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Sample records for poly heterocyclic molecules

  1. Organic heterocyclic molecules become superalkalis.

    PubMed

    Reddy, G Naaresh; Giri, Santanab

    2016-09-21

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

  2. Dissociative Ionization of Aromatic and Heterocyclic Molecules

    NASA Technical Reports Server (NTRS)

    Huo, Winifred M.

    2003-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Connell, John W.

    1991-01-01

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

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

    PubMed

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

    2016-09-12

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  6. 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.

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

    PubMed

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

    2009-01-22

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

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

    PubMed

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

    2009-01-22

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

  9. 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…

  10. N-Heterocyclic Olefins as Organocatalysts for Polymerization: Preparation of Well-Defined Poly(propylene oxide)**

    PubMed Central

    Naumann, Stefan; Thomas, Anthony W; Dove, Andrew P

    2015-01-01

    The metal-free polymerization of propylene oxide (PO) using a special class of alkene—N-heterocyclic olefins (NHOs)—as catalysts is described. Manipulation of the chemical structure of the NHO organocatalyst allows for the preparation of the poly(propylene oxide) in high yields with high turnover (TON>2000), which renders this the most active metal-free system for the polymerization of PO reported to date. The resulting polyether displays predictable end groups, molar mass, and a low dispersity (ĐM<1.09). NHOs with an unsaturated backbone are essential for polymerization to occur, while substitution at the exocyclic carbon atom has an impact on the reaction pathway and ensures the suppression of side reactions. PMID:26136456

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

    PubMed Central

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

    2015-01-01

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

  12. 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.

  13. New cadmium(II) halides modified by N-heterocyclic molecules

    NASA Astrophysics Data System (ADS)

    Wang, Tie-Gang; Li, Su; Yu, Jie-Hui; Xu, Ji-Qing

    2015-03-01

    Under the solvothermal condition, the reaction of CdI2, bpp and KI at pH = 8 afforded compound [CdI2(bpp)] (bpp = 1,2-bis(4-pyridyl)propane) 1, while at the ambient conditions, the reactions of CdX2, dabco and KX at pH = 4-5 produced compounds [H2(dabco)][CdBr4]·H2O (dabco = 1,4-diazabicyclo[2,2,2]octane) 2 and [(Hdabco)CdI3] 3. X-ray single-crystal diffraction analysis reveals that (i) compound 1 possesses a one-dimensional (1-D) zigzag chain structure. The large volume bpp molecule controls the Cd2+ ion to adopt a tetrahedral geometric configuration; (ii) both compounds 2 and 3 are mononuclear. Interestingly, in the same pH environments, dabco was in situ diprotonated in compound 2, while dabco was in situ monoprotonated in compound 3. The templating effect as well as the X- ion maybe plays a key role in the protonated degree for dabco in an acidic environment. The photoluminescence analysis indicates that compound 1 emits the strong green light, which should be attributed to a combination of two types of charge transfers: the charge transfer between Cd2+ and I-; the charge transfer between Cd2+ and bpp.

  14. Histone-poly(A) hybrid molecules as tools to block nuclear pores.

    PubMed

    Cremer, G; Wojtech, E; Kalbas, M; Agutter, P S; Prochnow, D

    1995-04-01

    Histone-poly(A) hybrid molecules were used for transport experiments with resealed nuclear envelopes and after attachment of a cleavable cross-linker (SASD) to identify nuclear proteins. In contrast to histones, the hybrid molecules cannot be accumulated in resealed nuclear envelopes, and in contrast to poly(A), the export of hybrids from preloaded nuclear envelopes is completely impaired. The experiments strongly confirm the existence of poly(A) as an export signal in mRNA which counteracts the nuclear location signals (NLS) in histones. The contradicting transport signals in the hybrid molecules impair translocation through the nuclear pore complex. The failure to accumulate hybrid molecules into resealed nuclear envelopes results from the covalent attachment of polyadenylic acid to histones in a strict 1:1 molar ratio. This was demonstrated in control transport experiments where radiolabeled histones were simply mixed with nonlabeled poly(A) or radiolabeled poly(A) mixed with nonlabeled histones. In comparison, control uptake experiments with histones covalently linked to a single UMP-mononucleotide are strongly enhanced. Such controls exclude the conceivable possibility of a simple masking of the nuclear location signal in the histones by the covalent attached poly(A) moiety. Photoreactive histone-poly(A) hybrid analogs serve to identify nuclear envelope proteins--presumably in the nuclear pore--with molecular weights of 110, 80, and 71.4 kDa.

  15. 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.

