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Sample records for poly heterocyclic molecules

  1. Quantum Transport Through Heterocyclic Molecules

    NASA Astrophysics Data System (ADS)

    Maiti, Santanu K.; Karmakar, S. N.

    We explore electron transport properties in molecular wires made of heterocyclic molecules (pyrrole, furan and thiophene) by using the Green's function technique. Parametric calculations are given based on the tight-binding model to describe the electron transport in these wires. It is observed that the transport properties are significantly influenced by (a) the heteroatoms in the heterocyclic molecules and (b) the molecule-to-electrodes coupling strength. Conductance (g) shows sharp resonance peaks associated with the molecular energy levels in the limit of weak molecular coupling, while they get broadened in the strong molecular coupling limit. These resonances get shifted with the change of the heteroatoms in these heterocyclic molecules. All the essential features of the electron transfer through these molecular wires become much more clearly visible from the study of our current-voltage (I-V) characteristics, and they provide several key information in the study of molecular transport.

  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. Amino Azaxylylenes Photogenerated from o-Amido Imines: Photoassisted Access to Complex Spiro-Poly-Heterocycles.

    PubMed

    Mukhina, Olga A; Kuznetsov, Dmitry M; Cowger, Teresa M; Kutateladze, Andrei G

    2015-09-21

    Upon irradiation, cyclic imines containing o-amido groups are shown to produce reactive intermediates, amino azaxylylenes, which undergo intramolecular cycloadditions to tethered unsaturated pendants to yield complex N,O-heterocycles having an additional spiro-connected nitrogen heterocyclic moiety. Modular assembly of the photoprecursors allows expeditious increase of the complexity of the target poly-heterocyclic scaffolds with a minimal number of experimentally simple reaction steps. The photocyclization and subsequent postphotochemical transformations are accompanied by an increase of Lovering's fsp3 factor, thus producing unprecedented three-dimensional molecular architectures, and offering extended sampling of chemical space.

  5. The proton affinities of saturated and unsaturated heterocyclic molecules

    NASA Astrophysics Data System (ADS)

    Kabli, Samira; van Beelen, Eric S. E.; Ingemann, Steen; Henriksen, Lars; Hammerum, Steen

    2006-03-01

    The proton affinities derived from G3-calculations of 23 five-membered ring heteroaromatic molecules agree well with the experimentally determined values available in the literature. The calculated local proton affinities show that the principal site of protonation of the heteroaromatic compounds examined is an atom of the ring, carbon when there is only one heteroatom in the ring, and nitrogen where there are two or more heteroatoms. The experimental proton affinities of non-aromatic cyclic ethers, amines and thioethers are also in excellent agreement with the calculated values, with two exceptions (oxetane, N-methylazetidine). The literature proton affinities of the four simple cyclic ethers, oxetane, tetrahydrofuran, tetrahydropyran and oxepane were confirmed by Fourier Transform Ion Cyclotron Resonance (FT-ICR) mass spectrometry, in order to examine the disagreement between the values predicted by extrapolation or additivity for tetrahydrofuran and tetrahydropyran and those determined by experiment and by calculation. The proton affinity differences between the pairs tetrahydropyran/1,4-dioxane, piperidine/morpholine and related compounds show that introduction of an additional oxygen atom in the ring considerably lowers the basicity.

  6. 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

  7. Rectifications in organic single-molecule diodes alkanethiolate-terminated heterocyclics

    NASA Astrophysics Data System (ADS)

    An, Yipeng; Zhang, Mengjun; Wang, Tianxing; Wang, Guangtao; Fu, Zhaoming

    2016-02-01

    Based on the non-equilibrium Green's function formalism combined with the ab initio density functional theory, we investigate the rectifying behaviors of the organic single-molecule S(CH2)11-terminated with a variety of heterocyclics (i.e., BIPY, PHE, PHEPY, and PYR) coupled with two semi-infinite Au electrodes. Our quantum transport calculation results show that the BIPY and PHE nanojunctions show the high-efficiency rectifying effects. While, differently, the current-voltage (I-V) curves of PHEPY and PYR nanojunctions display the insulating and linear characters, respectively. The corresponding electronic transport mechanisms are analyzed in detail. Our calculation results demonstrate that these investigated organic single-molecule nanojunctions have the potential applications in rectifiers and molecular wires.

  8. 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…

  9. Shape-Controllable Formation of Poly-imidazolium Salts for Stable Palladium N-Heterocyclic Carbene Polymers

    PubMed Central

    Zhao, Huaixia; Li, Liuyi; Wang, Yangxin; Wang, Ruihu

    2014-01-01

    The imidazolium-based main-chain organic polymers are one of promising platforms in heterogeneous catalysis, the size and outer morphology of polymer particles are known to have important effects on their physical properties and catalytic applications, but main-chain ionic polymers usually generate amorphous or spherical particles. Herein, we presented a versatile and facile synthetic route for size- and shape-controllable synthesis of main-chain poly-imidazolium particles. The wire-shaped, spherical and ribbon-shaped morphologies of poly-imidazolium particles were readily synthesized through quaternization of bis-(imidazol-1-yl)methane and 2,4,6-tris(4-(bromomethyl)phenyl)-1,3,5-triazine, and the modification of their size and morphology were realized through adjusting solvent polarity, solubility, concentration and temperatures. The direct complexation of the particles with Pd(OAc)2 produced ionic polymers containing palladium N-heterocyclic carbene units (NHCs) with intactness of original morphologies. The particle morphologies have a significant effect on catalytic performances. Wire-shaped palladium-NHC polymer shows excellent catalytic activity and recyclabilty in heterogeneous Suzuki-Miyaura cross-coupling reaction. PMID:24969738

  10. Inhibition of T24 and RT4 Human Bladder Cancer Cell Lines by Heterocyclic Molecules

    PubMed Central

    Zhao, Zhi-Feng; Wang, Kai; Guo, Feng-Fu; Lu, Hua

    2017-01-01

    Background Bladder cancer is a major widespread tumor of the genitourinary tract. Around 30% of patients with superficial cancers develop invasive and metastatic pathology. Material/Methods Some new heterocyclic 4-methyl coumarin derivatives were designed using molecular modeling studies to evaluate their potential against bladder cancer lines T24 and RT-4. The designed compounds that showed good binding affinity to T24 and RT4 were synthesized, with excellent yield. The synthesized compounds after structural evaluation were further evaluated for their antiproliferative activity by cell viability assay, cell cycle analysis, and apoptosis assay. Results The compound BC-14 exhibited the best cytotoxicity against T24 cells, but were not highly active against RT4 cells. Conclusions The results of the present study may suggest the selectivity pattern of the synthesized compounds. These results should be explored further with chemical modification for other cancer types. PMID:28260746

  11. 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.

  12. Imidazolium-Based Poly(Ionic Liquid)s Featuring Acetate Counter Anions: Thermally Latent and Recyclable Precursors of Polymer-Supported N-Heterocyclic Carbenes for Organocatalysis.

    PubMed

    Lambert, Romain; Coupillaud, Paul; Wirotius, Anne-Laure; Vignolle, Joan; Taton, Daniel

    2016-07-01

    Statistical copoly(ionic liquid)s (coPILs), namely, poly(styrene)-co-poly(4-vinylbenzylethylimidazolium acetate) are synthesized by free-radical copolymerization in methanolic solution. These coPILs serve to in situ generate polymer-supported N-heterocyclic carbenes (NHCs), referred to as polyNHCs, due to the noninnocent role of the weakly basic acetate counter-anion interacting with the proton in C2-position of pendant imidazolium rings. Formation of polyNHCs is first evidenced through the quantitative formation of NHC-CS2 units by chemical postmodification of acetate-containing coPILs, in the presence of CS2 as electrophilic reagent (= stoichiometric functionalization of polyNHCs). The same coPILs are also employed as masked precursors of polyNHCs in organocatalyzed reactions, including a one-pot two-step sequential reaction involving benzoin condensation followed by addition of methyl acrylate, cyanosilylation, and transesterification reactions. The catalytic activity can be switched on and off successively upon thermal activation, thanks to the deprotonation/reprotonation equilibrium in C2-position. NHC species are thus in situ released upon heating at 80 °C (deprotonation), while regeneration of the coPIL precursor occurs at room temperature (reprotonation), triggering its precipitation in tetrahydrofuran. This also allows recycling the coPIL precatalyst by simple filtration, and reusing it for further catalytic cycles. The different organocatalyzed reactions tested can thus be performed with excellent yields after several cycles.

  13. A structure-activity relationship study on multi-heterocyclic molecules: two linked thiazoles are required for cytotoxic activity

    PubMed Central

    Kim, Seong Jong; Lin, Chun Chieh; Pan, Chung-Mao; Rananaware, Dimple P.; Ramsey, Deborah M.

    2013-01-01

    We report the synthesis, cytotoxicity, and phenotypic analysis of oxazole and thiazole containing fragments. Evaluating the optimal size and heterocycle for growth inhibition and apoptosis showed that activity required at least two thiazoles sequentially connected. This is the first detailed comparison of biological activity between multi-heterocyclic containing fragments. PMID:23524379

  14. Cyclic poly(alpha-peptoid)s and their block copolymers from N-heterocyclic carbene-mediated ring-opening polymerizations of N-substituted N-carboxylanhydrides.

    PubMed

    Guo, Li; Zhang, Donghui

    2009-12-23

    N-Heterocyclic carbene (NHC)-mediated ring-opening polymerization (ROP) of N-substituted N-carboxylanhydride ((N)R-NCA) yields cyclic poly(alpha-peptoid)s with controlled molecular weights (M(n) = 3-30 kg mol(-1)) and narrow molecular weight distributions (PDI = 1.04-1.12). The reactions exhibit characteristics of a living polymerization with minimal chain transfer. This enables the facile synthesis of cyclic diblock copoly(alpha-peptoid)s through sequential monomer addition. The cyclic polymer architectures were verified by MALDI-TOF mass spectrometry and intrinsic viscosity measurements. Mark-Houwink-Sakurada plot analyses revealed that cyclic poly(alpha-peptoid)s prepared from NHC-mediated polymerizations exhibit lower intrinsic viscosities than their linear analogues prepared from primary amine-initiated polymerizations. The ratio of their intrinsic viscosities is consistent with the former being mostly cyclic.

  15. Ring expansion reactions of pentaphenylborole with dipolar molecules as a route to seven-membered boron heterocycles.

    PubMed

    Huang, Kexuan; Martin, Caleb D

    2015-02-16

    Reactions of pentaphenylborole with isocyanates, benzophenone, and benzaldehyde produced new seven-membered heterocycles in high yields. For 1-adamantyl isocyanate, a BNC5 heterocycle was obtained from the insertion of the C-N moiety into the five-membered borole, whereas for 4-methoxyphenyl isocyanate, a BOC5 heterocycle was generated from the insertion of the C-O unit. These reactions are believed to occur via a mechanism wherein coordination of the nucleophile to the borole (1-adamantyl, N-coordination or O-coordination for 4-methoxyphenyl) is followed by ring expansion to afford the observed seven-membered heterocycles. The selectivity to form B-O- or B-N-containing heterocycles is based on the polarization of the isocyanate implying tunable reactivity for the system. Having observed that isocyanates react as 1,2-dipoles with pentaphenylborole, we examined benzophenone and benzaldehyde, which both reacted to insert C-O units into the ring. This represents a new efficient method for preparing rare seven-membered boracycles.

  16. Rhodium(III)-Catalyzed ortho C-H Heteroarylation of (Hetero)aromatic Carboxylic Acids: A Rapid and Concise Access to π-Conjugated Poly-heterocycles.

    PubMed

    Qin, Xurong; Li, Xiaoyu; Huang, Quan; Liu, Hu; Wu, Di; Guo, Qiang; Lan, Jingbo; Wang, Ruilin; You, Jingsong

    2015-06-08

    Rh(III)-catalyzed oxidative C-H/C-H cross-coupling between (hetero)aromatic carboxylic acids and various heteroarenes has been accomplished to construct highly functionalized ortho-carboxy-substituted bi(hetero)aryls. The use of a carboxy group as the directing group obviates tedious steps for installation and removal of extra directing groups, and enables a facile one-step synthesis of ortho-carboxy bi(hetero)aryls. The method provides opportunities for rapid assembly of a library of important fluorene and coumarin-type poly-heterocycles through intramolecular electrophilic substitution or oxidative lactonization. As illustrative examples, the strategy developed herein greatly streamlines accesses to a variety of appealing polyheterocycles such as DTPO (5H-dithieno[3,2-b:2',3'-d]pyran-5-one), CPDTO (cyclopentadithiophen-4-one), and indenothiophenes.

  17. 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.

  18. Trifluoromethylated heterocycles.

    PubMed

    Gakh, Andrei A; Shermolovich, Yuriy

    2014-01-01

    This review is a follow-up to the previous chapter, "Monofluorinated Heterocycles" (Topics in Heterocyclic Chemistry, 2012, 33-63), and presents an overview of synthetic chemistry of heterocycles with only one trifluoromethyl group directly attached to the ring (trifluoromethylated heterocycles). Particular attention is given to the modern direct trifluoromethylation methods, including catalytic reactions, organometallic reagents, carbene and hypervalent chemistry, utilization of ionic nucleophilic and electrophilic trifluoromethylating agents, and to other pertinent trends. One of the emphases of the review is compounds with biomedical potential.

  19. Poly(ethylene glycol)-graft-poly(vinyl acetate) single-chain nanoparticles for the encapsulation of small molecules.

    PubMed

    Bartolini, Arianna; Tempesti, Paolo; Resta, Claudio; Berti, Debora; Smets, Johan; Aouad, Yousef G; Baglioni, Piero

    2017-02-08

    Amphiphilic poly(ethylene glycol)-graft-poly(vinyl acetate) copolymers with a low degree of grafting undergo self-folding in water driven by hydrophobic interactions, resulting in single-chain nanoparticles (SCNPs) possessing a hydrodynamic radius of about 10 nm. A temperature scan revealed a lower critical solution temperature (LCST)-type phase behavior. In addition, SAXS data collected close to the LCST showed that these SCNPs aggregate into one-dimensional elongated objects, preferentially. With respect to the typical linear complex-structured polymer chains, this material is ideally suited for industrial and/or biomedical applications because of its simple molecular architecture and persistence of SCNPs up to 100 mg mL(-1). The so-obtained single-chain globular particles are able to swell upon loading with small hydrophobic molecules therefore promoting solubilization of flavors or drugs, which could be of interest in the food and pharmaceutical industry.

  20. N-Heterocyclic carbene-mediated zwitterionic polymerization of N-substituted N-carboxyanhydrides toward poly(α-peptoid)s: kinetic, mechanism, and architectural control.

    PubMed

    Guo, Li; Lahasky, Samuel H; Ghale, Kushal; Zhang, Donghui

    2012-06-06

    N-Heterocyclic carbene (NHC)-mediated polymerizations of N-butyl N-carboxyanhydride (Bu-NCA) to produce cyclic poly(N-butyl glycine)s (c-NHC-PNBGs) have been investigated in various solvents with NHCs having differing steric and electronic properties. Control over the polymer molecular weight (MW) and polymerization rate is strongly dependent on the solvent and the NHC structure. Kinetic studies reveal that the propagating intermediates for the polymerization in low dielectric solvents (e.g., THF or toluene) maintain cyclic architectures with two chain ends in close contact through Coulombic interaction. The NHCs not only initiate the polymerization, but also mediate the chain propagation as intramolecular counterions. Side reactions are significantly suppressed in low dielectric solvents due to the reduced basicity and nucleophilicity of the negatively charged chain ends of the zwitterions, resulting in quasi-living polymerization behavior. By contrast, the two charged chain ends of the zwitterionic species are fully dissociated in high dielectric solvents. The chain propagation proceeds as in conventional anionic polymerizations, wherein side reactions (e.g., transamidation) compete with chain propagation, resulting in significantly diminished control over polymer MW. The cyclic zwitterionic propagating species can be converted into their linear polymeric analogues (l-NHC-PNBGs) by end-capping with electrophiles (e.g., acetyl chloride) or the NHC-free cyclic analogues (c-PNBGs) by treatment with NaN(TMS)(2), as evidenced by MALDI-TOF MS, NMR, and SEC analysis.

  1. Patterning protein molecules on poly(ethylene glycol) coated Si(111).

    PubMed

    Jun, Yongseok; Cha, Taewoon; Guo, Athena; Zhu, X-Y

    2004-08-01

    We demonstrate spatially localized immobilization of protein molecules on high-density poly(ethylene glycol) (PEG) coated Si(111). Patterns of HO- and CH3O-terminated PEG regions are formed on silicon surfaces based on soft lithography techniques and an efficient reaction between alcohol functional groups and chlorine-terminated silicon. Activation of the HO-terminated PEG brush is achieved via either partial oxidation to form aldehyde groups or via attachment of efficient leaving groups. Protein molecules are covalently immobilized to these activated regions on the PEG/Si surface.

  2. Probing Cellular Molecules with PolyA-Based Engineered Aptamer Nanobeacon.

    PubMed

    Chen, Lizhen; Chao, Jie; Qu, Xiangmeng; Zhang, Hongbo; Zhu, Dan; Su, Shao; Aldalbahi, Ali; Wang, Lianhui; Pei, Hao

    2017-03-08

    Adenosine triphosphate (ATP) is a central metabolite that is of critical importance in many cellular processes. The development of sensitive and selective methods for the detection of ATP level in vivo is crucial in diagnostic and theranostic applications. In this work, we have developed a polyA-based aptamer nanobeacon (PAaptNB) with improved efficiency and speed of ATP analysis. We found that the dissociation constants and competitive binding kinetics of the PAaptNB could be programmably regulated by adjusting the polyA length. When the polyA length reached to 30 bases, a 10 μM detection limit for ATP assay with PAaptNB can be achieved (∼10-fold improvement compared with the conventional thiol-based aptamer nanobeacon). The feasibility of the PAaptNB for in vivo assay was further demonstrated by imaging intracellular ATP molecules. This study provides a new strategy to construct high-efficiency and high-speed biosensors for cellular molecules analysis, which holds great potential in bioanalysis and theranostic applications.

  3. KrF pulsed laser ablation of thin films made from fluorinated heterocyclic poly(naphthyl-imide)s.

    PubMed

    Damaceanu, Mariana-Dana; Rusu, Radu-Dan; Olaru, Mihaela Adriana; Timpu, Daniel; Bruma, Maria

    2012-06-01

    Among the many aspects of laser ablation, development of conical structures induced by excimer laser radiation on polyimide surfaces has been thoroughly investigated. Because the mechanisms that produce these surface textures are not fully understood, two theories, photochemical bond breaking and thermal reaction, have been introduced. Here we present the first study of ultraviolet laser ablation behavior of thin films made from fluorinated poly(naphthyl-imide)s containing oxadiazole rings and the investigation of the mechanism of cone-like structure formation at two laser fluences, 57 and 240 mJ/cm(2). The morphology of thin films before and after laser ablation was studied by using various spectroscopy techniques such as Fourier transform infrared spectroscopy, time-resolved emission and X-ray photoelectron spectroscopy, atomic force microscopy, and contact angle measurements. All of the data suggest impurities shielded at low fluence radiation (57 mJ/cm(2)) and a radiation hardening process at high value fluence (240 mJ/cm(2)), which are proposed as the main mechanisms for laser ablation of our polyimide films, and we bring evidence to support them.

  4. Intense quenching of fluorescence intensity of poly(vinyl pyrrolidone) molecules in presence of gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Behera, M.; Ram, S.

    2013-12-01

    We study the quenching of fluorescence intensity of 40 g/L poly(vinyl pyrrolidone) PVP molecules by varying the content of gold nanoparticles (GNPs) from 1 to 5 μM in 1-butanol. A profound exponential decay of the emission band intensity in the π ← nπ* band of the PVP molecules at ~392 nm upon gradual addition of the GNPs demonstrates an existence of an excited state interaction of NPs with the PVP molecules in a gold colloid in 1-butanol. Such quenching is caused by the non-bonding electron transfer from the O-atom of carbonyl group of the PVP molecules to the surface of the GNP. X-ray photoemission spectroscopy (XPS) study corroborates the spectroscopic results. A linear Stern-Volmer plot with a quenching constant of 2.23 × 106 M-1 reveals dynamic quenching in a non-aqueous NF. A mechanism of fluorescence quenching was proposed in support of XPS and images taken from hybrid nanostructure using transmission electron microscope. Study on quenching of fluorescence intensity of PVP fluorophore in the presence of GNPs is useful for optoelectronic devices and biosensors.

  5. Immobilization of oriented protein molecules on poly(ethylene glycol)-coated Si(111).

    PubMed

    Cha, Taewoon; Guo, Athena; Jun, Yongseok; Pei, Duanqing; Pei, Duanquing; Zhu, Xiao-Yang

    2004-07-01

    A high-density poly(ethylene glycol) (PEG)-coated Si(111) surface is used for the immobilization of polyhistidine-tagged protein molecules. This process features a number of properties that are highly desirable for protein microarray technology: (i) minimal nonspecific protein adsorption; (ii) highly uniform surface functionality; (iii) controlled protein orientation; and (iv) highly specific immobilization reaction without the need of protein purification. The high-density PEG-coated silicon surface is obtained from the reaction of a multi-arm PEG (mPEG) molecule with a chlorine terminated Si(111) surface to give a mPEG film with thickness of 5.2 nm. Four out of the eight arms on each immobilized mPEG molecule are accessible for linking to the chelating iminodiacetic acid (IDA) groups for the binding of Cu(2+) ions. The resulting Cu(2+)-IDA-mPEG-Si(111) surface is shown to specifically bind 6x histidine-tagged protein molecules, including green fluorescent protein (GFP) and sulfotransferase (ST), but otherwise retains its inertness towards nonspecific protein adsorption. We demonstrate a particular advantage of this strategy: the possibility of protein immobilization without the need of prepurification. Surface concentrations of relevant chemical species are quantitatively characterized at each reaction step by X-ray photoelectron spectroscopy (XPS). This kind of quantitative analysis is essential in tuning surface concentration and chemical environment for optimal sensitivity in probe-target interaction.

  6. Synthesis and characterization of cyclic and linear helical poly(alpha-peptoids)s by N-heterocyclic carbene-mediated ring-opening polymerizations of N-substituted N-carboxyanhydrides.

    PubMed

    Guo, Li; Li, Jinhai; Brown, Zachary; Ghale, Kushal; Zhang, Donghui

    2011-01-01

    Cyclic poly(alpha-peptoid)s [a.k.a. poly(N-R-glycine)] with chiral aromatic side-chains [R = (R)- or (S)-CHMePh] have been synthesized by N-heterocyclic carbene-mediated ring-opening polymerization of N-substituted N-carboxyanhydrides (N(R-NCA)). Their linear analogs have been prepared by primary amine-initiated polymerization of the corresponding N(R-NCA). Poly[(R)/(S)-N-CHMePh-glycine] with polymer molecular weights (MWs) in the range of 4-15 kg mol(-1) and low MW distribution (Polydispersity index (PDI) < 1.15) can be readily accessed by these methods. Their high MW analogs were not obtained due to the competitive formation of cyclic oligomeric species that result from intramolecular transamidation. Intrinsic viscosity measurements confirm the architectural difference between the polymers prepared by the two methods and reveals that both cyclic and linear poly[(S)-N-CHMePh-glycine]s behave as random-coil polymers in 0.1M LiBr/Dimethylformamide (DMF) solution. Circular dichroism analysis suggests that the cyclic and linear poly(alpha-peptoid)s retain polyproline I helix conformations, analogously to previously reported linear oligomers. Differential scanning calorimetry analysis reveals that cyclic and linear poly[(S)-N-CHMePh-glycine] are both amorphous with the glass transition temperature of the cyclic polymers (T(g) = 122 degrees C) being notably higher than that of the linear analogs (T(g) = 112 degrees C) with identical MW. These results are consistent with the absence of chain ends, causing the polymers to have reduced segmental mobilities.

  7. 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.

  8. 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.

  9. Synthesis of saturated N-heterocycles.

    PubMed

    Vo, Cam-Van T; Bode, Jeffrey W

    2014-04-04

    Saturated N-heterocycles are prevalent in biologically active molecules and are increasingly attractive scaffolds in the development of new pharmaceuticals. Unlike their aromatic counterparts, there are limited strategies for facile construction of substituted saturated N-heterocycles by convergent, predictable methods. In this Synopsis, we discuss recent advances in the synthesis of these compounds, focusing on approaches that offer generality and convenience from widely available building blocks.

  10. Single molecule detection of double-stranded DNA in poly(methylmethacrylate) and polycarbonate microfluidic devices.

    PubMed

    Wabuyele, M B; Ford, S M; Stryjewski, W; Barrow, J; Soper, S A

    2001-10-01

    Single photon burst techniques were used to detect double-stranded DNA molecules in poly(methylmethacrylate) (PM MA) and polycarbonate (PC) microfluidic devices. A confocal epi-illumination detection system was constructed to monitor the fluorescence signature from single DNA molecules that were multiply labeled with the mono-intercalating dye, TOPRO-5, which possessed an absorption maximum at 765 nm allowing excitation with a solid-state diode laser and fluorescence monitoring in the near-infrared (IR). Near-IR excitation minimized autofluorescence produced from the polymer substrate, which was found to be significantly greater when excitation was provided in the visible range (488 nm). A solution containing lambda-DNA (48.5 kbp) was electrokinetically transported through the microfluidic devices at different applied voltages and solution pH values to investigate the effects of polymer substrate on the transport rate and detection efficiency of single molecular events. By applying an autocorrelation analysis to the data, we were able to obtain the molecular transit time of the individual molecules as they passed through the 7 microm laser beam. It was observed that the applied voltage for both devices affected the transport rate. However, solution pH did not alter the transit time for PM MA-based devices since the electroosmotic flow of PMMA was independent of solution pH. In addition, efforts were directed toward optimizing the sampling efficiency (number of molecules passing through the probe volume) by using either hydrodynamically focused flows from a sheath generated by electrokinetic pumping from side channels or reducing the channel width of the microfluidic device. Due to the low electroosmotic flows generated by both PMMA and PC, tight focusing of the sample stream was not possible. However, in PMMA devices, flow gating was observed by applying field strengths > -120 V/cm to the sheath flow channels. By narrowing the microchannel width, the number of

  11. Reactions of simple aromatic heterocycles with niobium cluster ions (n<=30)

    NASA Astrophysics Data System (ADS)

    Pfeffer, Britta; Jaberg, Stephanie; Niedner-Schatteburg, Gereon

    2009-11-01

    Prior work on benzene activation by size selected niobium cluster cations and anions of up to 30 atoms is extended systematically through studying aromatic poly- and heterocyclic molecules such as naphthalene, pyridine, thiophene, pyrrole, furan, and benzofuran. Naphthalene is found to act much like benzene when reacting under single collision conditions with individual clusters. The most likely process is carbidization through complete dehydrogenation. Some clusters of particular sizes (most notably n=19) fail to activate both homocyclic molecules. Instead seemingly intact adsorption is observed which proves that activation is kinetically hindered at some point. All of the five studied heterocyclic aromatic molecules react unconditionally and by complete dehydrogenation with cationic niobium clusters, while they only attach to or react with anionic clusters larger than a minimum size of n=19-21. These findings are taken as strong evidence for initial coordination to the metal clusters of the heterocycles through their lone pair orbitals. The paper comprehends the observations in terms of cluster surface structure and reactivity.

  12. Synthesis of functionalized tetrasubstituted pyrazolyl heterocycles--a review.

    PubMed

    Dadiboyena, Sureshbabu; Nefzi, Adel

    2011-11-01

    Heterocyclic chemistry constitutes an essential branch of organic chemistry and heterocycles are widely known to display an array of biological properties. Pyrazoles represent key structural motifs in heterocyclic chemistry and are present in a large number of biologically active molecules relevant to the pharmaceutical and agrochemical industries. Compounds incorporating the pyrazolyl structural unit are being developed in a wide variety of therapeutic areas including CNS, metabolic diseases, and oncology. The current review summarizes recent advances in the synthesis of tetrasubstituted pyrazoles. The contents are discussed in five sections: (a) 1,3-dipolar cycloadditions, (b) related 1,3-dipolar cycloadditions, (c) condensations, (d) allenylphosphonates, and (e) synthesis of fused pyrazole containing heterocycles.

  13. Conformational sensitivity of conjugated poly(ethylene oxide)-poly(amidoamine) molecules to cations adducted upon electrospray ionization - a mass spectrometry, ion mobility and molecular modeling study.

    PubMed

    Tintaru, Aura; Chendo, Christophe; Wang, Qi; Viel, Stéphane; Quéléver, Gilles; Peng, Ling; Posocco, Paola; Pricl, Sabrina; Charles, Laurence

    2014-01-15

    Tandem mass spectrometry and ion mobility spectrometry experiments were performed on multiply charged molecules formed upon conjugation of a poly(amidoamine) (PAMAM) dendrimer with a poly(ethylene oxide) (PEO) linear polymer to evidence any conformational modification as a function of their charge state (2+ to 4+) and of the adducted cation (H(+)vs Li(+)). Experimental findings were rationalized by molecular dynamics simulations. The G0 PAMAM head-group could accommodate up to three protons, with protonated terminal amine group enclosed in a pseudo 18-crown-6 ring formed by the PEO segment. This particular conformation enabled a hydrogen bond network which allowed long-range proton transfer to occur during collisionally activated dissociation. In contrast, lithium adduction was found to mainly occur onto oxygen atoms of the polyether, each Li(+) cation being coordinated by a 12-crown-4 pseudo structure. As a result, for the studied polymeric segment (Mn=1500gmol(-1)), PEO-PAMAM hybrid molecules exhibited a more expanded shape when adducted to lithium as compared to proton.

  14. Tunable drug release profiles from salicylate-based poly(anhydride-ester) matrices using small molecule admixtures

    PubMed Central

    Ouimet, Michelle A; Snyder, Sabrina S; Uhrich, Kathryn E

    2013-01-01

    Poly(anhydride-esters) with salicylic acid, a nonsteroidal anti-inflammatory drug, chemically incorporated into the polymer backbone provide high inherent drug loading. These poly(anhydride-esters) hydrolytically degrade to release salicylic acid over extended time periods (>30 days); however, an initial lag period of no salicylic acid release is observed. This lag period could be unfavorable in applications where immediate salicylic acid release is desired. Poly(anhydride-esters) with short (2 days) and long (11 days) lag periods were admixed with various small molecules as a means to shorten or eliminate the lag period. Salicylic acid, larger salicylic acid prodrugs, and 1:1 combinations of the two were physically admixed, each at 1%, 5%, and 10% (w/w). All admixtures resulted in immediate salicylic acid release and a decrease in glass transition temperatures compared to polymer alone. By varying the amounts of salicylic acid and salicylic acid prodrugs incorporated into the polymer matrix, immediate and constant salicylic acid release profiles over varied time periods were achieved. PMID:24078768

  15. Stereoselectively fluorinated N-heterocycles: a brief survey.

    PubMed

    Hu, Xiang-Guo; Hunter, Luke

    2013-11-29

    The stereoselective incorporation of fluorine atoms into N-heterocycles can lead to dramatic changes in the molecules' physical and chemical properties. These changes can be rationally exploited for the benefit of diverse fields such as medicinal chemistry and organocatalysis. This brief review will examine some of the effects that fluorine substitution can have in N-heterocycles, including changes to the molecules' stability, their conformational behaviour, their hydrogen bonding ability, and their basicity. Finally, some methods for the synthesis of stereoselectively fluorinated N-heterocycles will also be reviewed.

  16. 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.

  17. Pd-Catalyzed Heterocycle Synthesis in Ionic Liquids

    NASA Astrophysics Data System (ADS)

    Li, Jianxiao; Jiang, Huanfeng

    Heterocyclic and fused heterocyclic compounds are ubiquitously found in natural products and biologically interesting molecules, and many currently marketed drugs hold heterocycles as their core structure. In this chapter, recent advances on Pd-catalyzed synthesis of heterocycles in ionic liquids (ILs) are reviewed. In palladium catalysis, ILs with different cations and anions are investigated as an alternative recyclable and environmentally benign reaction medium, and a variety of heterocyclic compounds including cyclic ketals, quinolones, quinolinones, isoindolinones, and lactones are conveniently constructed. Compared to the traditional methods, these new approaches have many advantages, such as environmentally friendly synthetic procedure, easy product and catalyst separation, recyclable medium, which make them have the potential applications in industry.

  18. Catechol-derivatized poly(vinyl alcohol) as a coating molecule for magnetic nanoclusters

    NASA Astrophysics Data System (ADS)

    Burnand, David; Monnier, Christophe A.; Redjem, Anthony; Schaefer, Mark; Rothen-Rutishauser, Barbara; Kilbinger, Andreas; Petri-Fink, Alke

    2015-04-01

    Surface functionalization of superparamagnetic iron oxide nanoparticles (SPIONs) remains indispensable in promoting colloidal stability and biocompatibility. We propose a well-defined and characterized synthesis of a new catechol-functionalized RAFT (reversible addition-fragmentation chain transfer) poly(vinyl alcohol) polymer, which can be anchored onto hydrophobic SPIONs via a one-pot emulsion ligand exchange process. Both single and clustered nanoparticles are obtained and can be separated from each other. As clustered SPIONs are receiving increasing attention, this new macroligand might be of considerable interest for both basic and applied sciences.

  19. Ionic liquid catalyzed synthesis and characterization of heterocyclic and optically active poly (amide-imide)s incorporating L-amino acids.

    PubMed

    Zahmatkesh, Saeed

    2011-02-01

    N,N'-pyromelliticdiimido-di-L-alanine (1), N,N'-Pyromelliticdiimido-di-L-phenylalanine (2), and N,N'-Pyromelliticdiimido-di-L-leucine (3) were prepared from the reaction of Pyromellitic dianhydride with corresponding L-amino acids in a mixture of glacial acetic acid and pyridine solution (3/2 ratio) under refluxing conditions. A series of poly (amide-imide)s containing L-amino acids were prepared from the synthesized dicarboxylic acids with two synthetic aromatic diamines in an ionic liquid (IL) as a green, safe and eco-friendly medium and also reactions catalysis agent. Evaluation of data shows that IL is the better polyamidation medium than the reported method and the catalysis stand on the higher inherent viscosities of the obtained PAIs and the rate of polymerizations beyond the greener reaction conditions and deletion of some essential reagents in conventional manners. Characterization were performs by means of IR, MS and (1)H NMR spectroscopy, elemental analysis, specific rotation, thermogravimetric analysis and differential scanning calorimetric techniques. Molecular weights of the obtained polymers were evaluated viscometrically, and the measured inherent viscosities were in the range 0.43-0.85 dL/g. These polymers were readily soluble in many organic solvents. These polymers still kept good thermal stability with glass transition temperatures in the range of 94-154°C, and the decomposition temperature under the nitrogen atmosphere for 10% weight-loss temperatures in excess of 308°C.

  20. Heterocycles from methylenecyclopropanes.

    PubMed

    Yu, Lei; Liu, Mingxuan; Chen, Fenglin; Xu, Qing

    2015-08-21

    The discovery of a series of novel organic reactions has made methylenecyclopropanes (MCPs) some of the most popular building blocks in synthetic organic chemistry during the past two decades. Among reported works, the construction of heterocycles from MCPs has highlighted new synthetic methodologies that afford more opportunities for the quick synthesis of elaborately substituted products, and this should draw a great deal of attention. However, reviews in this area are insufficient, and the latest monograph on heterocycle synthesis from MCPs was published 12 years ago. This review aims to summarize the novel organic reactions of MCPs to produce heterocycles published in recent years, which have provided specific and powerful tools for organic synthesis.

  1. Spin-polarized electron transport through magnetic poly-BIPO molecule: the role of soliton-antisoliton separation

    NASA Astrophysics Data System (ADS)

    Sadeghi, N.; Ketabi, S. A.; Shahtahmassebi, N.; Abolhassani, M. R.

    2016-02-01

    Spin-polarized transport through a one-dimensional metal/poly-BIPO/metal model junction with the soliton-antisoliton separation is investigated. Nonlinear spin and charge densities are considered in magnetic poly-BIPO molecule, as a neutral soliton and charged antisoliton with different separations. The calculations are performed based on Su-Schrieffer-Heeger Hamiltonian which is extended with Heisenberg and Hubbard Hamiltonians to include the spin and electron-electron interactions. The spin-dependent transport properties are obtained within the framework of the Landauer-Büttiker formalism based on Green's function theory. This study demonstrates the reduction in current and spin polarization as the separation between soliton and antisoliton centers is increased. We have found that when the soliton-antisoliton separation is less than 14 sites, the spin polarization is almost 100 % plato, over the voltage ranges more than 0.3 V. Also the energy differences between the soliton-antisoliton mid-gap states for up- and down-spin electrons and the Fermi energy of the system are reduced. However, for the soliton-antisoliton separation lengths more than 14 sites, these quantities tend to constant values with enhancement of the distance between the excitation centers.

  2. In vitro transfection mediated by dendrigraft poly(L-lysines): the effect of structure and molecule size.

    PubMed

    Hofman, Jakub; Buncek, Martin; Haluza, Radovan; Streinz, Ludvik; Ledvina, Miroslav; Cigler, Petr

    2013-02-01

    Dendritic poly(L-lysines) (DGL) constitute promising nanomaterials applicable as a nonviral gene-delivery vector. In this study, we evaluate the transfection abilities of four DGL generations with special emphasis on the systematic description of the relationship of how generation (i.e., molecule size) affects the transfection efficacy. Using Hep2 cells, we demonstrated that the capability of unmodified DGL to deliver plasmid is of a magnitude lower than that of jetPEI. On the other hand, employing the Hep2 cell line stably transduced with eGFP, we observed that DGL G5 delivers the siRNA oligonucleotide with the same efficiency as Lipofectamine 2000. In further experiments, it was shown that DGL affords excellent ability to bind DNA, protect it against DNase I attack, and internalize it into cells.

  3. 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.

  4. 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

  5. Selective light emission in nonbonding electron transitions in poly(vinyl pyrrolidone) molecules on spin-coating in thin layers.

    PubMed

    Mishra, A; Ram, S

    2009-12-24

    It is shown that polymer molecules of poly(vinyl pyrrolidone) (PVP) rearranged in thin layers present surface-enhanced light emission in selective bands over a wide 260-860 nm range of spectrum. Four bands occur in spin-coated films by a dilute solution in water at 288, 395, 560, and 760 nm upon irradiating with an ultraviolet 200-250 nm light. The second and third bands are strong by contributing 82% intensity of the spectrum. Randomly dispersed PVP molecules in solution exhibit a single band (broad) at 425 nm {pi(0) <-- n(1)pi(2)* transition in the nonbonding electrons n(1) in the C=O (2s(2)p(4)) group of pyrrolidone ring} and a harmonic band 650-860 nm (weak) of roughly twice its wavelength. In films, this band is split up into two well-separated pi(0) <-- n(1)pi(2)* (395 nm) and pi(0) <-- n(2)pi(1)* (560 nm) bands. Localized nonbonding electrons n(2) of the C-N (2s(2)p(3)) moiety of pyrrolidone ring excite and emit part of the energy in the pi(0) <-- n(2)pi(1)* transition with as much intensity as in the pi(0) <-- n(1)pi(2)* band. Localization of n(1) and n(2) electrons on molecular layers of films favors the resonance >N-C=O structure with three C=O stretching bands 1615, 1635, and 1665 cm(-1) against a single band 1638 cm(-1) in randomly dispersed molecules (solution). The C-N stretching frequency is decreased by 30 cm(-1). Results are useful for molecular designing of optical films for down-energy conversion, optical switching, and biological sensors.

  6. Novel Effects of Compressed CO2 Molecules on Structural Ordering and Charge Transport in Conjugated Poly(3-hexylthiophene) Thin Films

    DOE PAGES

    Jiang, Naisheng; Sendogdular, Levent; Sen, Mani; ...

    2016-10-06

    We report the effects of compressed CO2 molecules as a novel plasticization agent for poly(3- hexylthiophene) (P3HT) conjugated polymer thin films. In-situ neutron reflectivity experiment demonstrated the excess sorption of CO2 molecules in the P3HT thin films (about 40 nm in thickness) at low pressure (P = 8.2 MPa) under the isothermal condition of T = 36 °C, which is far below the polymer bulk melting point. The results evidenced that these CO2 molecules accelerated the crystallization process of the polymer on the basis of ex-situ grazing incidence Xray diffraction measurements after drying the films via rapid depressurization to atmosphericmore » pressure: not only the out-of-plane lamellar ordering of the backbone chains but also intra-plane π-π stacking of the side chains were significantly improved, when compared to those in the control P3HT films subjected to conventional thermal annealing (at T = 170 °C). Electrical measurements elucidated that the CO2-annealed P3HT thin films exhibited enhanced charge carrier mobility along with decreased background charge carrier concentration and trap density compared to those in the thermally annealed counterpart. This is attributed to the CO2-induced increase in polymer chain mobility that can drive the detrapping of molecular oxygen and healing of conformational defects in the polymer thin film. Given the universality of the excess sorption of CO2regardless of the type of polymers, the present findings suggest that the CO2 annealing near the critical point can be useful as a robust processing strategy for improving structural and electrical characteristics of other semiconducting conjugated polymers and related systems such as polymer: fullerene bulk heterojunction films.tion films.« less

  7. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals.

    PubMed

    Vitaku, Edon; Smith, David T; Njardarson, Jon T

    2014-12-26

    Nitrogen heterocycles are among the most significant structural components of pharmaceuticals. Analysis of our database of U.S. FDA approved drugs reveals that 59% of unique small-molecule drugs contain a nitrogen heterocycle. In this review we report on the top 25 most commonly utilized nitrogen heterocycles found in pharmaceuticals. The main part of our analysis is divided into seven sections: (1) three- and four-membered heterocycles, (2) five-, (3) six-, and (4) seven- and eight-membered heterocycles, as well as (5) fused, (6) bridged bicyclic, and (7) macrocyclic nitrogen heterocycles. Each section reveals the top nitrogen heterocyclic structures and their relative impact for that ring type. For the most commonly used nitrogen heterocycles, we report detailed substitution patterns, highlight common architectural cores, and discuss unusual or rare structures.

  8. Absorption and Quantum Yield of Single Conjugated Polymer Poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) Molecules

    PubMed Central

    2017-01-01

    We simultaneously measured the absorption and emission of single conjugated polymer poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) molecules in a poly(methyl methacrylate) (PMMA) matrix using near-critical xenon to enhance the photothermal contrast for direct absorption measurements. We directly measured the number of monomers and the quantum yield of single conjugated polymer molecules. Simultaneous absorption and emission measurements provided new insight into the photophysics of single conjugated polymers under optical excitation: quenching in larger molecules is more efficient than in smaller ones. Photoinduced traps and defects formed under prolonged illumination lead to decrease of both polymer fluorescence and absorption signals with the latter declining slower. PMID:28221806

  9. Poly-(amidoamine) dendrimers with a precisely core positioned sulforhodamine B molecule for comparative biological tracing and profiling.

