable of hydrogen bonding with H20 changing their spectra, complicating their remote detection on the surfaces of icy bodies. Moreover, we have studied the photo-chemistry of these interesting compounds under astrophysical conditions and will use our lab studies to assess a potential interstellar heritage of these compounds in carbonaceous chondrites.

  14. A molecular mechanical model for N-heterocyclic carbenes.

    PubMed

    Gehrke, Sascha; Hollóczki, Oldamur

    2016-08-10

    In this work we present a set of force fields for nine synthetically relevant and/or structurally interesting N-heterocyclic carbenes, including imidazol-, thiazol-, triazol-, imidazolidin-, and pyridine-ylidenes. The bonding parameters were calculated by using a series of geometry optimizations by ab initio methods. For fitting the non-bonding interactions, a water molecule was employed as a probe. The interaction energy between the carbene and the probe molecule was sampled along two coordinates for each carbene, representing the interaction through the lone pair, or the π system of the molecule. The corresponding reference interaction energies were obtained by CCSD(T)/CBS calculations. To describe the direction dependence of the intermolecular potential energy, an extra, massless Coulombic interaction site was included for all carbenes, which represents the lone pair of the divalent carbon atom. The resulting fitted carbene force field (CaFF) showed a robust behavior regarding probe molecule, as changing the molecular mechanical water model, or employing, instead, an OPLS methanol molecule did not introduce significant deviations in the potential energies. The obtained CaFF models are easy to merge with standard OPLS or AMBER force fields, therefore the molecular simulations of a large number of N-heterocyclic carbenes becomes available. PMID:27426687

  15. Conformational Characteristics of Poly(tetrafluoroethylene) (PTFE) Based Upon Ab Initio Electronic Structure Calculations on Model Molecules

    NASA Technical Reports Server (NTRS)

    Smith, Grant D.; Jaffe, R. L.; Yoon, D. Y.; Arnold, James O. (Technical Monitor)

    1994-01-01

    Conformational energy contours of perfluoroalkanes, determined from ab initio calculations, confirm the well-known spitting of trans states into two minima at plus or minus 17 degrees but also show that the gauche states split as well, with minima at plus or minus 124 degrees and plus or minus 84 in order to relieve steric crowding. The directions of such split distortions from the perfectly staggered states are strongly coupled for adjacent pairs of bonds in a manner identical to the intradyad pair for poly (isobutylene) chains. These conformational characteristics are fully represented by a six-state rotational isomeric state (RIS) model for PTFE comprised of t(+), t(-), g(sup +)+, g(sup +)-, g(sup -) + and g(sup -)-states, located at the split energy minima. The resultant 6 x 6 statistical weight matrix is described by first-order interaction parameters for the g+(+) (ca. 0.6 kcal/mol) and g+- (ca. 2.0 kcal/mol) states, and second order parameters for the g(sup +)+g(sup +)+ (ca 0.6 kcal/mol) and g(sup +)+g(sup -)+ (ca. 1.0 kcal/mol) states. This six-state RIS model, without adjustment of the geometric or energy parameters as determined from the ab initio calculations, predicts the unperturbed chain dimensions and the fraction of gauche bonds as a function of temperature for PTFE in good agreement with available experimental values.

  16. Analysis of heterocyclic aromatic amines.

    PubMed

    Murkovic, M

    2007-09-01

    Heterocyclic aromatic amines are formed in protein and amino acid-rich foods at temperatures above 150 degrees C. Of more than twenty heterocyclic aromatic amines identified ten have been shown to have carcinogenic potential. As nutritional hazards, their reliable determination in prepared food, their uptake and elimination in living organisms, including humans, and assessment of associated risks are important food-safety issues. The concentration in foods is normally in the low ng g(-1) range, which poses a challenge to the analytical chemist. Because of the complex nature of food matrixes, clean-up and enrichment of the extracts are also complex, usually involving both cation-exchange (propylsulfonic acid silica gel, PRS) and reversed-phase purification. The application of novel solid-phase extraction cartridges with a wettable apolar phase combined with cation-exchange characteristics simplified this process--both the polar and apolar heterocyclic aromatic amines were recovered in one fraction. Copper phthalocyanine trisulfonate bonded to cotton ("blue cotton") or rayon, and molecular imprinted polymers have also been successfully used for one-step sample clean-up. For analysis of the heterocyclic aromatic amines, liquid chromatography with base-deactivated reversed-phase columns has been used, and, recently, semi-micro and capillary columns have been introduced. The photometric, fluorimetric, or electrochemical detectors used previously have been replaced by mass spectrometers. Increased specificity and sub-ppb sensitivities have been achieved by the use of the selected-reaction-monitoring mode of detection of advanced MS instrumentation, for example the triple quadrupole and Q-TOF instrument combination. Gas chromatography, also with mass-selective detection, has been used for specific applications; the extra derivatization step needed for volatilization has been balanced by the higher chromatographic resolution. PMID:17546447

  17. Ion condensation behavior and dynamics of water molecules surrounding the sodium poly(methacrylic acid) chain in water: a molecular dynamics study.

    PubMed

    Chung, Yung-Ting; Huang, Ching-I

    2012-03-28

    All-atom molecular dynamics simulations are used to study the condensation behavior of monovalent (Na(+)) and multivalent (Ca(2+)) salt counterions associated with the co-ions (Cl(-)) surrounding the charged poly(methacrylic acid) (PMAA) chain in water. The study is extended to the influences on chain conformation, local arrangement, and dynamics of water in the highly diluted aqueous solutions. We find that even when the salt ions are monovalent, they attract more than one charged monomer and act as a bridging agent within the chain, as the multivalent salt ions. In principle, the salt ions bridge between not only the "non-adjacent" but also the "adjacent" charged monomers, leading to a more coil-like and a locally stretched conformation, respectively. With an increase in the salt concentration, the amount of coiled-type condensed ions increase and reach a maximum when the chain conformation becomes the most collapsed; whereas, the stretched-type shows an opposite trend. Our results show that the attractive interactions through the condensed salt ions between the non-adjacent monomers are responsible for the conformational collapse. When the salt concentration increases high enough, a significant increase for the stretched-type condensed ions makes an expansion effect on the chain. These stretched-type salt ions, followed by the adsorption of the co-ions and water molecules, tend to form a multilayer organization outside surrounding the PMAA chain. Thus, the expansion degree of the chain conformation is greatly limited. When only the monovalent Na(+) ions are present in the solutions, water molecules are primarily adsorbed into either the condensed Na(+) ions or the COO(-) groups. These adsorbed water molecules form hydrogen bonds with each other and enhance the local bridging behavior associated with the Na(+) condensation on the resultant chain conformation. With an increase in the amount of multivalent Ca(2+) salt ions, more water molecules are bonded directly

  18. N- and O-heterocycles Produced from the Irradiation of Benzene and Naphthalene in H2O/NH3-containing Ices

    NASA Astrophysics Data System (ADS)

    Materese, Christopher K.; Nuevo, Michel; Sandford, Scott A.

    2015-02-01

    Aromatic heterocyclic molecules are an important class of molecules of astrophysical and biological significance that include pyridine, pyrimidine, and their derivatives. Such compounds are believed to exist in interstellar and circumstellar environments, though they have never been observed in the gas phase. Regardless of their presence in the gas phase in space, numerous heterocycles have been reported in carbonaceous meteorites, which indicates that they are formed under astrophysical conditions. The experimental work described here shows that N- and O-heterocyclic molecules can form from the ultraviolet (UV) irradiation of the homocyclic aromatic molecules benzene (C6H6) or naphthalene (C10H8) mixed in ices containing H2O and NH3. This represents an alternative way to generate aromatic heterocycles to those considered before and may have important implications for astrochemistry and astrobiology.

  19. Bioactive heterocycles containing endocyclic N-hydroxy groups

    PubMed Central

    Rani, Reshma; Granchi, Carlotta

    2014-01-01

    Drug-likeness rules consider N-O single bonds as “structural alerts” which should not be present in a perspective drug candidate. In most cases this concern is correct, since it is known that N-hydroxy metabolites of branded drugs produce reactive species that cause serious side effects. However, this dangerous reactivity of the N-OH species generally takes place when the nitrogen atom is not comprised in a cyclic moiety. In fact, the same type of metabolic behavior should not be expected when the nitrogen atom is included in the ring of an aromatic heterocyclic scaffold. Nevertheless, heterocycles bearing endocyclic N-hydroxy portions have so far been poorly studied as chemical classes that may provide new therapeutic agents. This review provides an overview of N-OH-containing heterocycles with reported bioactivities that may be considered as therapeutically relevant and, therefore, may extend the chemical space available for the future development of novel pharmaceuticals. A systematic treatment of the various chemical classes belonging to this particular family of molecules is described along with a discussion of the biological activities associated to the most important examples. PMID:25466924

  20. Heterocyclic Scaffolds: Centrality in Anticancer Drug Development.

    PubMed

    Ali, Imran; Lone, Mohammad Nadeem; Al-Othman, Zeid A; Al-Warthan, Abdulrahman; Sanagi, Mohd Marsin

    2015-01-01

    Cancer has been cursed for human beings for long time. Millions people lost their lives due to cancer. Despite of the several anticancer drugs available, cancer cannot be cured; especially at the late stages without showing any side effect. Heterocyclic compounds exhibit exciting medicinal properties including anticancer. Some market selling heterocyclic anticancer drugs include 5-flourouracil, methortrexate, doxorubicin, daunorubicin, etc. Besides, some natural products such as vinblastine and vincristine are also used as anticancer drugs. Overall, heterocyclic moeities have always been core parts in the expansion of anticancer drugs. This article describes the importance of heterocyclic nuclei in the development of anticancer drugs. Besides, the attempts have been made to discuss both naturally occurring and synthetic heterocyclic compounds as anticancer agents. In addition, some market selling anticancer heterocyclic compounds have been described. Moreover, the efforts have been made to discuss the mechanisms of actions and recent advances in heterocyclic compounds as anticancer agents. The current challenges and future prospectives of heterocyclic compounds have also been discussed. Finally, the suggestions for syntheses of effective, selective, fast and human friendly anticancer agents are discussed into the different sections. PMID:25751009

  1. Heterocyclic methacrylates for clinical applications. II. Room temperature polymerizing systems for potential clinical use.

    PubMed

    Patel, M P; Braden, M

    1991-09-01

    A number of useful room temperature polymerizing resins were formulated, based on poly(ethyl methacrylate) powder and a range of low shrinkage heterocyclic methacrylate monomers. N,N-dimethyl-p-toluidine or p-tolyl diethanolamine were used as activating amines, but the latter material is less active and some care is necessary with respect to the source of the monomer. Isobornyl methacrylate is a useful diluent monomer to reduce the exotherm. PMID:1742408

  2. Aminoazoles as Key Reagents in Multicomponent Heterocyclizations

    NASA Astrophysics Data System (ADS)

    Chebanov, Valentin A.; Gura, Katerina A.; Desenko, Sergey M.

    Because of the significant role in biological processes in living cells and the diverse types of physiological activities, heterocyclic compounds are in focus of intense investigations by academic and applied-oriented chemists. Considerably, a scientific renaissance of heterocycles during the last decades is closely related to the development of multicomponent approaches to their synthesis. Multicomponent methodology fundamentally different from two-component or sequential processes together with other innovative synthetic methods like microwave- and ultrasonic-assisted reactions offer some new possibilities in constructing heterocyclic systems with high level of molecular diversity and complexity. An overview of known multicomponent heterocyclizations using aminoazoles as a key reagent and their rich synthetic potential for obtaining five-, six-, and seven-membered heterocycles is presented. A special attention is paid to the tuning of chemo- and regio- and positional selectivity of some reactions as well as to the application of nonclassical activation methods based on microwave and ultrasonic irradiation.

  3. The stretching of single poly-ubiquitin molecules: Static versus dynamic disorder in the non-exponential kinetics of chain unfolding

    NASA Astrophysics Data System (ADS)

    Chatterjee, Debarati; Cherayil, Binny J.

    2011-04-01

    Static disorder has recently been implicated in the non-exponential kinetics of the unfolding of single molecules of poly-ubiquitin under a constant force [Kuo, Garcia-Manyes, Li, Barel, Lu, Berne, Urbakh, Klafter, and Fernández, Proc. Natl. Acad. Sci. U.S.A. 107, 11336 (2010), 10.1073/pnas.1006517107]. In the present paper, it is suggested that dynamic disorder may provide a plausible, alternative description of the experimental observations. This suggestion is made on the basis of a model in which the barrier to chain unfolding is assumed to be modulated by a control parameter r that evolves in a parabolic potential under the action of fractional Gaussian noise according to a generalized Langevin equation. The treatment of dynamic disorder within this model is pursued using Zwanzig's indirect approach to noise averaging [Acc. Chem. Res. 23, 148 (1990)]. In conjunction with a self-consistent closure scheme developed by Wilemski and Fixman [J. Chem. Phys. 58, 4009 (1973), 10.1063/1.1679757; ibid. 60, 866 (1974), 10.1063/1.1681162], this approach eventually leads to an expression for the chain unfolding probability that can be made to fit the corresponding experimental data very closely.

  4. High-performance liquid chromatography separation of small molecules on a porous poly (trimethylol propane triacrylate-co-N-isopropylacrylamide-co-ethylene dimethacrylate) monolithic column.

    PubMed

    Liu, Haiyan; Bai, Xiaomei; Wei, Dan; Yang, Gengliang

    2014-01-10

    A porous monolith was prepared by in situ free-radical polymerization using N-isopropylacrylamide (NIPAAm) and trimethylol propane triacrylate (TMPTA) as functional monomers, ethylene dimethacrylate (EDMA) as crosslinking agent. The chemical group of the monolith was assayed by a Fourier transform infrared spectroscopy (FT-IR) method and the morphology of optimized monolithic column was characterized by scanning electron microscopy (SEM). The mechanical strength and permeability have been studied in detail as well. The run-to-run and column-to-column reproducibility of the retention times were less than 0.9% and 3.0%, respectively. Furthermore, the influence of temperature and mobile phase composition on the separation of aromatic compounds was investigated. The results indicated that poly (trimethylol propane triacrylate-co-N-isopropylacrylamide-co-ethylenedimethacrylate) (TMPTA-co-NIPAAm-co-EDMA) monolithic column not only had high porosity and strong rigidity, but also was a promising tool for analyzing small molecule compounds with a short analysis time by controlling the column temperature. PMID:24290767

  5. Acridine: a versatile heterocyclic nucleus.

    PubMed

    Kumar, Ramesh; Kaur, Mandeep; Kumari, Meena

    2012-01-01

    Acridine is a heterocyclic nucleus. It plays an important role in various medicines. A number of therapeutic agents are based on acridine nucleus such as quinacrine (antimalarial), acriflavine and proflavine (antiseptics), ethacridine (abortifacient), amsacrine and nitracine (anticancer), and tacrine. Acridine is obtained from high boiling fraction of coal tar. It is also obtained in nature from plant and marine sources. Acridine undergoes a number of reactions such as nucleophilic addition, electrophilic substitution, oxidation, reduction, reductive alkylation and photoalkylation. The present review article summarizes the synthesis, reaction, literature review and pharmaceutical importance of acridine. PMID:22574501

  6. Trends in research of antitrypanosomal agents among synthetic heterocycles.

    PubMed

    Kryshchyshyn, Anna; Kaminskyy, Danylo; Grellier, Philippe; Lesyk, Roman

    2014-10-01

    To date treatment of trypanosomiasis urgently requires new effective and non-toxic drugs. The article covers some of the achievements in the search for new antitrypanosomal agents; also the "validated" biological targets used in the antitrypanosomal agents design are outlined. The major part of the manuscript focuses on the synthetic small molecules, such as thiosemicarbazone and thiazole (as their cyclic analogues) derivatives, benzofuran derivatives, heterocycles bearing nitro group etc. Also, the attractiveness of metal complexes and well known drugs as sources for antitrypanosomal agent design is discussed. PMID:25072876

  7. Gas phase radiolysis and vacuum ultraviolet photolysis of heterocyclic organic compounds. Progress report, Feburary 1, 1979-February 1, 1980

    SciTech Connect

    Scala, A.A.; Nguyen, D.; Rourke, W.; Caputo, M.

    1980-01-01

    The long-range objective of our research group is to gain a better understanding of the processes by which complex organic molecules react when they absorb large amounts of energy. This progress report describes the results of our recent work in three areas: diradicals derived from heterocyclic compounds; trimethylene diradicals from various sources; and ion-molecule reactions.

  8. Catalytic asymmetric synthesis of enantioenriched heterocycles bearing a C-CF3 stereogenic center.

    PubMed

    Huang, Yi-Yong; Yang, Xing; Chen, Zhuo; Verpoort, Francis; Shibata, Norio

    2015-06-01

    Given the important agricultural and medicinal application of optically pure heterocycles bearing a trifluoromethyl group at the stereogenic carbon center in the heterocyclic framework, the exploration of efficient and practical synthetic strategies to such types of molecules remains highly desirable. Catalytic enantioselective synthesis has one clear advantage that it is more cost-effective than other synthetic methods, but remains limited by challenges in achieving excellent yield and stereoselectivities with a low catalyst loading. Thus far, numerous models of organo- and organometal-catalyzed asymmetric reactions have been exploited to achieve this elusive goal over the past decade. This review article describes recent progress on this research topic, and focuses on an understanding of the catalytic asymmetric protocols exemplified in the catalytic enantioselective synthesis of a wide range of complex enantioenriched trifluoromethylated heterocycles. PMID:25736019

  9. Heterocyclics as corrosion inhibitors for acid media

    SciTech Connect

    Ajmal, M.; Khan, M.A.W.; Ahmad, S.; Quraishi, M.A.

    1996-12-01

    The available literature on the use of heterocyclic compounds as corrosion inhibitors in acid media has been reviewed. It has been noted that the workers in this field have either used sulfur or nitrogen containing heterocyclic compounds for studying inhibition action. The authors have synthesized compounds containing sulfur and nitrogen both in the same ring and studied their inhibition action in acid media. These compounds were found to be better inhibitors than those containing either atoms alone.

  10. Conjugated Polymers with Repeated Sequences of Group 16 Heterocycles Synthesized through Catalyst-Transfer Polycondensation.

    PubMed

    Tsai, Chia-Hua; Fortney, Andria; Qiu, Yunyan; Gil, Roberto R; Yaron, David; Kowalewski, Tomasz; Noonan, Kevin J T

    2016-06-01

    Periodic π-conjugated polymers of the group 16 heterocycles (furan, thiophene, and selenophene) were synthesized with controlled chain lengths and relatively low dispersities using catalyst-transfer polycondensation. The optical gap and redox potentials of these copolymers were fine-tuned by altering the heterocycle sequence, and atomic force microscopy revealed nanofibrillar morphologies for all the materials. Grazing incidence wide-angle X-ray scattering of the thiophene-selenophene copolymers indicated that the π-stacking distance increased with incorporation of the larger heteroatom (from ∼3.7-4.0 Å), while the lamellar spacing decreased (from ∼15.8-15.2 Å). The study also revealed that periodic sequences allow electronic properties to be tuned while retaining nanofibrillar morphologies similar to those observed for poly(3-hexylthiophene). PMID:27104362

  11. Thermally Stable Heterocyclic Imines as New Potential Nonlinear Optical Materials

    NASA Technical Reports Server (NTRS)

    Nesterov, Volodymyr V.; Antipin, Mikhail Y.; Nesterov, Vladimir N.; Moore, Craig E.; Cardelino, Beatriz H.; Timofeeva, Tatiana V.

    2004-01-01

    In the course of a search for new thermostable acentric nonlinear optical crystalline materials, several heterocyclic imine derivatives were designed, with the general structure D-pi-A(D'). Introduction of a donor amino group (D') into the acceptor moiety was expected to bring H-bonds into their crystal structures, and so to elevate their melting points and assist in an acentric molecular packing. Six heterocycle-containing compounds of this type were prepared, single crystals were grown for five of them, and these crystals were characterized by X-ray analysis. A significant melting temperature elevation was found for all of the synthesized compounds. Three of the compounds were also found to crystallize in acentric space groups. One of the acentric compounds is built as a three-dimensional H-bonded molecular network. In the other two compounds, with very similar molecular structure, the molecules form one-dimensional H-bonded head-to-head associates (chains). These chains are parallel in two different crystallographic directions and form very unusual interpenetrating chain patterns in an acentric crystal. Two of the compounds crystallized with centrosymmetric molecular packing.

  12. Astronomical searches for nitrogen heterocycles

    NASA Astrophysics Data System (ADS)

    Charnley, Steven B.; Kuan, Yi-Jehng; Huang, Hui-Chun; Botta, Oliver; Butner, Harold M.; Cox, Nick; Despois, Didier; Ehrenfreund, Pascale; Kisiel, Zbigniew; Lee, Ying-Ying; Markwick, Andrew J.; Peeters, Zan; Rodgers, Steven D.

    We have conducted extensive astronomical searches for the N-bearing ring molecules pyridine, quinoline and isoquinoline towards the circumstellar envelopes of carbon-rich stars, and for interstellar pyrimidine in hot molecular cores. Here we report the derived upper limits on the column densities of these molecules, and summarize the current status of these observations.

  13. Heterocycle-to-Heterocycle Route to Quinoline-4-amines: Reductive Heterocyclization of 3-(2-Nitrophenyl)isoxazoles

    PubMed Central

    Coffman, Keith C.; Duong, Vy; Bagdasarian, Alex L.; Fettinger, James C.; Haddadin, Makhlouf J.

    2015-01-01

    A variety of quinoline-4-amines were synthesized from substituted 3-(2-nitrophenyl)isoxazoles utilizing Zn0 or Fe0 dust and HOAc via a reductive heterocyclization process. The starting isoxazoles were synthesized from readily available starting materials. A brief survey of functional groups tolerated in this reductive heterocyclization was performed and several 10-amino-3,4-dihydrobenzo[b][1,6]naphthyridin-1(2H)-one and 9-amino-3,4-dihydroacridin-1(2H)-one examples were synthesized. PMID:26257574

  14. Heterocyclic chalcone analogues as potential anticancer agents.

    PubMed

    Sharma, Vikas; Kumar, Vipin; Kumar, Pradeep

    2013-03-01

    Chalcones, aromatic ketones and enones acting as the precursor for flavonoids such as Quercetin, are known for their anticancer effects. Although, parent chalcones consist of two aromatic rings joined by a three-carbon α,β-unsaturated carbonyl system, various synthetic compounds possessing heterocyclic rings like pyrazole, indole etc. are well known and proved to be effective anticancer agents. In addition to their use as anticancer agents in cancer cell lines, heterocyclic analogues are reported to be effective even against resistant cell lines. In this connection, we hereby highlight the potential of various heterocyclic chalcone analogues as anticancer agents with a brief summary about therapeutic potential of chalcones, mechanism of anticancer action of various chalcone analogues, and current and future prospects related to the chalcones-derived anticancer research. Furthermore, some key points regarding chalcone analogues have been reviewed by analyzing their medicinal properties. PMID:22721390

  15. The C-H bond dissociation enthalpies in fused N-heterocyclic compounds

    NASA Astrophysics Data System (ADS)

    Wang, Ying-Xing; Zheng, Wen-Rui; Ding, Lan-Lan

    2016-03-01

    The C-H bond dissociation enthalpies (BDEs) of the 26 N, O, S-containing mono-heterocyclic compounds were evaluated using the composite high-level ab initio methods G3 and G4. The C-H BDEs for 32 heterocyclic compounds were calculated using 8 types of density functional theory (DFT) methods. Comparing with the experimental values, the BMK method gave the lowest root mean square error (RMSE) of 7.2 kJ/mol. Therefore, the C-H BDEs of N-fused-heterocyclic compounds at different positions were investigated by the BMK method. By NBO analysis two linear relationships between the C-H BDEs of quinoline and isoquinoline with natural charges qC/ e in molecules and with natural charges qC/ e in radicals were found. The substituent effects on C(α)-H BDEs in N-fused-heterocyclic compounds were also discussed. It was found that there are two linear relationships between the C(α)-H BDEs of quinoline and isoquinoline derivatives with natural charges qC(α)/ e for the EDGs and CEGs substituents.

  16. Pentacyclic triterpenoids with nitrogen- and sulfur-containing heterocycles: synthesis and medicinal significance.

    PubMed

    Kvasnica, Miroslav; Urban, Milan; Dickinson, Niall J; Sarek, Jan

    2015-09-01

    Triterpenoids are natural compounds with a variety of biological activities and are usually produced by plants as secondary metabolites. In recent decades, scientists focused on the properties of triterpenoids have discovered many activities, such as antitumor, antiviral, antimicrobial, anti-inflammatory and others. Thousands of new triterpenoids with various skeletal modifications have now been synthesized. One of the most important modifications is the formation of a new heterocyclic ring. The simple fact that the vast majority of currently used drugs are heterocyclic compounds has encouraged a lot of researches to synthesize analogous triterpenoid derivatives in order to find new molecules with higher activities and consequently optimize their pharmacological profile. The biological properties of triterpenoid heterocycles are very promising and many of them have been studied, especially as antitumor agents. This review is mainly focused on the synthesis of various types of nitrogen and occasionally sulfur-containing heterocyclic triterpenoids for their potential use as future drugs in medicine and in addition discusses their overall biological activities. PMID:26030604

  17. The boron-carbon-nitrogen heterocyclic rings

    NASA Astrophysics Data System (ADS)

    Srivastava, Ambrish Kumar; Misra, Neeraj

    2015-04-01

    The heterocyclic rings containing B, C and N atoms, also known as azaborines, are systematically studied. The electronic properties of these BCN rings are explored by using second order perturbation theory and their aromaticity is discussed by the nucleus independent chemical shifts. These heterocyclic rings are found to be chemically more reactive than benzene and borazine, due to smaller HOMO-LUMO gap and non-zero dipole moment. However, the aromaticity of these BCN rings is less than benzene but two or three times that of borazine.

  18. Multi-Component Reactions in Heterocyclic Chemistry

    NASA Astrophysics Data System (ADS)

    Müller, Thomas J. J.; Orru, Romano V. A.; Chebanov, Valentin A.; Sakhno, Yana I.; Saraev, Vyacheslav E.; Muravyova, Elena A.; Andrushchenko, Anastasia Yu.; Desenko, Sergey M.; Akhmetova, V. R.; Khabibullina, G. R.; Rakhimova, E. B.; Vagapov, R. A.; Khairullina, R. R.; Niatshina, Z. T.; Murzakova, N. N.; Maslivets, Andrey N.; Voskressensky, Leonid G.; Danagulyan, Gevorg G.; Murtchyan, Armen D.; Tumanyan, Araksya K.; Banfi, Luca; Basso, Andrea; de Moliner, Fabio; Guanti, Giuseppe; Petricci, Elena; Riva, Renata; Taddei, Maurizio; Naimi-Jamal, M. Reza; Mashkouri, Sara; Sharifi, Ali; Przhevalski, Nikolai M.; Rozhkova, Elena N.; Tokmakov, Gennadii P.; Magedov, Igor V.; Armisheva, M. N.; Rassudihina, N. A.; Vahrin, M. I.; Gein, V. L.; Shaabani, Ahmad; Rezayan, Ali Hossein; Sarvary, Afshin; Heidary, Marjan; Ng, Seik Weng; Beliaev, Nikolai A.; Mokrushin, Vladimir S.; Paramonov, Igor V.; Ilyin, Alexey; Garkushenko, Anna K.; Dushek, Maria A.; Sagitullina, Galina P.; Sagitullin, Reva S.; Kysil, Volodymyr; Khvat, Alexander; Tsirulnikov, Sergey; Tkachenko, Sergey; Ivachtchenko, Alexandre; Gein, Vladimir L.; Panova, Olga S.; Ilyn, Alexey P.; Kravchenko, Dmitri V.; Potapov, Victor V.; Ivachtchenko, Alexandre V.; Vichegjanina, V. N.; Levandovskaya, E. B.; Gein, V. L.; Vahrin, M. I.; Vladimirov, I. N.; Zorina, A. A.; Nosova, N. V.; Gein, V. L.; Fedorova, O. V.; Vahrin, M. I.

    Multi-component and domino reactions are efficient and effective methods in the sustainable and diversity-oriented synthesis of heterocycles. In particular, transition metal-catalyzed multi-component sequences have recently gained considerable interest. Based upon the Sonogashira entry to alkynones, alkenones, and intermediate allenes, we have opened new avenues to the one-pot synthesis of numerous classes of heterocyclic frameworks in an MCR fashion. This methodological approach has now found various applications in one-pot syntheses of functional chromophores, pharmaceutically active compounds, and marine alkaloids and derivatives.

  19. The fabrication of monolithic capillary column based on poly (bisphenol A epoxy vinyl ester resin-co-ethylene glycol dimethacrylate) and its applications for the separation of small molecules in high performance liquid chromatography.

    PubMed

    Niu, Wenjing; Wang, Lijuan; Bai, Ligai; Yang, Gengliang

    2013-07-01

    A new polymeric monolith was synthesized in fused-silica capillary by in situ polymerization technique. In the polymerization, bisphenol A epoxy vinyl ester resin (VER) was used as the functional monomer, ethylene glycol dimethacrylate (EDMA) as the crosslinking monomer, 1,4-butanediol, 1-propanol and water as the co-porogens, and azobisisobutyronitrile (AIBN) as the initiator. The conditions of polymerization have been optimized. Morphology of the prepared poly (VER-co-EDMA) monolith was investigated by the scanning electron microscopy (SEM); pore properties were assayed by mercury porosimetry and nitrogen adsorption. The optimized poly (VER-co-EDMA) monolith showed a uniform structure, good permeability and mechanical stability. Then, the column was used as the stationary phase of high performance liquid chromatography (HPLC) to separate the mixture of benzene derivatives. The best column efficiency achieved for phenol was 235790 theoretical plates per meter. Baseline separations of benzene derivatives and halogenated benzene compounds under optimized isocratic mode conditions were achieved with high column efficiency. The column showed good reproducibility: the relative standard deviation (RSD) values based on the retention times (n=3) for run-to-run, column-to-column and batch-to-batch were less than 0.98, 1.68, 5.48%, respectively. Compared with poly (BMA-co-EDMA) monolithic column, the proposed monolith exhibited more efficiency in the separation of small molecules. PMID:23726080

  20. Supramolecular hydrogen-bonded structures between melamine and N-heterocycles

    NASA Astrophysics Data System (ADS)

    Makowski, Sophia J.; Lacher, Monika; Lermer, Claudia; Schnick, Wolfgang

    2012-04-01

    Melamine (M) forms hydrogen bonded adducts with the N-heterocycles tris(2-pyridyl)-triazine (TPTZ) and tetrakis(4-N-methylpyridinumyl)porphyrin tetratosylate (TMPyP-Tos). The 4:3 adduct 4M·3TPTZ was obtained under solvent-free conditions and the 3:1 adduct 3M·TMPyP-Tos·9H2O in aqueous solution. In both adduct phases N-heterocycles are arranged in π-π stacks and melamine molecules are arranged perpendicular to these stacks. Whereas cohesion between the extended π-systems of N-heterocycles is mainly achieved by dispersive interactions no stacking interactions between melamine molecules occur. Melamine units are orientated in such a way to be located most suitable as donors and acceptors, respectively, for a dense hydrogen bonding network. In 4M·3TPTZ all molecules are involved in hydrogen bonding, whereas in 3M·TMPyP-Tos·9H2O hydrogen bridges are primarily formed between melamine, tosylate and water units and the macrocycle TMPyP is mainly bound by electrostatic interactions.

  1. [Chalcones and their heterocyclic analogs as potential antifungal chemotherapeutic agents].

    PubMed

    Opletalová, V; Sedivý, D

    1999-11-01

    Chalcones and their heterocyclic analogues show various biological effects, e.g. anti-inflammatory, antitumour, antibacterial, antituberculous, antiviral, antiprotozoal, gastroprotective, and others. The present review discusses in greater detail the fungistatic and fungicide properties of these compounds and presents also their chemical structures. The mechanism of antifungal effects of chalcones and their analogues has not been investigated in greater detail. Due to the presence of a reactive ketovinyl moiety in the molecule the compounds of this type are able to react with the thiol groups of enzymes. It cannot be excluded that chalcones interfere with the normal function of the membranes of fungi and moulds. Further investigation of chemical, physical, and biological properties of chalcones and their analogues could lead to the elucidation of the mechanism of their action and finding of effective fungicidal and fungistatic agents in this group of organic substances. PMID:10748740

  2. SnAP reagents for the one-step synthesis of medium-ring saturated N-heterocycles from aldehydes

    NASA Astrophysics Data System (ADS)

    Vo, Cam-Van T.; Luescher, Michael U.; Bode, Jeffrey W.

    2014-04-01

    Interest in saturated N-heterocycles as scaffolds for the synthesis of bioactive molecules is increasing. Reliable and predictable synthetic methods for the preparation of these compounds, especially medium-sized rings, are limited. We describe the development of SnAP (Sn amino protocol) reagents for the transformation of aldehydes into seven-, eight- and nine-membered saturated N-heterocycles. This process occurs under mild, room-temperature conditions and offers exceptional substrate scope and functional-group tolerance. Air- and moisture-stable SnAP reagents are prepared on a multigram scale from inexpensive starting materials by simple reaction sequences. These new reagents and processes allow widely available aryl, heteroaryl and aliphatic aldehydes to be converted into diverse N-heterocycles, including diazepanes, oxazepanes, diazocanes, oxazocanes and hexahydrobenzoxazonines, by a single synthetic operation.

  3. One-Step Synthetic Access to Isosteric and Potent Anticancer Nitrogen Heterocycles with the Benzo[c]phenanthridine Scaffold.

    PubMed

    Steinhauer, Tamara N; Girreser, Ulrich; Meier, Christopher; Cushman, Mark; Clement, Bernd

    2016-06-01

    A versatile one-step two-component cyclization to build new tetracyclic nitrogen heterocycles is described. Ortho-methylhetarenecarbonitrile components were condensed with aldehydes to access a large library of differently substituted ring systems. The heterocyclic core can be easily modified by variation of the position of the endocyclic nitrogen atom in the o-methylhetarenecarbonitrile substrate. The manner of the nucleophilic attack that leads to the condensation can be triggered by different electron-density distribution in the molecule induced by the position of the nitrogen atom. Taking this into account, there is an electronic preference that leads to either pyridophenanthrolines or the corresponding pyridoazacarbazoles as the main products. We demonstrate the high antitumor potential of some of our synthesized heterocycles, which is strongly dependent on the substitution pattern introduced through the aldehyde component. The position and number of endocyclic nitrogen atoms play an important role regarding cytotoxicity of the studied compounds. PMID:27151929

  4. Installing amino acids and peptides on N-heterocycles under visible-light assistance

    PubMed Central

    Jin, Yunhe; Jiang, Min; Wang, Hui; Fu, Hua

    2016-01-01

    Readily available natural α-amino acids are one of nature’s most attractive and versatile building blocks in synthesis of natural products and biomolecules. Peptides and N-heterocycles exhibit various biological and pharmaceutical functions. Conjugation of amino acids or peptides with N-heterocycles provides boundless potentiality for screening and discovery of diverse biologically active molecules. However, it is a great challenge to install amino acids or peptides on N-heterocycles through formation of carbon-carbon bonds under mild conditions. In this article, eighteen N-protected α-amino acids and three peptides were well assembled on phenanthridine derivatives via couplings of N-protected α-amino acid and peptide active esters with substituted 2-isocyanobiphenyls at room temperature under visible-light assistance. Furthermore, N-Boc-proline residue was successfully conjugated with oxindole derivatives using similar procedures. The simple protocol, mild reaction conditions, fast reaction, and high efficiency of this method make it an important strategy for synthesis of diverse molecules containing amino acid and peptide fragments. PMID:26830014

  5. Toward Multiple Conductance Pathways with Heterocycle-Based Oligo(phenyleneethynylene) Derivatives.

    PubMed

    Miguel, Delia; Álvarez de Cienfuegos, Luis; Martín-Lasanta, Ana; Morcillo, Sara P; Zotti, Linda A; Leary, Edmund; Bürkle, Marius; Asai, Yoshihiro; Jurado, Rocío; Cárdenas, Diego J; Rubio-Bollinger, Gabino; Agraït, Nicolás; Cuerva, Juan M; González, M Teresa

    2015-11-01

    In this paper, we have systematically studied how the replacement of a benzene ring by a heterocyclic compound in oligo(phenyleneethynylene) (OPE) derivatives affects the conductance of a molecular wire using the scanning tunneling microscope-based break junction technique. We describe for the first time how OPE derivatives with a central pyrimidine ring can efficiently link to the gold electrode by two pathways presenting two different conductance G values. We have demonstrated that this effect is associated with the presence of two efficient conductive pathways of different length: the conventional end-to-end configuration, and another with one of the electrodes linked directly to the central ring. This represents one of the few examples in which two defined conductive states can be set up in a single molecule without the aid of an external stimulus. Moreover, we have observed that the conductance through the full length of the heterocycle-based OPEs is basically unaffected by the presence of the heterocycle. All these results and the simplicity of the proposed molecules push forward the development of compounds with multiple conductance pathways, which would be a breakthrough in the field of molecular electronics. PMID:26452050

  6. Installing amino acids and peptides on N-heterocycles under visible-light assistance.

    PubMed

    Jin, Yunhe; Jiang, Min; Wang, Hui; Fu, Hua

    2016-01-01

    Readily available natural α-amino acids are one of nature's most attractive and versatile building blocks in synthesis of natural products and biomolecules. Peptides and N-heterocycles exhibit various biological and pharmaceutical functions. Conjugation of amino acids or peptides with N-heterocycles provides boundless potentiality for screening and discovery of diverse biologically active molecules. However, it is a great challenge to install amino acids or peptides on N-heterocycles through formation of carbon-carbon bonds under mild conditions. In this article, eighteen N-protected α-amino acids and three peptides were well assembled on phenanthridine derivatives via couplings of N-protected α-amino acid and peptide active esters with substituted 2-isocyanobiphenyls at room temperature under visible-light assistance. Furthermore, N-Boc-proline residue was successfully conjugated with oxindole derivatives using similar procedures. The simple protocol, mild reaction conditions, fast reaction, and high efficiency of this method make it an important strategy for synthesis of diverse molecules containing amino acid and peptide fragments. PMID:26830014

  7. Preparation of a novel porous poly (trimethylol propane triacrylate-co-ethylene dimethacrylate) monolithic column for highly efficient HPLC separations of small molecules.

    PubMed

    Bai, Xiaomei; Liu, Haiyan; Wei, Dan; Yang, Gengliang

    2014-02-01

    A novel poly (trimethylol propane triacrylate-co-ethylene dimethacrylate) [poly (TMPTA-co-EDMA)] monolith was prepared by in situ free-radical polymerization in a 50 mm × 4.6mm i.d. stainless steel column and was investigated for high performance liquid chromatography (HPLC). The porous structure of monolith was optimized by changing the conditions of polymerization. The chemical group of the monolithic column was confirmed by a Fourier transform infrared spectroscopy (FT-IR) method and the morphology of column structure was characterized by scanning electron microscopy (SEM). The mechanical strength and permeability were also studied. Finally, a series of low-molecular-weight organic compounds were utilized to evaluate the retention behaviors of the monolithic column. The result demonstrated that the prepared column exhibited an RP-chromatographic behavior and good separation performance. The method reproducibility was obtained by evaluating the run-to-run and column-to-column with relative standard deviations (RSDs) less than 0.7% (n=6) and 2.9% (n=6), respectively, which indicated that prepared monolithic columns had good reproducibility and stability. PMID:24401444

  8. Covalent Polymers Containing Discrete Heterocyclic Anion Receptors

    PubMed Central

    Rambo, Brett M.; Silver, Eric S.; Bielawski, Christopher W.; Sessler, Jonathan L.

    2010-01-01

    This chapter covers recent advances in the development of polymeric materials containing discrete heterocyclic anion receptors, and focuses on advances in anion binding and chemosensor chemistry. The development of polymers specific for anionic species is a relatively new and flourishing area of materials chemistry. The incorporation of heterocyclic receptors capable of complexing anions through non-covalent interactions (e.g., hydrogen bonding and electrostatic interactions) provides a route to not only sensitive but also selective polymer materials. Furthermore, these systems have been utilized in the development of polymers capable of extracting anionic species from aqueous environments. These latter materials may lead to advances in water purification and treatment of diseases resulting from surplus ions. PMID:20871791

  9. Synthesis of amino heterocycle aspartyl protease inhibitors.

    PubMed

    Chambers, Rachel K; Khan, Tanweer A; Olsen, David B; Sleebs, Brad E

    2016-06-14

    Aspartyl proteases are important pharmacological targets. Historically aspartyl proteases have been commonly targeted with transition state derived peptidomimetics. The strategy to develop aspartyl protease inhibitors has undertaken a dramatic paradigm shift in the last 10 years. The pharmaceutical industry in 2005 disclosed several scaffolds or "head groups" that prompted the field to move beyond peptidomimetic derived inhibitors. Since the discovery of the first amino heterocycle aspartyl protease inhibitor, the amino hydantoin, industry and academia have positioned themselves for a foothold on the new molecular space, designing a variety of related "head groups". Both the design and synthetic efforts involved in constructing these scaffolds are varied and complex. Here we highlight the synthetic strategies used to access these amino heterocycle scaffolds. PMID:27143279

  10. Structural mechanisms of photoeffect in polyimide structures containing heterocyclic fragments

    SciTech Connect

    Aleksandrova, E. L.

    2006-11-15

    Trends in the variation in the quantum yields of charge-carrier photogeneration in polyimide structures containing heterocyclic fragments are studied. It is shown that the efficiency of sensitization of polyimides depends on the donor and acceptor properties of the fragments of monomeric units of the polyimide. It is established that the range of spectral sensitivity for heterocyclic fragments representing intramolecular complexes with charge transport is wider than that for heterocycles that do not represent such complexes.

  11. Diverse trifluoromethyl heterocycles from a single precursor.

    PubMed

    Honey, Mark A; Pasceri, Raffaele; Lewis, William; Moody, Christopher J

    2012-02-01

    Ethyl 2-diazo-4,4,4-trifluoro-3-oxobutanoate is a highly versatile intermediate for the synthesis of a wide range of trifluoromethyl heterocycles. With the use of rhodium(II) or copper(II) catalyzed carbene X-H insertion reactions as key steps, a diverse set of trifluoromethyl-oxazoles, -thiazoles, -imidazoles, -1,2,4-triazines, and -pyridines are available from the diazoketoester, either directly in a single step or with just one additional step. PMID:22264218

  12. Monoamine oxidase inhibitory activities of heterocyclic chalcones.

    PubMed

    Minders, Corné; Petzer, Jacobus P; Petzer, Anél; Lourens, Anna C U

    2015-11-15

    Studies have shown that natural and synthetic chalcones (1,3-diphenyl-2-propen-1-ones) possess monoamine oxidase (MAO) inhibition activities. Of particular importance to the present study is a report that a series of furanochalcones acts as MAO-B selective inhibitors. Since the effect of heterocyclic substitution, other than furan (and more recently thiophene, piperidine and quinoline) on the MAO inhibitory properties of the chalcone scaffold remains unexplored, the aim of this study was to synthesise and evaluate further heterocyclic chalcone analogues as inhibitors of the human MAOs. For this purpose, heterocyclic chalcone analogues that incorporate pyrrole, 5-methylthiophene, 5-chlorothiophene and 6-methoxypyridine substitution were examined. Seven of the nine synthesised compounds exhibited IC50 values <1 μM for the inhibition of MAO-B, with all compounds exhibiting higher affinities for MAO-B compared to the MAO-A isoform. The most potent MAO-B inhibitor (4h) displays an IC50 value of 0.067 μM while the most potent MAO-A inhibitor (4e) exhibits an IC50 value of 3.81 μM. It was further established that selected heterocyclic chalcones are reversible and competitive MAO inhibitors. 4h, however, may exhibit tight-binding to MAO-B, a property linked to its thiophene moiety. We conclude that high potency chalcones such as 4h represent suitable leads for the development of MAO-B inhibitors for the treatment of Parkinson's disease and possibly other neurodegenerative disorders. PMID:26432037

  13. Heterocycle Formation via Palladium-Catalyzed C–H Functionalization

    PubMed Central

    Mei, Tian-Sheng; Kou, Lei; Ma, Sandy; Engle, Keary M.; Yu, Jin-Quan

    2016-01-01

    Heterocyclic compounds are ubiquitous in natural products, pharmaceuticals, and agrochemicals. Therefore, the design of novel protocols to construct heterocycles more efficiently is a major area of focus in the organic chemistry. In the past several years, cyclization reactions based upon palladium-catalyzed C–H activation have received substantial attention due to their capacity for expediting heterocycle synthesis. This review discusses strategies for heterocycle synthesis via palladium-catalyzed C–H bond activation and highlights recent examples from the literature. PMID:27397938

  14. Water purification by reverse osmosis using heterocyclic polymer membranes

    NASA Technical Reports Server (NTRS)

    Scott, H.

    1972-01-01

    Pyrrone (polyimidazopyrrolone) polymers are a new class of thermally stable, radiation and chemical resistant aromatic-heterocyclic polymers featuring a greater chemical and mechanical durability than cellulose acetate.

  15. Thermo-reversible gelation of rod-coil and coil-rod-coil molecules based on poly(dimethyl siloxane) and perylene imides and self-sorting of the homologous pair.

    PubMed

    Dahan, Elianne; Sundararajan, Pudupadi R

    2014-08-01

    Organogels with perylene derivatives and phthalocyanines reported in the literature so far involve self-assembly promoted by hydrogen bonds, in addition to aromatic and van der Waals interactions. Although the self assembly of these types of molecules without a hydrogen bonding group in the structure occurs in solution or during crystallization, the gelation studies reported so far incorporated a hydrogen bonding pair of the type N-H···O=C in the structure of the molecule. We present a case of thermo-reversible gelation without a hydrogen bonding group in the structure of (1) a coil-rod-coil molecule based on perylenetetracarboxylic diimide (PTCDI) and poly(dimethyl siloxane) (PDMS) and (2) a rod-coil molecule with perylene dicarboxylic imide (PDI) and PDMS. However IR spectroscopy shows the presence of multiple types of hydrogen bonding between the solvents and the gelator molecules. In addition, publications so far on gelation of perylene diimide based molecules involve groups attached to both imide nitrogens and with or without substitution in the bay position. We discuss here the gelation with a Mono-substituted perylene imide. The PDMS segment was attached to one side of PDI (Mono-PDMS) or to both imide nitrogens of PTCDI (Di-PDMS). The Mono-PDMS is an inverse macromolecular surfactant applicable to non-aqueous systems, and the Di-PDMS is a Gemini surfactant. The PDMS segment that we attached to PTCDI here is longer than most substituents used by other authors. These molecules gel propylamine, as well as mixed solvents of hexane-water and diisopropylamine-water. Both hexane and diisopropylamine dissolve Mono-PDMS and Di-PDMS at room temperature and addition of water results in precipitation. However, heating the solution to about 70 °C, adding water (5-15 wt%) and slowly cooling the solution, lead to gelation. The Di-PDMS forms fibers which are not flat but curved as an eaves trough. The Mono-PDMS forms hollow spheres. Although the Mono-PDMS and Di

  16. Trapping and release of cargo molecules from a micro-stamped mesoporous thin film controlled by Poly(NIPAAm-co-AAm)

    PubMed Central

    Russell, Melissa M.; Raboin, Lorraine; Guardado-Alvarez, Tania M.; Zink, Jeffrey I.

    2014-01-01

    Materials that utilize the micropatterned structure of a mesoporous silica film to successfully load and release cargo using a thermal sensitive polymer are presented in this paper. Films with pore sizes of ~2 nm and ~5 nm aligned in the pulling direction were synthesized using evaporation induced self-assembly techniques. The pores are exposed using a new method of stamping micropatterns without the use hydrofluoric acid. A well studied temperature dependent polymer (poly(N-isopropylacrylamide-co-Acrylamide)) was grafted onto the surface of these films to act as a temperature activated gatekeeper. Below the lower critical solution temperature (LCST) the polymer is erect and can block the pore openings, trapping cargo inside the pores. When the temperature is above the LCST the polymer collapses and unblocks the pores, allowing cargo to escape. The loading capacities as well as the reusability of these films were studied. PMID:25368448

  17. Trapping and release of cargo molecules from a micro-stamped mesoporous thin film controlled by Poly(NIPAAm-co-AAm).

    PubMed

    Russell, Melissa M; Raboin, Lorraine; Guardado-Alvarez, Tania M; Zink, Jeffrey I

    2014-05-01

    Materials that utilize the micropatterned structure of a mesoporous silica film to successfully load and release cargo using a thermal sensitive polymer are presented in this paper. Films with pore sizes of ~2 nm and ~5 nm aligned in the pulling direction were synthesized using evaporation induced self-assembly techniques. The pores are exposed using a new method of stamping micropatterns without the use hydrofluoric acid. A well studied temperature dependent polymer (poly(N-isopropylacrylamide-co-Acrylamide)) was grafted onto the surface of these films to act as a temperature activated gatekeeper. Below the lower critical solution temperature (LCST) the polymer is erect and can block the pore openings, trapping cargo inside the pores. When the temperature is above the LCST the polymer collapses and unblocks the pores, allowing cargo to escape. The loading capacities as well as the reusability of these films were studied. PMID:25368448

  18. Spectroscopic study of sorption of nitrogen heterocyclic compounds on phyllosilicates

    SciTech Connect

    Chattopadhyay, S.; Traina, S.J.

    1999-03-02

    The present study focused on understanding the sorption characteristics of acridine (AcN) and acridine-9-carboxylic acid (AcNCOOH), two typical nitrogen heterocyclic compounds (NHCs), on well-characterized phyllosilicates (hectorite, saponite, and muscovite). Results presented in this article show that the degree of sorption of NHCs on phyllosilicates was dependent on the nature of the participating sorbates and sorbents. Sorption of the selected NHCs was pH-dependent, with maximum sorption occurring at low pH conditions, especially at pH < pK{sub a} of the NHC. Though sorption of the cationic forms of the NHCs on clays was preferred, neutral, zwitterionic, and anionic species of NHCs also sorbed on the clay surfaces. Spectroscopic studies have shown that sorbed NHC molecules formed clusters on clay surfaces, which acted as templates for molecular aggregation. Finally, the authors have also found that the clay surfaces promoted protonation of neutral AcN molecules at low sorbate concentrations.

  19. Paramagnetic carbon-13 shifts induced by the free radical tempo. 2. Nitrogen heterocycles

    SciTech Connect

    Qui, Z.W.; Grant, D.M.; Pugmire, R.J.

    1984-02-08

    With use of the free radical Tempo as a shift and relaxation reagent, both paramagnetic shifts and spin-lattice relaxation rates of nitrogen heterocycles are reported. Paramagnetic shifts of these compounds are larger than the corresponding shifts of the aromatic hydrocarbons, indicating a stronger interaction between nitrogen heterocyclic compounds and Tempo. Paramagnetic shifts increase with the number of nitrogen atoms per molecule. For pyridine type compounds, both shift and relaxation data show that the stronger interaction is not at the adjacent positions to the nitrogen atoms. It would appear in these heterocyclic complexes with Tempo that the nitrogen atoms tend to orient away from the N-O group in Tempo. In contrast, imidazole and indole exhibit a much stronger interaction with the Tempo due to hydrogen bond formation, and the positions near the N-H group exhibit larger paramagnetic shifts and relaxation rates. An approximate static model involving an indole-Tempo, hydrogen-bond complex accounts for the relaxation data from which both an equilibrium constant of complexation and a hydrogen-bond distance in the indole-Tempo complex could be estimated.

  20. Recent advances in novel heterocyclic scaffolds for the treatment of drug-resistant malaria.

    PubMed

    Kumar, Sahil; Singh, Rajesh K; Patial, Babita; Goyal, Sachin; Bhardwaj, T R

    2016-01-01

    Malaria is a major public health problem all over the world, particularly in tropical and subtropical countries due to the development of resistance and most deadly infection is caused by Plasmodium falciparum. There is a direct need for the discovery of new drugs with unique structures and mechanism of action to treat sensitive and drug-resistant strains of various plasmodia for radical cure of this disease. Traditional compounds such as quinine and related derivatives represent a major source for the development of new drugs. This review presents recent modifications of 4-aminoquinoline and 8-aminoquinolone rings as leads to novel active molecules which are under clinical trials. The review also encompasses the other heterocyclic compounds emerged as potential antimalarial agents with promising results such as acridinediones and acridinone analogues, pyridines and quinolones as antimalarials. Miscellaneous heterocyclics such as tetroxane derivatives, indole derivatives, imidazolopiperazine derivatives, biscationic choline-based compounds and polymer-linked combined antimalarial drugs are also discussed. At last brief introduction to heterocyclics in natural products is also reviewed. Most of them have been under clinical trials and found to be promising in the treatment of drug-resistant strains of Plasmodium and others can be explored for the same purpose. PMID:25775094

  1. Single molecule detection of PARP1 and PARP2 interaction with DNA strand breaks and their poly(ADP-ribosyl)ation using high-resolution AFM imaging.

    PubMed

    Sukhanova, Maria V; Abrakhi, Sanae; Joshi, Vandana; Pastre, David; Kutuzov, Mikhail M; Anarbaev, Rashid O; Curmi, Patrick A; Hamon, Loic; Lavrik, Olga I

    2016-04-01

    PARP1 and PARP2 are implicated in the synthesis of poly(ADP-ribose) (PAR) after detection of DNA damage. The specificity of PARP1 and PARP2 interaction with long DNA fragments containing single- and/or double-strand breaks (SSBs and DSBs) have been studied using atomic force microscopy (AFM) imaging in combination with biochemical approaches. Our data show that PARP1 localizes mainly on DNA breaks and exhibits a slight preference for nicks over DSBs, although the protein has a moderately high affinity for undamaged DNA. In contrast to PARP1, PARP2 is mainly detected at a single DNA nick site, exhibiting a low level of binding to undamaged DNA and DSBs. The enhancement of binding affinity of PARP2 for DNA containing a single nick was also observed using fluorescence titration. AFM studies reveal that activation of both PARPs leads to the synthesis of highly branched PAR whose size depends strongly on the presence of SSBs and DSBs for PARP1 and of SSBs for PARP2. The initial affinity between the PARP1, PARP2 and the DNA damaged site appears to influence both the size of the PAR synthesized and the time of residence of PARylated PARP1 and PARP2 on DNA damages. PMID:26673720

  2. Single molecule detection of PARP1 and PARP2 interaction with DNA strand breaks and their poly(ADP-ribosyl)ation using high-resolution AFM imaging

    PubMed Central

    Sukhanova, Maria V.; Abrakhi, Sanae; Joshi, Vandana; Pastre, David; Kutuzov, Mikhail M.; Anarbaev, Rashid O.; Curmi, Patrick A.; Hamon, Loic; Lavrik, Olga I.

    2016-01-01

    PARP1 and PARP2 are implicated in the synthesis of poly(ADP-ribose) (PAR) after detection of DNA damage. The specificity of PARP1 and PARP2 interaction with long DNA fragments containing single- and/or double-strand breaks (SSBs and DSBs) have been studied using atomic force microscopy (AFM) imaging in combination with biochemical approaches. Our data show that PARP1 localizes mainly on DNA breaks and exhibits a slight preference for nicks over DSBs, although the protein has a moderately high affinity for undamaged DNA. In contrast to PARP1, PARP2 is mainly detected at a single DNA nick site, exhibiting a low level of binding to undamaged DNA and DSBs. The enhancement of binding affinity of PARP2 for DNA containing a single nick was also observed using fluorescence titration. AFM studies reveal that activation of both PARPs leads to the synthesis of highly branched PAR whose size depends strongly on the presence of SSBs and DSBs for PARP1 and of SSBs for PARP2. The initial affinity between the PARP1, PARP2 and the DNA damaged site appears to influence both the size of the PAR synthesized and the time of residence of PARylated PARP1 and PARP2 on DNA damages. PMID:26673720

  3. Preparation and characterization of poly(triallyl isocyanurate-co-trimethylolpropane triacrylate) monolith and its applications in the separation of small molecules by liquid chromatography.

    PubMed

    Zhong, Jing; Hao, Mengbei; Li, Ruo; Bai, Ligai; Yang, Gengliang

    2014-03-14

    A new polymeric monolith was prepared in stainless-steel column and fused-silica capillary, respectively, by atom transfer radical polymerization technique. In the polymerization, triallyl isocyanurate (TAIC) was used as the functional monomer; trimethylolpropane triacrylate (TMPTA) as the crosslinking agent; polyethylene glycol 200 and 1,2-propanediol as the co-porogens; carbon tetrachloride as the initiator and ferrous chloride as the catalyst. The conditions of polymerization were optimized. Morphology of the prepared poly(TAIC-co-TMPTA) monolith was investigated by scanning electron microscopy; pore properties were assayed by mercury porosimetry and nitrogen adsorption. The characterization indicated that the prepared reversed-phase monolith possessed uniform structure, good permeability and mechanical stability. The column was used as the stationary phase of reversed phase high performance liquid chromatography (RP-HPLC) and capillary liquid chromatography (CLC) to separate the mixture of aromatic compounds. The new column performed around 125,000 theoretical plates per meter. The column showed good reproducibility: the relative standard deviation values of the retention factor values for aromatic compounds were less than 1.52% (n=7, column-to-column). PMID:24556171

  4. Iridium-catalyzed enantioselective hydrogenation of unsaturated heterocyclic acids.

    PubMed

    Song, Song; Zhu, Shou-Fei; Pu, Liu-Yang; Zhou, Qi-Lin

    2013-06-01

    Spiral binding: A highly enantioselective hydrogenation of unsaturated heterocyclic acids has been developed by using chiral iridium/spirophosphino oxazoline catalysts (see scheme; BArF(-) =tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, Boc=tert-butoxycarbonyl). This reaction provided an efficient method for the preparation of optically active heterocyclic acids with excellent enantioselectivities. PMID:23610004

  5. 40 CFR 721.10003 - Manganese heterocyclic tetraamine complex (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... complex (generic). 721.10003 Section 721.10003 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10003 Manganese heterocyclic tetraamine complex (generic). (a) Chemical... as manganese heterocyclic tetraamine complex (PMNs P-98-625/626/627/628/629 and P-00-614/617)...