  16. A combined molecular dynamic and quantum mechanic study of the solvent and guest molecule effect on the stability and length of heterocyclic peptide nanotubes.

    PubMed

    Izadyar, Mohammad; Khavani, Mohammad; Housaindokht, Mohammad Reza

    2015-05-01

    Molecular dynamic simulations were performed to investigate the stability of heterocyclic peptide nanotubes composed of 1,4-disubstituted-1,2,3-triazol ε-amino acid. 45 ns MD simulations were conducted on the cyclic peptide nanotube (CPNT) and cyclic peptide dimer in methanol, chloroform, and water and revealed that these structures are more stable in nonpolar solvents. MM-PBSA and MM-GBSA calculations were employed to analyze the solvent effect on the stability and length of the CPNT. These calculations showed that CPNT in chloroform was more stable and longer as compared to other solvents. In addition, the effect of the guest molecule (ethanol) inside the dimer and CPNT was investigated. The obtained results confirmed that guest molecule(s) stabilized the dimer and CPNT in all solvents. Quantum chemistry calculations on the cyclic peptide dimer were performed at the M06-2X/6-31G(d) level in the gas phase and three solvents. The obtained results from the quantum chemistry study were in good agreement with the MD simulation results. DFT calculations showed that the guest molecule stabilized the dimer structure and electrostatically interacted with the cyclic peptide dimer. Finally, for investigation of the solvent effects on the hydrogen bonds of the cyclic peptide dimer, NBO and AIM analysis were performed.

  17. 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.

  18. Single molecule studies of solvent-dependent diffusion and entrapment in poly(dimethylsiloxane) thin films.

    PubMed

    Lange, Jeffrey J; Culbertson, Christopher T; Higgins, Daniel A

    2008-12-15

    Single molecule microscopic and spectroscopic methods are employed to probe the mobility and physical entrapment of dye molecules in dry and solvent-loaded poly(dimethylsiloxane) (PDMS) films. PDMS films of approximately 220 nm thickness are prepared by spin casting dilute solutions of Sylgard 184 onto glass coverslips, followed by low temperature curing. A perylene diimide dye (BPPDI) is used to probe diffusion and molecule-matrix interactions. Two classes of dye-loaded samples are investigated: (i) those incorporating dye dispersed throughout the films ("in film" samples) and (ii) those in which the dye is restricted primarily to the PDMS surface ("on film" samples). Experiments are performed under dry nitrogen and at various levels of isopropyl alcohol (IPA) loading from the vapor phase. A PDMS-coated quartz-crystal microbalance is employed to monitor solvent loading and drying of the PDMS and to ensure equilibrium conditions are achieved. Single molecules are shown to be predominantly immobile under dry conditions and mostly mobile under IPA-saturated conditions. Quantitative methods for counting the fluorescent spots produced by immobile single molecules in optical images of the samples demonstrate that the population of mobile molecules increases nonlinearly with IPA loading. Even under IPA saturated conditions, the population of fixed molecules is found to be greater than zero and is greatest for "in film" samples. Fluorescence correlation spectroscopy is used to measure the apparent diffusion coefficient for the mobile molecules, yielding a mean value of D = 1.4(+/-0.4) x 10(-8) cm(2)/s that is virtually independent of IPA loading and sample class. It is concluded that a nonzero population of dye molecules is physically entrapped within the PDMS matrix under all conditions. The increase in the population of mobile molecules under high IPA conditions is attributed to the filling of film micropores with solvent, rather than by incorporation of molecularly

  19. Effect of heterocycles on field-effect transistor performances of donor-acceptor-donor type small molecules

    NASA Astrophysics Data System (ADS)

    Chini, Mrinmoy Kumar; Mahale, Rajashree Y.; Chatterjee, Shyambo

    2016-09-01

    Two D-A-D small molecules comprising triphenylamine and diketopyrrolopyrrole were synthesized having either furan or thiophene connected to the fused lactam ring. In this design, furan/thiophene diketopyrrolopyrrole acts as an acceptor and triphenylamine acts as a donor. Propeller shaped triphenylamine has its effect on packing, processability and plays a vital role in determining the π-π molecular orbital stacking in such compounds and thus the mobility of charge carriers. With TDPPT and FDPPT, maximum hole carrier mobility obtained is 2.88 × 10-3 cm2 V-1 s-1 and 1.60 × 10-3 cm2 V-1 s-1, respectively using bottom gate bottom contact field-effect transistor.

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

    NASA Astrophysics Data System (ADS)

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

    2003-08-01

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

  1. Selective Small Molecule Inhibition of Poly(ADP-Ribose) Glycohydrolase (PARG)

    PubMed Central

    Finch, Kristin E.; Knezevic, Claire E.; Nottbohm, Amanda C.; Partlow, Kathryn C.; Hergenrother, Paul J.