    PubMed

    Wu, Lin-Ping; Ficker, Mario; Mejlsøe, Søren L; Hall, Arnaldur; Paolucci, Valentina; Christensen, Jørn B; Trohopoulos, Panagiotis N; Moghimi, Seyed M

    2017-01-28

    We report on a simple robust procedure for synthesis of generation-4 poly-(amidoamine) (PAMAM) dendrimers with a precisely core positioned single sulforhodamine B molecule. The labelled dendrimers exhibited high fluorescent quantum yields where the absorbance and fluorescence spectrum of the fluorophore was not affected by pH and temperature. Since the stoichiometry of the fluorophore to the dendrimer is 1:1, we were able to directly compare uptake kinetics, the mode of uptake, trafficking and safety of dendrimers of different end-terminal functionality (carboxylated vs. pyrrolidonated) by two phenotypically different human endothelial cell types (the human brain capillary endothelial cell line hCMEC/D3 and human umbilical vein endothelial cells), and without interference of the fluorophore in uptake processes. The results demonstrate comparable uptake kinetics and a predominantly clathrin-mediated endocytotic mechanism, irrespective of dendrimer end-terminal functionality, where the majority of dendrimers are directed to the endo-lysosomal compartments in both cell types. A minor fraction of dendrimers, however, localize to endoplasmic reticulum and the Golgi apparatus, presumably through the recycling endosomes. In contrast to amino-terminated PAMAM dendrimers, we confirm safety of carboxylic acid- and pyrrolidone-terminated PAMAM dendrimers through determination of cell membrane integrity and comprehensive respiratory profiling (measurements of mitochondrial oxidative phosphorylation and determination of its coupling efficiency). Our dendrimer core-labelling approach could provide a new conceptual basis for improved understanding of dendrimer performance within biological settings.

  10. 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.

  11. 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.

  12. 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.

  13. Photochemistry of hydrogen bonded heterocycles probed by photodissociation experiments and ab initio methods.

    PubMed

    Slavíček, Petr; Fárník, Michal

    2011-07-14

    In this perspective article, we focus on the photochemistry of five-membered nitrogen containing heterocycles (pyrrole, imidazole and pyrazole) in clusters. These heterocycles represent paradigmatic structures for larger biologically active heterocyclic molecules and complexes. The dimers of the three molecules are also archetypes of different bonding patterns: N-H···π interaction, N-H···N hydrogen bond and double hydrogen bond. We briefly review available data on photochemistry of the title molecules in the gas phase, but primarily we focus on the new reaction channels opened upon the complexation with other heterocycles or solvent molecules. Based on ab initio calculations we discuss various possible reactions in the excited states of the clusters: (1) hydrogen dissociation, (2) hydrogen transfer between the heterocyclic units, (3) molecular ring distortion, and (4) coupled electron-proton transfer. The increasing photostability with complexity of the system can be inferred from experiments with photodissociation in these clusters. A unified view on photoinduced processes in five-membered N-heterocycles is provided. We show that even though different deactivation channels are energetically possible for the complexed heterocycles, in most cases the major result is a fast reconstruction of the ground state. The complexed or solvated heterocycles are thus inherently photostable although the stability can in principle be achieved via different reaction routes.

  14. Celastrol suppresses expression of adhesion molecules and chemokines by inhibiting JNK-STAT1/NF-κB activation in poly(I:C)-stimulated astrocytes

    PubMed Central

    An, Soo Yeon; Youn, Gi Soo; Kim, Hyejin; Choi, Soo Young; Park, Jinseu

    2017-01-01

    In the central nervous system, viral infection can induce inflammation by up-regulating pro-inflammatory mediators that contribute to enhanced infiltration of immune cells into the central nervous areas. Celastrol is known to exert various regulatory functions, including anti-microbial activities. In this study, we investigated the regulatory effects and the mechanisms of action of celastrol against astrocytes activated with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic dsRNA, as a model of pro-inflammatory mediated responses. Celastrol significantly inhibited poly(I:C)-induced expression of adhesion molecules, such as ICAM-1/VCAM-1, and chemokines, such as CCL2, CXCL8, and CXCL10, in CRT-MG human astroglioma cells. In addition, celastrol significantly suppressed poly(I:C)-induced activation of JNK MAPK and STAT1 signaling pathways. Furthermore, celastrol significantly suppressed poly(I:C)-induced activation of the NF-κB signaling pathway. These results suggest that celastrol may exert its regulatory activity by inhibiting poly(I:C)-induced expression of pro-inflammatory mediators by suppressing activation of JNK MAPK-STAT1/NF-κB in astrocytes. PMID:28027722

  15. Heterocyclic chemistry in crop protection.

    PubMed

    Lamberth, Clemens

    2013-10-01

    An overview is given of the significance of heterocycles in crop protection chemistry, which is enormous as more than two-thirds of all agrochemicals launched to the market within the last 20 years belong to this huge group of chemicals. This review focuses on two important aspects of heterocyclic agrochemistry: the different roles of heterocyclic scaffolds in crop protection agents and the major possibilities for their synthesis.

  16. Preparation and evaluation of poly(alkyl methacrylate-co-methacrylic acid-co-ethylene dimethacrylate) monolithic columns for separating polar small molecules by capillary liquid chromatography.

    PubMed

    Lin, Shu-Ling; Wu, Yu-Ru; Lin, Tzuen-Yeuan; Fuh, Ming-Ren

    2015-04-29

    In this study, methacrylic acid (MAA) was incorporated with alkyl methacrylates to increase the hydrophilicity of the synthesized ethylene dimethacrylate-based (EDMA-based) monoliths for separating polar small molecules by capillary LC analysis. Different alkyl methacrylate-MAA ratios were investigated to prepare a series of 30% alkyl methacrylate-MAA-EDMA monoliths in fused-silica capillaries (250-μm i.d.). The porosity, permeability, and column efficiency of the synthesized MAA-incorporated monolithic columns were characterized. A mixture of phenol derivatives is employed to evaluate the applicability of using the prepared monolithic columns for separating small molecules. Fast separation of six phenol derivatives was achieved in 5 min with gradient elution using the selected poly(lauryl methacrylate-co-MAA-co-EDMA) monolithic column. In addition, the effect of acetonitrile content in mobile phase on retention factor and plate height as well as the plate height-flow velocity curves were also investigated to further examine the performance of the selected poly(lauryl methacrylate-co-MAA-co-EDMA) monolithic column. Moreover, the applicability of prepared polymer-based monolithic column for potential food safety applications was also demonstrated by analyzing five aflatoxins and three phenicol antibiotics using the selected poly(lauryl methacrylate-co-MAA-co-EDMA) monolithic column.

  17. 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.

  18. Synthesis of medicinally privileged heterocycles through dielectric heating.

    PubMed

    Bandyopadhyay, Debasish; Banik, Bimal K

    2017-02-23

    This review summarizes the potential application of microwave irradiation (dielectric heating) to synthesize biologically important heterocyclic small molecules in the recent past. A huge number of heterocyclic compounds are present in various natural sources like plant, marine microbe or other organisms and many of them possess unique biological activity. In addition to nature-derived heterocyclic compounds, a large number of synthetic heterocycles are being used as medicines. This review describes the relevant recent examples of microwave irradiation to accomplish various chemical transformations accelerated by a variety of catalysts which include, but not limited to, Lewis acids, other metal containing catalysts, organocatalysts, heterogeneous catalysts, phase-transfer catalysts, solid-supported catalysts, inorganic catalysts (bases, acids and salts) and so on. Although there are an increasing number of reports on application of dielectric heating in various other fields, this review is focused on a large number of new and novel strategies related to synthetic organic chemistry. The discussion is mostly organized by the disease type although some reactions/molecules can certainly be placed in multiple sections. Since green chemistry is an extremely emerging and comparatively new field of research, attempts to stimulate more activities on green medicinal chemistry are provided. Discussion related to the concurrent effect of microwaves, catalysts and/or solvents, supports to constitute expeditious and general route for the syntheses of medicinally important heterocyclic compounds and pharmacophores has also been included. While every effort has been made to include all pertinent reports in this field, any omission is unintentional.

  19. Improved small molecule drug release from in situ forming poly(lactic-co-glycolic acid) scaffolds incorporating poly(β-amino ester) and hydroxyapatite microparticles.

    PubMed

    Fisher, Paul D; Palomino, Pablo; Milbrandt, Todd A; Hilt, J Zach; Puleo, David A

    2014-01-01

    In situ forming implants are an attractive choice for controlled drug release into a fixed location. Currently, rapidly solidifying solvent exchange systems suffer from a high initial burst, and sustained release behavior is tied to polymer precipitation and degradation rate. The present studies investigated addition of hydroxyapatite (HA) and drug-loaded poly(β-amino ester) (PBAE) microparticles to in situ forming poly(lactic-co-glycolic acid) (PLGA)-based systems to prolong release and reduce burst. PBAEs were synthesized, imbibed with simvastatin (osteogenic) or clodronate (anti-resorptive), and then ground into microparticles. Microparticles were mixed with or without HA into a PLGA solution, and the mixture was injected into buffer, leading to precipitation and creating solid scaffolds with embedded HA and PBAE microparticles. Simvastatin release was prolonged through 30 days, and burst release was reduced from 81 to 39% when loaded into PBAE microparticles. Clodronate burst was reduced from 49 to 32% after addition of HA filler, but release kinetics were unaffected after loading into PBAE microparticles. Scaffold dry mass remained unchanged through day 15, with a pronounced increase in degradation rate after day 30, while wet scaffolds experienced a mass increase through day 25 due to swelling. Porosity and pore size changed throughout degradation, likely due to a combination of swelling and degradation. The system offers improved release kinetics, multiple release profiles, and rapid solidification compared to traditional in situ forming implants.

  20. Improved small molecule drug release from in situ forming poly(lactic-co-glycolic acid) scaffolds incorporating poly(β-amino ester) and hydroxyapatite microparticles

    PubMed Central

    Fisher, Paul D.; Palomino, Pablo; Milbrandt, Todd A.; Hilt, J. Zach; Puleo, David A.

    2014-01-01

    In situ forming implants are an attractive choice for controlled drug release into a fixed location. Currently, rapidly solidifying solvent exchange systems suffer from a high initial burst, and sustained release behavior is tied to polymer precipitation and degradation rate. The present studies investigated addition of hydroxyapatite (HA) and drug-loaded poly(β-amino ester) (PBAE) microparticles to in situ forming poly(lactic-co-glycolic acid) (PLGA)–based systems to prolong release and reduce burst. PBAEs were synthesized, imbibed with simvastatin (osteogenic) or clodronate (anti-resorptive), and then ground into microparticles. Microparticles were mixed with or without HA into a PLGA solution, and the mixture was injected into buffer, leading to precipitation and creating solid scaffolds with embedded HA and PBAE microparticles. Simvastatin release was prolonged through 30 days, and burst release was reduced from 81% to 39% when loaded into PBAE microparticles. Clodronate burst was reduced from 49% to 32% after addition of HA filler, but release kinetics were unaffected after loading into PBAE microparticles. Scaffold dry mass remained unchanged through day 15, with a pronounced increase in degradation rate after day 30, while wet scaffolds experienced a mass increase through day 25 due to swelling. Porosity and pore size changed throughout degradation, likely due to a combination of swelling and degradation. The system offers improved release kinetics, multiple release profiles, and rapid solidification compared to traditional in situ forming implants. PMID:24903524

  1. Interaction of small molecules with double-stranded RNA: spectroscopic, viscometric, and calorimetric study of hoechst and proflavine binding to PolyCG structures.

    PubMed

    Sinha, Rangana; Hossain, Maidul; Kumar, Gopinatha Suresh

    2009-04-01

    Design and synthesis of new small molecules binding to double-stranded RNA necessitate complete understanding of the molecular aspects of the binding of many existing molecules. Toward this goal, in this work we evaluated the biophysical aspects of the interaction of a DNA intercalator (proflavine) and a minor groove binder (hoechst 33258) with two polymorphic forms of polyCG, namely, the right-handed Watson-Crick base paired A-form and the left-handed Hoogsteen base paired H(L)-form, by absorption, fluorescence, and viscometry experiments. The energetics of the interaction of these molecules with the RNA structures has also been elucidated by isothermal titration calorimetry (ITC). Results suggest that proflavine strongly intercalates in both forms of polyCG, whereas hoechst shows mainly groove-binding modes. The binding of both drugs to both forms of RNA resulted in significant conformational change to the RNA structure with the bound molecules being placed in the chiral RNA helix. ITC profiles for both proflavine and hoechst show two binding sites. Binding of proflavine to both forms of RNA is endothermic and entropy driven in the first site and exothermic and enthalpy driven in the second site, whereas hoechst binding to both forms of RNA is exothermic and enthalpy driven in the first site and endothermic and entropy driven in the second site. This study suggests that the binding affinity characteristics and energetics of interaction of these DNA binding molecules with the RNA conformations are significantly different and may serve as data for future development of effective structure-selective RNA-based drugs.

  2. Structure and Proton Conductivity in Mixtures of Poly(acrylic acid) and Imidazole

    NASA Astrophysics Data System (ADS)

    Yang, Han-Chang; Griffin, Philip J.; Winey, Karen I.; University of Pennsylvania Team

    2015-03-01

    Proton conductivity in polymer electrolyte membranes (PEMs) typically involves water, which requires that during operation the humidity of the PEM be carefully controlled. In contrast, anhydrous protic polymer membranes promote proton transport by incorporating heterocyclic molecules, such as imidazole and its derivatives, into acid-containing polymers. In this work, we explore the interplay between nanoscale-structure and proton conduction of poly(acrylic acid) (PAA) blended at varying compositions with 2-ethyl-4-methylimidazole (EMI). We present the glass transition temperature from differential scanning calorimetry, morphology characterization from X-ray scattering, and proton conductivity from electrical impedance spectroscopy.

  3. 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.

  4. Preparation and Evaluation of Poly(N-isopropylacrylamide-co-hexanediol diacrylate-co-ethylene dimethacrylate) Monolithic Column and its Applications in the Separation of Small Molecules.

    PubMed

    Ma, Yamin; Liu, Haiyan; Wei, Aile; Qin, Junxiao; Zhang, Shiqi; Zhang, Wen; Bai, Ligai

    2016-11-01

    Poly(N-isopropylacrylamide-co-hexanediol diacrylate-co-ethylene dimethacrylate) [poly(NIPAAm-co-HDDA-co-EDMA)] monolithic column was prepared via in situ polymerization reaction. In order to investigate the porous properties of the monoliths prepared, the morphology was characterized by the scanning electron microscopy; the chemical group of the monolithic column was confirmed by a Fourier transform infrared spectroscopy method. The surface area was 39.1 m(2)/g by the nitrogen adsorption-desorption experiment. With methanol as the mobile phase, the permeability of the monolithic column was calculated as 3.2330 × 10(-14) m(2) Then it was used as the stationary phase of high performance liquid chromatography. The results indicted that poly(NIPAAm-co-HDDA-co-EDMA) monolithic column was good to separate small molecules by controlling the temperature. Column efficiency for p-chloronitrobenzene was 4,680 plates/m. Repeatability was defined by determining run-to-run and column-to-column variation of the retention times of aromatic compounds, expressed as relative standard deviation (RSD = standard deviation/mean × 100%), and the values were <0.58% and 3.1%, respectively.

  5. Practical and innate carbon-hydrogen functionalization of heterocycles.

    PubMed

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

    2012-12-06

    Nitrogen-rich heterocyclic compounds have had a profound effect on human health because 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, C-H functionalization of medicinally important heterocycles that does not rely on pre-functionalized starting materials is an underdeveloped area. Unfortunately, the innate properties of heterocycles that make them so desirable for biological applications--such as aqueous solubility and their ability to act as ligands--render them challenging substrates for direct chemical functionalization. Here we report that zinc sulphinate salts can be used to transfer alkyl radicals to heterocycles, allowing for the mild (moderate temperature, 50 °C or less), direct and operationally simple formation of medicinally relevant C-C bonds while reacting in a complementary fashion to other innate C-H functionalization methods (Minisci, borono-Minisci, electrophilic aromatic substitution, transition-metal-mediated C-H insertion and C-H deprotonation). We prepared a toolkit of these reagents and studied their reactivity across a wide range of heterocycles (natural products, drugs and building blocks) without recourse to protecting-group chemistry. The reagents can even be used in tandem fashion in a single pot in the presence of water and air.

  6. Nanomedicine strategy for optimizing delivery to outer hair cells by surface-modified poly(lactic/glycolic acid) nanoparticles with hydrophilic molecules

    PubMed Central

    Wen, Xingxing; Ding, Shan; Cai, Hui; Wang, Junyi; Wen, Lu; Yang, Fan; Chen, Gang

    2016-01-01

    Targeted drug delivery to outer hair cells (OHCs) in the cochlea by nanomedicine strategies forms an effective therapeutic approach for treating hearing loss. Surface chemistry plays a deciding role in nanoparticle (NP) biodistribution, but its influence on such distribution in the cochlea remains largely unknown. Herein, we report the first systematic comparison of poly(lactic/glycolic acid) nanoparticles (PLGA NPs) with or without surface modification of hydrophilic molecules for optimizing the delivery to OHCs both in vitro and in vivo. NPs that were surface modified with poloxamer 407 (P407), chitosan, or methoxy poly(ethylene glycol) and the unmodified NPs were highly biocompatible with L929 and House Ear Institute-organ of Corti 1 cells as well as cochlear tissues. Interestingly, among all the examined NPs, P407-PLGA NPs showed the greatest cellular uptake and prominent fluorescence in cochlear imaging. More importantly, we provide novel evidence that the surface-modified NPs reached the organ of Corti and were transported into the OHCs at a higher level. Together, these observations suggest that surface modification with hydrophilic molecules will allow future clinical applications of PLGA NPs, especially P407-PLGA NPs, in efficient hearing loss therapy. PMID:27877041

  7. A Comprehensive Review of N-Heterocycles as Cytotoxic Agents.

    PubMed

    Kumar, Dinesh; Jain, Subheet Kumar

    2016-01-01

    Scientific community is striving to understand the role of heterocycles and fused heterocycles in drug discovery programme due to its impact on multi-drug resistance (MDR) of anticancer drugs. Architecting of various scaffolds for cancer treatment has become gradually increased in many years. Till now there is no treatment which is so proficient that it can cure the cancer from the roots. Hence, it is very necessary to design novel anticancer agents with minimum side effects. Synthesis of hybrids from natural leads is one of the rationale approaches in medicinal chemistry. It remains a big challenge to invent new efficient drugs to beat cancer. The design and synthesis of fused molecules as anticancer agents is one of the great innovations of modern era. In drug discovery archetype, a variety of heterocycles have been considered for the development of novel lead compounds. This article presents some recent advancements in the field of anticancer heterocyclic agents all around the world and also attracted the structure activity relationship along with the structure of the most promising molecules along with IC50 values against various human cancer cell lines.

  8. Heterocyclic Nanographenes and Other Polycyclic Heteroaromatic Compounds: Synthetic Routes, Properties, and Applications.

    PubMed

    Stępień, Marcin; Gońka, Elżbieta; Żyła, Marika; Sprutta, Natasza

    2017-02-22

    Two-dimensionally extended, polycyclic heteroaromatic molecules (heterocyclic nanographenes) are a highly versatile class of organic materials, applicable as functional chromophores and organic semiconductors. In this Review, we discuss the rich chemistry of large heteroaromatics, focusing on their synthesis, electronic properties, and applications in materials science. This Review summarizes the historical development and current state of the art in this rapidly expanding field of research, which has become one of the key exploration areas of modern heterocyclic chemistry.

  9. Joining Forces: Fermentation and Organic Synthesis for the Production of Complex Heterocycles.

    PubMed

    Gober, Claire M; Joullié, Madeleine M

    2016-11-04

    Commercial application of many promising heterocyclic natural products is limited by their natural abundance. While organic synthesis provides access to many natural products, total synthesis of numerous complex molecules is not economically feasible. In recent years, the combination of fermentation and organic synthesis has provided a new route for the production of complex heterocycles that are inaccessible by typical synthetic methods. This JOCSynopsis will review examples of how this union of disciplines has overcome obstacles in both academia and industry.

  10. Joining Forces: Fermentation and Organic Synthesis for the Production of Complex Heterocycles

    PubMed Central

    Gober, Claire M.; Joullié, Madeleine M.

    2016-01-01

    Commercial application of many promising heterocyclic natural products is limited by their natural abundance. While organic synthesis provides access to many natural products, total synthesis of numerous complex molecules is not economically feasible. In recent years, the combination of fermentation and organic synthesis has provided a new route for the production of complex heterocycles that are inaccessible by typical synthetic methods. This JOCSynopsis will review examples of how this union of disciplines has overcome obstacles in both academia and industry. PMID:27427903

  11. Controlling the association of adamantyl-substituted poly{N-[tris(hydroxymethyl)methyl]acrylamide} and a beta-cyclodextrin/epichlorohydrin polymer by a small drug molecule--naproxen.

    PubMed

    Mislovicová, Danica; Kogan, Grigorij; Gosselet, Noëlle Martine; Sébille, Bernard; Soltés, Ladislav

    2007-01-01

    Two polymeric substances, a poly{N-[tris(hydroxymethyl)methyl]acrylamide} (THMMA) substituted with adamantyl moieties and a beta-cyclodextrin/epichlorohydrin polycondensate, formed a host-guest type complex, which resulted in the gel formation upon mixing of these two compounds at appropriate conditions. Introduction of a drug molecule, i.e., naproxen, that was able to fill the beta-cyclodextrin cavities, thus expulsing adamantyl moieties, led to disruption of such association and inhibition of gel formation. The conditions required for the association of the two polymeric components and formation of the gel, as well as the dynamics of its inhibition by addition of naproxen was established. The procedure of using solutions of two associating polymers and an appropriate drug competitor can be used at targeted viscosupplementation.

  12. Room-temperature high-spin organic single molecule: nanometer-sized and hyperbranched poly[1,2,(4)-phenylenevinyleneanisylaminium].

    PubMed

    Fukuzaki, Eiji; Nishide, Hiroyuki

    2006-01-25

    Poly[1,2,(4)-phenylenevinyleneanisylaminium] 1 was synthesized by one-pot palladium-catalyzed polycondensation of N-(3-bromo-4-vinylphenyl)-N-(4-methoxyphenyl)-N-(4-vinylphenyl)amine 3 and subsequent oxidation with the thianthrene cation radical tetrafluoroborate: compound 1 three-directionally satisfies a non-Kekulé-type pi-conjugation and the ferromagnetic connectivity of the unpaired electrons of the triarylaminium cationic radical. The average molecular weight of the polymer was 4700-5900 (degree of polymerization = 11-14), which gave a single molecular-based and globular-shaped image of ca. 15 nm diameter by atomic and magnetic force microscopies under ambient conditions. The aminium polyradical 1 with a spin concentration (determined by iodometry) of 0.65 spin/unit displayed an average S (spin quantum number) value of 7/2 even at 70 degrees C according to NMR and magnetization measurements.

  13. Single-molecule tracking study of the permeability and transverse width of individual cylindrical microdomains in solvent-swollen polystyrene-block-poly(ethylene oxide) films

    SciTech Connect

    Sapkota, Dol Raj; Tran-Ba, Khanh-Hoa; Elwell-Cuddy, Trevor; Higgins, Daniel A.; Ito, Takashi

    2016-11-04

    Understanding the properties of solvent-swollen block copolymer (BCP) microdomains is important for better solvent-based control of microdomain morphology, orientation, and permeability. In this study, single-molecule tracking (SMT) was explored to assess the permeability and transverse width of individual cylindrical microdomains in solvent-swollen polystyrene-block-poly(ethylene oxide) (PS-b-PEO) films. PS-b-PEO films comprising shear-elongated cylindrical PEO microdomains were prepared by sandwiching its benzene or tetrahydrofuran (THF) solution between two glass substrates. In this paper, SMT measurements were performed at different drying times to investigate the effects of solvent evaporation on the microdomain properties. SMT data showed one-dimensional (1D) motions of single fluorescent molecules (sulforhodamine B) based on their diffusion within the cylindrical microdomains. Microdomain permeability and transverse width were assessed from the single-molecule diffusion coefficients (DSMT) and transverse variance of the 1D trajectories (σδ2), respectively. The DSMT and σδ2 values from individual 1D trajectories were widely distributed with no evidence of correlation on a single molecule basis, possibly because the individual microdomains in a film were swollen to different extents. On average, microdomain permeability (D) and effective radius (r) gradually decreased within the first 3 days of drying due to solvent evaporation, and changed negligibly thereafter. PS-b-PEO films prepared from THF solutions exhibited larger changes in D and r as compared with those from benzene solutions due to the better swelling of the PEO microdomains by THF. Importantly, changes in D were more prominent than those in r, suggesting that the permeability of the PEO microdomains is very susceptible to the presence of solvent. Finally, these results reveal the unique capability of SMT to assess the

  14. Single-molecule tracking study of the permeability and transverse width of individual cylindrical microdomains in solvent-swollen polystyrene-block-poly(ethylene oxide) films

    DOE PAGES

    Sapkota, Dol Raj; Tran-Ba, Khanh-Hoa; Elwell-Cuddy, Trevor; ...

    2016-11-04

    Understanding the properties of solvent-swollen block copolymer (BCP) microdomains is important for better solvent-based control of microdomain morphology, orientation, and permeability. In this study, single-molecule tracking (SMT) was explored to assess the permeability and transverse width of individual cylindrical microdomains in solvent-swollen polystyrene-block-poly(ethylene oxide) (PS-b-PEO) films. PS-b-PEO films comprising shear-elongated cylindrical PEO microdomains were prepared by sandwiching its benzene or tetrahydrofuran (THF) solution between two glass substrates. In this paper, SMT measurements were performed at different drying times to investigate the effects of solvent evaporation on the microdomain properties. SMT data showed one-dimensional (1D) motions of single fluorescent molecules (sulforhodaminemore » B) based on their diffusion within the cylindrical microdomains. Microdomain permeability and transverse width were assessed from the single-molecule diffusion coefficients (DSMT) and transverse variance of the 1D trajectories (σδ2), respectively. The DSMT and σδ2 values from individual 1D trajectories were widely distributed with no evidence of correlation on a single molecule basis, possibly because the individual microdomains in a film were swollen to different extents. On average, microdomain permeability (D) and effective radius (r) gradually decreased within the first 3 days of drying due to solvent evaporation, and changed negligibly thereafter. PS-b-PEO films prepared from THF solutions exhibited larger changes in D and r as compared with those from benzene solutions due to the better swelling of the PEO microdomains by THF. Importantly, changes in D were more prominent than those in r, suggesting that the permeability of the PEO microdomains is very susceptible to the presence of solvent. Finally, these results reveal the unique capability of SMT to assess the properties of individual cylindrical microdomains in a solvent

  15. Structural characterization of new defective molecules in poly(amidoamide) dendrimers by combining mass spectrometry and nuclear magnetic resonance.

    PubMed

    Tintaru, Aura; Ungaro, Rémi; Liu, Xiaoxiuan; Chen, Chao; Giordano, Laurent; Peng, Ling; Charles, Laurence

    2015-01-01

    A new side-reaction occurring during divergent synthesis of PAMAM dendrimers (generations G0-G2) was revealed by mass spectrometric detection of defective molecules with a net gain of a single carbon atom as compared to expected compounds. Combining MS/MS experiments performed on different electrosprayed precursor ions (protonated molecules and lithiated adducts) with NMR analyses allowed the origin of these by-products to be elucidated. Modification of one ethylenediamine end-group of perfect dendrimers into a cyclic imidazolidine moiety was induced by formaldehyde present at trace level in the methanol solvent used as the synthesis medium. Dendrimers studied here were purposely constructed from a triethanolamine core to make them more flexible, as compared to NH3- or ethylenediamine-core PAMAM, and hence improve their interaction with DNA. Occurrence of this side-reaction would be favored by the particular flexibility of the dendrimer branches.

  16. Inquiring the mechanism of formation, encapsulation, and stabilization of gold nanoparticles by poly(vinyl pyrrolidone) molecules in 1-butanol

    NASA Astrophysics Data System (ADS)

    Behera, M.; Ram, S.

    2013-02-01

    We present a plausible mechanism of formation, encapsulation, and stabilization of gold nanoparticles (GNPs) in presence of poly(vinyl pyrrolidone) (PVP) in 1-butanol in support of UV-visible, Raman, Fourier transform infrared spectroscopy (FTIR), zetapotential, X-ray photoelectron spectrum (XPS), and transmission electron microscopy. A surface plasmon resonance band at 533 nm in the UV-visible spectrum reveals formation of ~20 nm spherical GNPs in the non-hydrocolloid. In the FTIR spectrum, selective enhancement in the intensity of C-H stretching and red-shift in the C=O band suggests that PVP encapsulate GNP by an interaction between PVP and GNP that occurs via O-atom of pyrrolidone ring. Raman and XPS spectrum well supports the findings of FTIR spectrum. Zeta potential of -15.22 mV at 7.5 pH found in PVP-capped GNP strongly recommends the role of electrosteric effect towards the observed colloidal stability. Microscopic image demonstrates a thin coating of amorphous PVP layer around GNPs in a core-shell structure. Probing the mechanism of formation, encapsulation, and stabilization of GNP could provide essential information for development of bimetallic NPs for catalytic applications.

  17. 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.

  18. Novel Effects of Compressed CO2 Molecules on Structural Ordering and Charge Transport in Conjugated Poly(3-hexylthiophene) Thin Films

    SciTech Connect

    Jiang, Naisheng; Sendogdular, Levent; Sen, Mani; Endoh, Maya K.; Koga, Tadanori; Fukuto, Masafumi; Akgun, Bulent; Satija, Sushil K.; Nam, Chang-Yong

    2016-10-06

    We report the effects of compressed CO2 molecules as a novel plasticization agent for poly(3- hexylthiophene) (P3HT) conjugated polymer thin films. In-situ neutron reflectivity experiment demonstrated the excess sorption of CO2 molecules in the P3HT thin films (about 40 nm in thickness) at low pressure (P = 8.2 MPa) under the isothermal condition of T = 36 °C, which is far below the polymer bulk melting point. The results evidenced that these CO2 molecules accelerated the crystallization process of the polymer on the basis of ex-situ grazing incidence Xray diffraction measurements after drying the films via rapid depressurization to atmospheric pressure: not only the out-of-plane lamellar ordering of the backbone chains but also intra-plane π-π stacking of the side chains were significantly improved, when compared to those in the control P3HT films subjected to conventional thermal annealing (at T = 170 °C). Electrical measurements elucidated that the CO2-annealed P3HT thin films exhibited enhanced charge carrier mobility along with decreased background charge carrier concentration and trap density compared to those in the thermally annealed counterpart. This is attributed to the CO2-induced increase in polymer chain mobility that can drive the detrapping of molecular oxygen and healing of conformational defects in the polymer thin film. Given the universality of the excess sorption of CO2regardless of the type of polymers, the present findings suggest that the CO2 annealing near the critical point can be useful as a robust processing strategy for improving structural and electrical characteristics of other semiconducting conjugated polymers and related systems such as polymer: fullerene bulk heterojunction films.tion films.

  19. Effect of the size of solvent molecules on the single-chain mechanics of poly(ethylene glycol): implications on a novel design of a molecular motor.

    PubMed

    Luo, Zhonglong; Zhang, Bo; Qian, Hu-Jun; Lu, Zhong-Yuan; Cui, Shuxun

    2016-10-20

    Excluded-volume (EV) interaction, also known as the EV effect, can drive the collapse of polymer chains in a polymer solution and promote the crystallization of polymer chains. Herein we report, for the first time, the effect of EV interaction on the single-chain mechanics of a polymer, poly(ethylene glycol) (PEG). By using AFM-based single-molecule force spectroscopy, the single-chain mechanics of a PEG chain has been detected in various nonpolar organic solvents with different molecule sizes. It is observed that the nonpolar solvents can be classified into two categories. In the small-sized organic solvents (e.g., tetrachloroethane and n-nonane), PEG presents its inherent elasticity, which is consistent with the theoretical single-chain elasticity from quantum mechanical calculations. However, in the middle-sized solvents (e.g., n-dodecane and n-hexadecane), the single-chain entropic elasticity of PEG is influenced by EV interactions noticeably, which indicates that the PEG chain tends to adopt a compact conformation under these conditions. To stretch a PEG chain from a free state to a fully extended state, more energy (1.54 kBT per repeating unit) is needed in small-sized organic solvents than in middle-sized organic solvents. It is expected that a partially stretched PEG chain would shrink to some extent when the solvent is changed from a middle-sized organic solvent to a small-sized one. Accordingly, a novel design of a PEG-based single-molecule motor that works with solvent stimuli is proposed.

  20. 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.

  1. Single-molecule tracking studies of flow-induced microdomain alignment in cylinder-forming polystyrene-poly(ethylene oxide) diblock copolymer films.

    PubMed

    Tran-Ba, Khanh-Hoa; Higgins, Daniel A; Ito, Takashi

    2014-09-25

    Flow-based approaches are promising routes to preparation of aligned block copolymer microdomains within confined spaces. An in-depth characterization of such nanoscale morphologies within macroscopically nonuniform materials under ambient conditions is, however, often challenging. In this study, single-molecule tracking (SMT) methods were employed to probe the flow-induced alignment of cylindrical microdomains (ca. 22 nm in diameter) in polystyrene-poly(ethylene oxide) diblock copolymer (PS-b-PEO) films. Films of micrometer-scale thicknesses were prepared by overlaying a benzene solution droplet on a glass coverslip with a rectangular glass plate, followed by solvent evaporation under a nitrogen atmosphere. The microdomain alignment was quantitatively assessed from SMT data exhibiting the diffusional motions of individual sulforhodamine B fluorescent probes that preferentially partitioned into cylindrical PEO microdomains. Better overall microdomain orientation along the flow direction was observed near the substrate interface in films prepared at a higher flow rate, suggesting that the microdomain alignment was primarily induced by shear flow. The SMT data also revealed the presence of micrometer-scale grains consisting of highly ordered microdomains with coherent orientation. The results of this study provide insights into shear-based preparation of aligned cylindrical microdomains in block copolymer films from solutions within confined spaces.

  2. 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.

  3. Catalytic C-H bond silylation of aromatic heterocycles.

    PubMed

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

    2015-12-01

    This protocol describes a method for the direct silylation of the carbon-hydrogen (C-H) bond of aromatic heterocycles using inexpensive and abundant potassium tert-butoxide (KOt-Bu) as the catalyst. This catalytic cross-dehydrogenative coupling of simple hydrosilanes and various electron-rich aromatic heterocycles enables the synthesis of valuable silylated heteroarenes. The products thus obtained can be used as versatile intermediates, which facilitate the divergent synthesis of pharmaceutically relevant compound libraries from a single Si-containing building block. Moreover, a variety of complex Si-containing motifs, such as those produced by this protocol, are being actively investigated as next-generation therapeutic agents, because they can have improved pharmacokinetic properties compared with the original all-carbon drug molecules. Current competing methods for C-H bond silylation tend to be incompatible with functionalities, such as Lewis-basic heterocycles, that are often found in pharmaceutical substances; this leaves de novo synthesis as the principal strategy for preparation of the target sila-drug analog. Moreover, competing methods tend to be limited in the scope of hydrosilane that can be used, which restricts the breadth of silicon-containing small molecules that can be accessed. The approach outlined in this protocol enables the chemoselective and regioselective late-stage silylation of small heterocycles, including drugs and drug derivatives, with a broad array of hydrosilanes in the absence of precious metal catalysts, stoichiometric reagents, sacrificial hydrogen acceptors or high temperatures. Moreover, H2 is the only by-product generated. The procedure normally requires 48-75 h to be completed.

  4. Nickel-Catalyzed Reactions Directed toward the Formation of Heterocycles.

    PubMed

    Kurahashi, Takuya; Matsubara, Seijiro

    2015-06-16

    Heterocycles have garnered significant attention because they are important functional building blocks in various useful molecules, such as pharmaceuticals, agricultural chemicals, pesticides, and materials. Several studies have been conducted regarding the preparation of heterocyclic skeletons with an emphasis on selectivity and efficiency. Three strategies are typically employed to construct cyclic molecules, namely, cyclization, cycloaddition, and ring-size alterations. Although each method has certain advantages, cycloaddition may be superior from the viewpoint of divergence. Specifically, cycloadditions enable the construction of rings from several pieces. However, the construction of heterocycles via cycloadditions is more challenging than the construction of carbocycles. For heterocycle construction, simple pericyclic reactions rarely work smoothly because of the large HOMO-LUMO gap unless well-designed combinations, such as electron-rich dienes and aldehydes, are utilized. Thus, a different approach should be employed to prepare heterocycles via cycloadditions. To this end, the use of metallacycles containing heteroatoms is expected to serve as a promising solution. In this study, we focused on the preparation of heteroatom-containing nickelacycles. Because nickel possesses a relatively high redox potential and an affinity for heteroatoms, several methods were developed to synthesize heteronickelacycles from various starting materials. The prepared nickelacycles were demonstrated to be reasonable intermediates in cycloaddition reactions, which were used to prepare various heterocycles. In this Account, we introduce the following four methods to prepare heterocycles via heteronickelacycles. (1) Direct oxidative insertion of Ni(0) to α,β-unsaturated enone derivatives: treatment of 3-ethoxycarbonyl-4-phenyl-3-buten-2-one with Ni(0) afforded an oxa-nickelacycle, which reacted with alkynes to give pyrans. (2) Substitution of a part of a cyclic compound with

  5. Heterocycles from α-aminonitriles.

    PubMed

    Otto, Nicola; Opatz, Till

    2014-10-06

    Owing to their various modes of reactivity, α-aminonitriles represent versatile building blocks for the construction of a wide range of nitrogen heterocycles. The present Concept article focuses on synthetic methodologies using their bifunctional nature which is the basis of their reactivity as α-amino carbanions and as iminium ions. Reactions exclusively taking place on either the amine or on the nitrile moiety will not be considered.

  6. N- AND O-HETEROCYCLES PRODUCED FROM THE IRRADIATION OF BENZENE AND NAPHTHALENE IN H{sub 2}O/NH{sub 3}-CONTAINING ICES

    SciTech Connect

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

    2015-02-20

    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 (C{sub 6}H{sub 6}) or naphthalene (C{sub 10}H{sub 8}) mixed in ices containing H{sub 2}O and NH{sub 3}. This represents an alternative way to generate aromatic heterocycles to those considered before and may have important implications for astrochemistry and astrobiology.

  7. Effect of monomer mixture composition on structure and chromatographic properties of poly(divinylbenzene-co-ethylvinylbenzene-co-2-hydroxyethyl methacrylate) monolithic rod columns for separation of small molecules.

    PubMed

    Smirnov, Konstantin N; Dyatchkov, Ivan A; Telnov, Maxim V; Pirogov, Andrey V; Shpigun, Oleg A

    2011-07-29

    Porous poly(divinylbenzene-co-ethylvinylbenzene-co-2-hydroxyethyl methacrylate) monoliths were synthesized via thermally initiated free-radical polymerization in confines of surface-vinylized glass columns (150 mm × 3 mm i.d.) and applied to the reversed-phase separation of low-molecular-weight aromatic compounds. In order to compensate for the polymer shrinkage during the synthesis and prevent the monolith from detachment from the column wall, polymerization was conducted under nitrogen pressure. The reaction proceeded at 60°C for 22 h. 2,2'-Azo-bis-isobutironitrile was used as the initiator and 1-dodecanol was used as the porogen. A series of monoliths with different monomer ratios were obtained. All the monoliths had high specific surface areas ranging from 370 to 490 m(2)/g. In the studied range of monomer mixture compositions, the mechanical stability of the stationary phase in water/acetonitrile eluents was found to be high enough and practically insensitive to the fraction of 2-hydroxyethyl methacrylate (HEMA). Increasing the molar fraction of HEMA from 10.5% to 14.7% resulted in the decrease of column permeability by two orders of magnitude (from 1.1×10(-12) to 1.8×10(-14) m(2)) and led to weaker retention of alkylbenzenes. The higher HEMA content was shown to reduce the plate height of the columns in the separation of small molecules from 160-490 μm to 40-76 μm. This was attributed mainly to the decrease of the domain size of the monoliths leading to lower eddy dispersion and mass transfer resistance in the column.

  8. Bioactive heterocycles containing endocyclic N-hydroxy groups.

    PubMed

    Rani, Reshma; Granchi, Carlotta

    2015-06-05

    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.

  9. 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

  10. APPLICATIONS OF MULTICOMPONENT ASSEMBLY PROCESSES TO THE FACILE SYNTHESES OF DIVERSELY FUNCTIONALIZED NITROGEN HETEROCYCLES.

    PubMed

    Donald, James R; Granger, Brett A; Hardy, Simon; Sahn, James J; Martin, Stephen F

    2012-01-01

    Several multicomponent assembly processes have been developed for the synthesis of intermediates that may be elaborated by a variety of cyclizations to generate a diverse array of highly functionalized heterocycles from readily-available starting materials. The overall approach enables the efficient preparation of libraries of small molecules derived from fused, privileged scaffolds.

  11. 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.

  12. Comparison of Computational Methods Applied to Oxazole, Thiazole, and Other Heterocyclic Compounds

    DTIC Science & Technology

    1993-01-01

    E ~~ ~ ~~~~~ T hia ole a n(t eWee o c c i o p u d Comparison of Computational Methods Applied to Oxazole , Thiazole, and Other Heterocyclic Compounds0...including 6-31G’ and MP2/6-31G* ab initio calculations, were performed for the oxazole and thiazole het- erocycles. The results indicate a scatter among the...methods sensitive to the nature of the heterocycle. This was in particular evident in the oxazole molecule, where AMI gave a singularly high value of

  13. Late-stage functionalization of biologically active heterocycles through photoredox catalysis.

    PubMed

    Dirocco, Daniel A; Dykstra, Kevin; Krska, Shane; Vachal, Petr; Conway, Donald V; Tudge, Matthew

    2014-05-05

    The direct CH functionalization of heterocycles has become an increasingly valuable tool in modern drug discovery. However, the introduction of small alkyl groups, such as methyl, by this method has not been realized in the context of complex molecule synthesis since existing methods rely on the use of strong oxidants and elevated temperatures to generate the requisite radical species. Herein, we report the use of stable organic peroxides activated by visible-light photoredox catalysis to achieve the direct methyl-, ethyl-, and cyclopropylation of a variety of biologically active heterocycles. The simple protocol, mild reaction conditions, and unique tolerability of this method make it an important tool for drug discovery.

  14. Recent advanced in bioactive systems containing pyrazole fused with a five membered heterocycle.

    PubMed

    Raffa, Demetrio; Maggio, Benedetta; Raimondi, Maria Valeria; Cascioferro, Stella; Plescia, Fabiana; Cancemi, Gabriella; Daidone, Giuseppe

    2015-06-05

    In this review we report the recent advances in bioactive system containing pyrazole fused with a five membered heterocycle, covering the time span of the last decade. All of them are represented around the common structure of the pyrazole ring fused with another five membered heterocycle containing the nitrogen, sulfur and oxygen atoms in all their possible combinations. The classification we have used is based in terms of the therapeutic area providing, when possible, some general conclusions on the targets and mechanisms of action as well as the structure-activity relationships of the molecules.