  6. Modeling anti-Trypanosoma cruzi activity of N-oxide containing heterocycles.

    PubMed

    Boiani, Mariana; Cerecetto, Hugo; Gonzalez, Mercedes; Gasteiger, Johann

    2008-01-01

    In the present study a systematic approach was used to model the anti-T. cruzi activity of a series of N-oxide containing heterocycles belonging to four chemical families with a wide structural diversity. The proposed mode of action implies the reduction of the N-oxide moiety; however, the biochemical mechanism underlying the anti-T. cruzi activity is still unkown. For structural representation two types of descriptors were analyzed: quantum chemical (AM1) global descriptors and properties coded by radial distribution function (RDF). Both types of descriptors point to the relevance of electronic properties. The local-RDF (LRDF) identified an electrophilic center at 4.1-4.9 A from the oxygen atom of the N-oxide moiety, although other properties are required to explain the biological activity. While the mode of action of N-oxide containing heterocycles is still unknown, the results obtained here strengthen the importance of the electrophilic character of the molecule and the possible participation of the heterocycle in a reduction process. The ability of these descriptors to distinguish among activity classes was assessed using Kohonen neural networks, and the best clustering descriptors were later used for model building. Different learning algorithms were used for model development, and stratified 10-fold cross-validation was used to evaluate the performance of each classifier. The best results were obtained using k-nearest neighbors (k-NN) and decision tree (J48) methods combined with global descriptors. Since tree-based methods are easily translated into classification rules, the J48 model is a useful tool in the de novo construction of new N-oxide containing heterocycle lead structures. PMID:18163603

  7. Assembly of functionalized carbocycles or N-heterocycles through a domino electrocyclization-[1,2] migration reaction sequence.

    PubMed

    Jana, Navendu; Driver, Tom G

    2015-10-14

    The development of processes that streamline the synthesis of complex, functionalized carbocycles and heterocycles remains a hotly pursued topic because their scaffolds are present in a range of bioactive molecules and electronic materials. Although the Nazarov reaction has emerged to be useful in the synthesis of carbocycles and heterocycles, using an electrocyclization to trigger a migration remains underdeveloped. By constructing several bonds in one operation, domino reaction sequences are particularly effective at improving the efficiency of synthesis. The use of transition metal catalysts has the potential to render these processes stereoselective. This review examines the use of electrocyclization-[1,2] migrations to construct molecules and is organized by the type of ring constructed and the order of the two steps in this process. PMID:26275170

  8. Synthesis and NMR Spectral Analysis of Amine Heterocycles: The Effect of Asymmetry on the [superscript 1]H and [superscript 13]C NMR Spectra of N,O-Acetals

    ERIC Educational Resources Information Center

    Saba, Shahrokh; Ciaccio, James A.; Espinal, Jennifer; Aman, Courtney E.

    2007-01-01

    The stereochemical investigation is conducted to give students the combined experience of chemical synthesis of amines and N-heterocycles and structural stereochemical analysis using NMR spectroscopy. Students are introduced to the concept of topicity-stereochemical relationships between ligands within a molecule by synthesizing N,O-acetals.

  9. Synthesis and biodistribution of 211At-labeled, biotinylated, and charge-modified poly-L-lysine: evaluation for use as an effector molecule in pretargeted intraperitoneal tumor therapy.

    PubMed

    Lindegren, Sture; Andersson, Håkan; Jacobsson, Lars; Bäck, Tom; Skarnemark, Gunnar; Karlsson, Börje

    2002-01-01

    Poly-L-lysine (7, 21, and 204 kDa) has been evaluated as an effector carrier for use in pretargeted intraperitoneal tumor therapy. For the synthesis, the epsilon-amino groups on the poly-L-lysine were modified in three steps utilizing conjugate biotinylation with biotin amidocaproate N-hydroxysuccinimide ester (BANHS), conjugate radiolabeling with (211)At using the intermediate reagent N-succinimidyl 3-(trimethylstannyl)benzoate (m-MeATE), and charge modification using succinic anhydride, resulting in an increase in the molecular weight of approximately 80% of the final product. The labeling of the m-MeATE reagent and subsequent conjugation of the polymer were highly efficient with overall radiochemical yields in the range of 60-70%. The in vitro avidin binding ability of the modified polymer was almost complete (90-95%), as determined by binding to avidin beads using a convenient filter tube assay. Following intraperitoneal (ip) injection in athymic mice, the 13 kDa polymer product was cleared mainly via the kidneys with fast kinetics (biological half-live T(b) approximately 2 h) and with low whole-body retention. The clearance of the 38 kDa polymer was distributed between kidneys and liver, and the 363 kDa polymer was mainly sequestered by the liver with a T(b) of 8 h. Increased tissue uptake in the thyroid, lungs, stomach, and spleen following the distribution of the large effector molecules (38 and 363 kDa) suggests that degradation of the polymers by the liver may release some of the label as free astatine/astatide. PMID:12009939

  10. Features of the reaction of heterocyclic analogs of chalcone with lanthanide shift reagents

    SciTech Connect

    Turov, A.V.; Khilya, V.P.

    1994-10-01

    The PMR spectra of heterocyclic analogs of 2-hydroxychalcone containing thiazole, benzofuran, triazole, imidazole, benzodioxane, or pyridine rings in the presence of lanthanide shift reagents are studied. It is found that the most effective reagent for modifying the spectra of these compounds is Yb(fod)3. The broadening of the spectra of 2-hydroxy chalcones in the presence of lanthanide shift reagents is explained by the dynamic effects of complex formation. An example is given of the determination of the conformation of molecules of 2-hydroxychalcone by the simultaneous use of lanthanide shift reagents and the homonuclear Overhauser effect. 9 refs., 1 fig., 1 tab.

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

    PubMed Central

    2013-01-01

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

  12. Synthesis of heterocycles: Indolo (2,1-a) isoquinolines, renewables, and aptamer ligands for cellular imaging

    SciTech Connect

    Beasley, Jonathan

    2013-01-01

    In this thesis, we explore both total syntheses and methodologies of several aromatic heterocyclic molecules. Extensions of the Kraus indole synthesis toward 2-substituted and 2,3-disubstituted indoles, as well as biologically attractive indolo[2,1-a]isoquinolines are described. Recent renewable efforts directed to commodity maleic acid and the first reported furan-based ionic liquids are described. Our total synthesis of mRNA aptamer ligand PDC-Gly, and its dye coupled forms, plus aminoglycoside dye coupled ligands used in molecular imaging, are described.

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

    PubMed

    Baumann, Marcus; Baxendale, Ian R

    2013-01-01

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

  14. N-Heterocyclic Carbenes as Promotors for the Rearrangement of Phosphaketenes to Phosphaheteroallenes: A Case Study for OCP to OPC Constitutional Isomerism.

    PubMed

    Li, Zhongshu; Chen, Xiaodan; Benkő, Zoltán; Liu, Liu; Ruiz, David A; Peltier, Jesse L; Bertrand, Guy; Su, Chen-Yong; Grützmacher, Hansjörg

    2016-05-10

    The concept of isomerism is essential to chemistry and allows defining molecules with an identical composition but different connectivity (bonds) between their atoms (constitutional isomers) and/or a different arrangement in space (stereoisomers). The reaction of phosphanyl ketenes, (NHP)-P=C=O (NHP=N-heterocyclic phosphenium) with N-heterocyclic carbenes (NHCs) leads to phosphaheteroallenes (NHP)-O-P=C=NHC in which the PCO unit has been isomerized to OPC. Based on the isolation of several intermediates and DFT calculations, a mechanism for this fundamental isomerisation process is proposed. PMID:27060924

  15. Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed C-H Bond Activation

    PubMed Central

    Lewis, Jared C.; Bergman, Robert G.; Ellman, Jonathan A.

    2008-01-01

    azoles, azolines, dihydroquinazolines, pyridines, and quinolines, with a wide range of functionalized olefins. We demonstrated the utility of this methodology in the synthesis of natural products, drug candidates, and other biologically active molecules. In addition, we developed conditions to directly arylate these heterocycles with aryl halides. Our initial conditions that used PCy3 as a ligand were successful only for aryl iodides. However, efforts designed to avoid catalyst decomposition led to the development of ligands based on 9-phosphabicyclo[4.2.1]nonane (Phoban) that also facilitated the coupling of aryl bromides. We then replicated the unique coordination environment, stability, and catalytic activity of this complex using the much simpler tetrahydrophosphepine ligands and developed conditions that coupled aryl bromides bearing diverse functional groups without the use of a glovebox or purified reagents. With further mechanistic inquiry, we anticipate that researchers will better understand the details of the aforementioned Rh-catalyzed C-H bond functionalization reactions, resulting in the design of more efficient and robust catalysts, expanded substrate scope, and new transformations. PMID:18616300

  16. Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed C-H Bond Activation

    SciTech Connect

    Lewis, Jared; Bergman, Robert; Ellman, Jonathan

    2008-02-04

    heterocycles, including azoles, azolines, dihydroquinazolines, pyridines, and quinolines, with a wide range of functionalized olefins. They demonstrated the utility of this methodology in the synthesis of natural products, drug candidates, and other biologically active molecules. In addition, they developed conditions to directly arylate these heterocycles with aryl halides. The initial conditions that used PCy{sub 3} as a ligand were successful only for aryl iodides. However, efforts designed to avoid catalyst decomposition led to the development of ligands based on 9-phosphabicyclo[4.2.1]nonane (Phoban) that also facilitated the coupling of aryl bromides. They then replicated the unique coordination environment, stability, and catalytic activity of this complex using the much simpler tetrahydrophosphepine ligands and developed conditions that coupled aryl bromides bearing diverse functional groups without the use of a glovebox or purified reagents. With further mechanistic inquiry, they anticipate that researchers will better understand the details of the aforementioned Rh-catalyzed C-H bond functionalization reactions, resulting in the design of more efficient and robust catalysts, expanded substrate scope, and new transformations.

  17. Mutagenic Potency of Food-Derived Heterocyclic Amines

    SciTech Connect

    Felton, J S; Knize, M G; Wu, R W; Colvin, M E; Hatch, F T; Malfatti, M A

    2006-10-26

    The understanding of mutagenic potency has been primarily approached using ''quantitative structure activity relationships'' (QSAR). Often this method allows the prediction of mutagenic potency of the compound based on its structure. But it does not give the underlying reason why the mutagenic activities differ. We have taken a set of heterocyclic amine structures and used molecular dynamic calculations to dock these molecules into the active site of a computational model of the cytochrome P-450 1A1 enzyme. The calculated binding strength using Boltzman distribution constants was then compared to the QSAR value (HF/6-31G* optimized structures) and the Ames/Salmonella mutagenic potency. Further understanding will only come from knowing the complete set of mutagenic determinants. These include the nitrenium ion half-life, DNA adduct half-life, efficiency of repair of the adduct, and ultimately fixation of the mutation through cellular processes. For two isomers, PhIP and 3-Me-PhIP, we showed that for the 100-fold difference in the mutagenic potency a 5-fold difference can be accounted for by differences in the P450 oxidation. The other factor of 20 is not clearly understood but is downstream from the oxidation step. The application of QSAR (chemical characteristics) to biological principles related to mutagenesis is explored in this report.

  18. Preparation and evaluation of monolithic poly(N-vinylcarbazole-co-1,4-divinylbenzene) capillary columns for the separation of small molecules.

    PubMed

    Koeck, Rainer; Fischnaller, Martin; Bakry, Rania; Tessadri, Richard; Bonn, Guenther K

    2014-09-01

    Short-term polymerization or the so-called low-conversion polymerization was applied for the preparation of N-vinylcarbazole (NVC) and 1,4-divinylbenzene (DVB) monolithic capillary columns. The synthesis was carried out by thermally initiated free radical copolymerization under the influence of inert micro- (toluene) and macroporogen (1-decanol) and α,α'-azoisobutyronitrile (AIBN) as radical initiator. The morphological and porous properties were studied by scanning electron microscopy (SEM), nitrogen adsorption, and mercury intrusion porosimetry (MIP). The copolymerization process was studied by monomer conversion measurements. This approach led to increased porosity and specific surface area. A specific surface area above 400 m(2)/g of the monolith and a distinct bimodal pore size distribution were obtained. The chromatographic performance was determined in terms of theoretical plate heights and number of theoretical plates. The lowest plate height value was found to be 3.9 μm (corresponding to ≈256,000 plates per meter) applying methylparaben utilizing an 80 mm × 0.2 mm i.d. monolithic capillary. The developed NVC/DVB monolithic supports showed high separation efficiency towards small molecules, which was exemplified applying reversed-phase (RP) separation of alkylbenzenes, beta-blockers, flavanoids, parabens, and phenones. The loading capacity was analyzed for isocratic separation of seven alkylbenzenes and was found to be up to 77 ng total mass of alkylbenzenes. Furthermore, a long-term stability test of 1,000 consecutive runs was performed and resulted in a maximum variance of 0.97, 0.85, and 0.16 % RSD for resolution, peak width at half height, and retention times, respectively. The material was proven to have a high permeability of 1.11E-14 m(2), applying water as a mobile phase. PMID:25056873

  19. Stretched poly(methyl methacrylate) gel aligns small organic molecules in chloroform. stereochemical analysis and diastereotopic proton NMR assignment in ludartin using residual dipolar couplings and 3J coupling constant analysis.

    PubMed

    Gil, Roberto R; Gayathri, Chakicherla; Tsarevsky, Nicolay V; Matyjaszewski, Krzysztof

    2008-02-01

    Poly(methyl methacrylate) (PMMA) gels prepared by copolymerizing methyl methacrylate (MMA) and various amounts of ethylene glycol dimethacrylate (EGDMA) in the presence of the radical initiator V-70 (2,2'-azobis(2,4-dimethyl-4-methoxyvaleronitrile)) can orient small organic molecules when swollen in NMR tubes with CDCl(3). The aligning properties of the stretched PMMA gels were evaluated by monitoring the quadrupolar splitting of the (2)H NMR signal of CDCl(3), and the aligning degree is proportional to the cross-linking density. Natural abundance one-bond (1)H-(13)C residual dipolar couplings (RDCs) for menthol measured in the gels depended on the cross-link density. The stereochemistry and assignment of the diastereotopic protons of the gastroprotective and nonsteroidal aromatase inhibitor sesquiterpene lactone ludartin, isolated from Stevia yaconensis var. subeglandulosa, were unambiguously determined using a combination of natural abundance one-bond (1)H-(13)C RDCs measured in a PMMA gel and a (3)J coupling constant analysis. PMID:18177050

  20. Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

    PubMed Central

    Hemmerling, Franziska

    2016-01-01

    Summary This review highlights the biosynthesis of heterocycles in polyketide natural products with a focus on oxygen and nitrogen-containing heterocycles with ring sizes between 3 and 6 atoms. Heterocycles are abundant structural elements of natural products from all classes and they often contribute significantly to their biological activity. Progress in recent years has led to a much better understanding of their biosynthesis. In this context, plenty of novel enzymology has been discovered, suggesting that these pathways are an attractive target for future studies. PMID:27559404

  1. N-Heterocyclic Carbene Catalyzed [4 + 2] Annulation Reactions with in Situ Generated Heterocyclic ortho-Quinodimethanes.

    PubMed

    Xu, Jianfeng; Yuan, Shiru; Miao, Maozhong

    2016-08-01

    An efficient strategy for the in situ generation of heterocyclic ortho-quinodimethanes (oQDMs) from 2-methyl-heteroarene-3-carboxylic esters by N-heterocyclic carbene (NHC) catalysis is disclosed. These heterocyclic oQDMs undergo highly enantioselective [4 + 2] annulation reactions with isatin-derived ketimines to afford optically pure heteroarene-fused δ-lactams bearing a quaternary stereogenic center. The main features of this reaction include challenging direct C(sp(3))-H bond functionalizations, excellent enantioselectivities, readily available starting materials, mild reaction conditions, high efficiency, and operational simplicity. PMID:27391039

  2. Heterocyclic compounds as carbonic anhydrase inhibitor.

    PubMed

    Husain, Asif; Madhesia, Diwakar

    2012-12-01

    The carbonic anhydrases (CAs, EC 4.2.1.1) constitute interesting targets for the design of pharmacological agents useful in the treatment or prevention of a variety of disorders such as, glaucoma, acid-base disequilibria, epilepsy, and other neuromuscular diseases, altitude sickness, edema, and obesity. A quite new and unexpected application of the CA inhibitors (CAIs) is with regard to their potential use in the management (imaging and treatment) of hypoxic tumors. A series of sulfonamides, including some clinically used derivatives like acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, benzolamide, and sulpiride, or indisulam, a compound in clinical development as antitumor drug, as well as the sulfamate antiepileptic drug topiramate have been reported to inhibit various human carbonic anhydrase isozyme. Various heterocyclic sulfonamides have been reported in this review with their potency to inhibit different carbonic anhydrases isozymes. PMID:21981003

  3. New heterocyclic compounds: Synthesis and antitrypanosomal properties.

    PubMed

    Pomel, S; Dubar, F; Forge, D; Loiseau, P M; Biot, C

    2015-08-15

    Three new series of quinoline, quinolone, and benzimidazole derivatives were synthesized and evaluated in vitro against Trypanosoma brucei gambiense. In the quinoline series, the metallo antimalarial drug candidate (ferroquine, FQ) and its ruthenium analogue (ruthenoquine, RQ, compound 13) showed the highest in vitro activities with IC50 values around 0.1 μM. Unfortunately, both compounds failed to cure Trypanosoma brucei brucei infected mice in vivo. The other heterocyclic compounds were active in vitro with IC50 values varying from 0.8 to 34 μM. One of the most interesting results was a fluoroquinolone derivative (compound 2) that was able to offer a survival time of 8 days after a treatment at the single dose of 100 μmol/kg by intraperitoneal route. Although no clear-cut structure-activity relationships emerged, further pharmacomodulations are worth to be developed in this series. PMID:25835356

  4. Coumarin heterocyclic derivatives: chemical synthesis and biological activity.

    PubMed

    Medina, Fernanda G; Marrero, Joaquín G; Macías-Alonso, Mariana; González, Magdalena C; Córdova-Guerrero, Iván; Teissier García, Ariana G; Osegueda-Robles, Soraya

    2015-09-23

    This review highlights the broad range of science that has arisen from the synthesis of coumarin-linked and fused heterocycle derivatives. Specific topics include their synthesis and biological activity. PMID:26151411

  5. SPECTROSCOPIC STUDY OF SORPTION OF NITROGEN HETEROCYCLIC COMPOUNDS ON PHYLLOSILICATES

    EPA Science Inventory

    The present study focused on understanding the sorption characteristics of acridine (AcN)and acridine-9-carboxylic acid (AcNCOOH), two typical nitrogen heterocyclic compounds (NHCs), on well-characterized phyllosilicates (hectorite, saponite, and muscovite). Results presented in...

  6. Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates.

    PubMed

    Haji, Mohammad

    2016-01-01

    Multicomponent reactions (MCRs) are one of the most important processes for the preparation of highly functionalized organic compounds in modern synthetic chemistry. As shown in this review, they play an important role in organophosphorus chemistry where phosphorus reagents are used as substrates for the synthesis of a wide range of phosphorylated heterocycles. In this article, an overview about multicomponent reactions used for the synthesis of heterocyclic compounds bearing a phosphonate group on the ring is given. PMID:27559377

  7. Protonation of Homoenolate Equivalents Generated by N-Heterocyclic Carbenes

    PubMed Central

    Maki, Brooks E.; Chan, Audrey; Scheidt, Karl A.

    2010-01-01

    Homoenolate equivalents are generated by Lewis basic N-heterocyclic carbene catalysts and then protonated to generate efficiently saturated esters from unsaturated aldehydes. This reactivity is extended to the generation of β-acylvinyl anions from alkynyl aldehydes. The asymmetric protonation of a homoenolate equivalent generated from a β,β-disubstituted aldehyde can be accomplished with a chiral N-heterocyclic carbene. PMID:22347730

  8. A Stable Heterocyclic Amino(phosphanylidene-σ(4) -phosphorane) Germylene.

    PubMed

    Del Rio, Natalia; Baceiredo, Antoine; Saffon-Merceron, Nathalie; Hashizume, Daisuke; Lutters, Dennis; Müller, Thomas; Kato, Tsuyoshi

    2016-04-01

    A new stable heterocyclic germylene, in which the divalent germanium atom lies between a nitrogen atom and a phosphanylidene phosphorane group, was synthesized. Experimental and theoretical studies revealed the peculiar effect of phosphanylidene phosphorane substituent, which is a stronger π-donor towards germanium than an amino group is. Because of the weak phosphorus-germanium π-bond, this new germylene compound shows an enhanced reactivity compared to classical N-heterocyclic germylenes. PMID:26954722

  9. Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

    PubMed Central

    2016-01-01

    Summary Multicomponent reactions (MCRs) are one of the most important processes for the preparation of highly functionalized organic compounds in modern synthetic chemistry. As shown in this review, they play an important role in organophosphorus chemistry where phosphorus reagents are used as substrates for the synthesis of a wide range of phosphorylated heterocycles. In this article, an overview about multicomponent reactions used for the synthesis of heterocyclic compounds bearing a phosphonate group on the ring is given. PMID:27559377

  10. Utilization of N-X bonds in the synthesis of N-heterocycles.

    PubMed

    Minakata, Satoshi

    2009-08-18

    Nitrogen-containing heterocycles--such as aziridines, pyrrolidines, piperidines, and oxazolines--frequently show up as substructures in natural products. In addition, some of these species show potent biological activities. Therefore, researchers would like to develop practical and convenient methods for constructing these heterocycles. Among the available methods, the transfer of N(1) units to organic molecules, especially olefins, is a versatile method for the synthesis of N-heterocycles. This Account reviews some of our recent work on the synthesis of N-heterocycles using the N-X bond. A nitrogen-halogen bond bearing an electron-withdrawing group on the nitrogen can be converted to a halonium ion. In the presence of C-C double bonds, these species produce three-membered cyclic halonium intermediates, which can be strong electrophiles and can produce stereocontrolled products. N-Halosuccinimides are representative sources of halonium ions, and the nitrogen of succinimide is rarely used in organic synthesis. If the nitrogen could act as a nucleophile, after releasing halonium ions to C-C double bonds, we expect great advances would be possible in the stereoselective functionalization of olefins. We chose N-chloro-N-sodio-p-toluenesulfonamide (chloramine-T, CT), an inexpensive and commercially available reagent, as our desired reactant. In the presence of a catalytic amount of CuCl or I(2) and AgNO(3), we achieved the direct aziridination of olefins with CT. The reaction catalyzed by I(2) could be carried out in water or silica-water as a green process. The reaction of iodoolefins with CT gave pyrrolidine derivatives under extremely mild conditions with complete stereoselectivity. We also extended the utility of the N-chloro-N-metallo reagent, which is often unstable and difficult to work with. Although CT does not react with electron-deficient olefins without a metal catalyst or an additive, we found that N-chloro-N-sodiocarbamates react with electron

  11. Quantitative relationship between mutagenicity and structure of heterocyclic analogs of pyrene and phenanthrene

    SciTech Connect

    Baskin, I.I.; Lyubimova, I.K.; Abilev, S.K.

    1994-12-31

    In this work, the authors investigated quantitative relationships between mutagenicity and chemical structures of certain heterocyclic analogs of pyrene and phenanthrene that have yet to be examined. Compounds were synthesized using the methods described earlier. The compounds were tested for mutagenic activity by Ames` method. They used the strain Salmonella typhimurium TA1538 (his D3052, rfa, uvr), which registered the reading frame shift mutations. Analysis of the data suggests that the most considerable increases in mutagenicity occur with two nitro groups at positions 2 and 7. When nitro groups occur at other positions, the molecule displayed no mutagenicity, irrespective of the number of groups. Two amino groups at the same position, one amino and one carboxyl group, or chlorine atoms impart a weaker mutagenicity to the molecule. The mutagenic properties were lost on shifting the amino groups from positions 2,7 to 1,6.

  12. Advances in nickel-catalyzed cycloaddition reactions to construct carbocycles and heterocycles.

    PubMed

    Thakur, Ashish; Louie, Janis

    2015-08-18

    Transition-metal catalysis has revolutionized the field of organic synthesis by facilitating the construction of complex organic molecules in a highly efficient manner. Although these catalysts are typically based on precious metals, researchers have made great strides in discovering new base metal catalysts over the past decade. This Account describes our efforts in this area and details the development of versatile Ni complexes that catalyze a variety of cycloaddition reactions to afford interesting carbocycles and heterocycles. First, we describe our early work in investigating the efficacy of N-heterocyclic carbene (NHC) ligands in Ni-catalyzed cycloaddition reactions with carbon dioxide and isocyanate. The use of sterically hindered, electron donating NHC ligands in these reactions significantly improved the substrate scope as well as reaction conditions in the syntheses of a variety of pyrones and pyridones. The high reactivity and versatility of these unique Ni(NHC) catalytic systems allowed us to develop unprecedented Ni-catalyzed cycloadditions that were unexplored due to the inefficacy of early Ni catalysts to promote hetero-oxidative coupling steps. We describe the development and mechanistic analysis of Ni/NHC catalysts that couple diynes and nitriles to form pyridines. Kinetic studies and stoichiometric reactions confirmed a hetero-oxidative coupling pathway associated with this Ni-catalyzed cycloaddition. We then describe a series of new substrates for Ni-catalyzed cycloaddition reactions such as vinylcyclopropanes, aldehydes, ketones, tropones, 3-azetidinones, and 3-oxetanones. In reactions with vinycyclopropanes and tropones, DFT calculations reveal noteworthy mechanistic steps such as a C-C σ-bond activation and an 8π-insertion of vinylcyclopropane and tropone, respectively. Similarly, the cycloaddition of 3-azetidinones and 3-oxetanones also requires Ni-catalyzed C-C σ-bond activation to form N- and O-containing heterocycles. PMID:26200651

  13. Computational design of fused heterocyclic energetic materials

    NASA Astrophysics Data System (ADS)

    Tsyshevskiy, Roman; Pagoria, Philip; Batyrev, Iskander; Kuklja, Maija

    A continuous traditional search for effective energetic materials is often based on a trial and error approach. Understanding of fundamental correlations between the structure and sensitivity of the materials remains the main challenge for design of novel energetics due to the complexity of the behavior of energetic materials. State of the art methods of computational chemistry and solid state physics open new compelling opportunities in simulating and predicting a response of the energetic material to various external stimuli. Hence, theoretical and computational studies can be effectively used not only for an interpretation of sensitivity mechanisms of widely used explosives, but also for identifying criteria for material design prior to its synthesis and experimental characterization. We report here, how knowledge on thermal stability of recently synthesized materials of LLM series is used for design of novel fused heterocyclic energetic materials, including DNBTT (2,7-dinitro-4H,9H-bis([1, 2, 4"]triazolo)[1,5-b:1',5'-e][1, 2, 4, 5]tetrazine), compound with high thermal stability, which is on par or better than that of TATB. This research is supported by ONR (Grant N00014-12-1-0529), NSF XSEDE resources (Grant DMR-130077) and DOE NERSC resources (Contract DE-AC02-05CH11231).

  14. MICROBIAL DEGRADATION OF NITROGEN, OXYGEN AND SULFUR HETEROCYCLIC COMPOUNDS UNDER ANAEROBIC CONDITIONS: STUDIES WITH AQUIFER SAMPLES

    EPA Science Inventory

    The potential for anaerobic biodegradation of 12 heterocyclic model compounds was studied. Nine of the model compounds were biotransformed in aquifer slurries under sulfate-reducing or methanogenic conditions. The nitrogen and oxygen heterocyclic compounds were more susceptible t...

  15. Recent advances in the electrochemical construction of heterocycles

    PubMed Central

    2014-01-01

    Summary Due to the fact that the major portion of pharmaceuticals and agrochemicals contains heterocyclic units and since the overall number of commercially used heterocyclic compounds is steadily growing, heterocyclic chemistry remains in the focus of the synthetic community. Enormous efforts have been made in the last decades in order to render the production of such compounds more selective and efficient. However, most of the conventional methods for the construction of heterocyclic cores still involve the use of strong acids or bases, the operation at elevated temperatures and/or the use of expensive catalysts and reagents. In this regard, electrosynthesis can provide a milder and more environmentally benign alternative. In fact, numerous examples for the electrochemical construction of heterocycles have been reported in recent years. These cases demonstrate that ring formation can be achieved efficiently under ambient conditions without the use of additional reagents. In order to account for the recent developments in this field, a selection of representative reactions is presented and discussed in this review. PMID:25550752

  16. Ring Enlargement of Three-Membered Boron Heterocycles upon Reaction with Organic π Systems: Implications for the Trapping of Borylenes.

    PubMed

    Krasowska, Małgorzata; Bettinger, Holger F

    2016-07-18

    New low-energy pathways for the reaction between substituted boriranes and borirenes with unsaturated hydrocarbons (ethyne or ethene) were discovered using density functional and coupled cluster theory. The interaction between the π bond of the hydrocarbon and the empty p orbital of the boron center leads to ring expansion of the three-membered to a five-membered boron heterocycle. The reactions are strongly exothermic and have low or even no barriers. They involve intermediates with a pentacoordinate boron center with two hydrocarbon molecules coordinating to boron akin to metal-olefin complexes. These borylene complexes are shallow minima on the potential energy surfaces. But significantly higher barriers for ring formation are computed for 1,5-cyclooctadiene and dibenzocyclooctatetraene complexes of borylenes, making these complexes likely detectable under appropriate experimental conditions. Our computational findings have implications for the interpretation of trapping experiments of thermally generated small borylenes with excess of small π systems. Because of very low barriers for reactions of three-membered boron heterocycles with π systems and the at least locally large excess of the latter under such conditions, formation of five-membered boron heterocycles should be considered. PMID:27305278

  17. Biological Screening of Newly Synthesized BIAN N-Heterocyclic Gold Carbene Complexes in Zebrafish Embryos

    PubMed Central

    Farooq, Muhammad; Abu Taha, Nael; Butorac, Rachel R.; Evans, Daniel Anthony; Elzatahry, Ahmed A.; Elsayed, Elsayed Ahmed; Wadaan, Mohammad A. M.; Al-Deyab, Salem S.; Cowley, Alan H.

    2015-01-01

    N-Heterocyclic carbene (NHC) metal complexes possess diverse biological activities but have yet to be extensively explored as potential chemotherapeutic agents. We have previously reported the synthesis of a new class of NHC metal complexes N-heterocyclic with acetate [IPr(BIAN)AuOAc] and chloride [IPr(BIAN)AuCl] ligands. In the experiments reported herein, the zebrafish embryos were exposed to serial dilutions of each of these complexes for 10–12 h. One hundred percent mortality was observed at concentrations ≥50 µM. At sub-lethal concentrations (10–30 µM), both compounds influenced zebrafish embryonic development. However, quite diverse categories of abnormalities were found in exposed embryos with each compound. Severe brain deformation and notochord degeneration were evident in the case of [IPr(BIAN)AuOAc]. The zebrafish embryos treated with [IPr(BIAN)AuCl] exhibited stunted growth and consequently had smaller body sizes. A depletion of 30%–40% glutathione was detected in the treated embryos, which could account for one of the possible mechanism of neurotoxicity. The fact that these compounds are capable of both affecting the growth and also compromising antioxidant systems by elevating intracellular ROS production implies that they could play an important role as a new breed of therapeutic molecules. PMID:26501273

  18. One-Step Synthesis of Diverse Pyridine-Containing Heterocycles with 3-Ethoxycyclobutanones at Room Temperature.

    PubMed

    Lin, Yun; Yang, Xinglin; Pan, Weidong; Rao, Yu

    2016-05-01

    An efficient and convenient approach toward a diversity-oriented synthesis of bioactive pyridine-containing fused heterocycles is described. Through a Lewis acid catalyzed union of 3-ethoxycyclobutanones with various heterocyclic amines, a broad range of heterocyclic compounds were prepared readily at ambient temperature with excellent regioselectivity. PMID:27115560

  19. Synthesis of heterocyclic systems based on mono- and dicarbonyl adamantane derivatives

    NASA Astrophysics Data System (ADS)

    Kon'kov, S. A.; Moiseev, I. K.; Zemtsova, M. N.; Bormasheva, K. M.

    2014-05-01

    Examples of the synthesis of various heterocycles containing an adamantane moiety based on mono- and dicarbonyl adamantane derivatives are considered. Systems in which the adamantane cage is spiro-connected to a heterocyclic ring or is a part of substituent in the heterocycle are presented. Data on the biological activities of such derivatives are given. The bibliography includes 85 references.

  20. Activation of small molecules by phosphorus biradicaloids.

    PubMed

    Hinz, Alexander; Kuzora, Rene; Rosenthal, Uwe; Schulz, Axel; Villinger, Alexander

    2014-11-01

    The reactivity of biradicaloid [P(μ-NTer)]2 was employed to activate small molecules bearing single, double, and triple bonds. Addition of chalcogens (O2 , S8 , Sex and Tex ) led to the formation of dichalcogen-bridged P2 N2 heterocycles, except from the reaction with molecular oxygen, which gave a P2 N2 ring featuring a dicoordinated P(III) and a four-coordinated P(V) center. In formal [2πe+2πe] addition reactions, small unsaturated compounds such as ethylene, acetylene, acetone, acetonitrile, tolane, diphenylcarbodiimide, and bis(trimethylsilyl)sulfurdiimide are readily added to the P2 N2 heterocycle of the biradicaloid [P(μ-NTer)]2 , yielding novel heteroatom cage compounds. The synthesis, reactivity, and bonding of the biradicaloid [P(μ-NTer)]2 were studied in detail as well as the synthesis, properties, and structural features of all addition products. PMID:25266101

  1. Heterocyclic Curcumin Derivatives of Pharmacological Interest: Recent Progress.

    PubMed

    Martinez-Cifuentes, Maximiliano; Weiss-Lopez, Boris; Santos, Leonardo S; Araya-Maturana, Ramiro

    2015-01-01

    Curcumin, a natural yellow polyphenol, is isolated from the herb Curcuma longa L. (turmeric), a member of the ginger family. It has been extensively studied due to their multiple pharmacological properties. Nevertheless, curcumin has disadvantages such as poor water solubility, poor bioavailability and rapid metabolism, which has prompted the search for analogues that overcome these shortcomings while maintaining or improving their good pharmacological properties. Among the main curcumin analogues that have been developed, the heterocyclic curcuminoids show a high interest. In this review, we describe recent progress in the synthesis and pharmacological properties of new heterocyclic curcumin derivatives. The most recent developments in anti-cancer, anti-Alzheimer, anti-bacterial and anti-oxidants heterocyclic curcumin derivatives are covered. PMID:25915614

  2. Heterocyclic N-Oxides - An Emerging Class of Therapeutic Agents.

    PubMed

    Mfuh, A M; Larionov, O V

    2015-01-01

    Heterocyclic N-oxides have emerged as potent compounds with anticancer, antibacterial, antihypertensive, antiparasitic, anti-HIV, anti-inflammatory, herbicidal, neuroprotective, and procognitive activities. The N-oxide motif has been successfully employed in a number of recent drug development projects. This review surveys the emergence of this scaffold in the mainstream medicinal chemistry with a focus on the discovery of the heterocyclic N-oxide drugs, N-oxide-specific mechanisms of action, drug-receptor interactions and synthetic avenues to these compounds. As the first review on this subject that covers the developments since 1950s to date, it is expected that it will inspire wider implementation of the heterocyclic N-oxide motif in the rational design of new medicinal agents. PMID:26087764

  3. Mutagenic activity and heterocyclic amine content of the human diet

    SciTech Connect

    Knize, M.G.; Dolbeare, F.A.; Cunningham, P.L.; Felton, J.S.

    1993-01-15

    The mutagenic activity and the mass amount of heterocyclic amines responsible for the mutagenic activity have been measured in some cooked foods. Cooked meats are the predominant source of mutagenic activity in the diet with values ranging from 0 to 10,000 revertants per gram reported in the Ames/Salmonelia test with strain TA98. Several heterocyclic amines are present and have been quantified using solid-phase extraction followed by HPLC. Frying at higher temperatures and for longer times produces the greatest mutagenic response, and concomitantly, the largest amounts of heterocyclic amines. Most of the mutagenic activity in fried meat samples can be accounted for by MelQx, DiMelQx and IQ, although other heterocylic amines are present and PHIP mutagenic activity becomes significant at higher temperatures. Non-meat products such as baked breads can also form significant mutagenic activity, particularly when overcooked. Commercially prepared hamburgers made from meat substitutes such as tofu, wheat gluten or tempeh and fried at 210{degrees}C have up to 10% of the mutagenic activity of a fried beef patty cooked under the same conditions. When detected, amounts of heterocyclic amines in fried beef patties range from a total of 0.35 ng/g for commercial beef hamburgers to 142 ng/g for a beef patty cooked over a barbecue. Dietary intake is expected to have a large range, from less than one microgram per day to over 50 micrograms per day based on current knowledge of known heterocyclic amine chemicals and heterocyclic amine-containing foods.

  4. Synthesis of new carbo- and heterocyclic analogues of 8-HETE and evaluation of their activity towards the PPARs.

    PubMed

    Caijo, Frédéric; Mosset, Paul; Grée, René; Audinot-Bouchez, Valérie; Boutin, Jean; Renard, Pierre; Caignard, Daniel-Henri; Dacquet, Catherine

    2005-10-15

    A new class of dual PPARs alpha and gamma agonists was developed. These compounds are structural analogues of the arachidonic acid metabolite, the 8-(S)-HETE. A versatile strategy has been introduced to prepare the target molecules having different carbo- and heterocyclic cores and to modulate the unsaturations on the side chains. Their affinity towards the PPARs alpha and gamma receptors is reported, together with their transactivation percentage. Most of these derivatives have a good activity as dual agonists but the quinoline-derived products appear as the most promising compounds. PMID:16137885

  5. Pressure Effects in Polycyclic Aromatic Nitrogenated Heterocycles (PANHs): Diagnostic Qualities and Cosmobarometry Potential

    NASA Astrophysics Data System (ADS)

    Montgomery, Wren; Sephton, Mark A.

    2016-03-01

    The influence of polycyclic aromatic nitrogen heterocycles (PANHs), which have been suggested as contributors to the interstellar IR emission bands, on interstellar emission features is difficult to constrain because their infrared characteristics are strongly similar to those for polycyclic aromatic hydrocarbons (PAHs). One possible solution is to seek a means of visualizing the presence of PANHs that provides information that is distinct from that for PAHs. Although PANHs and PAHs have similar infrared characteristics in many settings, this relationship may not be universally maintained. We have used in situ high-pressure synchrotron-source Fourier transform infrared spectroscopy to determine that the responses of two representative molecules, acridine and anthracene, differ at high pressures (>ca. 1 GPa). Because there are a number of high-pressure environments that can be remotely observed by infrared spectroscopy, they represent a potential to glimpse the distribution of PANHs across the cosmos.

  6. 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

  7. 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.

  8. Synthesis, spectroscopic (UV-vis and GIAO NMR), crystallographic and theoretical studies of triazine heterocyclic derivatives

    NASA Astrophysics Data System (ADS)

    Khan, Salman A.; Obaid, Abdullah Y.; Al-Harbi, Laila M.; Arshad, Muhammad Nadeem; Şahin, Onur; Ersanlı, Cem Cüneyt; Abdel-Rehman, R. M.; Asiri, Abdullah M.; Hursthouse, Michael B.

    2015-09-01

    This work presents the synthesis and characterization of triazine heterocyclic derivatives. The spectroscopic properties like nuclear magnetic resonance [NMR, (1H and 13C)] were recorded in CDCl3 solution and Ultraviolet-Visible (UV-vis) absorption spectrums of compounds, 5,6-diphenyl-[1,2,4]triazin-3-ylamine (1), (5,6-diphenyl-[1,2,4]triazin-3-yl)-hydrazine (2) and 5,6-diphenyl-4H-[1,2,4] triazine-3-thione (3), were recorded in the range of 200-800 nm, using chloroform as base solvent. Molecular geometry of compounds with triazine heterocyclic derivative in the ground state have been calculated using the density functional theory (DFT) with 6-31G(d,p) basis set and compared with the X-ray experimental data. The calculated results show that the optimized geometry can well reproduce the crystal structures. Total static dipole moment (μ), the average linear polarizability (α) and the first hyperpolarizability (β) values of the investigated molecules have been computed using the same methods. The energetic behavior of compounds in solvent media has been examined using B3LYP method with the 6-31G(d,p) basis set by applying the polarizable continuum model (PCM). The total energy of compounds decreases with increasing polarity of the solvent. Frontier molecular orbitals and the molecular electrostatic potential (MEP), 1H NMR, and 13C NMR of three triazine derivatives were investigated using theoretical calculations. The linear polarizabilities and first hyperpolarizabilities of the studied molecules indicate that the compounds 1-3 can be used as a good nonlinear optical material (NLO). Isotropic chemical shifts were calculated using the gauge-invariant atomic orbital (GIAO) method. Comparison of the NMR chemical shifts, absorption wavelengths with the experimental values revealed that DFT and time dependent-density functional theory (TD-DFT) method produce generally closer to good results.

  9. An epidemiologic approach to studying heterocyclic amines.

    PubMed

    Sinha, Rashmi

    2002-09-30

    Diets containing substantial amounts of red meat may increase the risk of colorectal, pancreatic, breast, prostate, and renal cancer. The association with red meat intake may be due to a combination of factors, such as content of fat, protein, and iron, and/or meat preparation (e.g. cooking or preserving methods). Laboratory results have shown that meats cooked at high temperatures contain heterocyclic amines (HCAs) known to be mutagenic and carcinogenic in animals. Many older epidemiologic studies of colon cancer using surrogates for HCA exposure from meat (for example, doneness level, surface browning, frying, intake of gravy) have produced suggestive but inconsistent results. These discrepancies may have resulted in part from having used dietary questionnaires that combined meat-cooking practices in ways that made the intake of HCAs difficult to estimate. Thus, over the last decade we have taken a multidisciplinary approach to investigating whether the association with red meat intake can be explained by meat-cooking practices that produce mutagens/carcinogens. To estimate intake, a database for HCAs have been developed and used in conjunction with a validated meat-cooking food frequency questionnaire (FFQ). To develop biological markers of internal exposure, a metabolic study was conducted where subjects consumed controlled amounts of meat cooked at low and high temperatures. The role of meat type, cooking methods, doneness levels, and meat-cooking mutagens were examined in case-control studies of colorectal adenomas, lung, and breast cancers using both questionnaire information and biomarkers. In a case-control study of colorectal adenomas, an increased risk was associated with a high intake of red meat. Most of this risk was due to intake of red meat cooked until well/very well done and/or by high-temperature cooking techniques such as grilling. Linking the FFQ information to HCA database, the impact several HCAs on risk was evaluated. An increased risk was

  10. Greener Alternatives to Expedient Synthesis of Heterocycles and Nanomaterial

    EPA Science Inventory

    A brief account of reactions involving microwave (MW) exposure of neat reactants or catalyzed by mineral support surfaces, such as alumina, silica, clay, or their ‘doped’ versions, for the rapid one-pot assembly of heterocyclic compounds [1] from in situ generated reactive interm...

  11. Trifluoromethyl nitrogen heterocycles: synthetic aspects and potential biological targets.

    PubMed

    Meyer, F

    2016-02-21

    Recent advances regarding the synthetic chemistry of fluorinated aziridines, azetidines, pyrrolidines and their lactam/amino acid counterparts are presented. These heterocycles are of high importance both as building blocks for more complex structures and as active parts of medicinal chemistry-oriented compounds. PMID:26783567

  12. Homogeneous rhodium(i)-catalysis in de novo heterocycle syntheses.

    PubMed

    Neuhaus, James D; Willis, Michael C

    2016-06-14

    Recent research has led to the development of mild, efficient and selective catalytic systems based on Rh(i) complexes. This review summarises the applications of these catalysts to the synthesis of heterocycles from simple building blocks. Included herein are approaches based on cycloisomerisation, cycloaddition, hydroacylation and hydroarylation reactions, as well as various tandem and domino procedures and carbonylation processes. PMID:27197887

  13. GREENER SYNTHESIS OF HETEROCYCLIC COMPOUNDS USING MICROWAVE IRRADIATION

    EPA Science Inventory

    An introduction of our interest in the microwave-assisted greener synthesis of a variety of heterocyclic compounds will be presented. It involves microwave (MW) exposure of neat reactants (undiluted) catalyzed by the surfaces of recyclable mineral supports, such as alumina, sili...

  14. Greener Synthetic Alternatives to Heterocycles, Nanomaterials and Nanocomposites

    EPA Science Inventory

    Microwave (MW) expedited reaction of neat reactants or catalyzed by mineral support surfaces, such as alumina, silica, clay, or their ‘doped’ versions, for the rapid one-pot assembly of heterocyclic compounds from in situ generated reactive intermediates via enamines or using hyp...

  15. Greener and Expeditious Synthesis of Bioactive Heterocycles using Microwave Irradiation

    EPA Science Inventory

    The utilization of green chemistry techniques is dramatically reducing chemical waste and reaction times as has recently been proven in several organic syntheses and chemical transformations. To illustrate these advantages in the synthesis of bio-active heterocycles, we have stud...

  16. Synthesis and antitubercular activity of heterocycle substituted diphenyl ether derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite being an ancient disease, tuberculosis (TB) remains the leading single-agent infectious disease killer in the world. The emerging serious problem due to TB control and clinical management prompted us to synthesize novel series of heterocyclic substituted diphenyl ether derivatives and determ...

  17. Solvent-Free Synthesis of Heterocyclic Compounds Using Microwave Technology

    NASA Astrophysics Data System (ADS)

    Ahmad, Natiq Ghanim

    The synthesis of heterocyclic compounds containing pyrimidine, pyrazoline, isoxazoline and cyclohexanone ring from chalcone derivatives containing 3,4-dimethoxyphenyl group and furfuryl ring group under dry condition using microwaves. The structures of these compounds were confirmed by IR, H1 NMR and physical constants.

  18. Modern advances in heterocyclic chemistry in drug discovery.

    PubMed

    Taylor, Alexandria P; Robinson, Ralph P; Fobian, Yvette M; Blakemore, David C; Jones, Lyn H; Fadeyi, Olugbeminiyi

    2016-07-12

    New advances in synthetic methodologies that allow rapid access to a wide variety of functionalized heterocyclic compounds are of critical importance to the medicinal chemist as it provides the ability to expand the available drug-like chemical space and drive more efficient delivery of drug discovery programs. Furthermore, the development of robust synthetic routes that can readily generate bulk quantities of a desired compound help to accelerate the drug development process. While established synthetic methodologies are commonly utilized during the course of a drug discovery program, the development of innovative heterocyclic syntheses that allow for different bond forming strategies are having a significant impact in the pharmaceutical industry. This review will focus on recent applications of new methodologies in C-H activation, photoredox chemistry, borrowing hydrogen catalysis, multicomponent reactions, regio- and stereoselective syntheses, as well as other new, innovative general syntheses for the formation and functionalization of heterocycles that have helped drive project delivery. Additionally, the importance and value of collaborations between industry and academia in shaping the development of innovative synthetic approaches to functionalized heterocycles that are of greatest interest to the pharmaceutical industry will be highlighted. PMID:27282396

  19. Journey of poly-nucleotides through OmpF porin.

    PubMed

    Hadi-Alijanvand, Hamid; Rouhani, Maryam

    2015-05-21

    OmpF is an abundant porin in many bacteria which attracts attention as a promising biological nanopore for DNA sequencing. We study the interactions of OmpF with pentameric poly-nucleotides (poly-Ns) in silico. The poly-N molecule is forced to translocate through the lumen of OmpF. Subsequently, the structural and dynamical effects of translocation steps on protein and poly-N molecules are explored in detail. The external loops of OmpF are introduced as the main region for discrimination of poly-Ns based on their organic bases. Structural network analyses of OmpF in the presence or absence of poly-Ns characterize special residues in the structural network of porin. These residues pave the way for engineering OmpF protein. The poly-N-specific pattern of OmpF's local conductance is detected in the current study. Computing the potential of mean force for translocation steps, we define the energetic barrier ahead of poly-N to move through OmpF's lumen. We suggest that fast translocation of the examined poly-N molecules through OmpF seems unattainable by small external driving forces. Our computational results suggest some abilities for OmpF porin like OmpF's potential for being used in poly-N sequencing. PMID:25965338

  20. 1,1-Hydroboration of Fused Azole-Isoindole Analogues as an Approach for Construction of B,N-Heterocycles and Azole-Fused B,N-Naphthalenes.

    PubMed

    Shi, Yong-gang; Yang, Deng-Tao; Mellerup, Soren K; Wang, Nan; Peng, Tai; Wang, Suning

    2016-04-01

    Three isoelectronic analogues of pyrido[2,1-a]isoindole have been found to undergo a facile 1,1-hydroboration with HBMes2 borane, which provides a new and convenient method for the synthesis of B,N-heterocycles 1a-3a in high yields. Compounds 1a-3a can undergo photoelimination upon irradiation at 300 nm, generating heterocycle-fused B,N-naphthalene molecules 1b-3b, which display distinct yellow-green and blue fluorescent colors, respectively. Compound 1a undergoes thermal elimination, producing 1b at 280 °C, while compound 2a only undergoes partial elimination, forming 2b at 320 °C. Compound 3a is thermally stable up to 320 °C. PMID:27003110

  1. Construction of porous cationic frameworks by crosslinking polyhedral oligomeric silsesquioxane units with N-heterocyclic linkers

    PubMed Central

    Chen, Guojian; Zhou, Yu; Wang, Xiaochen; Li, Jing; Xue, Shuang; Liu, Yangqing; Wang, Qian; Wang, Jun

    2015-01-01

    In fields of materials science and chemistry, ionic-type porous materials attract increasing attention due to significant ion-exchanging capacity for accessing diversified applications. Facing the fact that porous cationic materials with robust and stable frameworks are very rare, novel tactics that can create new type members are highly desired. Here we report the first family of polyhedral oligomeric silsesquioxane (POSS) based porous cationic frameworks (PCIF-n) with enriched poly(ionic liquid)-like cationic structures, tunable mesoporosities, high surface areas (up to 1,025 m2 g−1) and large pore volumes (up to 0.90 cm3 g−1). Our strategy is designing the new rigid POSS unit of octakis(chloromethyl)silsesquioxane and reacting it with the rigid N-heterocyclic cross-linkers (typically 4,4′-bipyridine) for preparing the desired porous cationic frameworks. The PCIF-n materials possess large surface area, hydrophobic and special anion-exchanging property, and thus are used as the supports for loading guest species PMo10V2O405−; the resultant hybrid behaves as an efficient heterogeneous catalyst for aerobic oxidation of benzene and H2O2-mediated oxidation of cyclohexane. PMID:26062725

  2. Light Emitting Heterojunctions Based on Fully Conjugated Heterocyclic Aromatic Rigid-rod Polymer PBT

    NASA Astrophysics Data System (ADS)

    Bai, S. J.; Wu, C. C.; Cheng, H. Y.; Wang, W.

    2003-03-01

    Poly(p-phenylenebenzobisthiazole), PBT, is a heterocyclic aromatic rigid-rod polymer having a fully conjugated backbone, excellent stabilities and opto-electronic properties. We investigated multi-layer heterojunctions of PBT and low molar compounds of 3-(2-benzothiazoly)-7-(diethylamino), C6, and tris-(8-hydroxyquinoline) aluminum, Alq3, using PBT as a hole injecting and transporting material. A PBT polymer with an intrinsic viscosity of 18.0 dL/g was dissolved in Lewis acid and spin-coated onto an indium-tin-oxide (ITO) substrate. The acid was removed via coagulation. The low molar compounds were evaporated onto the ITO substrate or the thin PBT film on the ITO substrate. UV-Vis absorption spectra over 200 to 800 nm revealed different band gaps for PBT, C6 and Alq3. Scanning electron microscopy determined that the resultant PBT and low molar compound layer thicknesses were about 23 nm and 50 nm, respectively. Aluminum was evaporated onto the multilayer heterojunction as an electron injector for electroluminescence response leading to a lower I-V threshold voltage and a higher emission brightness. This was mainly because of significant balance in the numbers of the hole and the electron injected and transported in the heterojunctions.

  3. Cytotoxic gold(I) N-heterocyclic carbene complexes with phosphane ligands as potent enzyme inhibitors.

    PubMed

    Rubbiani, Riccardo; Salassa, Luca; de Almeida, Andreia; Casini, Angela; Ott, Ingo

    2014-06-01

    Organometallic gold complexes with N-heterocyclic carbene (NHC) ligands have been demonstrating promising properties as novel anticancer agents. Gold(I) NHC complexes containing different phosphanes as secondary ligands were shown to trigger strong cytotoxic effects in cancer cells, and their effective uptake into the cells was quantified by atomic absorption spectroscopy. Moreover, the new compounds strongly inhibited the activity of the seleno-enzyme thioredoxin reductase (TrxR) and of the zinc-finger enzyme poly(ADP-ribose) polymerase 1 (PARP-1). In the case of TrxR inhibition, their activity depended clearly on the size of the alkyl/aryl residues of phosphorus atoms. Density functional theory (DFT) calculations showed that the Au-P bond of the triphenylphosphane complex [Au(I) (NHC)(PPh3 )]I had a lower bond dissociation energy compared to trialkylphosphane complexes [Au(I) (NHC)(PR3 )]I, indicating a higher kinetic reactivity of this particular compound. In fact, [Au(I) (NHC)(PPh3 )]I triggered an enhanced inhibitory activity against PARP-1. PMID:24677779

  4. Construction of porous cationic frameworks by crosslinking polyhedral oligomeric silsesquioxane units with N-heterocyclic linkers

    NASA Astrophysics Data System (ADS)

    Chen, Guojian; Zhou, Yu; Wang, Xiaochen; Li, Jing; Xue, Shuang; Liu, Yangqing; Wang, Qian; Wang, Jun

    2015-06-01

    In fields of materials science and chemistry, ionic-type porous materials attract increasing attention due to significant ion-exchanging capacity for accessing diversified applications. Facing the fact that porous cationic materials with robust and stable frameworks are very rare, novel tactics that can create new type members are highly desired. Here we report the first family of polyhedral oligomeric silsesquioxane (POSS) based porous cationic frameworks (PCIF-n) with enriched poly(ionic liquid)-like cationic structures, tunable mesoporosities, high surface areas (up to 1,025 m2 g-1) and large pore volumes (up to 0.90 cm3 g-1). Our strategy is designing the new rigid POSS unit of octakis(chloromethyl)silsesquioxane and reacting it with the rigid N-heterocyclic cross-linkers (typically 4,4‧-bipyridine) for preparing the desired porous cationic frameworks. The PCIF-n materials possess large surface area, hydrophobic and special anion-exchanging property, and thus are used as the supports for loading guest species PMo10V2O405- the resultant hybrid behaves as an efficient heterogeneous catalyst for aerobic oxidation of benzene and H2O2-mediated oxidation of cyclohexane.

  5. Construction of porous cationic frameworks by crosslinking polyhedral oligomeric silsesquioxane units with N-heterocyclic linkers.

    PubMed

    Chen, Guojian; Zhou, Yu; Wang, Xiaochen; Li, Jing; Xue, Shuang; Liu, Yangqing; Wang, Qian; Wang, Jun

    2015-01-01

    In fields of materials science and chemistry, ionic-type porous materials attract increasing attention due to significant ion-exchanging capacity for accessing diversified applications. Facing the fact that porous cationic materials with robust and stable frameworks are very rare, novel tactics that can create new type members are highly desired. Here we report the first family of polyhedral oligomeric silsesquioxane (POSS) based porous cationic frameworks (PCIF-n) with enriched poly(ionic liquid)-like cationic structures, tunable mesoporosities, high surface areas (up to 1,025 m(2) g(-1)) and large pore volumes (up to 0.90 cm(3) g(-1)). Our strategy is designing the new rigid POSS unit of octakis(chloromethyl)silsesquioxane and reacting it with the rigid N-heterocyclic cross-linkers (typically 4,4'-bipyridine) for preparing the desired porous cationic frameworks. The PCIF-n materials possess large surface area, hydrophobic and special anion-exchanging property, and thus are used as the supports for loading guest species PMo10V2O40(5-); the resultant hybrid behaves as an efficient heterogeneous catalyst for aerobic oxidation of benzene and H2O2-mediated oxidation of cyclohexane. PMID:26062725

  6. Heterocyclic amines: occurrence and prevention in cooked food.

    PubMed Central

    Robbana-Barnat, S; Rabache, M; Rialland, E; Fradin, J

    1996-01-01

    This article deals with the mutagenic heterocyclic amines, especially the aminoimidazoazaarenes family, isolated from cooked foods. The conditions which lead to their occurrence in foods are discussed. This formation primarily depends on the characteristics of the food, such as the type of the food and the presence of precursors, water, and lipids. Secondarily, it depends on the cooking modes where the temperature is considered to be the most important factor involved in their formation. As their formation during cooking represents a health risk, we present some ways and means to limit their formation by alternative cooking methods that tend to decrease heterocyclic amine concentrations in foods as they are implicated in cancer risks. PMID:8919766

  7. Copper-catalyzed direct amidation of heterocycles with N-fluorobenzenesulfonimide.

    PubMed

    Wang, Sichang; Ni, Zhangqin; Huang, Xin; Wang, Jichao; Pan, Yuanjiang

    2014-11-01

    A highly efficient amidation reaction of heterocycles with N-fluorobenzenesulfonimide (NFSI) has been developed, presumably proceeding via C-H bond activation. Cuprous iodide was employed as the catalyst, and various α-amidated heterocycle derivatives have been generated in good to excellent yields. This chemistry endowed an economic method of synthesis of valuable amidated heterocycles through a direct C-N bond-coupling processes. PMID:25310043

  8. Construction of heterocyclic structures by trivalent cerium salts promoted bond forming reactions.

    PubMed

    Properzi, Roberta; Marcantoni, Enrico

    2014-02-01

    Cerium(III) salts have recently gained increasing attention in the synthetic community, owing to the powerful features that are reviewed in detail in this tutorial. This review reports significant examples of cerium(III) promoted synthesis of heterocyclic structures, initially dealing with the synthesis of five- and six-membered ring nitrogen containing heterocycles, then describing the preparation of their oxygenated analogues and finally discussing the achievement of seven-membered rings and mixed heterocyclic motifs. PMID:24217370

  9. Molecule nanoweaver

    DOEpatents

    Gerald, II; Rex E.; Klingler, Robert J.; Rathke, Jerome W.; Diaz, Rocio; Vukovic, Lela

    2009-03-10

    A method, apparatus, and system for constructing uniform macroscopic films with tailored geometric assemblies of molecules on the nanometer scale. The method, apparatus, and system include providing starting molecules of selected character, applying one or more force fields to the molecules to cause them to order and condense with NMR spectra and images being used to monitor progress in creating the desired geometrical assembly and functionality of molecules that comprise the films.