    2012-01-01

    The poly(ADP-ribose) (PAR) post-translational modification is essential for diverse cellular functions, including regulation of transcription, response to DNA damage, and mitosis. Cellular PAR is predominantly synthesized by the enzyme poly(ADP-ribose) polymerase-1 (PARP-1). PARP-1 is a critical node in the DNA damage response pathway, and multiple potent PARP-1 inhibitors have been described, some of which show considerable promise in the clinic for the treatment of certain cancers. Cellular PAR is efficiently degraded by poly(ADP-ribose) glycohydrolase (PARG), an enzyme for which no potent, readily accessible, and specific inhibitors exist. Herein we report the discovery of small molecules that effectively inhibit PARG in vitro and in cellular lysates. These potent PARG inhibitors can be produced in two chemical steps from commercial starting materials and have complete specificity for PARG over the other known PAR glycohydrolase (ADP-ribosylhydrolase 3, ARH3) and over PARP-1, and thus will be useful tools to study the biochemistry of PAR signaling. PMID:22220926

  2. Single-molecule studies of oligomer extraction and uptake of dyes in poly(dimethylsiloxane) films.

    PubMed

    Lange, Jeffrey J; Collinson, Maryanne M; Culbertson, Christopher T; Higgins, Daniel A

    2009-12-15

    Single-molecule microscopic methods were used to probe the uptake, mobility, and entrapment of dye molecules in cured poly(dimethylsiloxane) (PDMS) films as a function of oligomer extraction. The results are relevant to the use of PDMS in microfluidic separations, pervaporation, solid-phase microextraction, and nanofiltration. PDMS films were prepared by spin-casting dilute solutions of Sylgard 184 onto glass coverslips, yielding approximately 1.4 microm thick films after curing. Residual oligomers were subsequently extracted from the films by "spin extraction". In this procedure, 200 microL aliquots of isopropyl alcohol were repeatedly dropped onto the film surface and spun off at 2000 rpm. Samples extracted 5, 10, 20, and 40 times were investigated. Dye molecules were loaded into these films by spin-casting nanomolar dye solutions onto the films. Both neutral perylene diimide (N,N'-bis(butoxypropyl)perylene-3,4,9,10-tetracarboxylic diimide) and cationic rhodamine 6G (R6G) dyes were employed. The films were imaged by confocal fluorescence microscopy. The images obtained depict nonzero populations of fixed and mobile molecules in all films. Cross-correlation methods were used to quantitatively determine the population of fixed molecules in a given region, while a Bayesian burst analysis was used to obtain the total population of molecules. The results show that the total amount of dye loaded increases with increased oligomer extraction, while the relative populations of fixed and mobile molecules decrease and increase, respectively. Bulk R6G data also show greater dye loading with increased oligomer extraction.

  3. Radical C-H functionalization to construct heterocyclic compounds.

    PubMed

    Yu, Jin-Tao; Pan, Changduo

    2016-02-01

    Heterocyclic compounds are widely present in natural products, pharmaceuticals and bioactive molecules. Thus, organic and pharmaceutical chemists have been making extensive efforts to construct those heterocyclic frameworks through developing versatile and efficient synthetic strategies. The direct C-H functionalization via the radical pathway has emerged as a promising and dramatic approach towards heterocycles with high atom- and step-economy. Heterocyclic compounds such as coumarins, furans, benzofurans, xanthones, benzothiazoles, indoles, indolines, oxindoles, quinolines, isoquinolines, quinoxaline, and phenanthridines have been successfully synthesized by C-H functionalization through the radical pathway. In this review, recent advances on radical C-H functionalization to construct heterocyclic compounds are highlighted with discussions.

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

    PubMed

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

    2014-10-01

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

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

    PubMed

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

    2014-10-01

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

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

    PubMed

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

    2011-06-28

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

  7. 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.

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

    PubMed

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

    2015-12-16

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

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

    PubMed

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

    2015-12-16

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

  10. Graphane versus graphene: a computational investigation of the interaction of nucleobases, aminoacids, heterocycles, small molecules (CO2, H2O, NH3, CH4, H2), metal ions and onium ions.