  15. Heterocycle synthesis by copper facilitated addition of heteroatoms to alkenes, alkynes and arenes.

    PubMed

    Chemler, Sherry R; Fuller, Peter H

    2007-07-01

    The de novo synthesis of small organic heterocyclic molecules has benefited from recent protocols for copper-facilitated additions of heteroatoms to alkenes, alkynes and arenes. This tutorial review summarizes a number of these recent contributions. Copper salts can facilitate bond formations due to their ability to serve as Lewis acids, oxidizing agents and transition metal catalysts. The current understanding of the mechanisms of these reactions is presented. This review should be of interest to chemists involved in the synthesis of heterocycles and those investigating transition metal facilitated reactions.

  16. 2-Alkynylbenzaldoxime: a versatile building block for the generation of N-heterocycles.

    PubMed

    He, Linman; Nie, Hongming; Qiu, Guanyinsheng; Gao, Yueqiu; Wu, Jie

    2014-12-07

    2-Alkynylbenzaldoxime as a versatile building block has been applied widely for the construction of N-heterocycles in organic synthesis. Since it could be easily transferred to isoquinoline N-oxide via intramolecular 6-endo cyclization in the presence of metal catalysts or electrophiles, the subsequent [3 + 2] cycloaddition/nucleophilic addition and rearrangement could be expected. On the other hand, a Beckmann rearrangement could occur first since an oxime moiety is present in the molecule, which would then undergo an intramolecular cyclization to furnish nitrogen-containing heterocycles. This review reports the recent advancement in the generation of N-heterocycles starting from 2-alkynylbenzaldoximes via tandem reactions based on different reaction types.

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

    PubMed

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

    2015-06-08

    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.

  18. The Modern Face of Synthetic Heterocyclic Chemistry.

    PubMed

    Cabrele, Chiara; Reiser, Oliver

    2016-11-04

    The synthesis of heterocycles is arguably one of the oldest and at the same time one of the youngest disciplines of organic chemistry. Groundbreaking principles to form heterocycles, mainly by condensation reactions, were recognized in the beginning of the 19th century, and many of the classical reactions discovered at that time are still of great value today. In the 21st century, the wealth of synthetic methodology toward heterocycles is overwhelming, and catalysis, in particular, as one of the cornerstones of green and sustainable chemistry has contributed in a major way to these developments. This perspective tries the impossible by discussing some recent advances in the construction of heterocycles, focusing on catalytic methodology. We are aware that we do not come close to giving adequate credit to the great creativity of chemists in the field.

  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

    2013-07-05

    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.

  20. The tert-amino effect in heterocyclic chemistry. Synthesis of spiro heterocycles.

    PubMed

    D'yachenko, Elisaveta V; Glukhareva, Tatiana V; Dyudya, Lyudmila V; Eltsov, Oleg V; Morzherin, Yury Yu

    2005-09-30

    The tert-amino reaction effect was examined. A new method to synthesize spiro heterocycles is presented. It was shown that the "tert-amino effect" could be applied to the formation of spiro-fused heterocycles. The formation of spiro compounds proceeds in most cases in good yields in a one-pot reaction.

  1. 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.

  2. Aldo-X Bifunctional Building Blocks for the Synthesis of Heterocycles.

    PubMed

    Ravichandiran, Palanisamy; Lai, Bingbing; Gu, Yanlong

    2017-02-01

    Compounds containing oxygen, nitrogen, or sulfur atoms inside the rings are attracting much attention and interest due to their biological importance. In recent years, several methods for the synthesis of such molecules have been reported by using aldo-X bifunctional building blocks (AXB3 s) as substrates; these are a wide class of organic molecules that contain at least two reactive sites, among them, one aldehyde, acetal, or semiacetal group was involved. Because of the multiple reactivities, AXB3 s are widely used in the one-pot synthesis of biologically important heterocycles. This review summarizes the synthesis of important heterocycles by using AXB3 s as pivotal components in establishing multicomponent reactions, tandem reactions, and so forth. In many cases, the established reaction systems with AXB3 s were characterized by some green properties, such as easy access to the substrate, mild and environmentally benign conditions, and wide scope of the substrate.

  3. Recent advances in rhodium-catalyzed asymmetric synthesis of heterocycles.

    PubMed

    Chen, Wen-Wen; Xu, Ming-Hua

    2017-02-01

    Heterocycles are crucial structural motifs that are ubiquitously present in biologically active natural products and pharmaceutically important compounds. Over the past few decades, great attention has been paid to develop efficient methodologies for the construction of diverse enantioenriched heterocyclic frameworks. This review focuses on the recent impressive progress and advances in the asymmetric synthesis of heterocycles under rhodium catalysis.

  4. 40 CFR 721.5925 - Bis heterocyclic phenylene derivative (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Bis heterocyclic phenylene derivative... Specific Chemical Substances § 721.5925 Bis heterocyclic phenylene derivative (generic). (a) Chemical... as bis heterocyclic phenylene derivative (PMN P-01-0432) is subject to reporting under this...

  5. 40 CFR 721.5925 - Bis heterocyclic phenylene derivative (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Bis heterocyclic phenylene derivative... Specific Chemical Substances § 721.5925 Bis heterocyclic phenylene derivative (generic). (a) Chemical... as bis heterocyclic phenylene derivative (PMN P-01-0432) is subject to reporting under this...

  6. 40 CFR 721.5925 - Bis heterocyclic phenylene derivative (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Bis heterocyclic phenylene derivative... Specific Chemical Substances § 721.5925 Bis heterocyclic phenylene derivative (generic). (a) Chemical... as bis heterocyclic phenylene derivative (PMN P-01-0432) is subject to reporting under this...

  7. 40 CFR 721.5925 - Bis heterocyclic phenylene derivative (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Bis heterocyclic phenylene derivative... Specific Chemical Substances § 721.5925 Bis heterocyclic phenylene derivative (generic). (a) Chemical... as bis heterocyclic phenylene derivative (PMN P-01-0432) is subject to reporting under this...

  8. 40 CFR 721.5925 - Bis heterocyclic phenylene derivative (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Bis heterocyclic phenylene derivative... Specific Chemical Substances § 721.5925 Bis heterocyclic phenylene derivative (generic). (a) Chemical... as bis heterocyclic phenylene derivative (PMN P-01-0432) is subject to reporting under this...

  9. Combinatorial Libraries of Bis-Heterocyclic Compounds with Skeletal Diversity

    PubMed Central

    Soural, Miroslav; Bouillon, Isabelle; Krchňák, Viktor

    2009-01-01

    Combinatorial solid-phase synthesis of bis-heterocyclic compounds, characterized by the presence of two heterocyclic cores connected by a spacer of variable length/structure, provided structurally heterogeneous libraries with skeletal diversity. Both heterocyclic rings were assembled on resin in a combinatorial fashion. PMID:18811208

  10. Heterocyclic 1,7-disubstituted indole sulfonamides are potent and selective human EP3 receptor antagonists.

    PubMed

    Hategan, Georgeta; Polozov, Alexandre M; Zeller, Wayne; Cao, Hua; Mishra, Rama K; Kiselyov, Alex S; Ramirez, Jose; Halldorsdottir, Gudrún; Andrésson, Thornorkell; Gurney, Mark E; Singh, Jasbir

    2009-12-01

    We have developed a pharmacophore model for the EP(3) receptor antagonists based on its endogenous ligand PGE(2). This ligand-based design yielded a series of novel peri-substituted [4.3.0] bicyclic aromatics featuring 1-alklyaryl 7-heterocyclic sulfonamide substituents. The synthesized molecules are potent antagonists of human EP(3) receptor in vitro and show inhibition of rat platelets aggregation. Optimized derivatives display high selectivity over IP, FP, and other EP receptor panels.

  11. 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.

  12. 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.

  13. Covalent Polymers Containing Discrete Heterocyclic Anion Receptors

    NASA Astrophysics Data System (ADS)

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

    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 noncovalent interactions (e.g., hydrogen bonding and electrostatic interactions) provides a route to not only sensitive but also selective polymeric materials. Furthermore, these systems have been utilized in the development of polymers capable of extracting anionic species from aqueous media. These latter materials may lead to advances in water purification and treatment of diseases resulting from surplus ions.

  14. Syntheses of Novel Nitrogen and Phosphorus Heterocycles.

    DTIC Science & Technology

    2014-09-26

    Chemicals and Materials Research Department, Ultrasystems, Inc. under Contract F49620-82-C-0021, "Syntheses of Novel Nitrogen and Phosphorus Hetero- * cycles ...ADl-NISS9 449 SYNTHESES OF NOVEL NITROGEN AND PHOSPHORUS HETEROCYCLES In (U) ULTRRSYSTENS INC IRVINE CR K L PRCIOREK ET RL. 26 RPR 85 SN-209?-F RFOSR...MICROCOPY RESOLUTION TEST CHART NATIONAL BURE&U OF STAOACS-963-A SR-I"I" s, -Ŕ 500 4 SYNTHESES OF NOVEL NITROGEN AND PHOSPHORUS HETEROCYCLES Contract No

  15. 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

    2016-06-06

    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.

  16. Advancements in the Synthesis and Applications of Cationic N-Heterocycles through Transition Metal-Catalyzed C-H Activation.

    PubMed

    Gandeepan, Parthasarathy; Cheng, Chien-Hong

    2016-02-18

    Cationic N-heterocycles are an important class of organic compounds largely present in natural and bioactive molecules. They are widely used as fluorescent dyes for biological studies, as well as in spectroscopic and microscopic methods. These compounds are key intermediates in many natural and pharmaceutical syntheses. They are also a potential candidate for organic light-emitting diodes (OLEDs). Because of these useful applications, the development of new methods for the synthesis of cationic N-heterocycles has received a lot of attention. In particular, many C-H activation methodologies that realize high step- and atom-economies toward these compounds have been developed. In this review, recent advancements in the synthesis and applications of cationic N-heterocycles through C-H activation reactions are summarized. The new C-H activation reactions described in this review are preferred over their classical analogs.

  17. 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

    2014-08-07

    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

  18. N,S,O-Heterocycles in Aged Champagne Reserve Wines and Correlation with Free Amino Acid Concentrations.

    PubMed

    Le Menn, Nicolas; Marchand, Stephanie; de Revel, Gilles; Demarville, Dominique; Laborde, Delphine; Marchal, Richard

    2017-03-14

    Champagne regulations allow winegrowers to stock still wines to compensate for quality shifts in vintages, mainly due to climate variations. According to their technical requirements and house style, Champagne producers use these stored wines in their blends to enhance complexity. The presence of lees and aging at low pH (2.95-3.15), as in Champagne wines, lead to several modifications in wine composition. These conditions, combined with extended aging, result in the required environment for the Maillard chemical reaction, involving aromatic molecules, including sulfur, oxygen, and nitrogen heterocycles (such as thiazole, furan, and pyrazine derivatives), which may have a sensory impact on wine. Some aromatic heterocycles in 50 monovarietal wines aged from 1 to 27 years provided by Veuve Clicquot Ponsardin Champagne house were determined by the SPME-GC-MS method. The most interesting result highlighted a strong correlation between certain heterocycle concentrations and wine age. The second revealed a correlation between heterocyclic compound and free amino acid concentrations measured in the wines, suggesting that these compounds are potential aromatic precursors when wine is aged on lees and, thus, potential key compounds in the bouquet of aged Champagnes. The principal outcome of these assays was to reveal, for the first time, that aromatic heterocycle concentrations in Champagne base wines are correlated with wine age.

  19. International Society of Heterocyclic Chemistry--17th international congress. 1-6 August 1999, Vienna, Austria.

    PubMed

    Daneshtalab, M

    1999-10-01

    Approximately 1200 scientists attended this congress of heterocyclic chemistry, which focused on: New synthetic methods in heterocyclic chemistry; synthesis of bioactive heterocycles including natural products; heterocycles and asymmetric synthesis; heterocycles in bioorganic chemistry; new heterocyclic materials; structure and properties of heterocyclic compounds; solid-phase synthesis, combinatorial chemistry and heterocyclic scaffolds. These topics were covered in 600 posters and 100 plenary, invited and oral presentations. This report summarizes the highlights of the presentations related to the category of the synthesis of bioactive heterocycles including natural products.

  20. Discovery of novel heterocyclic factor VIIa inhibitors.

    PubMed

    Rai, Roopa; Kolesnikov, Aleksandr; Sprengeler, Paul A; Torkelson, Steven; Ton, Tony; Katz, Bradley A; Yu, Christine; Hendrix, John; Shrader, William D; Stephens, Robin; Cabuslay, Ronnell; Sanford, Ellen; Young, Wendy B

    2006-04-15

    Structure-activity relationships and binding mode of novel heterocyclic factor VIIa inhibitors will be described. In these inhibitors, a highly basic 5-amidinoindole moiety has been successfully replaced with a less basic 5-aminopyrrolo[3,2-b]pyridine scaffold.

  1. The Structure of Poly-2,5-Benzoxazole (ABPBO) and Poly-2,6-Benzothiazole (ABPBT) Fibers By X-Ray Diffraction

    DTIC Science & Technology

    1985-07-01

    AFWAL-TR-85-4097 ADA \\bC \\ Uq THE STRUCTURE OF POLY-2,5-BENZOXAZOLE (ABPBO) AND POLY-2,6-BENZOTHIAZOLE (ABPBT) FIBERS BY X-RAY DIFFRACTION Albert V...Classification) THE STRUCTURE OF POLY-2,5-BENZOXAZOLE (ABPBO) AND POLY-2,6-BENZOTHIAZOLE (ABPBT) FIBERS BY X-RAY DIFFRACTION 12. PERSONAL AUTHOR(S) W. Wade Adams...and identify by block number) FIELD GROUP SUB-GROUP Polybenzoxazole Unit Cell ABPBO Aromatic Heterocyclic 07 04 Polymer 11 04 19. ABSTRACT (Continue

  2. Chirality Synchronization of Hydrogen-Bonded Complexes of Achiral N-Heterocycles.

    PubMed

    Buchs, Jens; Vogel, Laura; Janietz, Dietmar; Prehm, Marko; Tschierske, Carsten

    2017-01-02

    2,4-Diamino-6-phenyl-1,3,5-triazines carrying a single oligo(ethylene oxide) (EO) chain form an optically isotropic mesophase composed of a conglomerate of macroscopic chiral domains with opposite sense of chirality even though the constituent molecules are achiral. This mesophase was proposed to result from the helical packing of hydrogen-bonded triazine aggregates, providing long-range chirality synchronization. The results provide first evidence for macroscopic achiral symmetry breaking upon conglomerate formation in an amorphous isotropic phase formed by hydrogen-bonded associates of simple N-heterocycles that are related to prebiotic molecules.

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

    PubMed

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

    2016-02-02

    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.

  4. 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

    2015-11-04

    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.

  5. 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

  6. Enhanced Release of Molecules upon Ultraviolet (UV) Light Irradiation from Photoresponsive Hydrogels Prepared from Bifunctional Azobenzene and Four-Arm Poly(ethylene glycol).

    PubMed

    Rastogi, Shiva K; Anderson, Hailee E; Lamas, Joseph; Barret, Scott; Cantu, Travis; Zauscher, Stefan; Brittain, William J; Betancourt, Tania

    2017-03-07

    Advances in biosensors and drug delivery are dependent on hydrogels that respond to external stimuli. In this work, we describe the preparation and characterization of photoresponsive hydrogels prepared by cross-linking of di-NHS ester of azobenzoic acid and four-armed, amine-terminated poly(ethylene glycol). The porous structure and composition of the hydrogels were confirmed by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. The reversible photoisomerization of the azobenzene-containing hydrogel cross-linkers in the gels was confirmed by absorption spectroscopy. Specifically, the photoisomerization of the cross-linkers between their trans and cis configurations was observed by monitoring the absorbance of the hydrogels at the two characteristic peaks of azobenzene (π-π* at 330 nm and n-π* at 435 nm). The effect of photoisomerization on the hydrogel structure was investigated by microscopy. Ultraviolet (UV) irradiation-induced reduction in hydrogel size was observed, which may be a result of the inherently smaller footprint of the cis azobenzene conformation, as well as dipole-dipole interactions between the polar cis azobenzene and the polymer network. The UV-triggered reduction in hydrogel size was accompanied by enhanced release of the near-infrared fluorescent dye Alexa Fluor 750 (AF750). Enhanced release of AF750 was observed in samples irradiated with UV versus dark control. Together, these data demonstrate the potential of these systems as reversible photoresponsive biomaterials.

  7. 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).

  8. 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

  9. Fluorous Mixture Synthesis of Two Libraries with Novel Hydantoin- and Benzodiazepinedione-Fused Heterocyclic Scaffolds

    PubMed Central

    Zhang, Wei; Lu, Yimin; Chen, Christine Hiu-Tung; Zeng, Lu; Kassel, Daniel B.

    2007-01-01

    Diversity-oriented synthesis (DOS) and fluorous mixture synthesis (FMS) are two aspects of combinatorial chemistry. DOS generates library scaffolds with skeletal, substitution, and stereochemistry variations, whereas FMS is a highly efficient tool for library production. The combination of these two aspects in solution-phase synthesis of two novel heterocyclic compound libraries is presented in this paper. Mixtures of different fluorous amino acids undergo [3+2] cycloadditions followed by post-condensation reactions. The mixtures are then demixed by fluorous HPLC. Fluorous tags are removed by cyclization to afford hydantoin- and benzodiazepinedione-fused heterocyclic compounds as individual, pure and structurally defined molecules. The application of MS-directed HPLC and parallel four-channel LC/MS analysis further increases the efficiency of FMS. PMID:16961407

  10. Ruthenium Catalysis in the Synthesis of Six-Membered Heterocycles

    NASA Astrophysics Data System (ADS)

    Zhang, Min

    Owing to the cost-effectiveness and versatility of ruthenium in catalysis, the utilization of ruthenium for developing atom and step-economic methodologies, allowing for the synthesis of six-membered heterocycles, is of particular importance in synthetic chemistry because of the important value of such compounds employed in discovering biologically and pharmacologically active compositions, the preparation of novel materials with specific functions, etc. This chapter highlights the recent 15 years' advances on ruthenium-catalyzed synthesis of six-membered heterocycles, with particular focus on the related approaches and mechanistic basis, which includes the synthesis of N-heterocycles, O-heterocycles, N,O-heterocycles, and other type of heteroatom-heterocycles.

  11. Cytotoxic Action of Carboxyborane Heterocyclic Amine Adducts

    PubMed Central

    Miller, Merrill C.; Sood, Anup; Spielvogel, Bernard F.; Bastow, Ken

    1997-01-01

    The heterocyclic carboxyborane amines were found to be potent cytotoxic agents in the murine L1210 lymphoid leukemia and human HeLa suspended carcinoma cells. These agents were observed to inhibit HeLa DNA topoisomerase II activity ~ 200 μM and L1210 topoisomerase II activity ≥ 100 μM. These agents did not cause DNA protein linked breaks themselves, but upon incubation for 14-24 hr did enhance the ability of VP-16 to cause cleavable complexes. The heterocyclic amineboranes inhibited DNA synthesis and caused DNA strand scission. They were additive with VP-16 in affording these results as well as inhibiting colony growth of L1210 cells after co-incubation for 1 hr. The agents inhibited in vitro PKC phosphorylation of both L1210 lymphoid leukemia and human topoisomerase II enzyme. PMID:18475792

  12. Isolatable organophosphorus(III)-tellurium heterocycles.

    PubMed

    Nordheider, Andreas; Chivers, Tristram; Schön, Oliver; Karaghiosoff, Konstantin; Athukorala Arachchige, Kasun S; Slawin, Alexandra M Z; Woollins, J Derek

    2014-01-13

    A new structural arrangement Te3 (RP(III) )3 and the first crystal structures of organophosphorus(III)-tellurium heterocycles are presented. The heterocycles can be stabilized and structurally characterized by the appropriate choice of substituents in Tem (P(III) R)n (m=1: n=2, R=OMes* (Mes*=supermesityl or 2,4,6-tri-tert-butylphenyl); n=3, R=adamantyl (Ad); n=4, R=ferrocene (Fc); m=n=3: R=trityl (Trt), Mesor by the installation of a P(V) 2 N2 anchor in RP(III) [TeP(V) (tBuN)(μ-NtBu)]2 (R=Ad, tBu).

  13. 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

  14. Upgrading carbon dioxide by incorporation into heterocycles.

    PubMed

    Yu, Bing; He, Liang-Nian

    2015-01-01

    Carbon dioxide is commonly regarded as the primary greenhouse gas, but from a synthetic standpoint can be utilized as an alternative and sustainable C1 synthon in organic synthesis rather than a waste. This results in the production of organic carbonates, carboxylic acids, and derivatives. Recently, CO2 has emerged as an appealing tool for heterocycle synthesis under mild conditions without using stoichiometric amounts of organometallic reducing reagents. This Minireview summarizes recent advances on methodologies for CO2 incorporation into N-, O-, and C-nucleophiles to provide various heterocycles, including cyclic carbamates, benzoxazine-2-one, 4-hydroxyquinolin-2-one, quinazoline-2,4(1 H,3 H)-diones, benzimidazolones, α-alkylidene cyclic carbonate.

  15. Heterocyclic Amaryllidaceae Alkaloids: Biosynthesis and Pharmacological Applications.

    PubMed

    Hotchandani, Tarun; Desgagne-Penix, Isabel

    2017-01-01

    Amaryllidaceae alkaloids (AAs), which are natural heterocyclic compounds, are isolated from Amaryllidaceae plants such as narcissus, snowdrop and spider lily. AAs have been extensively studied due to their multiple pharmacological properties. Nevertheless, knowledge of AA synthesis in plants is lacking and most genes encoding enzymes involved in their production remain unknown. AAs are structurally complex compounds which are challenging for total chemical synthesis that is economically viable. Therefore the understanding of AA biosynthesis could allow for the development of biotechnologies for the production of natural AAs or analogues, maintaining or improving their pharmacological properties. In this review, we describe the progress regarding the biosynthesis and pharmacological properties of AAs. The most recent developments in neurological, anti-cancer and anti-microbial bioactivities of heterocyclic AAs are covered.

  16. Sodium phosphaethynolate as a building block for heterocycles.

    PubMed

    Chen, Xiaodan; Alidori, Simone; Puschmann, Florian Frank; Santiso-Quinones, Gustavo; Benkő, Zoltán; Li, Zhongshu; Becker, Gerd; Grützmacher, Hans-Friedrich; Grützmacher, Hansjörg

    2014-02-03

    Phosphorus-containing heterocycles have evolved from laboratory curiosities to functional components, such as ligands in catalytically active metal complexes or molecular constituents in electronic devices. The straightforward synthesis of functionalized heterocycles on a larger scale remains a challenge. Herein, we report the use of the phosphaethynolate (OCP)(-) anion as a building block for various sterically unprotected and functionalized hydroxy substituted phosphorus heterocycles. Because the resulting heterocycles are themselves anions, they are building blocks in their own right and allow further facile functionalization. This property may be of interest in coordination chemistry and material science.

  17. 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.

  18. Synthesis of Pharmacological Heterocyclic Derivatives Based Surfactants.

    PubMed

    El-Sayed, Refat; Fadda, Ahmed A

    2016-01-01

    Synthesis of chromenopyrimidine derivatives and the related fused system carried out by the reaction of chromene derivative 1 with various reagents under suitable reaction conditions. Condensation of stearoyl chloride with these heterocycles, then, propoxylated the products using propylene oxide to produce surface active agents having a twofold capacity as surface and antimicrobial dynamic specialists which may be served in the production of medications, pesticides, beautifying agents or may be utilized as an antimicrobial. Some of the surface properties and antimicrobial activity were resolved.

  19. Exploration of Visible-Light Photocatalysis in Heterocycle Synthesis and Functionalization: Reaction Design and Beyond.

    PubMed

    Chen, Jia-Rong; Hu, Xiao-Qiang; Lu, Liang-Qiu; Xiao, Wen-Jing

    2016-09-20

    pyridazine derivatives in good yields and selectivity. Moreover, we have demonstrated that this photocatalysis can serve as a mild and highly selective tool for direct functionalization of heterocycles because of its powerful capability to controllably generate diverse reactive intermediates under mild reaction conditions. Guided by the fundamental principles of photocatalysis and the redox properties of the photocatalysts, we successfully developed an array of dual-catalyst systems by combining the photocatalysts with palladium, nickel, or amine, enabling efficient and selective coupling reactions. An intriguing phototandem catalytic system using a single photocatalyst was also identified for the development of cascade reactions. Notably, some of the newly developed methodologies have also been successfully utilized for late-stage modification of biologically active natural compounds and complex molecules and as key steps for formal synthesis of natural products. This Account presents a panoramic view and the logic of our recent contributions to the design, development, and application of photocatalytic systems and reactions that provide not only methods for the efficient synthesis of heterocycles but also useful insights into the exploration of new photochemical reactions.

  20. Theoretical study of ionization and one-electron oxidation potentials of N-heterocyclic compounds.

    PubMed

    Sviatenko, Liudmyla K; Gorb, Leonid; Hill, Frances C; Leszczynski, Jerzy

    2013-05-15

    A number of density functionals was utilized to predict gas-phase adiabatic ionization potentials (IPs) for nitrogen-rich heterocyclic compounds. Various solvation models were applied to the calculation of difference in free energies of solvation of oxidized and reduced forms of heterocyclic compounds in acetonitrile (AN) for correct reproduction of their standard oxidation potentials. We developed generally applicable protocols that could successfully predict the gas-phase adiabatic ionization potentials of nitrogen-rich heterocyclic compounds and their standard oxidation potentials in AN. This approach is supported by a MPW1K/6-31+G(d) level of theory which uses SMD(UA0) approximation for estimation of solvation energy of neutral molecules and PCM(UA0) model for ionized ones. The mean absolute derivation (MAD) and root mean square error (RMSE) of the current theoretical models for IP are equal to 0.22 V and 0.26, respectively, and for oxidation potentials MAD = 0.13 V and RMSE = 0.17.

  1. Caffeine and other xanthines as cytochemical blockers and removers of heterocyclic DNA intercalators from chromatin.

    PubMed

    Lyles, Mark B; Cameron, Ivan L

    2002-01-01

    Caffeine (CAF) and other xanthines non-covalently bind with the cationic fluorescent dye acridine orange (AO) and with other heterocyclic mutagens and carcinogens that are known to intercalate into double-stranded DNA (dsDNA). Fluorescence microscopy and spectrofluorometry studies were employed to test the ability of caffeine and certain other methyl substituted xanthines, with different binding affinities for AO, to inhibit and to reverse the intercalation of AO and other heterocyclic agents from intercalation with the DNA of nuclear chromatin of air-dried cells. Results indicated that xanthines with binding affinity for AO greater than 150 m(-1) block the AO molecule in a concentration dependent manner and comply with mass action kinetics. Thus CAF and other xanthines can be used to either inhibit intercalation of AO into nuclear DNA or to remove AO once intercalated into nuclear DNA. The interactions between other planar heterocyclics, xanthines, and nuclear chromatin dsDNA were also found to be non-covalent. Studies are needed to determine the ability of CAF and other xanthines to block and/or remove polyaromatic hydrocarbon (PAH) intercalators from the DNA of living cells.

  2. Formation of Haloacetonitriles, Haloacetamides, and Nitrogenous Heterocyclic Byproducts by Chloramination of Phenolic Compounds.

    PubMed

    Nihemaiti, Maolida; Le Roux, Julien; Hoppe-Jones, Christiane; Reckhow, David A; Croué, Jean-Philippe

    2017-01-03

    The potential formation of nitrogenous disinfection byproducts (N-DBPs) was investigated from the chloramination of nitrogenous and non-nitrogenous aromatic compounds. All molecules led to the formation of known N-DBPs (e.g., dichloroacetonitrile, dichloroacetamide) with various production yields. Resorcinol, a major precursor of chloroform, also formed di/trichloroacetonitrile, di/trichloroacetamide, and haloacetic acids, indicating that it is a precursor of both N-DBPs and carbonaceous DBPs (C-DBPs) upon chloramination. More detailed experiments were conducted on resorcinol to understand N-DBPs formation mechanisms and to identify reaction intermediates. Based on the accurate mass from high resolution Quadrupole Time-of-Flight GC-MS (GC-QTOF) and fragmentation patterns from electronic impact and positive chemical ionization modes, several products were tentatively identified as nitrogenous heterocyclic compounds (e.g., 3-chloro-5-hydroxy-1H-pyrrole-2-one with dichloromethyl group, 3-chloro-2,5-pyrroledione). These products were structurally similar to the heterocyclic compounds formed during chlorination, such as the highly mutagenic MX (3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone) or halogenated pyrroles. To our knowledge, this is the first time that the formation of halogenated nitrogenous heterocyclic compounds is reported from chloramination process. The formation of these nitrogenous byproducts during chloramination might be of concern considering their potential toxicity.

  3. 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.

  4. Sulphur-Containing Heterocycles as Antimycobacterial Agents: Recent Advances in Thiophene and Thiadiazole Derivatives.

    PubMed

    Krátký, Martin; Vinsova, Jarmila

    2016-01-01

    The global tuberculosis epidemic and emergence of drug resistance call for intensive research on new antimycobacterial agents. Recent development is focused mainly on heterocyclic molecules. In many cases, introduction of sulphur has improved antimicrobial activity; many drugs feature a sulphur heterocycle. Thiophene derivatives and thiadiazoles including derived ortho-condensed heterocycles have been found to have a wide range of biological activities. This review highlights the recent progress in the field with a focus on whole-cell antimycobacterial activity of the agents as well as targeting of enzymes from Mycobacterium tuberculosis. Some of the compounds have exhibited high activity with submicromolar minimum inhibitory concentrations including activity against drug-resistant strains and/or IC50 values for a range of enzymes as their targets (InhA, dehydroquinase, Pks13, carbonic anhydrases, DprE1). Mechanisms of action, toxicity, and structure-activity relationships are also discussed. Several compounds have exhibited promising in vitro and in vivo activities and safety profiles, thus constituting novel, promising leads.

  5. 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.

  6. Pentannulation of Heterocycles by Virtue of Precious Metal Catalysis.

    PubMed

    Petrović, Martina; Occhiato, Ernesto G

    2016-03-04

    Pentannulated heterocycles are the key structural subunit of many natural and biologically active compounds. Over the last decades, many precious metal-assisted pentannulations have been described as a consequence of an extensive research. This Focus Review gives an overview of precious metal-catalyzed reactions applied to the synthesis of cyclopenta-fused heterocycles in the last five years.

  7. 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)...

  8. Iron-Catalyzed Synthesis of Sulfur-Containing Heterocycles.

    PubMed

    Bosset, Cyril; Lefebvre, Gauthier; Angibaud, Patrick; Stansfield, Ian; Meerpoel, Lieven; Berthelot, Didier; Guérinot, Amandine; Cossy, Janine

    2016-10-13

    An iron-catalyzed synthesis of sulfur- and sulfone-containing heterocycles is reported. The method is based on the cyclization of readily available substrates and proceeded with high efficiency and diastereoselectivity. A variety of sulfur-containing heterocycles bearing moieties suitable for subsequent functionalization are prepared. Illustrative examples of such postcyclization modifications are also presented.

  9. Alkynylation of heterocyclic compounds using hypervalent iodine reagent.

    PubMed

    Kamlar, M; Císařová, I; Veselý, J

    2015-03-14

    The alkynylation of various nitrogen- and/or sulphur-containing heterocyclic compounds using hypervalent iodine TMS-EBX by utilization of tertiary amines under mild conditions is described. The developed metal-free methodology furnishes the corresponding alkynylated heterocycles bearing quaternary carbon in high yields.

  10. Thermochemistry and Dynamics of Reactive Species: Nitrogen-rich Substituted Heterocycles, and Anionic Components of Ionic Liquids

    DTIC Science & Technology

    2012-02-23

    Am. Chem. Soc. 130, 7214-15 (2008). 2. N. Eyet, S. M. Villano, and V. M. Bierbaum, "Anchoring the gas-phase acidity scale: From formic acid to...molecule flow reactor was employed to obtain gas phase acidities , and negative ion photoelectron spectroscopy provided electron affinities and... acidities . The focus of these studies was nitrogen-rich five- and six-member heterocycles, azoles and azines. One special focus in this project was the

  11. Synthesis of anionic phosphorus-containing heterocycles by intramolecular cyclizations involving N-functionalized phosphinecarboxamides.

    PubMed

    Robinson, Thomas P; Goicoechea, Jose M

    2015-04-07

    We report that the 2-phosphaethynolate anion (PCO(-)) reacts with propargylamines in the presence of a proton source to afford novel N-derivatized phosphinecarboxamides bearing alkyne functionalities. Deprotonation of these species gives rise to novel five- and six-membered anionic heterocycles resulting from intramolecular nucleophilic attack of the resulting phosphide at the alkyne functionality (via 5-exo-dig or 6-endo-dig cyclizations, respectively). The nature of the substituents on the phosphinecarboxamide can be used to influence the outcome of these reactions. This strategy represents a unique approach to phosphorus-containing heterocylic systems that are closely related to known organic molecules with interesting bio-active properties.

  12. 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

  13. 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.

  14. Unusual intermolecular "through-space" j couplings in p-se heterocycles.

    PubMed

    Sanz Camacho, Paula; Athukorala Arachchige, Kasun S; Slawin, Alexandra M Z; Green, Timothy F G; Yates, Jonathan R; Dawson, Daniel M; Woollins, J Derek; Ashbrook, Sharon E

    2015-05-20

    Solid-state NMR spectra of new P-Se heterocycles based on peri-substituted naphthalene motifs show the presence of unusual J couplings between Se and P. These couplings are between atoms in adjacent molecules and occur "through space", rather than through conventional covalent bonds. Experimental measurements are supported by relativistic DFT calculations, which confirm the presence of couplings between nonbonded atoms, and provide information on the pathway of the interaction. This observation improves the understanding of J couplings and offers insight into the factors that affect crystal packing in solids, for future synthetic exploitation.

  15. 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.

  16. The influence of the eluent composition on the retention of derivatives of some aromatic heterocyclic compounds in reversed-phase high-performance liquid chromatography

    NASA Astrophysics Data System (ADS)

    Kurbatova, S. V.; Saifutdinov, B. R.

    2009-07-01

    The influence of the composition of water-acetonitrile eluents on the retention of derivatives of aromatic heterocyclic compounds in reversed-phase high-performance liquid chromatography was studied. The coefficients of the displacement of acetonitrile molecules from the adsorption layer and equilibrium constants of quasi-chemical reactions of sorption and solvation of sorbate molecules were determined. For the investigated chromatographic systems, the applicability scope of the basic adsorption retention models are discussed.

  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. Unconventional interactions between water and heterocyclic nitrogens in protein structures.

    PubMed

    Stollar, Elliott J; Gelpí, Jose Luis; Velankar, Sameer; Golovin, Adel; Orozco, Modesto; Luisi, Ben F

    2004-10-01

    We report an unusual interaction in which a water molecule approaches the heterocyclic nitrogen of tryptophan and histidine along an axis that is roughly perpendicular to the aromatic plane of the side chain. The interaction is distinct from the well-known conventional aromatic hydrogen-bond, and it occurs at roughly the same frequency in protein structures. Calculations indicate that the water-indole interaction is favorable energetically, and we find several cases in which such contacts are conserved among structural orthologs. The indole-water interaction links side chains and peptide backbone in turn regions, connects the side chains in beta-sheets, and bridges secondary elements from different domains. We suggest that the water-indole interaction can be indirectly responsible for the quenching of tryptophan fluorescence that is observed in the folding of homeodomains and, possibly, many other proteins. We also observe a similar interaction between water and the imidazole nitrogens of the histidine side chain. Taken together, these observations suggest that the unconventional water-indole and water-imidazole interactions provide a small but favorable contribution to protein structures.

  19. Electron spin relaxation of a boron-containing heterocyclic radical

    NASA Astrophysics Data System (ADS)

    Eaton, Sandra S.; Huber, Kirby; Elajaili, Hanan; McPeak, Joseph; Eaton, Gareth R.; Longobardi, Lauren E.; Stephan, Douglas W.

    2017-03-01

    Preparation of the stable boron-containing heterocyclic phenanthrenedione radical, (C6F5)2B(O2C14H8), by frustrated Lewis pair chemistry has been reported recently. Electron paramagnetic resonance measurements of this radical were made at X-band in toluene:dichloromethane (9:1) from 10 to 293 K, in toluene from 180 to 293 K and at Q-band at 80 K. In well-deoxygenated 0.1 mM toluene solution at room temperature hyperfine splittings from 11B, four pairs of 1H, and 5 pairs of 19F contribute to an EPR spectrum with many resolved lines. Observed hyperfine couplings were assigned based on DFT calculations and account for all of the fluorines and protons in the molecule. Rigid lattice g values are gx = 2.0053, gy = 2.0044, and gz = 2.0028. Near the melting point of the solvent 1/Tm is enhanced due to motional averaging of g and A anisotropy. Increasing motion above the melting point enhances 1/T1 due to contributions from tumbling-dependent processes. The overall temperature dependence of 1/T1 from 10 to 293 K was modeled with the sum of contributions of a process that is linear in T, a Raman process, spin rotation, and modulation of g anisotropy by molecular tumbling. The EPR measurements are consistent with the description of this compound as a substituted aromatic radical, with relatively small spin density on the boron.

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

    PubMed

    Hemmerling, Franziska; Hahn, Frank

    2016-01-01

    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.

  1. 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

  2. Complexation of heterocyclic ligands with DNA in aqueous solution

    NASA Astrophysics Data System (ADS)

    Baranovskii, S. F.; Bolotin, P. A.; Evstigneev, M. P.; Chernyshev, D. N.

    2008-03-01

    We have used spectrophotometry to study self-association and complexation with DNA by organic heterocyclic compounds in the acridine and phenothiazine series: proflavin, thionine, and methylene blue. Based on the experimental concentration dependences of the molar absorption coefficient of the molecules in an aqueous buffer solution (0.01 M NaCl, 0.01 M Na2EDTA, 0.01 M Tris, pH 7.4, T = 298 K), we have determined the equilibrium dimerization constants for the dyes and the DNA complexation parameters using the Scatchard and McGhee-von Hippel models. The observed increase in the cooperativity parameters as the dimerization constants of the ligands increase allowed us to hypothesize that the same interactions occur between dye molecules adsorbed on DNA as in their self-association. The equilibrium DNA-binding constants for the ligands, obtained using the McGhee-von Hippel cooperative model, are (20.9 ± 2.7)·103 M-1 for proflavin and (33.8 ± 4.1)·103 M-1 for thionine. Using the Scatchard model, taking into account intercalation and “external” binding of ligands with DNA, we determined the DNA complexation constants for methylene blue: (26.4 ± 4.6)·103 and (96 ± 17)·103 M-1 respectively. Based on analysis of the data obtained, we hypothesized that the predominant type of binding with DNA is intercalation binding in the case of proflavin and thionine, and “external” binding with the DNA surface in the case of methylene blue.

  3. Formation of a new copper(II) dimer through heterocyclic ligand ring opening reaction: Supramolecular features and magnetic properties

    NASA Astrophysics Data System (ADS)

    Gonçalves, Bruna Lisboa; Gervini, Vanessa Carratu; Flores, Alex Fabiani Claro; Junior, Jorge Luiz Pimentel; Bortoluzzi, Adailton João; Burrow, Robert Alan; Duarte, Rafael; da Silva, Robson Ricardo; Vicenti, Juliano Rosa de Menezes

    2017-01-01

    Two new compounds were synthesized and characterized in this work: the heterocycle (Z)-1-(4-(hydroxyimino)-3,5-dimethyl-1-(methylcarbamothioyl)-4,5-dihydro-1H-pyrazol-5-yl)-4-methylthiosemicarbazide and a copper(II) thiosemicarbazonato dimeric complex. Green prismatic single crystals of the dimer were obtained by the reaction of the heterocycle with copper(II) chloride dihydrate. Both compounds were essentially characterized by spectroscopic methods and X-ray diffraction crystallography. The crystal structures revealed molecules connected through supramolecular hydrogen bond interactions and copper(II) centers in a slightly distorted square-pyramidal environment. SQUID magnetometry performed for the dimer revealed both ferromagnetic and antiferromagnetic interactions in the studied complex, presenting a critical temperature of 19 K.

  4. Heterocycles in Peptidomimetics and Pseudopeptides: Design and Synthesis †

    PubMed Central

    Cerminara, Iole; Chiummiento, Lucia; Funicello, Maria; Guarnaccio, Ambra; Lupattelli, Paolo

    2012-01-01

    This minireview provides a brief outline of the peculiar aspects of the preparation of peptidomimetic and pseudopeptidic structures containing heterocycles. In particular novel tricyclic structures are investigated as potential drugs. PMID:24281380

  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. 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

  7. 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

  8. A novel method for heterocyclic amide-thioamide transformations.

    PubMed

    Fathalla, Walid; Ali, Ibrahim A I; Pazdera, Pavel

    2017-01-01

    In this paper, we introduce a novel and convenient method for the transformation of heterocyclic amides into heteocyclic thioamides. A two-step approach was applied for this transformation: Firstly, we applied a chlorination of the heterocyclic amides to afford the corresponding chloroheterocycles. Secondly, the chloroherocycles and N-cyclohexyl dithiocarbamate cyclohexylammonium salt were heated in chloroform for 12 h at 61 °C to afford heteocyclic thioamides in excellent yields.

  9. A novel method for heterocyclic amide–thioamide transformations

    PubMed Central

    Ali, Ibrahim A I; Pazdera, Pavel

    2017-01-01

    In this paper, we introduce a novel and convenient method for the transformation of heterocyclic amides into heteocyclic thioamides. A two-step approach was applied for this transformation: Firstly, we applied a chlorination of the heterocyclic amides to afford the corresponding chloroheterocycles. Secondly, the chloroherocycles and N-cyclohexyl dithiocarbamate cyclohexylammonium salt were heated in chloroform for 12 h at 61 °C to afford heteocyclic thioamides in excellent yields. PMID:28228858

  10. Optoelectronic studies on heterocyclic bases of deoxyribonucleic acid for DNA photonics.

    PubMed

    El-Diasty, Fouad; Abdel-Wahab, Fathy

    2015-10-01

    The optoelectronics study of large molecules, particularly π-stacking molecules, such as DNA is really an extremely difficult task. We perform first electronic structure calculations on the heterocyclic bases of 2'-deoxyribonucleic acid based on Lorentz-Fresnel dispersion theory. In the UV-VIS range of spectrum, many of the optoelectronic parameters for DNA four bases namely adenine, guanine, cytosine and thymine are calculated and discussed. The results demonstrate that adenine has the highest hyperpolarizability, whereas thymine has the lowest hyperpolarizability. Cytosine has the lower average oscillator energy and the higher lattice energy. Thymine infers the most stable nucleic base with the lower phonon energy. Thymine also has the highest average oscillator energy and the lower lattice energy. Moreover, the four nucleic acid bases have large band gap energies less than 5 eV with a semiconducting behavior. Guanine shows the smallest band gap and the highest Fermi level energy, whereas adenine elucidates the highest band gap energy.