  10. Synthesis of N-bridgehead heterocycles from saccharide benzimidazoles.

    PubMed

    Sallam, Mohammed A E; Waagen, Viggo; Anthonsen, Thorleif

    2008-02-01

    Treatment of D-arabino-tetritol-1-yl-benzimidazole with P-toluenesulfonyl chloride (1molequiv) in pyridine, afforded the N-bridgehead heterocycles, 2R,3R,4S-trihydroxy-1:2:3:4-tetrahydropyridino[1,2-a]benzimidazole. The structure of the latter compound was determined by acylation, (1)H, and (13)C NMR spectroscopy and mass spectrometry. PMID:18031718

  11. Reductive dechlorination of the nitrogen heterocyclic herbicide picloram

    SciTech Connect

    Ramanand, K.; Nagarajan, A.; Suflita, J.M. )

    1993-07-01

    Halogenated heterocyclic chemicals are widely used for manufacture of pesticides, pharmaceuticals, dyes, and explosives. Often they are environmentally mobile and can contaminate ground water reserves. Picloram, a broad spectrum herbicide, has a half life in the soil of as long as 1 year. This paper reports on the reductive dehalogenation of picloram in anoxic freshwater sediments, though not when sulfate or nitrate was available as a terminal electron acceptor, and its subsequent conversion to an unidentified product. 25 refs., 4 figs, 1 tab.

  12. Heterocycle Synthesis via Direct C-H/N-H Coupling

    PubMed Central

    Nadres, Enrico T.; Daugulis, Olafs

    2012-01-01

    A method for five- and six-membered heterocycle formation by palladium-catalyzed C-H/N-H coupling is presented. The method employs a picolinamide directing group, PhI(OAc)2 oxidant, and toluene solvent at 80–120 °C. Cyclization is effective for sp2 as well as aliphatic and benzylic sp3 C-H bonds. PMID:22206416

  13. Exploring the Fate of Nitrogen Heterocycles in Complex Prebiotic Mixtures

    NASA Technical Reports Server (NTRS)

    Smith, Karen E.; Callahan, Michael P.; Cleaves, Henderson J.; Dworkin, Jason P.; House, Christopher H.

    2011-01-01

    A long standing question in the field of prebiotic chemistry is the origin of the genetic macromolecules DNA and RNA. DNA and RNA have very complex structures with repeating subunits of nucleotides, which are composed of nucleobases (nitrogen heterocycles) connected to sugar-phosphate. Due to the instability of some nucleobases (e.g. cytosine), difficulty of synthesis and instability of D-ribose, and the likely scarcity of polyphosphates necessary for the modern nucleotides, alternative nucleotides have been proposed for constructing the first genetic material. Thus, we have begun to investigate the chemistry of nitrogen heterocycles in plausible, complex prebiotic mixtures in an effort to identify robust reactions and potential alternative nucleotides. We have taken a complex prebiotic mixture produced by a spark discharge acting on a gas mixture of N2, CO2, CH4, and H2, and reacted it with four nitrogen heterocycles: uracil, 5-hydroxymethyluracil, guanine, and isoxanthopterin (2-amino-4,7-dihydroxypteridine). The products of the reaction between the spark mixture and each nitrogen heterocycle were characterized by liquid chromatography coupled to UV spectroscopy and Orbitrap mass spectrometry. We found that the reaction between the spark mixtUl'e and isoxanthopterin formed one major product, which was a cyanide adduct. 5-hydroxymethyluracil also reacted with the spark mixture to form a cyanide adduct, uracil-5-acetonitrile, which has been synthesized previously by reacting HCN with S-hydroxymethyluracil. Unlike isoxanthopterin, the chromatogram of the 5-hydroxymethyluracil reaction was much more complex with multiple products including spark-modified dimers. Additionally, we observed that HMU readily self-polymerizes in solution to a variety of oligomers consistent with those suggested by Cleaves. Guanine and uracil, the biological nucleobases, did not react with the spark mixture, even at high temperature (100 C). This suggests that there are alternative

  14. Heterocyclic compounds and aromatic diglycosides from Bretschneidera sinensis.

    PubMed

    Liu, Chun-Mei; Li, Bo; Shen, Yun-Heng; Zhang, Wei-Dong

    2010-09-24

    Two new heterocyclic compounds, bretschneiderazines A and B (1, 2), three new aromatic diglycosides, bretschneiderosides A-C (3-5), and three known aromatic diglycosides, 6-8, were isolated from Bretschneidera sinensis. The structure of bretschneiderazine A (1) was confirmed by single-crystal X-ray diffraction analysis. Bretschneiderazine A (1) showed moderate activity against the NCI-H446 cell line. PMID:20722446

  15. Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

    PubMed Central

    2010-01-01

    Summary This review covers all of the common methods for the syntheses of aromatic and heterocyclic perfluoroalkyl sulfides, a class of compounds which is finding increasing application as starting materials for the preparation of agrochemicals, pharmaceutical products and, more generally, fine chemicals. A systematic approach is taken depending on the mode of incorporation of the SRF groups and also on the type of reagents used. PMID:20978611

  16. Heterocyclic tautomerism: reassignment of two crystal structures of 2-amino-1,3-thiazolidin-4-one derivatives.

    PubMed

    Gzella, Andrzej K; Kowiel, Marcin; Suseł, Aneta; Wojtyra, Magdalena N; Lesyk, Roman

    2014-08-01

    The structures of 5-(2-hydroxyethyl)-2-[(pyridin-2-yl)amino]-1,3-thiazolidin-4-one, C10H11N3O2S, (I), and ethyl 4-[(4-oxo-1,3-thiazolidin-2-yl)amino]benzoate, C12H12N2O3S, (II), which are identical to the entries with refcodes GACXOZ [Váňa et al. (2009). J. Heterocycl. Chem. 46, 635-639] and HEGLUC [Behbehani & Ibrahim (2012). Molecules, 17, 6362-6385], respectively, in the Cambridge Structural Database [Allen (2002). Acta Cryst. B58, 380-388], have been redetermined at 130 K. This structural study shows that both investigated compounds exist in their crystal structures as the tautomer with the carbonyl-imine group in the five-membered heterocyclic ring and an exocyclic amine N atom, rather than the previously reported tautomer with a secondary amide group and an exocyclic imine N atom. The physicochemical and spectroscopic data of the two investigated compounds are the same as those of GACXOZ and HEGLUC, respectively. In the thiazolidin-4-one system of (I), the S and chiral C atoms, along with the hydroxyethyl group, are disordered. The thiazolidin-4-one fragment takes up two alternative locations in the crystal structure, which allows the molecule to adopt R and S configurations. The occupancy factors of the disordered atoms are 0.883 (2) (for the R configuration) and 0.117 (2) (for the S configuration). In (I), the main factor that determines the crystal packing is a system of hydrogen bonds, involving both strong N-H...N and O-H...O and weak C-H...O hydrogen bonds, linking the molecules into a three-dimensional hydrogen-bond network. On the other hand, in (II), the molecules are linked via N-H...O hydrogen bonds into chains. PMID:25093365

  17. Mutagenic activity of heterocyclic amines in cooked foods

    SciTech Connect

    Felton, J.S.; Knize, M.G.; Dolbeare, F.A.

    1993-01-19

    Mutagenic heterocyclic amines are generated in foods when they are cooked at temperatures over 150[degrees]C. These compounds are present from 0.1 to 50 ppb depending on the food and the cooking conditions. These heterocyclic amines are not only present in cooked red meat, fish, chicken, and in baked and fried foods derived from grain. Mutagenicity of fried beef hamburgers cooked at 230[degrees]C is 800 [plus minus] 37 TA98 revertants per gram cooked weight. We measured 2-amino-3,8-dimethylimidazo(4,5-flquinoxaline (MelQx), 2-amino-3,4,8-trimethylimidazo[4,5-flquinoxaline (DiMeIQx), and 2-amino-3-methylimidazo[4,5-flquinoline (IQ) formation at this temperature and found 3.0 [plus minus] 2.0,1.0 [plus minus] 0.18, and 0.06 [plus minus] 0.03 ng/g, respectively. 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was found at a higher concentration of 9.6 ng/g. We have shown these heterocyclic amines are capable of producing both reverse and forward mutations in Salmonella bacteria and forward mutations in Chinese Hamster Cells.

  18. Mutagenic activity of heterocyclic amines in cooked foods

    SciTech Connect

    Felton, J.S.; Knize, M.G.; Dolbeare, F.A.

    1993-01-19

    Mutagenic heterocyclic amines are generated in foods when they are cooked at temperatures over 150{degrees}C. These compounds are present from 0.1 to 50 ppb depending on the food and the cooking conditions. These heterocyclic amines are not only present in cooked red meat, fish, chicken, and in baked and fried foods derived from grain. Mutagenicity of fried beef hamburgers cooked at 230{degrees}C is 800 {plus_minus} 37 TA98 revertants per gram cooked weight. We measured 2-amino-3,8-dimethylimidazo(4,5-flquinoxaline (MelQx), 2-amino-3,4,8-trimethylimidazo[4,5-flquinoxaline (DiMeIQx), and 2-amino-3-methylimidazo[4,5-flquinoline (IQ) formation at this temperature and found 3.0 {plus_minus} 2.0,1.0 {plus_minus} 0.18, and 0.06 {plus_minus} 0.03 ng/g, respectively. 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was found at a higher concentration of 9.6 ng/g. We have shown these heterocyclic amines are capable of producing both reverse and forward mutations in Salmonella bacteria and forward mutations in Chinese Hamster Cells.

  19. Compositions comprising a polypeptide having cellulolytic enhancing activity and a heterocyclic compound and uses thereof

    DOEpatents

    Xu, Feng; Sweeney, Matthew; Quinlan, Jason

    2016-08-02

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a heterocyclic compound. The present invention also relates to methods of using the compositions.

  20. In Silico Olefin Metathesis with Ru-Based Catalysts Containing N-Heterocyclic Carbenes Bearing C60 Fullerenes.

    PubMed

    Martínez, Juan Pablo; Vummaleti, Sai Vikrama Chaitanya; Falivene, Laura; Nolan, Steven P; Cavallo, Luigi; Solà, Miquel; Poater, Albert

    2016-05-01

    Density functional theory calculations have been used to explore the potential of Ru-based complexes with 1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene (SIMes) ligand backbone (A) being modified in silico by the insertion of a C60 molecule (B and C), as olefin metathesis catalysts. To this end, we investigated the olefin metathesis reaction catalyzed by complexes A, B, and C using ethylene as the substrate, focusing mainly on the thermodynamic stability of all possible reaction intermediates. Our results suggest that complex B bearing an electron-withdrawing N-heterocyclic carbene improves the performance of unannulated complex A. The efficiency of complex B is only surpassed by complex A when the backbone of the N-heterocyclic carbene of complex A is substituted by two amino groups. The particular performance of complexes B and C has to be attributed to electronic factors, that is, the electronic-donating capacity of modified SIMes ligand rather than steric effects, because the latter are predicted to be almost identical for complexes B and C when compared to those of A. Overall, this study indicates that such Ru-based complexes B and C might have the potential to be effective olefin metathesis catalysts. PMID:27059290

  1. Laboratory Infrared Spectra of Polycyclic Aromatic Nitrogen Heterocycles: Quinoline, and Phenanthridine in Solid Argon and H2O

    NASA Technical Reports Server (NTRS)

    Bernstein, M. P.; Mattioda, A. L.; Sandford, S. A.; Hudgins, D. M.

    2004-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are common throughout the universe. Their detection and identification are based on telescopic infrared (IR) spectra compared with laboratory data. Polycyclic Aromatic Nitrogen Heterocycles (PANHs) are heterocyclic aromatics i.e., PAHs with carbon atoms replaced by a nitrogen atom. These molecules should be present in the interstellar medium, but have received relatively little attention. We present mid-IR spectra of two PANHs, quinoline (C9H7N), and phenanthridine (C13H9N) isolated in solid argon and frozen in solid H2O at 12 K, conditions yielding data directly comparable to astronomical observations. In contrast to simple PAHs, that do not interact strongly with solid H2O, the nitrogen atoms in PANHs are potentially capable of hydrogen bonding with H2O. Whereas the IR spectrum of phenanthridine in H2O is similar to that of the same compound isolated in an argon matrix, quinoline absorptions shift up to 16 cm(sup -1) (0.072 mm) between argon and H2O. Thus, astronomers will not always be able to rely on IR band positions of matrix isolated PANHs to correctly interpret the absorptions of PANHs frozen in H2O ice grains. Furthermore, our data suggest that relative band areas also vary, so determining column densities to better than a factor of 3 will require knowledge of the matrix in which the PANH is embedded and laboratory studies of relevant samples.

  2. From the N-Heterocyclic Carbene-Catalyzed Conjugate Addition of Alcohols to the Controlled Polymerization of (Meth)acrylates.

    PubMed

    Ottou, Winnie Nzahou; Bourichon, Damien; Vignolle, Joan; Wirotius, Anne-Laure; Robert, Fredéric; Landais, Yannick; Sotiropoulos, Jean-Marc; Miqueu, Karinne; Taton, Daniel

    2015-06-22

    Among various N-heterocyclic carbenes (NHCs) tested, only 1,3-bis(tert-butyl)imidazol-2-ylidene (NHC(tBu) ) proved to selectively promote the catalytic conjugate addition of alcohols onto (meth)acrylate substrates. This rather rare example of NHC-catalyzed 1,4-addition of alcohols was investigated as a simple means to trigger the polymerization of both methyl methacrylate and methyl acrylate (MMA and MA, respectively). Well-defined α-alkoxy poly(methyl (meth)acrylate) (PM(M)A) chains, the molar masses of which could be controlled by the initial [(meth)acrylate]0/[ROH]0 molar ratio, were ultimately obtained in N,N-dimethylformamide at 25 °C. A hydroxyl-terminated poly(ethylene oxide) (PEO-OH) macro-initiator was also employed to directly access PEO-b-PMMA amphiphilic block copolymers. Investigations into the reaction mechanism by DFT calculations revealed the occurrence of two competitive concerted pathways, involving either the activation of the alcohol or that of the monomer by NHC(tBu) . PMID:26013759

  3. Studies on protein poly(ADP-ribosylation) using high resolution gel electrophoresis.

    PubMed

    Boulikas, T

    1990-08-25

    Analysis of poly(ADP-ribose) synthesized in cellular lysates or in isolated nuclei on 100-cm-long thin gels of 20% polyacrylamide, 2.5 M urea permits determination of the exact size of poly(ADP-ribose) molecules using labeled oligonucleotides as molecular weight markers. The size and concentration of poly(ADP-ribose) molecules increase at time intervals during its synthesis. Differences in the concentration of poly(ADP-ribose) size classes among cell lines are also shown. Inhibition of poly(ADP-ribose) degradation by ethacridine that directly interacts with the polymer and inhibits its hydrolysis by poly(ADP-ribose) glycohydrolase shows a dramatic increase in both polymer size and concentration. Use of alkaline conditions for the hydrolysis of poly(ADP-ribose)-protein linkages reveals a specific shortening of all size classes of poly(ADP-ribose) compared with its size in preparations obtained by extensive digestion of nuclei with nucleases, RNases, and proteases. PMID:2167322

  4. Diastereoselective synthesis of CF3-substituted, epoxide-fused heterocycles with β-(trifluoromethyl)vinylsulfonium salts.

    PubMed

    Fritz, Sven P; West, Thomas H; McGarrigle, Eoghan M; Aggarwal, Varinder K

    2012-12-21

    CF(3)-substituted vinyl diphenylsulfonium triflate is an effective annulation reagent for the formation of α-CF(3) substituted, epoxide-fused heterocycles (pyrrolidines, piperidines, and tetrahydrofurans). This simple method affords a variety of valuable heterocyclic building blocks in a highly diastereoselective manner (dr >20:1). PMID:23231752

  5. Post-Training Intrahippocampal Injection of Synthetic Poly-Alpha-2,8-Sialic Acid-Neural Cell Adhesion Molecule Mimetic Peptide Improves Spatial Long-Term Performance in Mice

    ERIC Educational Resources Information Center

    Florian, Cedrick; Foltz, Jane; Norreel, Jean-Chretien; Rougon, Genevieve; Roullet, Pascal

    2006-01-01

    Several data have shown that the neural cell adhesion molecule (NCAM) is necessary for long-term memory formation and might play a role in the structural reorganization of synapses. The NCAM, encoded by a single gene, is represented by several isoforms that differ with regard to their content of alpha-2,8-linked sialic acid residues (PSA) on their…

  6. Stacking Interactions between 9-Methyladenine and Heterocycles Commonly Found in Pharmaceuticals.

    PubMed

    An, Yi; Doney, Analise C; Andrade, Rodrigo B; Wheeler, Steven E

    2016-05-23

    Complexes of 9-methyladenine with 46 heterocycles commonly found in drugs were located using dispersion-corrected density functional theory, providing a representative set of 408 unique stacked dimers. The predicted binding enthalpies for each heterocycle span a broad range, highlighting the strong dependence of heterocycle stacking interactions on the relative orientation of the interacting rings. Overall, the presence of NH and carbonyl groups lead to the strongest stacking interactions with 9-methyadenine, and the strength of π-stacking interactions is sensitive to the distribution of heteroatoms within the ring as well as the specific tautomer considered. Although molecular dipole moments provide a sound predictor of the strengths and orientations of the 28 monocyclic heterocycles considered, dipole moments for the larger fused heterocycles show very little correlation with the predicted binding enthalpies. PMID:27074615

  7. Poly(A) RNA and Paip2 act as allosteric regulators of poly(A)-binding protein.

    PubMed

    Lee, Seung Hwan; Oh, Jungsic; Park, Jonghyun; Paek, Ki Young; Rho, Sangchul; Jang, Sung Key; Lee, Jong-Bong

    2014-02-01

    When bound to the 3' poly(A) tail of mRNA, poly(A)-binding protein (PABP) modulates mRNA translation and stability through its association with various proteins. By visualizing individual PABP molecules in real time, we found that PABP, containing four RNA recognition motifs (RRMs), adopts a conformation on poly(A) binding in which RRM1 is in proximity to RRM4. This conformational change is due to the bending of the region between RRM2 and RRM3. PABP-interacting protein 2 actively disrupts the bent structure of PABP to the extended structure, resulting in the inhibition of PABP-poly(A) binding. These results suggest that the changes in the configuration of PABP induced by interactions with various effector molecules, such as poly(A) and PABP-interacting protein 2, play pivotal roles in its function. PMID:24293655

  8. Photo-induced dynamics in heterocyclic aromatic molecules probed by femtosecond XUV transient absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Lackner, Florian; Chatterley, Adam S.; Pemmaraju, Chaitanya D.; Neumark, Daniel M.; Leone, Stephen R.; Gessner, Oliver

    2016-05-01

    We report on the ring-opening and dissociation dynamics of strong-field ionized selenophene (C4 H4 Se), studied by transient XUV absorption spectroscopy at the Se 3d edge. The table-top experiments are facilitated by high-order harmonic generation coupled with a gas phase transient XUV absorption setup that is optimized for the study of organic compounds. Employing element-specific core-to-valence transitions, the ultrafast molecular dynamics are monitored from the perspective of the well-localized Se atoms. Spectral features are assigned based on first principles TDDFT calculations for a large manifold of electronic states. We observe signatures of rapidly (~ 35 fs) decaying highly excited molecular cations, the formation of ring-opened products on a 100 fs time scale and, most notably, the elimination of bare Se+ ions in a very rapid multi-step process. A delayed onset of the Se+ ions provides direct evidence that both selenium-carbon bonds are broken within only ~ 130 fs and that a sequential mechanism, presumably an initial ring-opening followed by a subsequent breaking of the second bond, is required to eliminate the atomic fragments.

  9. New iodocuprates(I) with N-heterocyclic molecules as the cations

    SciTech Connect

    Zhao, Jin-Jing; Zhang, Xiao; Wang, Yan-Ning; Jia, Hong-Li; Yu, Jie-Hui; Xu, Ji-Qing

    2013-11-15

    Under the hydrothermal conditions, the reactions between CuI, KI and bp/bpp (bp=4,4′-bipiperidine, bpp=1,3-bis(4-piperidyl)propane) in an acidic alcohol solution produced three new organically templated iodocuprates(I) as [H{sub 2}bp]{sub 2}[Cu{sub 2}I{sub 6}] 1, [tmbp][Cu{sub 2}I{sub 4}] 2 and [tmbpp] 2 [Cu{sub 4}I{sub 8}]·2H{sub 2}O 3 (tmbp{sup 2+}=N,N,N′,N′-tetramethyl-4,4′-bipiperidinium; tmbpp{sup 2+}=N,N,N′,N′-tetramethyl-1,3-bis(4-piperidyl)propane dication). X-ray analysis revealed that (i) tmbp{sup 2+} and tmbpp{sup 2+} in compounds 2 and 3 originated from the complete N-alklation of bp/bpp with CH{sub 3}OH; (ii) templated by H{sub 2}bp{sup 2+}, the inorganic anion [Cu{sub 2}I{sub 6}]{sup 2−} of 1 possesses a dinuclear structure, whereas templated by tmbp{sup 2+}, the inorganic anion [Cu{sub 2}I{sub 4}]{sup 2−} of 2 exhibits a one-dimensional (1D) chain structure; (iii) templated by tmbpp{sup 2+}, the inorganic anion [Cu{sub 4}I{sub 8}]{sup 4−} of 3 shows a cubane-like structure modified by four terminal I{sup −} ions. The photoluminescence analysis indicates that compounds 1 and 2 emit blue light, while compound 3 emits green light. - Graphical abstract: By employing hydrothermal in situ N-alkylation of bp/bpp with CH{sub 3}OH, three new organically templated iodocuprates(I) were obtained. Display Omitted - Highlights: • Three new organically templated iodocuprates(I) were reported. • Cations tmbp{sup 2+} and tmbpp{sup 2+} originated from in situ alkylation of bp/bpp with CH{sub 3}OH. • H{sup +} and I{sup −} play a key role in alkylation of bp/bpp with CH{sub 3}OH. • Photoluminescence emission for iodocuprates(I) is related to Cu···Cu interaction.

  10. Spectral behaviour of linked heterocyclic systems and related dyes

    NASA Astrophysics Data System (ADS)

    Savarino, Piero; Viscardi, Guido; Quagliotto, Pierluigi; Barni, Ermanno

    1993-08-01

    A wide series of electronic spectra of assembled heterocyclic systems (pyridine or quinoline, benzoor pyrido-X-azole), of their quaternary salts and of the related polymethine dyes has been considered in the light of general relationships obtained. The position and the intensity of the main bands depend on electronic and steric factors according to the relative positions of the linked rings, the nature of heteroatoms, the number and the position of positive charges and the length of the chromogens. A self-consistent set of simple rules was obtained, which explained and justified peculiar behaviours and/or apparent exceptions.

  11. N-Heterocyclic carbene boranes are good hydride donors.

    PubMed

    Horn, Markus; Mayr, Herbert; Lacôte, Emmanuel; Merling, Everett; Deaner, Jordan; Wells, Sarah; McFadden, Timothy; Curran, Dennis P

    2012-01-01

    The nucleophilicity parameters (N) of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene borane and 1,3-dimethylimidazol-2-ylidene borane are 9.55 and 11.88. This places N-heterocyclic carbene boranes (NHC-boranes) among the most nucleophilic classes of neutral hydride donors. Reductions of highly electron-poor C═N and C═C bonds provide hydrogenation products along with new, stable borylated products. The results suggest that NHC-boranes have considerable untapped potential as neutral organic reductants. PMID:22149270

  12. Methanol dehydrogenation by iridium N-heterocyclic carbene complexes.

    PubMed

    Campos, Jesús; Sharninghausen, Liam S; Manas, Michael G; Crabtree, Robert H

    2015-06-01

    A series of homogeneous iridium bis(N-heterocyclic carbene) catalysts are active for three transformations involving dehydrogenative methanol activation: acceptorless dehydrogenation, transfer hydrogenation, and amine monoalkylation. The acceptorless dehydrogenation reaction requires base, yielding formate and carbonate, as well as 2-3 equivalents of H2. Of the few homogeneous systems known for this reaction, our catalysts tolerate air and employ simple ligands. Transfer hydrogenation of ketones and imines from methanol is also possible. Finally, N-monomethylation of anilines occurs through a "borrowing hydrogen" reaction. Notably, this reaction is highly selective for the monomethylated product. PMID:25615426

  13. Tailor-made N-heterocyclic carbenes for nanoparticle stabilization.

    PubMed

    Richter, Christian; Schaepe, Kira; Glorius, Frank; Ravoo, Bart Jan

    2014-03-25

    N-heterocyclic carbenes (NHCs) represent a leading class of ligands in organometallic chemistry, but have been rarely exploited as stabilizers for metal nanoparticles (NPs). We report the first example of NHC stabilized Pd-NPs that demonstrate long term stability. These NHC Pd-NPs were synthesized by a facile ligand exchange protocol using rationally designed long chained NHCs (LC-NHCs). Furthermore, we demonstrate that the surface modification of Pd-NPs results in significant chemoselectivity in a model reaction. PMID:24522886

  14. O,S-Heterocyclic stannylenes: synthesis and reactivity.

    PubMed

    Karwasara, Surendar; Jha, Chandan Kumar; Sinhababu, Soumen; Nagendran, Selvarajan

    2016-04-25

    Commercially available N-oxide (2-mercaptopyridine-N-oxide) is used as a ligand instead of an oxidizing agent to stabilize the compounds of main group elements in low-valent states. The isolated compounds [(C5H4NOS)2Sn (), (C5H4NOS)SnCl () and (C5H4NOS)GeCl ()] are the first structurally characterized examples of O,S-heterocyclic stannylenes and germylenes with interesting bonding features. Further, the reaction of compound with SbCl3 afforded the rare dichlorodiantimony oxide [{(C5H4NOS)SbCl}2O] () unprecedentedly. PMID:27049924

  15. Pyrazolopyridines as potent PDE4B inhibitors: 5-Heterocycle SAR

    SciTech Connect

    Mitchell, Charlotte J.; Ballantine, Stuart P.; Coe, Diane M.; Cook, Caroline M.; Delves, Christopher J.; Dowle, Mike D.; Edlin, Chris D.; Hamblin, J. Nicole; Holman, Stuart; Johnson, Martin R.; Jones, Paul S.; Keeling, Sue E.; Kranz, Michael; Lindvall, Mika; Lucas, Fiona S.; Neu, Margarete; Solanke, Yemisi E.; Somers, Don O.; Trivedi, Naimisha A.; Wiseman, Joanne O.

    2012-05-03

    Following the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective phosphodiesterase 4B inhibitors, [Hamblin, J. N.; Angell, T.; Ballentine, S., et al. Bioorg. Med. Chem. Lett.2008, 18, 4237] the SAR of the 5-position was investigated further. A range of substituted heterocycles showed good potencies against PDE4. Optimisation using X-ray crystallography and computational modelling led to the discovery of 16, with sub-nM inhibition of LPS-induced TNF-{alpha} production from isolated human peripheral blood mononuclear cells.

  16. N-Heterocyclic Carbene Complexes in Oxidation Reactions

    NASA Astrophysics Data System (ADS)

    Jurčík, Václav; Cazin, Catherine S. J.

    This chapter describes applications of N-heterocyclic carbenes (NHCs) in oxidation chemistry. The strong σ-donation capabilities of the NHCs allow an efficient stabilisation of metal centres in high oxidation states, while high metal-NHC bond dissociation energies suppress their oxidative decomposition. These properties make NHCs ideal ligands for oxidation processes. The first part of this chapter is dedicated to the reactivity of NHC-metal complexes towards molecular oxygen whilst the second half highlights all oxidation reactions catalysed by such complexes. These include oxidation of alcohols and olefins, oxidative cyclisations, hydrations of alkynes and nitriles, oxidative cleavage of alkenes and the oxidation of methane.

  17. Toxicity of six heterocyclic nitrogen compounds to Daphnia pulex

    SciTech Connect

    Perry, C.M.; Smith, S.B.

    1988-10-01

    The authors determined the relative toxicities to the aquatic crustacean Daphnia pulex of the six heterocyclic nitrogen compounds: 3-(1-methyl-2-pyrrolidinyl)pyridine (nicotine), 2-pyrrolidinone, 1-methylpyrrolidine, 2-(2-hydroxyethyl)pyridine, 2-amino-4,6-dimethylpyridine, and 2-amino-4,7(1H,8H)-pteridinedione(isoxanthopterin). These compounds were selected because they were detected in lake trout or walleyes and were commercially available. Daphnia pulex was used as the test organism because it is endemic to the Great Lakes, is easy to culture, has parthenogenic reproduction, constant genetic makeup over generations, and is sensitive to ecological stress.

  18. A selected ion flow tube, SIFT, study of the reactions of H3O+, NO+ and O2+ ions with several N- and O-containing heterocyclic compounds in support of SIFT-MS

    NASA Astrophysics Data System (ADS)

    Wang, Tianshu; Spanel, Patrik; Smith, David

    2004-10-01

    We present the results of a selected ion flow tube (SIFT) study of the reactions of H3O+, NO+ and O2+ ions with 11 N-containing heterocyclic compounds and seven O-containing heterocyclic compounds, M. Most of these compounds have more than one functional group and some of them are known to occur in biological fluids and other media. The major objective is to provide the required kinetic data (rate coefficients and product ions) to extend the library for selected ion flow tube mass spectrometry, SIFT-MS, to allow these compounds to be detected and quantified in humid air samples. The results show that the H3O+ reactions are very simple, leading only to a stable protonated molecule, MH+, which facilitates SIFT-MS analyses. The NO+ reactions are also relatively simple, again mostly producing a single product ion species, which is variously M+, (M-H)+ and NO+M, so NO+ is a suitable precursor ion species for the analysis of these compounds. Generally speaking, the O2+ reactions result in more than one product ion following dissociative charge transfer and so O2+ precursor ions are less suitable for SIFT-MS analyses of these heterocyclics. Some attention is given to the formation of the hydrates of the MH+ product ions via three-body association and/or switching reactions (in most cases only the monohydrate is produced), since these hydrates must be included in the SIFT-MS analyses of these heterocyclic compounds.

  19. Selective Activation of Fluoroalkenes with N-Heterocyclic Carbenes: Synthesis of N-Heterocyclic Fluoroalkenes and Polyfluoroalkenyl Imidazolium Salts.

    PubMed

    Leclerc, Matthew C; Gorelsky, Serge I; Gabidullin, Bulat M; Korobkov, Ilia; Baker, R Tom

    2016-06-01

    Selective reactions between nucleophilic N,N'-diaryl-heterocyclic carbenes (NHCs) and electrophilic fluorinated alkenes afford NHC fluoroalkenes in high yields. These stable compounds undergo efficient and selective fluoride abstraction with Lewis acids to give polyfluoroalkenyl imidazolium salts. These salts react at Cβ with pyrrolidine to give ammonium fluoride-substituted salts, which give rise to conjugated imidazolium-enamine salts through loss of HF. Alternatively, reaction with 4-(dimethylamino)-pyridine provides a Cα-pyridinium-substituted NHC fluoroalkene. These compounds were studied using multinuclear NMR spectroscopy, mass spectrometry, and X-ray crystallography. Insight into their electronic structure and reactivity was gained through the use of DFT calculations. PMID:27142160

  20. Multiparameter single-molecule fluorescence measurements of DNA intercalating fluorophores

    NASA Astrophysics Data System (ADS)

    Bowen, Benjamin P.; Enderlein, Jorg; Woodbury, Neal W. T.

    2003-06-01

    Experiments using single-molecules of TOTO-1 intercalated into dsDNA were performed to investigate the DNA sequence dependence on the fluorescence detectable with single-molecule fluorescence spectroscopy. Previous work has shown that there is a difference in the fluorescence lifetime when TOTO-1 is intercalated in poly-AT DNA or in poly-GC DNA. The fluorescence detected from single-molecules in this work for poly-GC and poly-AT DNA showed fluorescence lifetimes of 2.1 and 1.8 nsec, respectively. Analysis of the fluorescence intensity detected from single-molecules of TOTO-1 was performed by fluorescence cross-correlation spectroscopy. TOTO-1 is shown to spend large amounts of time in dark states. These dark states reduce the detectable fluorescence intensity to approximately 10 photons per millisecond on average.

  1. A highly active water-soluble cross-coupling catalyst based on dendritic polyglycerol N-heterocyclic carbene palladium complexes.

    PubMed

    Meise, Markus; Haag, Rainer

    2008-01-01

    A new water-soluble polyglycerol derivative functionalized with N-heterocyclic carbene palladium complexes was prepared and applied as catalyst for Suzuki cross-coupling reactions in water. The complex displays a metal loading of around 65 metal centers per dendrimeric molecule, which is estimated to contain 130 chelating groups and thus corresponds approximately to the formation of 2:1 NHC/metal complexes. Monomeric analogues were also synthesized to validate the reactivity of the dendritic catalyst. Both types of catalysts were tested with various aryl bromides and arylboronic acids. Turnover frequencies of up to 2586 h(-1) at 80 degrees C were observed with the dendritic catalyst along with turnover numbers of up to 59 000, which are among the highest turnover numbers reported for polymer-supported catalysts in neat water. The dendritic catalyst could be used (reused) in five consecutive reactions without loss in activity. PMID:18702166

  2. Microwave-Assisted Syntheses of Bioactive Seven-Membered, Macro-Sized Heterocycles and Their Fused Derivatives.

    PubMed

    Driowya, Mohsine; Saber, Aziza; Marzag, Hamid; Demange, Luc; Bougrin, Khalid; Benhida, Rachid

    2016-01-01

    This review describes the recent advances in the microwave-assisted synthesis of 7-membered and larger heterocyclic compounds. Several types of reaction for the cyclization step are discussed: Ring Closing Metathesis (RCM), Heck and Sonogashira reactions, Suzuki-Miyaura cross-coupling, dipolar cycloadditions, multi-component reactions (Ugi, Passerini), etc. Green syntheses and solvent-free procedures have been introduced whenever possible. The syntheses discussed herein have been selected to illustrate the huge potential of microwave in the synthesis of highly functionalized molecules with potential therapeutic applications, in high yields, enhanced reaction rates and increased chemoselectivity, compared to conventional methods. More than 100 references from the recent literature are listed in this review. PMID:27517892

  3. Interstellar molecules

    NASA Astrophysics Data System (ADS)

    Smith, D.

    1987-09-01

    Some 70 different molecular species have so far been detected variously in diffuse interstellar clouds, dense interstellar clouds, and circumstellar shells. Only simple (diatomic and triatomic) species exist in diffuse clouds because of the penetration of destructive UV radiations, whereas more complex (polyatomic) molecules survive in dense clouds as a result of the shielding against this UV radiation provided by dust grains. A current list of interstellar molecules is given together with a few other molecular species that have so far been detected only in circumstellar shells. Also listed are those interstellar species that contain rare isotopes of several elements. The gas phase ion chemistry is outlined via which the observed molecules are synthesized, and the process by which enrichment of the rare isotopes occurs in some interstellar molecules is described.

  4. Interstellar Molecules

    ERIC Educational Resources Information Center

    Solomon, Philip M.

    1973-01-01

    Radioastronomy reveals that clouds between the stars, once believed to consist of simple atoms, contain molecules as complex as seven atoms and may be the most massive objects in our Galaxy. (Author/DF)

  5. Modeling Molecules

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The molecule modeling method known as Multibody Order (N) Dynamics, or MBO(N)D, was developed by Moldyn, Inc. at Goddard Space Flight Center through funding provided by the SBIR program. The software can model the dynamics of molecules through technology which stimulates low-frequency molecular motions and properties, such as movements among a molecule's constituent parts. With MBO(N)D, a molecule is substructured into a set of interconnected rigid and flexible bodies. These bodies replace the computation burden of mapping individual atoms. Moldyn's technology cuts computation time while increasing accuracy. The MBO(N)D technology is available as Insight II 97.0 from Molecular Simulations, Inc. Currently the technology is used to account for forces on spacecraft parts and to perform molecular analyses for pharmaceutical purposes. It permits the solution of molecular dynamics problems on a moderate workstation, as opposed to on a supercomputer.

  6. Enumerating molecules.

    SciTech Connect

    Visco, Donald Patrick, Jr.; Faulon, Jean-Loup Michel; Roe, Diana C.

    2004-04-01

    This report is a comprehensive review of the field of molecular enumeration from early isomer counting theories to evolutionary algorithms that design molecules in silico. The core of the review is a detail account on how molecules are counted, enumerated, and sampled. The practical applications of molecular enumeration are also reviewed for chemical information, structure elucidation, molecular design, and combinatorial library design purposes. This review is to appear as a chapter in Reviews in Computational Chemistry volume 21 edited by Kenny B. Lipkowitz.

  7. Biological properties of novel ruthenium- and osmium-nitrosyl complexes with azole heterocycles.

    PubMed

    Novak, Maria S; Büchel, Gabriel E; Keppler, Bernhard K; Jakupec, Michael A

    2016-06-01

    Since the discovery that nitric oxide (NO) is a physiologically relevant molecule, there has been great interest in the use of metal nitrosyl compounds as antitumor pharmaceuticals. Particularly interesting are those complexes which can deliver NO to biological targets. Ruthenium- and osmium-based compounds offer lower toxicity compared to other metals and show different mechanisms of action as well as different spectra of activity compared to platinum-based drugs. Novel ruthenium- and osmium-nitrosyl complexes with azole heterocycles were studied to elucidate their cytotoxicity and possible interactions with DNA. Apoptosis induction, changes of mitochondrial transmembrane potential and possible formation of reactive oxygen species were investigated as indicators of NO-mediated damage by flow cytometry. Results suggest that ruthenium- and osmium-nitrosyl complexes with the general formula (indazolium)[cis/trans-MCl4(NO)(1H-indazole)] have pronounced cytotoxic potency in cancer cell lines. Especially the more potent ruthenium complexes strongly induce apoptosis associated with depolarization of mitochondrial membranes, and elevated reactive oxygen species levels. Furthermore, a slight yet not unequivocal trend to accumulation of intracellular cyclic guanosine monophosphate attributable to NO-mediated effects was observed. PMID:26961253

  8. Searching for new energetic materials: Computational design of novel nitro-substituted heterocyclic explosives

    NASA Astrophysics Data System (ADS)

    Tsyshesvky, Roman; Pagoria, Philip; Kuklja, Maija

    2015-06-01

    The continuous search for safe and powerful energetic materials is an exciting research challenge that attracts experts in material science, chemistry, physics, and engineering. Elucidation of meaningful correlations between sensitivity and structures of explosives is a fundamental problem, which ought to be resolved to ensure successful design of new materials and improvements of existing energetics. In this report, quantum-chemical DFT study of thermal decomposition of a series of recently synthesized oxadiazole-based explosives, BNFF (3,4-bis(4-Nitro-1,2,5-oxadiazol-3-yl)-1,2,5-oxadiazole-N-oxide), BNFF-1 (3,4-bis(4-nitro-1,2,5-oxadiazol-3-yl)-1,2,5-oxadiazole) and ANFF-1 (3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(4-nitro-1,2,5-oxadiazol-3-yl)-1,2,5-oxadiazole) is presented. We also show how the knowledge of discovered correlations between structures and thermal stability of these compounds is used to design several novel candidate heterocyclic energetic molecules, including DNBTT (2,7-dinitro-4H,9H-bis([1,2,4]triazolo)[1,5-b:1',5'-e][1,2,4,5]tetrazine), compound with high thermal stability, which is on par or better than that of TATB.

  9. [Chalcones and their heterocyclic analogs as potential therapeutic agents in bacterial diseases].

    PubMed

    Opletalová, V

    2000-11-01

    Chalcones and their heterocyclic analogues possess a number of biological effects. Their antifungal effects were reported in the previous communication (Opletalová V., Sedivý D.: Ces. a Slov. Farm. 48, 252 (1999)). The present review is devoted to the antibacterial activity of these compounds. For antibacterial activity, the presence of the enone aggregate in the molecule is important. Hydrogenated analogues are less effective or ineffective, saturated brominated analogues are effective probably after a metabolic transformation into unsaturated alpha-bromochalcone. In the rings, substitution with a hydroxyl is advantageous, in some cases also substitution with a lipophilic substituent, e.g. a halogen or an alkyl, proved to be advantageous. On the other hand, substitution with amino groups often results in a decrease in effectiveness. Effectiveness of chalcones and their derivatives against gram-positive microorganisms is usually higher than against gram-negative bacteria. Some analogues, however, inhibited also the growth of gram-negative strains. With regard to increased incidence of tuberculosis in recent years, antimycobacterial effectiveness of chalcones and their derivatives is especially interesting. PMID:11367546

  10. Synthesis and Properties of Novel Silver-Containing DNA Molecules.

    PubMed

    Eidelshtein, Gennady; Fardian-Melamed, Natalie; Gutkin, Vitaly; Basmanov, Dmitry; Klinov, Dmitry; Rotem, Dvir; Levi-Kalisman, Yael; Porath, Danny; Kotlyar, Alexander

    2016-06-01

    Migration of silver atoms from silver nano-particles selectively to a double-stranded poly(dG)-poly(dC) polymer leads to metallization of the DNA. As a result the DNA molecules become shorter and thicker (higher), as evident from the atomic force microscopy imaging analysis. The metalized molecules can be detected by transmission and scanning electron microscopy in contrast to the initial non-metalized ones. PMID:27116695

  11. Comparative analysis of polycyclic aromatic sulfur heterocycles isolated from four shale oils. [Polycyclic aromatic sulfur heterocycles; thiophenes

    SciTech Connect

    Willey, C.; Pelroy, R.; Stewart, D.

    1981-12-01

    This report describes the isolation of sulfur heterocycle fractions from four shale oils (Paraho, Geokinetics, Occidental, and Rio Blanco), the use of capillary column gas chromatography and mass spectrometry for the identification of individual mixture components, and a reverse (Ames) and forward mutation assay with Salmonella typhimurium to screen for possible health hazards. The major components of the Polycyclic Aromatic Sulfur Heterocycles (PASH) fractions for all four shale oils were found to be two- to three-ringed parent and alkylated thiophene compounds. In all cases the PASH fractions showed no more specific mutagenic response than the neutral PAC fractions from which they were isolated. The only mutagenic response which was detected in the PASH fractions was for the Rio Blanco shale oil and showed specific mutagenic response similar to the neutral PAC fraction from which it was isolated. Finally, the forward mutation 8-azaguanine test was apparently more sensitive than the Ames histidine reversion test in detecting mutagenic activity for the chemical fractions from the shale oils.

  12. Reactivities of vinyl azides and their recent applications in nitrogen heterocycle synthesis

    PubMed Central

    Hu, Bao; DiMagno, Stephen G.

    2015-01-01

    Nitrogen heterocycles are abundant in natural products and pharmaceuticals. An emerging interest among synthetic chemists is to apply vinyl azides as a pivotal three-atom synthon for the construction of structurally complex and diverse N-heterocyclic skeletons. The unique features of the azide group connected to an alkene moiety permit vinyl azides to function as electrophiles, nucleophiles, or radical acceptors; their access to diverse reaction pathways provides great opportunities to generate highly reactive intermediates with often unusual or unconventional reactivities. This tutorial review will systematically illustrate the reactivities of vinyl azides and describe recent breakthroughs in the development of new transformations that create N-heterocycles. PMID:25731154

  13. Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues.

    PubMed

    Driowya, Mohsine; Saber, Aziza; Marzag, Hamid; Demange, Luc; Benhida, Rachid; Bougrin, Khalid

    2016-01-01

    This review describes the formation of six-membered heterocyclic compounds and their fused analogues under microwave activation using modern organic transformations including cyclocondensation, cycloaddition, multicomponents and other modular reactions. The review is divided according to the main heterocycle types in order of increasing complexity, starting with heterocyclic systems containing one, two and three heteroatoms and their fused analogues. Recent microwave applications are reviewed, with special focus on the chemistry of bioactive compounds. Selected examples from the 2006 to 2015 literature are discussed. PMID:27089315

  14. The oxime portmanteau motif: released heteroradicals undergo incisive EPR interrogation and deliver diverse heterocycles.

    PubMed

    Walton, John C

    2014-04-15

    Selective syntheses are now available for compounds of many classes, based on C-centered radicals, exploiting a diverse range of mechanisms. The prospect for chemistry based around N- and O-centered radicals is probably more favorable because of the importance of heterocycles as biologically active materials. Heteroradical chemistry is still comparatively underdeveloped due to the need for safe and easy ways of generating them. Oxime esters appeared promising candidates to meet this need because literature reports and our EPR spectroscopic examinations showed they readily dissociated on photolysis with production of a pair of N- and O-centered radicals. It soon became apparent that a whole suite of benign oxime-containing molecules could be pressed into service. The bimodality of the oxime motif meant that by suitable choice of functionality the reactions could be directed to yield selectively products from either the N-centered radicals or from the O-centered radicals. We found that on one hand photolyses of acetophenone oxime esters of carboxylic acids yielded alicyclics. On the other hand, aromatic and heteroaromatic acyl oximes (as well as dioxime oxalates) afforded good yields of phenanthridines and related heterocycles. Easily prepared oxime oxalate amides released carbamoyl radicals, and pleasingly, β-lactams were thereby obtained. Oxime carbonates and oxime carbamates, available via our novel 1,1'-carbonyldiimidazole (CDI)-based preparations, were accessible alternatives for iminyl radicals and hence for phenanthridine preparations. In their second modes, these compounds proved their value as precursors for exotic alkoxycarbonyloxyl and carbamoyloxyl radicals. Microwave-assistance was shown to be a particularly convenient procedure with O-phenyl oxime ethers. The iminyl radicals generated from such precursors with alkene, alkyne, and aromatic acceptor substituents furnished pyrrole, quinoline, phenanthridine, benzonaphthiridine, indolopyridine, and other

  15. The Oxime Portmanteau Motif: Released Heteroradicals Undergo Incisive EPR Interrogation and Deliver Diverse Heterocycles

    PubMed Central

    2014-01-01

    Conspectus Selective syntheses are now available for compounds of many classes, based on C-centered radicals, exploiting a diverse range of mechanisms. The prospect for chemistry based around N- and O-centered radicals is probably more favorable because of the importance of heterocycles as biologically active materials. Heteroradical chemistry is still comparatively underdeveloped due to the need for safe and easy ways of generating them. Oxime esters appeared promising candidates to meet this need because literature reports and our EPR spectroscopic examinations showed they readily dissociated on photolysis with production of a pair of N- and O-centered radicals. It soon became apparent that a whole suite of benign oxime-containing molecules could be pressed into service. The bimodality of the oxime motif meant that by suitable choice of functionality the reactions could be directed to yield selectively products from either the N-centered radicals or from the O-centered radicals. We found that on one hand photolyses of acetophenone oxime esters of carboxylic acids yielded alicyclics. On the other hand, aromatic and heteroaromatic acyl oximes (as well as dioxime oxalates) afforded good yields of phenanthridines and related heterocycles. Easily prepared oxime oxalate amides released carbamoyl radicals, and pleasingly, β-lactams were thereby obtained. Oxime carbonates and oxime carbamates, available via our novel 1,1'-carbonyldiimidazole (CDI)-based preparations, were accessible alternatives for iminyl radicals and hence for phenanthridine preparations. In their second modes, these compounds proved their value as precursors for exotic alkoxycarbonyloxyl and carbamoyloxyl radicals. Microwave-assistance was shown to be a particularly convenient procedure with O-phenyl oxime ethers. The iminyl radicals generated from such precursors with alkene, alkyne, and aromatic acceptor substituents furnished pyrrole, quinoline, phenanthridine, benzonaphthiridine, indolopyridine

  16. Palladium-catalysed C-H activation of aliphatic amines to give strained nitrogen heterocycles

    NASA Astrophysics Data System (ADS)

    McNally, Andrew; Haffemayer, Benjamin; Collins, Beatrice S. L.; Gaunt, Matthew J.

    2014-06-01

    The development of new chemical transformations based on catalytic functionalization of unactivated C-H bonds has the potential to simplify the synthesis of complex molecules dramatically. Transition metal catalysis has emerged as a powerful tool with which to convert these unreactive bonds into carbon-carbon and carbon-heteroatom bonds, but the selective transformation of aliphatic C-H bonds is still a challenge. The most successful approaches involve a `directing group', which positions the metal catalyst near a particular C-H bond, so that the C-H functionalization step occurs via cyclometallation. Most directed aliphatic C-H activation processes proceed through a five-membered-ring cyclometallated intermediate. Considering the number of new reactions that have arisen from such intermediates, it seems likely that identification of distinct cyclometallation pathways would lead to the development of other useful chemical transformations. Here we report a palladium-catalysed C-H bond activation mode that proceeds through a four-membered-ring cyclopalladation pathway. The chemistry described here leads to the selective transformation of a methyl group that is adjacent to an unprotected secondary amine into a synthetically versatile nitrogen heterocycle. The scope of this previously unknown bond disconnection is highlighted through the development of C-H amination and carbonylation processes, leading to the synthesis of aziridines and β-lactams (respectively), and is suggestive of a generic C-H functionalization platform that could simplify the synthesis of aliphatic secondary amines, a class of small molecules that are particularly important features of many pharmaceutical agents.

  17. catena-Poly[[[(oxamide dioxime-κ2N,N')copper(II)]-μ-L-tartrato-κ4O1,O2:O3,O4] tetrahydrate]: a chiral nanochannel framework hosting solvent water molecules.

    PubMed

    Bélombé, Michel M; Nenwa, Justin; Kouamo, Jean S T Wankap; Ponou, Siméon; Fischer, Andreas

    2012-05-01

    The crystal structure of the title compound, {[Cu(C(4)H(4)O(6))(C(2)H(6)N(4)O(2))]·4H(2)O}(n), contains the central Cu(II) cation in a distorted octahedral coordination, symmetrically chelated by the two imine N atoms of a neutral oxamide dioxime (H(2)oxado) ligand [Cu-N = 1.9829 (16) Å] and unsymmetrically bis-chelated by two halves of the L-(+)-tartrate(2-) (tart) ligands, each half being linked to the Cu(II) cation via the deprotonated carboxylate group and protonated hydroxy group [Cu-O = 1.9356 (14) and 2.4674 (13) Å, respectively]. The extended asymmetric unit is defined by twofold axes, one passing through the Cu(II) cation and the centre of the oxamide dioxime (H(2)oxado) ligand and the another two (symmetry related) bisecting the central C-C bonds of the tartrate ions. The structure is chiral, consisting of enantiomeric linear-chain polymers oriented along [001], with virtual monomeric {Cu(tart(0.5))(2)(H(2)oxado)} repeat units and with the chains interleaved face-to-face into `twin pillars'. Nanochannels exist, running parallel to the c axis and bisecting a and b, which host `double strings' of solvent water molecules. Extensive hydrogen bonding (O-H···O and N-H···O) between the chains and solvent water molecules, together with extended π-σ interactions, consolidate the bulk crystal structure. PMID:22552305

  18. Continuous-Flow N-Heterocyclic Carbene Generation and Organocatalysis.

    PubMed

    Di Marco, Lorenzo; Hans, Morgan; Delaude, Lionel; Monbaliu, Jean-Christophe M

    2016-03-18

    Two methods were assessed for the generation of common N-heterocyclic carbenes (NHCs) from stable imidazol(in)ium precursors using convenient and straightforward continuous-flow setups with either a heterogeneous inorganic base (Cs2 CO3 or K3 PO4 ) or a homogeneous organic base (KN(SiMe3 )2 ). In-line quenching with carbon disulfide revealed that the homogeneous strategy was most efficient for the preparation of a small library of NHCs. The generation of free nucleophilic carbenes was next telescoped with two benchmark NHC-catalyzed reactions; namely, the transesterification of vinyl acetate with benzyl alcohol and the amidation of N-Boc-glycine methyl ester with ethanolamine. Both organocatalytic transformations proceeded with total conversion and excellent yields were achieved after extraction, showcasing the first examples of continuous-flow organocatalysis with NHCs. PMID:26880372

  19. Poly(oligonucleotide)

    PubMed Central

    2015-01-01

    Here we report the preparation of poly(oligonucleotide) brush polymers and amphiphilic brush copolymers from nucleic acid monomers via graft-through polymerization. We describe the polymerization of PNA-norbornyl monomers to yield poly-PNA (poly(peptide nucleic acid)) via ring-opening metathesis polymerization (ROMP) with the initiator, (IMesH2)(C5H5N)2(Cl)2RuCHPh.1 In addition, we present the preparation of poly-PNA nanoparticles from amphiphilic block copolymers and describe their hybridization to a complementary single-stranded DNA (ssDNA) oligonucleotide. PMID:25077676

  20. Mutagenic activity and heterocyclic amine content of heated foods

    SciTech Connect

    Knize, M.G.; Johansson, M.; Jones, A.L.; Blakley, M.; Felton, J.S.

    1994-12-31

    Cooked foods were extracted and analyzed for mutagenic activity and assayed for known heterocyclic amines (HAs) by the Ames/Salmonella test and HPLC, respectively. Fried meats contain HAs (predominantly PhIP, MeIQx, DiMeIQx, and A{alpha}C) that are potent promutagens in bacteria, mutagenic in cultured mammalian cells, and carcinogenic in rodents and in nonhuman primates. Meats contain levels ranging from undetectable (< 0.1 ppb) to 50 ppb of known HAs when fried at temperatures from 190 to 250{degrees}C. These identified compounds are responsible for ca 75% of the measured mutagenic activity in Salmonella strain TA98. Barbecued beef and chicken have up to several thousand TA98 revertants per gram (rev/g) of cooked meat, with only ca 30% of the mutagenic activity accounted for by known heterocyclic amines. Some heated nonmeat foods also contain potent mutagenic activity. Toasted breads, cereals and snack foods have 0 to 10 TA98 rev/g, but overtoasting yields up to 40 rev/g, wheat and gluten-containing products are associated with higher activity. Grain-based coffee-substitute powders and instant coffees have 190 to 380 rev/g in TA98, and 1100 to 4000 rev/g in strain YG1024. The identify of the compounds responsible for the mutagenic activity are unknown in these non-meat foods. Toasted grain-based foods probably contribute less than 10% of the total mutagenic activity of the diet, with meat products responsible for the reminder. The finding of varying amounts of known and unknown mutagens in some cooked foods may be responsible for the poorly understood variation in human cancer incidence worldwide.

  1. MUTAGENICITY IN SALMONELLA OF SULFUR-CONTAINING POLYCYCLIC AROMATIC HETEROCYCLES AND THEIR DIHYDRODIOL DERIVATIVES

    EPA Science Inventory

    Polycyclic aromatic sulfur heterocycles (PASH) are common constituents of cigarette smoke, fossil fuel-derived materials, and their combustion byproducts. Many PASH are known mutagens and carcinogens. However, unlike their nonsulfur-containing counterparts, relatively little is k...

  2. Microwave-Assisted Synthesis of Bio-Active Heterocycles and Fine Chemicals in Aqueous Media

    EPA Science Inventory

    Human health, especially in the aging population, mostly depends on various medicines, and researchers are combating against emerging diseases by new drug discovery. Heterocyclic compounds hold a special place among pharmaceutically active natural products as well as synthetic co...

  3. MICROWAVE-ASSISTED GREENER SYNTHESIS OF PHARMACEUTICALLY ACTIVE HETEROCYCLES UNDER BENIGN CONDITIONS

    EPA Science Inventory

    Green chemistry is a rapidly developing new field that provides us a proactive avenue for the sustainable development of future science and technologies. Environmentally benign protocols have been developed for the synthesis of various pharmaceutically active heterocycles namely ...