    PubMed

    Umadevi, Deivasigamani; Narahari Sastry, G

    2015-11-11

    Graphane has emerged as a two-dimensional hydrocarbon with interesting physical properties and potential applications. Understanding the interaction of graphane with various molecules and ions is crucial to appreciate its potential applications. We investigated the interaction of nucleobases, aminoacids, saturated and unsaturated heterocycles, small molecules, metal ions and onium ions with graphane by using density functional theory calculations. The preferred orientations of these molecules and ions on the graphane surface have been analysed. The binding energies of graphane with these molecules have been compared with the corresponding binding energies of graphene. Our results reveal that graphane forms stable complexes with all the molecules and ions yet showing lesser binding affinity when compared to graphene. As an exemption, the preferential strong binding of H2O with graphane than graphene reveals the fact that graphane is more hydrophilic than graphene. Charge transfer between graphane and the molecules and ions have been found to be an important factor in determining the binding strength of the complexes. The effect of the interaction of these molecules and ions on the HOMO-LUMO energy gap of graphane has also been investigated.

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

    PubMed

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

    2003-09-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

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

    PubMed

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

    2013-01-01

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

  14. 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.

  15. 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

  16. Synthesis and characterization of various ruthenium small molecules and metallopolymers for potential use in photovoltaic devices and luminescence properties of N-heterocyclic carbenes and trifluoro methylated tris(pyrazolyl)borate silver (I) acid-base adducts

    NASA Astrophysics Data System (ADS)

    Chitikuri, Shylaja

    This thesis with its 66 pages, 1 table, 29 figures and 47 references, deals with two major topics involving structure and properties of selected metal complexes and their use in electronic devices. The first chapter discusses the development of ruthenium-based metallopolymer and small molecular complexes toward possible utilization as active materials for solar cells. Such complexes have been found to be good "black absorbers" with solid-state absorption that spans the entire visible region into the near-infrared, representing an impressive overlap with the solar radiation that is more favorable than common molecular solar cell active materials. The second chapter includes photophysical studies of different metallo N-heterocyclic carbenes and acid-base adducts comprising fluorinated tris(pyrazolyl)borate silver(I) complexes coordinated to different solvent and aromatic molecules. These species have been investigated and found to exhibit unusual photophysical properties, including metal-free phosphorescence at room temperature with high quantum yield, multi-color emission from a single compound, and selective sensing of temperature and hazardous vapors.

  17. 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.

  18. 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.

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

    PubMed

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

    2014-03-28

    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. PMID:24697481

  20. 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.

  1. 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.

  2. 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.

  3. Plasticization of poly(vinylpyrrolidone) thin films under ambient humidity: insight from single-molecule tracer diffusion dynamics.

    PubMed

    Bhattacharya, Sukanya; Sharma, Dharmendar Kumar; Saurabh, Saumya; De, Suman; Sain, Anirban; Nandi, Amitabha; Chowdhury, Arindam

    2013-06-27

    Studies on diffusion dynamics of single molecules (SMs) have been useful in revealing inhomogeneity of polymer thin films near and above the glass-transition temperature (T(g)). However, despite several applications of polymer thin films where exposure to solvent (or vapor) is common, the effect of absorbed solvent molecules on local morphology and rigidity of polymer matrices is yet to be explored in detail. High-T(g) hydrophilic polymers such as poly(vinylpyrrolidone) (PVP) are used as pharmaceutical coatings for drug release in aqueous medium, as they readily absorb moisture, which results in effective lowering of the T(g) and thereby leads to plasticization. The effect of moisture absorption on swelling and softening of PVP thin films was investigated by visualizing the diffusion dynamics of rhodamine 6G (Rh6G) tracer molecules at various ambient relative humidities (RH). Wide-field epifluorescence microscopy, in conjunction with high-resolution SM tracking, was used to monitor the spatiotemporal evolution of individual tracers under varied moisture contents of the matrix. In the absence of atmospheric moisture, Rh6G molecules in dry PVP films are translationally inactive, suggestive of rigid local environments. Under low moisture contents (RH 30-50%), translational mobility remains arrested but rotational motion is augmented, indicating slight swelling of the polymer network which marks the onset of plasticization. The translational mobility of Rh6G was found to be triggered only at a threshold ambient RH, beyond which a large proportion of tracers exhibit extensive diffusion dynamics. Interestingly, SM tracking data at higher moisture contents of the film (RH ≥ 60%) reveal that the distributions of dynamic parameters (such as diffusivity) are remarkably broad, spanning several orders of magnitude. Furthermore, Rh6G molecules display a wide variety of translational motion even at a fixed ambient RH, clearly pointing out the extremely inhomogeneous

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

    SciTech Connect

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

    2007-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2016-09-01

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

  7. 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

    2012-12-01

    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.

  8. 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.

  9. 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.