  11. Potential antitumor agents. 29. Quantitative structure-activity relationships for the antileukemic bisquaternary ammonium heterocycles.

    PubMed

    Denny, W A; Atwell, G J; Baguley, B C; Cain, B F

    1979-02-01

    Quantitative relationships between physicochemical drug properties and antileukemic (L1210) efficacy have been examined for a series of bisquaternary ammonium heterocycles employing multiple variable regression analysis. Three measures of biologic response were examined: ILSmax, the percentage increase in mean life span of leukemic animals at the LD10 dose; D40, the drug dose necessary to provide 40% increase in life span; and CI (=LD 10/D40), the chemotherapeutic index. A cross correlation matrix between these three measures and the LD10 values demonstrates ILSmax and CI to be independent of toxicity. D40 is highly inversely correlated with LD10 and positively correlated with ILSmax, suggesting that this parameter measures a composite of both drug selectivity and toxicity. Superior regression equations resulted at all stages employing ILSmax as a measure of antitumor selectivity. Acceptable equations modeling LD10 could not be obtained. There was a parabolic relationship between agent lipophilic-hydrophilic balance, measured as chromatographic Rm values, and ILSmax. To reduce residual variance in the L1210 screening data, not accepted by this parabolic equation, measures of agent-DNA interaction were investigated as possible indices of site fit. Relative levels of drug-DNA interaction were obtained by spectrofluorimetric quantitation of drug displacement of DNA-bound ethidium. Addition to regression equations of agent C50 values for calf thymus DNA, those micromolar drug concentrations necessary to displace 50% of the ethidium bound to that DNA, provided a significant reduction in the screening data variance. C50 values for drug interactions with poly[d(A-T)] and poly[d(G-C)] were also investigated as possible indicators of drug selectivity towards different DNA sites. Marked differences were observed in the C50 values for the two synthetic nucleic acids, with those for calf thymus DNA and poly[d(G-C)] proving highly covariant. A regression equation containing a

  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.

  13. Mechanism and nature of the different viscosity sensitivities of hemicyanine dyes with various heterocycles.

    PubMed

    Cao, Jianfang; Hu, Chong; Liu, Fei; Sun, Wen; Fan, Jiangli; Song, Fengling; Sun, Shiguo; Peng, Xiaojun

    2013-06-03

    A series of hemicyanine derivatives are excellent fluorescent viscosity sensors in live cells and in imaging of living tissues due to their low quantum yields in solution but large fluorescence enhancements in viscous environments. Herein, three carbazole-based hemicyanine dyes with different heterocycles are studied. They have different background quantum yields, and hence different sensitivities to viscosity detection, large Stokes shifts, and high sensitivity. Better understanding of the structure-property relationships for viscosity sensitivity could benefit the design of improved dyes. Computational studies on these dyes reveal the mechanism of viscosity sensitivity of fluorescent molecular rotors and the nature of the difference in viscosity sensitivity of the three dyes. The results show that the greatly raised HOMO and greatly lowered LUMO in the S1 state compared with the S0 state are responsible for the large Stokes shift of the three dyes. The heterocyclic moieties have the primary influence on the LUMO levels of the three hemicyanine dyes. Rotation about the C-C bond adjacent to the carbazole moiety of the three dyes drives the molecule toward a small energy gap between the ground state and the first excited state, which causes mainly nonradiative deactivation. The oscillator strengths in the lowest singlet excited state drop rapidly with increasing rotation between 0 and 95°, which leads to a dark state for these dyes when fully twisted at 95°. We draw a mechanistic picture at the molecular level to illustrate how these dyes work as viscosity-sensitive fluorescent probes. The activation barriers and energy gaps of C-C bond rotation strongly depend on the choice of heterocycle, which plays a major role in reducing fluorescence quantum yield in the free state and provides high sensitivity to viscosity detection in viscous environments for the carbazole-based hemicyanine dyes.

  14. Preparation of a poly(3'-azido-3'-deoxythymidine-co-propargyl methacrylate-co-pentaerythritol triacrylate) monolithic column by in situ polymerization and a click reaction for capillary liquid chromatography of small molecules and proteins.

    PubMed

    Lin, Zian; Yu, Ruifang; Hu, Wenli; Zheng, Jiangnan; Tong, Ping; Zhao, Hongzhi; Cai, Zongwei

    2015-07-07

    Combining free radical polymerization with click chemistry via a copper-mediated azide/alkyne cycloaddition (CuAAC) reaction in a "one-pot" process, a facile approach was developed for the preparation of a poly(3'-azido-3'-deoxythymidine-co-propargyl methacrylate-co-pentaerythritol triacrylate) (AZT-co-PMA-co-PETA) monolithic column. The resulting poly(AZT-co-PMA-co-PETA) monolith showed a relatively homogeneous monolithic structure, good permeability and mechanical stability. Different ratios of monomers and porogens were used for optimizing the properties of a monolithic column. A series of alkylbenzenes, amides, anilines, and benzoic acids were used to evaluate the chromatographic properties of the polymer monolith in terms of hydrophobic, hydrophilic and cation-exchange interactions, and the results showed that the poly(AZT-co-PMA-co-PETA) monolith exhibited more flexible adjustment in chromatographic selectivity than that of the parent poly(PMA-co-PETA) and AZT-modified poly(PMA-co-PETA) monoliths. Column efficiencies for toluene, DMF, and formamide with 35,000-48,000 theoretical plates per m could be obtained at a linear velocity of 0.17 mm s(-1). The run-to-run, column-to-column, and batch-to-batch repeatabilities of the retention factors were less than 4.2%. In addition, the proposed monolith was also applied to efficient separation of sulfonamides, nucleobases and nucleosides, anesthetics and proteins for demonstrating its potential.

  15. Heteroleptic Cycloplatinated N-Heterocyclic Carbene Complexes: A New Approach to Highly Efficient Blue-Light Emitters.

    PubMed

    Fuertes, Sara; Chueca, Andrés J; Arnal, Lorenzo; Martín, Antonio; Giovanella, Umberto; Botta, Chiara; Sicilia, Violeta

    2017-04-07

    New heteroleptic compounds of platinum(II)-containing cyclometalated N-heterocyclic carbenes, [PtCl(R-C^C*)(PPh3)] [R-CH^C*-κC* = 3-methyl-1-(naphthalen-2-yl)-1H-imidazol-2-ylidene (R-C = Naph; 1A), 1-[4-(ethoxycarbonyl)phenyl]-3-methyl-1H-imidazol-2-ylidene (R = CO2Et; 1B), and [Pt(R-C^C*)(py)(PPh3)]PF6 (py = pyridine; R-C = Naph, 2A; R = CO2Et, 2B], have been prepared and fully characterized. All of them were obtained as the trans-(C*,PPh3) isomer in high yields. The selectivity of their synthesis has been explained in terms of the degree of transphobia (T) of pairs of ligands in trans positions. X-ray diffraction studies on both 2A and 2B revealed that only in 2A, containing a C^C* with a more extended π system, do the molecules assemble themselves into head-to-tail pairs through intermolecular π···π contacts. The photophysical properties of 2A and 2B and those of the related compounds [Pt(NC-C^C*)(PPh3)L]PF6 [NC-CH^C*-κC* = 1-(4-cyanophenyl)-3-methyl-1H-imidazol-2-ylidene; L = pyridine (py; 2C), 2,6-dimethylphenylisocyanide (CNXyl; 3C), and 2-mercapto-1-methylimidazole (MMI; 4C)] have been examined to analyze the influence of the R substituent on R-C^C* (R-C = Naph; R = CO2Et, CN) and that of the ancillary ligands (L) on them. Experimental data and time-dependent density functional theory calculations showed the similarity of the electronic features associated with R-C^C* (R = CN, CO2Et) and their difference with respect to R-C^C* (R-C = Naph). All of the compounds are very efficient blue emitters in poly(methyl methacrylate) films under an argon atmosphere, with QY values ranging from 68% (2B) to 93% (2C). In the solid state, the color of the emission changes to yellowish-orange for compounds 2A (λmax = 600 nm) and 3C (λmax = 590 nm) because of the formation of aggregates through intermolecular π···π interactions. 2C and 3C were chosen to fabricate fully solution-processed electroluminescent devices with blue-light (2C), yellow-orange-light (3C

  16. 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...

  17. 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.

  18. Spectral characteristics of heterocyclic compounds with a chain structure, cooled in an ultrasonic jet

    NASA Astrophysics Data System (ADS)

    Povedailo, V. A.; Yakovlev, D. L.

    2006-11-01

    We have recorded the fluorescence excitation spectra of three heterocyclic compounds with a chain structure [BPO (2-phenyl-5-(4-diphenylyl)oxazole), POPOP (1,4-di[2-(5-phenyloxazolyl)]benzene, and TOPOT (1,4-di[2-(5-n-tolyloxazolyl)]benzene] and the fluorescence spectra of POPOP, under conditions where the molecules were cooled in an ultrasonic helium jet. A line structure is observed in the spectra of POPOP and TOPOT; for the BPO molecules, whose configuration changes considerably during electronic excitation, vibrational structure is apparent only in the low-frequency region of the excitation spectrum, and a diffuse spectrum is recorded starting from ν 0 0 + 200 cm-1. For all the compounds, in the spectra we recorded vibrations with frequencies up to 100 cm-1, arising due to the flexibility of the molecular structure. The rotational contours of the lines for the electronic and vibronic transitions of the POPOP molecules (Trot = 10.5 K) and TOPOT molecules (Trot = 15 K) are structureless and bell-shaped. The degree of polarization of the fluorescence Pfl for the jet-cooled POPOP molecules for excitation of vibrations along the absorption band up to 2000 cm-1 above ν 0 0 is practically constant (˜8.4%) and matches Pfl for high-temperature vapors.

  19. Recent advances in the electrochemical construction of heterocycles.

    PubMed

    Francke, Robert

    2014-01-01

    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.

  20. 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

  1. Construction of Nine-Membered Heterocycles through Palladium-Catalyzed Formal [5+4] Cycloaddition.

    PubMed

    Yang, Li-Cheng; Rong, Zi-Qiang; Wang, Ya-Nong; Tan, Zher Yin; Wang, Min; Zhao, Yu

    2017-03-06

    The first catalytic formal [5+4] cycloaddition to prepare nine-membered heterocycles is presented. Under palladium catalysis, the reaction of N-tosyl azadienes and substituted vinylethylene carbonates (VECs) proceeds smoothly to produce benzofuran-fused heterocycles in uniformly high efficiency. Highly diastereoselective functionalization of the nine-membered heterocycles through peripheral attack is also demonstrated.

  2. Iron-Catalyzed Arylation of Heterocycles via Directed C–H Bond Activation

    PubMed Central

    2015-01-01

    The iron-catalyzed arylation of aromatic heterocycles, such as pyridines, thiophenes, and furans, has been achieved. The use of an imine directing group allowed for the ortho functionalization of these heterocycles with complete conversion in 15 min at 0 °C. Yields up to 88% were observed in the synthesis of 15 heterocyclic biaryls. PMID:24450989

  3. Syntheses and Reactions of Chalcogen-containing Heterocycles.

    PubMed

    Sashida, Haruki

    2016-01-01

    The advances in my laboratory for the past 20-25 years concerning the chemistry of chalcogen-containing heterocycles are reviewed. The intramolecular cyclization of the chalcogenols (-TeH, -SeH, -SH) into a triple bond or appropriate leaving group produced various chalcogen-containing heterocycles. The reactions of the obtained products were examined: the reactions of 1-benzo- and 2-benzopyrylium salts containing a tellurium or selenium element with several nucleophiles, including alkoxides, amines, the cyanide ion, an active methyl compound (acetone), Grignard reagents, copper reagents, and tin reagents, along with hydrogenation and hydrolysis reactions, provided corresponding chromes or isochromes having various functional groups at the 2- or 1-C position. Isothiocyanate and isoselenocyanate were used as chalcogen sources for the preparation of five- or six-membered heterocycles. In addition, double intramolecular cyclization, ring-expansion reactions, electrophilic cyclization and iodocyclization were also carried out.

  4. 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.

  5. Transition metal-free one-pot synthesis of nitrogen-containing heterocycles.

    PubMed

    Kumari, Simpal; Kishore, Dharma; Paliwal, Sarvesh; Chauhan, Rajani; Dwivedi, Jaya; Mishra, Aakanksha

    2016-02-01

    One-pot heterocyclic synthesis is an exciting research area as it can open routes for the development of otherwise complex transformations in organic synthesis. Heterocyclic compounds show wide spectrum of applications in medicinal chemistry, chemical biology, and materials science. These heterocycles can be generated very efficiently through highly economical and viable routes using one-pot synthesis. In particular, the metal-free one-pot synthetic protocols are highly fascinating due to several advantages for the industrial production of heterocyclic frameworks. This comprehensive review is devoted to the transition metal-free one-pot synthesis of nitrogen-containing heterocycles from the period 2010-2013.

  6. Molecular docking and pharmacophore studies of heterocyclic compounds as Heat shock protein 90 (Hsp90) Inhibitors

    PubMed Central

    Baby, Suby T; Sharma, Shailendra; Enaganti, Sreenivas; Cherian, P. Roby

    2016-01-01

    Heat Shock Protein 90 was a key molecular chaperone involved in the proteome stability maintenance and its interference in many signaling networks associated with cancer progression, makes it of an important target for cancer therapeutics. The present study aimed to identify potential lead molecule among the selected heterocyclic compounds against Human Hsp90 (PDB: 1YET) through docking using GOLD 3.1 and pharmacophore studies using Discovery studio 2.1. On the basis of the GOLD Fitness scores, the compounds Q1G and T21 showed better binding affinity. Further the analyzed structure pharmacophore results are in consistence with the docking results indicating that both these compounds show antagonistic activity towards HSP90 respectively.

  7. 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.

  8. β-Diketo Building Blocks for MCRs-Based Syntheses of Heterocycles

    NASA Astrophysics Data System (ADS)

    Del Duque, Maria Mar Sanchez; Allais, Christophe; Isambert, Nicolas; Constantieux, Thierry; Rodriguez, Jean

    In the context of sustainable chemistry, because of economic and ecological increasing pressure, domino multicomponent reactions (MCRs) constitute a central academic and industrial investigation domain in diversity-oriented synthesis of functionalized heterocycles. Although isocyanide-based MCRs generally predominate nowadays, the use of 1,3-dicarbonyls as substrates, proposed as early as 1882 by Hantzsch, proved to be highly efficient, but have been relatively unexplored until recently. In the last few years, such transformations received a growing attention as new useful methodologies valuable for the selective direct access to highly functionalized small organic molecules of primary synthetic and biological value. This review focuses on the more significant recent developments on the use of β-diketo building blocks for MCRs published in the last 5 years.

  9. PRESSURE EFFECTS IN POLYCYCLIC AROMATIC NITROGENATED HETEROCYCLES (PANHs): DIAGNOSTIC QUALITIES AND COSMOBAROMETRY POTENTIAL

    SciTech Connect

    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.

  10. 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.

  11. 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.

  12. DNA sequence-selective C8-linked pyrrolobenzodiazepine-heterocyclic polyamide conjugates show anti-tubercular-specific activities.

    PubMed

    Brucoli, Federico; Guzman, Juan D; Basher, Mohammad A; Evangelopoulos, Dimitrios; McMahon, Eleanor; Munshi, Tulika; McHugh, Timothy D; Fox, Keith R; Bhakta, Sanjib

    2016-12-01

    New chemotherapeutic agents with novel mechanisms of action are in urgent need to combat the tuberculosis pandemic. A library of 12 C8-linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD)-heterocyclic polyamide conjugates (1-12) was evaluated for anti-tubercular activity and DNA sequence selectivity. The PBD conjugates were screened against slow-growing Mycobacterium bovis Bacillus Calmette-Guérin and M. tuberculosis H37Rv, and fast-growing Escherichia coli, Pseudomonas putida and Rhodococcus sp. RHA1 bacteria. DNase I footprinting and DNA thermal denaturation experiments were used to determine the molecules' DNA recognition properties. The PBD conjugates were highly selective for the mycobacterial strains and exhibited significant growth inhibitory activity against the pathogenic M. tuberculosis H37Rv, with compound 4 showing MIC values (MIC=0.08 mg l(-1)) similar to those of rifampin and isoniazid. DNase I footprinting results showed that the PBD conjugates with three heterocyclic moieties had enhanced sequence selectivity and produced larger footprints, with distinct cleavage patterns compared with the two-heterocyclic chain PBD conjugates. DNA melting experiments indicated a covalent binding of the PBD conjugates to two AT-rich DNA-duplexes containing either a central GGATCC or GTATAC sequence, and showed that the polyamide chains affect the interactions of the molecules with DNA. The PBD-C8 conjugates tested in this study have a remarkable anti-mycobacterial activity and can be further developed as DNA-targeted anti-tubercular drugs.

  13. 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...

  14. 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.

  15. Toxicity of six heterocyclic nitrogen compounds to Daphnia pulex

    USGS Publications Warehouse

    Perry, Cynthia M.; Smith, Stephen B.

    1988-01-01

    We determined the relative toxicities to the aquatic crustacean Daphniz pulex of six heterocyclic nitrogen compunds. These compounds were selected because they were detected in lake trout or walleyes and were commercially available. Stress to the daphnid populations may affect forage fish populations that depend either directly or indirectly on zooplankton as a food source in the Great Lakes.

  16. Recent Developments in the Chemistry of N-Heterocyclic Phosphines

    NASA Astrophysics Data System (ADS)

    Gudat, Dietrich

    This chapter gives a survey on five- and six-membered phosphorus-nitrogen heterocyclic compounds whose rings combine a phosphazene (>N-P = N-) or phosphazane (>N-P(X)-N<) unit with an unsaturated C2 or C3 building block. Representatives contain structurally diverse species like aromatic 1,3,2-diazaphosphinines and (benzo)-1,3,2-diazaphospholes, cationic counterparts of subvalent main-group carbene analogues like 1,3,2-diazaphospholenium ions and phosphenium-diketiminates, and neutral heterocycles like 1,3,2-diazaphospholenes featuring unusual structures and reactivities. The exploration of these species developed rapidly in the last two decades in the wake of cutting edge research on multiple bonding and low coordination in the chemistry of heavier main-group elements, and the discovery of stable carbenes. This review summarizes the elaboration of synthetic approaches for different types of N-heterocyclic phosphine derivatives, discusses their characterization by physical and computational methods which furnished a thorough understanding of structure and bonding, and finally highlights accomplishments in the exploration of the chemical properties at the border of classical organic heterocyclic chemistry and molecular inorganic chemistry.

  17. 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.

  18. 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...

  19. 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...

  20. 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...

  1. Umpolung of Michael acceptors catalyzed by N-heterocyclic carbenes.

    PubMed

    Fischer, Christian; Smith, Sean W; Powell, David A; Fu, Gregory C

    2006-02-08

    N-Heterocyclic carbenes can catalyze beta-alkylations of a range of alpha,beta-unsaturated esters, amides, and nitriles that bear pendant leaving groups to form a variety of ring sizes. In this process, the nucleophilic catalyst transiently transforms the normally electrophilic beta carbon into a nucleophilic site through an unanticipated addition-tautomerization sequence.

  2. Enantioselective N-heterocyclic carbene-catalyzed synthesis of trifluoromethyldihydropyridinones.

    PubMed

    Wang, Dong-Ling; Liang, Zhi-Qin; Chen, Kun-Quan; Sun, De-Qun; Ye, Song

    2015-06-05

    The enantioselective N-heterocyclic carbene-catalyzed [4 + 2] cyclocondensation of α-chloroaldehydes and trifluoromethyl N-Boc azadienes was developed, giving the corresponding 3,4-disubstituted-6-trifluoromethyldihydropyridin-2(1H)-ones in good yields with exclusive cis-selectivities and excellent enantioselectivities.

  3. Synthesis and properties of heterocyclic type I photoinitiators

    NASA Astrophysics Data System (ADS)

    Liska, R.; Knaus, S.; Wendrinsky, J.

    1999-05-01

    The synthesis and properties of a series of new heterocyclic hydroxyalkylphenone-analogous photoinitiators (PIs) is described. The PIs are obtained by reaction of aromatic organolithium compounds with nitriles or by Friedel-Craft's-acylation. Preliminary photocalorimetric tests and UV absorption data are included.

  4. Acyl anion free N-heterocyclic carbene organocatalysis.

    PubMed

    Ryan, Sarah J; Candish, Lisa; Lupton, David W

    2013-06-21

    Reaction discovery using N-heterocyclic carbene organocatalysis has been dominated by the chemistry of acyl anion equivalents. Recent studies demonstrate that NHCs are far more diverse catalysts, with a variety of reactions discovered that proceed without acyl anion equivalent formation. In this tutorial review selected examples of acyl anion free NHC catalysis using carbonyl compounds are presented.

  5. 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...

  6. N/S-heterocyclic contaminant removal from fuels by the mesoporous metal-organic framework MIL-100: the role of the metal ion.

    PubMed

    Van de Voorde, Ben; Boulhout, Mohammed; Vermoortele, Frederik; Horcajada, Patricia; Cunha, Denise; Lee, Ji Sun; Chang, Jong-San; Gibson, Emma; Daturi, Marco; Lavalley, Jean-Claude; Vimont, Alexandre; Beurroies, Isabelle; De Vos, Dirk E

    2013-07-03

    The influence of the metal ion in the mesoporous metal trimesate MIL-100(Al(3+), Cr(3+), Fe(3+), V(3+)) on the adsorptive removal of N/S-heterocyclic molecules from fuels has been investigated by combining isotherms for adsorption from a model fuel solution with microcalorimetric and IR spectroscopic characterizations. The results show a clear influence of the different metals (Al, Fe, Cr, V) on the affinity for the heterocyclic compounds, on the integral adsorption enthalpies, and on the uptake capacities. Among several factors, the availability of coordinatively unsaturated sites and the presence of basic sites next to the coordinative vacancies are important factors contributing to the observed affinity differences for N-heterocyclic compounds. These trends were deduced from IR spectroscopic observation of adsorbed indole molecules, which can be chemisorbed coordinatively or by formation of hydrogen bonded species. On the basis of our results we are able to propose an optimized adsorbent for the deep and selective removal of nitrogen contaminants out of fuel feeds, namely MIL-100(V).

  7. Study of the relationship between decomposition energies of various heterocycles derived by using the PM3 method

    NASA Astrophysics Data System (ADS)

    Zubkov, V. A.; Bogdanova, S. E.; Yakimansky, A. V.

    1996-01-01

    Experimental and circumstantial data were employed to assess the reliability of PM3-calculated energies of heterocycle decompositions which result in a biradical and a molecule with a closed shell. Calculated decomposition energies ( ED) reproduced the relationship between experimental ED for oxazole, imidazole and thiazole although the calculated ED values were lower than the experimental ones. In the case of the heterocycles (HCs) containing carbonyl groups (malemide, oxazinone, etc.) the variations in ED values calculated for distinct HCs and different decomposition pathways of the same HC correlated in many cases with variations in the stabilities of the biradicals formed during the HC decompositions. The differences in relative stabilities of the resulting molecules with a closed shell, the variations in the capacity for decomposition between five- and six-membered HCs, and the differences in the heats of formation for isomeric HCs were also found to affect the ED values for HCs containing carbonyl groups. ED values for six-membered HCs containing only nitrogen atoms as heteroatoms were higher than those for other HCs considered but lower than that for benzene. A decrease in ED with an increase in the number of nitrogen atoms in such HCs seemed to be caused by the known capacity of nitrogen atoms to draw the electron density off an aromatic ring thereby weakening the bond strengths of the ring.

  8. Direct, metal-free amination of heterocyclic amides/ureas with NH-heterocycles and N-substituted anilines in POCl3.

    PubMed

    Deng, Xiaohu; Roessler, Armin; Brdar, Ivana; Faessler, Roger; Wu, Jiejun; Sales, Zachary S; Mani, Neelakandha S

    2011-10-21

    A POCl(3)-mediated, direct amination reaction of heterocyclic amides/ureas with NH-heterocycles or N-substituted anilines is described. Compared to the existing methods, this operationally simple protocol provides unique reactivity and functional group compatibility because of the metal-free, acidic reaction conditions. The yields are generally excellent.

  9. Development and understanding of new membranes based on aromatic polymers and heterocycles for fuel cells

    NASA Astrophysics Data System (ADS)

    Li, Wen

    Direct methanol fuel cells (DMFC) are appealing as a power source for portable devices as they do not require recharging with an electrical outlet. However, the DMFC technology is confronted with the high crossover of methanol fuel from the anode to the cathode through the currently used Nafion membrane, which not only wastes the fuel but also poisons the cathode platinum catalyst. With an aim to overcome the problems encountered with the Nafion membrane, this dissertation focuses on the design and development of new polymeric membrane materials for DMFC and a fundamental understanding of their structure-property-performance relationships. Several polymeric blend membranes based on acid-base interactions between an aromatic acidic polymer such as sulfonated ploy(ether ether ketone) (SPEEK) and an aromatic basic polymer such as heterocycle tethered poly(sulfone) (PSf) have been explored. Various heterochylces like nitro-benzimidazole (NBIm), 1H-Perimidine (PImd), and 5-amino-benzotriazole (BTraz) have been tethered to PSf to understand the influence of pKa values and the size of the hetrocycles. The blend membranes show lower methanol crossover and better performance in DMFC than plain SPEEK due to an enhancement in proton conductivity through acid-base interactions and an insertion of the heterocycle side groups into the ionic clusters of SPEEK as indicated by small angle X-ray scattering and TEM data. The SPEEK/PSf-PImd blend membrane shows the lowest methanol crossover due to the larger size of the side groups, while the SPEEK/PSf-BTraz blend membrane shows the highest proton conductivity and maximum power density. To further investigate the methanol-blocking effect of the heterocycles, N,N'-Bis-(1H-benzimidazol-2-yl)-isophthalamide (BBImIP) having two amino-benzimidazole groups bonded to a phenyl ring has been incorporated into sulfonated polysulfone (SPSf) and SPEEK membranes. With two 2-amino-benzimidazole groups, which could greatly increase the proton

  10. Novel inorganic heterocycles from dimetalated carboranylamidinates.

    PubMed

    Harmgarth, Nicole; Gräsing, Daniel; Dröse, Peter; Hrib, Cristian G; Jones, Peter G; Lorenz, Volker; Hilfert, Liane; Busse, Sabine; Edelmann, Frank T

    2014-04-07

    Mono- and dianionic carboranylamidinates are readily available in one-pot reactions directly from o-carborane (1). In situ-monolithiation of 1 followed by treatment with N,N'-diisopropylcarbodiimide, (i)PrN=C=N(i)Pr, or N,N'-dicyclohexylcarbodiimide, CyN=C=NCy, provided the lithium carboranylamidinates (o-C2B10H10C(NH(i)Pr)(=N(i)Pr)-κ(2)C,N)Li(DME) (2a) and (o-C2B10H10C(NH(i)Cy)(=N(i)Cy)-κ(2)C,N)Li(THF)2 (2b). Controlled hydrolysis of 2a,b afforded the free carboranylamidines o-C2B10H11C(NH(i)R)(=N(i)R) (3a: R = (i)Pr, 3b: R = Cy). The first dimetalated carboranylamidinates, o-C2B10H10C(N(i)Pr)(=N(i)Pr)Li2(DME)2 (4a) (DME = 1,2-dimethoxyethane) and o-C2B10H10C(N(i)Pr)(=N(i)Pr)Li2(THF)4 (4b), were prepared in high yield (83% yield) directly from 1 using a simple one-pot synthetic protocol. Treatment of 4b with 2 equiv. of Me3SiCl afforded the disilylated derivative o-C2B10H10-κ(2)C,N-[C(N(i)PrSiMe3)(=N(i)Pr)]SiMe3 (5). Dianionic 4b also served as an excellent precursor for novel inorganic heterocycles incorporating the closo-1,2-C2B10H10 cage, including the unsymmetrical distannene [o-C2B10H10C(N(i)Pr)(=N(i)Pr)-κ(2)C,N]Sn=Sn[((i)PrN)2C(n)Bu]2 (6) and the azaphosphole derivative [o-C2B10H10C(N(i)Pr)(=N(i)Pr)-κ(2)C,N]PPh (7). Surprisingly, it was found that the synthesis of new inorganic ring systems from dianionic carboranylamidinates can also be achieved by employing only 1 equiv. of n-butyllithium in the generation of the anionic carboranylamidinate intermediates. Using this straightforward one-pot synthetic protocol, the Group 14 metallacycles [o-C2B10H10C(NCy)(=NCy)-κ(2)C,N]SiR2 (R = Cl (8), Me (9), Ph (10)) and [o-C2B10H10C(NCy)([=NCy)-κ(2)C,N]GeCl2 (11) have become accessible. The same synthetic strategy could be successfully adapted to prepare the corresponding Group 4 metallocene derivatives Cp2Ti[o-C2B10H10C(NCy)(=NCy)-κ(2)C,N] (12) and Cp2Zr[o-C2B10H10C(NCy)(=NCy)-κ(2)C,N] (13). The molecular structures of 2b, 3b, 4b, 5, 6, 7, 10, 12, and 13 were

  11. Brønsted-acid-catalyzed asymmetric multicomponent reactions for the facile synthesis of highly enantioenriched structurally diverse nitrogenous heterocycles.

    PubMed

    Yu, Jie; Shi, Feng; Gong, Liu-Zhu

    2011-11-15

    potential as chiral catalysts for multicomponent protocols that unavoidably release water molecules during the course of the reaction. We present a detailed investigation of several MCRs catalyzed by chiral phosphoric acids, including Biginelli and Biginelli-like reactions; 1,3-dipolar cycloadditions; aza Diels-Alder reactions; and some other cyclization reactions. These approaches have enabled the facile preparation of 3,4-dihydropyrimidinones, pyrrolidines, piperidines, and dihydropyridines with high optical purity. The synthetic applications of these new protocols are also discussed, together with theoretical studies of the reaction transition states that address the regio- and stereochemistry. In addition, we briefly illustrate the application of a recently developed strategy that involves relay catalysis by a binary system consisting of a chiral phosphoric acid and a metal complex. This technique has provided access to new reactions that generate structurally diverse and complex heterocycles. Enantioselective organocatalytic MCRs remain a challenge, but we illustrate success on several fronts with chiral phosphoric acids as the primary catalysts. Further progress will undoubtedly provide even better access to the chiral nitrogen-containing heterocycles that are not only prevalent as natural products but also serve as key chiral building blocks in organic synthesis.

  12. Decolorization of Azo, Triphenyl Methane, Heterocyclic, and Polymeric Dyes by Lignin Peroxidase Isoenzymes from Phanerochaete chrysosporium.

    PubMed

    Ollikka, P; Alhonmäki, K; Leppänen, V M; Glumoff, T; Raijola, T; Suominen, I

    1993-12-01

    The ligninolytic enzyme system of Phanerochaete chrysosporium decolorizes several recalcitrant dyes. Three isolated lignin peroxidase isoenzymes (LiP 4.65, LiP 4.15, and LiP 3.85) were compared as decolorizers with the crude enzyme system from the culture medium. LiP 4.65 (H2), LiP 4.15 (H7), and LiP 3.85 (H8) were purified by chromatofocusing, and their kinetic parameters were found to be similar. Ten different types of dyes, including azo, triphenyl methane, heterocyclic, and polymeric dyes, were treated by the crude enzyme preparation. Most of the dyes lost over 75% of their color; only Congo red, Poly R-478, and Poly T-128 were decolorized less than the others, 54, 46, and 48%, respectively. Five different dyes were tested for decolorization by the three purified isoenzymes. The ability of the isoenzymes to decolorize the dyes in the presence of veratryl alcohol was generally comparable to that of the crude enzyme preparation, suggesting that lignin peroxidase plays a major role in the decolorization and that manganese peroxidase is not required to start the degradation of these dyes. In the absence of veratryl alcohol, the decolorization activity of the isoenzymes was in most cases dramatically reduced. However, LiP 3.85 was still able to decolorize 20% of methylene blue and methyl orange and as much as 60% of toluidine blue O, suggesting that at least some dyes can function as substrates for isoenzyme LiP 3.85 but not to the same extent for LiP 4.15 or LiP 4.65. Thus, the isoenzymes have different specificities towards dyes as substrates.

  13. Decolorization of Azo, Triphenyl Methane, Heterocyclic, and Polymeric Dyes by Lignin Peroxidase Isoenzymes from Phanerochaete chrysosporium

    PubMed Central

    Ollikka, Pauli; Alhonmäki, Kirsi; Leppänen, Veli-Matti; Glumoff, Tuomo; Raijola, Timo; Suominen, Ilari

    1993-01-01

    The ligninolytic enzyme system of Phanerochaete chrysosporium decolorizes several recalcitrant dyes. Three isolated lignin peroxidase isoenzymes (LiP 4.65, LiP 4.15, and LiP 3.85) were compared as decolorizers with the crude enzyme system from the culture medium. LiP 4.65 (H2), LiP 4.15 (H7), and LiP 3.85 (H8) were purified by chromatofocusing, and their kinetic parameters were found to be similar. Ten different types of dyes, including azo, triphenyl methane, heterocyclic, and polymeric dyes, were treated by the crude enzyme preparation. Most of the dyes lost over 75% of their color; only Congo red, Poly R-478, and Poly T-128 were decolorized less than the others, 54, 46, and 48%, respectively. Five different dyes were tested for decolorization by the three purified isoenzymes. The ability of the isoenzymes to decolorize the dyes in the presence of veratryl alcohol was generally comparable to that of the crude enzyme preparation, suggesting that lignin peroxidase plays a major role in the decolorization and that manganese peroxidase is not required to start the degradation of these dyes. In the absence of veratryl alcohol, the decolorization activity of the isoenzymes was in most cases dramatically reduced. However, LiP 3.85 was still able to decolorize 20% of methylene blue and methyl orange and as much as 60% of toluidine blue O, suggesting that at least some dyes can function as substrates for isoenzyme LiP 3.85 but not to the same extent for LiP 4.15 or LiP 4.65. Thus, the isoenzymes have different specificities towards dyes as substrates. Images PMID:16349103

  14. 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…

  15. 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

  16. Click Chemistry Route to the Synthesis of Unusual Amino Acids, Peptides, Triazole-Fused Heterocycles and Pseudodisaccharides.

    PubMed

    Chandrasekaran, Srinivasan; Ramapanicker, Ramesh

    2017-01-01

    Conjugation of different molecular species using copper(I)-catalyzed click reaction between azides and terminal alkynes is among the best available methods to prepare multifunctional compounds. The effectiveness of this method has provided wider acceptance to the concept of click chemistry, which is now widely employed to synthesize densely functionalized organic molecules. This article summarizes the contributions from our group in the development of new methods for the synthesis of functional molecules using copper(I)-catalyzed click reactions. We have developed very efficient methods for the synthesis of peptides and amino acids conjugated with carbohydrates, thymidine and ferrocene. We have also developed an efficient strategy to synthesize triazole-fused heterocycles from primary amines, amino alochols and diols. Finally, an interesting method for the synthesis of pseudodisaccharides linked through triazoles, starting from carbohydrate-derived donor-acceptor cyclopropanes is discussed.

  17. High-throughput screening of metal-N-heterocyclic carbene complexes against biofilm formation by pathogenic bacteria.

    PubMed

    Bernardi, Thierry; Badel, Stéphanie; Mayer, Pascal; Groelly, Jérome; de Frémont, Pierre; Jacques, Béatrice; Braunstein, Pierre; Teyssot, Marie-Laure; Gaulier, Christelle; Cisnetti, Federico; Gautier, Arnaud; Roland, Sylvain

    2014-06-01

    A set of molecules including a majority of metal-N-heterocyclic carbene (NHC) complexes (metal=Ag, Cu, and Au) and azolium salts were evaluated by high-throughput screening of their activity against biofilm formation associated with pathogenic bacteria. The anti-planktonic effects were compared in parallel. Representative biofilm-forming strains of various genera were selected (Listeria, Pseudomonas, Staphylococcus, and Escherichia). All the compounds were tested at 1 mg L(-1) by using the BioFilm Ring Test. An information score (IS, sum of the activities) and an activity score (AS, difference between anti-biofilm and anti-planktonic activity) were determined from normalized experimental values to classify the most active molecules against the panel of bacterial strains. With this method we identified lipophilic Ag(I) and Cu(I) complexes possessing aromatic groups on the NHC ligand as the most efficient at inhibiting biofilm formation.

  18. Regioselective acceptorless dehydrogenative coupling of N-heterocycles toward functionalized quinolines, phenanthrolines, and indoles.

    PubMed

    Talwar, Dinesh; Gonzalez-de-Castro, Angela; Li, Ho Yin; Xiao, Jianliang

    2015-04-20

    A new strategy has been developed for the oxidant- and base-free dehydrogenative coupling of N-heterocycles at mild conditions. Under the action of an iridium catalyst, N-heterocycles undergo multiple sp(3) CH activation steps, generating a nucleophilic enamine that reacts in situ with various electrophiles to give highly functionalized products. The dehydrogenative coupling can be cascaded with Friedel-Crafts addition, resulting in a double functionalization of the N-heterocycles.

  19. Heterocycles as key substrates in multicomponent reactions: the fast lane towards molecular complexity.

    PubMed

    Isambert, Nicolas; Lavilla, Rodolfo

    2008-01-01

    Heterocycles display an intrinsic reactivity which enables rich, versatile and productive transformations. Taking into account their ubiquitous presence in natural products and drugs, the development of new, fast and efficient preparative protocols for these structures remains an urgent task in Organic Synthesis. Multicomponent reactions using heterocyclic chemistry offer new possibilities to exploit this exclusive reactivity. Recent results show relevant examples of such transformations. Several approaches which allow the construction of complex heterocyclic compounds from simple starting materials using this principle have been analyzed.

  20. A fluorous, Pummerer cyclative-capture strategy for the synthesis of N-heterocycles.

    PubMed

    McAllister, Laura A; McCormick, Rosemary A; James, Karen M; Brand, Stephen; Willetts, Nigel; Procter, David J

    2007-01-01

    A fluorous, cyclative-capture strategy based on a new Pummerer cyclization process allows rapid access to tagged, heterocyclic frameworks. Convenient modification of the fluorous, heterocyclic scaffolds by using a variety of approaches including Pd-catalyzed cross-couplings is possible. Traceless, reductive cleavage of the fluorous-phase tag or oxidative cleavage and further elaboration, completes a strategy for the high-throughput, fluorous-phase synthesis of a diverse range of N-heterocycles.

  1. Isocyanide-Based Multicomponent Reactions for the Synthesis of Heterocycles.

    PubMed

    Váradi, András; Palmer, Travis C; Notis Dardashti, Rebecca; Majumdar, Susruta

    2015-12-23

    Multicomponent reactions (MCRs) are extremely popular owing to their facile execution, high atom-efficiency and the high diversity of products. MCRs can be used to access various heterocycles and highly functionalized scaffolds, and thus have been invaluable tools in total synthesis, drug discovery and bioconjugation. Traditional isocyanide-based MCRs utilize an external nucleophile attacking the reactive nitrilium ion, the key intermediate formed in the reaction of the imine and the isocyanide. However, when reactants with multiple nucleophilic groups (bisfunctional reactants) are used in the MCR, the nitrilium intermediate can be trapped by an intramolecular nucleophilic attack to form various heterocycles. The implications of nitrilium trapping along with widely applied conventional isocyanide-based MCRs in drug design are discussed in this review.

  2. 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

  3. Heterocyclic Regioisomer Enumeration (HREMS): A Cheminformatics Design Tool.

    PubMed

    Tyagarajan, Sriram; Lowden, Christopher T; Peng, Zhengwei; Dykstra, Kevin D; Sherer, Edward C; Krska, Shane W

    2015-06-22

    We report the development and implementation of a cheminformatics tool which aids in the design of compounds during exploratory chemistry and lead optimization. The Heterocyclic Regioisomer Enumeration and MDDR Search (HREMS) tool allows medicinal chemists to build greater structural diversity into their synthetic planning by enabling a systematic, automated enumeration of heterocyclic regioisomers of target structures. To help chemists overcome biases arising from past experience or synthetic accessibility, the HREMS tool further provides statistics on clinical testing for each enumerated regioisomer substructure using an automated search of a commercial database. Ready access to this type of information can help chemists make informed choices on the targets they will pursue being mindful of past experience with these structures in drug development. This tool and its components can be incorporated into other cheminformatics workflows to leverage their capabilities in triaging and in silico compound enumeration.

  4. Coordination chemistry of N-heterocyclic nitrenium-based ligands.

    PubMed

    Tulchinsky, Yuri; Kozuch, Sebastian; Saha, Prasenjit; Mauda, Assaf; Nisnevich, Gennady; Botoshansky, Mark; Shimon, Linda J W; Gandelman, Mark

    2015-05-04

    Comprehensive studies on the coordination properties of tridentate nitrenium-based ligands are presented. N-heterocyclic nitrenium ions demonstrate general and versatile binding abilities to various transition metals, as exemplified by the synthesis and characterization of Rh(I) , Rh(III) , Mo(0) , Ru(0) , Ru(II) , Pd(II) , Pt(II) , Pt(IV) , and Ag(I) complexes based on these unusual ligands. Formation of nitrenium-metal bonds is unambiguously confirmed both in solution by selective (15) N-labeling experiments and in the solid state by X-ray crystallography. The generality of N-heterocyclic nitrenium as a ligand is also validated by a systematic DFT study of its affinity towards all second-row transition and post-transition metals (Y-Cd) in terms of the corresponding bond-dissociation energies.

  5. Synthesis of heterocycles by formal cycloadditions of isocyanides.

    PubMed

    Kruithof, Art; Ruijter, Eelco; Orru, Romano V A

    2015-03-01

    Synthetic methodology for the synthesis of heterocycles is of continuous and high interest with applications in materials, catalysis, and medicines. Multicomponent reactions are suitable tools to efficiently generate chemically diverse sets of heterocycles with sufficient structural complexity. Especially isocyanides have proven to be particularly versatile building blocks in these one-pot processes. Due to their electronic structure, isocyanides are able to act sequentially or simultaneously as a nucleophile and an electrophile. Traditionally, isocyanides are therefore frequently used in multicomponent chemistry. In the recent literature, numerous reactions have been reported that involve formal cycloadditions of isocyanides with conjugated heterodienes. This Focus Review aims at mapping this reactivity and at providing insight into the relationship between the various reported reaction partners and the observed reactivity modes.

  6. Isocyanide-Based Multicomponent Reactions for the Synthesis of Heterocycles

    PubMed Central

    Váradi, András; Palmer, Travis C.; Dardashti, Rebecca Notis; Majumdar, Susruta

    2016-01-01

    Multicomponent reactions (MCRs) are extremely popular owing to their facile execution, high atom-efficiency and the high diversity of products. MCRs can be used to access various heterocycles and highly functionalized scaffolds, and thus have been invaluable tools in total synthesis, drug discovery and bioconjugation. Traditional isocyanide-based MCRs utilize an external nucleophile attacking the reactive nitrilium ion, the key intermediate formed in the reaction of the imine and the isocyanide. However, when reactants with multiple nucleophilic groups (bisfunctional reactants) are used in the MCR, the nitrilium intermediate can be trapped by an intramolecular nucleophilic attack to form various heterocycles. The implications of nitrilium trapping along with widely applied conventional isocyanide-based MCRs in drug design are discussed in this review. PMID:26703561

  7. 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.