  4. Improving Grubbs' II type ruthenium catalysts by appropriately modifying the N-heterocyclic carbene ligand.

    PubMed

    Vieille-Petit, Ludovic; Luan, Xinjun; Gatti, Michele; Blumentritt, Sascha; Linden, Anthony; Clavier, Hervé; Nolan, Steven P; Dorta, Reto

    2009-07-01

    The introduction of N-heterocyclic carbene ligands that incorporate correctly substituted naphthyl side chains leads to increased activity and stability in second generation ruthenium metathesis catalysts. PMID:19557281

  5. Asymmetric Hydrogenation of Seven-Membered C=N-containing Heterocycles and Rationalization of the Enantioselectivity.

    PubMed

    Balakrishna, Bugga; Bauzá, Antonio; Frontera, Antonio; Vidal-Ferran, Anton

    2016-07-18

    Iridium(I) complexes with phosphine-phosphite ligands efficiently catalyze the enantioselective hydrogenation of diverse seven-membered C=N-containing heterocyclic compounds (eleven examples; up to 97 % ee). The P-OP ligand L3, which incorporates an ortho-diphenyl substituted octahydrobinol phosphite fragment, provided the highest enantioselectivities in the hydrogenation of most of the heterocyclic compounds studied. The observed stereoselection was rationalized by means of DFT calculations. PMID:27333576

  6. 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

  7. Steroids with a side chain containing a heterocyclic fragment: synthesis and transformations

    NASA Astrophysics Data System (ADS)

    Baranovskii, Aleksander V.; Litvinovskaya, Raisa P.; Khripach, Vladimir A.

    1993-07-01

    The latest data on the methods for the formation of the side chains of steroids containing a heterocyclic fragment are surveyed and described systematically. Attention is concentrated on the methods for the transformation of heterocycles in order to achieve the stereoselective formation of chiral centres in the side chain characteristic of a series of natural polyhydroxysteroids - ecdysones, brassinosteroids, vitamin D metabolites, etc. The bibliography includes 133 references.

  8. Transition-Metal-Catalyzed Denitrogenative Transannulation: Converting Triazoles into Other Heterocyclic Systems

    PubMed Central

    Chattopadhyay, Buddhadeb

    2012-01-01

    Transition metal catalyzed denitrogenative transannulation of a triazole ring has recently received considerable attention as a new concept for the construction of diverse nitrogen-containing heterocyclic cores. This method allows a single-step synthesis of complex nitrogen heterocycles from easily available and cheap triazole precursors. In this Minireview, recent progress of the transition metal catalyzed denitrogenative transannulation of a triazole ring, which was discovered in 2007, is discussed. PMID:22121072

  9. 8-Azido double-stranded RNA photoaffinity probes. Enzymatic synthesis, characterization, and biological properties of poly(I,8-azidoI).poly(C) and poly(I,8-azidoI).poly(C12U) with 2',5'-oligoadenylate synthetase and protein kinase.

    PubMed

    Li, S W; Moskow, J J; Suhadolnik, R J

    1990-04-01

    The technique of photoaffinity labeling has been applied to the double-stranded RNA (dsRNA)-dependent enzyme 2',5'-oligoadenylate (2-5A) synthetase to provide a means for the examination of RNA-protein interaction(s) in the dsRNA allosteric binding domain of this enzyme. The synthesis, characterization, and biological properties of the photoaffinity probe poly[( 32P]I,8-azidoI).poly(C) and its mismatched analog poly[( 32P]I,8-azidoI).poly(C12U), which mimic the parent molecules poly(I).poly(C) and poly(I).poly(C12U), are described. The efficacy of poly[( 32P]I,8-azidoI).poly(C) and poly[( 32P]I,8-azidoI).poly(C12U) as allosteric site-directed activators is demonstrated using highly purified 2-5A synthetase from rabbit reticulocyte lysates and from extracts of interferon-treated HeLa cells. The dsRNA photoprobes activate these two 2-5A synthetases. Saturation of 2-5A synthetase is observed at 6 x 10(-4) g/ml poly[( 32P]I,8-azidoI).poly(C) following photolysis for 20 s at 0 degrees C. The photoincorporation of poly[( 32P]I,8-azidoI).poly(C) is specific, as demonstrated by the prevention of photoincorporation by native poly(I).poly(C). DNA, poly(I), and poly(C) are not competitors of poly[( 32P]I,8-azidoI).poly(C). Following UV irradiation of 2-5A synthetase with poly[( 32P]I,8-azidoI).poly(C), the reaction mixture is treated with micrococcal nuclease to hydrolyze azido dsRNA that is not cross-linked to the enzyme. A radioactive band of 110 kDa (the same as that reported for native rabbit reticulocyte lysate 2-5A synthetase) is observed following sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The specific photolabeling of the 2-5A synthetase suggests that the azido dsRNA is intrinsic to the allosteric binding domain. The utility of poly[( 32P]I,8-azidoI).poly(C) for the detection of dsRNA-dependent binding proteins and the isolation of peptides at or near the allosteric binding site is discussed. PMID:2318823

  10. RNA targeting by small molecule alkaloids: Studies on the binding of berberine and palmatine to polyribonucleotides and comparison to ethidium

    NASA Astrophysics Data System (ADS)

    Islam, Md. Maidul; Suresh Kumar, Gopinatha

    2008-03-01

    The binding affinity, energetics and conformational aspects of the interaction of isoquinoline alkaloids berberine and palmatine to four single stranded polyribonucleotides polyguanylic acid [poly(G)], polyinosinic acid [poly(I)], polycytidylic acid [poly(C)] and polyuridylic acid [poly(U)] were studied by absorption, fluorescence, isothermal titration calorimetry and circular dichroism spectroscopy and compared with ethidium. Berberine, palmatine and ethidium binds strongly with poly(G) and poly(I) with affinity in the order 10 5 M -1 while their binding to poly(C) and poly(U) were very weak or practically nil. The same conclusions have also emerged from isothermal titration calorimetric studies. The binding of all the three compounds to poly(C) and poly(I) was exothermic and favored by both negative enthalpy change and positive entropy change. Conformational change in the polymer associated with the binding was observed in poly(I) with all the three molecules and poly(U) with ethidium but not in poly(G) and poly(C) revealing differences in the orientation of the bound molecules in the hitherto different helical organization of these polymers. These fundamental results may be useful and serve as database for the development of futuristic RNA based small molecule therapeutics.

  11. Poly(Arylene Ether Imidazole) Surface Films

    NASA Technical Reports Server (NTRS)

    Connell, John W.; Towell, Timothy W.; Tompkins, Stephen S.

    1993-01-01

    Films adhere well to some substrates, provide smooth surfaces, and facilitate release from molds. Thin films of thermoplastic poly(arylene ether imidazole)s (PAEI's) particularly suitable for use as surface modifiers for graphite/epoxy or graphite/bismaleimide composite panels. Molecule of PAEI includes imidazole groups along its backbone that co-cure with epoxies or bismaleimides during processing. Films thermally stable and resistant to bombardment by energetic electrons.

  12. Post-training intrahippocampal injection of synthetic poly-α-2,8-sialic acid-neural cell adhesion molecule mimetic peptide improves spatial long-term performance in mice

    PubMed Central

    Florian, Cédrick; Foltz, Jane; Norreel, Jean-Chrétien; Rougon, Geneviève; Roullet, Pascal

    2006-01-01

    Several data have shown that the neural cell adhesion molecule (NCAM) is necessary for long-term memory formation and might play a role in the structural reorganization of synapses. The NCAM, encoded by a single gene, is represented by several isoforms that differ with regard to their content of α-2,8-linked sialic acid residues (PSA) on their extracellular domain. The carbohydrate PSA is known to promote plasticity, and PSA-NCAM isoforms remain expressed in the CA3 region of the adult hippocampus. In the present study, we investigated the effect on spatial memory consolidation of a PSA gain of function by injecting a PSA mimetic peptide (termed pr2) into the dorsal hippocampus. Mice were subjected to massed training in the spatial version of the water maze. Five hours after the last training session, experimental mice received an injection of pr2, whereas control mice received PBS or reverse peptide injections in the hippocampal CA3 region. Memory retention was tested at different time intervals: 24 h, 1 wk, and 4 wk. The results showed that the post-training infusion of pr2 peptide significantly increases spatial performance whenever it was assessed after the training phase. By contrast, administration of the control reverse peptide did not affect retention performance. These findings provide evidence that (1) PSA-NCAM is involved in memory consolidation processes in the CA3 hippocampal region, and (2) PSA mimetic peptides can facilitate the formation of long-term spatial memory when injected during the memory consolidation phase. PMID:16705136

  13. Infrared Spectroscopy of Matrix-Isolated Polycyclic Aromatic Compounds and their Ions. 6; Polycyclic Aromatic Nitrogen Heterocycles

    NASA Technical Reports Server (NTRS)

    Mattioda, A. L.; Hudgins, Douglas M.; Bauschlicher, C. W., Jr.; Rosi, M.; Allamandola, L. J.; DeVincenzi, D. (Technical Monitor)

    2002-01-01

    The matrix-isolation technique has been employed to measure the mid-infrared spectra of several polycyclic aromatic nitrogen heterocycles in both neutral and cationic forms. The species studied include: 7,8 benzoquinoline (C13H9N); 2-azapyrene (C15H9N); 1- and 2-azabenz(a)anthracene (C17H11N); and 1-, 2-, and 4-azachrysene (also C17H11N). The experimentally measured band frequencies and intensities for each molecule are tabulated and compared with their theoretically calculated values computed using density functional theory at the B3LYP/4-31G level. The overall agreement between experiment and theory is quite good, in keeping with previous investigations involving the parent aromatic hydrocarbons. Several interesting spectroscopic trends are found to accompany nitrogen substitution into the aromatic framework of these compounds. First, for the neutral species, the nitrogen atom produces a significant increase in the total integrated infrared intensity across the 1600 - 1100/cm region and plays an essential role in the molecular vibration that underlies an uncharacteristically intense, discrete feature that is observed near 1400/cm in the spectra of 7,8 benzoquinoline, 1-azabenz(a)anthracene, and 4-azachrysene. The origin of this enhanced infrared activity and the nature of the new 1400/cm vibrational mode are explored. Finally, in contrast to the parent hydrocarbon species, these aromatic nitrogen heterocycles possess a significant permanent dipole moment. Consequently, these dipole moments and the rotational constants are reported for these species in their neutral and ionized forms.

  14. Heterocyclic derivatives of 3-substituted-1,1,1-trifluoro-2-propanones as inhibitors of esterolytic enzymes.

    PubMed

    Székács, A; Halarnkar, P P; Olmstead, M M; Prag, K A; Hammock, B D

    1990-01-01

    A series of (alkylthio)trifluoropropanones containing a heterocyclic moiety was synthesized. The compounds were tested for in vitro inhibition of four hydrolytic enzymes including insect juvenile hormone esterase (JHE), eel acetylcholinesterase (AChE), yeast lipase (LP), and bovine alpha-chymotrypsin. The I50 values ranged from 10(-3) to 10(-7) M. 3-(2-Pyridylthio)-1,1,1-trifluoro-2-propanone was found to be the most potent inhibitor as compared to the other tested heterocyclic analogues with an I50 value of 98 nM against JHE from the fifth-instar larvae of Trichoplusia ni. Results from X-ray crystallography showed that the compound exists in a tetrahedral gem-diol form stabilized by an intramolecular hydrogen bond in the solid state. X-ray crystallography of a less potent inhibitor, 3-(4-pyridylthio)-1,1,1-trifluoro-2- propanone, showed that it also exists in the hydrated form, but it lacks an intramolecular hydrogen bond. These results provide indirect support that trifluoromethyl ketones are transition-state mimic inhibitors of esterases, and the bearing of the results on the transition-state mimic theory is discussed. The I50 values against AChE were in the micromolar range. Compounds containing a imidazolyl, triazolyl, and pyrimidyl moiety showed the highest inhibition of this enzyme. Differential selectivity of inhibition was associated with the bond distances between the nitrogen and the carbonyl group as in the natural substrate, when measured in the molecules in their minimal energy conformations. Inhibition of LP was moderate to weak, when compared to JHE and AChE. None of the tested compounds showed significant inhibition of alpha-chymotrypsin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2133080

  15. Caffeine-based gold(I) N-heterocyclic carbenes as possible anticancer agents: synthesis and biological properties.

    PubMed

    Bertrand, Benoît; Stefan, Loic; Pirrotta, Marc; Monchaud, David; Bodio, Ewen; Richard, Philippe; Le Gendre, Pierre; Warmerdam, Elena; de Jager, Marina H; Groothuis, Geny M M; Picquet, Michel; Casini, Angela

    2014-02-17

    A new series of gold(I) N-heterocyclic carbene (NHC) complexes based on xanthine ligands have been synthesized and characterized by mass spectrometry, NMR, and X-ray diffraction. The compounds have been tested for their antiproliferative properties in human cancer cells and nontumorigenic cells in vitro, as well as for their toxicity in healthy tissues ex vivo. The bis-carbene complex [Au(caffein-2-ylidene)2][BF4] (complex 4) appeared to be selective for human ovarian cancer cell lines and poorly toxic in healthy organs. To gain preliminary insights into their actual mechanism of action, two biologically relevant in cellulo targets were studied, namely, DNA (more precisely a higher-order DNA structure termed G-quadruplex DNA that plays key roles in oncogenetic regulation) and a pivotal enzyme of the DNA damage response (DDR) machinery (poly-(adenosine diphosphate (ADP)-ribose) polymerase 1 (PARP-1), strongly involved in the cancer resistance mechanism). Our results indicate that complex 4 acts as an efficient and selective G-quadruplex ligand while being a modest PARP-1 inhibitor (i.e., poor DDR impairing agent) and thus provide preliminary insights into the molecular mechanism that underlies its antiproliferative behavior. PMID:24499428

  16. Polymeric Nanomedicines Based on Poly(lactide) and Poly(lactide-co-glycolide)

    PubMed Central

    Tong, Rong; Gabrielson, Nathan P.; Fan, Timothy M.; Cheng, Jianjun

    2013-01-01

    Small molecule chemotherapeutics often have undesired physiochemical and pharmacological properties, such as low solubility, severe side effect and narrow therapeutic index. To address these challenges, polymeric nanomedicine drug delivery technology has been routinely employed, in particular with the use of biodegradable and biocompatible polyesters, such as poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA). Here we review the development and use of PLA and PLGA for the delivery of chemotherapeutic agents in the forms of polymer-drug conjugates and nanoconjugates. PMID:23914135

  17. Redox-labelled poly(ethylene glycol) used as a diffusion probe in poly(ethylene glycol) melts

    SciTech Connect

    Haas, O.; Velasquez, C.; Porat, Z.

    1995-12-01

    Ferrocene labelled monomethyl poly(ethylene glycol) MPEG with molecular weights of 1900 and 750 was prepared and used as an electrochemical diffusion probe in poly(ethylene glycol) melts. Cyclic voltammetry and chronoamperometry were used in connection with microdisk electrodes to measure the diffusion coefficient of redox tagged molecules using melted poly(ethylene glycol) as a solvent. The molecular weight of the solvent polymer was 750, 2000 and 20000. Results from the temperature dependency of the diffusion process and of the viscosity and conductivity of the polymer electrolyte are presented and discussed.

  18. Electrospun nanofibers of polyCD/PMAA polymers and their potential application as drug delivery system.

    PubMed

    Oliveira, Michele F; Suarez, Diego; Rocha, Júlio Cézar Barbosa; de Carvalho Teixeira, Alvaro Vianna Novaes; Cortés, Maria E; De Sousa, Frederico B; Sinisterra, Rubén D

    2015-09-01

    Herein, we used an electrospinning process to develop highly efficacious and hydrophobic coaxial nanofibers based on poly-cyclodextrin (polyCD) associated with poly(methacrylic acid) (PMAA) that combines polymeric and supramolecular features for modulating the release of the hydrophilic drug, propranolol hydrochloride (PROP). For this purpose, polyCD was synthesized and characterized, and its biocompatibility was assessed using fibroblast cytotoxicity tests. Moreover, the interactions between the guest PROP molecule and both polyCD and βCD were found to be spontaneous. Subsequently, PROP was encapsulated in uniaxial and coaxial polyCD/PMAA nanofibers. A lower PROP burst effect (reduction of approximately 50%) and higher modulation were observed from the coaxial than from the uniaxial fibers. Thus, the coaxial nanofibers could potentially be a useful strategy for developing a controlled release system for hydrophilic molecules. PMID:26046289

  19. Rhenium and technetium tricarbonyl complexes of N-heterocyclic carbene ligands.

    PubMed

    Chan, Chung Ying; Pellegrini, Paul A; Greguric, Ivan; Barnard, Peter J

    2014-10-20

    A strategy for the conjugation of N-heterocyclic carbene (NHC) ligands to biomolecules via amide bond formation is described. Both 1-(2-pyridyl)imidazolium or 1-(2-pyridyl)benzimidazolium salts functionalized with a pendant carboxylic acid group were prepared and coupled to glycine benzyl ester using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide. A series of 10 rhenium(I) tricarbonyl complexes of the form [ReX(CO)3(ĈN)] (ĈN is a bidentate NHC ligand, and X is a monodentate anionic ligand: Cl(-), RCO2(-)) were synthesized via a Ag2O transmetalation protocol from the Re(I) precursor compound Re(CO)5Cl. The synthesized azolium salts and Re(I) complexes were characterized by elemental analysis and by (1)H and (13)C NMR spectroscopy, and the molecular structures for one imidazolium salt and seven Re(I) complexes were determined by single-crystal X-ray diffraction. (1)H NMR and mass spectrometry studies for an acetonitrile-d3 solution of [ReCl(CO)3(1-(2-pyridyl)-3-methylimidazolylidene)] show that the monodentate chloride ligand is labile and exchanges with this solvent yielding a cationic acetonitrile adduct. For the first time the labeling of an NHC ligand with technetium-99m is reported. Rapid Tc-99m labeling was achieved by heating the imidazolium salt 1-(2-pyridyl)-3-methylimidazolium iodide and Ag2O in methanol, followed by the addition of fac-[(99m)Tc(OH2)3(CO)3](+). To confirm the structure of the (99m)Tc-labeled complex, the equivalent (99)Tc complex was prepared, and mass spectrometric studies showed that the formed Tc complexes are of the form [(99m/99)Tc(CH3CN)(CO)3(1-(2-pyridyl)-3-methylimidazolylidene)](+) with an acetonitrile molecule coordinated to the metal center. PMID:25280253

  20. Silylation of C-H bonds in aromatic heterocycles by an Earth-abundant metal catalyst

    NASA Astrophysics Data System (ADS)

    Toutov, Anton A.; Liu, Wen-Bo; Betz, Kerry N.; Fedorov, Alexey; Stoltz, Brian M.; Grubbs, Robert H.

    2015-02-01

    Heteroaromatic compounds containing carbon-silicon (C-Si) bonds are of great interest in the fields of organic electronics and photonics, drug discovery, nuclear medicine and complex molecule synthesis, because these compounds have very useful physicochemical properties. Many of the methods now used to construct heteroaromatic C-Si bonds involve stoichiometric reactions between heteroaryl organometallic species and silicon electrophiles or direct, transition-metal-catalysed intermolecular carbon-hydrogen (C-H) silylation using rhodium or iridium complexes in the presence of excess hydrogen acceptors. Both approaches are useful, but their limitations include functional group incompatibility, narrow scope of application, high cost and low availability of the catalysts, and unproven scalability. For this reason, a new and general catalytic approach to heteroaromatic C-Si bond construction that avoids such limitations is highly desirable. Here we report an example of cross-dehydrogenative heteroaromatic C-H functionalization catalysed by an Earth-abundant alkali metal species. We found that readily available and inexpensive potassium tert-butoxide catalyses the direct silylation of aromatic heterocycles with hydrosilanes, furnishing heteroarylsilanes in a single step. The silylation proceeds under mild conditions, in the absence of hydrogen acceptors, ligands or additives, and is scalable to greater than 100 grams under optionally solvent-free conditions. Substrate classes that are difficult to activate with precious metal catalysts are silylated in good yield and with excellent regioselectivity. The derived heteroarylsilane products readily engage in versatile transformations enabling new synthetic strategies for heteroaromatic elaboration, and are useful in their own right in pharmaceutical and materials science applications.

  1. Theoretical Insights into the Catalytic Mechanism of N-Heterocyclic Olefins in Carboxylative Cyclization of Propargyl Alcohol with CO2.

    PubMed

    Li, Weiyi; Yang, Na; Lyu, Yajing

    2016-07-01

    The mechanism of carboxylative cyclization of propargyl alcohol with CO2 catalyzed by N-heterocyclic olefins (NHOs) has been studied by density functional theory calculations. The calculations reveal that the catalytic reaction tends to proceed via the NHO-mediated basic ionic pair mechanism, in which free NHO primarily acts as a basic precursor to trigger the carboxylation of propargyl alcohol with CO2, leading to a [NHOH](+)[carbonate](-) ion pair intermediate. Then, the catalytic cycle proceeds, including isomerization of the [NHOH](+)[carbonate](-) ion pair intermediate, intramolecular nucleophilic addition of the carbonate oxygen anion to the alkynyl group, and protonation of the alkenyl carbon anion with an external propargyl alcohol molecule. Molecule orbital and nature population analysis discloses that the preference for the basic ionic pair mechanism is due to the favorable orbital and charge interactions between the α-carbon atom of NHO and the hydroxyl hydrogen of propargyl alcohol. The [NHOH](+) cation has proven to be crucial for stabilizing the [carbonate](-) anion, which allows the reaction to proceed through a more thermodynamically stable pathway. The investigations of the effect of substituents of NHOs predict that N-substituents with a strong electron donating effect and a bulky steric effect might improve the catalytic activity of NHOs for the reaction. PMID:27266858

  2. Electrospray ionization for determination of non-polar polyaromatic hydrocarbons and polyaromatic heterocycles in heavy crude oil asphaltenes.

    PubMed

    Molnárné Guricza, Lilla; Schrader, Wolfgang

    2015-03-01

    Electrospray ionization (ESI) is the most common ionization method in atmospheric pressure ionization mass spectrometry because of its easy use and handling and because a diverse range of components can be effectively ionized from high to medium polarity. Usually, ESI is not employed for the analysis of non-polar hydrocarbons, but under some circumstances, they are effectively ionized. Polyaromatic hydrocarbons and aromatic heterocycles can form radical ions and protonated molecules after ESI, which were detected by Fourier transform ion cyclotron resonance mass spectrometry. The highly condensed aromatic structures are obtained from a heavy crude oil, and the results show class distribution from pure hydrocarbons up to more non-basic nitrogen-containing species. By using different solvent compositions [toluene/methanol (50/50 v/v), dichloromethane/methanol (50/50 v/v), dichloromethane/acetonitrile (50/50 v/v) and chloroform], the results show that the lack of proton donor agent helps to preserve the radical formation that was created at the metal/solution interface inside the electrospray capillary. The results demonstrate that with an appropriate selection of solvent and capillary voltage, the ratio between the detected radical ion and protonated molecule form can be manipulated. Therefore, ESI can be expanded for the investigation of asphaltene and other polyaromatic systems beyond the polar constituents as non-polar hydrocarbons can be efficiently analyzed. PMID:25800191

  3. Preliminary Studies on the Activity of Mixed Polyphenol-Heterocyclic Systems Against B16-F10 Melanoma Cancer Cells.

    PubMed

    Duy Vo, Duc; Rouaud, Isabelle; Le Devehat, Francoise; Gautier, Fabien; Barillé-Nion, Sophie; Juin, Philippe; Levoin, Nicolas; Boustie, Joël; Grée, René

    2016-01-01

    The Bcl-2 family includes 26 proteins involved in apoptosis. Cancer cells can develop the ability to avoid apoptosis through the upregulation and/or down regulation of such proteins Bax, Bcl-xL or Mcl-1, especially during chemoresistance progress. These proteins engaged in a network of dynamic interactions that control apoptosis triggering have become attractive therapeutic targets in cancers including melanoma. Among them, the Bax/Bcl-xL interaction appears critical in maintaining mitochondria integrity. Therefore a series of mixed polyphenol-heterocyclic molecules, were rationally designed by molecular docking as Bax/Bcl-xL inhibitors. It has been screened against B16-F10 melanoma cancer cells for a preliminary investigation of their cytotoxicity. All these compounds exhibited a significant cytotoxicity against these cancer cells, in the 0.3-6 .M range. A pyrazole-type molecule, which had a submicromolar IC50 value with an excellent selectivity index (14), is the most promising derivative for further development. PMID:26825069

  4. Supramolecular hydrogen-bonding patterns of co-crystals containing the active pharmaceutical ingredient (API) phloroglucinol and N-heterocycles.

    PubMed

    Cvetkovski, Aleksandar; Bertolasi, Valerio; Ferretti, Valeria

    2016-06-01

    The active pharmaceutical ingredient phloroglucinol (PHL) has been taken as an illustrative molecule to explore the intermolecular interactions which can be established with other molecular entities to build PHL pharmaceutical co-crystals. The crystal structures of five newly synthesized co-crystals are reported, where PHL is crystallized with N-heterocycles, namely 2-hydroxy-6-methylpyridine (1), 2,4-dimethyl-6-hydroxypyrimidine (2), 4-phenylpyridine (3), 2-hydroxypyridine (4) and 2,3,5,6-tetramethylpyrazine (5). The structural characteristics of these co-crystals, as far as the hydrogen-bonding networks and the crystalline architectures are concerned, are strongly dependent on the chemical features of the coformer molecules, as well as on their size and shape. A detailed analysis of the intermolecular interactions established in all the PHL co-crystals of known structures has allowed the recognition of some regularities in the packing modes that can be useful in the design of new supramolecular adducts forming predictable structural motifs. PMID:27240764

  5. Molecular Basis of the Receptor Interactions of Polysialic Acid (polySia), polySia Mimetics, and Sulfated Polysaccharides.

    PubMed

    Zhang, Ruiyan; Loers, Gabriele; Schachner, Melitta; Boelens, Rolf; Wienk, Hans; Siebert, Simone; Eckert, Thomas; Kraan, Stefan; Rojas-Macias, Miguel A; Lütteke, Thomas; Galuska, Sebastian P; Scheidig, Axel; Petridis, Athanasios K; Liang, Songping; Billeter, Martin; Schauer, Roland; Steinmeyer, Jürgen; Schröder, Jens-Michael; Siebert, Hans-Christian

    2016-05-01

    Polysialic acid (polySia) and polySia glycomimetic molecules support nerve cell regeneration, differentiation, and neuronal plasticity. With a combination of biophysical and biochemical methods, as well as data mining and molecular modeling techniques, it is possible to correlate specific ligand-receptor interactions with biochemical processes and in vivo studies that focus on the potential therapeutic impact of polySia, polySia glycomimetics, and sulfated polysaccharides in neuronal diseases. With this strategy, the receptor interactions of polySia and polySia mimetics can be understood on a submolecular level. As the HNK-1 glycan also enhances neuronal functions, we tested whether similar sulfated oligo- and polysaccharides from seaweed could be suitable, in addition to polySia, for finding potential new routes into patient care focusing on an improved cure for various neuronal diseases. The knowledge obtained here on the structural interplay between polySia or sulfated polysaccharides and their receptors can be exploited to develop new drugs and application routes for the treatment of neurological diseases and dysfunctions. PMID:27136597

  6. Heterocyclic amine content in commercial ready to eat meat products.

    PubMed

    Puangsombat, Kanithaporn; Gadgil, Priyadarshini; Houser, Terry A; Hunt, Melvin C; Smith, J Scott

    2011-06-01

    Heterocyclic amines (HCAs) are produced in meats cooked at high temperature, which are potent mutagens and a risk factor for human cancers. The aim of this study was to estimate the amount of HCAs in some commonly consumed ready-to-eat (RTE) meat products. The RTE products were purchased from a local grocery store, and HCA were analyzed using an analytical method based on solid-phase extraction followed by HPLC. The primary HCAs in these samples were PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine) (not detected-7.9 ng/g) and MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline) (not detected-3.6 ng/g). Products ranked in order of increasing total HCA content: pepperoni (0.05 ng/g)

  7. Formation of heterocyclic amines in cooked chicken legs.

    PubMed

    Chiu, C P; Yang, D Y; Chen, B H

    1998-06-01

    The effects of frying and microwave cooking on generation of heterocyclic amines (HAs) in chicken legs with skin and without skin were studied. Chicken legs were microwave-cooked at 2,450 MHz for 5, 10, and 15 min with an output power of 700 W. Frying of chicken legs was conducted at 100 and 150 degrees C for 15 min and at 200 degrees C for 5, 10, and 15 min. The various HAs were analyzed by HPLC with diode-array detection. Results showed that both the varieties and contents of HAs and the weight losses of chicken legs increased along with increasing cooking temperature and time. With skin both the amounts of HAs and weight losses of chicken legs were less than those without skin under the same heating conditions. The weight losses of microwave-cooked chicken legs were higher than those of fried chicken legs. The formation of the aminomethylimidazoquinoline type of HAs could be reduced by choosing microwave cooking in place of frying. Frying led to the formation of both the aminomethylimidazoquinoline and the carboline types of HAs. PMID:9709255

  8. Ruthenium olefin metathesis catalysts featuring unsymmetrical N-heterocyclic carbenes.

    PubMed

    Paradiso, Veronica; Bertolasi, Valerio; Costabile, Chiara; Grisi, Fabia

    2016-01-14

    New ruthenium Grubbs' and Hoveyda-Grubbs' second generation catalysts bearing N-alkyl/N-isopropylphenyl N-heterocyclic carbene (NHC) ligands with syn or anti backbone configuration were obtained and compared in model olefin metathesis reactions. Different catalytic efficiencies were observed depending on the size of the N-alkyl group (methyl or cyclohexyl) and on the backbone configuration. The presence of an N-cyclohexyl substituent determined the most significant reactivity differences between catalysts with syn or anti phenyl groups on the backbone. In particular, anti catalysts proved highly efficient, especially in the ring-closing metathesis (RCM) of encumbered diolefins, while syn catalysts showed low efficiency in the RCM of less hindered diolefins. This peculiar behavior, rationalized through DFT studies, was found to be related to the high propensity of these catalysts to give nonproductive metathesis events. Enantiopure anti catalysts were also tested in asymmetric metathesis reactions, where moderate enantioselectivities were observed. The steric and electronic properties of unsymmetrical NHCs with the N-cyclohexyl group were then evaluated using the corresponding rhodium complexes. While steric factors proved unimportant for both syn and anti NHCs, a major electron-donating character was found for the unsymmetrical NHC with anti phenyl substituents on the backbone. PMID:26608162

  9. Frustrated N-heterocyclic carbene-silylium ion Lewis pairs.

    PubMed

    Silva Valverde, Miguel F; Theuergarten, Eileen; Bannenberg, Thomas; Freytag, Matthias; Jones, Peter G; Tamm, Matthias

    2015-05-28

    The reaction of the N-heterocyclic carbene 1,3-di-tert-butyl-4,5-dimethylimidazolin-2-ylidene () with trimethylsilyl iodide, triflate and triflimidate [Me3SiX, X = I, CF3SO3 (OTf), (CF3SO2)2N (NTf2)] by mixing the neat, liquid starting materials afforded the corresponding 2-(trimethylsilyl)imidazolium salts [()SiMe3]X as highly reactive, white crystalline solids. Only the triflimidate (X = NTf2) proved to be stable in solution and could be characterized by means of NMR spectroscopy (in C6D5Br) and X-ray diffraction analysis, whereas dissociation into free and Me3SiOTf was observed for the triflate system, in agreement with the trend derived by DFT calculations; the iodide was too insoluble for characterization. The compounds [()SiMe3]X showed the reactivity expected for frustrated carbene-silylium pairs, and treatment with carbon dioxide, tert-butyl isocyanate and diphenylbutadiyne gave the 1,2-addition products [()CO2SiMe3]X (X = I, OTf, NTf2), [()C(NtBu)OSiMe3]OTf and [()C(Ph)C(SiMe3)CCPh]OTf, respectively. Upon reaction with [AuCl(PPh3)], metal-chloride bond activation was observed, with formation of the cationic gold(i) complexes [()Au(PPh3)]X (X = OTf, NTf2). PMID:25912291

  10. Mechanisms of nitrogen heterocycle influence on turbine fuel stability

    NASA Technical Reports Server (NTRS)

    Daniel, S. R.; Worstell, J. H.

    1980-01-01

    Lewis bases were extracted from a Utah COED syncrude via ligand exchange. Addition of this extract to Jet A at levels as low as 5 ppm N produced deterioration of stability in both JFTOT and accelerated storage tests (7 days at 394 K with 13:1air to fuel ratio). Comparable effects on Jet A stability were obtained by addition of pyridine and quinoline, while pyrrole and indole were less detrimental at the same concentration level. The weight of deposit produced accelerated storage tests was found to be proportional to the concentration of added nitrogen compound. Over the narrow temperature range accessible with the experimental method, Arrhenius plots obtained by assuming specific rate to be proportional to the weight of material deposited in seven days exhibit greater slopes in the presence of those nitrogen compounds producing the greater deposition rates. It is shown that despite variation in appearance the elemental composition and spectral characteristics of the deposits are unaffected by addition of the nitrogen compounds. The linearity of the Arrhenius plots and of a plot of Arrhenius slope versus intercept for all the compounds suggests a constancy of mechanism over the range of temperature and heterocycles studied.

  11. Determination of heterocyclic amines in braised sauce beef.

    PubMed

    Yao, Y; Peng, Z Q; Wan, K H; Shao, B; Shi, J M; Zhang, Y W; Wang, F L; Hui, T

    2013-12-01

    A simplified and improved analysis method to determine the content of heterocyclic amines (HAs) was developed. Samples were extracted with ethyl acetate, and macrosubstances were removed by centrifugation. The eluent used consisted of methanol/ammonia water (9:1, v/v), and the eluates were directly mixed for further HPLC analysis. A binary mobile phase consisting of 0.05 M ammonium acetate-acetic acid and acetonitrile was used for the separation of 12 HAs, and the excitation and emission wavelengths of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) were adjusted to the same 315 and 410 nm, respectively. This method was further applied to determine the content of HAs in "Jiang Niu Rou", namely braised sauce beef. Nine kinds of HAs were found in the samples and the total amounts of HAs ranged from 4.33 to 27.15 ng/g. The sterilized samples contained more HAs than un-sterilized samples. PMID:23870900

  12. Surface activity of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) copolymers

    SciTech Connect

    Alexandridis, P.; Athanassiou, V.; Fukuda, Shinya; Hatton, T.A. )

    1994-08-01

    The surface tension of aqueous solutions of seven poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-PPO-PEO) Pluronic copolymers, covering a wide range of molecular weights (3400-14600) and PPO/PEO ratios (0.19-1.79), was determined over the 10[sup [minus]5]-10% w/v concentration range, at two temperatures (25 and 35[degree]C). Two breaks (changes in slope) were observed in the surface tension vs log concentration curve for most of the copolymers. The low-concentration break, occurring at bulk copolymer concentrations of approximately 10[sup [minus]3]%, is believed to originate from rearrangement of the copolymer molecules on the surface at complete coverage of the air/water interface. The breaks at the high-concentration part of the surface tension curve occurred at concentrations that correspond to the critical micellization concentration values as determined by a dye solubilization technique. The surface area per copolymer molecule, A, increased as a function of the number of EO segments, N[sub EO], obeying a scaling law (A [approx] N[sub EO][sup 1/2]) similar to that of lower molecular weight C[sub i]E[sub j] nonionic surfactants. 56 refs., 6 figs., 2 tabs.

  13. Phase Behavior of a Poly(ethylene oxide)-Poly(ethylethylene)/Water/Dodecane System

    NASA Astrophysics Data System (ADS)

    Kossuth, M. B.; Bates, F. S.

    1998-03-01

    Recently, we investigated the phase behavior of a series of low molecular weight poly(ethylene oxide)-poly(ethylethylene) (PEO-PEE) block copolymers in the presence of water (D.A. Hajduk, M.B. Kossuth, M.A. Hillmyer, and F.S. Bates, submitted to J. Phys. Chem. B). These molecules are chemically similar to the C_nEOm surfactants but have molecular weights roughly an order of magnitude greater. PEO is hydrophilic, while PEE is strongly hydrophobic. Current work involves the addition of a third component, dodecane, to create a ternary surfactant/water/oil system. The phase behavior of this system will be discussed and compared to that of chemically similar small molecule surfactants. Noteworthy results include the appearance of a bicontinuous cubic phase, which was not seen in the aqueous solutions, and the relative sizes of the phase windows.

  14. Synthesis and Regioselective Reaction of Some Unsymmetrical Heterocyclic Chalcone Derivatives and Spiro Heterocyclic Compounds as Antibacterial Agents.

    PubMed

    El-Hashash, Maher A; Rizk, Sameh A; Atta-Allah, Saad R

    2015-01-01

    A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl)-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone of imidazo[2,1-b]thiadiazole derivative 4 via two thermal routes. In one pot reaction of 4-bromoacetophenone, diethyloxalate, and 2-amino-5-aryl-1,3,4-thiadiazole derivatives in MW irradiation (W 250 and T 150 °C) under eco-friendly conditions afforded an unsuitable yield of the desired chalcone 4d. The chalcone derivatives 4 were used as a key starting material to synthesize some new spiroheterocyclic compounds via Michael and aza-Michael adducts. The chalcone 4f was similar to the aryl-oxo-vinylamide derivatives for the inhibition of tyrosine kinase and cancer cell growth. The electron-withdrawing substituents, such as halogens, and 2-amino-1,3,4-thiadiazole moeity decreasing the electron density, thereby decreasing the energy of HOMO, and the presence of imidazothiadiazole moiety should improve the antibacterial activity. Thus, the newly synthesized compounds were evaluated for their anti-bacterial activity against (ATCC 25923), (ATCC 10987), (ATCC 274,) and (SM514). The structure of the newly synthesized compounds was confirmed by elemental analysis and spectroscopic data. PMID:26690393

  15. Activation of 7-Silanorbornadienes by N-Heterocyclic Carbenes: A Selective Way to N-Heterocyclic-Carbene-Stabilized Silylenes.

    PubMed

    Lutters, Dennis; Severin, Claudia; Schmidtmann, Marc; Müller, Thomas

    2016-05-11

    The synthesis of hydridosilylenes Ter(H)Si: 3a (Ter: 2,6-bis(2,4,6-trimethylphenyl)phenyl) and Ter*(H)Si: 3b (Ter*: 2,6-bis(2,4,6-triiso-propylphenyl)phenyl) stabilized by the N-heterocyclic carbene (NHC) ImMe4 is reported. The synthesis of stabilized hydridosilylenes 3 was accomplished by a previously unknown NHC-induced fragmentation of silanorbornadiene derivatives. Structural studies of the stabilized silylenes 3 and of its Fe(CO)4 complex 12 accompanied by a theoretical analysis of their bonding situation indicate that stabilized silylenes such as 3 can be regarded as neutral silyl anion equivalents. A computational investigation of the reaction course indicate a virtual one-step reaction between the NHC and the silanorbornadiene. A theoretical assessment of the scope and limitations of this reaction suggests that it is general and can be used also for the synthesis of other carbene analogues such as germylenes and phosphinidenes. PMID:27120697

  16. Electrophilic Activation of P-Alkynes in the Synthesis of P-Substituted and P-Centered Heterocycles.

    PubMed

    Gupta, Akhil; Flynn, Bernard L

    2016-05-20

    Electrophilic activation of alkynylphosphine oxides and phosphonates provides a novel approach to the synthesis of P-substituted and P-centered heterocycles. Iodocyclization affords a heteroaryl iodide that can, among other things, be used in reiterative alkyne coupling and iodocyclization to give cyclic phosphonates and other cyclization reactions to give π-rich P-heterocycles. PMID:27088459

  17. Mind Molecules

    PubMed Central

    Snyder, Solomon H.

    2011-01-01

    Scientific styles vary tremendously. For me, research is largely about the unfettered pursuit of novel ideas and experiments that can test multiple ideas in a day, not a year, an approach that I learned from my mentor Julius “Julie” Axelrod. This focus on creative conceptualizations has been my métier since working in the summers during medical school at the National Institutes of Health, during my two years in the Axelrod laboratory, and throughout my forty-five years at Johns Hopkins University School of Medicine. Equally important has been the “high” that emerges from brainstorming with my students. Nothing can compare with the eureka moments when, together, we sense new insights and, better yet, when high-risk, high-payoff experiments succeed. Although I have studied many different questions over the years, a common theme emerges: simple biochemical approaches to understanding molecular messengers, usually small molecules. Equally important has been identifying, purifying, and cloning the messengers' relevant biosynthetic, degradative, or target proteins, at all times seeking potential therapeutic relevance in the form of drugs. In the interests of brevity, this Reflections article is highly selective, and, with a few exceptions, literature citations are only of findings of our laboratory that illustrate notable themes. PMID:21543333

  18. Identification of Biologically Active, HIV TAR RNA-Binding Small Molecules Using Small Molecule Microarrays

    PubMed Central

    2015-01-01

    Identifying small molecules that selectively bind to structured RNA motifs remains an important challenge in developing potent and specific therapeutics. Most strategies to find RNA-binding molecules have identified highly charged compounds or aminoglycosides that commonly have modest selectivity. Here we demonstrate a strategy to screen a large unbiased library of druglike small molecules in a microarray format against an RNA target. This approach has enabled the identification of a novel chemotype that selectively targets the HIV transactivation response (TAR) RNA hairpin in a manner not dependent on cationic charge. Thienopyridine 4 binds to and stabilizes the TAR hairpin with a Kd of 2.4 μM. Structure–activity relationships demonstrate that this compound achieves activity through hydrophobic and aromatic substituents on a heterocyclic core, rather than cationic groups typically required. Selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) analysis was performed on a 365-nucleotide sequence derived from the 5′ untranslated region (UTR) of the HIV-1 genome to determine global structural changes in the presence of the molecule. Importantly, the interaction of compound 4 can be mapped to the TAR hairpin without broadly disrupting any other structured elements of the 5′ UTR. Cell-based anti-HIV assays indicated that 4 inhibits HIV-induced cytopathicity in T lymphocytes with an EC50 of 28 μM, while cytotoxicity was not observed at concentrations approaching 1 mM. PMID:24820959

  19. Pyridylidene ligand facilitates gold-catalyzed oxidative C–H arylation of heterocycles

    PubMed Central

    Hata, Kazuhiro; Ito, Hideto

    2015-01-01

    Summary Triaryl-2-pyridylidene effectively facilitates the gold-catalyzed oxidative C–H arylation of heteroarenes with arylsilanes as a unique electron-donating ligand on gold. The employment of the 2-pyridylidene ligand, which is one of the strongest electron-donating N-heterocyclic carbenes, resulted in the rate acceleration of the C–H arylation reaction of heterocycles over conventional ligands such as triphenylphosphine and a classical N-heterocyclic carbene. In situ observation and isolation of the 2-pyridylidene-gold(III) species, as well as a DFT study, indicated unusual stability of gold(III) species stabilized by strong electron donation from the 2-pyridylidene ligand. Thus, the gold(I)-to-gold(III) oxidation process is thought to be facilitated by the highly electron-donating 2-pyridylidene ligand. PMID:26877796

  20. Synthesis, Evaluation of Anticancer Activity and QSAR Study of Heterocyclic Esters of Caffeic Acid

    PubMed Central

    Hajmohamad Ebrahim Ketabforoosh, Shima; Amini, Mohsen; Vosooghi, Mohsen; Shafiee, Abbas; Azizi, Ebrahim; Kobarfard, Farzad

    2013-01-01

    Caffeic acid phenethyl ester (CAPE) suppresses the growth of transformed cells such as human breast cancer cells, hepatocarcinoma , myeloid leukemia, colorectal cancer cells, fibrosarcoma, glioma and melanoma. A group of heterocyclic esters of caffeic acid was synthesized using Mitsunobu reaction and the esters were subjected to further structural modification by electrooxidation of the catechol ring of caffeic acid esters in the presence of sodium benzenesulfinate and sodium toluensulfinate as nucleophiles. Both heterocyclic esters of caffeic acid and their arylsulfonyl derivatives were evaluated for their cytotoxic activity against HeLa, SK-OV-3, and HT-29 cancer cell lines. HeLa cells showed the highest sensitivity to the compounds and heterocyclic esters with no substituent on catechol ring showed better activity compared to their substituted counterparts. QSAR studies reemphasized the importance of molecular shape of the compounds for their cytotoxic activity. PMID:24523750

  1. Fusing porphyrins with polycyclic aromatic hydrocarbons and heterocycles for optoelectronic applications

    SciTech Connect

    Thompson, Mark E.; Diev, Viacheslav; Hanson, Kenneth; Forrest, Stephen R.

    2015-08-18

    A compound that can be used as a donor material in organic photovoltaic devices comprising a non-activated porphyrin fused with one or more non-activated polycyclic aromatic rings or one or more non-activated heterocyclic rings can be obtained by a thermal fusion process. The compounds can include structures of Formula I: ##STR00001## By heating the reaction mixture of non-activated porphyrins with non-activated polycyclic aromatic rings or heterocyclic rings to a fusion temperature and holding for a predetermined time, fusion of one or more polycyclic rings or heterocyclic rings to the non-activated porphyrin core in meso,.beta. fashion is achieved resulting in hybrid structures containing a distorted porphyrin ring with annulated aromatic rings. The porphyrin core can be olygoporphyrins.

  2. Dearomatization Reactions of N-Heterocycles Mediated by Group 3 Complexes

    SciTech Connect

    Miller, Kevin L; Williams, Bryan N; Benitez, Diego; Carver, Colin T; Ogilby, Kevin R; Tkatchouk, Ekaterina; Goddard, William A; Diaconescu, Paula L

    2010-01-13

    Group 3 (Sc, Y, Lu, La) benzyl complexes supported by a ferrocene diamide ligand are reactive toward aromatic N-heterocycles by mediating their coupling and, in a few cases, the cleavage of their C-N bonds. When these complexes reacted with 2,2'-bipyridine or isoquinoline, they facilitated the alkyl migration of the benzyl ligand onto the pyridine ring, a process accompanied by the dearomatization of the N-heterocycle. The products of the alkyl-transfer reactions act as hydrogen donors in the presence of aromatic N-heterocycles, ketones, and azobenzene. Experimental and computational studies suggest that the hydrogen transfer takes place through a concerted mechanism. An interesting disproportionation reaction of the dearomatized, alkyl-substituted isoquinoline complexes is also reported.

  3. Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams

    NASA Astrophysics Data System (ADS)

    Behenna, Douglas C.; Liu, Yiyang; Yurino, Taiga; Kim, Jimin; White, David E.; Virgil, Scott C.; Stoltz, Brian M.

    2012-02-01

    The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures.

  4. Food heating and the formation of heterocyclic aromatic amine mutagens/carcinogens

    SciTech Connect

    Knize, M.G.; Salmon, C.P.; Felton, J.S.

    1997-12-31

    Several heterocyclic amines that are mutagenic and carcinogenic have been found as cooking products of muscle meats and some grain-based foods. Amounts in meats range from undetectable levels (less than 0.5 ppb) after boiling, microwave-cooking, and baking, to tens to hundreds of ppb for frying/grilling at high temperatures. A mutagenic response, believed to be caused by aromatic amines, was shown with some toasted foods, but the identity of the mutagenic chemicals are different from those found in meats. The airborne products from cooking also contain many of the same heterocyclic amines. Commercial cooking generally forms less of the heterocyclic amines than home cooking due to industry cooking practices.

  5. Ligand-Promoted Meta-C-H Arylation of Anilines, Phenols, and Heterocycles.

    PubMed

    Wang, Peng; Farmer, Marcus E; Huo, Xing; Jain, Pankaj; Shen, Peng-Xiang; Ishoey, Mette; Bradner, James E; Wisniewski, Steven R; Eastgate, Martin D; Yu, Jin-Quan

    2016-07-27

    Here we report the development of a versatile 3-acetylamino-2-hydroxypyridine class of ligands that promote meta-C-H arylation of anilines, heterocyclic aromatic amines, phenols, and 2-benzyl heterocycles using norbornene as a transient mediator. More than 120 examples are presented, demonstrating this ligand scaffold enables a wide substrate and coupling partner scope. Meta-C-H arylation with heterocyclic aryl iodides as coupling partners is also realized for the first time using this ligand. The utility for this transformation for drug discovery is showcased by allowing the meta-C-H arylation of a lenalidomide derivative. The first steps toward a silver-free protocol for this reaction are also demonstrated. PMID:27384126

  6. Structural and spectral comparisons between isomeric benzisothiazole and benzothiazole based aromatic heterocyclic dyes

    NASA Astrophysics Data System (ADS)

    Wang, Yin-Ge; Wang, Yue-Hua; Tao, Tao; Qian, Hui-Fen; Huang, Wei

    2015-09-01

    A pair of isomeric heterocyclic compounds, namely 3-amino-5-nitro-[2,1]-benzisothiazole and 2-amino-6-nitrobenzothiazole, are used as the diazonium components to couple with two N-substituted 4-aminobenzene derivatives. As a result, two pairs of isomeric aromatic heterocyclic azo dyes have been produced and they are structurally and spectrally characterized and compared including single-crystal structures, electronic spectra, solvatochromism and reversible acid-base discoloration, thermal stability and theoretically calculations. It is concluded that both benzisothiazole and benzothiazole based dyes show planar molecular structures and offset π-π stacking interactions, solvatochromism and reversible acid-base discoloration. Furthermore, benzisothiazole based aromatic heterocyclic dyes exhibit higher thermal stability, larger solvatochromic effects and maximum absorption wavelengths than corresponding benzothiazole based ones, which can be explained successfully by the differences of their calculated isomerization energy, dipole moment and molecular band gaps.

  7. Selective Release of Aromatic Heterocycles from Ruthenium Tris(2-pyridylmethyl)amine with Visible Light

    PubMed Central

    Li, Ao; White, Jessica K.; Arora, Karan; Herroon, Mackenzie K.; Martin, Philip D.; Schlegel, H. Bernhard; Podgorski, Izabela; Turro, Claudia; Kodanko, Jeremy J.

    2016-01-01

    Three complexes of the general formula [Ru(TPA)L2](PF6)2 [TPA = tris(2-pyridylmethyl)amine], where L = pyridine (1), nicotinamide (2), and imidazole (3), were prepared and characterized spectroscopically. X-ray crystallographic data were obtained for 1 and 3. Complexes 1–3 show strong absorption in the visible region and selective release of heterocycles upon irradiation with visible light. Time-dependent density functional theory calculations are consistent with the presence of singlet metal-to-ligand charge-transfer bands in the visible region in 1–3. Caged heterocycles 1–3 are highly stable in solution in the dark, including in cell growth media. Cell viability data show no signs of toxicity of 1–3 against PC-3 cells at concentrations up to 100 μM under light and dark conditions, consistent with Ru(TPA) acting as a nontoxic and effective photocaging group for aromatic heterocycles. PMID:26670781

  8. Synthesis and Selective Cytotoxic Activities on Rhabdomyosarcoma and Noncancerous Cells of Some Heterocyclic Chalcones.

    PubMed

    Do, Tuong-Ha; Nguyen, Dai-Minh; Truong, Van-Dat; Do, Thi-Hong-Tuoi; Le, Minh-Tri; Pham, Thanh-Quan; Thai, Khac-Minh; Tran, Thanh-Dao

    2016-01-01

    Chemically diverse heterocyclic chalcones were prepared and evaluated for cytotoxicity, aiming to push forward potency and selectivity. They were tested against rhabdomyosarcoma (RMS) and noncancerous cell line (LLC-PK1). The influence of heteroaryl patterns on rings A and B was studied. Heterocycle functionalities on both rings, such as phenothiazine, thiophene, furan and pyridine were evaluated. Notably, the introduction of three methoxy groups at positions 3, 4, 5 on ring B appears to be critical for cytotoxicity. The best compound, with potent and selective cytotoxicity (IC50 = 12.51 μM in comparison with the value 10.84 μM of paclitaxel), contains a phenothiazine moiety on ring A and a thiophene heterocycle on ring B. Most of the potential compounds only show weak cytoxicity on the noncancerous cell line LLC-PK1. PMID:27005608

  9. Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams.

    PubMed

    Behenna, Douglas C; Liu, Yiyang; Yurino, Taiga; Kim, Jimin; White, David E; Virgil, Scott C; Stoltz, Brian M

    2012-02-01

    The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures. PMID:22270628

  10. Heterocyclic N-Oxides – An Emerging Class of Therapeutic Agents

    PubMed Central

    Mfuh, Adelphe M.; Larionov, Oleg V.

    2016-01-01

    Heterocyclic N-oxides have emerged as potent compounds with anticancer, antibacterial, antihypertensive, antiparasitic, anti-HIV, anti-inflammatory, herbicidal, neuroprotective, and procognitive activities. The N-oxide motif has been successfully employed in a number of recent drug development projects. This review surveys the emergence of this scaffold in the mainstream medicinal chemistry with a focus on the discovery of the heterocyclic N-oxide drugs, N-oxide-specific mechanisms of action, drug-receptor interactions and synthetic avenues to these compounds. As the first review on this subject that covers the developments since 1950s to date, it is expected that it will inspire wider implementation of the heterocyclic N-oxide motif in the rational design of new medicinal agents. PMID:26087764

  11. Seasonal variations of atmospheric heterocyclic aromatic amines in Beijing, China

    NASA Astrophysics Data System (ADS)

    Dong, Xueling; Liu, Dameng; Gao, Shaopeng

    2013-02-01

    Heterocyclic aromatic amines (HAAs) belong to a group of substances associated with a high mutagenic and carcinogenic potential. This study reports that carcinogenic HAAs may be present in airborne particles. Airborne particles (PM10) were sampled from March 2005 to January 2006 at four urban sites in Beijing. Collected particulate matter was analyzed for six HAAs using high-performance liquid chromatography (HPLC) with fluorescence and UV detection. Clear seasonal variations of HAAs were observed with seasonal mass concentrations ranging from 0.66 ± 0.20 ng m- 3 (summer) to 19.76 ± 14.38 ng m- 3 (autumn). The carcinogenic amino-imidazo-azaarenes, including 2-Amino-3-methyl-3H-imidazo[4,5-f] quinoline (IQ), 2-Amino-3,4-dimethyl-3H-imidazo[4,5-f] quinoline (MeIQ), and 2-Amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP), were the major components with 75.2-87.0% of the total HAAs during the whole year except for summer. 3-Amino-1-methyl-5H-pyrido[3,4-b] indole (Trp-P-2), 2-Amino-9H-pyrido[2,3-b] indole (AαC), and 2-Amino-3-methyl-9H-pyrido[2,3-b] indole (MeAαC), with similar structures, were found to have similar seasonal patterns and strong correlations (r = 0.63-0.90) throughout the observation, which indicates that they most likely come from similar emission sources. Positive correlations between site-specific HAA concentrations and the relative humidity were observed. Of the different sites studied, the total HAA concentrations were most abundant at commercial sites and the smallest at residential sites. The combustion aerosols emitted from cooking, coal, and petroleum may be the sources of these carcinogens in the atmosphere, and cooking emissions may probably play an important role in Beijing's HAAs pollution.

  12. Analysis of cooked foods for new heterocyclic aromatic amines

    SciTech Connect

    Knize, M.G.; Felton, J.S.

    1997-12-31

    Heterocyclic aromatic amines (HAA), which are formed in meats during cooking, are a potential dietary health hazard as they are potent mutagens in bacterial test systems and carcinogens in laboratory animals. Several novel HAA have been (partially) characterized in cooked foods: dimethylimidazopyridine (DMIP), a trimethylimidazopyridine (TMIP), and dimethylimidazofuropyridine (IFP). A solid-phase-extraction method for the analysis of these compounds was developed. Samples were homogenized in 0.1 M HCl:CH3OH (7:3), centrifuged and the supernatant applied to a C18 cartridge coupled to an SCX cartridge. The C18 cartridge trapped contaminants while allowing the HAA to pass to the SCX cartridge where they were retained. The C18 cartridge was discarded, while the SCX cartridge was washed sequentially with 0.1 M HCl, CH3OH, water, and 1 M CH3COONH4. HAA were eluted with CH3OH:NH4OH (9:1), dried under nitrogen, redissolved in CH2Cl2:CH3OH (19:1), and applied to a PRS cartridge. The PRS cartridge was washed with 0.1 M HCl, 0.1 M HCl:CH3OH (3:2), and water before elution with CH3OH:NH4OH (9:1). The purified extract was analyzed by reversed phase HPLC with UV and fluorescence detection. The presence of DMIP, 1,5,6-TMIP, and IFP was detected in grilled and pan-fried ground beef. Recoveries of the new HAA for this extraction procedure will be presented.

  13. Structural properties of poly C-scleroglucan complexes.

    PubMed

    Sletmoen, Marit; Stokke, Bjørn T

    2005-10-15

    Successive changes of solvent conditions can be used to dissociate and reassociate the triple-helical structure of (1,3)-beta-D-glucans. Ultramicroscopic techniques have revealed a blend of circular and other structures following renaturation. When this solvent exchange process is carried out in the presence of certain polynucleotides, the process creates a novel macromolecular complex. Here, we use size exclusion chromatography (SEC) to study such (1,3)-beta-D-glucan-polynucleotide complexes. Online multi-angle laser-light scattering (MALLS) and refractive index (RI) detectors allowed determination of molecular weight and radius of gyration of the molecules. An ultraviolet (UV) detector allowed specific detection of the polynucleotide. The poly-cytidylic acid (poly C) shifted to coelution with the linear fraction of the scleroglucan following the renaturation of poly C-scleroglucan blends, indicating that poly C is incorporated in linear, but not in circular, structures of scleroglucan. This conclusion was consistent with AFM topographs that revealed a decreased fraction of circular structures upon addition of poly C during the renaturation process. The combined information about radius of gyration (R(g)) and molecular weight (M(w)) allowed us to conclude that the poly C-scleroglucan complexes are more dense and have a higher persistence length than linear scleroglucan triple helixes. The experimentally determined mass per unit length was used as a basis for elucidating possible molecular arrangements within the poly C-scleroglucan complex. PMID:16013056

  14. Reactions of organonitrogen molecules with Ni(100)

    SciTech Connect

    Schoofs, G.R.; Benziger, J.B.