  10. Gold-Catalyzed Synthesis of Heterocycles

    NASA Astrophysics Data System (ADS)

    Arcadi, Antonio

    2014-04-01

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

  11. Practical and innate C–H functionalization of heterocycles

    PubMed Central

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

    2012-01-01

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

  12. Effects of temperature and alkyl groups of poly(alkyl methacrylate)s on inter- and intramolecular interactions of excited singlet states of pyrenyl guest molecules.

    PubMed

    Abraham, Shibu; Atvars, Teresa D Z; Weiss, Richard G

    2010-09-30

    Temperature-induced changes in the static and dynamic characteristics of the fluorescence from pyrene and N,N-dimethyl-3-(pyren-1-yl)propan-1-amine (PyC3NMe2) have been used to determine the locations and mobilities of these probes in the anisotropic environments provided by films of 5 poly(alkyl methacrylate) (PAMA) polymers in which alkyl is ethyl, butyl, isobutyl, cyclohexyl, and hexadecyl. Whereas emission from pyrene reports on the polarity of the guest sites and the ability of molecules to diffuse translationally between sites, emission from PyC3NMe2 yields information about the fluidity and the shape of the guest sites. Data have been obtained from 20 to >400 K, a range that spans the onsets of several relaxation processes in the hosts. Those data indicate that the pyrenyl groups reside near to ester functionalities in most of the PAMAs, although the distance from them (and the main chains) depends upon the bulkiness of the alkyl groups. Among the most important conclusions derived from this research is that the rates of segmental relaxation phenomena near the probe molecules--and not free volume, as was concluded previously from fluorescence measurements in polyethylene films--are the dominant contributors to the fluorescence changes. Of practical importance, changes in those rates have permitted the onset temperatures of many of the relaxation phenomena occurring in the vicinity of the probes to be located.

  13. The compatibility of Tacrine molecule with poly(n-butylcyanoacrylate) and Chitosan as efficient carriers for drug delivery: A molecular dynamics study.

    PubMed

    Eslami, Mahboobeh; Nikkhah, Sousa Javan; Hashemianzadeh, Seyed Majid; Sajadi, Seyed Abolfazl Seyed

    2016-01-20

    According to the critical role of drug delivery in the treatment of diseases of the central nervous system (CNS), the selection of a suitable carrier plays an important role in the greater effectiveness of drugs. Due to good biocompatibility, biodegradability and low toxicity of polymeric nanoparticles, especially poly(n-butylcyanoacrylate) (PBCA) and Chitosan, these nanoparticles are considered as efficient carriers in drug delivery to the brain. In order to investigate the compatibility of these two polymers with different degrees of polymerization versus a Tacrine unit as the most well known drug for the treatment of Alzheimer's disease, molecular dynamics simulation (MD) is used as a principal tool for studying molecular systems. Interaction energy of the polymer/Tacrine systems, the radius of gyration of the Chitosan and PBCA during the simulation time, solubility and Flory-Huggins interaction parameters has been calculated. According to the results, the Tacrine molecule exhibited higher compatibility with PBCA than Chitosan. Moreover, the interaction between the Tacrine molecules and PBCA nanoparticles became stronger by increasing the length of polymer chain while it was not observed as a regular trend for Chitosan/Tacrine systems. By using these MD simulations, it is possible to find the most appropriate polymer as an efficient drug carrier. We note that the methodology applied here for modeling the polymer/Tacrine system is not restricted to the specific formulations of Tacrine and Chitosan (or PBCA) in the current work and can be extended to various other traditional or new drugs and different polymer drug carriers.

  14. 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.

  15. Rh-Catalyzed Five-Membered Heterocycle Synthesis

    NASA Astrophysics Data System (ADS)

    Kathiravan, Subban; Nicholls, Ian A.

    The following sections are included: * Introduction * Rhodium-catalyzed nitrogen containing five-membered heterocycle synthesis * Rhodium-catalyzed oxygen containing five-membered heterocycle synthesis * Rhodium-catalyzed sulfur containing five-membered heterocycle synthesis * Rhodium-catalyzed phosphorous containing five-membered heterocycle synthesis * Rhodium-catalyzed silicon containing five-membered heterocycle synthesis * Rhodium-catalyzed synthesis of bis-heterocycles * Conclusions and outlook * References

  16. 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

  17. 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

  18. 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.

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

    NASA Astrophysics Data System (ADS)

    Chatterjee, Debarati; Cherayil, Binny J.

    2011-04-01

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

  20. [The non-contact effect of substances containing benzene rings and heterocycles on biological systems].

    PubMed

    Frolov, Iu P

    2001-01-01

    It was found that some substances containing benzolic rings and heterocyclic structures have a noncontact effect on biosystems. Some results of experiments dealing with the noncontact effect on enzyme molecules, cells, and uni- and multicellular organisms are presented. Factors influencing the efficiency of the noncontact effect were revealed. PMID:11605403

  1. 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

    2014-05-01

    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.