  8. The chemistry and biological activity of heterocycle-fused quinolinone derivatives: A review.

    PubMed

    Shiro, Tomoya; Fukaya, Takayuki; Tobe, Masanori

    2015-06-05

    Among all heterocycles, the heterocycle-fused quinolinone scaffold is one of the privileged structures in drug discovery as heterocycle-fused quinolinone derivatives exhibit various biological activities allowing them to act as anti-inflammatory, anticancer, antidiabetic, and antipsychotic agents. This wide spectrum of biological activity has attracted a great deal of attention in the field of medicinal chemistry. In this review, we provide a comprehensive description of the biological and pharmacological properties of various heterocycle-fused quinolinone scaffolds and discuss the synthetic methods of some of their derivatives.

  9. 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

  10. 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

  11. 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)

  12. 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.

  13. Mobius Molecules

    ERIC Educational Resources Information Center

    Eckert, J. M.

    1973-01-01

    Discusses formation of chemical molecules via Mobius strip intermediates, and concludes that many special physics-chemical properties of the fully closed circular form (1) of polyoma DNA are explainable by this topological feature. (CC)

  14. 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.

  15. Ring cleavage of sulfur heterocycles: how does it happen?

    PubMed

    Bressler, D C; Norman, J A; Fedorak, P M

    Sulfur heterocycles are common constituents of petroleum and liquids derived from coal, and they are found in some secondary metabolites of microorganisms and plants. They exist primarily as saturated rings and thiophenes. There are two major objectives driving investigations of the microbial metabolism of organosulfur compounds. One is the quest to develop a process for biodesulfurization of fossil fuels, and the other is to understand the fates of organosulfur compounds in petroleum- or creosote-contaminated environments which is important in assessing bioremediation processes. For these processes to be successful, cleavage of different types of sulfur heterocyclic rings is paramount. This paper reviews the evidence for microbial ring cleavage of a variety of organosulfur compounds and discusses the few well-studied cases which have shown that the C-S bond is most susceptible to breakage leading to disruption of the ring. In most cases, the introduction of one or more oxygen atom(s) onto the adjacent C atom and/or onto the S atom weakens the C-S bond, facilitating its cleavage. Although much is known about the thiophene ring cleavage in dibenzothiophene, there is still a great deal to be learned about the cleavage of other sulfur heterocycles.

  16. 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.

  17. 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) .

  18. 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.

  19. 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.

  20. 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.

  1. Poly(ADP-ribosyl)ation in carcinogenesis.

    PubMed

    Masutani, Mitsuko; Fujimori, Hiroaki

    2013-12-01

    Cancer develops through diverse genetic, epigenetic and other changes, so-called 'multi-step carcinogenesis', and each cancer harbors different alterations and properties. Here in this article we review how poly(ADP-ribosyl)ation is involved in multi-step and diverse pathways of carcinogenesis. Involvement of poly- and mono-ADP-ribosylation in carcinogenesis has been studied at molecular and cellular levels, and further by animal models and human genetic approaches. PolyADP-ribosylation acts in DNA damage repair response and maintenance mechanisms of genomic stability. Several DNA repair pathways, including base-excision repair and double strand break repair pathways, involve PARP and PARG functions. These care-taker functions of poly(ADP-ribosyl)ation suggest that polyADP-ribosyation may mainly act in a tumor suppressive manner because genomic instability caused by defective DNA repair response could serve as a driving force for tumor progression, leading to invasion, metastasis and relapse of cancer. On the other hand, the new concept of 'synthetic lethality by PARP inhibition' suggests the significance of PARP activities for survival of cancer cells that harbor defects in DNA repair. Accumulating evidence has revealed that some PARP family molecules are involved in various signaling cascades other than DNA repair, including epigenetic and transcriptional regulations, inflammation/immune response and epithelial-mesenchymal transition, suggesting that poly(ADP-ribosyl)ation both promotes and suppresses carcinogenic processes depending on the conditions. Expanding understanding of poly(ADP-ribosyl)ation suggests that strategies to achieve cancer prevention targeting poly(ADP-ribosyl)ation for genome protection against life-long exposure to environmental carcinogens and endogenous carcinogenic stimuli.

  2. Catalytic Kinetic Resolution of Saturated N-Heterocycles by Enantioselective Amidation with Chiral Hydroxamic Acids.

    PubMed

    Kreituss, Imants; Bode, Jeffrey W

    2016-12-20

    The preparation of enantioenriched chiral compounds by kinetic resolution dates back to the laboratories of Louis Pasteur in the middle of the 19th century. Unlike asymmetric synthesis, this process can always deliver enantiopure material (ee > 99%) if the reactions are allowed to proceed to sufficient conversion and the selectivity of the process is not unity (s > 1). One of the most appealing and practical variants is acylative kinetic resolution, which affords easily separable reaction products, and several highly efficient enzymatic and small molecule catalysts are available. Unfortunately, this method is applicable to limited substrate classes such as alcohols and primary benzylamines. This Account focuses on our work in catalytic acylative kinetic resolution of saturated N-heterocycles, a class of molecules that has been notoriously difficult to access via asymmetric synthesis. We document the development of hydroxamic acids as suitable catalysts for enantioselective acylation of amines through relay catalysis. Alongside catalyst optimization and reaction development, we present mechanistic studies and theoretical calculation accounting for the origins of selectivity and revealing the concerted nature of many amide-bond forming reactions. Immobilization of the hydroxamic acid to form a polymer supported reagent allows simplification of the experimental setup, improvement in product purification, and extension of the substrate scope. The kinetic resolutions are operationally straight forward: reactions proceed at room temperature and open to air conditions, without generation of difficult-to-remove side products. This was utilized to achieve decagram scale resolution of antimalarial drug mefloquine to prepare more than 50 g of (+)-erythro-meflqouine (er > 99:1) from the racemate. The immobilized quasienantiomeric acyl hydroxamic acid reagents were also exploited for a rare practical implementation of parallel kinetic resolution that affords both enantiomers of

  3. Stereoelectronic basis for the kinetic resolution of N-heterocycles with chiral acylating reagents.

    PubMed

    Hsieh, Sheng-Ying; Wanner, Benedikt; Wheeler, Philip; Beauchemin, André M; Rovis, Tomislav; Bode, Jeffrey W

    2014-06-10

    The kinetic resolution of N-heterocycles with chiral acylating agents reveals a previously unrecognized stereoelectronic effect in amine acylation. Combined with a new achiral hydroxamate, this effect makes possible the resolution of various N-heterocycles by using easily prepared reagents. A transition-state model to rationalize the stereochemical outcome of this kinetic resolution is also proposed.

  4. Organocatalytic Enantioselective Synthesis of 1,4-Dioxanes and Other Oxa-Heterocycles by Oxetane Desymmetrization.

    PubMed

    Yang, Wen; Sun, Jianwei

    2016-01-26

    A new asymmetric synthesis of chiral 1,4-dioxanes and other oxa-heterocycles has been developed by means of organocatalytic enantioselective desymmetrization of oxetanes. This mild process proceeds with exceedingly high efficiency and enantioselectivity to establish the quaternary stereocenters. This method complements the existing, yet limited, strategies for the synthesis of these oxa-heterocycles.

  5. Rhodium(I)-Catalyzed Benzannulation of Heteroaryl Propargylic Esters: Synthesis of Indoles and Related Heterocycles.

    PubMed

    Li, Xiaoxun; Xie, Haibo; Fu, Xiaoning; Liu, Ji-Tian; Wang, Hao-Yuan; Xi, Bao-Min; Liu, Peng; Xu, Xiufang; Tang, Weiping

    2016-07-18

    A de novo synthesis of a benzene ring allows for the preparation of a diverse range of heterocycles including indoles, benzofurans, benzothiophenes, carbazoles, and dibenzofurans from simple heteroaryl propargylic esters using a unified carbonylative benzannulation strategy. Multiple substituents can be easily introduced to the C4-C7 positions of indoles and related heterocycles.

  6. ORGANOCOPPER-MEDIATED TWO-COMPONENT SN2'-SUBSTITUTION CASCADE TOWARDS N-FUSED HETEROCYCLES.

    PubMed

    Chernyak, D; Gevorgyan, V

    2012-03-01

    Organocuprates efficiently undergo reaction with heterocyclic propargyl mesylates at low temperature to produce N-fused heterocycles. The copper reagent plays a "double duty" in this cascade transformation, which proceeds through an SN2'-substitution followed by a consequent cycloisomerization step.

  7. 40 CFR 721.4100 - Tris(disubstituted alkyl) het-er-o-cy-cle.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Tris(disubstituted alkyl) het-er-o-cy-cle. 721.4100 Section 721.4100 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.4100 Tris(disubstituted alkyl) het-er-o-cy-cle. (a) Chemical...

  8. 40 CFR 721.4100 - Tris(disubstituted alkyl) het-er-o-cy-cle.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Tris(disubstituted alkyl) het-er-o-cy-cle. 721.4100 Section 721.4100 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.4100 Tris(disubstituted alkyl) het-er-o-cy-cle. (a) Chemical...

  9. N,N-bond-forming heterocyclization: synthesis of 3-alkoxy-2H-indazoles.

    PubMed

    Mills, Aaron D; Nazer, Musa Z; Haddadin, Makhluf J; Kurth, Mark J

    2006-03-31

    A one-step heterocyclization of o-nitrobenzylamines to 3-alkoxy-2H-indazoles is reported. The electronic nature of the nitrophenyl group, the steric and electronic nature of the R1-functionalized benzylic amine, and the nature of the alcoholic solvent affect the efficiency of this heterocyclization reaction (approximately 40-90%).

  10. Evaluation of the radial deformability of poly(dG)-poly(dC) DNA and G4-DNA using vibrating scanning polarization force microscopy.

    PubMed

    Wang, Huabin; Lin, Jiwei; Wang, Chunmei; Zhang, Xuehua; An, Hongjie; Zhou, Xingfei; Sun, Jielin; Hu, Jun

    2010-05-18

    Poly(dG)-poly(dC) DNA and G4-DNA are two types of synthetic molecules that are regarded as promising candidates for molecular nanodevices. In this work, vibrating scanning polarization force microscopy (VSPFM) was employed to study the radial deformability of these two molecules coadsorbed on a Ni(2+)-modified mica surface. The values of the radial compressive elastic modulus of these two types of molecules were found to be similar (approximately 5-10 MPa) when the external loading force was between approximately 0.04 and approximately 0.12 nN. However, G4-DNA molecules possessed higher stiffness than poly(dG)-poly(dC) DNA (approximately 20-40 vs approximately 10-20 MPa) when the loading force was larger than approximately 0.12 nN. The results will aid us in understanding these molecule's mechanical performances.

  11. 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.

  12. 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.

  13. Ketoprofen-poly(vinylpyrrolidone) physical interaction

    NASA Astrophysics Data System (ADS)

    Di Martino, Piera; Joiris, Etienne; Gobetto, Roberto; Masic, Admir; Palmieri, Giovanni F.; Martelli, Sante

    2004-04-01

    Amorphous solid solutions were obtained in different proportions by dissolving ketoprofen (Ket) and poly(vinylpyrrolidone) (PVP) K30 in methanol and by evaporating them under reduced pressure. Their physical properties were studied by powder X-ray diffraction and by differential scanning calorimetry and compared to that of same physical mixtures (PM). The interaction of Keto and poly(vinylpyrrolidone) K30 in the solid state was then investigated by 13C NMR CPMAS analysis. The results indicated that in the Ket-(PVP) co-precipitates, the ket molecules, interacting with their carboxylic group through hydrogen bonding with the poly(vinylpyrrolidone) moieties, are molecularly and irregularly dispersed within the amorphous solvendum that acts as mechanical substratum for amorphous stabilization. In their simple PM, no evidence exists of the Ket-polymer interaction during the considered time interval.

  14. Synthesis of 2-arylidenebenzocycloalkanones containing N-donor heterocyclic rings

    NASA Astrophysics Data System (ADS)

    Sun, S.-W.; Zhang, X.; Wang, G.-F.

    2016-12-01

    A series of 2-arylidenebenzocycloalkanones containing heterocyclic rings 1- 8 were prepared and characterized by IR, 1H NMR and elemental analyses. X-ray diffraction study of 6 reveals that the cyclohexyl ring of the 3,4-dihydronaphthalen-1(2 H)-one adopts a chair conformation with a maximum deviation of 0.547(3) Å and makes dihedral angles of 52.24(17)° and 11.23(16)°, respectively, with the benzene plane and the mean plane of the benzimidazole ring.

  15. 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.

  16. 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.

  17. Stereoselective synthesis of heterocyclic cage compounds by domino conjugate additions.

    PubMed

    Carreño, M Carmen; Luzón, Carmen García; Ribagorda, María

    2002-01-04

    Heterocyclic cage compounds have been stereoselectively synthesized from enantiopure [(S)R]-[(p-tolylsulfinyl)methyl]-p-quinols or their amine analogues and 2-(trimethylsilyloxy)furan in the presence of Bu4NF. The method is particularly valuable not only because of the stereochemical control but also because the reactions occur in an experimentally simple one-pot procedure through a domino sequence of three consecutive conjugate additions. The intermediate 1,4-adducts could be isolated when the reaction was carried out in the presence of BF3 x OEt2.

  18. QSAR of heterocyclic antifungal agents by flip regression

    NASA Astrophysics Data System (ADS)

    Deeb, Omar; Clare, Brian W.

    2008-12-01

    QSAR analysis of a set of 96 heterocyclics with antifungal activity was performed. The results reveals that a pyridine ring is more favorable than benzene as the 6-membered ring, for high activity, but thiazole is unfavorable as the 5-membered ring relative to imidazole or oxazole. Methylene is the spacer leading to the highest activity. The descriptors used are indicator variables, which account for identity of substituent, lipophilicity and volume of substituent, and total polarizability. Unlike previously reported results for this data set, our fits do not exceed the limitations set by the nature of the data itself.

  19. N-Heterocyclic-Carbene-Catalyzed Umpolung of Imines.

    PubMed

    Patra, Atanu; Mukherjee, Subrata; Das, Tamal Kanti; Jain, Shailja; Gonnade, Rajesh G; Biju, Akkattu T

    2017-03-01

    N-Heterocyclic carbene (NHC) catalysis has been widely used for the umpolung of aldehydes, and recently for the umpolung of Michael acceptors. Described herein is the umpolung of aldimines catalyzed by NHCs, and the reaction likely proceeds via aza-Breslow intermediates. The NHC-catalyzed intramolecular cyclization of aldimines bearing a Michael acceptor resulted in the formation of biologically important 2-(hetero)aryl indole 3-acetic-acid derivatives in moderate to good yields. The carbene generated from the bicyclic triazolium salt was found to be efficient for this transformation.

  20. 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.

  1. 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.

  2. Microbial degradation of poly(amino acid)s.

    PubMed

    Obst, Martin; Steinbüchel, Alexander

    2004-01-01

    Natural poly(amino acid)s are a group of poly(ionic) molecules (ionomers) with various biological functions and putative technical applications and play, therefore, an important role both in nature and in human life. Because of their biocompatibility and their synthesis from renewable resources, poly(amino acid)s may be employed for many different purposes covering a broad spectrum of medical, pharmaceutical, and personal care applications as well as the domains of agriculture and of environmental applications. Biodegradability is one important advantage of naturally occurring poly(amino acid)s over many synthetic polymers. The intention of this review is to give an overview about the enzyme systems catalyzing the initial steps in poly(amino acid) degradation. The focus is on the naturally occurring poly(amino acid)s cyanophycin, poly(epsilon-L-lysine) and poly(gamma-glutamic acid); but biodegradation of structurally related synthetic polyamides such as poly(aspartic acid) and nylons, which are known from various technical applications, is also included.

  3. 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.

  4. 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

    2016-06-06

    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.

  5. The Radio Spectra and - Inertial Defects Behavior of Planar Aromatic Heterocycles

    NASA Astrophysics Data System (ADS)

    McNaughton, Don; Jahn, Michaela K.; Grabow, Jens-Uwe; Godfrey, Peter; Travers, Michael; Wachsmuth, Dennis

    2016-06-01

    The simplest tricyclic aromatic nitrogen heterocyclic molecules 5,6 benzoquinoline and 7,8 benzoquinoline are possible candidates for detection of aromatic systems in the interstellar medium. Therefore the pure rotational spectra have been recorded using frequency-scanned Stark modulated, jet-cooled millimetre wave absorption spectroscopy (48-87 GHz) and Fourier Transform Microwave (FT MW) spectroscopy (2-26 GHz) of a supersonic rotationally cold molecular jet. Guided by ab initio molecular orbital predictions, spectral analysis of mm wave spectra, and higher resolution FT MW spectroscopy provided accurate rotational and centrifugal distortion constants together with 14N nuclear quadrupole coupling constants for both species. The determined inertial defects, along with those of similar species are used to develop an empirical formula for calculation of inertial defects of aromatic ring systems. The predictive ability of the formula is shown to be excellent for planar species with a number of pronounced out of plane vibrations. The resultant constants are of sufficient accuracy to be used in potential astrophysical searches. We gratefully acknowledge support from the Deutsche Forschungsgemeinschaft, the Deutsche Akademische Austauschdienst, as well as the Land Niedersachsen (J.-U.G). DMcN also thanks the Royal Society of Chemistry for their generous travel support.

  6. Chitosan Film Containing an Iron Complex: Synthesis and Prospects for Heterocyclic Aromatic Amines (HAAs) Recognition.

    PubMed

    da Silva, Maria Aparecida S; Abreu, Dieric S; Costa, Leandro A; Aguiar, Natanna de A; Paulo, Tércio F; Longhinotti, Elisane; Diógenes, Izaura C N

    2017-02-22

    Hybrid organic-inorganic materials have been seen as a promising approach to produce sensors for the detection and/or recognition of heterocyclic aromatic amines (HAAs). This work shows the synthesis of a hybrid film as a result of the incorporation of [Fe(CN)5(NH3)](3-) into chitosan (CS); CS-[(CN)5Fe(NH3)](3-). The sensitivity of CS-[(CN)5Fe(NH3)](3-) toward HAA-like species was evaluated by using pyrazine (pz) as probe molecule in vapor phase by means of electrochemistry and spectroscopic techniques. The crystallinity (SEM-EDS and XRD) decrease of CS-[(CN)5Fe(NH3)](3-) in comparison to CS was assigned to the disturbance of the hydrogen bond network within the polymer. Such conclusion was reinforced by the water contact angle measurements. The results presented in this work indicate physical and intermolecular interactions, mostly hydrogen bond, between [Fe(CN)5(NH3)](3-) and CS, where the complex is likely trapped in the polymer with its sixth coordination site available for substitution reactions.

  7. Computational study on fused five membered heterocyclic compounds containing tertiary oxygen

    NASA Astrophysics Data System (ADS)

    Dai, Yujie; Zhang, Tongcun; Piao, Ying'ai; Zhang, Xiuli; Hu, Yanying; Zhang, Liming; Jia, Shiru; He, Huixin

    2017-02-01

    The structure, stability and electronic properties of two fused five membered heterocyclic compounds containing tertiary oxygen have been investigated with quantum chemistry computation. The results show that 3H-4λ3-furo[1,2-a]furan (M1) and 2a1λ4-oxacyclopenta[cd]pentalene (M2) both own three Csbnd O bonds and especially in M2 the three Csbnd O bonds and angles are approximately identical. The two compounds are comparatively stable and M2 with three pentacycles is more stable than compound M1 according to the Csbnd O bond lengths, bond orders, Egap, electronegativity (χ), hardness (η), electrophilicity (ω), and aromaticity indexes. The aromaticity indexes such as NICS(0), NICS(1) and NICS(1)zz show that they both have strong aromaticity. The natural bonding orbital (NBO) analysis shows that oxygen atom takes hybrid orbitals composed of s and p orbital components to form σ(Csbnd O) bonds in compounds M1 and M2. The second order perturbation analysis shows that the occurrence of intramolecular charge transfer within the molecule exists in compound M1.

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

    NASA Astrophysics Data System (ADS)

    Tsyshevsky, Roman V.; Pagoria, Philip; Kuklja, Maija M.

    2017-01-01

    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 relationships between sensitivity and structures of explosives is a fundamental problem, which needs to be addressed to ensure successful design of new materials and improvements of existing energetics. In this paper, 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 interplay between the 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), the compound with high thermal stability, which is on predicted to be par or better than that of TATB.

  9. 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.

  10. Heterocyclic aramid nanoparticle-assisted graphene exfoliation for fabrication of pristine graphene-based composite paper

    NASA Astrophysics Data System (ADS)

    Mo, Yao; Liu, Qi; Fan, Jinchen; Shi, Penghui; Min, Yulin; Xu, Qunjie

    2015-07-01

    Mechanically strong, electrically conductive, and flexible pristine graphene-based composite paper was prepared based on heterocyclic aramid nanoparticle-assisted liquid-phase exfoliation of graphite. The macroscopic heterocyclic aramid yarns were split and assembled into heterocyclic aramid nanoparticles with the size of 30 nm by deprotonation in dimethylsulfoxide in the presence of potassium hydroxide. The obtained heterocyclic aramid nanoparticles dimethylsulfoxide dispersion was used as good medium solvent for highly efficiency liquid-phase exfoliation of graphite. The results demonstrated that the concentration of exfoliated graphene can facile reaches 2.72 mg/mL after direct sonication of 7 h with assist of heterocyclic aramid nanoparticles. After exfoliation, the self-assembled pristine graphene-based composite paper was fabricated by vacuum-assisted filtration. Due to the introduction of heterocyclic aramid nanoparticles, the self-assembled pristine graphene/heterocyclic aramid nanoparticles composite paper exhibited good mechanical property with tensile strength of 129.7 MPa, meantime, has a high electrical conductivity of 1.42 × 104 S/m.

  11. Thermal Decomposition and Stabilisation of Poly(vinyl Chloride)

    NASA Astrophysics Data System (ADS)

    Troitskii, B. B.; Troitskaya, L. S.

    1985-08-01

    The kinetics and mechanism of the thermal dehydrochlorination of poly(vinyl chloride) and low-molecular-weight chlorohydrocarbons which model various fragments of the polymer molecule, are discussed. Studies designed to determine the qualitative and quantitative compositions of the unstable fragments in poly(vinyl chloride) macromolecules by 13C NMR are examined. Attention is concentrated on the consideration of the mechanism of the action of the most effective thermostabilisers for the polymer - organotin compounds. The principal features of synergism in the stabilisation of poly(vinyl chloride) and the mechanism of the action of synergistic mixtures are analysed. The bibliography includes 107 references.

  12. 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

  13. Paternò-Büchi reaction between furan and heterocyclic aldehydes: oxetane formation vs. metathesis.

    PubMed

    D'Auria, Maurizio; Racioppi, Rocco; Viggiani, Licia

    2010-08-01

    The photochemical reaction of 2-substituted heterocyclic aldehydes with furan gave the corresponding exo oxetane derivatives through the excited triplet state. However, in situ the oxetane derivatives were converted through a metathesis reaction into the corresponding Z,E-butadienyl formate derivatives. On the contrary, 3-substituted heterocyclic aldehydes gave the corresponding exo oxetane derivatives. The effect of 2-substituted heterocyclic ring in order to facilitate the metathesis reaction is explained considering the possible participation of the pi aromatic orbitals in the oxetane C-O bond cleavage.

  14. 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.

  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. Electrical conductance of DNA molecules with varied density of itinerant pi electrons.

    PubMed

    Gao, Xu-Tuan; Fu, Xue; Mei, Liang-Mo; Xie, Shi-Jie

    2006-06-21

    The electrical transport of DNA is closely related to the density of itinerant pi electrons because of the strong electron-lattice interaction. The resistivities of two typical DNA molecules [poly(dG)-poly(dC) and lambda-DNA] with varied densities of itinerant pi electrons are calculated. It is found that the dependence of the resistivity on the density of itinerant pi electrons is symmetrical about the half-filling state of itinerant pi electrons in poly(dG)-poly(dC). At the half-filling state, the Peierls phase transition takes place and poly(dG)-poly(dC) has a large resistivity. When the density of itinerant pi electrons departs far from the half-filling state, the resistivity of poly(dG)-poly(dC) becomes small. For lambda-DNA, there is no Peierls phase transition due to the aperiodicity of its base pair arrangement. The resistivity of poly(dG)-poly(dC) decreases with increasing length of the molecular chain, but the resistivity of lambda-DNA increases with increasing length. The conducting mechanisms for poly(dG)-poly(dC) and a few lambda-DNA molecules with varied densities of itinerant pi electrons are analyzed.

  17. [Interaction of Dystamycin Dimeric Analog with Poly(dA) x poly(dT), Poly[d(A-T)] x poly[d(A-T)] and Duplex O23 at Origin of Replication of the Herpes Simplex Virus].

    PubMed

    Surovaya, A N; Bazhulina, N P; Lepehina, S Yu; Andronova, V L; Galegov, G A; Moiseeva, E D; Grokhovsky, S L; Gursky, G V

    2016-01-01

    The binding of distamycin dimeric analog (Pt-bis-Dst) to poly[d(A-T)] x poly[d(A-T)1, poly(dA) x poly(dT) and duplex O23 with the sequence 5'-GCCAATATATATATATTATTAGG-3' which is present at the origin of replication of herpes simplex virus OriS is investigated with the use of UV and CD spectroscopy. The distinction of the synthetic polyamide from a natural antibiotic lies in the fact that in the synthetic polyamide there are two distamycin moieties bound via a glycine cis-diamino platinum group. It was shown that the binding of Pt-bis-Dst to poly[d(A-T)] x poly[d(A-T)] and poly(dA) x poly(dT) reaches saturation if one molecule of the ligand occurs at approximately every 8 bp. With further increase in the ratio of the added ligand to the base pairs in CD spectra of complexes with poly[d(A-T)] x poly[d(A-T)], we observed that the maximum wavelength band tend to be shifted towards longer wavelengths, while in the spectral region of 290-310 nm a "shoulder", that was absent in the spectra of the complexes obtained at low polymer coverages by the ligand, appeared. At high molar concentration ratios of ligand to oligonucleotide Pt-bis-Dst can bind to poly[d(A-T)] x poly[d(A-T)] in the form of hairpins or may form associates by the interaction between the distamycin moieties of neighboring molecules of Pt-bis-Dst. The structure of the complexes is stabilized by interactions between pirrolcarboxamide moieties of two molecules of Pt-bis-Dst adsorbed on adjacent overlapping binding sites. These interactions are probably also responsible for the concentration-dependent spectral changes observed during the formation of a complex between Pt-bis-Dst and poly[d(A-T)] x poly[d(A-T)]. Spectral changes are almost absent in binding of Pt-bis-Dst to poly(dA) x poly(dT). Binding of Pt-bis-Dst to duplex O23 reaches saturation if two ligand molecules occur in a duplex that contains a cluster of 18 AT pairs. With increasing the molar concentration ratio of the ligand to the duplex CD

  18. 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 ...

  19. 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...

  20. Highly enantioselective [4 + 2] cyclization of chloroaldehydes and 1-azadienes catalyzed by N-heterocyclic carbenes.

    PubMed

    Jian, Teng-Yue; Sun, Li-Hui; Ye, Song

    2012-11-14

    Highly functionalized dihydropyridinones were synthesized via the N-heterocyclic carbene-catalyzed enantioselective [4 + 2] annulation of α-chloroaldehydes and azadienes. Hydrogenation of the resulted dihydropyridinones afforded the corresponding piperidinones with high enantiopurity.

  1. Rational design of bacitracin A derivatives by incorporating natural product derived heterocycles.

    PubMed

    Wagner, Björn; Schumann, Dirk; Linne, Uwe; Koert, Ulrich; Marahiel, Mohamed A

    2006-08-16

    Heterocycles display common structural motifs in nonribosomally produced peptides with an enormous impact on their bioactivity. In the case of the branched cyclic Bacitracin A, the thiazoline moiety is manufactured during NRPS peptide chain elongation. Here we describe a method to selectively alter the heterocyclic metal binding subunit of Bacitracin A by the synthesis of heterocyclic building blocks that were successfully coupled to the linear decapeptide and subsequently cyclized using the excised bacitracin PCP-TE bidomain. Utilization of this cyclase allowed the first generation of branched cyclic bacitracin derivatives containing thiazole and oxazoles. The generated bacitracin derivatives showed bactericidal activity, indicating the possibility of altering the biological important heterocyclic subunit and overcoming existing limitations for the application of bacitracin.

  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. Synthesis and biological evaluations of sulfa derivatives bearing heterocyclic moieties.

    PubMed

    Abdel-Monem, Wafaa R

    2004-01-01

    Some new sulfa derivatives bearing a heterocyclic moieties fural, pyrimidinone, thiazolidinone, benzimidazole and 1,2,4-triazinone and the related compounds 2-19 have been synthesized from treatment of sulfa drugs with thioisocyanate, acid chlorides, 3-chloro-1,2,4-triazines, aldehydes, esters and/or 2-methylbenzoxazole followed by ring closure reactions. Structures of the products have been deduced from their elemental analysis and spectral data. Significant antimicrobial activities were observed in vitro for some members of the series. Compounds 9b, 16 are highly active, while compounds 4b, 6d, 7,9a, 10 and 14 showing a moderate active towards gramme positive bacterium (b.subtilis). gramme negative bacterium (E. coli) and two fungi namely (A.nidulans & A.terreus).

  4. 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 (Cs2CO3 or K3PO4) 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.

  5. Aza-heterocyclic Receptors for Direct Electron Transfer Hemoglobin Biosensor.

    PubMed

    Kumar, Vinay; Kashyap, D M Nikhila; Hebbar, Suraj; Swetha, R; Prasad, Sujay; Kamala, T; Srikanta, S S; Krishnaswamy, P R; Bhat, Navakanta

    2017-02-07

    Direct Electron Transfer biosensors, facilitating direct communication between the biomolecule of interest and electrode surface, are preferable compared to enzymatic and mediator based sensors. Although hemoglobin (Hb) contains four redox active iron centres, direct detection is not possible due to inaccessibility of iron centres and formation of dimers, blocking electron transfer. Through the coordination of iron with aza-heterocyclic receptors - pyridine and imidazole - we report a cost effective, highly sensitive and simple electrochemical Hb sensor using cyclic voltammetry and chronoamperometry. The receptor can be either in the form of liquid micro-droplet mixed with blood or dry chemistry embedded in paper membrane on top of screen printed carbon electrodes. We demonstrate excellent linearity and robustness against interference using clinical samples. A truly point of care technology is demonstrated by integrating disposable test strips with handheld reader, enabling finger prick to result in less than a minute.

  6. Aza-heterocyclic Receptors for Direct Electron Transfer Hemoglobin Biosensor

    NASA Astrophysics Data System (ADS)

    Kumar, Vinay; Kashyap, D. M. Nikhila; Hebbar, Suraj; Swetha, R.; Prasad, Sujay; Kamala, T.; Srikanta, S. S.; Krishnaswamy, P. R.; Bhat, Navakanta

    2017-02-01

    Direct Electron Transfer biosensors, facilitating direct communication between the biomolecule of interest and electrode surface, are preferable compared to enzymatic and mediator based sensors. Although hemoglobin (Hb) contains four redox active iron centres, direct detection is not possible due to inaccessibility of iron centres and formation of dimers, blocking electron transfer. Through the coordination of iron with aza-heterocyclic receptors - pyridine and imidazole - we report a cost effective, highly sensitive and simple electrochemical Hb sensor using cyclic voltammetry and chronoamperometry. The receptor can be either in the form of liquid micro-droplet mixed with blood or dry chemistry embedded in paper membrane on top of screen printed carbon electrodes. We demonstrate excellent linearity and robustness against interference using clinical samples. A truly point of care technology is demonstrated by integrating disposable test strips with handheld reader, enabling finger prick to result in less than a minute.

  7. Aza-heterocyclic Receptors for Direct Electron Transfer Hemoglobin Biosensor

    PubMed Central

    Kumar, Vinay; Kashyap, D. M. Nikhila; Hebbar, Suraj; Swetha, R.; Prasad, Sujay; Kamala, T.; Srikanta, S. S.; Krishnaswamy, P. R.; Bhat, Navakanta

    2017-01-01

    Direct Electron Transfer biosensors, facilitating direct communication between the biomolecule of interest and electrode surface, are preferable compared to enzymatic and mediator based sensors. Although hemoglobin (Hb) contains four redox active iron centres, direct detection is not possible due to inaccessibility of iron centres and formation of dimers, blocking electron transfer. Through the coordination of iron with aza-heterocyclic receptors - pyridine and imidazole - we report a cost effective, highly sensitive and simple electrochemical Hb sensor using cyclic voltammetry and chronoamperometry. The receptor can be either in the form of liquid micro-droplet mixed with blood or dry chemistry embedded in paper membrane on top of screen printed carbon electrodes. We demonstrate excellent linearity and robustness against interference using clinical samples. A truly point of care technology is demonstrated by integrating disposable test strips with handheld reader, enabling finger prick to result in less than a minute. PMID:28169325

  8. N-Heterocyclic carbene metal complexes in medicinal chemistry.

    PubMed

    Oehninger, Luciano; Rubbiani, Riccardo; Ott, Ingo

    2013-03-14

    Metal complexes with N-heterocyclic carbene (NHC) ligands are widely used in chemistry due to their catalytic properties and applied for olefin metathesis among other reactions. The enhanced application of this type of organometallics has over the last few years also triggered a steadily increasing number of studies in the fields of medicinal chemistry, which take advantage of the fascinating chemical properties of these complexes. In fact it has been demonstrated that metal NHC complexes can be used to develop highly efficient metal based drugs with possible applications in the treatment of cancer or infectious diseases. Complexes of silver and gold have been biologically evaluated most frequently but also platinum or other transition metals have demonstrated promising biological properties.

  9. 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.

  10. Lactoperoxidase-catalyzed activation of carcinogenic aromatic and heterocyclic amines.

    PubMed

    Gorlewska-Roberts, Katarzyna M; Teitel, Candee H; Lay, Jackson O; Roberts, Dean W; Kadlubar, Fred F

    2004-12-01

    Lactoperoxidase, an enzyme secreted from the human mammary gland, plays a host defensive role through antimicrobial activity. It has been implicated in mutagenic and carcinogenic activation in the human mammary gland. The potential role of heterocyclic and aromatic amines in the etiology of breast cancer led us to examination of the lactoperoxidase-catalyzed activation of the most commonly studied arylamine carcinogens: 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), benzidine, 4-aminobiphenyl (ABP), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). In vitro activation was performed with lactoperoxidase (partially purified from bovine milk or human milk) in the presence of hydrogen peroxide and calf thymus DNA. Products formed during enzymatic activation were monitored by HPLC with ultraviolet and radiometric detection. Two of these products were characterized as hydrazo and azo derivatives by means of mass spectrometry. The DNA binding level of 3H- and 14C-radiolabeled amines after peroxidase-catalyzed activation was dependent on the hydrogen peroxide concentration, and the highest levels of carcinogen binding to DNA were observed at 100 microM H2O2. Carcinogen activation and the level of binding to DNA were in the order of benzidine > ABP > IQ > MeIQx > PhIP. One of the ABP adducts was identified, and the level at which it is formed was estimated to be six adducts/10(5) nucleotides. The susceptibility of aromatic and heterocyclic amines for lactoperoxidase-catalyzed activation and the binding levels of activated products to DNA suggest a potential role of lactoperoxidase-catalyzed activation of carcinogens in the etiology of breast cancer.

  11. 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

  12. Polyfunctional Lithium, Magnesium, and Zinc Alkenyl Reagents as Building Blocks for the Synthesis of Complex Heterocycles.

    PubMed

    Shen, Zhi-Liang; Dhayalan, Vasudevan; Benischke, Andreas D; Greiner, Robert; Karaghiosoff, Konstantin; Mayer, Peter; Knochel, Paul

    2016-04-18

    New conjunctive β-silylated organometallic reagents of Li, Mg, and Zn have been prepared and used for an expeditive construction of various polyfunctionalized 5-, 6-, and 7-membered heterocycles, such as furans, pyrroles, quinolines, benzo[b]thieno-[2,3-b]pyridine, naphthyridines, fused pyrazoles, and 2,3-dihydro-benzo[c]azepines. The latent silyl group has been converted into various carbon-carbon bonds in most heterocycle types.

  13. Construction of Polycyclic γ-Lactams and Related Heterocycles via Electron Catalysis

    PubMed Central

    2016-01-01

    Cascade radical cyclization of 1,6-enynes for the construction of biologically important polycyclic γ-lactams and related heterocycles is reported. In these radical cascade processes, three new C–C bonds are formed and transition metals are not required to run these sequences. The mild reaction conditions, broad substrate scope, and the importance of the heterocyclic products render the approach valuable. PMID:27978670

  14. 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

  15. Catalytic Aerobic Dehydrogenation of Nitrogen Heterocycles Using Heterogeneous Cobalt Oxide Supported on Nitrogen-Doped Carbon.

    PubMed

    Iosub, Andrei V; Stahl, Shannon S

    2015-09-18

    Dehydrogenation of (partially) saturated heterocycles provides an important route to heteroaromatic compounds. A heterogeneous cobalt oxide catalyst, previously employed for aerobic oxidation of alcohols and amines, is shown to be effective for aerobic dehydrogenation of various 1,2,3,4-tetrahydroquinolines to the corresponding quinolines. The reactions proceed in good yields under mild conditions. Other N-heterocycles are also successfully oxidized to their aromatic counterparts.

  16. Selective Access to Heterocyclic Sulfonamides and Sulfonyl Fluorides via a Parallel Medicinal Chemistry Enabled Method.

    PubMed

    Tucker, Joseph W; Chenard, Lois; Young, Joseph M

    2015-11-09

    A sulfur-functionalized aminoacrolein derivative is used for the efficient and selective synthesis of heterocyclic sulfonyl chlorides, sulfonyl fluorides, and sulfonamides. The development of a 3-step parallel medicinal chemistry (PMC) protocol for the synthesis of pyrazole-4-sulfonamides effectively demonstrates the utility of this reagent. This reactivity was expanded to provide rapid access to other heterocyclic sulfonyl fluorides, including pyrimidines and pyridines, whose corresponding sulfonyl chlorides lack suitable chemical stability.

  17. 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.

  18. Structural basis for the potent antisickling effect of a novel class of five-membered heterocyclic aldehydic compounds.

    PubMed

    Safo, Martin K; Abdulmalik, Osheiza; Danso-Danquah, Richmond; Burnett, James C; Nokuri, Samuel; Joshi, Gajanan S; Musayev, Faik N; Asakura, Toshio; Abraham, Donald J

    2004-09-09

    Naturally occurring five-membered heterocyclic aldehydes, including 5-hydroxymethyl-2-furfural, increase the oxygen affinity of hemoglobin (Hb) and strongly inhibit the sickling of homozygous sickle red blood (SS) cells. X-ray studies of Hb complexed with these compounds indicate that they form Schiff base adducts in a symmetrical fashion with the N-terminal alphaVal1 nitrogens of Hb. Interestingly, two cocrystal types were isolated during crystallization experiments with deoxygenated Hb (deoxyHb): one crystal type was composed of the low-affinity or tense (T) state Hb quaternary structure; the other crystal type was composed of high-affinity or relaxed state Hb (with a R2 quaternary structure). The R2 crystal appears to be formed as a result of the aldehydes binding to fully or partially ligated Hb in the deoxyHb solution. Repeated attempts to crystallize the compounds with liganded Hb failed, except on rare occasions when very few R state crystals were obtained. Oxygen equilibrium, high performance liquid chromatography (HPLC), antisickling, and X-ray studies suggest that the examined heterocyclic aldehydes may be acting to prevent polymerization of sickle hemoglobin (HbS) by binding to and stabilizing liganded Hb in the form of R2 and/or various relaxed state Hbs, as well as binding to and destabilizing unliganded T state Hb. The proposed mechanism may provide a general model for the antisickling effects of aldehyde containing small molecules that bind to N-terminal alphaVal1 nitrogens of Hb. The examined compounds also represent a new class of potentially therapeutic agents for treating sickle cell disease (SCD).

  19. The structures of heterocyclic complexes ruled by hydrogen bonds and halogen interactions: interaction strength and IR modes.

    PubMed

    Oliveira, Boaz G

    2014-04-24

    In this work, the existence of multiple interactions in heterocyclic complexes of C2H4O⋯nHCCl3 and C2H4S⋯nHCCl3 with n=2 and 3 was unveiled at the B3LYP/6-311++G(d,p) level of theory. The forward analyses of the vibrational spectra revealed the appearing of red-shifts in the H-C bond. In agreement with this and through the optimized geometries of these systems, an increase in the H-C bond length was also observed. Besides O⋯H and S⋯H, other hydrogen bonds formed between chlorine⋯hydrogen and mainly the halogen interactions formed by chlorine⋯chlorine were identified. Thereby, the vibration spectra of the heterocyclic complexes were reanalyzed with the purpose to locate new red-shifts, although only those characterized in H-C have been detected up to then. In addition to the correlation between the frequencies shifted to downward values followed by increases in the bond lengths, the interpretation of the red-shifts was conducted by means of the Bent rule of the hybridization theory. The interaction strength was examined in several viewpoints, and one of them was the relationship between the H-bond energies and the intermolecular electronic density computed by means of the Quantum Theory of Atoms in Molecules (QTAIM). Moreover, the prediction of the interaction strength was also made through the combination between vibration modes (red-shifts) and variation of topological parameters, such as the electronic density and Laplacian of the proton donor bond (C-H).

  20. 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.

  1. Poly(organophosphazenes) with azolylmethylphenoxy and pyridinoxy side groups to be used as proton exchange membranes in fuel cells

    NASA Astrophysics Data System (ADS)

    Ekanayake, Sujeewani K.

    2011-12-01

    Proton Exchange Membrane Fuel Cells (PEMFCs) are of great importance to many stationary and portable applications. The development of a more efficient, high-temperature tolerant membrane with a high protonic conductivity has become critical to the better performance of PEMFCs. Consequently, the focus of current research is more focused on synthesizing membranes which can function at a non-humidified high temperature environment. Because N-heterocycles such as azoles substituted on a polyphosphazene backbone have been found to be one of the best polymers in this regard, the focus of this dissertation is primarily on developing PEMs (proton exchange membranes) based on azole and pyridine substituted phosphazenes. In Chapter 1, an overview on PEMFCs as well as PEMs that have been synthesized to date is presented. The first part of the introduction is devoted to sulfonated fluorocarbon-based membrane, NafionRTM. Then the focus slowly shifts towards PEMs based on hydrocarbon polymers. The rest of Chapter 1 mainly revolves around polyphosphazene based PEMs. Chapter 2 describes the synthesis of trimeric, small-molecule, model compounds for high polymers. A series of hexakis(azolylmethylphenoxy)cyclotriphosphazenes where the azolyl groups are pyrazol, 1,2,4-triazol and 5-methyltetrazol and all three isomers of hexakis(pyridinoxy)cyclotriphosphazenes have been synthesized and characterized. The focus of Chapter 3 is on the synthesis of poly(dichlorophosphazene) by modifying a literature procedure reported by Wang (Macromolecules 2005, 38, 643--645) via one-pot in situ polycondensation. Chapter 3 also presents a preliminary study on ring opening polymerization. The focus of Chapter 4 is completely on the synthesis and characterization of azole and pyridine substituted polyphosphazenes. Chapter 5 includes film casting studies from both triazolphenol trimer and polymer to obtain corresponding composites and blends by mixing with commercially available poly(PMDA-ODA) amic acid

  2. 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.