    1988-02-11

    The adsorption and reaction of a variety of organonitrogen compounds on a Ni(100) surface have been examined with temperature-programmed reaction. Auger electron spectroscopy, and infrared spectroscopy. Monomethylamine adsorbs via the nitrogen lone pair of electrons and then undergoes C-N bond scission yielding adsorbed carbon, dihydrogen, and ammonia. Aniline ..pi..-bonds to the surface and polymerizes to form a thermally stable poly(aniline) surface film. Pyridine undergoes a temperature-induced orientational transformation. At low temperatures pyridine adsorbs with its ring parallel to the surface. At higher temperatures it appears to form an ..cap alpha..-pyridyl species with an activation barrier of 85 kJ/mol. Methyl groups on 2,6-lutidine sterically hinder this reaction. Methyl groups on 3,5-lutidine stabilize bonding via the nitrogen lone pair of electrons. The methyl groups on 3,5-lutidine increase electrophilic addition activity relative to pyridine and lead to polymerization of 3,5-lutidine, forming a thermally stable polymer film. Pyrimidine reacted in almost identical fashion to pyridine, suggesting that increased nucleophilic activity had little effect on the reaction behavior of heterocyclic compounds and that electrophilic reactions predominate.

  15. Stille Catalyst-Transfer Polycondensation Using Pd-PEPPSI-IPr for High-Molecular-Weight Regioregular Poly(3-hexylthiophene).

    PubMed

    Qiu, Yunyan; Mohin, Jacob; Tsai, Chia-Hua; Tristram-Nagle, Stephanie; Gil, Roberto R; Kowalewski, Tomasz; Noonan, Kevin J T

    2015-05-01

    A commercially available palladium N-heterocyclic carbene (Pd-NHC) precatalyst is used to initiate chain-growth polymerization of 2-bromo-3-hexyl-5-trimethylstannylthiophene. The molecular weight of the resultant poly(3-hexylthiophene) can be modulated (7 to 73 kDa, Đ = 1.14 to 1.53) by varying the catalyst concentration. Mass spectrometry data confirm control over the polymer end groups and (1)H NMR spectroscopy reveals that the palladium catalyst is capable of "ring-walking". A linear relationship between Mn and monomer conversion is observed. Atomic force microscopy and X-ray scattering verify the regioregular nature of the resultant polythiophene. PMID:25757046

  16. Synthesis and optimization of N-heterocyclic pyridinones as catechol-O-methyltransferase (COMT) inhibitors.

    PubMed

    Zhao, Zhijian; Harrison, Scott T; Schubert, Jeffrey W; Sanders, John M; Polsky-Fisher, Stacey; Zhang, Nanyan Rena; McLoughlin, Debra; Gibson, Christopher R; Robinson, Ronald G; Sachs, Nancy A; Kandebo, Monika; Yao, Lihang; Smith, Sean M; Hutson, Pete H; Wolkenberg, Scott E; Barrow, James C

    2016-06-15

    A series of N-heterocyclic pyridinone catechol-O-methyltransferase (COMT) inhibitors were synthesized. Physicochemical properties, including ligand lipophilic efficiency (LLE) and clogP, were used to guide compound design and attempt to improve inhibitor pharmacokinetics. Incorporation of heterocyclic central rings provided improvements in physicochemical parameters but did not significantly reduce in vitro or in vivo clearance. Nevertheless, compound 11 was identified as a potent inhibitor with sufficient in vivo exposure to significantly affect the dopamine metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC), and indicate central COMT inhibition. PMID:27133481

  17. Synthesis and Evaluation of Heterocyclic Catechol Mimics as Inhibitors of Catechol-O-methyltransferase (COMT)

    PubMed Central

    2015-01-01

    3-Hydroxy-4-pyridinones and 5-hydroxy-4-pyrimidinones were identified as inhibitors of catechol-O-methyltransferase (COMT) in a high-throughput screen. These heterocyclic catechol mimics exhibit potent inhibition of the enzyme and an improved toxicity profile versus the marketed nitrocatechol inhibitors tolcapone and entacapone. Optimization of the series was aided by X-ray cocrystal structures of the novel inhibitors in complex with COMT and cofactors SAM and Mg2+. The crystal structures suggest a mechanism of inhibition for these heterocyclic inhibitors distinct from previously disclosed COMT inhibitors. PMID:25815153

  18. Formation and Human Risk of Carcinogenic Heterocyclic Amines Formed from Natural Precursors in Meat

    SciTech Connect

    Knize, M G; Felton, J S

    2004-11-22

    A group of heterocyclic amines that are mutagens and rodent carcinogens form when meat is cooked to medium and well-done states. The precursors of these compounds are natural meat components: creatinine, amino acids and sugars. Defined model systems of dry-heated precursors mimic the amounts and proportions of heterocyclic amines found in meat. Results from model systems and cooking experiments suggest ways to reduce their formation and, thus, to reduce human intake. Human cancer epidemiology studies related to consumption of well-done meat products are listed and compared.

  19. Genetically modified CHO cells for studying the genotoxicity of heterocyclic amines from cooked foods

    SciTech Connect

    Thompson, L.H.; Wu, R.W.; Felton, J.S.

    1995-07-01

    We have developed metabolically competent CHO cells to evaluate the genotoxicity associated with heterocyclic amines, such as those that are present in cooked foods. Into repair-deficient UV5 cells we introduced cDNAs for expressing cytochrome P450IA2 and acetyltransferases. We then genetically reverted these transformed lines to obtain matched metabolically competent repair-deficient/proficient lines. For a high mutagenic response, we find a requirement for acetyltransferase with IQ but not with PhIP. This system allows for both quantifying mutagenesis and analyzing the mutational spectra produced by heterocyclic amines.

  20. [Design, synthesis and 5-HT/NE dual reuptake inhibitory activity of aromatic heterocyclic arylamidine derivatives].

    PubMed

    Wen, Hui; Yang, Jing; Zhang, Jian-jun; Wang, Ya-fang; Ji, Cheng-xue; Yang, Guang-zhong

    2009-03-01

    Based on the pharmacophore information and the analysis of structure-activity relationship of SSRIs and SNRIs, a series of substituted aromatic heterocyclic arylamidine derivatives were designed and synthesized in order to search for lead compounds with dual activity. All of them were new compounds, and their structures were confirmed by 1H NMR and HRMS. Preliminary in vitro pharmacological tests showed that all target compounds exhibited 5-HT reuptake inhibitory activity and some compounds exhibited NE reuptake inhibitory activity. These aromatic heterocyclic arylamidine designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well. PMID:19449528

  1. Asymmetric Reduction of Lactam-Based β-Aminoacrylates. Synthesis of Heterocyclic β(2)-Amino Acids.

    PubMed

    Campello, Hugo Rego; Parker, Jeremy; Perry, Matthew; Ryberg, Per; Gallagher, Timothy

    2016-08-19

    The ability to affect asymmetric reduction of heterocyclic β-aminoacrylates 1 (n = 1-3) has been assessed with pyrrolidine and piperidone variants generating the corresponding N-heterocyclic β(2)-amino acids 3b and 5b with high enantioselectivity (≥97% ee) using a Rh/WALPHOS catalyst combination. The use of the carboxylic acid substrate was essential; the corresponding esters do undergo reduction but led to racemic products. The seven-ring azepanone variant (as the carboxylic acid 9b) underwent reduction, but only a minimal level of asymmetric induction was observed. PMID:27508307

  2. Enantioselective synthesis of chiral heterocycles containing both chroman and pyrazolone derivatives catalysed by a chiral squaramide.

    PubMed

    Li, Jun-Hua; Du, Da-Ming

    2015-05-28

    An efficient chiral squaramide-catalysed enantioselective Michael addition of pyrazolin-5-ones to 3-nitro-2H-chromenes for the synthesis of chiral heterocyclic systems containing both chroman and pyrazolone derivatives has been developed. This reaction afforded the desired products in high to excellent yields (up to 98%) with high enantioselectivities (up to 96%) and excellent diastereoselectivities (up to 99 : 1) under very low catalyst loading (0.2 mol%). This catalytic asymmetric reaction provides an efficient route toward the synthesis of chiral heterocyclic systems containing both chroman and pyrazolone derivatives, which possess potential pharmaceutical activities. PMID:25882378

  3. A Versatile, Traceless C-H Activation-Based Approach for the Synthesis of Heterocycles.

    PubMed

    Zhou, Shuguang; Wang, Jinhu; Zhang, Feifei; Song, Chao; Zhu, Jin

    2016-05-20

    A versatile, traceless C-H activation-based approach for the synthesis of diversified heterocycles is reported. Rh(III)-catalyzed, N-amino-directed C-H alkenylation generates either olefination products or indoles (in situ annulation) in an atom- and step-economic manner at room temperature. The remarkable reactivity endowed by this directing group enables scale-up of the reaction to a 10 g scale at a very low catalyst loading (0.01 mol %/0.1 mol %). Ex situ annulation of olefination product provides entry into an array of heterocycles. PMID:27135982

  4. Enantioselective synthesis of dialkylated N-heterocycles by palladium-catalyzed allylic alkylation.

    PubMed

    Numajiri, Yoshitaka; Jiménez-Osés, Gonzalo; Wang, Bo; Houk, K N; Stoltz, Brian M

    2015-03-01

    The enantioselective synthesis of α-disubstituted N-heterocyclic carbonyl compounds has been accomplished using palladium-catalyzed allylic alkylation. These catalytic conditions enable access to various heterocycles, such as morpholinone, thiomorpholinone, oxazolidin-4-one, 1,2-oxazepan-3-one, 1,3-oxazinan-4-one, and structurally related lactams, all bearing fully substituted α-positions. Broad functional group tolerance was explored at the α-position in the morpholinone series. We demonstrate the utility of this method by performing various transformations on our useful products to readily access a number of enantioenriched compounds. PMID:25714704

  5. Ionic Liquid Promoted Diazenylation of N-Heterocyclic Compounds with Aryltriazenes under Mild Conditions.

    PubMed

    Cao, Dawei; Zhang, Yonghong; Liu, Chenjiang; Wang, Bin; Sun, Yadong; Abdukadera, Ablimit; Hu, Haiyan; Liu, Qiang

    2016-05-01

    An efficient, mild, and metal-free approach to direct diazenylation of N-heterocyclic compounds with aryltriazenes using Brønsted ionic liquid as a promoter has been developed for the first time. Many N-heterocyclic azo compounds were synthesized in good to excellent yields at room temperature under an open atmosphere. Notably, the promoter 1,3-bis(4-sulfobutyl)-1H-imidazol-3-ium hydrogen sulfate could be conveniently recycled and reused with the same efficacies for at least four cycles. PMID:27096379

  6. Synthesis of α-substituted vinylsulfonium salts and their application as annulation reagents in the formation of epoxide- and cyclopropane-fused heterocycles.

    PubMed

    Matlock, Johnathan V; Fritz, Sven P; Harrison, Stephen A; Coe, Diane M; McGarrigle, Eoghan M; Aggarwal, Varinder K

    2014-11-01

    The discovery of new methods for the synthesis of classes of potentially bioactive molecules remains an important goal for synthetic chemists. Vinylsulfonium salts have been used for the synthesis of a wide variety of small heterocyclic motifs; however, further developments to this important class of reagents has been focused on reaction with new substrates rather than development of new vinylsulfonium salts. We herein report the synthesis of a range of α-substituted vinylsulfonium tetraphenylborates (10 examples) in a 3 step procedure from commercially available styrenes. The important role of the tetraphenylborate counterion on the stability and accessibility of the vinylsulfonium salts is also detailed. The α-substituted vinylsulfonium tetraphenylborates gave good to excellent yields in the epoxyannulation of β-amino ketones (15 examples) and the cyclopropanation of allylic amines (4 examples). Hydrogenation of an epoxyannulation product proceeded with good diastereoselectivity. PMID:25310872

  7. Tunable and Efficient White Light Phosphorescent Emission Based on Single Component N-Heterocyclic Carbene Platinum(II) Complexes.

    PubMed

    Bachmann, Michael; Suter, Dominik; Blacque, Olivier; Venkatesan, Koushik

    2016-05-16

    A new class of cyclometalated pyridine N-heterocyclic carbene (NHC) Pt(II) complexes with electronically different alkyne derivatives (C≡CR; R = C6H4C(CH3)3 (1), C6H5 (2), C6H4F (3), C6H3(CF3)2 (4)) as ancillary ligands were synthesized, and the consequences of the electronic properties of the different substituted phenylacetylene ligands on the phosphorescent emission efficiencies were studied, where C≡CC6H4C(CH3)3 = 4-tert-butylphenylacetylene, C≡CC6H5 = phenylacetylene, C≡CC6H4F = 4-fluorophenylacetylene, and C≡CC6H3(CF3)2 = 3,5-bis(trifluoromethyl)phenylacetylene. Structural characterization, electrochemistry, and photophysical investigations were performed for all four compounds. Moreover, the emission quantum efficiencies and wavelength emission intensities of the complexes were also recorded in different weight percents in poly(methyl methacrylate) films (PMMA) and evaluated in the CIE-1931 chromaticity diagram. The square planar coordination geometry with the alkynyl ligands was corroborated for complexes 1, 2, and 3 by single crystal X-ray diffraction studies. These complexes show tunable monomeric high energy triplet emission and an additional concentration-dependent low-energy excimer-based phosphorescence. While adopting weight percent concentrations between 15 and 25%, the two emission bands covering the entire visible spectrum were obtained with these particular complexes displaying the properties of an efficient white light triplet emitter with excellent CIE-1931 coordinates (0.31, 0.33). On the basis of the high luminescent quantum efficiency of over 50% for white light emission, these compounds could be potentially useful for white organic light-emitting diodes (WOLEDs) based applications. PMID:27135529

  8. High-resolution atomic force microscopy of duplex and triplex DNA molecules

    NASA Astrophysics Data System (ADS)

    Klinov, Dmitry; Dwir, Benjamin; Kapon, Eli; Borovok, Natalia; Molotsky, Tatiana; Kotlyar, Alexander

    2007-06-01

    Double-stranded poly(dG)-poly(dC) and triple-stranded poly(dG)-poly(dG)-poly(dC) DNA were deposited on the modified surface of highly oriented pyrolitic graphite (HOPG) and visualized using atomic force microscopy with high-resolution (radius of ~1 nm) tips. The high resolution attained by this technique enabled us to detect single-stranded regions in double-stranded poly(dG)-poly(dC) and double-stranded and single-stranded regions in poly(dG)-poly(dG)-poly(dC) triplexes, as well as to resolve the helical pitch of the triplex molecules. We could also follow the reaction of G-strand extension in poly(dG)-poly(dC) by the Klenow exo- fragment of DNA polymerase I. This approach to molecular visualization could serve as a useful tool for the investigation of irregular structures in canonical DNA and other biopolymers, as well as studies of the molecular mechanisms of DNA replication and transcription.

  9. New Palladium-Catalyzed Approaches to Heterocycles and Carbocycles

    SciTech Connect

    Qinhua Huang

    2004-12-19

    The tert-butylimines of o-(1-alkynyl)benzaldehydes and analogous pyridinecarbaldehydes have been cyclized under very mild reaction conditions in the presence of I{sub 2}, ICl, PhSeCl, PhSCl and p-O{sub 2}NC{sub 6}H{sub 4}SCl to give the corresponding halogen-, selenium- and sulfur-containing disubstituted isoquinolines and naphthyridines, respectively. Monosubstituted isoquinolines and naphthyridines have been synthesized by the metal-catalyzed ring closure of these same iminoalkynes. This methodology accommodates a variety of iminoalkynes and affords the anticipated heterocycles in moderate to excellent yields. The Pd(II)-catalyzed cyclization of 2-(1-alkynyl)arylaldimines in the presence of various alkenes provides an efficient way to synthesize a variety of 4-(1-alkenyl)-3-arylisoquinolines in moderate to excellent yields. The introduction of an ortho-methoxy group on the arylaldimine promotes the Pd-catalyzed cyclization and stabilizes the resulting Pd(II) intermediate, improving the yields of the isoquinoline products. Highly substituted naphthalenes have been synthesized by the palladium-catalyzed annulation of a variety of internal alkynes, in which two new carbon-carbon bonds are formed in a single step under relatively mild reaction conditions. This method has also been used to synthesize carbazoles, although a higher reaction temperature is necessary. The process involves arylpalladation of the alkyne, followed by intramolecular Heck olefination and double bond isomerization. This method accommodates a variety of functional groups and affords the anticipated highly substituted naphthalenes and carbazoles in good to excellent yields. Novel palladium migratiodarylation methodology for the synthesis of complex fused polycycles has been developed, in which one or more sequential Pd-catalyzed intramolecular migration processes involving C-H activation are employed. The chemistry works best with electron-rich aromatics, which is in agreement with the idea that

  10. N-heterocyclic phosphenium cations: syntheses and cycloaddition reactions.

    PubMed

    Caputo, Christine A; Price, Jacquelyn T; Jennings, Michael C; McDonald, Robert; Jones, Nathan D

    2008-07-14

    A series of trifluoromethanesulfonate (OTf) salts of N-heterocyclic phospheniums (NHP) bearing phenyl (1a), para-methoxyphenyl (1b), 2,6-diisopropylphenyl (1c) and mesityl (1d) substituents is reported. The compounds are made by a modification to a literature procedure that improves the overall yields for and by 15 and 23%, respectively. Two unwanted side-products in the synthesis of , the diammonium salt, [(2,6-iPr-C6H3)N(H)2CH2CH2N(H)2(2,6-iPr-C6H3)]Cl2 (4) and the bisphosphine (2,6-iPr-C6H3)N(PCl2)CH2CH2N(PCl2)(2,6-iPr-C6H3) (5), are crystallographically characterized, as is the intermediate cyclic chlorophosphine, C1PN(4-OMe-C6H4)CH2CH2N(4-OMe-C6H4) (3b). The phenyl-substituted NHP is fully characterized, including by X-ray crystallography, for the first time; this compound contains a short P-O contact of 2.1850(14) A. Cycloaddition reactions of with 2,3-dimethyl-1,3-butadiene give the expected spirocyclic phospholeniums, 7,8-dimethyl-1,4-diaryl-1,4-diaza-5-phopshoniaspiro[4.4]non-7-ene, as their OTf salts (6a-d), while reactions with N,N'-dimesityl-1,4-diaza-1,3-butadiene give, except in the case of , which is too bulky to react, the aza analogues, 1,4-dimesityl-6,9-diaryl-1,4,6,9-tetraaza-5-phosphoniaspiro[4.4]non-2-ene (7a, 7b and 7d). The sterically congested is in thermal equilibrium with and free diazadiene, and undergoes a substitution reaction with 2,3-dimethyl-1,3-butadiene to give . PMID:18580983

  11. Selective C-O Hydrogenolysis and Decarboxylation of Biomass-Derived Heterocyclic Compounds over Heterogeneous Catalysts

    NASA Astrophysics Data System (ADS)

    Chia, Mei

    The catalytic deoxygenation of biomass-derived compounds through selective C-O hydrogenolysis, catalytic transfer hydrogenation and lactonization, and decarboxylation to value-added chemicals over heterogeneous catalysts was examined under liquid phase reaction conditions. The reactions studied involve the conversion or production of heterocyclic compounds, specifically, cyclic ethers, lactones, and 2-pyrones. A bimetallic RhRe/C catalyst was found to be selective for the hydrogenolysis of secondary C-O bonds for a broad range cyclic ethers and polyols. Results from experimentally-observed reactivity trends, NH3 temperature-programmed desorption, fructose dehydration reaction studies, and first-principles density functional theory (DFT) calculations are consistent with the hypothesis of a bifunctional catalyst which facilitates acid-catalyzed ring-opening and dehydration coupled with metal-catalyzed hydrogenation. C-O hydrogenolysis and fructose dehydration activities were observed to decrease with an increase in reduction temperature and a decrease in the number of surface metallic Re atoms measured by in situ X-ray absorption spectroscopy. No C-O hydrogenolysis activity was detected over RhRe/C under water-free conditions. The activation of water molecules by Re atoms on the surface of metallic Rh is suggested to result in the formation of Bronsted acidity over RhRe/C. The catalytic transfer hydrogenation and lactonization of levulinic acid and its esters to gamma-valerolactone was accomplished through the Meerwein-Ponndorf-Verley reaction over metal oxide catalysts using secondary alcohols as the hydrogen donor. ZrO2 was a highly active material for CTH under batch and continuous flow reaction conditions; the initial activity of the catalyst was repeatedly regenerable by calcination in air, with no observable loss in catalytic activity. Lastly, the 2-pyrone, triacetic acid lactone, is shown to be a promising biorenewable platform chemical from which a wide range

  12. MICROWAVE IRRADIATION IN BENIGN SYNTHESIS OF HETEROCYCLES, NOBLE NANOMETALS AND NANOCOMPOSITES

    EPA Science Inventory

    A brief historic account of reactions involving microwave (MW) exposure of neat reactants or catalyzed by mineral support surfaces, such as alumina, silica, clay, or their ‘doped’ versions, for the rapid one-pot assembly of heterocyclic compounds [1] from in situ generated reacti...

  13. "Decarbonization" of an imino N-heterocyclic carbene via triple benzyl migration from hafnium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An imino N-heterocyclic carbene underwent three sequential benzyl migrations upon reaction with tetrabenzylhafnium, resulting in complete removal of the carbene carbon from the ligand. The resulting eneamido-amidinato hafnium complex showed alkene polymerization activity comparable to that of a prec...

  14. Greener Synthesis of N-Heterocycles via Sustainable Applications of Nano-Catalysts

    EPA Science Inventory

    A brief historic account of reactions involving microwave (MW) exposure of neat reactants or catalysis by mineral surfaces, such as alumina, silica, clay, or their ‘doped’ versions, for the rapid one-pot assembly of heterocyclic compounds from in situ generated reactive intermedi...

  15. Organometallic rhenium(III) chalcogenide clusters: coordination of N-heterocyclic carbenes.

    PubMed

    Durham, Jessica L; Wilson, Wade B; Huh, Daniel N; McDonald, Robert; Szczepura, Lisa F

    2015-07-01

    The preparation of rhenium based octahedral clusters containing N-heterocyclic carbenes is described. These represent the first examples of [M6(μ3-Q)8](n+) or [M6(μ3-X)8](n+) clusters to contain a carbene ligand of any type (NHC, Fischer or Schrock). Surprisingly, the NHC ligands attenuate their luminescent properties. PMID:26041404

  16. Interactions of aromatic amino acids with heterocyclic ligand: An IR spectroscopic study

    NASA Astrophysics Data System (ADS)

    Tyunina, E. Yu.; Badelin, V. G.; Tarasova, G. N.

    2015-09-01

    The interactions of L-phenylalanine and L-tryptophan with nicotinic acid and uracyl in an aqueous buffer solution at pH 7.35 were studied by IR spectroscopy. The contributions of various functional groups to the complexation of aromatic amino acids with heterocyclic ligands were determined from the IR spectra of the starting substances and their mixtures.

  17. Trifluoromethylallylation of Heterocyclic C-H Bonds with Allylic Carbonates under Rhodium Catalysis.

    PubMed

    Choi, Miji; Park, Jihye; Sharma, Satyasheel; Jo, Hyeim; Han, Sangil; Jeon, Mijin; Mishra, Neeraj Kumar; Han, Sang Hoon; Lee, Jong Suk; Kim, In Su

    2016-06-01

    The rhodium(III)-catalyzed γ-trifluoromethylallylation of various heterocyclic C-H bonds with CF3-substituted allylic carbonates is described. These reactions provide direct access to linear CF3-containing allyl frameworks with complete trans-selectivity via C-H bond activation followed by a formal SN-type reaction pathway. PMID:27187625

  18. N-heterocyclic carbenes--catalysts for the preparation of polyhedral silsesquioxanes.

    PubMed

    Koželj, Matjaž; Orel, Boris

    2013-07-14

    N-Heterocyclic carbenes could be used as powerful catalysts for the preparation of various polyhedral silsesquioxanes. NHCs also catalyze a rearrangement of existing cages and a scrambling between two different cages at a concentration as low as 1 mol%. PMID:23689470

  19. INFLUENCE OF LIGNIN ON THE ADSORPTION OF HETERO-CYCLIC AROMATIC AMINES BY INSOLUBLE FIBER

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The prevention of colon cancer by dietary fiber is widely discussed. One possible mechanism is by adsorbing carcinogens and transporting them out of the body. It was shown that several model dietary fibers are able to adsorb heterocyclic aromatic amines (HAAs), a group of carcinogens mostly found in...

  20. 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

  1. N-Heterocyclic Carbene-Catalyzed Alcohol Acetylation: An Organic Experiment Using Organocatalysis

    ERIC Educational Resources Information Center

    Morgan, John P.; Shrimp, Jonathan H.

    2014-01-01

    Undergraduate students in the teaching laboratory have successfully used N-heterocyclic carbenes (NHCs) as organocatalysts for the acetylation of primary alcohols, despite the high water sensitivity of uncomplexed ("free") NHCs. The free NHC readily reacted with chloroform, resulting in an air- and moisture-stable adduct that liberates…

  2. Copper N-Heterocyclic Carbene: A Catalyst for Aerobic Oxidation or Reduction Reactions.

    PubMed

    Zhan, Le-Wu; Han, Lei; Xing, Ping; Jiang, Biao

    2015-12-18

    Copper N-heterocyclic carbene complexes can be readily used as catalysts for both aerobic oxidation of alcohols to aldehydes and reduction of imines to amines. Our methodology is universal for aromatic substrates and shows versatile tolerance to potential cascade reactions. A one-pot tandem synthetic strategy could afford useful imines and secondary amines via an oxidation-reduction strategy. PMID:26633757

  3. Transition Metal-Participated Synthesis and Utilization of N-containing Heterocycles: Exploring for Nitrogen Sources.

    PubMed

    Gao, Mingchun; Xu, Bin

    2016-06-01

    This account aims to describe our recent efforts on the synthesis and utilization of N-containing heterocycles, where transition metals participate in the synthesis. A variety of nitrogen sources, including amines, amides, hydrazones, pyrimidines, isocyanides, and copper nitrate, have been disclosed for the synthesis of diverse bioactive and pharmacologically interesting N-containing heterocycles under the participation of transition metals. The well-known nitrogen sources, such as amines and amides, were used for the construction of indoles, isatins, and quinolones. Dihydrophthalazines, isoquinolines, indazoles, and pyrazoles were obtained from hydrazones, while various pyrimidine-containing heterocycles were afforded through regioselective C-H functionalizations using pyrimidine as the directing group. Recent research has focused on the chemistry of isocyanides to achieve several kinds of heterocyclic compounds with high efficiency under the catalysis of transition metals (Pd, Rh, Mn, Cu), through oxidative cyanation reactions, sequential isocyanide insertions into C-H, N-H, or O-H bonds, and tandem radical annulation. More recently, an efficient route to isoxazolines has been reported using copper nitrate as a novel nitrogen source. PMID:27230734

  4. STRUCTURE-TOXICITY RELATIONSHIPS OF SELECTED NITROGENOUS HETEROCYCLIC COMPOUNDS. 3. RELATIONS USING MOLECULAR CONNECTIVITY

    EPA Science Inventory

    The objective of this investigation was to examine the QSAR between cellular response and molecular connectivity indexes for a series of 24 mono- and dinitrogen heterocyclic compounds that increase in ring attachment and methyl substitution and that have possible isomeric differe...

  5. Diverse N-Heterocyclic Ring Systems via Aza-Heck Cyclizations of N-(Pentafluorobenzoyloxy)sulfonamides.

    PubMed

    Hazelden, Ian R; Ma, Xiaofeng; Langer, Thomas; Bower, John F

    2016-09-01

    Aza-Heck cyclizations initiated by oxidative addition of Pd(0) -catalysts into the N-O bond of N-(pentafluoro-benzoyloxy)sulfonamides are described. These studies, which encompass only the second class of aza-Heck reaction developed to date, provide direct access to diverse N-heterocyclic ring systems. PMID:27460965

  6. Carcinogenicity in mice and rats of heterocyclic amines in cooked foods

    SciTech Connect

    Ohgaki, H.; Hasegawa, H.; Kato, T.; Suenaga, M.; Ubukata, M.; Sato, S.; Takayama, S.; Sugimura, T.

    1986-01-01

    Carcinogenicities of mutagenic heterocyclic amines in cooked foods have been tested in CDF/sub 1/ mice and F344 rats of both sexes. Eight heterocyclic amines - Trp-P-1, Trp-P-2, Glu-P-1, Glu-P-2, MeA..cap alpha..C, A..cap alpha..C, IQ, and MeIQ - were given to mice and/or rats at 0.02 to 0.08% in the diet continuously. In mice, all heterocyclic amines tested were demonstrated to be carcinogenic. Hepatocellular carcinomas were induced in a high incidence in all groups treated with heterocyclic amines. Hemangioendothelial sarcomas were also induced by Glu-P-1, Glu-P-2, MeA..cap alpha..C, and A..cap alpha..C. Most hemangioendothelial sarcomas were located in the interscapular brown adipose tissue. In mice given IQ, forestomach and lung tumors were also observed in a high incidence. Carcinogenicity tests on MeIQ are ongoing, and interim data by week 83 show that MeIQ also induces forestomach tumors in addition to liver tumors. In rats, hepatocellular carcinomas were induced by Trp-P-1, Glu-P-1, Glu-P-2, and IQ. In rats given Glu-P-1, Glu-P-2, and IQ, adenocarcinomas in the small and large intestines, squamous cell carcinomas in the Zymbal gland and clitoral gland were also observed in a high incidence.

  7. Bifunctional N-heterocyclic carbene-catalyzed highly enantioselective synthesis of spirocyclic oxindolo-β-lactams.

    PubMed

    Zhang, Han-Ming; Gao, Zhong-Hua; Ye, Song

    2014-06-01

    The N-heterocyclic carbene-catalyzed Staudinger reaction of ketenes with isatin-derived ketimines was investigated. The bifunctional NHCs with a free hydroxyl group were demonstrated as efficient catalysts for the reaction, giving the corresponding spirocyclic oxindolo-β-lactams in high yields with excellent diastereo- and enantioselectivities. PMID:24856000

  8. Expanded substrate scope and catalyst optimization for the catalytic kinetic resolution of N-heterocycles.

    PubMed

    Hsieh, Sheng-Ying; Binanzer, Michael; Kreituss, Imants; Bode, Jeffrey W

    2012-09-14

    The scope, reactivity, and selectivity of the chiral hydroxamic acid-catalyzed kinetic resolution of chiral amines are improved by a new catalyst structure and a more environmentally friendly reaction protocol. In addition to increasing selectivity across all substrates, these conditions make possible the resolution of N-heterocycles containing lactams or other basic functional groups that can inhibit the catalyst. PMID:22842709

  9. Rapid Construction of (-)-Paroxetine and (-)-Femoxetine via N-Heterocyclic Carbene Catalyzed Homoenolate Addition to Nitroalkenes.

    PubMed

    White, Nicholas A; Ozboya, Kerem E; Flanigan, Darrin M; Rovis, Tomislav

    2014-04-01

    A concise enantioselective synthesis of (-)-paroxetine (Paxil) and (-)-femoxetine has been achieved. Key to these syntheses is a N-heterocyclic carbene catalyzed homoenolate addition to a nitroalkene followed by in situ reduction of the nitro-group to rapidly access δ-lactams. PMID:25485210

  10. Rapid Construction of (-)-Paroxetine and (-)-Femoxetine via N-Heterocyclic Carbene Catalyzed Homoenolate Addition to Nitroalkenes

    PubMed Central

    White, Nicholas A.; Ozboya, Kerem E.; Flanigan, Darrin M.

    2014-01-01

    A concise enantioselective synthesis of (-)-paroxetine (Paxil) and (-)-femoxetine has been achieved. Key to these syntheses is a N-heterocyclic carbene catalyzed homoenolate addition to a nitroalkene followed by in situ reduction of the nitro-group to rapidly access δ-lactams. PMID:25485210

  11. Converting cycloalkanones into N-heterocycles: formal synthesis of (-)-gephyrotoxin 287C.

    PubMed

    Pichette, Simon; Winter, Dana K; Lessard, Jean; Spino, Claude

    2013-12-20

    The photochemical rearrangement of N-activated lactams enables their ring contraction concomitant with the migration of a carbon onto a nitrogen atom. When coupled with the Beckmann rearrangement, this photochemical ring contraction converts cycloalkanones into N-heterocycles in a few steps and in a stereospecific manner. To showcase the method, we performed an efficient formal synthesis of (-)-gephyrotoxin 287C. PMID:24188015

  12. Bypassing the Limitations of Directed C–H Functionalizations of Heterocycles

    PubMed Central

    Liu, Yue-Jin; Xu, Hui; Kong, Wei-Jun; Shang, Ming; Dai, Hui-Xiong; Yu, Jin-Quan

    2014-01-01

    In directed C–H activation reactions, nitrogen and sulfur atoms present in heterocyclic substrates coordinate strongly with metal catalysts. This coordination, which can lead to catalyst poisoning or C–H functionalization at an undesired position, limits the application of C–H activation reactions in heterocycle-based drug discovery.1–5 Herein, we report a robust and synthetically useful reaction that overcomes the complications associated with performing C–H functionalization reactions on heterocycles. Our approach employs a simple N-methoxy amide group, which serves as both a directing group and an anionic ligand to promote the in situ generation of the reactive PdX2 (X = ArCONOMe) species from a Pd(0) source using air as the sole oxidant. In this way, the PdX2 species is inherently anchored in close proximity with the target C–H bond adjacent to CONHOMe group, thus avoiding the interference from various heterocycles. Remarkably, this reaction overrides the conventional positional selectivity patterns observed with substrates containing strongly coordinating heteroatoms, including nitrogen, sulfur, and phosphorus. Thus, this operationally simple aerobic reaction demonstrates the feasibility of bypassing a fundamental limitation that has long plagued applications of directed C–H activation in medicinal chemistry. PMID:25383516

  13. N-Heterocyclic carbene/Brønsted acid cooperative catalysis as a powerful tool in organic synthesis.

    PubMed

    De Vreese, Rob; D'hooghe, Matthias

    2012-01-01

    The interplay between metals and N-heterocyclic carbenes (NHCs) has provided a window of opportunities for the development of novel catalytic strategies within the past few years. The recent successful combination of Brønsted acids with NHCs has added a new dimension to the field of cooperative catalysis, enabling the stereoselective synthesis of functionalized pyrrolidin-2-ones as valuable scaffolds in heterocyclic chemistry. This Commentary will briefly highlight the concept of N-heterocyclic carbene/Brønsted acid cooperative catalysis as a new and powerful methodology in organic chemistry. PMID:22509208

  14. Specific antibody immobilization with biotin-poly(L-lysine)-g-poly(ethylene glycol) and protein A on microfluidic chips.

    PubMed

    Wen, Xiufang; He, Hongyan; Lee, L James

    2009-10-31

    Highly efficient antibody immobilization is crucial for conducting high-performance immunoassays such as enzyme-linked immunosorbent assay (ELISA) in microarray and microfluidic biochips. In this study, a biotin-poly(L-lysine)-g-poly(ethylene glycol) (biotin-PLL-g-PEG) and protein A-based technique was developed to immobilize antibody on the surface of poly(methyl methacrylate) (PMMA) microchannels. First, PMMA surface was activated by oxygen plasma, followed by poly(acrylic acid) (PAA) grafting to add functional carboxyl group for subsequent binding. After the biotin-PLL-g-PEG molecules reacted with carboxyl groups through the electrostatic interactions, biotinylated protein A was immobilized on the surface through a linking molecule, neutravidin. To evaluate the applicability of this novel immobilization strategy, human interferon-gamma (IFN-gamma) was used as a model protein. Since protein A could better control the immobilization orientation, and the combination of biotin-PLL-g-PEG and PLL-g-PEG could adjust the conformation of antibodies, antigen capture efficiency and detection signals were significantly improved on the microchips by using this strategy. The optimal grafting conditions were also experimentally determined: the biotin grafting ratio of 0.189 in the PLL-g-PEG molecule and the mixture ratio of 85% (biotin-PLL-g-PEG to PLL-g-PEG). This surface modification can be applied for targeted drug delivery, biosensor and other immunoassay applications. PMID:19647744

  15. Cationic 5-phosphonio-substituted N-heterocyclic carbenes.

    PubMed

    Schwedtmann, Kai; Schoemaker, Robin; Hennersdorf, Felix; Bauzá, Antonio; Frontera, Antonio; Weiss, Robert; Weigand, Jan J

    2016-07-28

    NHO (N-heterocyclic olefin) 35(+) of which the gold complex 36(+) is readily accessible via the reaction with AuCl(tht). PMID:27334553

  16. Bioactivation of Heterocyclic Aromatic Amines by UDP Glucuronosyltransferases.

    PubMed

    Cai, Tingting; Yao, Lihua; Turesky, Robert J

    2016-05-16

    2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAA) that arise during the burning of tobacco and cooking of meats. UDP-glucuronosyltransferases (UGT) detoxicate many procarcinogens and their metabolites. The genotoxic N-hydroxylated metabolite of AαC, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), undergoes glucuronidation to form the isomeric glucuronide (Gluc) conjugates N(2)-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HON(2)-Gluc) and O-(β-d-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AαC-HN(2)-O-Gluc). AαC-HON(2)-Gluc is a stable metabolite but AαC-HN(2)-O-Gluc is a biologically reactive intermediate, which covalently adducts to DNA at levels that are 20-fold higher than HONH-AαC. We measured the rates of formation of AαC-HON(2)-Gluc and AαC-HN(2)-O-Gluc in human organs: highest activity occurred with liver and kidney microsomes, and lesser activity was found with colon and rectum microsomes. AαC-HN(2)-O-Gluc formation was largely diminished in liver and kidney microsomes, by niflumic acid, a selective inhibitor UGT1A9. In contrast, AαC-HON(2)-Gluc formation was less affected and other UGT contribute to N(2)-glucuronidation of HONH-AαC. UGT were reported to catalyze the formation of isomeric Gluc conjugates at the N(2) and N3 atoms of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), the genotoxic metabolite of PhIP. However, we found that the N3-Gluc of HONH-PhIP also covalently bound to DNA at higher levels than HONH-PhIP. The product ion spectra of this Gluc conjugate acquired by ion trap mass spectrometry revealed that the Gluc moiety was linked to the oxygen atom of HONH-PhIP and not the N3 imidazole atom of the oxime tautomer of HONH-PhIP as was originally proposed. UGT1A9, an abundant UGT isoform expressed in human liver and kidney, preferentially forms the O-linked Gluc conjugates of HONH

  17. Chemoprevention of heterocyclic amine-induced mammary carcinogenesis in rats.

    PubMed

    Hirose, Masao; Nishikawa, Akiyoshi; Shibutani, Makoto; Imai, Toshio; Shirai, Tomoyuki

    2002-01-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most prevalent carcinogenic heterocyclic amines in the environment, targeting the colon, prostate, pancreas, and mammary gland in rodents. Chemopreventive effects of synthetic and naturally occurring compounds on PhIP-induced rat mammary carcinogenesis were investigated in a series of experiments. In a PhIP feeding model, groups of 20-21 female F344 rats each, were treated with 0.02% PhIP alone or PhIP plus 0.5% 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), 1% green tea catechins, 1% alpha-tocopherol, 0.1% ellagic acid, or 1% chlorophyllin, each in the diet, or 0.1% caffeine in drinking water for 52 weeks. To assess the mechanism of HTHQ and caffeine inhibition of PhIP-induced carcinogenesis, effects of these compound on the in vitro metabolic activation of PhIP were examined in the presence of S9 mix. In the next series of experiments, the PhIP intragastric dose model was applied to allow separate investigation of the effects of chemicals during the initiation and postinitiation periods. In these experiments, female Sprague-Dawley rats were given eight intragastric doses of 100 mg/kg body weight during the first 4-8 weeks for initiation. Either during initiation or after initiation, or only after initiation, animals were treated with either corn or perilla oil at doses of 5 and 20%, conjugated fatty acid derived from safflower oil (CFA-S) or perilla oil (CFA-P) at a dose of 1%, arctiin at doses of 0.02 and 0.2% in the diet, or sodium nitrite (NaNO(2)) at a dose of 0.2% in drinking water. In the PhIP feeding model, administration of PhIP alone for 52 weeks induced adenocarcinomas in 40% of rats, but the incidence was remarkably reduced to 5% by the simultaneous treatment with 0.5% HTHQ, a strong lipophilic phenolic antioxidant, or to 10% by 0.1% caffeine. Administration of 1% chlorophyllin exerted similar, albeit weaker, effects. alpha-Tocopherol at a dose of 0.5% only reduced the multiplicity of

  18. Fe N-Heterocyclic Carbene Complexes as Promising Photosensitizers.

    PubMed

    Liu, Yizhu; Persson, Petter; Sundström, Villy; Wärnmark, Kenneth

    2016-08-16

    The photophysics and photochemistry of transition metal complexes (TMCs) has long been a hot field of interdisciplinary research. Rich metal-based redox processes, together with a high variety in electronic configurations and excited-state dynamics, have rendered TMCs excellent candidates for interconversion between light, chemical, and electrical energies in intramolecular, supramolecular, and interfacial arrangements. In specific applications such as photocatalytic organic synthesis, photoelectrochemical cells, and light-driven supramolecular motors, light absorption by a TMC-based photosensitizer and subsequent excited-state energy or electron transfer constitute essential steps. In this context, TMCs based on rare and expensive metals, such as ruthenium and iridium, are frequently employed as photosensitizers, which is obviously not ideal for large-scale implementation. In the search for abundant and environmentally benign solutions, six-coordinate Fe(II) complexes (Fe(II)L6) have been widely considered as highly desirable alternatives. However, not much success has been achieved due to the extremely short-lived triplet metal-to-ligand charge transfer ((3)MLCT) excited state that is deactivated by low-lying metal-centered (MC) states on a 100 fs time scale. A fundamental strategy to design useful Fe-based photosensitizers is thus to destabilize the MC states relative to the (3)MLCT state by increasing the ligand field strength, with special focus on making eg σ* orbitals on the Fe center energetically less accessible. Previous efforts to directly transplant successful strategies from Ru(II)L6 complexes unfortunately met with limited success in this regard, despite their close chemical kinship. In this Account, we summarize recent promising results from our and other groups in utilizing strongly σ-donating N-heterocyclic carbene (NHC) ligands to make strong-field Fe(II)L6 complexes with significantly extended (3)MLCT lifetimes. Already some of the first

  19. A 'bottom up', ab initio computational approach to understanding fundamental photophysical processes in nitrogen containing heterocycles, DNA bases and base pairs.

    PubMed

    Marchetti, Barbara; Karsili, Tolga N V; Ashfold, Michael N R; Domcke, Wolfgang

    2016-07-27

    The availability of non-radiative decay mechanisms by which photoexcited molecules can revert to their ground electronic state, without experiencing potentially deleterious chemical transformation, is fundamental to molecular photostability. This Perspective Article combines results of new ab initio electronic structure calculations and prior experimental data in an effort to systematise trends in the non-radiative decay following UV excitation of selected families of heterocyclic molecules. We start with the prototypical uni- and bicyclic molecules phenol and indole, and explore the structural and photophysical consequences of incorporating progressively more nitrogen atoms within the respective ring structures en route to the DNA bases thymine, cytosine, adenine and guanine. For each of the latter, we identify low energy non-radiative decay pathways via conical intersections with the ground state potential energy surface accessed by out-of-plane ring deformations. This is followed by summary descriptions and illustrations of selected rival (electron driven H atom transfer) non-radiative excited state decay processes that demand consideration once the nucleobases are merely components in larger biomolecular systems like nucleosides, and both individual and stacked base-pairs. PMID:26980149

  20. Titanium-catalyzed multicomponent couplings: efficient one-pot syntheses of nitrogen heterocycles.

    PubMed

    Odom, Aaron L; McDaniel, Tanner J

    2015-11-17

    Nitrogen-based heterocycles are important frameworks for pharmaceuticals, natural products, organic dyes for solar cells, and many other applications. Catalysis for the formation of heterocyclic scaffolds, like many C-C and C-N bond-forming reactions, has focused on the use of rare, late transition metals like palladium and gold. Our group is interested in the use of Earth-abundant catalysts based on titanium to generate heterocycles using multicomponent coupling strategies, often in one-pot reactions. To be of maximal utility, the catalysts need to be easily prepared from inexpensive reagents, and that has been one guiding principle in the research. For this purpose, a series of easily prepared pyrrole-based ligands has been developed. Titanium imido complexes are known to catalyze the hydroamination of alkynes, and this reaction has been used to advantage in the production of α,β-unsaturated imines from 1,3-enynes and pyrroles from 1,4-diynes. Likewise, catalyst design can be used to find complexes applicable to hydrohydrazination, coupling of a hydrazine and alkyne, which is a method for the production of hydrazones. Many of the hydrazones synthesized are converted to indoles through Fischer cyclization by addition of a Lewis acid. However, more complex products are available in a single catalytic cycle through coupling of isonitriles, primary amines, and alkynes to give tautomers of 1,3-diimines, iminoamination (IA). The products of IA are useful intermediates for the one-pot synthesis of pyrazoles, pyrimidines, isoxazoles, quinolines, and 2-amino-3-cyanopyridines. The regioselectivity of the reactions is elucidated in some detail for some of these heterocycles. The 2-amino-3-cyanopyridines are synthesized through isolable intermediates, 1,2-dihydro-2-iminopyridines, which undergo Dimroth rearrangement driven by aromatization of the pyridine ring; the proposed mechanism of the reaction is discussed. The IA-based heterocyclic syntheses can be accomplished

  1. Tensile behaviour of blends of poly(vinylidene fluoride) with poly(methyl methacrylate)

    NASA Technical Reports Server (NTRS)

    Cebe, Peggy; Chung, Shirley Y.

    1990-01-01

    Blends of poly(vinylidene fluoride) (PVF2) and poly(methyl methacrylate) (PMMA) were prepared over a wide concentration range and tested in tension at the same relative temperature below the glass transition. In nearly all blends, under conditions favoring disentanglement, (decrease in strain rate, or increase in test temperature), the yield stress and drawing stress decreased while the breaking strain increased. For materials with about the same degree of crystallinity, those with a higher proportion of amorphous PVF2 exhibited brittle-like behavior as a result of interlamellar tie molecules. In the semicrystalline blends, yield stress remains high as the test temperature approaches Tg, whereas in the amorphous blends the yield stress falls to zero near Tg. Results of physical aging support the role of interlamellar ties which cause semicrystalline blends to exhibit aging at temperatures above Tg.

  2. N-Heterocyclic carbene-catalyzed [3+3] cyclocondensation of bromoenals with aldimines: highly enantioselective synthesis of dihydropyridinones.

    PubMed

    Gao, Zhong-Hua; Chen, Xiang-Yu; Zhang, Han-Ming; Ye, Song

    2015-08-01

    The N-heterocyclic carbene-catalyzed [3+3] cyclocondensation of bromoenals and aldimines was developed to give the corresponding dihydropyridinones in good yields with excellent enantioselectivities. PMID:26121224

  3. An insight into the mechanism of the aerobic oxidation of aldehydes catalyzed by N-heterocyclic carbenes.

    PubMed

    Bortolini, O; Chiappe, C; Fogagnolo, M; Giovannini, P P; Massi, A; Pomelli, C S; Ragno, D

    2014-02-25

    N-Heterocyclic carbene catalysis for the aerobic oxidation and esterification of aromatic aldehydes was monitored by ESI-MS (MS/MS) and the key intermediates were intercepted and characterized using the charge-tag strategy. PMID:24413829

  4. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions.

    PubMed Central

    D'Amours, D; Desnoyers, S; D'Silva, I; Poirier, G G

    1999-01-01

    Poly(ADP-ribosyl)ation is a post-translational modification of proteins. During this process, molecules of ADP-ribose are added successively on to acceptor proteins to form branched polymers. This modification is transient but very extensive in vivo, as polymer chains can reach more than 200 units on protein acceptors. The existence of the poly(ADP-ribose) polymer was first reported nearly 40 years ago. Since then, the importance of poly(ADP-ribose) synthesis has been established in many cellular processes. However, a clear and unified picture of the physiological role of poly(ADP-ribosyl)ation still remains to be established. The total dependence of poly(ADP-ribose) synthesis on DNA strand breaks strongly suggests that this post-translational modification is involved in the metabolism of nucleic acids. This view is also supported by the identification of direct protein-protein interactions involving poly(ADP-ribose) polymerase (113 kDa PARP), an enzyme catalysing the formation of poly(ADP-ribose), and key effectors of DNA repair, replication and transcription reactions. The presence of PARP in these multiprotein complexes, in addition to the actual poly(ADP-ribosyl)ation of some components of these complexes, clearly supports an important role for poly(ADP-ribosyl)ation reactions in DNA transactions. Accordingly, inhibition of poly(ADP-ribose) synthesis by any of several approaches and the analysis of PARP-deficient cells has revealed that the absence of poly(ADP-ribosyl)ation strongly affects DNA metabolism, most notably DNA repair. The recent identification of new poly(ADP-ribosyl)ating enzymes with distinct (non-standard) structures in eukaryotes and archaea has revealed a novel level of complexity in the regulation of poly(ADP-ribose) metabolism. PMID:10455009

  5. Dimeric aluminum-phosphorus compounds as masked frustrated Lewis pairs for small molecule activation.

    PubMed

    Roters, Steffi; Appelt, Christian; Westenberg, Hauke; Hepp, Alexander; Slootweg, J Chris; Lammertsma, Koop; Uhl, Werner

    2012-08-14

    Hydroalumination of aryldialkynylphosphines RP(C≡C-(t)Bu)(2) (R = Ph, Mes) with equimolar quantities of diethylaluminum hydride afforded mixed alkenyl-alkynyl cyclic dimers in which the dative aluminum-phosphorus bonds are geminal to the exocyclic alkenyl groups. Addition of triethylaluminum to isolated 1 (R = Ph) or to the in situ generated species (R = Mes) caused diethylaluminum ethynide elimination to yield the arylethylphosphorus dimers 2 and 3. These possess a chair-like Al(2)C(2)P(2) heterocycle with intermolecular Al-P interactions. The boat conformation (4) was obtained by the reaction of (t)Bu-P(C≡C-(t)Bu)(2) with di(tert-butyl)aluminum hydride. Despite being dimeric, 2 behaves as a frustrated Lewis pair and activates small molecules. The reaction with carbon dioxide gave cis/trans isomeric AlPC(2)O heterocycles that differ only by the configuration of the exocyclic alkenyl unit. Four isomers resulted from the reaction with phenyl isocyanate. This is caused by cis/trans isomerization of the initial C=O adduct and subsequent rearrangement to the AlPC(2)N heterocycle, being the C=N adduct. PMID:22411491

  6. Physics of Molecules

    NASA Astrophysics Data System (ADS)

    Williams, D.; Murdin, P.

    2000-11-01

    Many varieties of molecule have been detected in the Milky Way and in other galaxies. The processes by which these molecules are formed and destroyed are now broadly understood (see INTERSTELLAR CHEMISTRY). These molecules are important components of galaxies in two ways. Firstly, radiation emitted by molecules enables us to trace the presence of diffuse gas, to infer its physical properties and ...

  7. Stabilities of nitrogen containing heterocyclic radicals and geometrical influences on non-radiative processes in organic molecules

    NASA Technical Reports Server (NTRS)

    Evleth, E. M.

    1971-01-01

    Theoretical and experimental work on generating radicals by removal of a hydrogen atom from pyrrole, imidazole, indole, and carbazole is reported. Photophysical studies on indolizine and related aza-derivatives show that materials having large S2-S1 energy gaps might exhibit upper state fluorescence. Photodecomposition quantum yields of a series of sterically hindered p-aminobenzene diazonium cations in water were found structurally and wavelength dependent and unquenched in aqueous sodium bromide solutions. Photodecomposition of diazonium materials did not produce a metastable species with a longer lifetime than 1 msec.

  8. Carbon-carbon bond-forming reactions of α-thioaryl carbonyl compounds for the synthesis of complex heterocyclic molecules.

    PubMed

    Biggs-Houck, James E; Davis, Rebecca L; Wei, Jingqiang; Mercado, Brandon Q; Olmstead, Marilyn M; Tantillo, Dean J; Shaw, Jared T

    2012-01-01

    Strategies for the formation of carbon-carbon bonds from the α-thioaryl carbonyl products of substituted lactams are described. Although direct functionalization is possible, a two step process of oxidation and magnesium-sulfoxide exchange has proven optimal. The oxidation step results in the formation of two diastereomers that exhibit markedly different levels of stability toward elimination, which is rationalized on the basis of quantum mechanical calculations and X-ray crystallography. Treatment of the sulfoxide with i-PrMgCl results in the formation of a magnesium enolate that will undergo an intramolecular Michael addition reaction to form two new stereogenic centers. The relationship between the substitution patterns of the sulfoxide substrate and the efficiency of the magnesium exchange reaction are also described. PMID:22023077

  9. Expanding insight into asymmetric palladium-catalyzed allylic alkylation of N-heterocyclic molecules and cyclic ketones.

    PubMed

    Bennett, Nathan B; Duquette, Douglas C; Kim, Jimin; Liu, Wen-Bo; Marziale, Alexander N; Behenna, Douglas C; Virgil, Scott C; Stoltz, Brian M

    2013-04-01

    Eeny, meeny, miny ... enaminones! Lactams and imides have been shown to consistently provide enantioselectivities substantially higher than other substrate classes previously investigated in the palladium-catalyzed asymmetric decarboxylative allylic alkylation. Several new substrates have been designed to probe the contributions of electronic, steric, and stereoelectronic factors that distinguish the lactam/imide series as superior alkylation substrates (see scheme). These studies culminated in marked improvements on carbocyclic allylic alkylation substrates. PMID:23447555

  10. An exploratory study on the peroxyl-radical-scavenging activity of 2,6-dimethyl-5-hepten-2-ol and its heterocyclic analogues

    NASA Astrophysics Data System (ADS)

    Stobiecka, Agnieszka; Sikora, Magdalena; Bonikowski, Radosław; Kula, Józef

    2016-03-01

    The structural properties and radical scavenging activity of 2,6-dimethyl-5-hepten-2-ol (1) and its new heterocyclic analogues, i.e. 2-methyl-4-(5-methylfuran-2-yl)-butan-2-ol (2) and 2-methyl-4-(5-methylthiophen-2-yl)-butan-2-ol (3) and have been studied by using the experimental and theoretical methods for the first time. Activity of title compounds against the peroxyl radical was determined by using standard fluorimetric test, i.e. the Oxygen Radical Absorbance Capacity assay (ORACFL). Furthermore, the electron-donating ability of odorants has been evaluated by using colorimetric ABTS assay. According to the experimental results obtained from the ORACFL test 2,6-dimethyl-5-hepten-2-ol was characterized by the highest activity in comparison with the novel counterparts. Nevertheless, all investigated compounds exhibited pronounced anti-peroxyl radical activity comparable to that exerted by the one of the most prominent antioxidant among the monoterpene alcohols, i.e. by linalool. On the other hand, the title compounds exerted relatively low capacity to quench the radical cation of ABTS. Theoretical calculations based on the Density Functional Theory (DFT) method with the hybrid functional B3LYP were carried out in order to investigate selected structural and electronic properties including the geometrical parameters as well as the energy of frontier molecular orbitals of parent molecules and the resulting radicals. Furthermore, the possible mechanism of peroxyl-radical-scavenging has been determined by using the thermodynamic descriptors such as the bond dissociation enthalpies (BDEs) and ionization potentials (IPs). These theoretical data pointed out the relevance of HAT mechanism in the peroxyl-radical-scavenging exhibited by 2,6-dimethyl-5-hepten-2-ol and its new heterocyclic analogues in polar and non-polar medium.

  11. Metal-assisted red light-induced DNA cleavage by ternary L-methionine copper(II) complexes of planar heterocyclic bases.

    PubMed

    Patra, Ashis K; Dhar, Shanta; Nethaji, Munirathinam; Chakravarty, Akhil R

    2005-03-01

    Ternary copper(II) complexes [Cu(l-met)B(Solv)](ClO4) (1-4), where B is a N,N-donor heterocyclic base like 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3) and dipyrido[3,2-a:2'],3'-c]phenazene (dppz, 4), are prepared and their DNA binding and photo-induced DNA cleavage activity studied (L-Hmet =L-methionine). Complex 2, structurally characterized by X-ray crystallography, shows a square pyramidal (4 + 1) coordination geometry in which the N,O-donor L-methionine and N,N-donor heterocyclic base bind at the basal plane and a solvent molecule is coordinated at the axial site. The complexes display a d-d band at approximately 600 nm in DMF and exhibit a cyclic voltammetric response due to the Cu(II)/Cu(I) couple near -0.1 V in DMF-Tris-HCl buffer. The complexes display significant binding propensity to the calf thymus DNA in the order: 4(dppz) > 3(dpq) > 2(phen> 1(bpy). Control cleavage experiments using pUC19 supercoiled DNA and distamycin suggest major groove binding for the dppz and minor groove binding for the other complexes. Complexes 2-4 show efficient DNA cleavage activity on UV (365 nm) or red light (632.8 nm) irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. The DNA cleavage activity of the dpq complex is found to be significantly more than its dppz and phen analogues. PMID:15726142

  12. Experimental and computational studies on the mechanism of zwitterionic ring-opening polymerization of δ-valerolactone with N-heterocyclic carbenes.