  2. Heterocyclics as corrosion inhibitors for acid media

    SciTech Connect

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

    1996-12-01

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

  3. 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.

  4. 40 CFR 721.10003 - Manganese heterocyclic tetraamine complex (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Manganese heterocyclic tetraamine... 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)...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Manganese heterocyclic tetraamine... Specific Chemical Substances § 721.10003 Manganese heterocyclic tetraamine complex (generic). (a) Chemical... as manganese heterocyclic tetraamine complex (PMNs P-98-625/626/627/628/629 and P-00-614/617)...

  6. 40 CFR 721.10003 - Manganese heterocyclic tetraamine complex (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Manganese heterocyclic tetraamine... 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)...

  7. 40 CFR 721.10003 - Manganese heterocyclic tetraamine complex (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Manganese heterocyclic tetraamine... 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. The fabrication of monolithic capillary column based on poly (bisphenol A epoxy vinyl ester resin-co-ethylene glycol dimethacrylate) and its applications for the separation of small molecules in high performance liquid chromatography.

    PubMed

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

    2013-07-01

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

  9. 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.

  10. In vitro disposition profiling of heterocyclic compounds.

    PubMed

    Keemink, Janneke; Wuyts, Benjamin; Nicolaï, Johan; Jonghe, Steven De; Stella, Alessandro; Herdewijn, Piet; Augustijns, Patrick; Annaert, Pieter

    2015-08-01

    Compound libraries that are screened for biological activity commonly contain heterocycles. Besides potency, drug-like properties need to be evaluated to ensure in vivo efficacy of test compounds. In this context, we determined hepatic and intestinal disposition profiles for 17 heterocyclic compounds. All studied compounds showed rapid uptake in suspended rat hepatocytes, whereas metabolism was poor and the rate-limiting step in hepatic elimination. In vitro assays demonstrated a relatively low solubility and high intestinal permeability. Based on these in vitro data, heterocycles were categorized in the biopharmaceutics classification system (BCS) and the biopharmaceutics drug disposition classification system (BDDCS) to predict disposition characteristics before clinical data are available. Our findings emphasized the importance to use hepatocytes in addition to microsomes to study metabolism, since the latter lack non-microsomal enzymes and cellular context. Moreover, intracellular exposure should be considered to gain insight in the relevant fraction of the compound available at the enzymatic site. Finally, the study reveals discrepancies associated with the classification of heterocycles in BCS versus BDDCS. These probably originate from the binary character of both systems.

  11. Monoamine oxidase inhibitory activities of heterocyclic chalcones.

    PubMed

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

    2015-11-15

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

  12. A Universal Isocyanide for Diverse Heterocycle Syntheses

    PubMed Central

    2015-01-01

    Novel scaffolds are of uttermost importance for the discovery of functional material. Three different heterocyclic scaffolds easily accessible from isocyanoacetaldehyde dimethylacetal 1 by multicomponent reaction (MCR) are described. They can be efficiently synthesized by a Ugi tetrazole multicomponent reaction of 1. We discuss the synthesis, 3D structures, and other physicochemical properties. PMID:25351886

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

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

  14. Discrete cage form of water hexamer in the hydrophilic channels assembled by heterocyclic azopyrrole

    NASA Astrophysics Data System (ADS)

    Zhang, Hongwei; Yin, Zhenming

    2015-07-01

    A heterocyclic azopyrrole compound, meso-diethyl-5,5‧-bis(thiazolyldiazo)-dipyrromethane (1), has been synthesized and its two crystals have been characterized by X-ray crystallography. The molecules of compound 1 self-assembled into channel structure in the crystal of 1·3H2O, whereas interlocked type dimer in the crystal of 1·CHCl3. In the 1-D hydrophilic channels of 1·3H2O, six water molecules were held together by eight O-H…O hydrogen bonds and formed discrete cage hexameric clusters. The dehydration/rehydration processes of the compound 1 are also studied.

  15. 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

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

    PubMed

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

    2015-11-01

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

  17. 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.