  3. Effect of aliphatic, monocarboxylic, dicarboxylic, heterocyclic and sulphur-containing amino acids on Leishmania spp. chemotaxis.

    PubMed

    Diaz, E; Zacarias, A K; Pérez, S; Vanegas, O; Köhidai, L; Padrón-Nieves, M; Ponte-Sucre, A

    2015-11-01

    In the sand-fly mid gut, Leishmania promastigotes are exposed to acute changes in nutrients, e.g. amino acids (AAs). These metabolites are the main energy sources for the parasite, crucial for its differentiation and motility. We analysed the migratory behaviour and morphological changes produced by aliphatic, monocarboxylic, dicarboxylic, heterocyclic and sulphur-containing AAs in Leishmania amazonensis and Leishmania braziliensis and demonstrated that L-methionine (10-12 m), L-tryptophan (10-11 m), L-glutamine and L-glutamic acid (10-6 m), induced positive chemotactic responses, while L-alanine (10-7 m), L-methionine (10-11 and 10-7 m), L-tryptophan (10-11 m), L-glutamine (10-12 m) and L-glutamic acid (10-9 m) induced negative chemotactic responses. L-proline and L-cysteine did not change the migratory potential of Leishmania. The flagellum length of L. braziliensis, but not of L. amazonensis, decreased when incubated in hyperosmotic conditions. However, chemo-repellent concentrations of L-alanine (Hypo-/hyper-osmotic conditions) and L-glutamic acid (hypo-osmotic conditions) decreased L. braziliensis flagellum length and L-methionine (10-11 m, hypo-/hyper-osmotic conditions) decreased L. amazonensis flagellum length. This chemotactic responsiveness suggests that Leishmania discriminate between slight concentration differences of small and structurally closely related molecules and indicates that besides their metabolic effects, AAs play key roles linked to sensory mechanisms that might determine the parasite's behaviour.

  4. Complexes of poly-N-vinylpyrrolidone with sulfonated tetraphenylporphins

    SciTech Connect

    Kulvelis, Yu. V. Lebedev, V. T.; Toeroek, Gy.; Klyubin, V. V.

    2007-05-15

    The interaction of sulfonated tetraphenylporphins H{sub 2}TPPS{sub 4}(HCl){sub 2} and in CuTPPS{sub 4} with poly-N-vinylpyrrolidone (PVP) is studied using small-angle neutron scattering, dynamic light scattering, visible spectrophotometry, and viscometry. It is shown that porphyrin molecules form complexes with PVP, thus charging the polymeric chain.

  5. Poly(lactic acid) and poly(lactic-co-glycolic acid) particles as versatile carrier platforms for vaccine delivery.

    PubMed

    Pavot, Vincent; Berthet, Morgane; Rességuier, Julien; Legaz, Sophie; Handké, Nadège; Gilbert, Sarah C; Paul, Stéphane; Verrier, Bernard

    2014-12-01

    The development of safe and effective vaccines for cancer and infectious diseases remains a major goal in public health. Over the last two decades, controlled release of vaccine antigens and immunostimulant molecules has been achieved using nanometer or micron-sized delivery vehicles synthesized using biodegradable polymers. In addition to achieving a depot effect, enhanced vaccine efficacy using such delivery vehicles has been attributed to efficient targeting of antigen presenting cells such as dendritic cells. Biodegradable and biocompatible poly(lactic acid) and poly(lactic-co-glycolic acid) polymers belong to one such family of polymers that have been a popular choice of material used in the design of these delivery vehicles. This review summarizes research findings from ourselves and others highlighting the promise of poly(lactic acid)- and poly(lactic-co-glycolic acid)-based vaccine carriers in enhancing immune responses.

  6. Dietary exposure to heterocyclic amines in high-temperature cooked meat and fish in Malaysia.

    PubMed

    Jahurul, M H A; Jinap, S; Ang, S J; Abdul-Hamid, A; Hajeb, P; Lioe, H N; Zaidul, I S M

    2010-08-01

    The intake of heterocyclic amines is influenced by the amount and type of meat and fish ingested, frequency of consumption, cooking methods, cooking temperature, and duration of cooking. In this study, the dietary intake of heterocyclic amines in Malaysia and their main sources were investigated. Forty-two samples of meat and fish were analysed by high-performance liquid chromatography with photodiode array detector to determine the concentration of the six predominant heterocyclic amines, namely: 2-amino-3-methylimidazo[4,5-f] quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f] quinoline(MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline (4,8-DiMeIQx), 2-amino-3,7,8-trimethylimidazo[4,5-f] quinoxaline (7,8-DiMeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Dietary intake data were obtained using a food-frequency questionnaire when interviewing 600 Malaysian respondents. The level of total heterocyclic amines in food samples studies ranged from not detected to 38.7 ng g(-1). The average daily intake level of heterocyclic amine was 553.7 ng per capita day(-1). The intake of PhIP was the highest, followed by MeIQx and MeIQ. The results reveal that fried and grilled chicken were the major dietary source of heterocyclic amines in Malaysia. However, the heterocyclic amine intake by the Malaysian population was lower than those reported from other regions.

  7. 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.

  8. Sugars, alkaloids, and heteroaromatics: exploring heterocyclic chemistry with alkoxyallenes.

    PubMed

    Brasholz, Malte; Reissig, Hans-Ulrich; Zimmer, Reinhold

    2009-01-20

    As master craftsmen, modern synthetic chemists are challenged to achieve remarkable feats of efficiency and elegance toward molecular targets. The nature of this pursuit necessitates the collection of synthetic repertoires that are tried and true. With methodologies and pathways increasingly scrutinized, the adept chemist must seek out propitious tools to incorporate into the arsenal. With this in mind, this Account highlights the versatility of alkoxyallenes as precursors to valuable heterocyclic building blocks for such efforts as natural product synthesis. Accessed by the etherification of either propargyl alcohols or propargylic halides, alkoxyallenes are obtained after base-catalyzed isomerizations of the propargylic ethers. A host of umpolung synthons are available through this scheme after metalation, generating C(3) nucleophiles synthetically equivalent to vital anionic and zwitterionic synthons. Reactions with a diverse set of heteroatomic electrophiles yield carbohydrates, spiroketals, alkaloids, and heteroaromatics via [3 + 2] or [3 + 3] cyclizations. By employing lithiated alkoxyallenes into transformation routes, the natural product chemist can utilize this methodology as a viable resource in stereoselective synthesis. A survey of our own utilization of alkoxyallenes along synthetic pathways toward natural product targets reveals their suitability for generating advantageous precursors. A set of four stereoisomeric 2,6-dideoxyhexoses were stereoselectively obtained after an initial lithiated alkoxyallene and lactaldehyde cyclization, followed by the oxidative ring opening of the dihydrofurans. Through the addition of a lithiated alkoxyallene to a functionalized benzaldehyde, an essential spiroketal diastereomer was rapidly achieved in a few steps. We greatly benefitted from alkoxyallenes in the construction of complex nitrogen-containing synthetic targets, whether pyrrolidine alkaloids, substituted imidazole derivatives, or functionalized pyridines. A

  9. Can creatine supplementation form carcinogenic heterocyclic amines in humans?

    PubMed

    Pereira, Renato Tavares dos Santos; Dörr, Felipe Augusto; Pinto, Ernani; Solis, Marina Yazigi; Artioli, Guilherme Giannini; Fernandes, Alan Lins; Murai, Igor Hisashi; Dantas, Wagner Silva; Seguro, Antônio Carlos; Santinho, Mirela Aparecida Rodrigues; Roschel, Hamilton; Carpentier, Alain; Poortmans, Jacques Remi; Gualano, Bruno

    2015-09-01

    There is a long-standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs). This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, does not cause a significant increase in HCA formation. HCAs detection was unrelated to creatine supplementation. Diet was likely to be the main factor responsible for HCAs formation after either placebo (n = 6) or creatine supplementation (n = 3). These results directly challenge the recently suggested biological plausibility for the association between creatine use and risk of testicular germ cell cancer. Creatine supplementation has been associated with increased cancer risk. In fact, there is evidence indicating that creatine and/or creatinine are important precursors of carcinogenic heterocyclic amines (HCAs). The present study aimed to investigate the acute and chronic effects of low- and high-dose creatine supplementation on the production of HCAs in healthy humans (i.e. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx), 2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-b])pyridine (IFP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx)). This was a non-counterbalanced single-blind crossover study divided into two phases, in which low- and high-dose creatine protocols were tested. After acute (1 day) and chronic supplementation (30 days), the HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx were assessed through a newly developed HPLC-MS/MS method. Dietary HCA intake and blood and urinary creatinine were also evaluated. Out of 576 assessments performed (from 149 urine samples), only nine (3 from creatine and 6 from placebo) showed quantifiable levels of HCAs (8-MeIQx: n = 3; 4,8-DiMeIQx: n = 2; PhIP: n = 4). Individual analyses revealed that diet rather than creatine supplementation was

  10. New fluorescent heterocyclic systems from imidazo[1,2-a]pyridine: Design, synthesis, spectral studies and quantum-chemical investigations

    NASA Astrophysics Data System (ADS)

    Pordel, Mehdi; Chegini, Hamed; Ramezani, Shirin; Daee, Mohammadreza

    2017-02-01

    Two new fluorescent heterocyclic systems dipyrido[1‧,2‧:1,2]imidazo[4,5-b:4,5-e]pyridine-13-carbonitrile and pyrido[1‧,2‧:1,2]imidazo[4,5-b]pyrido[2‧,1‧:2,3]imidazo[4,5-e]pyridine-13-carbonitrile were synthesized by one-pot reaction of imidazo[1,2-a]pyridine with 2-(imidazo[1,2-a]pyridin-3-yl)acetonitrile and 2-(imidazo[1,2-a]pyridin-2-yl)acetonitrile, respectively, in MeOH/KOH solution via the nucleophilic substitution of hydrogen in high yields. Spectral and analytical data have confirmed the structures of the synthesized dyes. The optical and solvatochromic properties of the compounds were investigated and the results showed that they exhibited interesting photophysical properties. Density functional theory (DFT) calculations of fluorescent dyes were performed to provide the optimized geometries and relevant frontier orbitals by using the B3LYP hybrid functional and the 6-311 ++ G(d,p) basis set. Calculated electronic absorption spectra were also obtained by time-dependent density functional theory (TD-DFT) method. In addition, electron density iso-surface map, intra- and intermolecular interactions of these fluorescent heterocyclic systems were evaluated by AIM (Atoms in Molecules) analysis.

  11. Enumeration of 166 billion organic small molecules in the chemical universe database GDB-17.

    PubMed

    Ruddigkeit, Lars; van Deursen, Ruud; Blum, Lorenz C; Reymond, Jean-Louis

    2012-11-26

    Drug molecules consist of a few tens of atoms connected by covalent bonds. How many such molecules are possible in total and what is their structure? This question is of pressing interest in medicinal chemistry to help solve the problems of drug potency, selectivity, and toxicity and reduce attrition rates by pointing to new molecular series. To better define the unknown chemical space, we have enumerated 166.4 billion molecules of up to 17 atoms of C, N, O, S, and halogens forming the chemical universe database GDB-17, covering a size range containing many drugs and typical for lead compounds. GDB-17 contains millions of isomers of known drugs, including analogs with high shape similarity to the parent drug. Compared to known molecules in PubChem, GDB-17 molecules are much richer in nonaromatic heterocycles, quaternary centers, and stereoisomers, densely populate the third dimension in shape space, and represent many more scaffold types.

  12. 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.

  13. 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.

  14. Synthesis and cytotoxic potential of heterocyclic cyclohexanone analogues of curcumin.

    PubMed

    Yadav, Babasaheb; Taurin, Sebastien; Rosengren, Rhonda J; Schumacher, Marc; Diederich, Marc; Somers-Edgar, Tiffany J; Larsen, Lesley

    2010-09-15

    A series of 18 heterocyclic cyclohexanone analogues of curcumin have been synthesised and screened for their activity in both adherent and non-adherent cancer cell models. Cytotoxicity towards MBA-MB-231 breast cancer cells, as well as ability to inhibit NF-kappaB transactivation in non-adherent K562 leukemia cells were investigated. Three of these analogues 3,5-bis(pyridine-4-yl)-1-methylpiperidin-4-one B1, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidin-4-one B10, and 8-methyl-2,4-bis((pyridine-4-yl)methylene)-8-aza-bicyclo[3.2.1]octan-3-one C1 showed potent cytotoxicity towards MBA-MB-231, MDA-MB-468, and SkBr3 cell lines with EC50 values below 1 microM and inhibition of NF-kappaB activation below 7.5 microM. The lead drug candidate, B10, was also able to cause 43% of MDA-MB-231 cells to undergo apoptosis after 18 h. This level of activity warrants further investigation for the treatment of ER-negative breast cancer and/or chronic myelogenous leukemia as prototypical cellular models for solid and liquid tumors.

  15. Homobimetallic Ruthenium-N-Heterocyclic Carbene Complexes For Olefin Metathesis

    NASA Astrophysics Data System (ADS)

    Sauvage, Xavier; Demonceau, Albert; Delaude, Lionel

    In this chapter, the synthesis and catalytic activity towards olefin metathesis of homobimetallic ruthenium (Ru)-alkylidene, -cyclodiene or -arene complexes bearing phosphine or N-heterocyclic carbene (NHC) ligands are reviewed. Emphasis is placed on the last category of bimetallic compounds. Three representatives of this new type of molecular scaffold were investigated. Thus, [(p-cymene)Ru(m-Cl)3RuCl (h2-C2H4)(L)] complexes with L = PCy3 (15a), IMes (16a), or IMesCl2 (16b) were prepared. They served as catalyst precursors for cross-metathesis (CM) of various styrene derivatives. These experiments revealed the outstanding aptitude of complex 16a (and to a lesser extent of 16b) to catalyze olefin metathesis reactions. Contrary to monometallic Ru-arene complexes of the [RuCl2(p-cymene)(L)] type, the new homobimetallic species did not require the addition of a diazo compound nor visible light illumination to initiate the ring-opening metathesis of norbornene or cyclooctene. When diethyl 2,2-diallylmalonate and N,N-diallyltosylamide were exposed to 16a,b, a mixture of cycloisomerization and ring-closing metathesis (RCM) products was obtained in a nonselective way. Addition of phenylacetylene enhanced the metathetical activity while completely repressing the cycloisomerization process.

  16. CEC separation of heterocyclic amines using methacrylate monolithic columns.

    PubMed

    Barceló-Barrachina, Elena; Moyano, Encarnación; Puignou, Lluís; Galceran, Maria Teresa

    2007-06-01

    Two methacrylate-based monolithic columns, one with a negatively charged group (sulfonic group) and another with a new monomer N,N-dimethylamino ethyl acrylate (DMAEA), were prepared and tested for the separation of basic compounds by CEC. This new monolithic stationary phase was prepared by the in situ polymerization of DMAEA with butyl methacrylate and ethylene dimethacrylate, using a ternary porogenic solvent consisting of water, 1-propanol and 1,4-butanediol. The performance of this column was evaluated by means of the analysis of a family of heterocyclic amines. Separation conditions such as pH, amount of organic modifier, ionic strength and elution mode (normal or counterdirectional flow) were studied. At the optimal running electrolyte composition, and using the counterdirectional mode, symmetrical electrochromatographic peaks were obtained, with the number of theoretical plates up to 30,000 and a good resolution between closely related peaks. The 2-acrylamido-2-methyl-1-propane-sulfonic acid column was used for CEC-MS, taking advantage of the compatibility of its elution mode (normal flow) with the MS coupling.

  17. Synthesis and anti-leishmanial activity of heterocyclic betulin derivatives.

    PubMed

    Alakurtti, Sami; Heiska, Tuomo; Kiriazis, Alexandros; Sacerdoti-Sierra, Nina; Jaffe, Charles L; Yli-Kauhaluoma, Jari

    2010-02-15

    Betulin, a naturally occurring abundant triterpene is converted in four steps to 3,28-di-O-acetyllupa-12,18-diene. When various 4-substituted urazoles were oxidized to the corresponding urazines with iodobenzene diacetate in the presence of 3,28-di-O-acetyllupa-12,18-diene, new heterocyclic betulin derivatives were produced. These betulin derivatives were examined in a microplate assay at 50 microM for their ability to inhibit the growth of Leishmania donovani axenic amastigotes, a species that causes the fatal visceral leishmaniasis. GI(50) (concentration for 50% growth inhibition) values of the most effective compounds were determined and their cytotoxicity on the human macrophage cell line THP-1 evaluated. The anti-leishmanial activity on L. donovani amastigotes growing in macrophages was also examined. The heterocycloadduct between 3,28-di-O-acetyllupa-12,18-diene and 4-methylurazine was the most effective derivative with an GI(50)=8.9 microM against L. donovani amastigotes.

  18. Muscarinic receptor subtype selectivity of novel heterocyclic QNB analogues

    SciTech Connect

    Baumgold, J.; Cohen, V.I.; Paek, R.; Reba, R.C. )

    1991-01-01

    In an effort at synthesizing centrally-active subtype-selective antimuscarinic agents, the authors derivatized QNB (quinuclidinyl benzilate), a potent muscarinic antagonist, by replacing one of the phenyl groups with less lipophilic heterocyclic moieties. The displacement of ({sup 3}H)-N-methyl scopolamine binding by these novel compounds to membranes from cells expressing ml - m4 receptor subtypes was determined. Most of the novel 4-bromo-QNB analogues were potent and slightly selective for ml receptors. The 2-thienyl derivative was the most potent, exhibiting a 2-fold greater potency than BrQNB at ml receptors, and a 4-fold greater potency than BrQNB at ml receptors, and a 4-fold greater potency at m2 receptors. This compound was also considerably less lipophilic than BrQNB as determined from its retention time on C18 reverse phase HPLC. This compound may therefore be useful both for pharmacological studies and as a candidate for a radioiodinated SPECT imaging agent for ml muscarinic receptors in human brain.

  19. 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.

  20. Non-Directed Allylic C-H Acetoxylation in the Presence of Lewis Basic Heterocycles.

    PubMed

    Malik, Hasnain A; Taylor, Buck L H; Kerrigan, John R; Grob, Jonathan E; Houk, K N; Du Bois, J; Hamann, Lawrence G; Patterson, Andrew W

    2014-06-01

    We outline a strategy to enable non-directed Pd(II)-catalyzed C-H functionalization in the presence of Lewis basic heterocycles. In a high-throughput screen of two Pd-catalyzed C-H acetoxylation reactions, addition of a variety of N-containing heterocycles is found to cause low product conversion. A pyridine-containing test substrate is selected as representative of heterocyclic scaffolds that are hypothesized to cause catalyst arrest. We pursue two approaches in parallel that allow product conversion in this representative system: Lewis acids are found to be effective in situ blocking groups for the Lewis basic site, and a pre-formed pyridine N-oxide is shown to enable high yield of allylic C-H acetoxylation. Computational studies with density functional theory (M06) of binding affinities of selected heterocycles to Pd(OAc)2 provide an inverse correlation of the computed heterocycle-Pd(OAc)2 binding affinities with the experimental conversions to products. Additionally, (1)H NMR binding studies provide experimental support for theoretical calculations.

  1. Rapid synthesis of fused N-heterocycles by transition-metal-free electrophilic amination of arene C-H bonds.

    PubMed

    Gao, Hongyin; Xu, Qing-Long; Yousufuddin, Muhammed; Ess, Daniel H; Kürti, László

    2014-03-03

    We disclose an efficient and operationally simple protocol for the preparation of fused N-heterocycles starting from readily available 2-nitrobiaryls and PhMgBr under mild conditions. More than two dozen N-heterocycles, including two bioactive natural products, have been synthesized using this method. A stepwise electrophilic aromatic cyclization mechanism was proposed by DFT calculations.

  2. A conjugate Lewis base-Brønsted acid catalyst for the sulfenylation of nitrogen containing heterocycles under mild conditions.

    PubMed

    Nalbandian, Christopher J; Miller, Eric M; Toenjes, Sean T; Gustafson, Jeffery L

    2017-01-26

    Catalysts that contain a thiourea tethered to a carboxylic acid were found to affect the sulfenylation of indoles and other N-heterocycles on the hour time scale at room temperature. The mild nature of these conditions allowed for the incorporation of diverse functionalities into more complex heterocycles.

  3. Hybrid Catalysis Enabling Room-Temperature Hydrogen Gas Release from N-Heterocycles and Tetrahydronaphthalenes.

    PubMed

    Kato, Shota; Saga, Yutaka; Kojima, Masahiro; Fuse, Hiromu; Matsunaga, Shigeki; Fukatsu, Arisa; Kondo, Mio; Masaoka, Shigeyuki; Kanai, Motomu

    2017-02-15

    Hybrid catalyst systems to achieve acceptorless dehydrogenation of N-heterocycles and tetrahydronaphthalenes-model substrates for liquid organic hydrogen carriers-were developed. A binary hybrid catalysis comprising an acridinium photoredox catalyst and a Pd metal catalyst was effective for the dehydrogenation of N-heterocycles, whereas a ternary hybrid catalysis comprising an acridinium photoredox catalyst, a Pd metal catalyst, and a thiophosphoric imide organocatalyst achieved dehydrogenation of tetrahydronaphthalenes. These hybrid catalyst systems allowed for 2 molar equiv of H2 gas release from six-membered N-heterocycles and tetrahydronaphthalenes under mild conditions, i.e., visible light irradiation at rt. The combined use of two or three different catalyst types was essential for the catalytic activity.

  4. Synthesis of Oxygen Heterocycles via Aromatic C-O Bond Formation Using Arynes.

    PubMed

    Miyabe, Hideto

    2015-07-09

    Most of the synthetic approaches to the benzo-fused heterocycles containing an oxygen atom have involved the use of phenol derivatives as a starting material. This review highlights the new synthetic approaches involving the aromatic C-O bond-forming process using arynes. The insertion of arynes into the C=O bond gives the unstable intermediates, [2 + 2] cycloaddition-type adducts, which can be easily converted into a variety of oxygen atom-containing heterocycles in a single operation. In this review, the syntheses of oxygen heterocycles, such as coumarin, chromene, xanthene, dihydrobenzofuran and benzofuran derivatives, via the insertion of arynes into the C=O bond of aldehydes or formamides are summarized.

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

    PubMed

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

    2016-01-04

    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.

  6. Synthesis of Carbazoles and Carbazole-Containing Heterocycles via Rhodium-Catalyzed Tandem Carbonylative Benzannulations.

    PubMed

    Song, Wangze; Li, Xiaoxun; Yang, Ka; Zhao, Xian-liang; Glazier, Daniel A; Xi, Bao-min; Tang, Weiping

    2016-04-01

    Polycyclic aromatic compounds are important constituents of pharmaceuticals and other materials. We have developed a series of Rh-catalyzed tandem carbonylative benzannulations for the synthesis of tri-, tetra-, and pentacyclic heterocycles from different types of aryl propargylic alcohols. These tandem reactions provide efficient access to highly substituted carbazoles, furocarbazoles, pyrrolocarbazoles, thiophenocarbazoles, and indolocarbazoles. While tricyclic heterocycles could be derived from vinyl aryl propargylic alcohols, tetra- and pentacyclic heterocycles were synthesized from diaryl propargylic alcohols. The tandem carbonylative benzannulation is initiated by a π-acidic rhodium(I) catalyst-mediated nucleophilic addition to alkyne to generate a key metal-carbene intermediate, which is then trapped by carbon monoxide to form a ketene species for 6π electrocyclization. Overall, three bonds and two rings are formed in all of these tandem carbonylative benzannulation reactions.

  7. Synthesis, screening and docking of small heterocycles as glycogen phosphorylase inhibitors.

    PubMed

    Schweiker, Stephanie S; Loughlin, Wendy A; Lohning, Anna S; Petersson, Maria J; Jenkins, Ian D

    2014-09-12

    A series of morpholine substituted amino acids (phenylalanine, leucine, lysine and glutamic acid) was synthesized. A fragment-based screening approach was then used to evaluate a series of small heterocycles, including morpholine, oxazoline, dihydro-1,3-oxazine, tetrahydro-1,3-oxazepine, thiazoline, tetrahydro-1,3-pyrimidine, tetrahydro-1,3-diazepine and hexahydro-1H-benzimidazole, as potential inhibitors of Glycogen Phosphorylase a. Thiazoline 7 displayed an improved potency (IC50 of 25 μM) and had good LE and LELP values, as compared to heterocycles 1, 5, 9-13 and 19 (IC50 values of 1.1 mM-23.9 mM). A docking study using the crystal structure of human liver Glycogen Phosphorylase, provided insight into the interactions of heterocycles 5, 7, 9-13 and 19 with Glycogen Phosphorylase.

  8. 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.

  9. 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

  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. Palladium-Copper Catalyzed Alkyne Activation as an Entry to Multicomponent Syntheses of Heterocycles

    NASA Astrophysics Data System (ADS)

    Müller, Thomas J. J.

    Alkynones and chalcones are of paramount importance in heterocyclic chemistry as three-carbon building blocks. In a very efficient manner, they can be easily generated by palladium-copper catalyzed reactions: ynones are formed from acid chlorides and terminal alkynes, and chalcones are synthesized in the sense of a coupling-isomerization (CI) sequence from (hetero)aryl halides and propargyl alcohols. Mild reaction conditions now open entries to sequential and consecutive transformations to heterocycles, such as furans, 3-halo furans, pyrroles, pyrazoles, substituted and annelated pyridines, annelated thiopyranones, pyridimines, meridianins, benzoheteroazepines and tetrahydro-β-carbolines, by consecutive coupling-cyclocondensation or CI-cyclocondensation sequences, as new diversity oriented routes to heterocycles. Domino reactions based upon the coupling-isomerization reaction (CIR) have been probed in the synthesis of antiparasital 2-substituted quinoline derivatives and highly luminescent spiro-benzofuranones and spiro-indolones.

  12. Tetrahydrofuran, tetrahydropyran, triazoles and related heterocyclic derivatives as HIV protease inhibitors

    PubMed Central

    Ghosh, Arun K; Anderson, David D

    2011-01-01

    HIV/AIDS remains a formidable disease with millions of individuals inflicted worldwide. Although treatment regimens have improved considerably, drug resistance brought on by viral mutation continues to erode their effectiveness. Intense research efforts are currently underway in search of new and improved therapies. This review is concerned with the design of novel HIV-1 protease inhibitors that incorporate heterocyclic scaffolds and which have been reported within the recent literature (2005–2010). Various examples in this review showcase the essential role heterocycles play as scaffolds and bioisosteres in HIV-1 protease inhibitor drug development. This review will hopefully stimulate the widespread application of these heterocycles in the design of other therapeutic agents. PMID:21806380

  13. 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.

  14. Catalysis of Heterocyclic Azadiene Cycloaddition Reactions by Solvent Hydrogen Bonding: Concise Total Synthesis of Methoxatin.

    PubMed

    Glinkerman, Christopher M; Boger, Dale L

    2016-09-28

    Although it has been examined for decades, no general approach to catalysis of the inverse electron demand Diels-Alder reactions of heterocyclic azadienes has been introduced. Typically, additives such as Lewis acids lead to nonproductive consumption of the electron-rich dienophiles without productive activation of the electron-deficient heterocyclic azadienes. Herein, we report the first general method for catalysis of such cycloaddition reactions by using solvent hydrogen bonding of non-nucleophilic perfluoroalcohols, including hexafluoroisopropanol (HFIP) and trifluoroethanol (TFE), to activate the electron-deficient heterocyclic azadienes. Its use in promoting the cycloaddition of 1,2,3-triazine 4 with enamine 3 as the key step of a concise total synthesis of methoxatin is described.

  15. Synthesis and research of benzylamides of some isocyclic and heterocyclic acids as potential anticonvulsants.

    PubMed

    Strupińska, Marzanna; Rostafińska-Suchar, Grazyna; Pirianowicz-Chaber, Elzbieta; Stables, James P; Jiang, Jeff; Paruszewski, Ryszard

    2013-01-01

    A series of benzylamides of isocyclic and heterocyclic acids was synthesized and tested in Anticonvulsant Screening Project (ASP) of Antiepileptic Drug Development Program (ADDP) of NIH. Near all synthesized derivatives of heterocyclic acids showed activity. All obtained derivatives of mono- and bicyclic isocyclic acids were inactive. The power of action of heterocyclic acids derivatives seems does not depend upon kind of heteroatom (N, O or S). One of the compounds (2-furoic acid benzylamide (4)) appeared most promising. It showed in minimal clonic seizure (6Hz) test (ASP) in rats after i. p. administration: MES ED50 = 36.5 mg/kg, TOX TD50 = 269.75 mg/kg, and PI = 7.39.

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

    DOEpatents

    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.

  17. Temperature dependent formation of heterocyclic aromatic amine mutagens/carcinogens during the cooking of meats

    SciTech Connect

    Knize, M.G.; Salmon, C.P.; Dewhirst, K.P.

    1995-12-01

    A series of heterocyclic aromatic amines that have been shown to be mutagenic and carcinogenic have been found as cooking products of muscle meats. Amounts range from undetectable levels (less than 0.1 ppb) when meats are boiled, microwave cooked, and baked, to tens to hundreds of ppb for frying/grilling at high meat surface temperatures. Griddle surface temperatures of 150{degrees}C and frying ground beef patties for six min per side form a total of 0.7 ppb of four heterocyclic amines, and a temperature of 230{degrees}C for six min per side forms 15 ppb. Beef and chicken appear to form more of the heterocyclic amines than fish, in part due to traditional cooking practices.

  18. Novel poly-silicon nanowire field effect transistor for biosensing application.

    PubMed

    Hsiao, Cheng-Yun; Lin, Chih-Heng; Hung, Cheng-Hsiung; Su, Chun-Jung; Lo, Yen-Ren; Lee, Cheng-Che; Lin, Horng-Chin; Ko, Fu-Hsiang; Huang, Tiao-Yuan; Yang, Yuh-Shyong

    2009-01-01

    A simple and low-cost method to fabricate poly-silicon nanowire field effect transistor (poly-Si NW FET) for biosensing application was demonstrated. The poly-silicon nanowire (poly-Si NW) channel was fabricated by employing the poly-silicon (poly-Si) sidewall spacer technique, which approach was comparable with current commercial semiconductor process and forsaken expensive E-beam lithography tools. The electronic properties of the poly-Si NW FET in aqueous solution were found to be similar to those of single-crystal silicon nanowire field effect transistors reported in the literature. A model biotin and avidin/streptavidin sensing system was used to demonstrate the biosensing capacity of poly-Si NW FET. The changes of I(D)-V(G) curves were consistent with an n-type FET affected by a nearby negatively (streptavidin) and positively (avidin) charged molecules, respectively. Specific electric changes were observed for streptavidin and avidin sensing when nanowire surface of poly-Si NW FET was modified with biotin and streptavidin at sub pM to nM range could be distinguished. With its excellent electric properties and the potential for mass commercial production, poly-Si NW FET can be a very useful transducer for a variety of biosensing applications.

  19. Can creatine supplementation form carcinogenic heterocyclic amines in humans?

    PubMed Central

    Pereira, Renato Tavares dos Santos; Dörr, Felipe Augusto; Pinto, Ernani; Solis, Marina Yazigi; Artioli, Guilherme Giannini; Fernandes, Alan Lins; Murai, Igor Hisashi; Dantas, Wagner Silva; Seguro, Antônio Carlos; Santinho, Mirela Aparecida Rodrigues; Roschel, Hamilton; Carpentier, Alain; Poortmans, Jacques Remi; Gualano, Bruno

    2015-01-01

    Abstract Creatine supplementation has been associated with increased cancer risk. In fact, there is evidence indicating that creatine and/or creatinine are important precursors of carcinogenic heterocyclic amines (HCAs). The present study aimed to investigate the acute and chronic effects of low- and high-dose creatine supplementation on the production of HCAs in healthy humans (i.e. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx),  2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-b])pyridine (IFP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx)). This was a non-counterbalanced single-blind crossover study divided into two phases, in which low- and high-dose creatine protocols were tested. After acute (1 day) and chronic supplementation (30 days), the HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx were assessed through a newly developed HPLC–MS/MS method. Dietary HCA intake and blood and urinary creatinine were also evaluated. Out of 576 assessments performed (from 149 urine samples), only nine (3 from creatine and 6 from placebo) showed quantifiable levels of HCAs (8-MeIQx: n = 3; 4,8-DiMeIQx: n = 2; PhIP: n = 4). Individual analyses revealed that diet rather than creatine supplementation was the main responsible factor for HCA formation in these cases. This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, did not cause increases in the carcinogenic HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx in healthy subjects. These findings challenge the long-existing notion that creatine supplementation could potentially increase the risk of cancer by stimulating the formation of these mutagens. Key points There is a long-standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs). This study provides compelling evidence

  20. Additive-Free Pd-Catalyzed α-Allylation of Imine-Containing Heterocycles.

    PubMed

    Kljajic, Marko; Puschnig, Johannes G; Weber, Hansjörg; Breinbauer, Rolf

    2017-01-06

    An additive-free Pd-catalyzed α-allylation of different imino-group-ontaining heterocycles is reported. The activation of α-CH pronucleophiles (pKa (DMSO) > 25) occurs without the addition of strong bases or Lewis acids using only the Pd/Xantphos catalyst system. The reaction scope has been studied for various 5- and 6-membered nitrogen-containing heterocycles (yields up to 96%). Mechanistic investigations suggest an initial allylation of the imine-N followed by a Pd-catalyzed formal aza-Claisen rearrangement.

  1. Medium-Ring Nitrogen Heterocycles through Migratory Ring Expansion of Metalated Ureas.

    PubMed

    Hall, Jessica E; Matlock, Johnathan V; Ward, John W; Gray, Katharine V; Clayden, Jonathan

    2016-09-05

    Simple benzo-fused nitrogen heterocycles (indolines, tetrahydroquinolines, and their homologues) undergo migratory ring expansion through deprotonation of their benzylic urea derivatives with lithium diisopropylamide (LDA) in the presence of N,N'-dimethylpropylideneurea (DMPU). The products of the reactions are benzodiazepines, benzodiazocines, and their homologues, with ring sizes of 8-12. The reactions tolerate a range of substituent patterns and types, and may exhibit enantiospecificity or diastereoselectivity. Considerable complexity is rapidly generated in an efficient synthesis of these otherwise difficult-to-obtain medium-ring nitrogen heterocycles.

  2. 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.

  3. 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

  4. Additive-Free Pd-Catalyzed α-Allylation of Imine-Containing Heterocycles

    PubMed Central

    2016-01-01

    An additive-free Pd-catalyzed α-allylation of different imino-group-ontaining heterocycles is reported. The activation of α-CH pronucleophiles (pKa (DMSO) > 25) occurs without the addition of strong bases or Lewis acids using only the Pd/Xantphos catalyst system. The reaction scope has been studied for various 5- and 6-membered nitrogen-containing heterocycles (yields up to 96%). Mechanistic investigations suggest an initial allylation of the imine-N followed by a Pd-catalyzed formal aza-Claisen rearrangement. PMID:27936786

  5. 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.

  6. 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.

  7. Palladium-catalyzed α-arylation of carbonyls in the de novo synthesis of aromatic heterocycles

    PubMed Central

    Potukuchi, Harish K.; Spork, Anatol P.

    2015-01-01

    Aromatic heterocycles are a very well represented motif in natural products and have found various applications in chemistry and material science, as well as being commonly found in pharmaceutical agents. Thus, new and efficient routes towards this class of compound are always desirable, particularly if they expand the scope of chemical methodology or facilitate more effective pathways to complex substitution patterns. This perspective covers recent developments in the de novo synthesis of aromatic heterocycles via palladium-catalysed α-arylation reactions of carbonyls, which is itself a powerful transformation that has undergone significant development in recent years. PMID:25789887

  8. Coupling reactions of alpha-bromocarboxylate with non-aromatic N-heterocycles.

    PubMed

    Brychtova, Katerina; Slaba, Barbora; Placek, Lukas; Jampilek, Josef; Raich, Ivan; Csollei, Jozef

    2009-08-13

    The conditions for the C-N bond forming reaction (C-N coupling reaction) between alpha-bromocarboxylate and nitrogen-containing non-aromatic heterocyclic rings under heterogeneous copper(I) oxide catalysis are investigated in this paper. All the generated compounds were fully characterized by IR, NMR and MS spectroscopy. Ab initio/DFT calculations of partial charges on nitrogen atoms in all the discussed heterocycles and on C((2)) of carboxylate under applied conditions were predicted. These in silico results correlate relatively with the experimental observations.

  9. Ruthenium(II)-Catalyzed Regioselective Ortho Amidation of Imidazo Heterocycles with Isocyanates.

    PubMed

    Shakoor, S M Abdul; Kumari, Santosh; Khullar, Sadhika; Mandal, Sanjay K; Kumar, Anil; Sakhuja, Rajeev

    2016-12-16

    Direct ortho amidation at the phenyl ring of 2-phenylimidazo heterocycles with aryl isocyanates has been achieved via a chelation-assisted cationic ruthenium(II) complex catalyzed mechanism. The methodology provides a straightforward, high-yielding regioselective approach toward the synthesis of an array of ortho-amidated phenylimidazo heterocycles without prior activation of C(sp(2))-H. This also reports the first method for coupling of aryl isocyanates with the imidazo[1,2-a]pyridine system via a pentacyclometalated intermediate. The methodology is found to be easily scalable and could be applied toward the selective ortho amidation of 2-heteroarylimidazo[1,2-a]pyridine frameworks.

  10. Synthesis, antibacterial, and antiviral evaluation of new heterocycles containing the pyridine moiety.

    PubMed

    Salem, Marwa S; Sakr, Sameh I; El-Senousy, Waled M; Madkour, Hassan M F

    2013-10-01

    A facile one-pot four-component reaction was utilized to construct 2-oxo-1,2-dihydropyridine-3-carbonitrile as a scaffold for the synthesis of many fused heterocyclic systems, namely, furopyridine, pyridothiadiazepinthione, and pyridotriazine, as well as non-fused heterocyclic systems such as phthalazin-2(1H)-ylnicotinonitrile, pyridin-2-yl-1H-pyrazole, and pyrazol-1-ylnicotino-nitrile,1-(3-cyanopyridin-2-yl)-1H-pyrazole. The new compounds were evaluated as antimicrobial and antiviral agents.

  11. 1-Azadienes in cycloaddition and multicomponent reactions towards N-heterocycles.

    PubMed

    Groenendaal, Bas; Ruijter, Eelco; Orru, Romano V A

    2008-11-21

    1-Azadienes are versatile building blocks for the efficient construction of various N-heterocycles. Depending on the substitution pattern and reaction partner, they may participate in a range of different reactions. An overview of recent methods for the generation of 1-azadienes is presented, as well as their application in cycloaddition, electrocyclization, and multicomponent reactions. Considering the broad range of reactivities and resulting heterocyclic scaffold structures, 1-azadienes are very useful reactive intermediates for the development of modular reaction sequences in diversity-oriented synthesis.

  12. Multiplicity of Diverse Heterocycles from Polymer-Supported α-Acylamino Ketones

    PubMed Central

    Pudelová, Nadĕžda; Krchňák, Viktor

    2009-01-01

    Polymer-supported α-acylamino ketones were transformed to seven types of structurally unrelated heterocyclic compounds. Syntheses involved variety of chemical routes and comprised diverse chemistries (C-C, C=C, C-N, C=N, C-O bond formations). Different sizes of heterocycles (4-, 5-, 6-, and 7-membered rings) were prepared, including dihydro-pyrrol-2-ones, pyrazin-2-ones, dihydro-triazepin-6-ones, morpholin-3-ones, imidazoles, β-lactams, and isoquinolin-1-ones. Further elaboration to fused ring systems was also documented. PMID:19689103

  13. 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.

  14. Formation of heterocyclic amines during cooking of duck meat.

    PubMed

    Liao, G Z; Wang, G Y; Zhang, Y J; Xu, X L; Zhou, G H

    2012-01-01

    Heterocyclic amines (HAs) are an important class of food mutagens and carcinogens produced in meat cooked at high temperature. In the present study, the effects of various cooking methods: boiling, microwave cooking, charcoal-grilling, roasting, deep-frying and pan-frying on the formation of HAs in duck breast were studied. The various HAs formed during cooking were isolated by solid-phase extraction and analysed by HPLC. Results showed that both the varieties and contents of HAs and the cooking loss of duck breast increase along with increasing cooking temperature and time. Pan-fried duck breasts contained the highest amount of total HAs, followed by charcoal-grilling, deep-frying, roasting, microwave cooking and boiling. 9H-pyrido[3,4-b]indole (norharman) and 1-methyl-9H-pyrido[3,4-b]indole (harman) were detected in all of the cooked duck meat, with levels in the range of 0.1-33 ng g⁻¹. 2-Amino-1-methyl-6-phenylimidazo[4,5-f]pyridine (PhIP) was formed easily in duck meat cooked by pan-frying and charcoal-grilling in the range of 0.9-17.8 ng g⁻¹. 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) was identified in duck meat cooked by charcoal-grilling and pan-frying, in the range of 0.4-4.2 ng g⁻¹. 2-Amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) was detected in amounts below 4.5 ng g⁻¹ in duck meat cooked by charcoal-grilling, roasting, deep-frying and pan-frying. The other HAs were detected in amounts below 10 ng g⁻¹. Colour development increased with cooking temperature, but no correlation with HAs' content was observed.

  15. 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.

  16. Broadband Dielectric Study on Dynamics of Poly(vinyl pyrrolidone)-Poly(ethylene glycol) Blend

    NASA Astrophysics Data System (ADS)

    Tsubotani, S.; Sudo, S.; Nakamura, H.; Shinyashiki, N.; Yagihara, S.; Sengwa, R. J.

    2004-04-01

    Dielectric measurements for blends of poly(vinyl pyrrolidone) (PVP) (Mw=40,000) and poly(ethylene glycol) (PEG) (Mw=400) with various compositions were carried out in the frequency range of 1μHz to 10GHz and temperatures range between 298 and 173K. Three relaxation processes were observed above 298K. The high frequency process (h1 process) is caused by the chain motion of PEG, the middle frequency process (m process) is caused by the segmental motion of PVP chains, and the low frequency process is caused by ionic impurities in the mixture. The relaxation time of h1 process increased with decreasing temperature and separated into two processes at 253K. Moreover h1 process was separated again at 223K. The relaxation time of h1 process was 100s at 208K. The glass transition is attributed to the motion of unfrozen PEG molecules.