    PubMed

    Acharya, Ashwin K; Chang, Young A; Jones, Gavin O; Rice, Julia E; Hedrick, James L; Horn, Hans W; Waymouth, Robert M

    2014-06-19

    Experimental and computational investigations of the zwitterionic ring-opening polymerization (ZROP) of δ-valerolactone (VL) catalyzed by the N-heterocyclic carbenes (NHC) 1,3-diisopropyl-4,5-dimethyl-imidazol-2-ylidene (1) and 1,3,4,5-tetramethyl-imidazol-2-ylidene (2) were carried out. The ZROP of δ-valerolactone generates cyclic poly(valerolactone)s whose molecular weights are higher than predicted from [VL]0/[NHC]0. Kinetic studies reveal the rate of polymerization is first order in [VL] and first order in [NHC]. Density functional theory (DFT) calculations were carried out to elucidate the key steps involved in the ring-opening of δ-valerolactone and its subsequent oligomerization. These studies have established that the initial steps of the mechanism involve nucleophilic attack of the NHC on δ-valerolactone to form a zwitterionic tetrahedral intermediate. DFT calculations indicate that the highest activation barrier of the entire mechanism is associated with the ring-opening of the tetrahedral intermediate formed from the NHC and δ-valerolactone, a result consistent with inefficient initiation to generate reactive zwitterions. The large barrier in this step is due to the fact that ring-opening requires a partial positive charge to develop next to the directly attached NHC moiety which already bears a delocalized positive charge. PMID:24702523

  13. Small polaron hopping transport along DNA molecules

    NASA Astrophysics Data System (ADS)

    Triberis, G. P.; Simserides, C.; Karavolas, V. C.

    2005-05-01

    We present a small polaron hopping model for interpreting the strong temperature (T) dependence of the electrical conductivity, σ, observed at high (h) temperatures along DNA molecules. The model takes into account the one-dimensional character of the system and the presence of disorder in the DNA double helix. Percolation-theoretical considerations lead to analytical expressions for the high temperature multiphonon-assisted small polaron hopping conductivity, the hopping distance and their temperature dependence. The experimental data for lambda phage DNA (λ-DNA) and poly(dA)-poly(dT) DNA follow nicely the theoretically predicted behaviour (lnσh~T-2/3). Moreover, our model leads to realistic values of the maximum hopping distances, supporting the idea of multiphonon-assisted hopping of small polarons between next nearest neighbours of the DNA molecular 'wire'. The low temperature case is also investigated.

  14. Single Molecule Raman Spectroscopy Under High Pressure

    NASA Astrophysics Data System (ADS)

    Fu, Yuanxi; Dlott, Dana

    2014-06-01

    Pressure effects on surface-enhanced Raman scattering spectra of Rhdoamine 6G adsorbed on silver nanoparticle surfaces was studied using a confocal Raman microscope. Colloidal silver nanoparticles were treated with Rhodamine 6G (R6G) and its isotopically substituted partner, R6G-d4. Mixed isotopomers let us identify single-molecule spectra, since multiple-molecule spectra would show vibrational transitions from both species. The nanoparticles were embedded into a poly vinyl alcohol film, and loaded into a diamond anvil cell for the high-pressure Raman scattering measurement. Argon was the pressure medium. Ambient pressure Raman scattering spectra showed few single-molecule spectra. At moderately high pressure ( 1GPa), a surprising effect was observed. The number of sites with observable spectra decreased dramatically, and most of the spectra that could be observed were due to single molecules. The effects of high pressure suppressed the multiple-molecule Raman sites, leaving only the single-molecule sites to be observed.

  15. Twisting motion dependent charge transport properties of poly(dG)-poly(dC) DNA molecular wire

    NASA Astrophysics Data System (ADS)

    Yudiarsah, E.; Suhendro, D. K.; Saleh, R.

    2014-09-01

    The effect of twisting motion of bases on charge transport properties of Poly(dG)-Poly(dC) DNA molecule have been studied. The effect is studied by taking into account twisting angle dependent on-site energy and hopping constant in the tight binding Hamiltonian of double-strand DNA model. The average kinetic energy of twisting motions is assumed to be proportional to system temperature. Transfer matrix method has been used in calculating the localization length of the molecule. The results show that increase in temperature shortens the localization length. The transmission probability of charge on the molecule was calculated using transfer and scattering matrix methods simultaneously on the DNA model sandwiched in between two metallic electrodes. The contacts between molecule and both electrodes were chosen such that the presence of metallic electrodes does not change the main features of transport properties of the molecule much. The temperature tends to widen the area with zero transmission around the Fermi energy. The I-V characteristic of the molecule connected to electrodes has been calculated from transmission probability within Landauer-Buttiker Formalism by assuming the voltage drops symmetrically at the contacts. The results show that temperature lowers the magnitude of the I-V characteristic and the differential conductance. In addition to that, the I-V characteristic and the differential conductance also decrease in magnitude with lowering the twisting frequency.

  16. Inhibitory effect of lichen constituents on mutagenicity induced by heterocyclic amines

    SciTech Connect

    Osawa, T.; Kumon, H.; Reece, C.A.; Shibamoto, T. )

    1991-01-01

    Physodic acid, one of the main constituents of Hypogymnia enteromorpha, inhibited the mutagenicity of indirect mutagens, including benzo(a)pyrene and heterocyclic amines in Salmonella typhimurium TA 98. In contrast, it was not effective against direct mutagens such as 6-nitropiperonal and adriamycin. Its antimutagenicity was not associated with free-radical scavenging or antioxidative activities. Physodic acid seemed to inhibit the formation of reactive metabolites, such as N-hydroxy-Trp-P-2, by blocking the hepatic microsomal oxidation systems. Another component of H. enteromorpha, physodalic acid, also inhibited mutagenicity of a heterocyclic amine, Trp-P-2, in S. typhimurium TA 98, even though it was reportedly mutagenic in S. typhimurium TA 100.

  17. Synthesis of Diverse Heterocyclic Scaffolds via Tandem Additions to Imine Derivatives and Ring-Forming Reactions

    PubMed Central

    Sunderhaus, James D.; Dockendorff, Chris; Martin, Stephen F.

    2009-01-01

    A novel strategy has been developed for the efficient syntheses of diverse arrays of heterocyclic compounds. The key elements of the approach comprise a Mannich-type, multicomponent coupling reaction in which functionalized amines, aromatic aldehydes, acylating agents, and π- and organometallic nucleophiles are combined to generate intermediates that are then further transformed into diverse heterocyclic scaffolds via a variety of cyclization manifolds. Significantly, many of these scaffolds bear functionality that may be exploited by further manipulation to create diverse collections of compounds having substructures found in biologically active natural products and clinically useful drugs. The practical utility of this strategy was exemplified by its application to the first, and extraordinarily concise synthesis of the isopavine alkaloid roelactamine. PMID:20625454

  18. Comparison of the activity of subsurface and surface microorganisms and their anaerobic transformation of heterocyclic compounds

    SciTech Connect

    Bollag, J.-M.

    1991-02-01

    Our interest in this research was mainly to compare the physiological characteristics of microorganisms derived from subsurface and surface environments and their ability to transform heterocyclic aromatic chemicals. We selected essentially indole and pyridine compounds as representatives of heterocyclic compounds. The samples investigated originated from the subsurface drillings at the Savannah River Plant, from surface samples in Pennsylvania, from municipal sewage of State College, Pennsylvania, and from pyridine-contaminated sites at Indianapolis. At different physiological conditions (aerobic, denitrifying, sulfate-reducing or methanogenic), different groups of microorganisms are active. Not only the thermodynamics of microbial physiology vary, but different metabolic pathways are used by the various types of microbial processes. Therefore, it was important to determine under which physiological conditions a compound was metabolized, and to clarify the metabolic conditions under which intermediate(s) were produced. 29 refs.

  19. Synthesis and Functionalization of Cyclic Sulfonimidamides: A Novel Chiral Heterocyclic Carboxylic Acid Bioisostere

    PubMed Central

    2012-01-01

    An efficient synthesis of aryl substituted cyclic sulfonimidamides designed as chiral nonplanar heterocyclic carboxylic acid bioisosteres is described. The cyclic sulfonimidamide ring system could be prepared in two steps from a trifluoroacetyl protected sulfinamide and methyl ester protected amino acids. By varying the amino acid, a range of different C-3 substituted sulfonimidamides could be prepared. The compounds could be further derivatized in the aryl ring using standard cross-coupling reactions to yield highly substituted cyclic sulfonimidamides in excellent yields. The physicochemical properties of the final compounds were examined and compared to those of the corresponding carboxylic acid and tetrazole derivatives. The unique nonplanar shape in combination with the relatively strong acidity (pKa 5–6) and the ease of modifying the chemical structure to fine-tune the physicochemical properties suggest that this heterocycle can be a valuable addition to the range of available carboxylic acid isosteres. PMID:24900513

  20. Difunctional and heterocyclic products from the ozonolysis of conjugated C sub 5 -C sub 8 cyclodienes

    SciTech Connect

    Griesbaum, K.; In Chan Jung; Mertens, H. )

    1990-11-23

    Ozonolyses of the conjugated C{sub 5}-C{sub 8} cyclodienes 1a-d in methanol, followed by reduction with DMS, have been examined. Monoozonolyses gave the corresponding unsaturated dialdehydes 2e as the primary products. In subsequent reactions, the dialdehydes 2e derived from the monoozonolyses of 1a, 1b, and 1c gave in high yields the heterocyclic compounds 7, 8k, and 9k, respectively. Diozonolyses of 1a-d gave the corresponding dialdehydes 3e as the primary products. In subsequent reactions, the dialdehydes 3e derived from 1b and 1c gave the heterocyclic compounds 8l, and 9l, respectively. In addition, aldehydes 2e and 3e underwent partial acetalization reactions with methanol.

  1. S-Methylidene Agents: Preparation of Chiral Non-Racemic Heterocycles

    PubMed Central

    Forbes, David C.; Bettigeri, Sampada V.; Patrawala, Samit A.; Pischek, Susanna C.; Standen, Michael C.

    2008-01-01

    Reaction of sulfur ylide with aldehyde, imine, and ketone functionality affords the desired three-membered heterocycle in excellent yield. The sulfur ylide is generated in situ upon decarboxylation of carboxymethylsulfonium betaine functionality. Of the seven carboxymethylsulfonium betaine derivatives surveyed, the highest level of conversion of π-acceptor to heterocycle was obtained having S-methyl and S-phenyl functionality bound to a thioacetate derivative. Methylene aziridinations and epoxidations involving the decarboxylation of carboxymethylsulfonium betaine functionality complements existing technologies with the advantages of the reaction protocol, levels of conversion and scope. While moderate levels of diastereocontrol were observed in the aziridination of imine functionality, the four oxiranes resolved using Jacobsen’s Co(II)-salen complex were obtained in both high yield and enantioselectivity. The isolated chiral non-racemic oxiranes constitute the formal synthesis of chelonin-B and combretastatin starting from 3-bromo-4-methoxybenzaldehyde and 3,4,5-trimethoxybenzaldehyde respectively. PMID:20049065

  2. Synthetic and Mechanistic Studies of Strained Heterocycle Opening Reactions Mediated by Zirconium(IV) Imido Complexes

    PubMed Central

    Blum, Suzanne A.; Rivera, Vicki A.; Ruck, Rebecca T.; Michael, Forrest E.; Bergman, Robert G.

    2005-01-01

    The reactions of the bis(cyclopentadienyl)(tert-butylimido)zirconium complex (Cp2Zr=N-t-Bu)(THF) (1) with epoxides, aziridines, and episulfides were investigated. Heterocycles without accessible β-hydrogens undergo insertion/protonation of the C–X bond to produce 1,2-amino alcohols (X = O) and 1,2-diamines (X = NR), whereas heterocycles with accessible β-hydrogens undergo elimination/protonation to produce allylic alcohols (X = O) and allylic sulfides (X = S). Mechanistic investigations support a stepwise pathway with zwitterionic intermediates for the first reaction class and a concerted pathway for the second reaction class. Additionally, the feasibility of chirality transfer from the planar-chiral ebthi (ebthi = ethylenebis(tetrahydroindenyl)) ligand was demonstrated with a chiral analogue, (ebthi)-Zr=NAr(THF) (Ar = 2,6-dimethylphenyl), 2, through the diastereoselective ring opening of meso epoxides. PMID:16508693

  3. NMR Signal Amplification by Reversible Exchange of Sulfur-Heterocyclic Compounds Found In Petroleum

    PubMed Central

    Coffey, Aaron M.; Goodson, Boyd M.; Chekmenev, Eduard Y.

    2016-01-01

    NMR hyperpolarization via Signal Amplification by Reversible Exchange (SABRE) was employed to investigate the feasibility of enhancing the NMR detection sensitivity of sulfur-heterocycles (specifically 2-methylthiophene and dibenzothiophenes), a family of compounds typically found in petroleum and refined petroleum products. SABRE hyperpolarization of sulfur-heterocycles (conducted in seconds) offers potential advantages of providing structural information about sulfur-containing contaminants in petroleum, thereby informing petroleum purification and refining to minimize sulfur content in refined products such as gasoline. Moreover, NMR spectroscopy sensitivity gains endowed by hyperpolarization potentially allows for performing structural assays using inexpensive, low-magnetic-field (ca. 1 T) high-resolution NMR spectrometers ideally suited for industrial applications in the field. PMID:27500206

  4. Ab initio study of mechanism of forming a Spiro-Si-heterocyclic ring compound

    NASA Astrophysics Data System (ADS)

    Lu, Xiuhui; Ji, Hua

    2013-04-01

    The mechanism of the cycloaddition reaction of forming a spiro-Si-heterocyclic ring compound between singlet dichloroalkylidenesilylene (Cl2C=Si :) and ethene has been investigated with CCSD(T)//MP2/6-31G* method. From the potential energy profile, it can be predicted that the reaction has one dominant reaction pathway. The presented rule of this reaction is that the 3 p unoccupied orbital of Si in dichloroalkylidene and the π orbital of ethene forming the π → p donor-acceptor bond, resulting in the formation of a three-membered ring intermediate. Ring-enlargement effect make the three-membered ring intermediate isomerizes to a four-membered ring silylene. Due to sp 3 hybridization of Si atom in the four-membered ring silylene, the four-membered ring silylene further combines with ethene to form a spiro-Si-heterocyclic ring compound.

  5. Nitrogen-heterocyclic compounds in meteorites - Significance and mechanisms of formation

    NASA Astrophysics Data System (ADS)

    Stoks, P. G.; Schwartz, A. W.

    1981-04-01

    Samples of the Murchison, Murray, and Orgueil carbonaceous meteorites were analyzed for nitrogen-heterocyclic compounds using gas chromatography, cation and anion exclusion liquid chromatography, and mass spectrometry. The H2O and HCOOH extracts, as well as the 3M-HCl hydrolyzate of the Allende sample were taken through all stages of analysis. Concentrations ranging from 114-655 ppb of the purines adenine, guanine, hypoxanthine, and xanthine were found to be present in acid extracts. All four biologically significant purines, as well as the pyrimidine uracil have been identified in meteorites. It was concluded that the suite of N-heterocyclic compounds identified in meteorites do not permit a clear distinction between mechanisms of synthesis such as the Fischer-Tropsch type, and other candidates.

  6. Decisive Interactions between the Heterocyclic Moiety and the Cluster Observed in Polyoxometalate-Surfactant Hybrid Crystals

    PubMed Central

    Otobe, Saki; Fujioka, Natsumi; Hirano, Takuro; Ishikawa, Eri; Naruke, Haruo; Fujio, Katsuhiko; Ito, Takeru

    2015-01-01

    Inorganic-organic hybrid crystals were successfully obtained as single crystals by using polyoxotungstate anion and cationic dodecylpyridazinium (C12pda) and dodecylpyridinium (C12py) surfactants. The decatungstate (W10) anion was used as the inorganic component, and the crystal structures were compared. In the crystal comprising C12pda (C12pda-W10), the heterocyclic moiety directly interacted with W10, which contributed to a build-up of the crystal structure. On the other hand, the crystal consisting of C12py (C12py-W10) had similar crystal packing and molecular arrangement to those in the W10 crystal hybridized with other pyridinium surfactants. These results indicate the significance of the heterocyclic moiety of the surfactant to construct hybrid crystals with polyoxometalate anions. PMID:25894221

  7. Clicking the Arsenic-Carbon Triple Bond: An Entry into a New Class of Arsenic Heterocycles.

    PubMed

    Pfeifer, Gregor; Papke, Martin; Frost, Daniel; Sklorz, Julian A W; Habicht, Marija; Müller, Christian

    2016-09-19

    Arsaalkynes can undergo regioselective and quantitative [3+2] cycloaddition reactions with organic azides to give hitherto unknown 3H-1,2,3,4-triazaarsole derivatives. The reaction product was obtained as a white, air- and moisture-stable solid, and the presence of a planar, five-membered arsenic heterocycle was unambiguously verified by means of X-ray crystallography. DFT calculations gave insight into the electronic structure of these novel compounds compared to tetrazoles and triazaphospholes. The coordination chemistry towards Re(I) was investigated and compared with the structurally related phosphorus-containing ligand. These preliminary investigations pave the way for a new class of arsenic heterocycles and fill the gap between the azaarsoles already known. PMID:27460759

  8. Carbonic Anhydrase Inhibitors. Part 541: Metal Complexes of Heterocyclic Sulfonamides: A New Class of Antiglaucoma Agents

    PubMed Central

    Scozzafava, Andrea; Jitianu, Andrei

    1997-01-01

    Metal complexes of heterocyclic sulfonamides possessing carbonic anhydrase (CA) inhibitory properties were recently shown to be useful as intraocular pressure (IOP) lowering agents in experimental animals, and might be developed as a novel class of antiglaucoma drugs. Here we report the synthesis of a heterocyclic sulfonamide CA inhibitor and of the metal complexes containing main group metal ions, such as Be(II), Mg(II), Al(III), Zn(II), Cd(II) and Hg(II) and the new sulfonamide as well as 5-amino-1,3,4-thiadiazole-2-sulfonamide as ligands. The new complexes were characterized by standard physico-chemical procedures, and assayed as inhibitors of three CA isozymes, CA I, II and IV. Some of them (but not the parent sulfonamides) strongly lowered IOP in rabbits when administered as a 2% solution into the eye. PMID:18475811

  9. Reagent-based DOS: developing a diastereoselective methodology to access spirocyclic- and fused heterocyclic ring systems.

    PubMed

    Damerla, V Surendra Babu; Tulluri, Chiranjeevi; Gundla, Rambabu; Naviri, Lava; Adepally, Uma; Iyer, Pravin S; Murthy, Y L N; Prabhakar, Nampally; Sen, Subhabrata

    2012-10-01

    Herein, we report a diversity-oriented-synthesis (DOS) approach for the synthesis of biologically relevant molecular scaffolds. Our methodology enables the facile synthesis of fused N-heterocycles, spirooxoindolones, tetrahydroquinolines, and fused N-heterocycles. The two-step sequence starts with a chiral-bicyclic-lactam-directed enolate-addition/substitution step. This step is followed by a ring-closure onto the built-in scaffold electrophile, thereby leading to stereoselective carbocycle- and spirocycle-formation. We used in silico tools to calibrate our compounds with respect to chemical diversity and selected drug-like properties. We evaluated the biological significance of our scaffolds by screening them in two cancer cell-lines. In summary, our DOS methodology affords new, diverse scaffolds, thereby resulting in compounds that may have significance in medicinal chemistry. PMID:22887684

  10. Synthesis and antifungal activity evaluation of new heterocycle containing amide derivatives.

    PubMed

    Wang, Xuesong; Gao, Sumei; Yang, Jian; Gao, Yang; Wang, Ling; Tang, Xiaorong

    2016-01-01

    A series of heterocycle containing amide derivatives (1-28) were synthesised by the combination of acyl chlorides (1a, 2a) and heterocyclic/homocyclic ring containing amines, and their in vitro antifungal activity was evaluated against five plant pathogenic fungi, namely Gibberella zeae, Helminthosporium maydis, Rhizoctonia solani, Botrytis cinerea and Sclerotinia sclerotiorum. Results of antifungal activity analysis indicated that some of the products showed good to excellent antifungal activity, as compound 2 showed excellent activity against G. zeae and R. solani and potent activity against H. maydi, B. cinerea and S. sclerotiorum, and compounds 1, 8 and 10 also displayed excellent antifungal potential against H. maydi, B. cinerea and S. sclerotiorum and good activity against R. solani when compared with the standard carbendazim. PMID:26140452

  11. Thermoresponse improvement of poly(N-isopropylacrylamide) hydrogels via formation of poly(sodium p-styrenesulfonate) nanophases.

    PubMed

    Li, Jingang; Cong, Houluo; Li, Lei; Zheng, Sixun

    2014-08-27

    The block copolymer networks composed of poly(N-isopropylacrylamide) (PNIPAM) and poly(sodium p-styrenesulfonate) were synthesized via sequential reversible addition-fragmentation chain transfer (RAFT) polymerization with α,ω-didithiobenzoate-terminated poly(sodium p-styrenesulfonate) (PSSNa) as the macromolecular chain transfer agent. It was found that the block copolymer networks were microphase-separated as evidenced by means of transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS). In the block copolymer networks, spherical or cylindrical PSSNa microdomains were finely dispersed into continuous PNIPAM matrixes. In comparison with unmodified PNIPAM hydrogel, the nanostructured hydrogels displayed improved thermoresponsive properties. In addition, the swelling ratios of the PSSNa-modified PNIPAM hydrogels were significantly higher than that of plain PNIPAM hydrogel. The improvement of thermoresponse was attributable to the formation of the PSSNa nanophases, which promoted the transportation of water molecules in the cross-linked networks. PMID:25036696

  12. One-Pot Two-Step Multicomponent Process of Indole and Other Nitrogenous Heterocycles or Amines toward α-Oxo-acetamidines.

    PubMed

    Martinez-Ariza, Guillermo; McConnell, Nicholas; Hulme, Christopher

    2016-04-15

    A cesium carbonate promoted three-component reaction of N-H containing heterocycles, primary or secondary amines, arylglyoxaldehydes, and anilines is reported. The key step involves a tandem sequence of N-1 addition of a heterocycle or an amine to preformed α-iminoketones, followed by an air- or oxygen-mediated oxidation to form α-oxo-acetamidines. The scope of the reaction is enticingly broad, and this novel methodology is applied toward the synthesis of various polycyclic heterocycles. PMID:27020621

  13. High temperature fuel cell membranes based on poly(arylene ether)s containing benzimidazole groups

    SciTech Connect

    Kim, Dae Sik; Kim, Yu Seung; Lee, Kwan - Soo; Boncella, James M; Kuiper, David; Guiver, Michael D

    2009-01-01

    Development of new high-performance polymer membranes that retain their proton conductivity under low humidity conditions is one of the most critical requirements to commercialize PEMFC systems. Current sulfonated proton exchange membranes acquire proton conductivity by water that solvates ion and carries proton. Consequently, a loss of water under low RH conditions immediately results in a loss of proton conductivity. One approach to maintain proton conductivity under low RH conditions is to replace water with a less volatile proton solvent. Kreuer has pointed out the possibility to develop fully polymeric proton-conducting membranes based on nitrogen-containing heterocycles such as imidazole, benzimidazole, and pyrazole. We have attempted to blend those less volatile proton solvent with sulfonated copolymers such as polystyrene sulfonic acid, Nafion, poly(arylene ether sulfone, BPSH-xx). [Ref. DOE review meeting 2007 and 2008] However, we observed that imidazole was slowly sublimated out as temperature and humidity increases which could cause poisoning of electro-catalyst, corrosion and losing conductivity. In this presentation, we report the synthesis of novel poly(arylene ether sulfone)s containing benzimidazole groups These benzimidazole containing polymer was blended with sulfonated poly(arylene ether sulfone). In the blend system, benzimidazole group attached to the polysulfone acts as a medium through the basic nitrogen for transfer of protons between the sulfonic acid groups. Proton conductivity of the blend membranes was investigated as a function of water content at 80 C and compared the performance with water based proton conduction system.

  14. Synthesis of coumarin/phenanthridine-fused heterocycles and their photochemical and thermochromic properties.

    PubMed

    Chen, Jiun-Jia; Li, Kuan-Ting; Yang, Ding-Yah

    2011-04-01

    Four coumarin and phenanthridine-fused heterocycles were efficiently synthesized using base-mediated annulation of N-alkylquinolinium iodide and coumarin as a key step. One compound is found to be sensitive to light and changes color upon UV irradiation; the others are sensitive to heat and possess negative thermochromic properties. A novel light- and heat-sensitive molecular skeleton is introduced. PMID:21355582

  15. Solid-phase development of a L-hydroxybenzotriazole linker for heterocycle synthesis using analytical constructs.

    PubMed

    Scicinski, J J; Congreve, M S; Jamieson, C; Ley, S V; Newman, E S; Vinader, V M; Carr, R A

    2001-01-01

    The development of a 1-hydroxybenzotriazole linker for the synthesis of heterocyclic derivatives is described, utilizing analytical construct methodology to facilitate the analysis of resin samples. A UV-chromophore-containing analytical construct enabled the accurate determination of resin loading and the automated monitoring of key reactions using only small quantities of resin. The syntheses of an array of isoxazole derivatives are reported. PMID:11442396

  16. Asymmetric Hydroformylation of Heterocyclic Olefins Mediated by Supramolecularly Regulated Rhodium-Bisphosphite Complexes.

    PubMed

    Rovira, Laura; Vaquero, Mónica; Vidal-Ferran, Anton

    2015-10-16

    Rhodium complexes derived from conformationally transformable α,ω-bisphosphite ligands combined with a suitable alkali metal BArF salt as a regulation agent (RA) provide high regio- and enantioselectivities in the asymmetric hydroformylation (AHF) of three heterocyclic olefins. The outcome of the AHF could be exquisitely regulated by choosing the appropriate RA with an increase in the ee, the reversal of the regioselectivity, or the complete suppression of one byproduct. PMID:26355601

  17. A chiral 6-membered N-heterocyclic carbene copper(I) complex that induces high stereoselectivity.

    PubMed

    Park, Jin Kyoon; Lackey, Hershel H; Rexford, Matthew D; Kovnir, Kirill; Shatruk, Michael; McQuade, D Tyler

    2010-11-01

    A chiral 6-membered annulated N-heterocyclic (6-NHC) copper complex that catalyzes β-borylations with high yield and enantioselectivity was developed. The chiral 6-NHC copper complex is easy to prepare on the gram scale and is very active, showing 10,000 turnovers at 0.01 mol % of catalyst without significant decrease of enantioselectivity and with useful reaction rates. PMID:20919706

  18. Synthesis of tricyclic heterocycles via a tandem aryl alkylation/heck coupling sequence.

    PubMed

    Alberico, Dino; Rudolph, Alena; Lautens, Mark

    2007-02-01

    A norbornene-mediated palladium-catalyzed sequence is described in which two alkyl-aryl bonds and one alkenyl-aryl bond are formed in one pot with use of microwave irradiation. A variety of symmetrical and unsymmetrical oxygen-, nitrogen-, silicon-, and sulfur-containing tricyclic heterocycles were synthesized from a Heck acceptor and an aryl iodide containing two tethered alkyl halides. This approach was further applied to the synthesis of a tricyclic mescaline analogue. PMID:17253794

  19. Insights into the structural patterns of the antileishmanial activity of bi- and tricyclic N-heterocycles.

    PubMed

    Herrera, Lizzi; Stephens, David E; D'Avila, Abigail; George, Kathryn G; Arman, Hadi; Zhang, Yu; Perry, George; Lleonart, Ricardo; Larionov, Oleg V; Fernández, Patricia L

    2016-08-01

    The influence of various structural patterns in a series of novel bi- and tricyclic N-heterocycles on the activity against Leishmania major and Leishmania panamensis has been studied and compounds that are active in the low micromolar region have been identified. Both quinolines and tetrahydrooxazinoindoles (TOI) proved to have significant antileishmanial activities, while substituted indoles were inactive. We have also showed that a chloroquine analogue induces Leishmania killing by modulating macrophage activation. PMID:27376396

  20. Catalytic Chemo- and Regioselective Coupling of 1,3-Dicarbonyls with N-Heterocyclic Nucleophiles.

    PubMed

    Kenny, Miles; Kitson, Daniel J; Franckevičius, Vilius

    2016-06-17

    The development of a decarboxylative palladium-catalyzed coupling of 1,3-dicarbonyl compounds with indole, pyrrole, imidazole, and pyrazole nucleophiles via an allylic linker under neutral conditions is disclosed. This process enables the installation of an all-carbon quaternary center and new C-C and C-N bonds in a single operation. Despite the weakly acidic nature of N-heterocycles, the reactions proceed with good efficiency and complete regio- and chemoselectivity. PMID:27211875

  1. Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

    PubMed Central

    Menon, Rajeev S; Biju, Akkattu T

    2016-01-01

    Summary N-Heterocyclic carbenes (NHCs) have emerged as a powerful class of organocatalysts that mediate a variety of organic transformations. The Benzoin reaction constitutes one of the earliest known carbon–carbon bond-forming reactions catalysed by NHCs. The rapid growth of NHC catalysis in general has resulted in the development of a variety of benzoin and benzoin-type reactions. An overview of such NHC-catalysed benzoin reactions is presented. PMID:27340440

  2. Two cytochromes P450 catalyze S-heterocyclizations in cabbage phytoalexin biosynthesis.

    PubMed

    Klein, Andrew P; Sattely, Elizabeth S

    2015-11-01

    Phytoalexins are abundant in edible crucifers and have important biological activities, yet no dedicated gene for their biosynthesis is known. Here, we report two new cytochromes P450 from Brassica rapa (Chinese cabbage) that catalyze unprecedented S-heterocyclizations in cyclobrassinin and spirobrassinin biosynthesis. Our results provide genetic and biochemical insights into the biosynthesis of a prominent pair of dietary metabolites and have implications for pathway discovery across >20 recently sequenced crucifers. PMID:26389737

  3. Alkyne-azide cycloaddition catalyzed by silver chloride and "abnormal" silver N-heterocyclic carbene complex.

    PubMed

    Ortega-Arizmendi, Aldo I; Aldeco-Pérez, Eugenia; Cuevas-Yañez, Erick

    2013-01-01

    A library of 1,2,3-triazoles was synthesized from diverse alkynes and azides using catalytic amounts of silver chloride instead of copper compounds. In addition, a novel "abnormal" silver N-heterocyclic carbene complex was tested as catalyst in this process. The results suggest that the reaction requires only 0.5% of silver complex, affording 1,2,3-triazoles in good yields. PMID:24307866

  4. Unprotected Amino Acids as Stable Radical Precursors for Heterocycle C-H Functionalization.

    PubMed

    Mai, Duy N; Baxter, Ryan D

    2016-08-01

    An efficient and general method for the C-H alkylation of heteroarenes using unprotected amino acids as stable alkyl radical precursors is reported. This one-pot procedure is performed open to air under aqueous conditions and is effective for several natural and unnatural amino acids. Heterocycles of varying structure are suitably functionalized, and reactivity trends reflect the nucleophilic character of the radical species generated. PMID:27452036

  5. Two cytochromes P450 catalyze S-heterocyclizations in cabbage phytoalexin biosynthesis

    PubMed Central

    Klein, Andrew P; Sattely, Elizabeth S

    2015-01-01

    Phytoalexins are abundant in edible crucifers and have important biological activities, yet no dedicated gene for their biosynthesis is known. Here, we report two new cytochromes P450 from Brassica rapa (Chinese cabbage) that catalyze unprecedented S-heterocyclizations in cyclobrassinin and spirobrassinin biosynthesis. Our results reveal the first genetic and biochemical insights into the biosynthesis of a prominent pair of dietary metabolites, and have implications for pathway discovery across >20 recently sequenced crucifers. PMID:26389737

  6. Actinide-lanthanide separation with solvents on the base of amides of heterocyclic diacids

    SciTech Connect

    Babain, V.A.; Alyapyshev, M.Y.; Tkachenko, L.I.

    2013-07-01

    The separation of actinides from lanthanides with a particular emphasis on Am(III) from Eu(III) with amides of heterocyclic dicarboxylic diacids was reviewed. It was shown that the di-amides of the 2,2'-dipyridyl-6,6'-dicarboxylic acid are the most promising ligands for the simultaneous selective recovery of actinides from HLLW (high level radioactive liquid waste) within the GANEX concept. (author)

  7. An Iridium(I) N-Heterocyclic Carbene Complex Catalyzes Asymmetric Intramolecular Allylic Amination Reactions.

    PubMed

    Ye, Ke-Yin; Cheng, Qiang; Zhuo, Chun-Xiang; Dai, Li-Xin; You, Shu-Li

    2016-07-01

    A chiral iridium(I) N-heterocyclic carbene complex was reported for the first time as the catalyst in the highly enantioselective intramolecular allylic amination reaction. The current method provides facile access to biologically important enantioenriched indolopiperazinones and piperazinones in good yields (74-91 %) and excellent enantioselectivities (92-99 % ee). Preliminary mechanistic investigations reveal that the C-H activation occurs at the position ortho to the N-aryl group of the ligand. PMID:27162135

  8. Platinum(iv) N-heterocyclic carbene complexes: their synthesis, characterisation and cytotoxic activity.

    PubMed

    Bouché, M; Dahm, G; Wantz, M; Fournel, S; Achard, T; Bellemin-Laponnaz, S

    2016-07-28

    Platinum(ii) N-heterocyclic carbene complexes have been oxidized by bromine or iodobenzene dichloride to provide the fully characterised corresponding platinum(iv) NHC complexes. Antiproliferative activities of Pt(iv) NHC complexes were assayed against several cancer cell lines and the results were correlated with respect to their stability. Mechanistic investigations revealed that mitochondrial dysfunction and ROS production were associated with the cytotoxic process induced by these compounds. PMID:27331604

  9. Synthesis, crystal structure, and luminescent properties of novel Eu3+ heterocyclic beta-diketonate complexes with bidentate nitrogen donors.

    PubMed

    Biju, S; Raj, D B Ambili; Reddy, M L P; Kariuki, B M

    2006-12-25

    New tris(heterocyclic beta-diketonato)europium(III) complexes of the general formula Eu(PBI)3.L [where HPBI = 3-phenyl-4-benzoyl-5-isoxazolone and L = H2O, 2,2'-bipyridine (bpy), 4,4'-dimethoxy-2,2'-bipyridine (dmbpy), 1,10-phenanthroline (phen), or 4,7-diphenyl-1,10-phenanthroline (bath)] were synthesized and characterized by elemental analysis, Fourier transform infrared spectroscopy (FT-IR), 1H NMR, high-resolution mass spectrometry, thermogravimetric analysis, and photoluminescence (PL) spectroscopy. Single-crystal X-ray structures have been determined for the complexes Eu(PBI)3.H2O.EtOH and Eu(PBI)3.phen. The complex Eu(PBI)3.H2O.EtOH is mononuclear, and the central Eu3+ ion is coordinated by eight oxygen atoms to form a bicapped trigonal prism coordination polyhedron. Six oxygens are from the three bidentate HPBI ligands, one is from a water molecule, and another is from an ethanol molecule. On the other hand, the crystal structure of Eu(PBI)3.phen reveals a distorted square antiprismatic geometry around the europium atom. The room-temperature PL spectra of the europium(III) complexes are composed of the typical Eu3+ red emission, assigned to transitions between the first excited state (5D0) and the multiplet (7F0-4). The results demonstrate that the substitution of solvent molecules by bidentate nitrogen ligands in Eu(PBI)3.H2O.EtOH richly enhances the quantum yield and lifetime values. To elucidate the energy transfer process of the europium complexes, the energy levels of the relevant electronic states have been estimated. Judd-Ofelt intensity parameters (Omega2 and Omega4) were determined from the emission spectra for Eu3+ ion based on the 5D0 --> 7F2 and 5D0 --> 7F4 electronic transitions, respectively, and the 5D0 --> 7F1 magnetic dipole allowed transition was taken as the reference. The high values obtained for the 4f-4f intensity parameter Omega2 for europium complexes suggest that the dynamic coupling mechanism is quite operative in these compounds

  10. Formation and Ecotoxicity of N-Heterocyclic Compounds on Ammoxidation of Mono- and Polysaccharides

    PubMed Central

    2013-01-01

    Ammoxidation of technical lignins under mild conditions is a suitable approach to artificial humic substances. However, carbohydrates as common minor constituents of technical lignins have been demonstrated to be a potential source of N-heterocyclic ecotoxic compounds. Ethyl acetate extracts of ammoxidation mixtures of the monosaccharides glucose and xylose exhibited considerable growth inhibiting activity in the OECD 201 test, with 4-methyl-1H-imidazole, 4-(hydroxymethyl)-1H-imidazole, and 3-hydroxypyridine being the most active compounds. The amount of N-heterocyclic compounds formed at moderate ammoxidation conditions (70 °C, 0.2 MPa O2, 3 h) was significantly lower for the polysaccharides cellulose and xylan (16–30 μg/g of educt) compared to glucose (15.4 mg). Ammoxidation at higher temperature is not recommendable for carbohydrate-rich materials as much higher amounts of N-heterocyclic compounds were formed from both monosaccharides (100 °C: 122.4–160.5 mg/g of educt) and polysaccharides (140 °C: 5.52–16.03 mg/g of educt). PMID:23967874

  11. Impact of Environmental Exposures on the Mutagenicity/Carcinogenicity of Heterocyclic Amines

    SciTech Connect

    Felton, J S; Knize, M G; Bennett, L M; Malfatti, M A; Colvin, M E; Kulp, K S

    2003-12-19

    Carcinogenic heterocyclic amines are produced from overcooked foods and are highly mutagenic in most short-term test systems. One of the most abundant of these amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), induces breast, colon and prostate tumors in rats. Human dietary epidemiology studies suggest a strong correlation between either meat consumption or well-done muscle meat consumption and cancers of the colon, breast, stomach, lung and esophagus. For over 20 years our laboratory has helped define the human exposure to these dietary carcinogens. In this report we describe how various environmental exposures may modulate the risk from exposure to heterocyclic amines, especially PhIP. To assess the impact of foods on PhIP metabolism in humans, we developed an LC/MS/MS method to analyze the four major PhIP urinary metabolites following the consumption of a single portion of grilled chicken. Adding broccoli to the volunteers' diet altered the kinetics of PhIP metabolism. At the cellular level we have found that PhIP itself stimulates a significant estrogenic response in MCF-7 cells, but even more interestingly, co-incubation of the cells with herbal teas appear to enhance the response. Numerous environmental chemicals found in food or the atmosphere can impact the exposure, metabolism, and cell proliferation response of heterocyclic amines.

  12. Trypanocidal activity of synthetic heterocyclic derivatives of active quinones from Tabebuia sp.

    PubMed

    Pinto, A V; Pinto, C N; Pinto, M do C; Rita, R S; Pezzella, C A; de Castro, S L

    1997-01-01

    Continuing a program on the chemistry and biological activity of compounds from the Brazilian flora, the lytic activity against bloodstream forms of T. cruzi of nine new heterocyclic naphthooxazole and naphthoimidazole derivatives obtained from the reaction of naphtoquinones isolated from Tabebuia sp. (Tecoma) with amino-containing reagents has been studied. Also for the first time the biological activity of allyl derivatives of lawsone, a natural quinone from Lausonia alba inactive against T. cruzi, is reported. The introduction of an allyl group in lawsone gives rise to O-allyl-lawsone and C-allyl-lawsone that showed activity against the parasite, with ID50 values of 420.7 +/- 71.1 and 330.7 +/- 62.4 mumol/l, respectively. The trypanocidal activity of the naphtho heterocyclics synthesized from the original quinones showed no concordant behavior in relation to the parent compound. Six of nine of the synthesized compounds presented lower ID50 values than crystal violet, indicating a general trend of activity among naphthalenic heterocyclics of the oxazole/imidazole type. However, their chemical structures do not endow them with the capacity of free radical generation by biological reduction as the quinoidal moiety, nor do they have chemical reducible appendage like the nitro group of nifurtimox and benznidazole, responsible for such behaviour. As a hypothesis, the pattern of their biological actions should be focused in other aspects of their chemical structures. Because of their polycyclic planar topology, these derivatives are potential candidates for experimental tests as DNA intercalating agents. PMID:9037448

  13. Tandem reactions initiated by copper-catalyzed cross-coupling: a new strategy towards heterocycle synthesis.

    PubMed

    Liu, Yunyun; Wan, Jie-Ping

    2011-10-21

    Copper-catalyzed cross-coupling reactions which lead to the formation of C-N, C-O, C-S and C-C bonds have been recognized as one of the most useful strategies in synthetic organic chemistry. During past decades, important breakthroughs in the study of Cu-catalyzed coupling processes demonstrated that Cu-catalyzed reactions are broadly applicable to a variety of research fields related to organic synthesis. Representatively, employing these coupling transformations as key steps, a large number of tandem reactions have been developed for the construction of various heterocyclic compounds. These tactics share the advantages of high atom economics of tandem reactions as well as the broad tolerance of Cu-catalyst systems. Therefore, Cu-catalyzed C-X (X = N, O, S, C) coupling transformation-initiated tandem reactions were quickly recognized as a strategy with great potential for synthesizing heterocyclic compounds and gained worldwide attention. In this review, recent research progress in heterocycle syntheses using tandem reactions initiated by copper-catalyzed coupling transformations, including C-N, C-O, C-S as well as C-C coupling processes are summarized. PMID:21879127

  14. Cytotoxic activity of the novel heterocyclic compound G-11 is primarily mediated through intrinsic apoptotic pathway.

    PubMed

    Saleh, Ayman M; Aziz, Mohammad A; Abdou, Ibrahim M; Taha, Mutasem O; Al-Qudah, Mahmoud A; Abadleh, Mohammed M; Aljada, Ahmad; Rizvi, Syed A

    2016-07-01

    Natural and chemically synthesized heterocyclic compounds have been explored for their potential use as anticancer agents. We had synthesized non-natural heterocyclic analogs and evaluated their anti-tumor activity by measuring effect on cell proliferation and induction of apoptosis in different cell lines. Previously, we identified a pyrazole-containing compound (G-11) showing cytotoxic effect towards leukemia and lymphoma cell lines. In this study, we further investigated the mechanistic aspects of anticancer properties of G-11 in HL-60 cell line. We demonstrated that cytotoxic effect of G-11 is mediated by caspase-dependent apoptosis. However, the involvement of mitochondrial dysfunction induced by G-11 was independent of caspases. G-11 triggered generation of ROS, caused disruption of mitochondrial transmembrane potential, increased release of cytochrome c to the cytosol, and altered the expression of Bcl-2 and Bax proteins. These results suggest significant involvement of intrinsic apoptotic pathway. This study comprehensively details the possible mechanisms of action of a novel heterocyclic compound which could find its potential use as an anticancer agent. PMID:27154302

  15. Asymmetric 1,3-Dipolar Cycloaddition Reactions Catalyzed by Heterocycle-Based Metal Complexes

    NASA Astrophysics Data System (ADS)

    Suga, Hiroyuki

    Highly enantioselective 1,3-dipolar cycloaddition reactions of several 1,3-dipoles, such as nitrones, nitrile oxides, nitrile imines, diazoalkanes, azomethine imines and carbonyl ylides, catalyzed by heterocyclic supramolecular type of metal complexes consisting of chiral heterocyclic compounds and metal salts were described in terms of their ability of asymmetric induction and enantioface differentiation. The scope and limitations of each cycloaddition reactions were also briefly described. Of the chiral hererocycle-based ligands, chiral bisoxazoline, 2,6-bis(oxazolinyl)pyridine, and related oxazoline ligands are shown to be quite effective in obtaining high levels of asymmtric induction. The combination of the bisoxazoline ligand derived from (1S,2R)-cis-1-amino-2-indanol and metal salts was especially efficient for asymmetric cycloaddition reactions of a number of 1,3-dipoles, such as nitrones, nitrile oxide, nitrile imines, diazoacetates and azomethine imines. The metals utilized for the heterocycle-based complexes show a crucial role for degree of asymmetric induction depending upon the 1,3-dipole used. High levels of enantioselectivity were achieved in 1,3-dipolar cycloaddition reactions of unstable carbonyl ylides with benzyloxyacetaldehyde derivatives, α-keto esters, 3-(2-alkenoyl)-2-oxazolidinones, and even vinyl ethers, which were catalyzed by Pybox-lanthanoid metal complexes.

  16. Effects of nitro-heterocyclic derivatives against Leishmania (Leishmania) infantum promastigotes and intracellular amastigotes.

    PubMed

    Petri e Silva, Simone Carolina Soares; Palace-Berl, Fanny; Tavares, Leoberto Costa; Soares, Sandra Regina Castro; Lindoso, José Angelo Lauletta

    2016-04-01

    Leishmaniasis is an overlooked tropical disease affecting approximately 1 million people in several countries. Clinical manifestation depends on the interaction between Leishmania and the host's immune response. Currently available treatment options for leishmaniasis are limited and induce severe side effects. In this research, we tested nitro-heterocyclic compounds (BSF series) as a new alternative against Leishmania. Its activity was measured in Leishmania (Leishmania) infantum promastigotes and intracellular amastigotes using MTT colorimetric assay. Additionally, we assessed the phosphatidylserine exposure by promastigotes, measured by flow cytometry, as well as nitric oxide production, measured by Griess' method. The nitro-heterocyclic compounds (BSF series) showed activity against L. (L.) infantum promastigotes, inducting the phosphatidylserine exposition by promastigotes, decreasing intracellular amastigotes and increasing oxide nitric production. The selectivity index was more prominent to Leishmania than to macrophages. Compared to amphotericin b, our compounds presented higher IC50, however the selectivity index was more specific to parasite than to amphotericin b. In conclusion, these nitro-heterocyclic compounds showed to be promising as an anti-Leishmania drug, in in vitro studies. PMID:26795261

  17. Optimization of the Central Heterocycle of α-Ketoheterocycle Inhibitors of Fatty Acid Amide Hydrolase

    PubMed Central

    Garfunkle, Joie; Ezzili, Cyrine; Rayl, Thomas J.; Hochstatter, Dustin G.; Hwang, Inkyu; Boger, Dale L.

    2008-01-01

    The synthesis and evaluation of a refined series of α-ketoheterocycles based on the oxazole 2 (OL-135) incorporating systematic changes in the central heterocycle bearing a key set of added substituents are described. The nature of the central heterocycle, even within the systematic and minor perturbations explored herein, significantly influenced the inhibitor activity: 1,3,4-oxadiazoles and 1,2,4-oxadiazoles 9 > tetrazoles, the isomeric 1,2,4-oxadiazoles 10, 1,3,4-thiadiazoles > oxazoles including 2 > 1,2-diazines > thiazoles > 1,3,4-triazoles. Most evident in these trends is the observation that introduction of an additional heteroatom at position 4 (oxazole numbering, N > O > CH) substantially increases activity that may be attributed to a reduced destabilizing steric interaction at the FAAH active site. Added heterocycle substituents displaying well defined trends may be utilized to enhance the inhibitor potency and, more significantly, to enhance the inhibitor selectivity. These trends, exemplified herein, emerge from both enhancements in the FAAH activity and simultaneous disruption of binding affinity for competitive off-target enzymes. PMID:18630870

  18. Carotenoids Play a Positive Role in the Degradation of Heterocycles by Sphingobium yanoikuyae

    PubMed Central

    Liu, Xiaorui; Gai, Zhonghui; Tao, Fei; Tang, Hongzhi; Xu, Ping

    2012-01-01

    Background Microbial oxidative degradation is a potential way of removing pollutants such as heterocycles from the environment. During this process, reactive oxygen species or other oxidants are inevitably produced, and may cause damage to DNA, proteins, and membranes, thereby decreasing the degradation rate. Carotenoids can serve as membrane-integrated antioxidants, protecting cells from oxidative stress. Findings Several genes involved in the carotenoid biosynthetic pathway were cloned and characterized from a carbazole-degrading bacterium Sphingobium yanoikuyae XLDN2-5. In addition, a yellow-pigmented carotenoid synthesized by strain XLDN2-5 was identified as zeaxanthin that was synthesized from β-carotene through β-cryptoxanthin. The amounts of zeaxanthin and hydrogen peroxide produced were significantly and simultaneously enhanced during the biodegradation of heterocycles (carbazole < carbazole + benzothiophene < carbazole + dibenzothiophene). These higher production levels were consistent with the transcriptional increase of the gene encoding phytoene desaturase, one of the key enzymes for carotenoid biosynthesis. Conclusions/Significance Sphingobium yanoikuyae XLDN2-5 can enhance the synthesis of zeaxanthin, one of the carotenoids, which may modulate membrane fluidity and defense against intracellular oxidative stress. To our knowledge, this is the first report on the positive role of carotenoids in the biodegradation of heterocycles, while elucidating the carotenoid biosynthetic pathway in the Sphingobium genus. PMID:22745775

  19. Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

    PubMed Central

    Shakoori, Alireza; Bremner, John B; Abdel-Hamid, Mohammed K; Willis, Anthony C; Haritakun, Rachada

    2015-01-01

    Summary Diversity-directed synthesis based on the cascade allylation chemistry of indigo, with its embedded 2,2’-diindolic core, has resulted in rapid access to new examples of the hydroxy-8a,13-dihydroazepino[1,2-a:3,4-b']diindol-14(8H)-one skeleton in up to 51% yield. Additionally a derivative of the novel bridged heterocycle 7,8-dihydro-6H-6,8a-epoxyazepino[1,2-a:3,4-b']diindol-14(13H)-one was produced when the olefin of the allylic substrate was terminally disubstituted. Further optimisation also produced viable one-pot syntheses of derivatives of the spiro(indoline-2,9'-pyrido[1,2-a]indol)-3-one (65%) and pyrido[1,2,3-s,t]indolo[1,2-a]azepino[3,4-b]indol-17-one (72%) heterocyclic systems. Ring-closing metathesis of the N,O-diallylic spiro structure and subsequent Claisen rearrangement gave rise to the new (1R,8aS,17aS)-rel-1,2-dihydro-1-vinyl-8H,17H,9H-benz[2',3']pyrrolizino[1',7a':2,3]pyrido[1,2-a]indole-8,17-(2H,9H)-dione heterocyclic system. PMID:25977722

  20. Pyrolysis of high-ash sewage sludge in a circulating fluidized bed reactor for production of liquids rich in heterocyclic nitrogenated compounds.

    PubMed

    Zuo, Wu; Jin, Baosheng; Huang, Yaji; Sun, Yu; Li, Rui; Jia, Jiqiang

    2013-01-01

    A circulating fluidized bed reactor was used for pyrolyzing sewage sludge with a high ash content to produce liquids rich in heterocyclic nitrogenated compounds. GC/MS and FTIR analyses showed that heterocyclic nitrogenated compounds and hydrocarbons made up 38.5-61.21% and 2.24-17.48% of the pyrolysis liquids, respectively. A fluidized gas velocity of 1.13 m/s, a sludge feed rate of 10.78 kg/h and a particle size of 1-2mm promoted heterocyclic nitrogenated compound production. Utilizing heterocyclic nitrogenated compounds as chemical feedstock could be a way for offsetting the cost of sewage sludge treatment. PMID:23131621

  1. TOF-SIMS analysis of N-heterocyclic compounds-implications for the Rosetta/COSIMA Mission

    NASA Astrophysics Data System (ADS)

    Le Roy, Léna; Briois, Christelle; Thirkell, Laurent; Cottin, Hervé; Fray, Nicolas; Poulet, Gilles; Hilchenbach, Martin

    The European Rosetta spacecraft launched on March 2004 will reach the comet 67/P-Churyumov-Gerasimenko in 2014 to perform the most exhaustive study ever achieved on comets (Glassmeier et al. 2007). The COmetary Secondary Ion Mass Analyser (COSIMA) carried on board will focus on chemical analysis of cometary dust grains collected in situ on a variety of metallic targets. COSIMA's goals are the in-situ characterisation of the atomic, molecular and isotopic composition of cometary dust grains. These analyses will provide inorganic and organic data about pristine solar system material (Kissel et al. 2007). COSIMA is a time-of-flight secondary ion mass spectrometer (TOF-SIMS) using an indium liquid metal ion source. Spectra inter-pretation of complex unknown samples with COSIMA instrument will be difficult due to the limited mass resolution (M/M of 2000 at m=100 amu) which excludes unambiguous compounds identification and requires preliminary work with reference samples. To help the interpretation of COSIMA spectra calibration laboratory work is in progress using the twin of the COSIMA flight instrument located at Katlenburg-Lindau (Germany) and the prototype of COSIMA in Orléans (France). Here we report the analysis of 100-400m deposits of organics performed with the COSIMA prototype based in Orléans. The organics are expected to be minor peaks, making their identification not simple. Nucleobase molecules, especially the purine bases, are among the building of the replicating molecules of life (DNA and RNA). Scour the universe in an attempt to find such a natural source of nucleobases is of fundamental significance in considerations of the origin of life (Lazcano Miller 1996) Therefore we focused our work on N-heterocyclic compounds which are believed to be present in comets or which belong to the chemical family of such molecules (Krueger Kissel 2006). Experiments have been performed on nine compounds: adenine, guanine, imidazole, 2-aminopyrimidine, cytosine

  2. Phenyl substituted Mg porphyrazines: The effect of annulation of a chalcogen-containing heterocycle on the spectral-luminescent properties

    NASA Astrophysics Data System (ADS)

    Knyukshto, V. N.; Volkovich, D. I.; Gladkov, L. L.; Kuzmitsky, V. A.; Ul-Haque, A.; Popkova, I. A.; Stuzhin, P. A.; Solovyov, K. N.

    2012-10-01

    We have performed complex experimental and theoretical investigations of the spectral-luminescent properties and electronic structure of new phthalocyanine analogs, Mg octaphenylporphyrazine and its derivatives with an annulated thiadiazole or selenadiazole ring instead of two phenyl groups. Fluorescence characteristics have been determined at 293 and 77 K: emission, excitation, and fluorescence polarization spectra; fluorescence quantum yield φ F , and lifetime τ F . Annulation of a five-membered chalcogen-containing heterocycle leads to splitting of the long-wavelength absorption band Q(0-0) and to the bathochromic shift of its longest wavelength component Q x (0-0), which increase upon passage from S to Se. At the same time, the fluorescence quantum yield φ F and lifetime τ F decrease, which is related to the intramolecular heavy-atom effect. The geometric structure of the ground state of the Mg porphyrazine molecules has been determined based on the density functional theory (DFT), and excited electronic states have been calculated with modified parametrization of the INDO/S method, INDO/Sm. Semiquantitatively, the calculated level positions of the lowest Q states and spectral shifts of Mg octaphenylporphyrazine and S-derivative agree with experimental data. For the range of the Soret band, calculated transition energies and their intensity distributions substantially depend on the dihedral angle γ between a phenyl ring and porphyrazine macrocycle. We show that, based on calculations at the angle γ = 60°, bands in the observed absorption spectra can be assigned with an accuracy of ˜2000 cm-1.

  3. 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.

  4. Synthesis, anticancer activity and molecular docking studies on a series of heterocyclic trans-cyanocombretastatin analogues as antitubulin agents

    PubMed Central

    Penthala, Narsimha Reddy; Zong, Hongliang; Ketkar, Amit; Madadi, Nikhil Reddy; Janganati, Venumadav; Eoff, Robert L.; Guzman, Monica L.; Crooks, Peter A.

    2015-01-01

    A series of heterocyclic combretastatin analogues have been synthesized and evaluated for their anticancer activity against a panel of 60 human cancer cell lines. The most potent compounds were two 3,4,5-trimethoxy phenyl analogues containing either an (Z)-indol-2-yl (8) or (Z)-benzo[b]furan-2-yl (12) moiety; these compounds exhibited GI50 values of <10 nM against 74% and 70%, respectively, of the human cancer cell lines in the 60-cell panel. Compounds 8, and 12 and two previously reported compounds in the same structural class, i.e. 29 and 31, also showed potent anti-leukemic activity against leukemia MV4-11 cell lines with LD50 values = 44 nM, 47 nM, 18 nM, and 180 nM, respectively. From the NCI anti-cancer screening results and the data from the in vitro toxicity screening on cultured AML cells, seven compounds: 8, 12, 21, 23, 25, 29 and 31 were screened for their in vitro inhibitory activity on tubulin polymerization in MV4-11 AML cells; at 50 nM, 8 and 29 inhibited polymerization of tubulin by >50%. The binding modes of the three most active compounds (8, 12 and 29) to tubulin were also investigated utilizing molecular docking studies. All three molecules were observed to bind in the same hydrophobic pocket at the interface of α- and β-tubulin that is occupied by colchicine, and were stablized by van der Waals’ interactions with surrounding tubulin residues. The results from the tubulin polymerization and molecular docking studies indicate that compounds 8 and 29 are the most potent anti-leukemic compounds in this structural class, and are considered lead compounds for further development as anti-leukemic drugs. PMID:25557492

  5. Non-basic high-performance molecules for solution-processed organic solar cells.

    PubMed

    van der Poll, Thomas S; Love, John A; Nguyen, Thuc-Quyen; Bazan, Guillermo C

    2012-07-17

    A new small molecule, p-DTS(FBTTh(2))(2), is designed for incorporation into solution-fabricated high-efficiency organic solar cells. Of primary importance is the incorporation of electron poor heterocycles that are not prone to protonation and thereby enable the incorporation of commonly used interlayers between the organic semiconductor and the charge collecting electrodes. These features have led to the creation of p-DTS(FBTTh(2))(2)/PC(71)BM solar cells with power conversion efficiencies of up to 7%. PMID:22674636

  6. Hydrogen bonding on the surface of poly(2-methoxyethyl acrylate).

    PubMed

    Li, Guifeng; Ye, Shen; Morita, Shigeaki; Nishida, Takuma; Osawa, Masatoshi

    2004-10-01

    Hydrogen bonding on the interface and in the bulk of a poly(2-methoxyethyl acrylate) (PMEA) thin film has been investigated by sum frequency generation, infrared reflection absorption, and Raman scattering measurements in different kinds of solutions containing hydrogen-bonding donators. These results indicate that the majority of the carbonyl groups on the PMEA surface are hydrogen-bonded with water or ethanol molecules, while the PMEA bulk is still dominated by the free carbonyl group. PMID:15453716

  7. Molecular recognition of poly(A) by small ligands: an alternative method of analysis reveals nanomolar, cooperative and shape-selective binding

    PubMed Central

    Çetinkol, Özgül Persil; Hud, Nicholas V.