  18. 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

  19. Solvent free selective dehydrogenation of indolic and carbazolic molecules with an iridium pincer catalyst.

    PubMed

    Brayton, Daniel F; Jensen, Craig M

    2014-06-01

    A previously known iridium POCOP pincer catalyst was found to selectively dehydrogenate the heterocyclic portion of several indolic and carbazolic molecules. These molecules were found to have an "activity window" (172-178 °C) upon which only the heterocyclic ring underwent dehydrogenation. All reactions were run solvent free, yields for selected substrates were excellent, and the products were isolated by either distillation or alumina plug filtration. PMID:24763968

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

    PubMed Central

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

    2014-01-01

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

  1. Diverse trifluoromethyl heterocycles from a single precursor.

    PubMed

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

    2012-02-01

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

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

    PubMed

    Dahan, Elianne; Sundararajan, Pudupadi R

    2014-08-01

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

  3. 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.

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

    PubMed Central

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

    2016-01-01

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

  5. Catalyst-Dependent Stereodivergent and Regioselective Synthesis of Indole-Fused Heterocycles through Formal Cycloadditions of Indolyl-Allenes.

    PubMed

    Mei, Liang-Yong; Wei, Yin; Tang, Xiang-Ying; Shi, Min

    2015-07-01

    Stereo- and regioselective construction of poly-heterocycles, especially those with several contiguous stereocenters, is still a challenge. In this paper, catalyst-dependent stereodivergent and regioselective synthesis of indole-fused heterocycles through formal cycloadditions of indolyl-allenes has been developed. The reaction features total reversion of an all-carbon quaternary stereocenter when a gold or platinum complex was employed as the catalyst through [3 + 2] cycloaddition of allene with indole, affording different diazabenzo[a]cyclopenta[cd]azulenes as epimers, respectively. In addition, in the presence of IPrAuCl and AgNTf2, highly regioselective exo-type [2 + 2] cycloaddition was observed, in which allene served as a 2C synthon. This methodology provides a simple and straightforward approach for the construction of indole-fused tricyclic systems under mild conditions in an atom-economical way.

  6. Selected heterocyclic compounds as antioxidants. Synthesis and biological evaluation.

    PubMed

    Tsolaki, E; Nobelos, P; Geronikaki, A; Rekka, E A

    2014-01-01

    Reactive oxygen species, oxidative stress, and oxidative damage are increasingly assigned important roles as harmful factors in pathological conditions and ageing. ROS are potentially reactive molecules derived from the reduction of molecular oxygen in the course of aerobic metabolism. ROS can also be produced through a variety of enzymes. Under normal circumstances, ROS concentrations are tightly controlled by physiological antioxidants. When excessively produced, or when antioxidants are depleted, ROS can impose oxidative damage to lipids, proteins, sugars and DNA. This reduction-oxidation imbalance, called oxidative stress, can subsequently contribute to the development and progression of tissue damage and play a role in the pathology of various diseases. An antioxidant is defined as "any substance that, when present at low concentrations compared with those of a substrate, significantly delays, prevents or removes oxidative damage to this target molecule". Despite evidence that oxidative damage contributes to a wide range of clinically important conditions, few antioxidants act as effective drugs in vivo. Inter alia, the difficulty of measuring antioxidant efficacy in vivo makes the interpretation of results from clinical trials difficult. A large number of synthetic compounds have been reported to possess antioxidant activity. Several of them derive from natural antioxidants, others have various structures. In this review, some of the most often reported classes of heterocyclic antioxidant compounds, as well as methods for evaluation of their antioxidant activity are discussed.

  7. 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.

  8. 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).

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

    PubMed

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

    2014-03-14

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

  10. 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

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

    PubMed

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

    2016-04-01

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

  12. Triplet photophysics of multichromophoric molecules. A study of poly(N-vinylcarbazole) and meso-2,4-dicarbazolylpentane in fluid solutions

    SciTech Connect

    Haggquist, G.W.; Burkhart, R.D.

    1995-03-27

    Delayed luminescence and transient absorption experiments have been carried out on fluid solutions of poly(N-vinylcarbazole) (PVCz) and meso-2,4-dicarbazolylpentane (DCP) in benzene, cyclohexane, and 1,1-dimethylformamide (DMF). The delayed emission spectra of dilute solutions of DCP in all the solvents are similar and consist of excimeric delayed fluorescence (EDF) with a small contribution from monomeric delayed fluorescence. For PVCz in both benzene and DMF the delayed emission consists primarily of EDF at a delay of 1 {mu}s, but this signal decays away quickly leaving the excimeric phosphorescence band at longer delay times. The transient absorption spectra for DCP depend markedly upon the solvent. In benzene and cyclohexane the absorption is due to the carbazolyl triplet state, but in DMF absorbance bands due to the triplet and to radical cations and anions are found. Transient absorption spectra were also recorded for PVCz in benzene and DMF. Again, ionic species predominate in DMF and triplet states predominate in benzene, while the triplet excimer is present in both solutions. It is concluded that a conformation suitable for triplet excimer formation can be achieved within PVCz polymeric coils but cannot be formed intramolecularly within DCP.