  17. Electronic transport in double-strand poly(dG)-poly(dC) DNA segments

    NASA Astrophysics Data System (ADS)

    Sarmento, R. G.; Albuquerque, E. L.; Sesion, P. D.; Fulco, U. L.; de Oliveira, B. P. W.

    2009-04-01

    We study the electronic properties of a double-strand quasiperiodic DNA molecule modeled by a one-dimensional effective Hamiltonian, which includes contributions from the nucleobasis system as well as the sugar-phosphate backbone. Our theoretical approach makes use of Dyson's equation together with a transfer-matrix treatment, considering an electronic tight-binding Hamiltonian model to investigate the electronic density of states (DOS) and the electronic transmissivity of sequences of DNA finite segments. To mimic the DNA segments, we consider the finite quasiperiodic sequences of Fibonacci's type, in a poly(dG)-poly(dC) configuration, whose building blocks are the bases guanine G and cytosine C. We compared the electronic transport found for the quasiperiodic structure to those using a sequence of natural DNA, as part of the human chromosome Ch22.

  18. 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 ...

  19. Crystal and molecular structure of a series of 15-crown-5-containing styryl heterocycles and their dimethoxy substituted analogues

    SciTech Connect

    Kuz'mina, L. G. Fedorova, O. A.; Andryukhina, E. N.; Mashura, M. M.; Gromov, S. P.; Alfimov, M. V.

    2006-05-15

    A comparative study of the molecular geometry and crystal packing of crown-containing styryl heterocycles and their dimethoxy substituted analogues is performed. It is established that all the compounds exhibit an identical type of distortions of the geometry of the central styryl fragment. These are the localization of the {pi}-electron density at the ethylene bond and the bond alternation in a half of the phenyl ring due to the conjugation of lone electron pairs of the oxygen substituents with the chromophore system of the molecule. A comparative analysis of the crystal packings of the compounds reveals extended separate hydrophilic and hydrophobic regions. The hydrophilic regions are built of crown ether fragments, and the hydrophobic regions consist of {pi}-conjugated and aromatic molecular fragments. The hydrophobic regions are characterized by a wide variety of packing motifs, among which stacking packing is absent. For two compounds, the formation of sandwich dimers that are preorganized to enter into the photochemical [2 + 2]cycloaddition reaction is observed.

  20. 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

  1. 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.

  2. Research on Aromatic Poly

    NASA Astrophysics Data System (ADS)

    Kiebooms, Rafael Hugo Ludo

    1995-11-01

    A detailed analysis of the literature indicated that substituents can only be used at the level of improving properties during processing, that end groups are only important for those polymers where the energy difference between the aromatic and quinoid structure is very small, and that stability of pi delocalisation is the most important tool for the design of low bandgap polymers. From our research it appeared that, based on a detailed NMR and FT-Raman analysis of oligomers and model compounds, the low band gap of PITN could be associated with the quinoid structure. However, a theoretical analysis of the UV-vis data of a series of aromatic isothianaphthene oligomers indicates that a substantial lowering of the band gap can be obtained in planar aromatic isothianaphthene systems. A parallel investigation of PTFITN, a soluble isothianaphthene analogue, gave some indications that this polymer should possess an aromatic structure. The aromatic structure makes it possible that the fluorines probably induce non planarity such that inter ring pi -conjugation is lowered to a considerable extent. This could explain the increased band gap of 2.1eV observed by Swann et al.^{[1] }. Analysis of a series of aza-analogues of PITN revealed that in these materials it should be possible to combine a planar aromatic geometry with enhanced processability. The 4,5-diaza and 4,7-diaza isothianaphthene polymers can therefore be considered as very promising low band gap materials. Finally, we showed that it is possible to combine the aromatic isothianaphthene ring system with another heterocycle such as thiophene in a formal copolymer. Through the development of a highly specific and efficient synthesis route to 1,3-dithienylisothianaphthene (DTI, 4), we established the basis for the further synthesis and study of formal copolymers with tailor-made electronic properties. ftn ^{[1]}M. J. Swann, G. Brooke, D. Bloor. Synth.Met., 55-57, 281-286, (1993).

  3. Recent developments on ultrasound-assisted one-pot multicomponent synthesis of biologically relevant heterocycles.

    PubMed

    Banerjee, Bubun

    2017-03-01

    Heterocycles are the backbone of organic compounds. Specially, N- &O-containing heterocycles represent privileged structural subunits well distributed in naturally occurring compounds with immense biological activities. Multicomponent reactions (MCRs) are becoming valuable tool for synthesizing structurally diverse molecular entities. On the other hand, the last decade has seen a tremendous outburst in modifying chemical processes to make them sustainable for the betterment of our environment. The application of ultrasound in organic synthesis is fulfilling some of the goals of 'green and sustainable chemistry' as it has some advantages over the traditional thermal methods in terms of reaction rates, yields, purity of the products, product selectivity, etc. Therefore the synthesis of biologically relevant heterocycles using one-pot multi-component technique coupled with the application of ultrasound is one of the thrusting areas in the 21st Century among the organic chemists. The present review deals with the "up to date" developments on ultrasound assisted one-pot multi-component synthesis of biologically relevant heterocycles reported so far.

  4. Acceptorless Dehydrogenation of N-Heterocycles by Merging Visible-Light Photoredox Catalysis and Cobalt Catalysis.

    PubMed

    He, Ke-Han; Tan, Fang-Fang; Zhou, Chao-Zheng; Zhou, Gui-Jiang; Yang, Xiao-Long; Li, Yang

    2017-03-06

    Herein, the first acceptorless dehydrogenation of tetrahydroquinolines (THQs), indolines, and other related N-heterocycles, by merging visible-light photoredox catalysis and cobalt catalysis at ambient temperature, is described. The potential applications to organic transformations and hydrogen-storage materials are demonstrated. Primary mechanistic investigations indicate that the catalytic cycle occurs predominantly by an oxidative quenching pathway.

  5. 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.

  6. Generation of (nonafluoro-tert-butoxy)methyl ponytails for enhanced fluorous partition of aromatics and heterocycles.

    PubMed

    Zhao, Xi; Ng, Wing Yan; Lau, Kai-Chung; Collis, Alana E C; Horváth, István T

    2012-03-21

    The reaction of sodium perfluoro-tert-butoxide with benzylic carbon-bromide bond(s) leads to the formation of (nonafluoro-tert-butoxy)methyl ponytail(s), which can enhance the fluorous solubility and partition of aromatics and heterocycles.

  7. 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...

  8. Lewis basicity modulation of N-heterocycles: a key for successful cross-metathesis.

    PubMed

    Lafaye, Kevin; Nicolas, Lionel; Guérinot, Amandine; Reymond, Sébastien; Cossy, Janine

    2014-10-03

    Cross-metathesis involving N-heteroaromatic olefinic derivatives is disclosed. The introduction of an appropriate substituent on the heteroaromatic ring decreases the Lewis basicity of the nitrogen atom, thus preventing the deactivation of the ruthenium-centered catalyst. The reaction is quite general in terms of both N-heterocycles and olefinic partners.

  9. 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.

  10. Bioactive Secondary Metabolites with Unique Aromatic and Heterocyclic Structures Obtained from Terrestrial Actinomycetes Species.

    PubMed

    Abdelfattah, Mohamed S; Arai, Midori A; Ishibashi, Masami

    2016-07-01

    Natural products from actinomycetes are important and valuable sources for drug discovery and the development of biological tools. The present review describes our recent study on the isolation of new natural products mainly possessing heterocyclic and aromatic ring structures with biological effects on cancer-related cellular pathways such as tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) and Wnt signaling.

  11. Acylsilanes in Iridium-Catalyzed Directed Amidation Reactions and Formation of Heterocycles via Siloxycarbenes.

    PubMed

    Becker, Peter; Pirwerdjan, Ramona; Bolm, Carsten

    2015-12-14

    Exposing ortho-amido aroylsilanes to visible light or heat leads to cyclization reactions that provide N-heterocyclic compounds via siloxycarbenes as key intermediates. The previously unreported starting materials have been prepared by directed amidations of aromatic acylsilanes in the presence of an iridium catalyst followed by N-alkylation.

  12. Synthesis of Nitrogen Heterocycles via Photochemical Ring Opening of Pyridazine N-Oxides.

    PubMed

    Portillo, Maribel; Maxwell, Michael A; Frederich, James H

    2016-10-07

    A photochemical method for the direct synthesis of 1H-pyrazoles from pyridazine N-oxides was developed. This chemistry features a regioselective approach to nonsymmetrically substituted pyridazine N-oxides. Herein, we highlight the first strategic use of photoinduced ring-opening reactions of 1,2-diazine N-oxides for the preparative synthesis of nitrogen heterocycles.

  13. A planar chiral [2.2]paracyclophane derived N-heterocyclic stannylene.

    PubMed

    Piel, Isabel; Dickschat, Julia V; Pape, Tania; Hahn, F Ekkehardt; Glorius, Frank

    2012-12-07

    The reaction of pseudo-ortho-4,12-N,N'-diphenyldiamino-[2.2]paracyclophane ((±)-3) with Sn[N(SiMe(3))(2)](2) results in the formation of the monomeric planar chiral N-heterocyclic stannylene (±)-4, featuring a unique [2.2]paracyclophane backbone, which has been characterized by an X-ray diffraction study.

  14. Synergism of the carbon-heterocyclic thion composition in the process of polyethylene thermooxidation

    NASA Astrophysics Data System (ADS)

    Struk, V. A.; Oparin, D. A.; Medved', A. V.; Orlovskii, S. V.; Gritsevich, A. I.

    2000-05-01

    It is shown by the methods of IR spectroscopy and differential thermal analysis that heterocyclic thions of thiophthalone, isoindoline, and phthalazine systems can be effectively used as inhibitors of thermooxidation of low-pressure charge-filled polyethylene. The effect of synergism of the thion-charge complex has been revealed. The possible mechanism of the protective action of these thions is discussed.

  15. 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...

  16. 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…

  17. Asymmetric Copper Hydride-Catalyzed Markovnikov Hydrosilylation of Vinylarenes and Vinyl Heterocycles

    PubMed Central

    2017-01-01

    We report a highly enantioselective CuH-catalyzed Markovnikov hydrosilylation of vinylarenes and vinyl heterocycles. This method has a broad scope and enables both the synthesis of isolable silanes and the conversion of crude products to chiral alcohols. Density functional theory calculations support a mechanism proceeding by hydrocupration followed by σ-bond metathesis with a hydrosilane. PMID:28117996

  18. "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...

  19. New Palladium-Catalyzed Approaches to Heterocycles and Carbocycles

    SciTech Connect

    Huang, Qinhua

    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 I2, ICl, PhSeCl, PhSCl and p-O2NC6H4SCl 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

  20. Paving the Way to Novel Phosphorus-Based Architectures: A Noncatalyzed Protocol to Access Six-Membered Heterocycles.

    PubMed

    Romero-Nieto, Carlos; López-Andarias, Alicia; Egler-Lucas, Carolina; Gebert, Florian; Neus, Jens-Peter; Pilgram, Oliver

    2015-12-21

    Phosphorus-based heterocycles provide access to materials with properties that are inaccessible from all-carbon architectures. The unique hybridization of phosphorus gives rise to electron-accepting capacities, a large variety of coordination reactions, and the possibility of controlling the electronic properties through phosphorus postfunctionalization. Herein, we describe a new noncatalyzed synthetic protocol to prepare fused six-membered phosphorus heterocycles. In particular, we report the synthesis of novel phosphaphenalenes. These fused systems exhibit the benefits of both five- and six-membered phosphorus heterocycles and enable a series of versatile postfunctionalization reactions. This work thus opens up new horizons in the field of conjugated materials.

  1. Recent advances in the synthesis of nitrogen heterocycles via radical cascade reactions using isonitriles as radical acceptors.

    PubMed

    Zhang, Bo; Studer, Armido

    2015-06-07

    Nitrogen heterocycles belong to a highly important class of compounds which are found in various natural products, biologically active structures, and medicinally relevant compounds. Therefore, there is continuing interest in the development of novel synthetic methods for the construction of nitrogen containing heterocycles. Recently, radical insertion reactions into isonitriles have emerged as an efficient and powerful strategy for the construction of nitrogen heterocycles, such as phenanthridines, indoles, quinolines, quinoxalines, and isoquinolines. This review highlights recent advances in this fast growing research area and also includes important pioneering studies in this area.

  2. 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.

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

    PubMed Central

    De Vreese, Rob

    2012-01-01

    Summary 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

  4. Dietary intake of heterocyclic amines and cancers of the esophagus and gastric cardia.

    PubMed

    Terry, Paul D; Lagergren, Jesper; Wolk, Alicja; Steineck, Gunnar; Nyrén, Olof

    2003-09-01

    The results of two epidemiological studies suggest that high intake of heterocyclic amines, which are formed on the surface of meats cooked at high temperatures, might be associated with increased risk of esophageal or cardia cancers. Our aim was to further investigate heterocyclic amine intake and risk of these cancers. We examined data from a nationwide, population-based, case-control study of risk factors for adenocarcinoma of the esophagus and gastric cardia and squamous cell carcinoma of the esophagus in Sweden, with 185, 258, and 165 cases, respectively, and 815 controls. Heterocyclic amine intake was estimated based on the frequency of consumption and degree of surface browning of commonly fried meats, and the consumption of pan juices. Statistically nonsignificant 50-70% higher risks of esophageal squamous cell carcinoma were observed among individuals in the highest quartile levels of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline, and 2-amino-1methyl-6-phenylimidazo[4,5-b]pyridine relative to those in the lowest. Dose-risk trends were evident. Subjects reporting high intake of all three heterocyclic amines had an odds ratio of 2.4 (95% confidence interval, 1.2-4.8) relative to those with low intake of all three substances. In contrast, no association was found with risk of adenocarcinoma of the esophagus or gastric cardia. Heterocyclic amine intake might be associated with an increase in risk of squamous cell carcinoma of the esophagus. Given the dearth of epidemiological data regarding these cancers and the lack of established biological mechanisms, confirmatory data are needed.

  5. The Sound of Silence: RNAi in Poly (ADP-Ribose) Research

    PubMed Central

    Blenn, Christian; Wyrsch, Philippe; Althaus, Felix R.

    2012-01-01

    Poly(ADP-ribosyl)-ation is a nonprotein posttranslational modification of proteins and plays an integral part in cell physiology and pathology. The metabolism of poly(ADP-ribose) (PAR) is regulated by its synthesis by poly(ADP-ribose) polymerases (PARPs) and on the catabolic side by poly(ADP-ribose) glycohydrolase (PARG). PARPs convert NAD+ molecules into PAR chains that interact covalently or noncovalently with target proteins and thereby modify their structure and functions. PAR synthesis is activated when PARP1 and PARP2 bind to DNA breaks and these two enzymes account for almost all PAR formation after genotoxic stress. PARG cleaves PAR molecules into free PAR and finally ADP-ribose (ADPR) moieties, both acting as messengers in cellular stress signaling. In this review, we discuss the potential of RNAi to manipulate the levels of PARPs and PARG, and consequently those of PAR and ADPR, and compare the results with those obtained after genetic or chemical disruption. PMID:24705085

  6. Switching the Biointerface of Displaceable Poly-p-xylylene Coatings.

    PubMed

    Guan, Zhen-Yu; Wu, Chih-Yu; Li, Yi-Jye; Chen, Hsien-Yeh

    2015-07-08

    A new class of functionalized poly-p-xylyene coating has been synthesized to provide switchable and displaceable surface properties for biomaterials. The switchability is achieved through a mechanism for detaching/attaching biomolecules and/or a mechanism through which the programmed restoration of functions or their replacement by other functions can be carried out. This advanced version of poly-p-xylylene comprises an integrated disulfide moiety within the functional side group, and the switching phenomenon between the immobilized functional molecules is triggered by the redox thiol-disulfide interchange reaction. These dynamically well-defined molecules on the surfaces respond simultaneously to altered biological properties and controlled biointerfacial functions, for example, switching wettability or reversibly altered cell adhesion activity. Poly-p-xylylenes are a key player in controlling surface properties for many important applications, such as medical implants, biosensors, bioMEMS devices, and microfluidics. The introduction of this new facet of poly-p-xylylenes enables the dynamic mimicry of biological functions relevant to the design of new biomaterials.

  7. 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.

  8. Influence of molecular environment on single-photon behavior of heterocyclic NLO chromophores and its implications for two-photon behavior

    NASA Astrophysics Data System (ADS)

    Baur, Jeffery W.; Alexander, Max D., Jr.; Banach, Michael J.; Reinhardt, Bruce A.; Prasad, Paras N.; Yaun, Lixiang; Vaia, Richard A.

    1998-10-01

    Over the past several years, organic molecules exhibiting significant two-photon absorbance have been of intense interest for a wide variety of applications including high speed communications, data storage, imaging, and optical limiting. However, it has been commonly observed that the local molecular environment can significantly affect the linear and nonlinear optical properties of the chromophores. In an effort to examine these effects, the influence of the solvent environment on the linear absorbance and photoluminescence of a series of donor-acceptor heterocyclic chromophores was examined. The Stoke's shift associated with one-photon absorbance and photoluminescence was observed to increase with increasing solvent polarity. This behavior is adequately described by the Lippert equation and is related to relaxation of the solvent molecules around an excited molecule. Additionally, it was observed that the spectral shape, as well as the solvent dependence, of two-photon and one-photon pumped photoluminescence were similar, thus indicating that the longest-lived luminescing excited state is independent of the method of excitation. These results have direct implications to two-photon applications which rely on up-converted fluorescence. They also yield insight into the structure-property relationships governing their linear and multi-photon behavior including the potential contributions to the effective two-photon cross-section from excited state absorbance.

  9. Solar CalPoly

    SciTech Connect

    Stannard, Sandra

    2016-06-15

    The target budget of INhouse was about $650,000 for all materials and student expenses of the Solar Decathlon competition. In order to reach our goal, Cal Poly students and faculty worked with the College of Architecture and Environmental Design’s External Relations office to actively fundraise for INhouse. Students connected with Cal Poly alumni through phone calls, postal mail, email, and live presentations to reach as many alumni in the state of California as possible. Before construction begun, students and faculty met on a weekly basis to determine what brands of materials for the home to use and who would be responsible for reaching out to the company to seek a donation. Our College of Architecture and Environmental Design’s administration was essential in helping us fundraise. For some time, the college was hoping to depend on about half of our fundraising expenses to be covered through the sale of INhouse. However, plans to sell the home fell through during the design development phase; the college turned to the sale of a different asset in to help us meet our goal. If we were to do this project again, completing the design concept and securing a future location of our home sooner would have enhanced our fundraising activities.

  10. 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%.

  11. 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.

  12. 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

  13. 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

    2013-04-02

    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.

  14. 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.

  15. 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

  16. The tert-amino effect in heterocyclic chemistry: synthesis of new fused pyrazolinoquinolizine and 1,4-oxazinopyrazoline derivatives.

    PubMed

    Prajapati, Dipak; Borah, Kalyan Jyoti

    2007-12-12

    The synthesis of novel fused heterocycles is based on reactions proceeding by the mechanism of the tert-amino effect, which generalizes cyclization of certain derivatives of 3-methyl-1-phenyl-2-pyrazolin-5-ones. Using this strategy a variety of fused heterocycles is obtained by the Knoevenagel condensation of 5-tert-amino-3-methyl-1-phenylpyrazolone-4-carboxal-dehyde 3 with active methylene compounds such as malononitrile and cyanoacetamide followed by cyclisation using anhydrous zinc chloride.

  17. Metal-free synthesis of N-fused heterocyclic iodides via C-H functionalization mediated by tert-butylhydroperoxide.

    PubMed

    Sharma, Krishna K; Patel, Dhananjay I; Jain, Rahul

    2015-10-21

    Direct, regioselective and metal-free synthesis of fused N-heterocyclic iodides is reported. This regioselective C-H functionalization is mediated by tert-butylhydroperoxide (TBHP), via dual activation of molecular iodine and a heterocyclic substrate, resulting in the in situ generation of electrophilic iodine species (I(+)), and free radical(s) (t)BuO˙ or (t)BuOO˙, driving the iodination reaction.

  18. Chemical Modification of Cyclodextrin and Amylose by Click Reaction and Its Application to the Synthesis of Poly-alkylamine-Modified Antibacterial Sugars.

    PubMed

    Yamamura, Hatsuo

    2017-01-01

    Cyclodextrin (CD) can be chemically modified into desired and sophisticated functional molecules. However, poly-modification often produces complicated mixtures, resulting in a low yield of the desired product. As the most promising procedure to solve such problems and to achieve poly-modification of the CD molecule, we present here the Huisgen 1,3-dipolar cycloaddition, known as a click reaction. This review will describe the results of our microwave-assisted click reaction for the poly-modification of CD and amylose molecules, and its application to the study of synthetic membrane active antibacterial derivatives.

  19. 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.

  20. Copper-Catalyzed Three-Component Annulations of Alkenes, Nitrosoarenes, and N-Hydroxyallylamines To Form Fused Oxazinane/Isoxazolidine Heterocycles.

    PubMed

    Kawade, Rahul Kisan; Liu, Rai-Shung

    2017-02-13

    One-pot cascade annulations among nitrosoarenes, alkenes, and N-hydroxyallylamines have been achieved with CuCl/O2 catalysts, forming fused oxazinane/isoxazolidine heterocycles with excellent diastereoselectivity (d.r. >20:1). To enhance the synthetic utility, we developed a successive cleavage of the two N-O bonds of the resulting heterocycles. A mechanism involving dipolar [3+2] cycloadditions of nitrone intermediates with their tethered alkenes is postulated for formation of these heterocycles.

  1. Formation of Ultracold Molecules

    SciTech Connect

    Cote, Robin

    2016-01-28

    Advances in our ability to slow down and cool atoms and molecules to ultracold temperatures have paved the way to a revolution in basic research on molecules. Ultracold molecules are sensitive of very weak interactions, even when separated by large distances, which allow studies of the effect of those interactions on the behavior of molecules. In this program, we have explored ways to form ultracold molecules starting from pairs of atoms that have already reached the ultracold regime. We devised methods that enhance the efficiency of ultracold molecule production, for example by tuning external magnetic fields and using appropriate laser excitations. We also investigates the properties of those ultracold molecules, especially their de-excitation into stable molecules. We studied the possibility of creating new classes of ultra-long range molecules, named macrodimers, thousand times more extended than regular molecules. Again, such objects are possible because ultra low temperatures prevent their breakup by collision. Finally, we carried out calculations on how chemical reactions are affected and modified at ultracold temperatures. Normally, reactions become less effective as the temperature decreases, but at ultracold temperatures, they can become very effective. We studied this counter-intuitive behavior for benchmark chemical reactions involving molecular hydrogen.

  2. Poly(L-aspartic acid) derivative soluble in a volatile organic solvent for biomedical application.

    PubMed

    Oh, Nam Muk; Oh, Kyung Taek; Youn, Yu Seok; Lee, Eun Seong

    2012-09-01

    In order to develop a novel functional poly(L-amino acid) that can dissolve in volatile organic solvents, we prepared poly[L-aspartic acid-g-(3-diethylaminopropyl)]-b-poly(ethylene glycol) [poly(L-Asp-g-DEAP)-b-PEG] via the conjugation of 3-diethylaminopropyl (DEAP) to carboxylate groups of poly(L-Asp) (M(n) 4 K)-b-PEG (M(n) 2 K). This poly(L-aspartic acid) derivative evidenced a relatively high solubility in volatile organic solvents such as dichloromethane, chloroform, and acetone. We fabricated a model nanostructure (i.e., polymeric micelle) using poly(L-Asp-g-DEAP)-b-PEG by the film rehydration method, which involves the simple removal of the volatile organic solvent (dichloromethane) used to dissolve polymer, reducing concerns about organic solvents remaining in a nano-sized particle. Interestingly, this micelle showed the pH-stimulated release of encapsulated model drug [i.e., doxorubicin (DOX)] due to the protonation of DEAP according to the pH of the solution. We expect that this poly(L-aspartic acid) derivative promises to provide pharmaceutical potential for constituting a new stimuli-sensitive drug carrier for various drug molecules.

  3. Single-Molecule Visualization of Living Polymerization

    DTIC Science & Technology

    2014-02-18

    siloxane bond†. Langmuir 24, 1343-1349 (2007). 4 M. Scholl, S. Ding, C. W. Lee & R. H. Grubbs. Synthesis and activity of a new generation of ruthenium ...Vougioukalakis & G. R. H. Ruthenium -based heterocyclic carbene-coordinated olefin metathesis catalysts. Chem Rev 110 (2010). 6 T. Lionnet, J. F. Allemand...2012). 10 X. Bantreil & S. P. Nolan. Synthesis of n-heterocyclic carbene ligands and derived ruthenium olefin metathesis catalysts. Nat Protoc 6, 69

  4. 1,3-Dien-5-ynes: Versatile Building Blocks for the Synthesis of Carbo- and Heterocycles.

    PubMed

    Aguilar, Enrique; Sanz, Roberto; Fernández-Rodríguez, Manuel A; García-García, Patricia

    2016-07-27

    1,3-Dien-5-ynes have been extensively used as starting materials for the synthesis of a wide number of different carbo- and heterocycles. The aim of this review is to give an overview of their utility in organic synthesis, highlighting the variety of compounds that can be directly accessed from single reactions over these systems. Thus, cycloaromatization processes are initially commented, followed by reactions directed toward the syntheses of five-membered rings, other carbocycles and, finally, heterocycles. The diverse methodologies that have been developed for the synthesis of each of these types of compounds from 1,3-dien-5-ynes are presented, emphasizing the influence of the reaction conditions and the use of additional reagents in the outcome of the transformations.

  5. 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.

  6. Physicochemical and Nonlinear Optical Properties of Novel Environmentally Benign Heterocyclic Azomethine Dyes: Experimental and Theoretical Studies

    PubMed Central

    Afzal, S. M.; Razvi, M. A. N.; Khan, Salman A.; Osman, Osman I.; Bakry, Ahmed H.; Asiri, Abdullah M.

    2016-01-01

    Novel heterocyclic azomethine dyes were prepared by the reaction of anthracene-9-carbaldehyde with different heterocyclic amines under microwave irradiation. Structures of the azomethine dyes were confirmed by the elemental analysis, mass spectrometry and several spectroscopic techniques. We studied absorbance and fluorescence spectra of the azomethine dyes in various solvents. They are found to be good absorbers and emitters. We also report photophysical properties like, extinction coefficient, oscillator strength, stokes shift and transition dipole moment. This reflects physicochemical behaviors of synthesized dyes. In addition, their intramolecular charge transfer and nonlinear optical properties, supported by natural bond orbital technique, were also studied computationally by density functional theory. The negative nonlinear refractive index and nonlinear absorption coefficient were measured for these dyes using the closed and open aperture Z-scan technique with a continuous wave helium-neon laser. These are found to vary linearly with solution concentration. PMID:27631371

  7. 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

  8. [How have we found any new reactions in the field of the heterocyclic chemistry?].

    PubMed

    Ikeda, Masazumi

    2004-04-01

    This review describes the discovery of new reactions in the field of heterocyclic chemistry. The reactions taken as typical examples involve 1) the photochemical ring transformations of quinolines to indole rings, 2) the ring transformations of indoles to quinazoline and quinoxaline rings, 3) the ring expansion reactions of indoles to 1H-1-benzazepines, 4) the intramolecular photo[2+2]cycloaddition reactions of 2- or 3-alkenyloxy-(or amino-)cyclohex-2-en-1-ones, 5) the syntheses of the nitrogen-containing heterocycles using the cyclizations of N-alkenylcarbamoylmethyl radicals, and 6) the general syntheses of bridged azabicyclic compounds using radical translocation/cyclization reactions. Modification of the water-soluble aminating agent hydroxylamine-O-sulfonic acid to the more powerful aminating agent O-mesitylenesulfonylhydroxylamine is also described.

  9. 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

  10. Carcinogenic heterocyclic amines in model systems and cooked foods: a review on formation, occurrence and intake.

    PubMed

    Skog, K I; Johansson, M A; Jägerstad, M I

    1998-01-01

    Frying or grilling of meat and fish products may generate low ppb levels of mutagenic/carcinogenic heterocyclic amines (HAs). Many heterocyclic amines are formed via the Maillard reaction from creatine, free amino acids and monosaccharides; compounds naturally occurring in protein-rich foods of animal origin. The formation and yield of HAs are dependent on physical parameters, such as cooking temperature and time, cooking technique and equipment, heat and mass transport, and on chemical parameters, especially the precursors to HAs. This paper reviews the current knowledge on the formation of HAs in cooked foods and model systems, and summarizes data on the content of HAs in various cooked foods, and estimates of the dietary intake of HAs. It should be noted that the presence of carcinogens of other types in food (e.g. nitrosamines, aromatic amines, cholesterol oxide products) and that their generation during frying and grilling are outside the scope of this review.

  11. Abiotic synthesis of purines and other heterocyclic compounds by the action of electrical discharges

    NASA Technical Reports Server (NTRS)

    Yuasa, S.; Flory, D.; Basile, B.; Oro, J.

    1984-01-01

    The synthesis of purines and pyrimidines using Oparin-Urey-type primitive earth atmospheres has been demonstrated by reacting methane, ethane, and ammonia in electrical discharges. Adenine, guaine, 4-aminoimidazole-5-carboxamide (AICA), and isocytosine have been identified by UV spectrometry and paper chromatography as the products of the reaction. The total yields of the identified heterocyclic compounds are 0.0023 percent. It is concluded that adenine synthesis occurs at a much lower concentration of hydrogen cyanide than has been shown by earlier studies. Pathways for the synthesis of purines from hydrogen cyanide are discussed, and a comparison of the heterocyclic compounds that have been identified in meteorites and in prebiotic reactions is presented.

  12. A simple route to phosphamethine cyanines from S,N-heterocyclic carbenes.

    PubMed

    Binder, Justin F; Corrente, Andrea M; Macdonald, Charles L B

    2016-02-07

    Although salts of thiazolium cations are known, many readily prepared iodide salts have eluded spectroscopic and structural characterization; herein, data for a variety of such salts are reported. It has been demonstrated that thiazolium cations can be deprotonated to generate S,N-heterocyclic carbenes and their "electron rich olefin" dimers, but use of the former has been largely overshadowed by that of the more common N-heterocyclic carbenes. We report herein that the deprotonation of thiazolium iodides and their subsequent reaction with a conveniently prepared triphosphenium precursor grants phosphamethine cyanine cations with solid-state geometry and electronic structure unlike those of NHC-stabilized cations. Protection of the phosphorus atom in such ions with elemental sulfur provides an air- and moisture-stable dithiophosphinium salt.

  13. 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.

  14. 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

  15. Biocatalysts for the formation of three- to six-membered carbo- and heterocycles.

    PubMed

    Lechner, Horst; Pressnitz, Desiree; Kroutil, Wolfgang

    2015-01-01

    During the last decade, the number of different types of enzymes applicable for organic synthesis as biocatalysts has significantly increased. Consequently, the spectrum of reactions has significantly expanded also for cyclisations. This review highlights heterologously expressable biocatalysts transforming non-natural substrates for the formation of three- to six-membered carbo- and heterocycles, excluding terpene cyclases as well as SAM-dependent enzymes. The review focuses on the non-natural substrate scope and the mechanism of the selected enzymes.

  16. Iron-Catalyzed C-H Alkylation of Heterocyclic C-H Bonds.

    PubMed

    Babu, Kaki Raveendra; Zhu, Nengbo; Bao, Hongli

    2017-01-06

    An efficient, iron-catalyzed C-H alkylation of benzothiazoles by using alkyl diacyl peroxides and alkyl tert-butyl peresters which are readily accessible from carboxylic acids to synthesize 2-alkylbenzothiazoles is developed. This reaction is environmentally benign and compatible with a broad range of functional groups. Various primary, secondary, and tertiary alkyl groups can be efficiently incorporated into diverse benzothiazoles. The effectiveness of this method is illustrated by late-stage functionalization of biologically active heterocycles.

  17. Rhodium-catalyzed intramolecular hydroarylation of 1-halo-1-alkynes: regioselective synthesis of semihydrogenated aromatic heterocycles.

    PubMed

    Murase, Hirohiko; Senda, Kousuke; Senoo, Masato; Hata, Takeshi; Urabe, Hirokazu

    2014-01-03

    The regioselective intramolecular hydroarylation of (3-halo-2-propynyl)anilines, (3-halo-2-propynyl) aryl ethers, or (4-halo-3-butynyl) aryl ethers was efficiently catalyzed by Rh2(OCOCF3)4 to give semihydrogenated aromatic heterocycles, such as 4-halo-1,2-dihydroquinolines, 4-halo-3-chromenes, or 4-(halomethylene)chromans, in good to excellent yields. Some synthetic applications taking advantage of the halo-substituents of the products are also illustrated.

  18. Tuning PCP-Ir complexes: the impact of an N-heterocyclic olefin.

    PubMed

    Iglesias, Manuel; Iturmendi, Amaia; Sanz Miguel, Pablo J; Polo, Victor; Pérez-Torrente, Jesús J; Oro, Luis A

    2015-08-11

    A new PCP-type ligand based on an N-heterocyclic olefin (NHO) scaffold has been prepared. The flexibility of this ligand, which is able to adopt facial coordination modes in Ir(I) or meridional in Ir(III) complexes, can be attributed to the dual nature (ylide-olefin) of the NHO scaffold. This results in a rare case of olefin "slippage" that is supported by X-ray crystallography and DFT calculations.

  19. N-Heterocyclic carbene-mediated oxidative esterification of aldehydes: ester formation and mechanistic studies.

    PubMed

    Maji, Biswajit; Vedachalan, Seenuvasan; Ge, Xin; Cai, Shuting; Liu, Xue-Wei

    2011-05-06

    An unexpected N-heterocyclic carbene-catalyzed esterification of α,β-unsaturated aldehydes including aromatic aldehydes with reactive cinnamyl bromides in the presence of air oxygen or MnO(2) as an oxidant is described. In the presence of oxygen, halogenated and electron-deficient aldehydes react smoothly to furnish esters in good yields. Great efforts have been made on mechanistic studies to deduce a plausible mechanism, based on the experimental results and isotopic labeling experiment.

  20. O,N,B-Containing eight-membered heterocycles by ring expansion of boroles with nitrones.

    PubMed

    Braunschweig, Holger; Krummenacher, Ivo; Mailänder, Lisa; Rauch, Florian

    2015-10-04

    By a ring expansion reaction of boroles with nitrones a straightforward route to eight-membered O,N,B-containing ring systems was developed, which present a new structural motif in heterocyclic chemistry. Formally, these compounds can be considered as BN-analogues of eight-membered ring ethers containing three double bonds. The X-ray crystallographic data of a series of these oxazaborocine derivatives show that they adopt a boat conformation in the solid state.

  1. 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)

  2. The flow synthesis of heterocycles for natural product and medicinal chemistry applications.

    PubMed

    Baumann, Marcus; Baxendale, Ian R; Ley, Steven V

    2011-08-01

    This article represents an overview of recent research from the Innovative Technology Centre in the field of flow chemistry which was presented at the FROST2 meeting in Budapest in October 2009. After a short introduction of this rapidly expanding field, we discuss some of our results with a main focus on the synthesis of heterocyclic compounds which we use in various natural product and medicinal chemistry programmes.

  3. 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

  4. Antioxidant Activity of Novel Fused Heterocyclic Compounds Derived from Tetrahydropyrimidine Derivative.

    PubMed

    Salem, Marwa Sayed; Farhat, Mahmoud; Errayes, Asma Omar; Madkour, Hassan Mohamed Fawzy

    2015-01-01

    6-(Benzo[d][1,3]dioxol-5-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile has been utilized for synthesis of the fused heterocyclic compounds namely thiazolopyrimidines, tetrazolopyrimidine, pyrimidoquinazoline, pyrimidothiazolopyrimidine, pyrimidothiazolotriazine and pyrrolothiazolopyrimidine derivatives. The newly synthesized compounds were characterized by IR, (1)H-NMR, (13)C-NMR, and mass spectral data. Antioxidant activities of all synthesized compounds were investigated.

  5. 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

  6. POLY-1,2,4-TRIAZOLES AND POLY-1,3,4-OXADIAZOLES FROM PRECURSOR POLY-N-ACYLHYDRAZIDINES,

    DTIC Science & Technology

    oxadiazole . Whereas, conversion of the precursor poly-N-acylhydrazidine predominantly to poly-1,2,4-triazole was affected by refluxing in solvents such... oxadiazole depending upon the heating rate. Poly-N-acylhydrazidine was of sufficient molecular weight to cast a clear yellow film which exhibited good...flexibility. The film, upon thermal treatment to temperatures as high as 300C, became brittle. The poly-1,3,4- oxadiazole and poly-1,2,4-triazole

  7. Effect of Aperiodicity on the Charge Transfer Through DNA Molecules

    NASA Astrophysics Data System (ADS)

    Ghosh, Angsula; Chaudhuri, Puspitapallab

    The effect of aperiodicity on the charge transfer process through DNA molecules is investigated using a tight-binding model. Single-stranded aperiodic Fibonacci polyGC and polyAT sequences along with aperiodic Rudin-Shapiro poly(GCAT) sequences are used in the study. Based on the tight-binding model, molecular orbital calculations of the DNA chains are performed and ionization potentials compared, as this might be relevant to understanding the charge transfer process. Charges migrate through the sequences in a multistep hopping process. Results for current conduction through aperiodic sequences are compared with those for the corresponding periodic sequences. We find that dinucleotide aperiodic Fibonacci sequences decrease the current while tetranucleotide aperiodic Rudin-Shapiro sequences increase the current when compared with the corresponding periodic sequences. The conductance in all cases decays exponentially as the sequence length increases.

  8. Solid-state synthesis of a conducting polythiophene via an unprecedented heterocyclic coupling reaction.

    PubMed

    Meng, Hong; Perepichka, Dmitrii F; Bendikov, Michael; Wudl, Fred; Pan, Grant Z; Yu, Wenjiang; Dong, Wenjian; Brown, Stuart

    2003-12-10

    Prolonged storage ( approximately 2 years) or gentle heating (50-80 degrees C) of crystalline 2,5-dibromo-3,4-ethylenedioxythiophene (DBEDOT) affords a highly conducting, bromine-doped poly(3,4-ethylenedioxythiophene) (PEDOT), as confirmed by solid-state NMR, FTIR, CV, and vis-NIR spectroscopies. The novel solid-state polymerization (SSP) does not occur for 2,5-dichloro-3,4-ethylenedioxythiophene (DCEDOT), and requires a much higher temperature (>130 degrees C) for 2,5-diiodo-3,4-ethylenedioxythiophene (DIEDOT). X-ray structural analysis of the above dihalothiophenes reveals short Hal.Hal distances between adjacent molecules in DBEDOT and DIEDOT, but not in DCEDOT. The polymerization may also occur in the melt but is significantly slower and leads to poorly conductive material. Detailed studies of the reaction were performed using ESR, DSC, microscopy, and gravimetric analyses. SSP starts on crystal defect sites; it is exothermic by 14 kcal/mol and requires activation energy of approximately 26 kcal/mol (for DBEDOT). The temperature dependence of the conductivity of SSP-PEDOT (sigma(rt) = 20-80 S/cm) reveals a slight thermal activation. It can be further increased by a factor of 2 by doping with iodine. Using this approach, thin films of PEDOT with conductivity as high as 20 S/cm were fabricated on insulating flexible plastic surfaces.

  9. 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

  10. Fluorocarbon and hydrocarbon N-heterocyclic (C5-C7) imidazole-based liquid crystals.

    PubMed

    Chen, Hongren; Hong, Fengying; Shao, Guang; Hang, Deyu; Zhao, Lei; Zeng, Zhuo

    2014-12-01

    By using three synthetic protocols, a series of fluorocarbon and hydrocarbon N-heterocyclic imidazole-based liquid crystals (LCs) and related imidazolium-based ionic liquid crystals (ILCs) have been prepared. The ring size of the N-heterocycle and the length of the N-terminal chain (on the imidazolium unit in the ILCs) were modified, and the influence of these structural parameters on liquid-crystal phases was investigated by means of polarizing optical microscopy (POM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). These new ILCs exhibit a disordered smectic phase (SmA), good thermal stabilities, a broad smectic phase range, a high dipole moment, relatively low melting points, but high clearing points and strong emission fluorescence relative to imidazole-based LCs. These encouraging results have led us to believe these fluorocarbon and hydrocarbon N-heterocyclic imidazole-based LCs and related imidazolium-based ILCs could be used as new liquid-crystalline materials.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. Role of Rydberg states in the photostability of heterocyclic dimers: the case of pyrazole dimer.

    PubMed

    Zilberg, Shmuel; Haas, Yehuda

    2012-11-26

    A new route for the nonradiative decay of photoexcited, H-bonded, nitrogen-containing, heterocyclic dimers is offered and exemplified by a study of the pyrazole dimer. In some of these systems the N(3s) Rydberg state is the lowest excited singlet state. This state is formed by direct light absorption or by nonradiative transition from the allowed ππ* state. An isomer of this Rydberg state is formed by H atom transfer to the other component of the dimer. The newly formed H-bonded radical pair is composed of two radicals (a H-adduct of pyrazole, a heterocyclic analogue of the NH(4) radical) and the pyrazolium π-radical. It is calculated to have a shallow local minimum and is the lowest point on the PES of the H-pyrazole/pyrazolium radical pair. This species can cross back to the ground state of the original dimer through a relatively small energy gap and compete with the H-atom loss channel, known for the monomer. In both Rydberg dimers, an electron occupies a Rydberg orbital centered mostly on one of the two components of the dimer. This Rydberg Center Shift (RCS) mechanism, proposed earlier (Zilberg, S.; Kahan, A.; Haas, Y. Phys. Chem. Chem. Phys. 2012, 14, 8836), leads to deactivation of the electronically excited dimer while keeping it intact. It, thus, may explain the high photostability of the pyrazole dimer as well as other heterocyclic dimers.