    2009-01-01

    A few drug-like molecules have recently been found to bind poly(A) and induce a stable secondary structure (Tm ≈ 60°C), even though this RNA homopolymer is single-stranded in the absence of a ligand. Here, we report results from experiments specifically designed to explore the association of small molecules with poly(A). We demonstrate that coralyne, the first small molecule discovered to bind poly(dA), binds with unexpectedly high affinity (Ka >107 M−1), and that the crescent shape of coralyne appears necessary for poly(A) binding. We also show that the binding of similar ligands to poly(A) can be highly cooperative. For one particular ligand, at least six ligand molecules are required to stabilize the poly(A) self-structure at room temperature. This highly cooperative binding produces very sharp transitions between unstructured and structured poly(A) as a function of ligand concentration. Given the fact that junctions between Watson–Crick and A·A duplexes are tolerated, we propose that poly(A) sequence elements and appropriate ligands could be used to reversibly drive transitions in DNA and RNA-based molecular structures by simply diluting/concentrating a sample about the poly(A)-ligand ‘critical concentration’. The ligands described here may also find biological or medicinal applications, owing to the 3′-polyadenylation of mRNA in living cells. PMID:19073699

  8. Poly(esterimide) bearing azobenzene units as photoaligning layer for liquid crystals

    NASA Astrophysics Data System (ADS)

    Węgłowski, Rafał; Piecek, Wiktor; Kozanecka-Szmigiel, Anna; Konieczkowska, Jolanta; Schab-Balcerzak, Ewa

    2015-11-01

    The custom synthesized azobenzene side-chain poly(esterimide) was used as an aligning material for nematic liquid crystal molecules. The anisotropy of the poly(esterimide) layer was generated by a linearly polarized UV light, as a consequence of multiple trans-cis-trans isomerization cycles. The photoalignment effect was studied by assembling a twisted nematic cell with a proper liquid crystal mixture and geometry to fulfill Mauguin's limit. The polarizing microscope pictures of the fabricated cells confirmed the twisted arrangement of liquid crystal molecules. The results of electro-optic measurements indicated a stronger anchoring of the liquid crystal molecules by photoaligned poly(esterimide) than that obtained in the case of a rubbed polyimide.

  9. Iron- and indium-catalyzed reactions toward nitrogen- and oxygen-containing saturated heterocycles.

    PubMed

    Cornil, Johan; Gonnard, Laurine; Bensoussan, Charlélie; Serra-Muns, Anna; Gnamm, Christian; Commandeur, Claude; Commandeur, Malgorzata; Reymond, Sébastien; Guérinot, Amandine; Cossy, Janine

    2015-03-17

    A myriad of natural and/or biologically active products include nitrogen- and oxygen-containing saturated heterocycles, which are thus considered as attractive scaffolds in the drug discovery process. As a consequence, a wide range of reactions has been developed for the construction of these frameworks, much effort being specially devoted to the formation of substituted tetrahydropyrans and piperidines. Among the existing methods to form these heterocycles, the metal-catalyzed heterocyclization of amino- or hydroxy-allylic alcohol derivatives has emerged as a powerful and stereoselective strategy that is particularly interesting in terms of both atom-economy and ecocompatibility. For a long time, palladium catalysts have widely dominated this area either in Tsuji-Trost reactions [Pd(0)] or in an electrophilic activation process [Pd(II)]. More recently, gold-catalyzed formation of saturated N- and O-heterocycles has received growing attention because it generally exhibits high efficiency and diastereoselectivity. Despite their demonstrated utility, Pd- and Au-complexes suffer from high costs, toxicity, and limited natural abundance, which can be barriers to their widespread use in industrial processes. Thus, the replacement of precious metals with less expensive and more environmentally benign catalysts has become a challenging issue for organic chemists. In 2010, our group took advantage of the ability of the low-toxicity and inexpensive FeCl3 in activating allylic or benzylic alcohols to develop iron-catalyzed N- and O-heterocylizations. We first focused on N-heterocycles, and a variety of 2,6-disubstituted piperidines as well as pyrrolidines were synthesized in a highly diastereoselective fashion in favor of the cis-compounds. The reaction was further extended to the construction of substituted tetrahydropyrans. Besides triggering the formation of heterocycles, the iron salts were shown to induce a thermodynamic epimerization, which is the key to reach the high

  10. Tautomers of 2-aminothiazole molecules in aqueous solutions explored by Raman, SERS and DFT methods

    NASA Astrophysics Data System (ADS)

    Chen, Xue; Hu, Yongjun; Gao, Jiao

    2013-10-01

    2-Aminothiazole, as a typical heterocyclic amine, may exist amino-imino tautomeric equilibrium in nature. In present report, the optimized structural parameters and vibrational wavenumbers of amino and imino tautomers of the molecule have been predicted by density functional theoretical (DFT) calculation. Comparing the experimental and the calculated Raman spectra, it indicates that the amino tautomer would be the main configuration in the 2-aminothiazole saturated solution. In the concentration-dependent SERS spectra of 2-aminothiazole adsorbed on gold nanoparticles, it is found that the tautomeric equilibrium shifts toward to the amino tautomer when the concentrations is decreased. While the amino tautomer is end-on the surface through the nitrogen atom of thiazole ring at the higher concentrations, the molecule becomes to stand on the metal surface by interacting simultaneously with two nitrogen atoms of the molecule in the diluted solution.

  11. Mutual influence between contiguous TMPyP4 ligands when bound to a synthetic double-stranded Poly(A)-Poly(U)

    NASA Astrophysics Data System (ADS)

    Tolstykh, G.; Kudrev, A.

    2015-10-01

    The cooperativity of TMPyP4 ligand binding to Poly(A)-Poly(U) polynucleotide were monitored in this study by fluorescence spectroscopy and UV-Vis absorbance spectroscopy. To solve the equilibrium binding model between a dye and substrate, a new computational approach has been proposed based collectively on Principal Component Analysis and the conditional probabilities method. This approach suggest that the absorbance and fluorescence variance during a titration is determined by spectral species formed in stepwise saturation of binding sites on Poly(A)-Poly(U) with porphyrin and a conformational changes on a macromolecule. Spectral species assigned to different forms of polymer-ligand complexes whose existences in equilibrium were postulated by the conditional probabilities method. The binding of TMPyP4 molecule to the Poly(A)-Poly(U) enhances the binding of additional molecules to that same receptor. The intrinsic binding constant to an isolated binding site lgKin = 6.4, the cooperativity parameter ω = 5.0, and number of monomers occupied by a ligand n = 2 (25 °C; pH 7) were calculated based upon the non-linear least-squares fitting procedure.

  12. Extended mechanistic aspects on photoinitiated polymerization of 1,6-hexanediol diacrylate by hexaarylbisimidazoles and heterocyclic mercapto compounds.

    PubMed

    Berdzinski, Stefan; Strehmel, Nadine; Lindauer, Heike; Strehmel, Veronika; Strehmel, Bernd

    2014-05-01

    Chlorine substituted hexaarylbisimidazole (o-Cl-HABI) efficiently initiates radical polymerization of multifunctional acrylic esters in the presence of a heterocyclic mercapto compound if the latter can form its tautomeric thione. Exposure of o-Cl-HABI results in lophyl radicals, which efficiently add to the thione in the first step while the second step releases a highly reactive thiyl radical from this intermediate. LC-MS and CID-MS measurements support this reaction scheme. Furthermore, photo-DSC experiments applying UV light between 320 and 380 nm showed that mercaptotriazole and phenylmercaptotriazole exhibited the best reactivity in the monomer 1,6-hexanediol diacrylate (HDDA) while alkyl substituted mercaptotriazoles showed less reactivity. Change of the triazole heterocycle by mercaptoimidazole resulted in a significant decrease of photoinitiation efficiency. This heterocycle does not form the corresponding thione in HDDA as shown by NMR measurements. Replacement of mercaptotriazole by an alkylthiol leads to a system showing the lowest photoinitiation efficiency in this series. Formation of thione structure in the case of heterocyclic mercapto compounds may cause higher reactivity of the heterocyclic mercapto compounds with the lophyl radical in the monomer chosen. PMID:24671230

  13. Identification of sulfur heterocycles in coal liquids and shale oils. Technical progress report, August 1, 1980-May 1, 1981

    SciTech Connect

    Lee, M. L.; Castle, R. N.

    1981-01-01

    The sulfur heterocycle separation scheme which was described in the last progress report was evaluated for quantitative recovery of individual components. The results indicate that recoveries can range from 10% to approx. 30% depending on the structure of the compound. During this period, 23 unsubstituted sulfur-containing heterocyclic ring systems were synthesized in oder to confirm GC/MS identifications and for biological testing. The four possible 3-ring heterocycles and the thirteen possible 4-ring heterocycles were tested for mutagenic activity in the histidine reversion (Ames assay) system. One of the 3-ring isomers, naphtho(1,2-b)-thiophene, and six of the 4-ring isomers induced mutations in Salmonella test strains. One of these compounds, phenanthro(3,4-b)thiophene, displayed approximately the same mutagenic activity as benzo(a)pyrene. A two-step adsorption chromatographic procedure was developed in order to fractionate synthetic fuels into various chemical-type classes for studying the relative concentrations and mutagenic activities of the various types. An SRC-II Heavy Distillate was fractionated into aliphatic hydrocarbons, polycyclic aromatic hydrocarbons, sulfur heterocycles, indoles and carbazoles, azaarenes, and amino polycyclic aromatic hydrocarbons. It was found that the amino-PAH fraction contained most of the mutagenic activity. A survey was made for compounds containing both nitrogen and sulfur heteroatoms in their structures. A number of these compounds were detected by GC using nitrogen- and sulfur-selective detection.

  14. Fascinating frontiers of N/O-functionalized N-heterocyclic carbene chemistry: from chemical catalysis to biomedical applications.

    PubMed

    John, Alex; Ghosh, Prasenjit

    2010-08-21

    The in vogue N-heterocyclic carbenes (NHCs) have attracted attention largely for its new found popularity in chemical catalysis and also for displaying promising traits in biomedical applications. The current perspective provides an account of our efforts in exploring the utility of N/O-functionalized N-heterocyclic carbenes in these two areas. On the catalysis front, we have employed the N/O-functionalized N-heterocyclic carbene based precatalysts for the C-C and C-N bond forming reactions like the Suzuki-Miyaura, Sonogashira and Hiyama cross-couplings, the base-free Michael addition, the alkene and alkyne hydroamination reactions and the ring-opening polymerization (ROP) of L-lactides that produce biodegradable polylactide polymers while on the biomedical application front, the anticancer and antimicrobial properties of these N/O-functionalized N-heterocyclic carbene complexes were evaluated. Towards this objective, the N-heterocyclic carbene chemistry of a variety of transition metals like Ag, Au, Ni and Pd has been investigated. PMID:20495733

  15. Bistable electronic switching in poly(arylenephthalides)

    NASA Astrophysics Data System (ADS)

    Zherebov, A. Yu.; Lachinov, A. N.; Genoe, J.; Tameev, A. R.; Vannikov, A. V.

    2008-06-01

    Experimental and theoretical data show that the phenomenon of bistable switching in thin films of poly(arylenephthalides) (PAPs), which was reported previously, has an electronic nature and is related to the unique properties of PAP molecules. This phenomenon has been studied in metal-PAP-metal and ITO-PAP-ITO structures (ITO = indium tin oxide) with various thicknesses of the polymer film. First results are reported that demonstrate the principal possibility of using thin PAP films as a basis for resistive nonvolatile electronic memory cells. These data show that the bistable switching is related primarily to the electronic properties of the polymer film and is not influenced by the oxidation of electrodes and/or the growth of metal filaments from the electrodes.

  16. The poly(adenylic acid)-protein complex is restricted to the nonpolysomal messenger ribonucleoprotein of Physarum polycephalum.

    PubMed

    Adams, D S; Noonan, D; Jeffery, W R

    1980-04-29

    The distribution of poly(adenylic acid) [poly(A)]-protein complexes in the polysomal and nonpolysomal messenger ribonucleoprotein (mRNP) fractions of Physarum polycephalum was examined in the present study. Poly-(A)-containing components released from the nonpolysomal mRNP by ribonuclease (RNase) digestion were quantitatively adsorbed to nitrocellulose filters at low ionic strength, were highly resistant to micrococcal nuclease under conditions in which free poly(A) was completely degraded, and sedimented as a 10-15S particle which was disrupted by sodium dodecyl sulfate and protease treatment. These are characteristics of the poly(A)-protein complex. In contrast,poly(A)-containing molecules released from the polysomes by RNase were refractive to nitrocellulose, were completely sensitive to micrococcal nuclease, and sedimented at 2-4 S, identical with the sedimentation exhibited by protein-free poly(A). Examination of the poly(A) sequences present in polysomal and nonpolysomal mRNP by polyacylamide gel electrophoresis showed that the former contained only very short sequences, averaging approximately 15 nucleotides, while the latter exhibited only much longer segments, averaging approximately 65 nucleotides. It is concluded that poly(A)-protein complexes are restricted to the nonpolysomal mRNP of Physarum and that the limiting factor in complex formation may be the length of the available poly(A) binding site. PMID:7378386

  17. Access to Structurally Diverse Quinoline-Fused Heterocycles via Rhodium(III)-Catalyzed C-C/C-N Coupling of Bifunctional Substrates.

    PubMed

    Yu, Songjie; Li, Yunyun; Zhou, Xukai; Wang, He; Kong, Lingheng; Li, Xingwei

    2016-06-17

    Rhodium(III)-catalyzed C-H activation of heteroarenes and functionalization with bifunctional substrates such as anthranils allows facile construction of quinoline-fused heterocycles under redox-neutral conditions. The couplings feature broad substrate scope and provide step-economical access to two classes of quinoline-fused condensed heterocycles. PMID:27267178

  18. Phase behavior of a mixture of poly(isoprene)-poly(oxyethylene) diblock copolymer and poly(oxyethylene) surfactant in water.

    PubMed

    Kunieda, Hironobu; Kaneko, Masaya; López-Quintela, M Arturo; Tsukahara, Masahiko

    2004-03-16

    The phase behavior of a mixture of poly(isoprene)-poly(oxyethylene) diblock copolymer (PI-PEO or C250EO70) and poly(oxyethylene) surfactant (C12EO3, C12EO5, C12EO6, C12EO7, and C12EO9) in water was investigated by phase study, small-angle X-ray scattering, and dynamic light scattering (DLS). The copolymer is not soluble in surfactant micellar cubic (I1), hexagonal (H1), and lamellar (Lalpha) liquid crystals, whereas an isotropic copolymer fluid phase coexists with these liquid crystals. Although the PI-PEO is relatively lipophilic, it increases the cloud temperatures of C12EO3-9 aqueous solutions at a relatively high PI-PEO content in the mixture. Most probably, in the copolymer-rich region, PI-PEO and C12EOn form a spherical composite micelle in which surfactant molecules are located at the interface and the PI chains form an oil pool inside. In the C12EO5/ and C12EO6/PI-PEO systems, one kind of micelles is produced in the wide range of mixing fraction, although macroscopic phase separation was observed within a few days after the sample preparation. On the other hand, small surfactant micelles coexist with copolymer giant micelles in C12EO7/ and C12EO9/PI-PEO aqueous solutions in the surfactant-rich region. The micellar shape and size are calculated using simple geometrical relations and compared with DLS data. Consequently, a large PI-PEO molecule is not soluble in surfactant bilayers (Lalpha phase), infinitely long rod micelles (H1 phase), and spherical micelles (I1 phase or hydrophilic spherical micelles) as a result of the packing constraint of the large PI chain. However, the copolymer is soluble in surfactant rod micelles (C12EO5 and C12EO6) because a rod-sphere transition of the surfactant micelles takes place and the long PI chains are incorporated inside the large spherical micelles. PMID:15835666

  19. Small-molecule caspase inhibitors

    NASA Astrophysics Data System (ADS)

    Zhenodarova, S. M.

    2010-02-01

    The review considers low-molecular weight inhibitors of caspases, cysteine proteases being key contributors to apoptosis (programmed cell death). The inhibitors with aspartic acid residues or various heterocyclic systems (both synthetic and natural) are covered. Their possible mechanisms of action are discussed. Data on inhibitor structure-activity relationship studies are systematically surveyed. The interactions of the non-peptide fragments of an inhibitor with the enzymes are examined. Examples of the use of some inhibitors for apoptosis suppression are provided.

  20. Probing the subglass relaxation behavior in model heterocyclic polymer networks by dielectric spectroscopy

    NASA Astrophysics Data System (ADS)

    Kramarenko, V. Yu.; Ezquerra, T. A.; Privalko, V. P.

    2001-11-01

    The subglass relaxation (β) in model heterocyclic polymer networks (HPNs) with a controlled ratio of trimerized mono- and diisocyanates was characterized by dielectric spectroscopy in the frequency domain. The β relaxation in the investigated HPNs follows the Arrhenius law with unusually low values of the preexponential factor (10-17<τβ0<10-15 s). However, little influence of the local environment, as characterized by the network density, on the apparent activation energies ΔEβ is observed. This fact, combined with their fairly low absolute values (50.4-58.3 kJ/mol), were considered as typical of a noncooperative relaxation in loosely packed regions of a glassy quasilattice. Both the intensity and dielectric strength of the β relaxation in HPNs increase with increasing apparent network density (i.e., with lower ratios of linear and network structures in the system, L/N). This effect was explained by a model assuming that the total, composition-invariant, free volume available was distributed between densely packed domains comprising linear, two-arm isocyanurate heterocycles (ISHs) and loosely packed, three-arm ISHs, which form continuous, three-dimensional network structures. The experimental data for HPNs confirm Ngai's correlation between the logarithm of the secondary β-relaxation time and the Kohlrausch-Williams-Watts stretching exponent for the primary α relaxation. It is suggested that the absence of conjugated bonds within isocyanurate heterocycles makes them sufficiently flexible to allow for specific conformational transitions, like the ``chair-boat-chair'' transition in the structurally similar cyclohexyl ring.

  1. Anionic and zwitterionic carboranyl N-heterocyclic carbene Au(i) complexes.

    PubMed

    Fisher, Steven P; El-Hellani, Ahmad; Tham, Fook S; Lavallo, Vincent

    2016-06-14

    The syntheses of the first carboranyl N-heterocyclic carbene complexes with transition metals are reported. Both unsymmetrical mono-anionic and symmetrical dianionic NHCs readily react with ClAuSMe2 to afford unusual zwitterionic and anionic Au(i) dimethyl sulfide adducts. The compounds are characterized by NMR, mass spectrometry, and single crystal X-ray diffraction studies. Percent buried volume (%Vbur) calculations indicate that replacement of an adamantyl group by a hydride substituted icosahedral carborane anion results in a 3.7% increase in %Vbur. PMID:26922968

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

    PubMed

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

    2016-08-01

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

  3. Carboxylation of terminal alkynes with CO2 using novel silver N-heterocyclic carbene complexes.

    PubMed

    Li, Shanshan; Sun, Jing; Zhang, Zhizhi; Xie, Ruixia; Fang, Xiangchen; Zhou, Mingdong

    2016-06-28

    Four novel N-heterocyclic carbene (NHC) silver complexes, , have been synthesized and characterized. The single X-ray crystal diffraction data indicate a dinuclear solid-state structure for and and a mononuclear structure for and . These complexes have been successfully used as efficient catalysts for the C-H activating carboxylation of terminal alkynes with CO2. A wide range of substrates with various functional groups afforded the corresponding aryl or alkyl substituted propiolic acids in good yields under mild conditions. Moreover, the role of bases and the reaction mechanism is thoroughly discussed. PMID:27263977

  4. N-Heterocyclic Carbene-Mediated Oxidative Electrosynthesis of Esters in a Microflow Cell.

    PubMed

    Green, Robert A; Pletcher, Derek; Leach, Stuart G; Brown, Richard C D

    2015-07-01

    An efficient N-heterocyclic carbene (NHC)-mediated oxidative esterification of aldehydes has been achieved in an undivided microfluidic electrolysis cell at ambient temperature. Productivities of up to 4.3 g h(-1) in a single pass are demonstrated, with excellent yields and conversions for 19 examples presented. Notably, the oxidative acylation reactions were shown to proceed with a 1:1 stoichiometry of aldehyde and alcohol (for primary alcohols), with remarkably short residence times in the electrolysis cell (<13 s), and without added electrolyte. PMID:26073623

  5. Latent ruthenium–indenylidene catalysts bearing a N-heterocyclic carbene and a bidentate picolinate ligand

    PubMed Central

    Schmid, Thibault E; Modicom, Florian; Dumas, Adrien; Borré, Etienne; Toupet, Loic

    2015-01-01

    Summary A silver-free methodology was developed for the synthesis of unprecedented N-heterocyclic carbene ruthenium indenylidene complexes bearing a bidentate picolinate ligand. The highly stable (SIPr)(picolinate)RuCl(indenylidene) complex 4a (SIPr = 1,3-bis(2-6-diisopropylphenyl)imidazolidin-2-ylidene) demonstrated excellent latent behaviour in ring closing metathesis (RCM) reaction and could be activated in the presence of a Brønsted acid. The versatility of the catalyst 4a was subsequently demonstrated in RCM, cross-metathesis (CM) and enyne metathesis reactions. PMID:26425213

  6. N-Heterocyclic Carbene Complexes of Rh: Reaction With Dioxygen Without Oxidation

    SciTech Connect

    Praetorius, J.M.; Allen, D.P.; Wang, R.; Webb, J.D.; Grein, F.; Kennepohl, P.; Crudden, C.M.

    2009-05-21

    The reaction of oxygen with rhodium complexes containing N-heterocyclic carbenes was found to give dioxygen complexes with rare square planar geometries and unusually short O-O bond lengths. Analysis of the bonding in these complexes by Rh L-edge X-ray absorption spectroscopy (XAS), Raman spectroscopy, and DFT calculations provides evidence for a bonding model in which singlet oxygen is bound to a Rh(I) d{sup 8} metal complex, rather than the more common Rh(III) d{sup 6} peroxo species with octahedral geometry and O-O bond lengths in the 1.4-1.5 {angstrom} range.

  7. Stereoselective Synthesis of Saturated Heterocycles via Pd-Catalyzed Alkene Carboetherification and Carboamination Reactions

    PubMed Central

    Wolfe, John P.

    2009-01-01

    The development of Pd-catalyzed carboetherification and carboamination reactions between aryl/alkenyl halides and alkenes bearing pendant heteroatoms is described. These transformations effect the stereoselective construction of useful heterocycles such as tetrahydrofurans, pyrrolidines, imidazolidin-2-ones, isoxazolidines, and piperazines. The scope, limitations, and applications of these reactions are presented, and current stereochemical models are described. The mechanism of product formation, which involves an unusual intramolecular syn-insertion of an alkene into a Pd-Heteroatom bond is also discussed in detail. PMID:19183704

  8. New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

    PubMed Central

    Suchodolski, Szymon; Wojtkielewicz, Agnieszka; Morzycki, Jacek W

    2015-01-01

    Summary The synthesis of a new type of Hoveyda–Grubbs 2nd generation catalyst bearing a modified N-heterocyclic carbene ligands is reported. The new catalyst contains an NHC ligand symmetrically substituted with chromanyl moieties. The complex was tested in model CM and RCM reactions. It showed very high activity in CM reactions with electron-deficient α,β-unsaturated compounds even at 0 °C. It was also examined in more demanding systems such as conjugated dienes and polyenes. The catalyst is stable, storable and easy to purify. PMID:26877801

  9. New extended {pi}-electron donors. Tetrathiafulvalene systems with heterocyclic spacer groups

    SciTech Connect

    Hansen, T.K.; Jensen, F.; Becher, J.

    1992-06-17

    Nine new heterocyclic {pi}-electron donors 10a-c, 11a-c, and 12a-c based upon the well-known TTF (tetrathiafulvalene) system, but incorporating a pyrrole, thiophene, or furan ring between the 1,3-thiole rings, have been synthesized. The compounds show two single-electron reversible oxidation waves in cyclic voltammetry. Some TCNQ complexes and conductivity measurements are reported, indicating the new compounds to be good candidates for {open_quotes}organic metals{close_quotes}. The influence of the central conjugated system on redox properties is discussed using MNDO-PM3 calculations. 17 refs., 5 figs., 1 tab.

  10. Synthesis and antibacterial activity of some heterocyclic chalcone analogues alone and in combination with antibiotics.

    PubMed

    Tran, Thanh-Dao; Nguyen, Thi-Thao-Nhu; Do, Tuong-Ha; Huynh, Thi-Ngoc-Phuong; Tran, Cat-Dong; Thai, Khac-Minh

    2012-01-01

    A series of simple heterocyclic chalcone analogues have been synthesized by Claisen Schmidt condensation reactions between substituted benzaldehydes and heteroaryl methyl ketones and evaluated for their antibacterial activity. The structures of the synthesized chalcones were established by IR and ¹H-NMR analysis. The biological data shows that compounds p₅, f₆ and t₅ had strong activities against both susceptible and resistant Staphylococcus aureus strains, but not activity against a vancomycin and methicillin resistant Staphylococcus aureus isolated from a human sample. The structure and activity relationships confirmed that compounds f₅, f₆ and t₅ are potential candidates for future drug discovery and development. PMID:22728362

  11. An abnormal N-heterocyclic carbene based nickel complex for catalytic reduction of nitroarenes.

    PubMed

    Vijaykumar, Gonela; Mandal, Swadhin K

    2016-05-01

    Herein we report the synthesis of a nickel(ii) dichloro complex bearing an abnormal N-heterocyclic carbene (aNHC). The NiCl2(aNHC)2 complex has been used as an efficient catalyst for the reduction of nitroarenes with hydrosilanes to give aromatic amines in good to excellent yields. This catalytic protocol can tolerate functional groups such as halides, alkenes or nitriles. Furthermore, the longevity of the catalyst was tested in successive catalytic cycles, which indicates a sustained catalytic activity over multiple catalytic cycles. PMID:27041677

  12. [Experimental evaluation of actoprotective activity of nitrogen-containing heterocyclic compounds derivatives in extreme conditions].

    PubMed

    Tsublova, E G; Ivanova, T G; Ivanova, T N; Iasnetsov, V V

    2013-07-01

    In experiments on nonlinear male mice the ability of new derivatives of nitrogen-containing heterocyclic compounds to increase the physical working capacity in conditions of hyperthermia, hypothermia and acute normobaric hypoxia and hypercapnia has been investigated. It is established, that pyridine derivative IBHF-11 has more expressed positive action in the said conditions. It provided increase of the working capacity of animals at all kinds of extreme influence, and the value of positive action was comparable, and in conditions of acute normobaric hypoxia and hypercapnia exceeded those at the reference products bemitil and bromantan. PMID:24341005

  13. 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

  14. Enantioselective conjugate addition of alkylboranes catalyzed by a copper-N-heterocyclic carbene complex.

    PubMed

    Yoshida, Mika; Ohmiya, Hirohisa; Sawamura, Masaya

    2012-07-25

    The first catalytic enantioselective conjugate addition of alkylboron compounds has been achieved. Reactions between alkylboranes and imidazol-2-yl α,β-unsaturated ketones proceeded with high enantioselectivity under the influence of a Cu(I) catalyst system, prepared in situ from CuCl, a new chiral imidazolium salt as a precursor for the N-heterocyclic carbene ligand, and PhOK. Alkylboranes are widely obtained via alkene hydroboration. A variety of functional groups are tolerated in alkylboranes and α,β-unsaturated ketones. PMID:22746339

  15. Greener and sustainable approaches to the synthesis of pharmaceutically active heterocycles.

    PubMed

    Polshettiwar, Vivek; Varma, Rajender S

    2007-11-01

    Green chemistry is a rapidly developing field providing a proactive avenue for the sustainable development of future science and technology. Green chemistry can be applied to the design of highly efficient, environmentally benign synthetic protocols to deliver life-saving medicines, and to accelerate lead optimization processes in drug discovery, while minimizing environmental impact. It also offers enhanced chemical process economics, concomitant with a reduced environmental burden. This review summarizes relatively environmentally benign protocols for the synthesis of pharmaceutically active heterocycles that highlight the advantages of using green chemistry, for example, by proceeding under microwave irradiation or in aqueous reaction media. PMID:17987524

  16. Herbicidal, plant growth inhibitory, and cytotoxic activities of bismuthines containing aromatic heterocycles.

    PubMed

    Céspedes, Carlos L; Lemus, Adela; Salazar, Juan R; Cabrera, Armando; Sharma, Pankaj

    2003-05-01

    This work presents the herbicidal and plant growth regulatory activities of tertiary bismuthines containing heterocyclic aromatic rings of the general formula (2-C(4)H(3)X)(3)Bi, where X = S (3), O (1), or NMe (2). Toxicity against Artemia salina and herbicidal activity on Lactuca sativa, Trifolium pratense, and Lolium multiflorum were tested. In addition to the effects on mitochondrial respiration obtained from roots of Phaseolus vulgaris, these compounds also demonstrated partial radical scavenging properties against 2,2-diphenyl-1-picrylhydrazyl (DPPH). The furyl substituent is the most important structural requirement for the activity measurements observed in this study. PMID:12720372

  17. A Ruthenium Catalyst for Olefin Metathesis Featuring an Anti-Bredt N-Heterocyclic Carbene Ligand

    PubMed Central

    Martin, David; Marx, Vanessa M.

    2016-01-01

    A ruthenium complex bearing an “anti-Bredt” N-heterocyclic carbene was synthesized, characterized and evaluated as a catalyst for olefin metathesis. Good conversions were observed at room temperature for the formation of di- and tri-substituted olefins by ring-closing metathesis. It also allowed for the ring-opening metathesis polymerization of cyclooctadiene, as well as for the cross-metathesis of cis-1,4-diacetoxy-2-butene with allyl-benzene, with enhanced Z/E kinetic selectivity over classical NHC-based catalysts.

  18. Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors.

    PubMed

    Florence, Gordon J; Fraser, Andrew L; Gould, Eoin R; King, Elizabeth F; Menzies, Stefanie K; Morris, Joanne C; Thomson, Marie I; Tulloch, Lindsay B; Zacharova, Marija K; Smith, Terry K

    2016-07-19

    Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world's poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin-inspired derivatives, namely 3,5-isoxazoles, furoxans, and furazans. Several of these compounds maintain low-micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment. PMID:27283448

  19. Influence of peripheral substituents on the optical properties of heterocyclic azo dyes

    NASA Astrophysics Data System (ADS)

    Derkowska-Zielinska, B.; Skowronski, L.; Kozlowski, T.; Smokal, V.; Kysil, A.; Biitseva, A.; Krupka, O.

    2015-11-01

    Optical properties, such as the real and imaginary parts of the dielectric function and the optical energy band gap, of new heterocyclic azo dyes thin films were investigated using spectroscopic ellipsometry combined with transmittance measurements. The topography of studied compounds was also examined by atomic force microscopy. It was found that the optical properties of the azo dyes materials strongly depend on the type of substitution in the azobenzene moiety, namely leads to a change in the value of refractive index, as well as bathochromic shifts of the absorption structure.

  20. Near-UV phosphorescent emitters: N-heterocyclic platinum(ii) tetracarbene complexes.

    PubMed

    Unger, Yvonne; Zeller, Alexander; Taige, Maria A; Strassner, Thomas

    2009-06-28

    Although examples of nickel(ii), palladium(ii) and platinum(ii) N-heterocyclic tetracarbene complexes are known in the literature, particularly platinum(ii) tetracarbene complexes are rare. We developed a new synthetic route via biscarbene acetate complexes, which make homoleptic as well as heteroleptic platinum(ii) tetracarbene complexes accessible. The reported photoluminescence data show that these complexes have good quantum yields and photostability and are a promising class of emitters for PhOLEDs. Characterization of the compounds includes a solid-state structure of the homoleptic complex bis(1,1'-diisopropyl-3,3'-methylenediimidazoline-2,2'-diylidene)platinum(ii) dibromide. PMID:19513490

  1. Development and Applications of Transesterification Reactions Catalyzed by N-Heterocyclic Olefins.

    PubMed

    Blümel, Marcus; Noy, Janina-Miriam; Enders, Dieter; Stenzel, Martina H; Nguyen, Thanh V

    2016-05-01

    A novel method to utilize N-heterocyclic olefins (NHOs), the alkylidene derivatives of N-heterocycic carbenes, as organocatalysts to promote transesterification reactions has been developed. Because of their strong Brønsted/Lewis basicity, NHOs can enhance the nucleophilicity of alcohols for their acylation reactions with carboxylic esters. This transformation can be employed in industrially relevant processes such as the production of biodiesel, the depolymerization of polyethylene terephthalate (PET) from plastic bottles for recycling purposes, and the ring-opening polymerization of cyclic esters to form biodegradable polymers such as polylactide (PLA) and polycaprolactone (PCL). PMID:27115463

  2. Insights into the mechanistic and synthetic aspects of the Mo/P-catalyzed oxidation of N-heterocycles.

    PubMed

    Larionov, Oleg V; Stephens, David; Mfuh, Adelphe M; Arman, Hadi D; Naumova, Anastasia S; Chavez, Gabriel; Skenderi, Behije

    2014-05-21

    A Mo/P catalytic system for an efficient gram-scale oxidation of a variety of nitrogen heterocycles to N-oxides with hydrogen peroxide as terminal oxidant has been investigated. Combined spectroscopic and crystallographic studies point to the tetranuclear Mo4P peroxo complex as one of the active catalytic species present in the solution. Based on this finding an optimized catalytic system has been developed. The utility and chemoselectivity of the catalytic system has been demonstrated by the synthesis of over 20 heterocyclic N-oxides. PMID:24643619

  3. Indirect C-H azidation of heterocycles via copper-catalyzed regioselective fragmentation of unsymmetrical λ3-iodanes.

    PubMed

    Lubriks, Dmitrijs; Sokolovs, Igors; Suna, Edgars

    2012-09-19

    A C-H bond of electron-rich heterocycles is transformed into a C-N bond in a reaction sequence comprising the formation of heteroaryl(phenyl)iodonium azides and their in situ regioselective fragmentation to heteroaryl azides. A Cu(I) catalyst ensures complete regiocontrol in the fragmentation step and catalyzes the subsequent 1,3-dipolar cycloaddition of the formed azido heterocycles with acetylenes. The heteroaryl azides can also be conveniently reduced to heteroarylamines by aqueous ammonium sulfide. The overall C-H to C-N transformation is a mild and operationally simple one-pot sequential multistep process. PMID:22913396

  4. Metal-catalyzed [6 + 3] cycloaddition of tropone with azomethine ylides: a practical access to piperidine-fused bicyclic heterocycles.

    PubMed

    Liu, Honglei; Wu, Yang; Zhao, Yan; Li, Zhen; Zhang, Lei; Yang, Wenjun; Jiang, Hui; Jing, Chengfeng; Yu, Hao; Wang, Bo; Xiao, Yumei; Guo, Hongchao

    2014-02-12

    The first metal-catalyzed [6 + 3] cycloaddition of tropone with azomethine ylides has been developed. With the use of a chiral ferrocenylphosphine-copper(I) complex as the catalyst, the asymmetric variant of the [6 + 3] cycloaddition has also been successfully achieved. The reactions proceeded smoothly under mild conditions, affording piperidine-fused bicyclic heterocycles in moderate to high yields with good to excellent diastereo- and enantioselectivies. The procedures are operationally simple and the catalysts are cheap and readily accessible, thus providing a practical approach to piperidine-fused bicyclic heterocycles. PMID:24450417

  5. Facile Gold-Catalyzed Heterocyclization of Terminal Alkynes and Cyanamides Leading to Substituted 2-Amino-1,3-Oxazoles.

    PubMed

    Rassadin, Valentin A; Boyarskiy, Vadim P; Kukushkin, Vadim Yu

    2015-07-17

    Facile gold-catalyzed heterocyclization based upon intermolecular trapping of the generated α-oxo gold carbenes with various cyanamides R(2)R(3)NCN (R(2)/R(3) = Alk/Alk, -(CH2)2O(CH2)2-, Ar/Ar, Ar/H) has been developed. In most cases, 2-amino-1,3-oxazoles functionalized at the nitrogen atom as well as at the fifth position of the heterocyclic ring (12 examples) were isolated in good to moderate yields. PMID:26135038

  6. Cationic bis-N-heterocyclic carbene (NHC) ruthenium complex: structure and application as latent catalyst in olefin metathesis.

    PubMed

    Rouen, Mathieu; Queval, Pierre; Falivene, Laura; Allard, Jessica; Toupet, Loïc; Crévisy, Christophe; Caijo, Frédéric; Baslé, Olivier; Cavallo, Luigi; Mauduit, Marc

    2014-10-13

    An unexpected cationic bis-N-heterocyclic carbene (NHC) benzylidene ether based ruthenium complex (2 a) was prepared through the double incorporation of an unsymmetrical unsaturated N-heterocyclic carbene (U2 -NHC) ligand that bore an N-substituted cyclododecyl side chain. The isolation and full characterization (including X-ray diffraction studies) of key synthetic intermediates along with theoretical calculations allowed us to understand the mechanism of the overall cationization process. Finally, the newly developed complex 2 a displayed interesting latent behavior during ring-closing metathesis, which could be "switched on" under acidic conditions. PMID:25212827

  7. Advanced poly-LED displays

    NASA Astrophysics Data System (ADS)

    Childs, Mark; Nisato, Giovanni; Fish, D.; Giraldo, Andrea; Jenkins, A. J.; Johnson, Mark T.

    2003-05-01

    Philips have been actively developing polymer OLED (poly-LED) displays as a future display technology. Their emissive nature leads to a very attractive visual appearance, with wide viewing angle, high brightness and fast response speed. Whilst the first generation of poly-LED displays are likely to be passive-matrix driven, power reduction and resolution increase will lead to the use of active-matrix poly-LED displays. Philips Research have designed, fabricated and characterized five different designs of active-matrix polymer-LED display. Each of the five displays makes use of a distinct pixel programming- or pixel drive-technique, including current programming, threshold voltage measurement and photodiode feedback. It will be shown that hte simplest voltage-programmed current-source pixel suffers from potentially unacceptable brightness non-uniformity, and that advanced pixel circuits can provide a solution to this. Optical-feedback pixel circuits will be discussed, showing that they can be used to improve uniformity and compensate for image burn-in due to polymer-LED material degradation, improving display lifetime. Philips research has also been active in developing technologies required to implement poly-LED displays on flexible substrates, including materials, processing and testing methods. The fabrication of flexible passive-matrix poly-LED displays will be presented, as well as the ongoing work to assess the suitability of processing flexible next-generation poly-LED displays.

  8. Poly-instanton inflation

    NASA Astrophysics Data System (ADS)

    Cicoli, Michele; Pedro, Francisco G.; Tasinato, Gianmassimo

    2011-12-01

    We propose a new inflationary scenario in type IIB Calabi-Yau compactifications, where the inflaton is a Kähler modulus parameterising the volume of an internal four-cycle. The inflaton potential is generated via poly-instanton corrections to the superpotential which give rise to a naturally flat direction due to their double exponential suppression. Given that the volume mode is kept stable during inflation, all the inflaton-dependent higher dimensional operators are suppressed. Moreover, string loop effects can be shown to be negligible throughout all the inflationary dynamics for natural values of the underlying parameters. The model is characterised by a reheating temperature of the order Trh simeq 106 GeV which requires Ne simeq 54 e-foldings of inflation. All the inflationary observables are compatible with current observations since the spectral index is ns simeq 0.96, while the tensor-to-scalar ratio is r simeq 10-5. The volume of the Calabi-Yau is of order 103 in string units, corresponding to an inflationary scale around 1015 GeV.

  9. Poly-instanton inflation

    SciTech Connect

    Cicoli, Michele; Pedro, Francisco G.; Tasinato, Gianmassimo E-mail: f.pedro1@physics.ox.ac.uk

    2011-12-01

    We propose a new inflationary scenario in type IIB Calabi-Yau compactifications, where the inflaton is a Kähler modulus parameterising the volume of an internal four-cycle. The inflaton potential is generated via poly-instanton corrections to the superpotential which give rise to a naturally flat direction due to their double exponential suppression. Given that the volume mode is kept stable during inflation, all the inflaton-dependent higher dimensional operators are suppressed. Moreover, string loop effects can be shown to be negligible throughout all the inflationary dynamics for natural values of the underlying parameters. The model is characterised by a reheating temperature of the order T{sub rh} ≅ 10{sup 6} GeV which requires N{sub e} ≅ 54 e-foldings of inflation. All the inflationary observables are compatible with current observations since the spectral index is n{sub s} ≅ 0.96, while the tensor-to-scalar ratio is r ≅ 10{sup −5}. The volume of the Calabi-Yau is of order 10{sup 3} in string units, corresponding to an inflationary scale around 10{sup 15} GeV.

  10. Synthesis and self-assembly of poly(3-hexylthiophene)-block-poly(acrylic acid)

    SciTech Connect

    Li, Zicheng; Ono, Robert J.; Wu, Zong-Quan; Bielawski, Christopher W.

    2011-01-01

    A modular and convenient synthesis of ethynyl end functionalized poly(3-hexylthiophene) in high purity is reported; this material facilitated access to poly(3-hexylthiophene)-block-poly(acrylic acid) which self-assembled into hierarchical structures.

  11. Length heteroplasmy of the polyC-polyT-polyC stretch in the dog mtDNA control region.

    PubMed

    Verscheure, Sophie; Backeljau, Thierry; Desmyter, Stijn

    2015-09-01

    Previously, the mitochondrial control region of 214 Belgian dogs was sequenced. Analysis of this data indicated length heteroplasmy of the polyT stretch in the polyC-polyT-polyC stretch from positions 16661 to 16674. Nine polyC-polyT-polyC haplotype combinations were observed, consisting of seven major haplotypes (highest signal intensity) combined with minor haplotypes (lower signal intensity) one T shorter than the major haplotype in all but three dogs. The longer the polyT stretch, the smaller was the difference in signal intensity between the major and minor haplotype peaks. Additional sequencing, cloning, and PCR trap experiments were performed to further study the intra-individual variation of this mitochondrial DNA (mtDNA) region. Cloning experiments demonstrated that the proportion of clones displaying the minor haplotypes also increased with the length of the polyT stretch. Clone amplification showed that in vitro polymerase errors might contribute to the length heteroplasmy of polyT stretches with at least 10 Ts. Although major and minor polyC-polyT-polyC haplotypes did not differ intra-individually within and between tissues in this study, interpretation of polyT stretch variation should be handled with care in forensic casework. PMID:25394743

  12. Reprogramming the assembly of unmodified DNA with a small molecule

    NASA Astrophysics Data System (ADS)

    Avakyan, Nicole; Greschner, Andrea A.; Aldaye, Faisal; Serpell, Christopher J.; Toader, Violeta; Petitjean, Anne; Sleiman, Hanadi F.

    2016-04-01

    The ability of DNA to store and encode information arises from base pairing of the four-letter nucleobase code to form a double helix. Expanding this DNA ‘alphabet’ by synthetic incorporation of new bases can introduce new functionalities and enable the formation of novel nucleic acid structures. However, reprogramming the self-assembly of existing nucleobases presents an alternative route to expand the structural space and functionality of nucleic acids. Here we report the discovery that a small molecule, cyanuric acid, with three thymine-like faces, reprogrammes the assembly of unmodified poly(adenine) (poly(A)) into stable, long and abundant fibres with a unique internal structure. Poly(A) DNA, RNA and peptide nucleic acid (PNA) all form these assemblies. Our studies are consistent with the association of adenine and cyanuric acid units into a hexameric rosette, which brings together poly(A) triplexes with a subsequent cooperative polymerization. Fundamentally, this study shows that small hydrogen-bonding molecules can be used to induce the assembly of nucleic acids in water, which leads to new structures from inexpensive and readily available materials.

  13. Reprogramming the assembly of unmodified DNA with a small molecule.

    PubMed

    Avakyan, Nicole; Greschner, Andrea A; Aldaye, Faisal; Serpell, Christopher J; Toader, Violeta; Petitjean, Anne; Sleiman, Hanadi F

    2016-04-01

    The ability of DNA to store and encode information arises from base pairing of the four-letter nucleobase code to form a double helix. Expanding this DNA 'alphabet' by synthetic incorporation of new bases can introduce new functionalities and enable the formation of novel nucleic acid structures. However, reprogramming the self-assembly of existing nucleobases presents an alternative route to expand the structural space and functionality of nucleic acids. Here we report the discovery that a small molecule, cyanuric acid, with three thymine-like faces, reprogrammes the assembly of unmodified poly(adenine) (poly(A)) into stable, long and abundant fibres with a unique internal structure. Poly(A) DNA, RNA and peptide nucleic acid (PNA) all form these assemblies. Our studies are consistent with the association of adenine and cyanuric acid units into a hexameric rosette, which brings together poly(A) triplexes with a subsequent cooperative polymerization. Fundamentally, this study shows that small hydrogen-bonding molecules can be used to induce the assembly of nucleic acids in water, which leads to new structures from inexpensive and readily available materials. PMID:27001733

  14. Zymosan enhances the mucosal adjuvant activity of poly(I:C) in a nasal influenza vaccine.

    PubMed

    Ainai, Akira; Ichinohe, Takeshi; Tamura, Shin-Ichi; Kurata, Takeshi; Sata, Tetsutaro; Tashiro, Masato; Hasegawa, Hideki

    2010-03-01

    The synthetic double-stranded RNA polyriboinocinic polyribocytidylic acid [poly(I:C)] is a potent mucosal adjuvant in mice immunized intranasally with an inactivated influenza vaccine. In an attempt, to increase the effectiveness of a nasal poly(I:C)-combined vaccine, the effect of zymosan, a cell wall extract from Saccharomyces cervisiae was investigated, on the adjuvant activity of poly(I:C) in BALB/c mice. The addition of zymosan (10 microg) as an adjuvant in mice which were immunized intranasally with a poly(I:C) (1-5 microg)-combined vaccine (1 microg) enhanced the ability of the mice to mount an effective immune response to a lethal dose of influenza virus, and resulted in a synergistic increase in secretory IgA and serum IgG antibody levels. To define the mechanism by which zymosan enhanced the adjuvant activity of poly(I:C), bone marrow-derived dendritic cells (BM-DCs) were cultured in the presence of poly(I:C) and/or zymosan. There was a synergistic increase in cytokine production (TNF-alpha, IL-6, IL-10, and IFN-beta) in BM-DCs, together with an increase in the expression of co-stimulatory molecules (CD86 and CD40) in response to co-treatment with poly(I:C) and zymosan. This synergistic effect on cytokine production was mimicked by co-treatment with poly(I:C) and a Toll-like receptor 2 (TLR2) ligand, which represented one of the components of zymosan. The results of the current study suggest that one of the mechanisms by which zymosan enhances the adjuvant activity of poly(I:C) is through increased cytokine production by DCs involving the synergistic activation of poly(I:C)-induced TLR3- and zymosan-induced TLR2-mediated signaling pathways. J. Med. Virol. 82:476-484, 2010. (c) 2010 Wiley-Liss, Inc. PMID:20087927

  15. Enzymatic DNA molecules

    NASA Technical Reports Server (NTRS)

    Joyce, Gerald F. (Inventor); Breaker, Ronald R. (Inventor)

    1998-01-01

    The present invention discloses deoxyribonucleic acid enzymes--catalytic or enzymatic DNA molecules--capable of cleaving nucleic acid sequences or molecules, particularly RNA, in a site-specific manner, as well as compositions including same. Methods of making and using the disclosed enzymes and compositions are also disclosed.

  16. Adhesion molecules and receptors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adhesion molecules are necessary for leukocyte trafficking and differentiation. They serve to initiate cell-cell interactions under conditions of shear, and they sustain the cell-cell and cell-matrix interactions needed for cellular locomotion. They also can serve directly as signaling molecules act...

  17. Molecules between the Stars.

    ERIC Educational Resources Information Center

    Verschuur, Gerrit L.

    1987-01-01

    Provides a listing of molecules discovered to date in the vast interstellar clouds of dust and gas. Emphasizes the recent discoveries of organic molecules. Discusses molecular spectral lines, MASERs (microwave amplification by stimulated emission of radiation), molecular clouds, and star birth. (TW)

  18. Differential specificity in the glomerular response profiles for alicyclic, bicyclic and heterocyclic odorants

    PubMed Central

    Johnson, Brett A.; Xu, Zhe; Pancoast, Paige; Kwok, Jennifer; Ong, Joan; Leon, Michael

    2008-01-01

    As part of our ongoing effort to relate stimulus to response in the olfactory system, we tested the hypothesis that the unique chemical structures and odors of various cyclic odorants would be associated with unique spatial response patterns in the glomerular layer of the rat olfactory bulb. To this end, rats were exposed to sets of odorants including monocyclic hydrocarbons, bicyclic compounds, and various heterocyclic structures containing oxygen or nitrogen in the ring. Relative activity across the entire layer was assessed by mapping uptake of 2-deoxyglucose into anatomically standardized data matrices. Whereas monocyclic hydrocarbons evoked patterns similar to those evoked by open-chained hydrocarbon odorants, a set of bicyclic compounds with structures and odors similar to camphor evoked uptake in paired ventral domains not previously associated with any other odorant chemical structures. Despite their unique odors as judged by humans, heterocyclic odorants either evoked uptake in previously characterized areas corresponding to their functional groups or stimulated weak or patchy patterns involving isolated glomeruli. While the patchiness of the patterns may be partly related to the rigidity of the compounds, which would be expected to restrict their interactions to only a few receptors, the weakness of the patterns suggests the possibility of species-specific odorant representations. We conclude that whereas some of the novel cyclic structures indeed were represented by unique patterns in the rat bulb, other unique structures were poorly represented, even when they evoked intense and unique odors in humans. PMID:16958095

  19. In vitro binding of mutagenic heterocyclic aromatic amines by Bifidobacterium pseudocatenulatum G4.

    PubMed

    Faridnia, F; Hussin, A S M; Saari, N; Mustafa, S; Yee, L Y; Manap, M Y A

    2010-06-01

    Consumption of probiotics has been associated with decreased risk of colon cancer and reported to have antimutagenic/ anti-carcinogenic properties. One possible mechanism for this effect involves physical binding of the mutagenic compounds, such as heterocyclic amines (HCAs), to the bacteria. Therefore, the objective of this study was to examine the binding capacity of bifidobacterial strains of human origin on mutagenic heterocyclic amines which are suspected to play a role in human cancers. In vitro binding of the mutagens Trp-p-2, IQ, MeIQx, 7,8DiMeIQx and PhIP by three bacterial strains in two media of different pH was analysed using high performance liquid chromatography. Bifidobacterium pseudocatenulatum G4 showed the highest decrease in the total HCAs content, followed by Bifidobacterium longum, and Escherichia coli. pH affects binding capacity; the highest binding was obtained at pH 6.8. Gram-positive tested strains were found to be consistently more effective than the gram-negative strain. There were significant decreases in the amount of HCAs in the presence of different cell concentrations of B. pseudocatenulatum G4; the highest decrease was detected at the concentration of 10(10) cfu/ml. The results showed that HCAs were able to bind with all bacterial strains tested in vitro, thus it may be possible to decrease their absorption by human intestine and increase their elimination via faeces. PMID:21831754

  20. Photochemical Conversion of Phenanthro[9,10-d]imidazoles into π-Expanded Heterocycles.

    PubMed

    Skonieczny, Kamil; Gryko, Daniel T

    2015-06-01

    We discovered that phenanthro[9,10-d]imidazoles bearing a 2-halogenoaryl substituent at position 2 undergo swift photochemically driven direct arylation, leading to barely known phenanthro[9',10':4,5]imidazo[1,2-f]phenanthridines. The reaction is high-yielding, and it does not require any sensitizer or base. The discovered process is tolerant of a variety of substituents present both at positions 1 and 2; i.e., strongly electron-donating and electron-withdrawing substituents are tolerated as well as various heterocyclic units. Steric hindrance does not affect this process. The evidence gathered here indicates that SRN1 mechanism is operating in this case with the formation of radical anion as a critical step, followed by heterolytic cleavage of a carbon-halogen bond. Also TfO groups were shown to undergo cyclization, which allows the use of salicylaldehydes in the construction of heterocyclic systems. Efficiency of this photochemically driven direct arylation has been demonstrated by the synthesis of two systems possessing 13 and 17 conjugated rings, respectively. Phenanthro[9',10':4,5]imidazo[1,2-f]phenanthridines are blue-emitters, and they exhibit strong fluorescence in solution and in the solid state in direct contrast to their precursors. PMID:25938658

  1. Bond cleavage reactions in oxygen and nitrogen heterocycles by a rhodium phosphine complex

    SciTech Connect

    Jones, W.D.; Dong, L.; Myers, A.W. )

    1995-02-01

    The reactions of (C[sub 5]Me[sub 5])Rh(PMe[sub 3])PhH with furan, 2,5-dimethylfuran, 2,3-dihydrofuran, dibenzofuran, pyrrole, 1-methylpyrrole, 2,5-dimethylpyrrole, 1,2,5-trimethylpyrrole, carbazole, 9-methylcarbazole, pyrrolidine, pyridine, 3,5-lutidine, 2,4,6-collidine, pyrazole, 3-methylpyrazole, and piperidine have been investigated. While the oxygen heterocycles give only C-H activation, the nitrogen heterocycles yield C-H and N-H insertion products. The chloro derivative (C[sub 5]Me[sub 5])Rh(PMe[sub 3])[2-(1-methylpyrrole)]Cl was found to crystallize in the monoclinic space group C2/c with a = 13.753 (6) A, b = 9.665 (5) A, c = 30.14 (2) A, [beta] = 99.77 (5)-[degree], Z = 8, and V = 3949 (4.1) A[sup 3] while (C[sub 5]Me[sub 5])Rh(PMe[sub 5])[2-(3,5-lutidine)]Cl was found to crystallize in the monoclinic space group P2[sub 1]/c with a = 14.976 (8) A, b = 8.613 (5) A, c = 17.12 (2) A, [beta] = 101.90 (6)[degree], Z = 4, and V = 2160 (5.2) A[sup 3]. 30 refs., 2 figs., 3 tabs.

  2. Synthesis of Amino- and Nitro-Substituted Heterocycles as Insensitive Energetic Materials

    SciTech Connect

    Pagoria, P F; Lee, G S; Mitchell, A R; Schmidt, R D

    2001-08-23

    In this paper we will describe the synthesis of several amino- and nitro-substituted heterocycles, examples from a continuing research project targeted at the synthesis of new, insensitive energetic materials that possess at least 80% the power of HMX (28% more power than TATB). Recently we reported the synthesis and scale-up of the insensitive energetic material, 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105). The energy content (81% the power of HMX) and thermal stability of LLM-105 make it a viable candidate material for insensitive boosters and deep oil perforation. We will report on recent synthetic improvements and several performance and safety tests performed on LLM-105, including a 1 in. cylinder shot and plate dent. We will also report on the synthesis and characterization of 4-amino-3,5-dinitropyrazole (LLM-116), an interesting new insensitive energetic material with a measured crystal density of 1.90 g/cc, to our knowledge the highest density yet measured for a five-membered heterocycle containing amino- and nitro-substituents. LLM-116 was synthesized by reacting 3,5-dinitropyrazole with 1,1,1-trimethylhydrazinium iodide (TMHI) in DMSO in the presence of base. The synthesis and characterization of 4-amino-5-nitro-1,2,3-triazole (ANTZ) and 43-dinitro-1,2,3-triazole (DNTZ), first described by Baryshnikov and coworkers, will also be presented along with the synthesis of several new energetic materials derived from ANTZ and DNTZ.

  3. PNPCB heterocycles via thermal and Lewis acid catalyzed trans-hydroborations.

    PubMed

    Fan, Louie; Stephan, Douglas W

    2016-05-31

    The compounds iPr2P(BH3)N3, tBu2PC[triple bond, length as m-dash]CR (R = Ph , tBu , Cy ) and Ph2PC[triple bond, length as m-dash]CR (R = Ph , tBu , Cy ) were reacted to give the products tBu2P(C[triple bond, length as m-dash]CR)NP(BH3)iPr2 (R = Ph , tBu , Cy ) and Ph2P(C[triple bond, length as m-dash]CR)NP(BH3)iPr2 (R = Ph , tBu , Cy ). Subsequent thermally induced or Lewis acid catalyzed intramolecular hydroboration of and afforded the PNPCB heterocyclic compounds Ph2P(C[double bond, length as m-dash]CHPh)NP(BH2)iPr2 and tBu2P(C[double bond, length as m-dash]CHPh)NP(BH2)iPr2, respectively. Compounds and were crystallographically characterized and the mechanisms and implications for the synthesis of inorganic heterocycles are considered. PMID:27177164

  4. Masked N-Heterocyclic Carbene-Catalyzed Alkylation of Phenols with Organic Carbonates.

    PubMed

    Lui, Matthew Y; Yuen, Alexander K L; Masters, Anthony F; Maschmeyer, Thomas

    2016-09-01

    An easily prepared masked N-heterocyclic carbene, 1,3-dimethylimidazolium-2-carboxylate (DMI-CO2 ), was investigated as a "green" and inexpensive organocatalyst for the alkylation of phenols. The process made use of various low-toxicity and renewable alkylating agents, such as dimethyl- and diethyl carbonate, in a focused microwave reactor. DMI-CO2 was found to be a very active catalyst and excellent yields of a range of aryl alkyl ethers were obtained under relatively benign conditions. The observed difference in the conversion behavior of phenol methylation, in the presence of either the carbene or 1,8-diazabicycloundec-7-ene (DBU) catalyst, was rationalized on the basis of mechanistic investigations. The primary mode of action for the N-heterocyclic carbene is nucleophilic catalysis. Activation of the dialkyl carbonate electrophile results in concomitant evolution of an organo-soluble alkoxide, which deprotonates the phenolic starting material. In contrast, DBU is initially protonated by the phenol and thus consumed. Subsequent regeneration and participation in nucleophilic catalysis only becomes significant after some phenolate alkylation occurs. PMID:27528488

  5. Generation of N-Heterocycles via Tandem Reactions of N '-(2-Alkynylbenzylidene)hydrazides.

    PubMed

    Qiu, Guanyinsheng; Wu, Jie

    2016-02-01

    As a powerful synthon, N '-(2-alkynylbenzylidene)hydrazides have been utilized efficiently for the construction of N-heterocycles. Since N '-(2-alkynylbenzylidene)hydrazides can easily undergo intramolecular 6-endo cyclization promoted by silver triflate or electrophiles, the resulting isoquinolinium-2-yl amides can proceed through subsequent transformations including [3 + 2] cycloaddition, nucleophilic addition, and [3 + 3] cycloaddition. Several unexpected rearrangements via radical processes were observed in some cases, which afforded nitrogen-containing heterocycles with molecular complexity. Reactive partners including internal alkynes, arynes, ketenimines, ketenes, allenoates, and activated alkenes reacted through [3 + 2] cycloaddition and subsequent aromatization, leading to diverse H-pyrazolo[5,1-a]isoquinolines with high efficiency. Nucleophilic addition to the in situ generated isoquinolinium-2-yl amide followed by aromatization also produced H-pyrazolo[5,1-a]isoquinoline derivatives when terminal alkynes, carbonyls, enamines, and activated methylene compounds were used as nucleophiles. Isoquinoline derivatives were obtained when indoles or phosphites were employed as nucleophiles in the reactions of N '-(2-alkynylbenzylidene)hydrazides. A tandem 6-endo cyclization and [3 + 3] cycloaddition of cyclopropane-1,1-dicarboxylates with N '-(2-alkynylbenzylidene)hydrazides was observed as well. Small libraries of these compounds were constructed. Biological evaluation suggested that some compounds showed promising activities for inhibition of CDC25B, TC-PTP, HCT-116, and PTP1B. PMID:26493018

  6. Heterocyclic amines: evaluation of their role in diet associated human cancer

    PubMed Central

    GOODERHAM, N. J.; MURRAY, S.; LYNCH, A. M.; EDWARDS, R. J.; YADOLLAHI-FARSANI, M.; BRATT, C.; RICH, K. J.; ZHAO, K.; MURRAY, B. P.; BHADRESA, S.; CROSBIE, S. J.; BOOBIS, A. R.; DAVIES, D. S.