  16. The mouse immune response to the double stranded polyribonucleotide complex poly(G) . poly(C).

    PubMed Central

    Gaffiero, G V; Robin, P; Nahon, E

    1984-01-01

    Ten inbred strains of mice were immunized with the double stranded polyribonucleotide complex polyguanylic . polycytidylic acid [poly(G) . poly(C)]. While some immunogenic properties of this duplex were comparable to those of other nucleic acids antigens, differences were also noted. High (SJL/J, BALB/c), low (DBA/2, AKR) and intermediate responders were observed; these differences were not abolished by adsorption of the duplex to MBSA. This pattern of immune response is distinct both from that observed with two other synthetic polyribonucleotide double helices [poly(A) . poly(U) and poly(I) . poly(C)] and with single stranded DNA. The anti-poly(G) . poly(C) activity was localized in the 7S region, whether the sera came from high or low responders, from mice immunized with or without a carrier, after one or several injections. In contrast with anti-poly(A) . poly(U) sera which do not react with poly(G) . poly(C), anti-poly(G) . poly(C) exhibited poly(A) . poly(U) binding activity; no clear relationship between the two activities, however, could be demonstrated. Thus a series of immunological properties differentiates poly(G) . poly(C) not only from the natural polydeoxyribonucleotide single stranded DNA, but also, and more unexpectedly, from two other double stranded polyribonucleotide complexes. These observations suggest that the mechanism controlling the antibody response to poly(G) . poly(C) differs from that regulating poly(A) . poly(U) and/or poly(I) . poly(C), and are to be connected with the fact that the anti-poly(G) . poly(C) antibodies occurring in the sera of patients with systemic lupus erythematosus did not correlate with the antibody activities directed toward the other duplexes. PMID:6697564

  17. [Endothelial cell adhesion molecules].

    PubMed

    Ivanov, A N; Norkin, I A; Puchin'ian, D M; Shirokov, V Iu; Zhdanova, O Iu

    2014-01-01

    The review presents current data concerning the functional role of endothelial cell adhesion molecules belonging to different structural families: integrins, selectins, cadherins, and the immunoglobulin super-family. In this manuscript the regulatory mechanisms and factors of adhesion molecules expression and distribution on the surface of endothelial cells are discussed. The data presented reveal the importance of adhesion molecules in the regulation of structural and functional state of endothelial cells in normal conditions and in pathology. Particular attention is paid to the importance of these molecules in the processes of physiological and pathological angiogenesis, regulation of permeability of the endothelial barrier and cell transmigration.

  18. 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

  19. 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.

  20. Hydration of B-DNA: comparison between the water network around poly(dG).poly(dC) and poly(dG-dC).poly(dG-dC) on the basis of Monte Carlo computations.

    PubMed

    Eisenhaber, F; Tumanyan, V G; Eisenmenger, F; Gunia, W

    1989-03-01

    A computational method is elaborated for studying the water environment around regular polynucleotide duplexes; it allows rigorous structural information on the hydration shell of DNA to be obtained. The crucial aspect of this Monte Carlo simulation is the use of periodical boundary conditions. The output data consists of local maxima of water density in the space near the DNA molecule and the properties of one- and two-membered water bridges as function of pairs of polar groups of DNA. In the present paper the results for poly(dG).poly(dC) and poly(dG-dC).poly(dG-dC) are presented. The differences in their hydration shells are of a purely structural nature and are caused by the symmetry of the polar groups of the polymers under study, the symmetry being reflected by the hydration shell. The homopolymer duplex hydration shell mirrors the mononucleotide repeat. The water molecules contacting the polynucleotide in the minor groove are located nearly in the plane midway between the planes of successive base pairs. One water molecule per base pair forms a water bridge facing two polar groups of bases from adjacent base pairs and on different strands making a "spine"-like structure. In contrast, the major groove hydration is stabilized exclusively by two-membered water bridges; the water molecules deepest in the groove are concentrated near the plane of the corresponding base pair. The alternating polymer is characterized by a marked dyad symmetry of the hydration shell corresponding to the axis between two successive base pairs. The minor groove hydration of the dCpdG step resembles the characteristic features of the homopolymer, but the bridge between the O2 oxygens of the other base-stacking type is formed by two water molecules. The major groove hydration is characterized by high probability of one-membered water bridges and by localization of a water molecule on the dyad axis of the dGpdC step. The found structural elements are discussed as reasonable invariants of

  1. 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.

  2. 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.

  3. 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)

  4. 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.

  5. Excited state electronic structures and photochemistry of heterocyclic annulated perylene (HAP) materials tuned by heteroatoms: S, Se, N, O, C, Si, and B.

    PubMed

    Zhao, Guang-Jiu; Han, Ke-Li

    2009-04-23

    Time-dependent density functional theory (TDDFT) method was performed to investigate the excited state electronic structures and photochemistry of a variety of heterocyclic annulated perylene (HAP) materials. The calculated electronic structures and photochemical properties of the newly synthesized S-, Se-, and N-heterocyclic annulated perylenes were in good agreement with the experimental results. Moreover, the O-, C-, Si-, and B-heterocyclic annulated perylenes were also theoretically designed and investigated by using the same computational methods in this work. As a result, we found that the electronic structures and photochemical properties of S-, Se-, N-, O-, and C-heterocyclic annulated perylenes are similar to each other. The energy levels of the LUMO orbital for the S-, Se-, N-, O-, and C-heterocyclic annulated perylenes become higher than those of unsubstituted perylene. At the same time, the energy gaps between LUMO and HOMO for these heterocyclic annulated perylenes are also increased in comparison with those of unsubstituted perylene. Hence, both absorption and fluorescence spectra of S-, Se-, N-, O-, and C-heterocyclic annulated perylenes are correspondingly blue-shifted relative to those of unsubstituted perylene. In addition, two bonds formed by heteroatoms with perylene are lengthened in the electronic excited state of S-, Se-, N-, O-, and C-heterocyclic annulated perylenes. On the contrary, these bonds formed by heteroatoms with perylene are shortened in the electronic excited state of Si- and B-heterocyclic annulated perylenes. Furthermore, energy levels of the LUMO orbital for Si- and B-heterocyclic annulated perylenes become significantly lowered in comparison with that of unsubstituted perylene. At the same time, energy gaps between LUMO and HOMO for Si- and B-heterocyclic annulated perylenes become decreased relative to those of unsubstituted perylene. Thus, both absorption and fluorescence spectra of Si- and B-heterocyclic annulated

  6. Design, Synthesis, and Antibacterial Activities of Novel Heterocyclic Arylsulphonamide Derivatives.

    PubMed

    Singh, Anuradha; Srivastava, Ritika; Singh, Ramendra K

    2017-02-13

    Design, synthesis, and antibacterial activities of a series of arylsulphonamide derivatives as probable peptide deformylase (PDF) inhibitors have been discussed. Compounds have been designed following Lipinski's rule and after docking into the active site of PDF protein (PDB code: 1G2A) synthesized later on. Furthermore, to assess their antibacterial activity, screening of the compound was done in vitro conditions against Gram-positive and Gram-negative bacterial strains. In silico, studies revealed these compounds as potential antibacterial agents and this fact was also supported by their prominent scoring functions. Antibacterial results indicated that these molecules possessed a significant activity against Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli with MIC values ranging from 0.06 to 0.29 μM. TOPKAT results showed that high LD50 values and the compounds were assumed non-carcinogenic when various animal models were studied computationally.

  7. Porous organic molecules

    NASA Astrophysics Data System (ADS)

    Holst, James R.; Trewin, Abbie; Cooper, Andrew I.

    2010-11-01

    Most synthetic materials that show molecular-scale porosity consist of one-, two- or three-dimensional networks. Porous metal-organic frameworks in particular have attracted a lot of recent attention. By contrast, discrete molecules tend to pack efficiently in the solid state, leaving as little empty space as possible, which leads to non-porous materials. This Perspective discusses recent developments with discrete organic molecules that are porous in the solid state. Such molecules, which may be either crystalline or amorphous, can be categorized as either intrinsically porous (containing permanent covalent cavities) or extrinsically porous (inefficiently packed). We focus on the possible advantages of organic molecules over inorganic or hybrid systems in terms of molecular solubility, choice of components and functionalities, and structural mobility and responsiveness in non-covalent extended solids. We also highlight the potential for 'undiscovered' porous systems among the large number of cage-like organic molecules that are already known.

  8. Interactions of sodium montmorillonite with poly(acrylic acid).

    PubMed

    Tran, Nguyen H; Dennis, Gary R; Milev, Adriyan S; Kannangara, G S Kamali; Wilson, Michael A; Lamb, Robert N

    2005-10-15

    The chemical-structural modifications of the natural clay sodium montmorillonite during interaction with poly(acrylic acid) were studied mainly by X-ray photoemission spectroscopy. Samples of modified montmorillonite were prepared from the reaction of sodium montmorillonite ( approximately 0.5 g) and an aqueous solution of poly(acrylic acid) (pH approximately 1.8, 50 g) at varying temperatures. X-ray diffraction indicated that the montmorillonite interlayer space ( approximately 13 A), formed by regular stacking of the silicate layers (dimension approximately 1x1000 nm), expanded to approximately 16 A as the reaction was carried out at room temperature and at 30 degrees C. At 60 degrees C, the interlayer space further expanded to approximately 20 A. The results of X-ray photoemission spectroscopy indicated that poly(acrylic acid) molecules exchange sodium ions on the surface of the silicate layers. These combined results allowed development of a reaction model that explains the dependency of the interlayer expansion with temperature. Information concerning the surface chemical reactions and systematic increases in the interlayer distances is particularly useful if montmorillonite and poly(acrylic acid) are to be used for formation of nanocomposite materials.

  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. 21 CFR 177.1635 - Poly(p-methylstyrene) and rubber-modified poly(p-methyl-styrene).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Poly(p-methylstyrene) and rubber-modified poly(p... Poly(p-methylstyrene) and rubber-modified poly(p-methyl-styrene). Poly(p-methylstyrene) and rubber... purposes of this section, poly(p-methylstyrene) and rubber-modified poly(p-methylstyrene) are...

  11. 21 CFR 177.1635 - Poly(p-methylstyrene) and rubber-modified poly(p-methyl-styrene).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Poly(p-methylstyrene) and rubber-modified poly(p... Poly(p-methylstyrene) and rubber-modified poly(p-methyl-styrene). Poly(p-methylstyrene) and rubber... purposes of this section, poly(p-methylstyrene) and rubber-modified poly(p-methylstyrene) are...

  12. 21 CFR 177.1635 - Poly(p-methylstyrene) and rubber-modified poly(p-methyl-styrene).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Poly(p-methylstyrene) and rubber-modified poly(p... Poly(p-methylstyrene) and rubber-modified poly(p-methyl-styrene). Poly(p-methylstyrene) and rubber... purposes of this section, poly(p-methylstyrene) and rubber-modified poly(p-methylstyrene) are...

  13. 21 CFR 177.1635 - Poly(p-methylstyrene) and rubber-modified poly(p-methyl-styrene).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Poly(p-methylstyrene) and rubber-modified poly(p... Poly(p-methylstyrene) and rubber-modified poly(p-methyl-styrene). Poly(p-methylstyrene) and rubber... purposes of this section, poly(p-methylstyrene) and rubber-modified poly(p-methylstyrene) are...

  14. Poly(citric acid)-block-poly(ethylene glycol) copolymers--new biocompatible hybrid materials for nanomedicine.

    PubMed

    Naeini, Ashkan Tavakoli; Adeli, Mohsen; Vossoughi, Manouchehr

    2010-08-01

    Linear-dendritic ABA triblock copolymers containing poly(ethylene glycol) (PEG) as B block and hyperbranched poly(citric acid) (PCA) as A blocks were synthesized through polycondensation. The molecular self-assembly of synthesized PCA-PEG-PCA copolymers in water led to formation of nanoparticles and fibers in different sizes and shapes depending on the time and size of PCA blocks. Ten days after dissolving PCA-PEG-PCA copolymers in water, the size of fibers had reached several millimeters. Mixing a water solution of fluorescein as a small guest molecule and PCA-PEG-PCA copolymers led to the encapsulation of fluorescein by products of molecular self-assembly. To investigate their potential application in nanomedicine and to understand the limitations and capabilities of these materials as nanoexcipients in biological systems, different types of short-term in vitro cytotoxicity experiments on the HT1080 cell line (human fibrosarcoma) and hemocompatibility tests were performed. From the clinical editor: This manuscript investigates the potentials of linear-dendritic ABA triblock copolymers containing poly(ethylene glycol) (PEG) as B block and hyperbranched poly(citric acid) (PCA) as A blocks for future applications in nanomedicine.

  15. An improved surface passivation method for single-molecule studies.

    PubMed

    Hua, Boyang; Han, Kyu Young; Zhou, Ruobo; Kim, Hajin; Shi, Xinghua; Abeysirigunawardena, Sanjaya C; Jain, Ankur; Singh, Digvijay; Aggarwal, Vasudha; Woodson, Sarah A; Ha, Taekjip

    2014-12-01

    We report a surface passivation method based on dichlorodimethylsilane (DDS)-Tween-20 for in vitro single-molecule studies, which, under the conditions tested here, more efficiently prevented nonspecific binding of biomolecules than the standard poly(ethylene glycol) surface. The DDS-Tween-20 surface was simple and inexpensive to prepare and did not perturb the behavior and activities of tethered biomolecules. It can also be used for single-molecule imaging in the presence of high concentrations of labeled species in solution.

  16. 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.

  17. Stability of Water/Poly(ethylene oxide)43-b-poly(ε-caprolactone)14/Cyclohexanone Emulsions Involves Water Exchange between the Core and the Bulk.

    PubMed

    Flores, Mario E; Martínez, Francisco; Olea, Andrés F; Shibue, Toshimichi; Sugimura, Natsuhiko; Nishide, Hiroyuki; Moreno-Villoslada, Ignacio

    2015-12-31

    The formation of emulsions upon reverse self-association of the monodisperse amphiphilic block copolymer poly(ethylene oxide)43-b-poly(ε-caprolactone)14 in cyclohexanone is reported. Such emulsions are not formed in toluene, chloroform, or dichloromethane. We demonstrate by magnetic resonance spectroscopy the active role of the solvent on the stabilization of the emulsions. Cyclohexanone shows high affinity for both blocks, as predicted by the Hansen solubility parameters, so that the copolymer chains are fully dissolved as monomeric chains. In addition, the solvent is able to produce hydrogen bonding with water molecules. Water undergoes molecular exchange between water molecules associated with the polymer and water molecules associated with the solvent, dynamics of major importance for the stabilization of the emulsions. Association of polymeric chains forming reverse aggregates is induced by water over a concentration threshold of 5 wt %. Reverse copolymer aggregates show submicron average hydrodynamic diameters, as seen by dynamic light scattering, depending on the polymer and water concentration.

  18. A comparative study on poly(xylitol sebacate) and poly(glycerol sebacate): mechanical properties, biodegradation and cytocompatibility.

    PubMed

    Li, Yuan; Huang, Wenchao; Cook, Wayne D; Chen, Qizhi

    2013-06-01

    In order to develop degradable elastomers with a satisfactory combination of flexibility and enzyme-mediated degradation rate, the mechanical properties, enzymatic degradation kinetics and biocompatibility of poly(xylitol sebcate) (PXS) has been systematically investigated in comparison with poly(glycerol sebacate) (PGS). Under the same level of crosslinked density, the PXS elastomer networks have approximately twice the stretchability (elongation at break) of their PGS counterparts. This observation is attributable to the relatively longer and more orientable xylitol monomers, compared with glycerol molecules. Although xylitol monomers have two more hydroxyl groups, we, surprisingly, found that the hydrophilic side chains did not accelerate the water attack on the ester bonds of the PXS network, compared with their PGS counterpart. This observation was attributed to a steric hindrance effect, i.e. the large-sized hydroxyl groups can shield ester bonds from the attack of water molecules. In conclusion, the use of polyols of more than three -OH groups is an effective approach enhancing flexibility, whilst maintaining the degradation rate of polyester elastomers. Further development could be seen in the copolymerization of PPS with appropriate thermoplastic polyesters, such as poly(lactic acid) and polyhydroxyalkanoate.

  19. Dynamics of Activated Molecules

    SciTech Connect

    Mullin, Amy S.

    2016-11-16

    Experimental studies have been performed to investigate the collisional energy transfer processes of gas-phase molecules that contain large amounts of internal energy. Such molecules are prototypes for molecules under high temperature conditions relevant in combustion and information about their energy transfer mechanisms is needed for a detailed understanding and modeling of the chemistry. We use high resolution transient IR absorption spectroscopy to measure the full, nascent product distributions for collisions of small bath molecules that relax highly vibrationally excited pyrazine molecules with E=38000 cm-1 of vibrational energy. To perform these studies, we developed new instrumentation based on modern IR light sources to expand our experimental capabilities to investigate new molecules as collision partners. This final report describes our research in four areas: the characterization of a new transient absorption spectrometer and the results of state-resolved collision studies of pyrazine(E) with HCl, methane and ammonia. Through this research we have gained fundamental new insights into the microscopic details of relatively large complex molecules at high energy as they undergo quenching collisions and redistribute their energy.

  20. Phosphine-catalyzed [3+2] cycloaddition reactions of azomethine imines with electron-deficient alkenes: a facile access to dinitrogen-fused heterocycles.

    PubMed

    Li, Zhen; Yu, Hao; Liu, Honglei; Zhang, Lei; Jiang, Hui; Wang, Bo; Guo, Hongchao

    2014-02-03

    An efficient method for the phosphine-catalyzed [3+2] cycloaddition reaction of azomethine imines with diphenylsulfonyl alkenes to give dinitrogen-fused bi- or tricyclic heterocyclic compounds in high yields has been described. Moreover, two phenylsulfonyl groups installed on the heterocyclic products could be conveniently removed or transformed to other functional groups, making the reaction more useful.

  1. Star PolyMOCs with Diverse Structures, Dynamics, and Functions by Three-Component Assembly.

    PubMed

    Wang, Yufeng; Gu, Yuwei; Keeler, Eric G; Park, Jiwon V; Griffin, Robert G; Johnson, Jeremiah A

    2017-01-02

    We report star polymer metal-organic cage (polyMOC) materials whose structures, mechanical properties, functionalities, and dynamics can all be precisely tailored through a simple three-component assembly strategy. The star polyMOC network is composed of tetra-arm star polymers functionalized with ligands on the chain ends, small molecule ligands, and palladium ions; polyMOCs are formed via metal-ligand coordination and thermal annealing. The ratio of small molecule ligands to polymer-bound ligands determines the connectivity of the MOC junctions and the network structure. The use of large M12 L24 MOCs enables great flexibility in tuning this ratio, which provides access to a rich spectrum of material properties including tunable moduli and relaxation dynamics.

  2. Star PolyMOCs with Diverse Structures, Dynamics, and Functions by Three-Component Assembly

    SciTech Connect

    Wang, Yufeng; Gu, Yuwei; Keeler, Eric G.; Park, Jiwon V.; Griffin, Robert G.; Johnson, Jeremiah A.

    2016-12-05

    We report star polymer metal–organic cage (polyMOC) materials whose structures, mechanical properties, functionalities, and dynamics can all be precisely tailored through a simple three-component assembly strategy. The star polyMOC network is composed of tetra-arm star polymers functionalized with ligands on the chain ends, small molecule ligands, and palladium ions; polyMOCs are formed via metal–ligand coordination and thermal annealing. The ratio of small molecule ligands to polymer-bound ligands determines the connectivity of the MOC junctions and the network structure. The use of large M12L24 MOCs enables great flexibility in tuning this ratio, which provides access to a rich spectrum of material properties including tunable moduli and relaxation dynamics.

  3. Enzymatic synthesis of poly(catechin)-antibiotic conjugates: an antimicrobial approach for indwelling catheters.

    PubMed

    Gonçalves, Idalina; Abreu, Ana S; Matamá, Teresa; Ribeiro, Artur; Gomes, Andreia C; Silva, Carla; Cavaco-Paulo, Artur

    2015-01-01

    Biofilm formation in urinary indwelling catheters is one of the most critical issues that patients face. Catheters were coated with poly(catechin)-antibiotic conjugates with enhanced antimicrobial properties. Catechin was conjugated with two antibiotics, namely trimethoprim (TMP) and sulfamethoxazole (SMZ) via activation with N,N'-disuccinimidyl carbonate (DSC) and subsequent coupling to molecules containing α-amine moieties. Silicone and polyurethane catheters were functionalized in situ through laccase oxidation of catechin-antibiotic conjugates. Four antimicrobial coatings were produced, namely with poly(catechin), poly(catechin)-TMP, poly(catechin)-SMZ and poly(catechin)-TMP-SMZ. The bacterial adhesion reduction was tested on the functionalized devices using gram-negative and gram-positive strains. The most significant reduction in adhesion was observed with poly(catechin)-TMP (gram-negative -85 % and gram-positive -87 %) and with poly(catechin)-TMP-SMZ (gram-negative -85 % and gram-positive -91 %). The cytotoxicity to mammalian cells was tested by indirect contact for 5 days and revealed that all the tested coatings supported more than 90 % of viable cells. A promising approach for the increase of the indwelling catheter lifespan was developed aiming to reduce catheter-associated chronic infections.

  4. 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.

  5. How surface interactions freeze polymer molecules at room temperature: a single molecule approach

    NASA Astrophysics Data System (ADS)

    Araújo, F. L.; Valente, G. T.; Faria, R. M.; Guimarães, F. E. G.

    2015-11-01

    The planar conformation assumed by polyfluorenes is used as a model system to investigate how solid surfaces interact with an individual polymer chain as well as to access the effects of substrates and interchain interactions on the polymer conformation. We demonstrate that confocal fluorescence microscopy is very sensitive to characterize photophysical processes associated to conformation assumed by a single conjugated unit of poly (9,9 dioctylfluorene) or PFO. Emissions from interacting molecules have been resolved for the first time between the energies of the planar (β phase) and the non-planar (amorphous) phase that were associated to perturbations of the primary chain conformation. But we have found the planar conformation is assumed by single PFO molecules due to strong interactions with the hydrophilic quartz surfaces. This PFO conformation persists frozen even at room temperature, although emission lines are significantly broadened due to interactions with vibrating substrate atoms.

  6. An image-based screen identifies a small molecule regulator of megakaryopoiesis

    PubMed Central

    Boitano, Anthony E.; de Lichtervelde, Lorenzo; Snead, Jennifer L.; Cooke, Michael P.; Schultz, Peter G.

    2012-01-01

    Molecules that control the lineage commitment of hematopoietic stem cells (HSCs) may allow the expansion of enriched progenitor populations for both research and therapeutic uses. In an effort to better understand and control the differentiation of HSCs to megakaryocytes, we carried out an image-based screen of a library of 50,000 heterocycles using primary human CD34+ cells. A class of naphthyridinone derivatives was identified that induces the differentiation of common myeloid progenitors (CMP) to megakaryocytes. Kinase profiling and subsequent functional assays revealed that these compounds act through inhibition of platelet-derived growth factor receptor (PDGFR) signaling in CMPs. Such molecules may ultimately have clinical utility in the treatment of thrombocytopenia. PMID:22891346

  7. 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)

  8. Investigating single molecule adhesion by atomic force spectroscopy.

    PubMed

    Stetter, Frank W S; Kienle, Sandra; Krysiak, Stefanie; Hugel, Thorsten

    2015-02-27

    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.

  9. Investigating Single Molecule Adhesion by Atomic Force Spectroscopy

    PubMed Central

    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

  10. Polyphosphate, an active molecule derived from probiotic Lactobacillus brevis, improves the fibrosis in murine colitis.

    PubMed

    Kashima, Shin; Fujiya, Mikihiro; Konishi, Hiroaki; Ueno, Nobuhiro; Inaba, Yuhei; Moriichi, Kentaro; Tanabe, Hiroki; Ikuta, Katsuya; Ohtake, Takaaki; Kohgo, Yutaka

    2015-08-01

    Inflammatory bowel disease frequently causes intestinal obstruction because of extensive fibrosis. This study investigated whether polyphosphate (poly P), an active molecule derived from Lactobacillus brevis, could improve the fibrosis in a model of chronic colitis. In this study, dextran sodium sulfate (DSS)-induced chronic colitis models and trinitrobenzene sulfonic acid (TNBS)-induced colitis models were used as models of fibrosis. To clarify the mechanism responsible for the observed effects, Caco-2/brush border epithelial (BBE) and naive T helper lymphocyte (THP)-1 cells were treated with lipopolysaccharide (LPS) to induce inflammation. Non-cancer human colon fibroblast (CCD-18) cells were treated with transforming growth factor beta 1 (TGF-β1) to induce fibrosis. The expression levels of fibrosis- and inflammation-associated molecules were evaluated by both a Western blotting analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). The histologic inflammation and fibrosis were significantly improved in the group administered poly P in both the DSS and TNBS colitis models. The levels of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were significantly decreased by poly P treatment. The expression levels of TGF-β1 and collagens in the colitis mice were decreased by poly P. The LPS-induced expressions of IL-1β and TGF-β1 in Caco-2/BBE cells and of TNF-α in THP-1 cells were reduced by poly P treatment. Poly P did not affect the expression of collagens and connective tissue growth factor in the CCD-18 cells. In conclusion, poly P suppresses intestinal inflammation and fibrosis by downregulating the expression of inflammation- and fibrosis-associated molecules in the intestinal epithelium. The administration of poly P is therefore a novel option to treat fibrosis because of chronic intestinal inflammation.

  11. 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

    2015-06-04

    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.

  12. Adsorption of N/S heterocycles in the flexible metal-organic framework MIL-53(Fe(III)) studied by in situ energy dispersive X-ray diffraction.

    PubMed

    Van de Voorde, Ben; Munn, Alexis S; Guillou, Nathalie; Millange, Franck; De Vos, Dirk E; Walton, Richard I

    2013-06-14

    The adsorption of N/S-containing heterocyclic organic molecules in the flexible iron(III) terephthalate MIL-53, Fe(III)(OH)(0.6)F(0.4)(O2C-C6H4-CO2)·(H2O), from the liquid phase was studied with in situ energy dispersive X-ray diffraction (EDXRD), in order to follow the adsorption-induced expansion of the structure. For comparison with the diffraction data, liquid phase adsorption isotherms were recorded for uptake of benzothiophene, benzothiazole and indole in isopropanol and in heptane. The solvent not only influences pore opening but is also a competing guest. The in situ EDXRD experiments allow the kinetics of guest uptake and the competition with solvent to be monitored directly. Indole uptake is limited; this adsorbate is barely capable of opening the closed, either hydrated or dehydrated, MIL-53(Fe) structure, or of penetrating the isopropanol-containing material in the concentration range under study. When isopropanol is used as a solvent, the guest molecules benzothiophene and benzothiazole must be present at a certain threshold concentration before substantial adsorption into the metal-organic framework takes place, eventually resulting in full opening of the structure. The fully expanded structures of benzothiophene or benzothiazole loaded MIL-53(Fe) materials have Imcm symmetry and a unit cell volume of ca. 1600 Å(3), and upon uptake of the guest molecules by the closed form (unit cell volume ~1000 Å(3)) no intermediate crystalline phases are seen. Successful uptake by MIL-53(Fe) requires that the adsorbate is primarily a good hydrogen bond acceptor; additionally, based on UV-visible spectroscopy, a charge-transfer interaction between the S atoms of benzothiophene and the aromatic rings in the MOF pore wall is proposed.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Insights into the formation of inorganic heterocycles via cyclocondensation of primary amines with group 15 and 16 halides.

    PubMed

    Chivers, Tristram; Laitinen, Risto S

    2017-01-31

    Cyclocondensation is a major preparative route for the generation of inorganic heterocycles especially in the case of ring systems involving a Group 15 or 16 element linked to nitrogen. This Perspective will consider recent experimental and computational studies involving the reactions of primary amines (or their synthetic equivalents) with pnictogen and chalcogen halides. The major focus will be a discussion of the identity and role of acyclic intermediates in the reaction pathways to ring formation, as well as the nature of the heterocycles so formed. The similarities and differences between the chemistry of group 15 and 16 systems are emphasised with a view to providing signposts for further investigations.

  18. Metal-Free Hydrogen Atom Transfer from Water: Expeditious Hydrogenation of N-Heterocycles Mediated by Diboronic Acid.

    PubMed

    Xia, Yun-Tao; Sun, Xiao-Tao; Zhang, Ling; Luo, Kai; Wu, Lei

    2016-11-21

    A hydrogenation of N-heterocycles mediated by diboronic acid with water as the hydrogen atom source is reported. A variety of N-heterocycles can be hydrogenated with medium to excellent yields within 10 min. Complete deuterium incorporation from stoichiometric D2 O onto substrates further exemplifies the H/D atom sources. Mechanism studies reveal that the reduction proceeds with initial 1,2-addition, in which diboronic acid synergistically activates substrates and water via a six-membered ring transition state.

  19. Gold-Catalyzed Ring Expansion of Alkynyl Heterocycles through 1,2-Migration of an Endocyclic Carbon-Heteroatom Bond.

    PubMed

    Chen, Ming; Sun, Ning; Xu, Wei; Zhao, Jidong; Wang, Gaonan; Liu, Yuanhong

    2015-12-14

    A mild and efficient gold-catalyzed oxidative ring-expansion of a series of alkynyl heterocycles using pyridine-N-oxide as the oxidant has been developed, which affords highly valuable six- or seven-membered heterocycles with wide functional group toleration. The reaction consists of a regioselective oxidation and a chemoselective migration of an endocyclic carbon-heteroatom bond (favored over C-H migration) with the order of migratory aptitude for carbon-heteroatom bonds being C-S>C-N>C-O. In the absence of an oxidant, polycyclic products are readily constructed through a ring-expansion/Nazarov cyclization reaction sequence.

  20. Reactions of carbonyl compounds with α,β-unsaturated nitriles as a convenient pathway to carbo- and heterocycles

    NASA Astrophysics Data System (ADS)

    Sharanin, Yu A.; Goncharenko, M. P.; Litvinov, Victor P.

    1998-05-01

    Published data on the methods for synthesis of carbo- and heterocyclic compounds based on reactions of α,β-unsaturated nitriles with carbonyl compounds and activated phenols are surveyed. It is demonstrated that all these reactions occur via nucleophilic addition of the carbanion generated from a carbonyl compound to the double bond of an unsaturated nitrile (the Michael reaction). The main routes of transformation of the adducts into carbo- and heterocyclic compounds are considered. The methods for regioselective preparation of fused 4H-pyrans or 1,4-dihydropyridines by varying conditions of cyclisation of Michael adducts are discussed. The bibliography includes 249 references.

  1. 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.

  2. Enantioselective Palladium-Catalyzed Carbene Insertion into the N-H Bonds of Aromatic Heterocycles.

    PubMed

    Arredondo, Vanessa; Hiew, Stanley C; Gutman, Eugene S; Premachandra, Ilandari Dewage Udara Anulal; Van Vranken, David L

    2017-03-15

    C3-substituted indoles and carbazoles react with α-aryl-α-diazoesters under palladium catalysis to form α-(N-indolyl)-α-arylesters and α-(N-carbazolyl)-α-arylesters. The products result from insertion of a palladium-carbene ligand into the N-H bond of the aromatic N-heterocycles. Enantioselection was achieved using a chiral bis(oxazoline) ligand, in many cases with high enantioselectivity (up to 99 % ee). The method was applied to synthesize the core of a bioactive carbazole derivative in a concise manner.

  3. A simple iridicycle catalyst for efficient transfer hydrogenation of N-heterocycles in water.

    PubMed

    Talwar, Dinesh; Li, Ho Yin; Durham, Emma; Xiao, Jianliang

    2015-03-27

    A cyclometalated iridium complex is shown to catalyse the transfer hydrogenation of various nitrogen heterocycles, including but not limited to quinolines, isoquinolines, indoles and pyridinium salts, in an aqueous solution of HCO2H/HCO2Na under mild conditions. The catalyst shows excellent functional-group compatibility and high turnover number (up to 7500), with catalyst loadings as low as 0.01 mol % being feasible. Mechanistic investigation of the quinoline reduction suggests that the transfer hydrogenation proceeds via both 1,2- and 1,4-addition pathways, with the catalytic turnover being limited by the step of hydride transfer.

  4. Complexing sorbents with heterocyclic amino groups for concentrating platinum-group metals

    SciTech Connect

    Myasoedova, G.V.; Shcherbinina, N.I.; Komozin, P.N.

    1995-06-01

    Sorbents prepared on the basis of amines, in particular, those bearing heterocyclic amino groups and nitrogen-containing matrices, hold much promise for the sorptifve sepatration of platinum-group metals. The results of the study of new complexing sorbents based on 2,4,6-triamino-1,3,5-triazine (melamine) and bearing 3(5)-methylpyrazole, imidazole, and benzimidazole groups are presented in this work. The sorption and complexing properties of the sorbents with respect to platinum-group metals were studied. The possibility of using new sorbents for the group concentration of platinum-group metals was demonstrated.

  5. [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.

  6. 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.

  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. Synthesis and antimicrobial evaluation of some new cyclooctanones and cyclooctane-based heterocycles.

    PubMed

    Ali, Korany A; Hosni, Hanaa M; Ragab, Eman A; El-Moez, Sherein I Abd

    2012-03-01

    The versatile synthon (E)-2-((dimethyl amino)methylene)cyclooctanone (2) was used as a key intermediate for the synthesis of cyclooctanones and cyclooctane-based heterocycles with pyrazole, isoxazole, pyrimidine, pyrazolopyrimidine, triazolopyrimidine and imidazopyrimidine derivatives via its reactions with several nitrogen nucleophiles. The newly synthesized compounds were screened in vitro for their antimicrobial activity against pathogenic microorganisms (Listeria monocytogenes, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans). Most of the tested compounds showed moderate to high antibacterial and antifungal effects against the tested pathogenic microorganisms. Among the synthesized compounds, 2-((p-sulfonamidophenyl)methylene)cyclooctanone (5) showed excellent activity against Listeria monocytogenes.

  9. Controlling self-assembly of diphenylalanine peptides at high pH using heterocyclic capping groups

    PubMed Central

    Martin, Adam D.; Wojciechowski, Jonathan P.; Robinson, Andrew B.; Heu, Celine; Garvey, Christopher J.; Ratcliffe, Julian; Waddington, Lynne J.; Gardiner, James; Thordarson, Pall

    2017-01-01

    Using small angle neutron scattering (SANS), it is shown that the existence of pre-assembled structures at high pH for a capped diphenylalanine hydrogel is controlled by the selection of N-terminal heterocyclic capping group, namely indole or carbazole. At high pH, changing from a somewhat hydrophilic indole capping group to a more hydrophobic carbazole capping group results in a shift from a high proportion of monomers to self-assembled fibers or wormlike micelles. The presence of these different self-assembled structures at high pH is confirmed through NMR and circular dichroism spectroscopy, scanning probe microscopy and cryogenic transmission electron microscopy. PMID:28272523

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

    PubMed

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

    2014-12-17

    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).

  11. 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. PMID:27594819

  12. Controlling self-assembly of diphenylalanine peptides at high pH using heterocyclic capping groups

    NASA Astrophysics Data System (ADS)

    Martin, Adam D.; Wojciechowski, Jonathan P.; Robinson, Andrew B.; Heu, Celine; Garvey, Christopher J.; Ratcliffe, Julian; Waddington, Lynne J.; Gardiner, James; Thordarson, Pall

    2017-03-01

    Using small angle neutron scattering (SANS), it is shown that the existence of pre-assembled structures at high pH for a capped diphenylalanine hydrogel is controlled by the selection of N-terminal heterocyclic capping group, namely indole or carbazole. At high pH, changing from a somewhat hydrophilic indole capping group to a more hydrophobic carbazole capping group results in a shift from a high proportion of monomers to self-assembled fibers or wormlike micelles. The presence of these different self-assembled structures at high pH is confirmed through NMR and circular dichroism spectroscopy, scanning probe microscopy and cryogenic transmission electron microscopy.

  13. Controlled Tethering Molecules via Crystal Surface Engineering

    NASA Astrophysics Data System (ADS)

    Cheng, Stephen Z. D.; Zheng, Joseph X.; Chen, William Y.

    2004-03-01

    So far, almost all experiments in tethering chain molecules onto substrates are via "grafting to" or "grafting from" polymerizations in addition to physical absorption. Issues concerning the uniformity of the tethered chain density and the molecular weight distribution of the chains tethered by polymerization always undermine the properties experimentally observed. We proposed a novel design to precisely control the tethering density of polystyrene (PS) brushes on a poly(ethylene oxide) (PEO) or a poly(L-lactic acid) (PLLA) lamellar crystal basal surface using PEO-b-PS or PLLA-b-PS diblock copolymers. As the crystallization temperature (Tc) increased in either a PEO-b-PS/mixed solution (chrolobenzene/octane) or a PLLA-b-PS/amyl acetate solution, the PEO or PLLA lamellar thickness (d) increased, and correspondingly, the number of folds per PEO or PLLA block was reduced. The reduced tethered density (Σ*) of the PS brushes thus increased. At an onset where the PS brushes are overcrowded within the solution, a drastic slope change in the relationship between (d)-1 and Tc occurs in both cases at a Σ* between 3 - 4. This illustrates that the weak to intermediate interaction changes of the PS brushes with their neighbors may be universally represented.

  14. Overview on poly(ADP-ribose) immuno-biomedicine and future prospects

    PubMed Central

    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 Mg2+. 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

  15. Synthesis and characterization of poly(D,L-lactide)-poly(ethylene glycol) multiblock poly(ether-ester-urethane)s

    NASA Astrophysics Data System (ADS)

    Haw, Tan Ching; Ahmad, Azizan; Anuar, Farah Hannan

    2015-09-01

    In this study, poly(D,L-lactide)-poly(ethylene glycol) multiblock poly(ether-ester-urethane)s was synthesized in the framework of environmental friendly products to meet the need for highly flexible polymers. Triblock copolymer with poly(ethylene glycol) as center block and poly(D,L-lactide) as side block were first synthesized by ring-opening polymerization of D,L-lactide, followed by chain extension reaction of triblocks using hexamethylene diisocyanate (HMDI). NMR and infra-red spectroscopies were used to determine the molecular composition whereas XRD analysis revealed crystallinity behavior of synthesized multiblock copolymers.

  16. Positronium ions and molecules

    NASA Technical Reports Server (NTRS)

    Ho, Y. K.

    1990-01-01

    Recent theoretical studies on positronium ions and molecules are discussed. A positronium ion is a three particle system consisting of two electrons in singlet spin state, and a positron. Recent studies include calculations of its binding energy, positron annihilation rate, and investigations of its doubly excited resonant states. A positronium molecule is a four body system consisting of two positrons and two electrons in an overall singlet spin state. The recent calculations of its binding energy against the dissociation into two positronium atoms, and studies of auto-detaching states in positronium molecules are discussed. These auto-dissociating states, which are believed to be part of the Rydberg series as a result of a positron attaching to a negatively charged positronium ion, Ps-, would appear as resonances in Ps-Ps scattering.

  17. Single-Molecule Bioelectronics

    PubMed Central

    Rosenstein, Jacob K.; Lemay, Serge G.; Shepard, Kenneth L.

    2014-01-01

    Experimental techniques which interface single biomolecules directly with microelectronic systems are increasingly being used in a wide range of powerful applications, from fundamental studies of biomolecules to ultra-sensitive assays. Here we review several technologies which can perform electronic measurements of single molecules in solution: ion channels, nanopore sensors, carbon nanotube field-effect transistors, electron tunneling gaps, and redox cycling. We discuss the shared features among these techniques that enable them to resolve individual molecules, and discuss their limitations. Recordings from each of these methods all rely on similar electronic instrumentation, and we discuss the relevant circuit implementations and potential for scaling these single-molecule bioelectronic interfaces to high-throughput arrayed sensing platforms. PMID:25529538

  18. MOLECULES IN {eta} CARINAE

    SciTech Connect

    Loinard, Laurent; Menten, Karl M.; Guesten, Rolf; Zapata, Luis A.; Rodriguez, Luis F.

    2012-04-10

    We report the detection toward {eta} Carinae of six new molecules, CO, CN, HCO{sup +}, HCN, HNC, and N{sub 2}H{sup +}, and of two of their less abundant isotopic counterparts, {sup 13}CO and H{sup 13}CN. The line profiles are moderately broad ({approx}100 km s{sup -1}), indicating that the emission originates in the dense, possibly clumpy, central arcsecond of the Homunculus Nebula. Contrary to previous claims, CO and HCO{sup +} do not appear to be underabundant in {eta} Carinae. On the other hand, molecules containing nitrogen or the {sup 13}C isotope of carbon are overabundant by about one order of magnitude. This demonstrates that, together with the dust responsible for the dimming of {eta} Carinae following the Great Eruption, the molecules detected here must have formed in situ out of CNO-processed stellar material.

  19. Polarization of deuterium molecules

    SciTech Connect

    J. F. J. van den Brand; H. J. Bulten; M. Ferro-Luzzi; Z.-L. Zhou; Ricardo Alarcon; T. Botto; M. Bouwhuis; Rolf Ent; Peter Heimberg; Douglas W. Higinbotham; Kees de Jager; J. Lang; D. J. de Lange; I. Passchier; H. R. Poolman; J. J. M. Steijger; O. Unal; H. de Vries

    1997-08-01

    For molecular systems, spin relaxation is expected to be suppressed compared to the case of atoms, since the paired electrons in a hydrogen or deuterium molecule are chemically stable, and only weakly interact with the spin of the nucleus. Such systems would be largely insensitive to polarization losses due to spin-exchange collisions, to the interaction of the electron spins with external fields (e.g. the RF-field of a bunched charged-particle beam), and/or to the presence of container walls. Here, we discuss the results of a recent experiment where we obtained evidence that nuclear polarization is maintained, when polarized atoms recombine to molecules on a copper surface (in a magnetic field of 23 mT and at a density of about 10{sup 12} molecules {center_dot} cm{sup -3}).

  20. Optical absorption and NMR spectroscopic studies on paramagnetic neodymium(III) complexes with beta-diketone and heterocyclic amines. The environment effect on 4f-4f hypersensitive transitions.

    PubMed

    Ansari, A A; Irfanullah, M; Iftikhar, K

    2007-08-01

    The optical absorption spectra of [Nd(acac)3(H2O)2].H2O, [Nd(acac)3bpy] and [Nd(acac)3phen(H2O)2] (where acac=acetylacetone, bpy=2,2'-bipyridyl and phen=1,10-phenanthroline) complexes in the visible region, in a series of non-aqueous solvents (methanol, ethanol, isopropanol, chloroform, acetonitrile, pyridine, nitrobenzene and dimethylsulphoxide) have been analyzed. The transition 4G(5/2)<--4I(9/2) (Nd-VI) located near the middle of the visible region (17,500 cm(-1)) is hypersensitive. Its behavior is in sharp contrast to many other typically weak and consistently unvaried, normal 4f-4f transitions. The oscillator strength of this transition for the chelate as well as its adducts with phen and bpy in any of the solvent employed is larger than the oscillator strength of Nd3+ aqua-ion. It is most intense in pyridine for all the complexes studied and, therefore, pyridine is the most effective in promoting f-f spectral intensity. The band shape and oscillator strength of the hypersensitive transitions display pronounced changes as compared to Nd3+ aqua-ion. The band shapes of the hypersensitive transitions show remarkable changes on passing from aqueous solution to various non-aqueous solutions, which is the result of change in the environment about the Nd(III) ion in the various solutions and suggests change in the environment about the Nd(III) ion in the various solutions and suggests coordination of solvent molecule(s), in some cases. A comparative account of hypersensitivity in the present complexes with those of other adducts of Nd(beta-diketoenolate)3 with heterocyclic amines is discussed. The NMR signals of heterocyclic amines have been shifted to high fields while the resonances due to acetylacetone moiety have moved to low fields. The paramagnetic shift in the complexes is dipolar in nature.