    1996-01-01

    1Heterocyclic amines are formed in parts per billion levels when meat is cooked. 2The heterocyclic amines MeIQx and PhIP are efficiently absorbed into the systemic circulation after ingestion of cooked food. 3We have shown that MeIQx and PhIP, both in vitro and in vivo, are substrates for human hepatic CYP1A2, which exclusively and efficiently catalyses their conversion to genotoxic hydroxylamines. 4MeIQx and PhIP are promutagens. MeIQx is a very powerful bacterial mutagen whereas PhIP is a more potent mammalian cell mutagen. Using a mammalian cell target gene, hprt, we have shown that PhIP induces a characteristic mutational ‘fingerprint’. 5MeIQx and PhIP are carcinogenic in bioassays. The PhIP mutational ‘fingerprint’ has been detected in the Apc gene of 5/8 colonic tumours induced by PhIP in rats. PMID:8807149

  7. Direct enantioseparation of nitrogen-heterocyclic pesticides on amylose-tris-(5-chloro-2-methylphenylcarbamate) by reversed-phase high-performance liquid chromatography.

    PubMed

    Yang, Wenwen; Qiu, Jing; Chen, Tianjin; Yang, Shuming; Hou, Shicong

    2012-12-01

    In this study, 11 nitrogen-heterocyclic pesticides were stereoselectively separated on amylose-tris-(5-chloro-2-methylphenylcarbamate) chiral stationary phase, using reversed-phase high-performance liquid chromatography with diode array detector and optical rotation detector at 426 nm. The effects of mobile phase composition and column temperature (5-40 °C) on separation were investigated. When acetonitrile and water were used as mobile phase, satisfactory separations were obtained on amylose-tris-(5-chloro-2-methylphenylcarbamate) for four pesticides with elution orders of (+)/(-)-simeconazole (1), (-)/(+)-nuarimol (3), (-)/(+)-carfentrazone-ethyl (4), and (-)/(+)/(-)/(+)-bromuconazole (9) and part separations for three with elution orders of (-)/(+)-famoxadone (6), (+)/(-)-fenbuconazole (10), and (-)/(+)-triapenthenol (11). Only two chromatographic peaks on diode array detector were obtained for diclobutrazol (2), cyproconazole (5), etaconazole (7), and metconazole (8), although they should have four stereoisomers in theory because of presences of two chiral centers in molecules. The stereoisomeric optical signals of all pesticides did not reverse with temperature changes but would reverse with different solvent types for some pesticides. These results will be useful to prepare and analyze individual enantiomers of chiral pesticides. PMID:22730202

  8. Infrared Spectroscopy of Matrix-Isolated Polycyclic Aromatic Compounds and Their Ions. 7; Phenazine, a Dual Substituted Polycyclic Aromatic Nitrogen Heterocycle

    NASA Technical Reports Server (NTRS)

    Mattioda, A. L.; Hudgins, D. M.; Bauschlicher, C. W., Jr.; Allamandola, L. J.

    2004-01-01

    The matrix-isolation technique has been employed to measure the mid-infrared spectra of phenazine (C12H8N2), a dual substituted Polycyclic Aromatic Nitrogen Heterocycle (PANH), in the neutral, cationic and anionic forms. The experimentally measured band frequencies and intensities are tabulated and compared with their calculated values as well as those of the non-substituted parent molecule, anthracene. The theoretical band positions and intensities were calculated using both the 3-31 G as well as the larger 6-3lG* Basis Sets. A comparison of the results can be found in the tables. The spectroscopic properties of phenazine and its cation are similar to those observed in mono-substituted PANHs, with one exception. The presence of a second nitrogen atom results in an additional enhancement of the cation's total integrated intensity, for the 1500-1000 cm(sup -1) (6.7 to 10 micron) region, over that observed for a mono-substituted PANH cation. The significance of this enhancement and the astrobiological implications of these results are discussed.

  9. A computational study on 3-azonia-, 3-phosphonia-, and 3-arsoniaspiro[2.2]pentanes and related three-membered heterocycles.

    PubMed

    Trujillo, Cristina; Sánchez-Sanz, Goar; Alkorta, Ibon; Elguero, José

    2014-11-10

    A theoretical study at the ab initio MP2/6-311++G(d,p) level of theory is carried out to characterize several heterocyclic spiro[2.2]pentane cations with N, P, and As as spiro atoms. The strain and relative stability of the spiropentanes are obtained through isodesmic reactions. Nucleus-independent chemical shifts (NICS) and 3D NICS isosurfaces show σ-aromatic characteristics, similar to those found in cyclopropane. The interaction with the Cl(-) anion, which results in four different stationary structures, is studied and characterized by means of the atoms in molecules methodology, and Cl⋅⋅⋅pnicogen, Cl⋅⋅⋅H, and Cl⋅⋅⋅C interactions are found. The most stable structure in all cases corresponds to opening of one of the three-membered rings, due to the attack of the Cl atom, and C-Cl bond formation. Furthermore, the reaction with the 3-boranuidaspiro[2.2]pentane anion results in the formation of a new compound through cleavage of one ring of both reactants. PMID:25164279

  10. Synthesis, characterization and crystal structure of some bidentate heterocyclic Schiff base ligands of 4-toluoyl pyrazolones and its mononuclear Cu(II) complexes

    NASA Astrophysics Data System (ADS)

    Vyas, Komal M.; Jadeja, R. N.; Gupta, Vivek K.; Surati, K. R.

    2011-03-01

    We depict the synthesis of a new set of six bidentate heterocyclic Schiff base ligands, formed by the condensation of three different 4-toluoyl pyrazolones with various aromatic amines in ethanolic medium. All of these ligands have been characterized on the basis of elemental analysis, IR, 1H NMR, 13C NMR and Mass spectral data. The molecular geometries of three of these ligands have been determined by single crystal X-ray study. It reveals that these ligands exist in amine-one tautomeric form in the solid state. The reaction of these ligands with copper(II) resulted in the formation of mononuclear complexes having the general composition [CuL 2(H 2O) 2] with two water molecules at axial positions. These complexes have been characterized on the basis of elemental analysis, Cu-estimation, molar conductivity, magnetic measurements, IR, UV-Visible, FAB-Mass, TG-DTA-DSC data, cyclic voltametric measurements and ESR spectral studies. ESR spectra and magnetic susceptibility measurements indicates distorted octahedral stereochemistry of Cu(II) complexes, while non-electrolytic behaviour of complexes indicates the absence of counter ion.

  11. Determinants of Activity at Human Toll-like Receptors 7 and 8: Quantitative Structure–Activity Relationship (QSAR) of Diverse Heterocyclic Scaffolds

    PubMed Central

    2015-01-01

    Toll-like receptor (TLR) 7 and 8 agonists are potential vaccine adjuvants, since they directly activate APCs and enhance Th1-driven immune responses. Previous SAR investigations in several scaffolds of small molecule TLR7/8 activators pointed to the strict dependence of the selectivity for TLR7 vis-à-vis TLR8 on the electronic configurations of the heterocyclic systems, which we sought to examine quantitatively with the goal of developing “heuristics” to define structural requisites governing activity at TLR7 and/or TLR8. We undertook a scaffold-hopping approach, entailing the syntheses and biological evaluations of 13 different chemotypes. Crystal structures of TLR8 in complex with the two most active compounds confirmed important binding interactions playing a key role in ligand occupancy and biological activity. Density functional theory based quantum chemical calculations on these compounds followed by linear discriminant analyses permitted the classification of inactive, TLR8-active, and TLR7/8 dual-active compounds, confirming the critical role of partial charges in determining biological activity. PMID:25192394

  12. Rapid Trimming of Cell Surface Polysialic Acid (PolySia) by Exovesicular Sialidase Triggers Release of Preexisting Surface Neurotrophin.

    PubMed

    Sumida, Mizuki; Hane, Masaya; Yabe, Uichiro; Shimoda, Yasushi; Pearce, Oliver M T; Kiso, Makoto; Miyagi, Taeko; Sawada, Makoto; Varki, Ajit; Kitajima, Ken; Sato, Chihiro

    2015-05-22

    As acidic glycocalyx on primary mouse microglial cells and a mouse microglial cell line Ra2, expression of polysialic acid (polySia/PSA), a polymer of the sialic acid Neu5Ac (N-acetylneuraminic acid), was demonstrated. PolySia is known to modulate cell adhesion, migration, and localization of neurotrophins mainly on neural cells. PolySia on Ra2 cells disappeared very rapidly after an inflammatory stimulus. Results of knockdown and inhibitor studies indicated that rapid surface clearance of polySia was achieved by secretion of endogenous sialidase Neu1 as an exovesicular component. Neu1-mediated polySia turnover was accompanied by the release of brain-derived neurotrophic factor normally retained by polySia molecules. Introduction of a single oxygen atom change into polySia by exogenous feeding of the non-neural sialic acid Neu5Gc (N-glycolylneuraminic acid) caused resistance to Neu1-induced polySia turnover and also inhibited the associated release of brain-derived neurotrophic factor. These results indicate the importance of rapid turnover of the polySia glycocalyx by exovesicular sialidases in neurotrophin regulation. PMID:25750127

  13. Solution, surface, and single molecule platforms for the study of DNA-mediated charge transport

    PubMed Central

    Muren, Natalie B.; Olmon, Eric D.; Barton, Jacqueline K.

    2012-01-01

    The structural core of DNA, a continuous stack of aromatic heterocycles, the base pairs, which extends down the helical axis, gives rise to the fascinating electronic properties of this molecule that is so critical for life. Our laboratory and others have developed diverse experimental platforms to investigate the capacity of DNA to conduct charge, termed DNA-mediated charge transport (DNA CT). Here, we present an overview of DNA CT experiments in solution, on surfaces, and with single molecules that collectively provide a broad and consistent perspective on the essential characteristics of this chemistry. DNA CT can proceed over long molecular distances but is remarkably sensitive to perturbations in base pair stacking. We discuss how this foundation, built with data from diverse platforms, can be used both to inform a mechanistic description of DNA CT and to inspire the next platforms for its study: living organisms and molecular electronics. PMID:22850865

  14. Increased Hydrogel Swelling Induced by Absorption of Small Molecules.

    PubMed

    Nam, Changwoo; Zimudzi, Tawanda J; Geise, Geoffrey M; Hickner, Michael A

    2016-06-01

    The water and small molecule uptake behavior of amphiphilic diacrylate terminated poly(dimethylsiloxane) (PDMSDA)/poly(ethylene glycol diacrylate) (PEGDA) cross-linked hydrogels were studied using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. These hydrogel networks absorbed more water as the PEGDA content of the network increased. In contrast to typical osmotic deswelling behavior that occurs when liquid water equilibrated hydrogels are immersed in small molecule solutions with water activities less than unity, water-swollen gels immersed in 2-acrylamido-2-methylpropanesulfonic acid (AMPS-H) solutions rapidly regained their water content within 4 min following an initial deswelling response. In situ ATR-FTIR analysis of the hydrogel film during the dynamic swelling experiment indicated that small molecule absorption into the gel played an important role in inducing gel reswelling in low water activity solutions. This aspect of polymer gel water uptake and interaction with small molecules is important for optimizing hydrogel coatings and hydrophilic polymer applications where there is an interaction between the internal chemical structure of the gel and electrolytes or other molecules in solution. PMID:27159118

  15. The Chemistry of Formazan Dyes: Synthesis and Characterization of a Stable Verdazyl Radical and a Related Boron-Containing Heterocycle

    ERIC Educational Resources Information Center

    Berry, David E.; Hicks, Robin G.; Gilroy, Joe B.

    2009-01-01

    This experiment describes the synthesis and characterization of a formazan dye, and its subsequent conversion to a stable verdazyl radical and a boron-nitrogen heterocycle (boratatetrazine). Each of these compounds is intensely colored and is prepared and handled under aerobic conditions, which often surprises students as free radicals are…

  16. Synthesis of 1-Substituted Isoquinolines by Heterocyclization of TosMIC Derivatives: Total Synthesis of Cassiarin A.

    PubMed

    Gutiérrez, Sara; Coppola, Anna; Sucunza, David; Burgos, Carolina; Vaquero, Juan J

    2016-07-15

    A new method for the synthesis of 1-substituted isoquinolines by a heterocyclization that involves α-benzyl TosMIC derivatives and different electrophiles has been developed. This methodology has been successfully applied to a total synthesis of cassiarin A, an alkaloid with potent antiplasmodial activity against Plasmodium falciparum. PMID:27351205

  17. Reactivity studies of pincer bis-protic N-heterocyclic carbene complexes of platinum and palladium under basic conditions

    PubMed Central

    Marelius, David C; Moore, Curtis E; Rheingold, Arnold L

    2016-01-01

    Summary Bis-protic N-heterocyclic carbene complexes of platinum and palladium (4) yield dimeric structures 6 when treated with sodium tert-butoxide in CH2Cl2. The use of a more polar solvent (THF) and a strong base (LiN(iPr)2) gave the lithium chloride adducts monobasic complex 7 or analogous dibasic complex 8. PMID:27559382

  18. Reactivity studies of pincer bis-protic N-heterocyclic carbene complexes of platinum and palladium under basic conditions.

    PubMed

    Marelius, David C; Moore, Curtis E; Rheingold, Arnold L; Grotjahn, Douglas B

    2016-01-01

    Bis-protic N-heterocyclic carbene complexes of platinum and palladium (4) yield dimeric structures 6 when treated with sodium tert-butoxide in CH2Cl2. The use of a more polar solvent (THF) and a strong base (LiN(iPr)2) gave the lithium chloride adducts monobasic complex 7 or analogous dibasic complex 8. PMID:27559382

  19. Atmospheric Hydrogenation of Esters Catalyzed by PNP-Ruthenium Complexes with an N-Heterocyclic Carbene Ligand.

    PubMed

    Ogata, Osamu; Nakayama, Yuji; Nara, Hideki; Fujiwhara, Mitsuhiko; Kayaki, Yoshihito

    2016-08-01

    New pincer ruthenium complexes bearing a monodentate N-heterocyclic carbene ligand were synthesized and demonstrated as powerful hydrogenation catalysts. With an atmospheric pressure of hydrogen gas, aromatic, heteroaromatic, and aliphatic esters as well as lactones were converted into the corresponding alcohols at 50 °C. This reaction protocol offers reliable access to alcohols using an easy operational setup. PMID:27439106

  20. A new one-pot synthesis of novel hetarylazo-heterocyclic colorants and study of their solvatochromic properties.

    PubMed

    Shawali, Ahmad S; Abdallah, Magda A; Kandil, Mohamed A

    2015-09-01

    A simple synthetic strategy for synthesis of new series of hetarylazo-heterocycles is described. The effects of solvent on their electronic absorption spectra were analyzed using Kamlet-Taft equation. The results of fitting coefficients indicated that the solvatochromism of the studied compounds is mainly due to the solvent polarity rather than the solvent basicity and acidity. PMID:27330835

  1. Optimized Syntheses of Cyclopentadienyl Nickel Chloride Compounds Containing "N"-Heterocyclic Carbene Ligands for Short Laboratory Periods

    ERIC Educational Resources Information Center

    Cooke, Jason; Lightbody, Owen C.

    2011-01-01

    Experiments are described for the preparation of imidazolium chloride precursors to "N"-heterocyclic carbenes and their cyclopentadienyl nickel chloride derivatives. The syntheses have been optimized for second- and third-year undergraduate laboratories that have a maximum programmed length of three hours per week. The experiments are flexible and…

  2. Tethered N-heterocyclic carbene-carboranes: unique ligands that exhibit unprecedented and versatile coordination modes at rhodium.

    PubMed

    Holmes, Jordan; Pask, Christopher M; Fox, Mark A; Willans, Charlotte E

    2016-05-11

    Four brand new hybrid ligands combining an N-heterocyclic carbene tethered with two isomeric nido-dicarbaundecaborane dianions, a neutral closo-dicarbadodecaborane or a closo-dicarbadodecaborane anion are described. Versatile coordination of the ligands to Rh(I) is demonstrated, in which both NHC and carborane moieties covalently coordinate a metal centre. PMID:27098432

  3. Pd-N-Heterocyclic Carbene (NHC) Organic Silica: Synthesis and Application in Carbon-Carbon Coupling Reactions

    EPA Science Inventory

    The first Pd-N-heterocyclic carbene (NHC) complex in the form of organic silica was prepared using sol-gel method and its application in Heck and Suzuki reaction were demonstrated. These C-C coupling reactions proceeded efficiently under the influence of microwave irradiation, wi...

  4. Synthesis and Properties of Chelating N-Heterocyclic Carbene Rhodium(I) Complexes: Synthetic Experiments in Current Organometallic Chemistry

    ERIC Educational Resources Information Center

    Mata, Jose A.; Poyatos, Macarena; Mas-Marza, Elena

    2011-01-01

    The preparation and characterization of two air-stable Rh(I) complexes bearing a chelating N-heterocyclic carbene (NHC) ligand is described. The synthesis involves the preparation of a Ag(I)-NHC complex and its use as carbene transfer agent to a Rh(I) precursor. The so obtained complex can be further reacted with carbon monoxide to give the…

  5. Sorocenols G and H, Anti-MRSA Oxygen Heterocyclic Diels-Alder-type Adducts from Sorocea muriculata Roots

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bioassay-guided fractionation of a root extract of Sorocea muriculata led to the isolation and identification of two new oxygen heterocyclic Diels-Alder-type adducts, sorocenols G (1) and H (2), along with lupeol-3-(3'R-hydroxytetradecanoate) and oxyresveratrol. The structures of 1 and 2 were eluci...

  6. Pathways to poly-victimization.

    PubMed

    Finkelhor, David; Ormrod, Richard; Turner, Heather; Holt, Melissa

    2009-11-01

    Some children, whom we have labeled poly-victims, experience very high levels of victimizations of different types. This article finds support for a conceptual model suggesting that there may be four distinct pathways to becoming such a poly-victim: (a) residing in a dangerous community, (b) living in a dangerous family, (c) having a chaotic, multiproblem family environment, or (d) having emotional problems that increase risk behavior, engender antagonism, and compromise the capacity to protect oneself. It uses three waves of the Developmental Victimization Survey, a nationally representative sample of children aged 2-17 years. All four hypothesized pathways showed significant independent association with poly-victim onset. For the younger children, the symptom score representing emotional problems was the only significant predictor. For the older children, the other three pathway variables were significant predictors--dangerous communities, dangerous families, and problem families--but not symptom score. Poly-victimization onset was also disproportionately likely to occur in the year prior to children's 7th and 15th birthday, corresponding roughly to the entry into elementary school and high school. The identification of such pathways and the ages of high onset should help practitioners design programs for preventing vulnerable children from becoming poly-victims. PMID:19837972

  7. Electrochemical measurements of diffusion coefficients of redox-labeled poly(ethylene glycol) dissolved in poly(ethylene glycol) melts

    SciTech Connect

    Haas, O.; Velazquez, C.S.; Porat, Z.; Murray, R.W.

    1995-10-12

    Ferrocene labeled monomethoxy-poly(ethylene glycol)s (MPEG) with molecular weights of 1900 and 750 were used as redox probe solutes in poly(ethylene glycol) melt solvents of molecular weight 750, 2000, and 20000. Cyclic voltammetry and chronoamperometry at microdisk electrodes were employed to measure the diffusion coefficients of the redox probes, which were independent of the probe concentration and varied between 10{sup -7} and 10{sup -10} cm{sup 2}/s. Diffusional activation barrier results also suggest that the ferrocene label does not significantly influence the diffusivity of the probe molecule in the host solvent. Activation barrier, viscosity, and ionic conductivity results show that the LiClO{sub 4} electrolyte does not influence the diffusion barrier or viscosity as long as the ether O/Li{sup +} ratio is >=250 (ca. 0.1 M) which is still a sufficient electrolyte concentration to allow quantitative electrochemical diffusion measurements. 21 refs., 7 figs., 2 tabs.

  8. Effect of interfacial structure on bioinert properties of poly(2-methoxyethyl acrylate)/poly(methyl methacrylate) blend films in water.

    PubMed

    Hirata, T; Matsuno, H; Kawaguchi, D; Yamada, N L; Tanaka, M; Tanaka, K

    2015-07-14

    In this study, we found that the surface made of a mixture of poly(2-methoxyethyl acrylate) (PMEA) and poly(methyl methacrylate) (PMMA) exhibited excellent blood compatibility by inhibiting platelet adhesion. To obtain a better understanding of this bioinertness, the polymer/water interface was characterized by neutron reflectivity measurements and sum frequency generation spectroscopy, in conjunction with bubble contact angle measurements. Based on the results, we can say that the outermost region of the blend film was reorganized in water. When the orientation of PMEA segments at the water interface became random with increasing immersion time, the fractional amount of lower-coordinated water molecules increased at the interface. Such an interfacial structure caused the suppression of platelet adhesion. PMID:26077905

  9. Ultracold polar KRb molecules

    NASA Astrophysics Data System (ADS)

    Neyenhuis, Brian; Chotia, Amodsen; Moses, Steven; Ye, Jun; Jin, Deborah

    2011-05-01

    Ultracold polar molecules in the quantum degenerate regime open the possibility of realizing quantum gases with long-range, and spatially anisotropic, interparticle interactions. Currently, we can create a gas of ultracold fermionic ground-state KRb molecules in with a peak density of 1012 cm-3 and a temperature just 1.4 times the Fermi temperature. We will report on efforts to further cool this gas of molecules. One possibility is to evaporatively cool a spin-polarized molecular Fermi gas confined in quasi-2D, where we would rely on dipole-dipole interactions for rethermalization. We acknowledge funding from NIST, NSF, and AFOSR-MURI.

  10. Poisson's spot with molecules

    SciTech Connect

    Reisinger, Thomas; Holst, Bodil; Patel, Amil A.; Smith, Henry I.; Reingruber, Herbert; Fladischer, Katrin; Ernst, Wolfgang E.; Bracco, Gianangelo

    2009-05-15

    In the Poisson-spot experiment, waves emanating from a source are blocked by a circular obstacle. Due to their positive on-axis interference an image of the source (the Poisson spot) is observed within the geometrical shadow of the obstacle. In this paper we report the observation of Poisson's spot using a beam of neutral deuterium molecules. The wavelength independence and the weak constraints on angular alignment and position of the circular obstacle make Poisson's spot a promising candidate for applications ranging from the study of large molecule diffraction to patterning with molecules.

  11. Poisson's spot with molecules

    NASA Astrophysics Data System (ADS)

    Reisinger, Thomas; Patel, Amil A.; Reingruber, Herbert; Fladischer, Katrin; Ernst, Wolfgang E.; Bracco, Gianangelo; Smith, Henry I.; Holst, Bodil

    2009-05-01

    In the Poisson-spot experiment, waves emanating from a source are blocked by a circular obstacle. Due to their positive on-axis interference an image of the source (the Poisson spot) is observed within the geometrical shadow of the obstacle. In this paper we report the observation of Poisson’s spot using a beam of neutral deuterium molecules. The wavelength independence and the weak constraints on angular alignment and position of the circular obstacle make Poisson’s spot a promising candidate for applications ranging from the study of large molecule diffraction to patterning with molecules.

  12. Investigating single molecule adhesion by atomic force spectroscopy.

    PubMed

    Stetter, Frank W S; Kienle, Sandra; Krysiak, Stefanie; Hugel, Thorsten

    2015-01-01

    Atomic force spectroscopy is an ideal tool to study molecules at surfaces and interfaces. An experimental protocol to couple a large variety of single molecules covalently onto an AFM tip is presented. At the same time the AFM tip is passivated to prevent unspecific interactions between the tip and the substrate, which is a prerequisite to study single molecules attached to the AFM tip. Analyses to determine the adhesion force, the adhesion length, and the free energy of these molecules on solid surfaces and bio-interfaces are shortly presented and external references for further reading are provided. Example molecules are the poly(amino acid) polytyrosine, the graft polymer PI-g-PS and the phospholipid POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine). These molecules are desorbed from different surfaces like CH3-SAMs, hydrogen terminated diamond and supported lipid bilayers under various solvent conditions. Finally, the advantages of force spectroscopic single molecule experiments are discussed including means to decide if truly a single molecule has been studied in the experiment. PMID:25867282

  13. Maprotiline inhibits LPS-induced expression of adhesion molecules (ICAM-1 and VCAM-1) in human endothelial cells

    PubMed Central

    Rafiee, Laleh; Hajhashemi, Valiollah; Javanmard, Shaghayegh Haghjooy

    2016-01-01

    Regardless of the known anti-inflammatory potential of heterocyclic antidepressants, the mechanisms concerning their modulating effects are not completely known. In our earlier work, maprotiline, a heterocyclic antidepressants, considerably inhibited infiltration of polymorphonuclear cell leucocytes into the inflamed paw. To understand the mechanism involved, we evaluated the effect of vascular cell adhesion molecule (VCAM-1), intracellular adhesion molecule (ICAM-1) expression in stimulated endothelial cells. Endothelial cells were stimulated with lipopolysaccharide (LPS) in the presence and absence of maprotiline (10-8 to 10-6 M) and ICAM-1 and VCAM-1 expression were measured using real-time quantitative reverse transcription polymerase chain reaction. Maprotiline significantly decreased the LPS-induced expression of VCAM-1 at all applied concentrations. The expression of ICAM-1 decreased in the presence of maprotiline at 10-6 M concentration (P<0.05). Since maprotiline inhibits the expression of adhesion molecules, ICAM-1 and VCAM-1 in LPS-stimulated human endothelial cells, it can be a possible way through which maprotiline exerts its anti-inflammatory properties. PMID:27168753

  14. Insulin/poly(ethylene glycol)-block-poly(L-lysine) Complexes: Physicochemical Properties and Protein Encapsulation.

    PubMed

    Pippa, Natassa; Kalinova, Radostina; Dimitrov, Ivaylo; Pispas, Stergios; Demetzos, Costas

    2015-06-01

    Insulin (INS) was encapsulated into complexes with poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLys), which is a polypeptide-based block copolymer (a neutral-cationic block polyelectrolyte). The particular cationic-neutral block copolymer can complex INS molecules in aqueous media via electrostatic interactions. Light-scattering techniques are used to study the complexation process and structure of the hybrid nanoparticles in a series of buffers, as a function of protein concentration. The physicochemical and structural characteristics of the complexes depend on the ionic strength of the aqueous medium, while the concentration of PEG-b-PLys was constant through the series of solutions. As INS concentration increased the size distribution of the complexes decreased, especially at the highest ionic strength. The size/structure of complexes diluted in biological medium indicated that the copolymer imparts stealth properties and colloidal and biological stability to the complexes, features that could in turn affect the clearance properties in vivo. Therefore, these studies could be a rational roadmap for designing the optimum complexes/effective nanocarriers for proteins and peptides. PMID:25974620

  15. Design and synthesis of 1,2,3-triazole-fused chiral medium-ring benzo-heterocycles, scaffolds mimicking benzolactams.

    PubMed

    Das Adhikary, Nirmal; Chattopadhyay, Partha

    2012-06-15

    Based on "amide-triazole bioequivalence" principle, 1,2,3-triazole-fused chiral medium ring benzo-heterocycles capable of mimicking benzolactams were designed. Their syntheses were accomplished by cycloaddition of different sugar-derived azidoalkynes. While triazole-fused eight-membered benzo-heterocycles were formed by exclusive intramolecuclar [3 + 2] cycloaddition, attempted preparation of seven-membered analogues led to some intermolecular cycloaddition resulting in a dimeric macrocyclic product, in addition to intramolecular cycloaddition furnishing the expected heterocycle. PMID:22647142

  16. Identification of cellular targets of a series of boron heterocycles using TIPA II-A sensitive target identification platform.

    PubMed

    Ward, Matthew S; Silva, Isba; Martinez, Walfre; Jefferson, Jameka; Rahman, Shakila; Garcia, Jeanie M; Kanichar, Divya; Roppiyakuda, Lance; Kosmowska, Ewa; Faust, Michelle A; Tran, Kim P; Chow, Felicia; Buglo, Elena; Zhou, Feimeng; Groziak, Michael P; Xu, H Howard

    2016-08-01

    One of the hurdles in the discovery of antibiotics is the difficulty of linking antibacterial compounds to their cellular targets. Our laboratory has employed a genome-wide approach of over-expressing essential genes in order to identify cellular targets of antibacterial inhibitors. Our objective in this project was to develop and validate a more sensitive disk diffusion based platform of target identification (Target Identification Platform for Antibacterials version 2; TIPA II) using a collection of cell clones in an Escherichia coli mutant (AS19) host with increased outer membrane permeability. Five known antibiotics/inhibitors and 28 boron heterocycles were tested by TIPA II assay, in conjunction with the original assay TIPA. The TIPA II was more sensitive than TIPA because eight boron heterocycles previously found to be inactive to AG1 cells in TIPA assays exhibited activity to AS19 cells. For 15 boron heterocycles, resistant colonies were observed within the zones of inhibition only on the inducing plates in TIPA II assays. DNA sequencing confirmed that resistant clones harbor plasmids with fabI gene as insert, indicating that these boron heterocycles all target enoyl ACP reductase. Additionally, cell-based assays and dose response curved obtained indicated that for two boron heterocycle inhibitors, the fabI cell clone in AG1 (wild-type) host cells exhibited at least 11 fold more resistance under induced conditions than under non-induced conditions. Moreover, TIPA II also identified cellular targets of known antibacterial inhibitors triclosan, phosphomycin, trimethoprim, diazaborine and thiolactomycin, further validating the utility of the new system. PMID:27301675

  17. The Real Role of N-Heterocyclic Carbene in Reductive Functionalization of CO2: An Alternative Understanding from Density Functional Theory Study.

    PubMed

    Zhou, Qinghai; Li, Yuxue

    2015-08-19

    The mechanisms of reductive functionalization of CO2 to formamide catalyzed by N-heterocyclic carbene (NHC) were comprehensively studied with DFT calculations. New activation mode with much lower energy barrier than those proposed before was discovered. In this reaction, NHC acts as neither a CO2 nor a silane activator, but as a precursor of the real catalyst, i.e., the in situ formed ionic liquid [NHCH](+)[Carbamate](-). In this loose contact ion pair, the negatively charged O atom of the carbamate anion becomes the new active site and is free to do nucleophilic attack. When amine is absent, CO2 will be converted into methanol. In this case, the NHC-CO2 adduct is the real catalytic species, the active site shifted from the carbene C atom to the negatively charged O atom. These new activation modes follow a pattern of "S(N)2@Si-Acceptor", in which the Si-H bond is activated via concerted backside S(N)2 nucleophilic attack by the negatively charged O atom, and the leaving hydride is directly accepted by a free CO2 molecule. The advantages of these new activation modes originate from the following points: (1) The ionic liquid [NHCH](+)[Carbamate](-) and NHC-CO2 adduct are thermodynamically more stable than NHC. (2) The active site of the NHC catalyst is extended outside a lot. Consequently, the large steric effect between the NHC arms and the substrates in transition state can be avoided to some extent. (3) The O atom has good silicon affinity. In addition, a free CO2 molecule, whose carbon atom is more electrophilic than those of the CO2 moieties in NHC-CO2 adduct and carbamate, acts as an efficient hydride acceptor. PMID:26220202

  18. Structure and Mechanism of Dimer-Monomer Transition of a Plant Poly(A)-Binding Protein upon RNA Interaction: Insights into Its Poly(A) Tail Assembly.

    PubMed

    Domingues, Mariane Noronha; Sforça, Mauricio Luis; Soprano, Adriana Santos; Lee, Jack; Souza, Tatiana de Arruda Campos Brasil de; Cassago, Alexandre; Portugal, Rodrigo Villares; Zeri, Ana Carolina de Mattos; Murakami, Mario Tyago; Sadanandom, Ari; Oliveira, Paulo Sergio Lopes de; Benedetti, Celso Eduardo

    2015-07-31

    Poly(A)-binding proteins (PABPs) play crucial roles in mRNA biogenesis, stability, transport and translational control in most eukaryotic cells. Although animal PABPs are well-studied proteins, the biological role, three-dimensional structure and RNA-binding mode of plant PABPs remain largely uncharacterized. Here, we report the structural features and RNA-binding mode of a Citrus sinensis PABP (CsPABPN1). CsPABPN1 has a domain architecture of nuclear PABPs (PABPNs) with a single RNA recognition motif (RRM) flanked by an acidic N-terminus and a GRPF-rich C-terminus. The RRM domain of CsPABPN1 displays virtually the same three-dimensional structure and poly(A)-binding mode of animal PABPNs. However, while the CsPABPN1 RRM domain specifically binds poly(A), the full-length protein also binds poly(U). CsPABPN1 localizes to the nucleus of plant cells and undergoes a dimer-monomer transition upon poly(A) interaction. We show that poly(A) binding by CsPABPN1 begins with the recognition of the RNA-binding sites RNP1 and RNP2, followed by interactions with residues of the β2 strands, which stabilize the dimer, thus leading to dimer dissociation. Like human PABPN1, CsPABPN1 also seems to form filaments in the presence of poly(A). Based on these data, we propose a structural model in which contiguous CsPABPN1 RRM monomers wrap around the RNA molecule creating a superhelical structure that could not only shield the poly(A) tail but also serve as a scaffold for the assembly of additional mRNA processing factors. PMID:26013164

  19. Poly(lactide)-block-poly([epsilon]-caprolactone-co-[epsilon]-decalactone)-block-poly(lactide) copolymer elastomers

    SciTech Connect

    Schneiderman, Deborah K.; Hill, Erin M.; Martello, Mark T.; Hillmyer, Marc A.

    2015-08-28

    Batch ring opening transesterification copolymerization of ε-caprolactone and ε-decalactone was used to generate statistical copolymers over a wide range of compositions and molar masses. Reactivity ratios determined for this monomer pair, rCL = 5.9 and rDL = 0.03, reveal ε-caprolactone is added preferentially regardless of the propagating chain end. Relative to poly(ε-caprolactone) the crystallinity and melting point of these statistical copolymers were depressed by the addition of ε-decalactone; copolymers containing greater than 31 mol% (46 wt%) ε-decalactone were amorphous. Poly(lactide)-block-poly(ε-caprolactone-co-ε-decalactone)-block-poly(lactide) triblock polymers were also prepared and used to explore the influence of midblock composition on the temperature dependent Flory-Huggins interaction parameter (χ). In addition, uniaxial extension tests were used to determine the effects of midblock composition, poly(lactide) content, and molar mass on the mechanical properties of these new elastomeric triblocks.

  20. Single-Molecule Enzymology

    SciTech Connect

    Xie, Xiaoliang; Lu, H PETER.

    1999-06-04

    Viewing a movie of an enzyme molecule made from molecular dynamics (MD) simulation, we see incredible details of molecular motions, be it a change of the conformation or the action of a chemical reaction.

  1. Of Molecules and Models.

    ERIC Educational Resources Information Center

    Brinner, Bonnie

    1992-01-01

    Presents an activity in which models help students visualize both the DNA process and transcription. After constructing DNA, RNA messenger, and RNA transfer molecules; students model cells, protein synthesis, codons, and RNA movement. (MDH)

  2. Gold (I) N-heterocyclic carbene complex inhibits mouse melanoma growth by p53 upregulation

    PubMed Central

    2014-01-01

    Background Cancer treatment using gold (I) complexes is becoming popular. In this study, a gold (I) N-heterocyclic complex designated as complex 3 was synthesized, its cytotoxicity was examined, and its anti-melanoma activity was evaluated in vitro and in vivo. Methods Viability of cancer cells was determined by MTT assay upon treatment with various concentrations of a gold (I) N-heterocyclic carbene complex (complex 3) in a dose and time dependent manner. Mouse melanoma cells B16F10 were selected for further apoptotic studies, including flowcytometric analysis of annexin binding, cell cycle arrest, intracellular ROS generation and loss in the mitochondrial membrane potential. ELISA based assays were done for caspase activities and western blots for determining the expression of various survival and apoptotic proteins. Immunocytology was performed to visualize the translocation of p53 to the nucleus. B16F10 cells were inoculated into mice and post tumor formation, complex 3 was administered. Immunohistology was performed to determine the expressions of p53, p21, NF-κB (p65 and p50), MMP-9 and VEGF. Student’s t test was used for determining statistical significance. The survival rate data were analyzed by Kaplan-Meier plots. Results Complex 3 markedly inhibited the growth of HCT 116, HepG2, and A549, and induced apoptosis in B16F10 cells with nuclear condensation, DNA fragmentation, externalization of phosphatidylserine, activation of caspase 3 and caspase 9, PARP cleavage, downregulation of Bcl-2, upregulation of Bax, cytosolic cytochrome c elevation, ROS generation, and mitochondrial membrane potential loss indicating the involvement of an intrinsic mitochondrial death pathway. Further, upregulation of p53, p-p53 (ser 15) and p21 indicated the role of p53 in complex 3 mediated apoptosis. The complex reduced tumor size, and caused upregulation of p53 and p21 along with downregulation of NF-κB (p65 and p50), VEGF and MMP-9. These results suggest that it induced

  3. Polyatomic molecule vibrations

    NASA Technical Reports Server (NTRS)

    1976-01-01

    Polyatomic molecule vibrations are analyzed as harmonic vibrations along normal coordinates. The energy eigenvalues are found for linear and nonlinear symmetric triatomic molecules for valence bond models of the potential function with arbitrary coupling coefficients; such models can usually be fitted to observed energy levels with reasonably good accuracy. Approximate normal coordinates for the H2O molecule are discussed. Degenerate vibrational modes such as occur in CO2 are analyzed and expressions for Fermi resonance between close-lying states of the same symmetry are developed. The bending modes of linear triatomic molecules are expressed in terms of Laguerre polynomials in cylindrical coordinates as well as in terms of Hermite polynomials in Cartesian coordinates. The effects of large-amplitude bending such as occur in the C3 molecule are analyzed, along with anharmonic effects, which split the usually degenerate bending mode energy levels. Finally, the vibrational frequencies, degeneracies, and symmetry properties of XY3, X2Y2, and XY4 type molecules are discussed.

  4. TLR3 Agonist Poly-IC Induces IL-33 and Promotes Myelin Repair

    PubMed Central

    Natarajan, Chandramohan; Yao, Song-Yi; Sriram, Subramaniam

    2016-01-01

    Background Impaired remyelination of demyelinated axons is a major cause of neurological disability. In inflammatory demyelinating disease of the central nervous system (CNS), although remyelination does happen, it is often incomplete, resulting in poor clinical recovery. Poly-IC a known TLR3 agonist and IL-33, a cytokine which is induced by poly-IC are known to influence recovery and promote repair in experimental models of CNS demyelination. Methodology and Principal Findings We examined the effect of addition of poly-IC and IL-33 on the differentiation and maturation of oligodendrocyte precursor cells (OPC) cultured in vitro. Both Poly-IC and IL-33 induced transcription of myelin genes and the differentiation of OPC to mature myelin forming cells. Poly-IC induced IL-33 in OPC and addition of IL-33 to in vitro cultures, amplified further, IL-33 expression suggesting an autocrine regulation of IL-33. Poly-IC and IL-33 also induced phosphorylation of p38MAPK, a signaling molecule involved in myelination. Following the induction of gliotoxic injury with lysolecithin to the corpus callosum (CC), treatment of animals with poly-IC resulted in greater recruitment of OPC and increased staining for myelin in areas of demyelination. Also, poly-IC treated animals showed greater expression of IL-33 and higher expression of M2 phenotype macrophages in the CC. Conclusion/Significance Our studies suggest that poly-IC and IL-33 play a role in myelin repair by enhancing expression of myelin genes and are therefore attractive therapeutic agents for use as remyelinating agents in human demyelinating disease. PMID:27022724

  5. Overview on poly(ADP-ribose) immuno-biomedicine and future prospects.

    PubMed

    Kanai, Yoshiyuki

    2016-01-01

    Poly(ADP-ribose), identified in 1966 independently by three groups Strassbourg, Kyoto and Tokyo, is synthesized by poly(ADP-ribose) polymerases (PARP) from NAD(+) as a substrate in the presence of Mg(2+). The structure was unique in that it has ribose-ribose linkage. In the early-1970s, however, its function in vivo/in vitro was still controversial and the antibody against it was desired to help clear its significance. Thereupon, the author tried to produce antibody against poly(ADP-ribose) in rabbits and succeeded in it for the first time in the world. Eventually, this success has led to the following two groundbreaking papers in Nature: "Naturally-occurring antibody against poly(ADP-ribose) in patients with autoimmune disease SLE", and "Induction of anti-poly(ADP-ribose) antibody by immunization with synthetic double-stranded RNA, poly(A)·poly(U)".On the way to the publication of the first paper, a reviewer gave me a friendly comment that there is "heteroclitic" fashion as a mechanism of the production of natural antibody. This comment was really a God-send for me, and became a train of power for publication of another paper, as described above. Accordingly, I thought this, I would say, episode is worth describing herein. Because of its importance in biomedical phenomena, a certain number of articles related to "heteroclitic" have become to be introduced in this review, although they were not always directly related to immuno-biological works on poly(ADP-ribose). Also, I tried to speculate on the future prospects of poly(ADP-ribose), product of PARP, as an immuno-regulatory molecule, including either induced or naturally-occurring antibodies, in view of "heteroclitic". PMID:27477457

  6. N-heterocyclic carbene metal complexes as bio-organometallic antimicrobial and anticancer drugs.

    PubMed

    Patil, Siddappa A; Patil, Shivaputra A; Patil, Renukadevi; Keri, Rangappa S; Budagumpi, Srinivasa; Balakrishna, Geetha R; Tacke, Matthias

    2015-01-01

    Late transition metal complexes that bear N-heterocyclic carbene (NHC) ligands have seen a speedy growth in their use as both, metal-based drug candidates and potentially active homogeneous catalysts in a plethora of C-C and C-N bond forming reactions. This review article focuses on the recent developments and advances in preparation and characterization of NHC-metal complexes (metal: silver, gold, copper, palladium, nickel and ruthenium) and their biomedical applications. Their design, syntheses and characterization have been reviewed and correlated to their antimicrobial and anticancer efficacies. All these initial discoveries help validate the great potential of NHC-metal derivatives as a class of effective antimicrobial and anticancer agents. PMID:26144266

  7. Heterocyclic amine mutagenicity/carcinogenicity: Influence of repair, metabolism, and structure

    SciTech Connect

    Felton, J.S.; Wu, R.; Knize, M.G.; Thompson, L.H.; Hatch, F.T.

    1993-01-15

    Cooking, heat processing, and pyrolysis of protein-rich foods induce the formation of structurally related heterocyclic aromatic amines that have been found to be mutagenic in bacteria, mammalian cells in culture and mice. All these compounds are potent mutagens and most are active below 1 ng/plate, in Ames/Salmonella tester strain TA1538 in the presence of S9 liver microsomal preparations from rat, mouse, or hamster. They are also potent in strains TA98, TA97, moderately active in TA1537, weakly active in TA100, and virtually inactive in TA1535 and TA102. Thus, they show powerful frameshift activity in reverting specific GC-rich sequences, but do not cause base substitution mutations or revert an AT-rich sequence. They are 100-fold less active in the uvrB+, repair-proficient strain TA1978, and in the case of IQ, cause insertions and large deletions not seen in TA1538.

  8. Susceptibility to Exposure to Heterocyclic Amines from Cooked Food: Role of UDP-glucuronosyltransferases

    SciTech Connect

    Malfatti, M A; Felton, J S

    2005-08-22

    A number of carcinogenic heterocyclic amines (PhIP, MeIQx, and DiMeIQx) are produced from the condensation of creatinine, hexoses and amino acids during the cooking of meat (1). There are many variables that impact the production and subsequent ingestion of these compounds in our diet. Temperature, type of meat product, cooking method, doneness, and other factors affect the quantity of these carcinogens consumed by humans. Estimates of ingestion of these carcinogens are 1-20 ng/kg body weight per day (2). Human case control studies that correlate meat consumption from well-done cooking practices with cancer incidence indicate excess tumors for breast, colon, stomach, esophagus, and possibly prostate (3-5).

  9. An Isolable, Photoswitchable N-Heterocyclic Carbene: On-Demand Reversible Ammonia Activation.

    PubMed

    Teator, Aaron J; Tian, Yuan; Chen, Mu; Lee, Jeehiun K; Bielawski, Christopher W

    2015-09-21

    The first isolable, photoswitchable N-heterocyclic carbene was synthesized and found to undergo reversible electrocyclic isomerization upon successive exposure to UV and visible radiation. The UV-induced ring closure afforded substantial changes to the electronic structure of the dithienylethene-based NHC, as evidenced by changes in the corresponding UV/Vis absorption and (13)C NMR spectra. Likewise, molecular orbital calculations revealed diminished electron density at the carbene nucleus upon photocyclization, consistent with the enhanced electrophilicity displayed by the ring-closed form. The photoswitchable NHC was successfully switched between its ring-opened and ring-closed states with high fidelity over multiple cycles. Furthermore, the ring-closed isomer was found to undergo facile N-H bond activation, allowing for the controlled capture and release of ammonia upon cycling between its isomeric states. PMID:26274507

  10. Antioxidant, anti-inflammatory and anti-hyperglycaemic activities of heterocyclic homoprostanoid derivatives.

    PubMed

    Manohara Reddy, S A; Mudgal, Jayesh; Bansal, Punit; Vasanthraju, S G; Srinivasan, K K; Rao, C Mallikarjuna; Gopalan Kutty, N

    2011-01-01

    A series of 19 heterocyclic homoprostanoids were synthesized from easily available oleic and ricinoleic acids and evaluated for their possible antioxidant, anti-inflammatory and anti-hyperlipidaemic activities. Compounds with thioxo- and oxoimidazole ring (1) and (2) have shown potent antioxidant activity with IC(50) values 0.23±0.09 and 0.41±0.01mM comparable with standard ascorbic acid. Compound (3) with a quinoxaline ring showed maximum inhibition of BSA denaturation at 1mM concentration and comparable with standard diclofenac. Incorporation of electron withdrawing substitutions like chloro- and nitro-groups in the quinoxaline ring has resulted in an increase anti-inflammatory activity. Test compounds (3), (3a) and (3c) showed modest inhibition of DPP-IV in vitro. However, the unsubstituted quinoxaline (3) and substituted quinoxalines (3b and 3c) reduced plasma glucose levels indicating the presence of hypoglycemic activity. PMID:21146413

  11. Oxygenated heterocyclic compounds to differentiate Citrus spp. essential oils through metabolomic strategies.

    PubMed

    Masson, Jerome; Liberto, Erica; Beolor, Jean-Claude; Brevard, Hugues; Bicchi, Carlo; Rubiolo, Patrizia

    2016-09-01

    This study aimed to characterise and discriminate 44 authenticated commercial samples of citrus essential oils (EO) from seven species (bergamot, lemon, bigarade, orange, mandarin, grapefruit, lime) by analysing the non-volatile oxygenated heterocyclic compounds (OHC) by UHPLC/TOF-HRMS, multivariate data analysis (PCA, PLS-DA) and metabolomic strategies; the OHC fraction includes coumarins, furocoumarins, and polymethoxylated flavonoids. Two different approaches were adopted: (i) targeted profiling based on quantifying 18 furocoumarins and coumarins, some of which are regulated by law, and (ii) targeted fingerprinting based on 140 OHCs reported in citrus essential oils, from which 38 discriminant markers were defined. This approach correctly discriminated the Citrus species; its "sensitivity" to relatively low adulteration rate (10%) was highly satisfactory. The proposed method is complementary to that of analysing the citrus EO volatile part by GC techniques. PMID:27041320

  12. Infrared Spectroscopy of Matrix-Isolated Polycyclic Aromatic Nitrogen Heterocycles (PANHs)

    NASA Technical Reports Server (NTRS)

    Mattioda, A. L.; Hudgins, D. M.; Bauschlicher, C. W.; Allamandola, L. J.; Biemesderfer, C. D.; Rosi, M.

    2002-01-01

    The mid-infrared spectra of the nitrogen-containing heterocyclic polycyclic aromatic compounds 1-azabenz[a]-anthracene; 2-azabenz[a]anthracene; 1-azachrysene; 2-azachrysene; 4-azachrysene; 2-azapyrene, and 7,8 benzoquinoline in their neutral and cation forms were investigated. The spectra of these species isolated in an argon matrix have been measured. Band frequencies and intensities were tabulated and these data compared with spectra computed using density functional theory at the B3LYP level. The overall agreement between experiment and theory is quite good, in keeping with earlier results on homonuclear polycyclic aromatic hydrocarbons. The differences between the spectral properties of nitrogen bearing aromatics and non-substituted, neutral polycyclic aromatic hydrocarbons will be discussed.

  13. Highly selective deuteration of pharmaceutically relevant nitrogen-containing heterocycles: a flow chemistry approach.

    PubMed

    Ötvös, Sándor B; Mándity, István M; Fülöp, Ferenc

    2011-08-01

    A simple and efficient flow-based technique is reported for the catalytic deuteration of several model nitrogen-containing heterocyclic compounds which are important building blocks of pharmacologically active materials. A continuous flow reactor was used in combination with on-demand pressure-controlled electrolytic D(2) production. The D(2) source was D(2)O, the consumption of which was very low. The experimental set-up allows the fine-tuning of pressure, temperature, and flow rate so as to determine the optimal conditions for the deuteration reactions. The described procedure lacks most of the drawbacks of the conventional batch deuteration techniques, and additionally is highly selective and reproducible. PMID:20842527

  14. Photocatalytic degradation of agricultural N-heterocyclic organic pollutants using immobilized nanoparticles of titania.

    PubMed

    Mahmoodi, Niyaz Mohammad; Arami, Mokhtar; Limaee, Nargess Yousefi; Gharanjig, Kamaladin

    2007-06-25

    Degradation and mineralization of two agricultural organic pollutants (Diazinon and Imidacloprid as N-heterocyclic aromatics) in aqueous solution by nanophotocatalysis using immobilized titania nanoparticles were investigated. Insecticides, Diazinon and Imidacloprid, are persistent pollutants in agricultural soil and watercourses. A simple and effective method was developed to immobilization of titania nanoparticles. UV-vis, ion chromatography (IC) and chemical oxygen demand (COD) analyses were employed. The effects of operational parameters such as H(2)O(2) and inorganic anions (NO(3)(-), Cl(-) and SO(4)(2-)) were investigated. The mineralization of Diazinon and Imidacloprid was evaluated by monitoring of the formed inorganic anions. The selected pollutants are effectively degraded following first order kinetics model. Results show that the nanophotocatalysis using immobilized titania nanoparticle is an effective method for treatment Diazinon and Imidacloprid from contaminated water. PMID:17145132

  15. Presence of heterocyclic aromatic amines (HAS) in smoked "Provola" cheese from Calabria (Italy).

    PubMed

    Naccari, C; Galceran, M T; Moyano, E; Cristani, M; Siracusa, L; Trombetta, D

    2009-02-01

    This study evaluated the residual levels of heterocyclic aromatic amines (HAs) in "Provola" cheese samples from Calabria, smoked using natural methods and using commercial buffered smoke. A comparative study of HAs concentrations was carried out on different portions of these samples: the rind, exterior part, core and on slice. Quantitative determination of HAs was carried out by HPLC using a fluorescence detector and analysis in HPLC-MS was conduced to confirm the presence of these amines. Residual levels of HAs were found in all naturally smoked "Provola" cheese samples. The results obtained showed that the smoking process performed using traditional methods contributes to HAs contamination while the use of commercial buffered smoke can be considered a safer technique for smoking of food. PMID:19056456

  16. Heterocyclic Scaffolds in the Design of Peptidomimetic Integrin Ligands: Synthetic Strategies, Structural Aspects, and Biological Activity.

    PubMed

    De Marco, Rossella; Mazzotti, Giacomo; Greco, Arianna; Gentilucci, Luca

    2016-01-01

    The integrin receptors represent valuable targets for therapeutic interventions; being overexpressed in many pathological states, their inhibition can be effective to treat a number of severe diseases. Since integrin functions are mediated by interactions with ECM protein ligands, the inhibition can be achieved by interfering with such interactions using small mimetics of the integrin-ligand recognition motifs (e.g. RGD, LDV, etc.). In this review, we focus on the antagonists with peptideheterocycle hybrid structures. The introduction of well-designed scaffolds has met considerable success in the rational design of highly stable, bioavailable, and conformationally defined antagonists. Two main approaches are discussed herein. The first approach is the use of scaffolds external to the main recognition motifs, aimed at improving conformational definition. In the second approach, heterocyclic cores are introduced within the recognition motifs, giving access to libraries of 3D diverse candidate antagonists. PMID:26265351

  17. Effect of heterocyclic capping groups on the self-assembly of a dipeptide hydrogel.

    PubMed

    Martin, Adam D; Wojciechowski, Jonathan P; Warren, Holly; in het Panhuis, Marc; Thordarson, Pall

    2016-03-14

    The mechanism and design rules associated with the self-assembly of short peptides into hydrogels is currently not well understood. In this work, four diphenylalanine-based peptides have been synthesised, bearing heterocyclic capping groups which have different degrees of hydrogen bonding potential and nitrogen substitution. For these four peptides, zeta potential and electrical impedance spectroscopy measurements were undertaken to monitor gelation, with the impedance data showing different gelation times for each peptide hydrogel. Through a combination of atomic force microscopy and rheological measurmeents, including dynamic strain and frequency sweeps, and thixotropic tests, the relationship between the mechanism of self-assembly in these hydrogels and their macroscopic behaviour can be established. It is observed that the degree of nitrogen substitution affects the self-assembly mechanisms of the hydrogels and as such, that there is an interplay between branching and bundling self-assembly pathways that are responsible for the final properties of each hydrogel. PMID:26860207

  18. 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

  19. Bioactive heterocyclic alkaloids with diterpene structure isolated from traditional Chinese medicines.

    PubMed

    Xu, Tengfei; Liu, Shu; Meng, Lulu; Pi, Zifeng; Song, Fengrui; Liu, Zhiqiang

    2016-07-15

    The diterpenoid alkaloids as one type of heterocyclic alkaloids have been found in many traditional herbal medicines, such as genus Consolida, Aconitum, and Delphinium (Ranunculaceae). Pharmacological researches have indicated that many diterpenoid alkaloids are the main bioactive components which have analgesic, anti-inflammatory, anti-microbial, anti-tumor, cardiotonic, and anti-arrhythmic activities. Studies focused on the determination, quantitation and pharmacological properties of these alkaloids have dramatically increased during the past few years. Up to now, newly discovered diterpenoid alkaloids with important biological activities have been isolated and synthesized. Considering their significant role and diffusely used in many disease treatments, we summarized the information of their analysis methods, bioactivity, metabolism and biotransformation in vivo as well as the pharmacological mechanisms. Based on above review, the further researches are suggested. PMID:26456661

  20. Proton-transfer polymerization (HTP): converting methacrylates to polyesters by an N-heterocyclic carbene.

    PubMed

    Hong, Miao; Chen, Eugene Y-X

    2014-10-27

    A new polymerization termed proton (H)-transfer polymerization (HTP) has been developed to convert dimethacrylates to unsaturated polyesters. HTP is catalyzed by a selective N-heterocyclic carbene capable of promoting intermolecular Umpolung condensation through proton transfer and proceeds through the step-growth propagation cycles via enamine intermediates. The role of the added suitable phenol, which is critical for achieving an effective HTP, is twofold: shutting down the radically induced chain-growth addition polymerization under HTP conditions (typically at 80-120 °C) and facilitating proton transfer after each monomer enchainment. The resulting unsaturated polyesters have a high thermal stability and can be readily cross-linked to robust polyester materials. PMID:25196055