  13. 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.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2013-06-01

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

  16. 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.

  17. 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)...

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

    PubMed

    Jana, Navendu; Driver, Tom G

    2015-10-14

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

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

    PubMed

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

    2002-01-01

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

  20. 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.

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

    PubMed

    Baumann, Marcus; Baxendale, Ian R

    2013-01-01

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

  2. 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

  3. 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.

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

    SciTech Connect

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

    1994-10-01

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

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

    PubMed

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

    2016-05-10

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

  6. 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.

  7. Direct functionalization of nitrogen heterocycles via Rh-catalyzed C-H bond activation.

    PubMed

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

    2008-08-01

    heterocycles, including azoles, azolines, dihydroquinazolines, pyridines, and quinolines, with a wide range of functionalized olefins. We demonstrated the utility of this methodology in the synthesis of natural products, drug candidates, and other biologically active molecules. In addition, we developed conditions to directly arylate these heterocycles with aryl halides. Our initial conditions that used PCy 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. We then replicated the unique coordination environment, stability, and catalytic activity of this complex using the much simpler tetrahydrophosphepine ligands and developed conditions that coupled aryl bromides bearing diverse functional groups without the use of a glovebox or purified reagents. With further mechanistic inquiry, we anticipate that researchers will better understand the details of the aforementioned Rh-catalyzed C-H bond functionalization reactions, resulting in the design of more efficient and robust catalysts, expanded substrate scope, and new transformations.

  8. Interspecies metabolism of heterocyclic aromatic amines

    SciTech Connect

    Turesky, R.J.; Welti, D.H.; Fay, L.B.

    1996-12-31

    2-Amino-3,8-dimethylimadazo[4,5-f]quinoxaline (MeIQx) and other heterocyclic aromatic amines (HAAs) are rodent carcinogens and potential human carcinogens formed in cooked meats and fish. Metabolic activation of MeIQx to a genotoxin occurs through cytochrome P450 mediated N-oxidation to form N-hydroxy-MeIQx which may undergo further activation by esterification to product species which bind to DNA. Pathways of MeIQx metabolism have been elucidated in rodents and nonhuman primates to develop strategies of human biomonitoring. In addition to N-oxidation, predominant routes of detoxification include direct conjugation at the exoyclic amino group with sulfate or glucuronic acid and cytochrome P450 mediated ring oxidation. Analysis of urine from five human subjects exposed to MeIQx reveals that phase II conjugation reactions to the exocyclic amine group are prominent detoxifaction pathways while heterocyclic ring oxidation is a minor pathway. Notably, the N{sup 2-} glucuronide conjugate of N-hydroxy-MeIQx is an important metabolite in human urine. Several other metabolites have been detected in human urine which have not been previously identified in rats or nonhuman primates. Similarities and differences exist in the metabolic processing of MeIQx by humans and other species and may be a critical determinant in assessing the human health risk of HAAs.

  9. 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.

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

    PubMed

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

    2014-09-01

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

  11. Photoluminescence spectral study of single cadmium selenide/zinc sulfide colloidal nanocrystals in poly(methyl methacrylate) and quantum dots molecules

    NASA Astrophysics Data System (ADS)

    Shen, Yaoming

    -dot molecules (QDMs), which are clusters of a few QDs, has attracted attention as a possible implementation of future quantum devices such as quantum cellular antomata. With the advances in crystal growth techniques, the fabrication methods for nanostructures have been improved continuously. Lateral QDMs have been achieved. As a side topic, lateral QDMs have been studied and the result is presented in the last chapter.

  12. Generating and trapping metalla-N-heterocyclic carbenes.

    PubMed

    Ruiz, Javier; García, Lucía; Vivanco, Marilín; Berros, Ángela; Van der Maelen, Juan Francisco

    2015-03-27

    By means of a combined experimental and theoretical approach, the electronic features and chemical behavior of metalla-N-heterocyclic carbenes (MNHCs, N-heterocyclic carbenes containing a metal atom within the heterocyclic skeleton) have been established and compared with those of classical NHCs. MNHCs are strongly basic (proton affinity and pK(a) values around 290 kcal mol(-1) and 36, respectively) with a narrow singlet-triplet gap (around 23 kcal mol(-1)). MNHCs can be generated from the corresponding metalla-imidazolium salts and trapped by addition of transition-metal complexes affording the corresponding heterodimetallic dicarbene derivatives, which can serve as carbene transfer agents.

  13. 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

  14. 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.

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

    PubMed

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

    2015-09-23

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

  16. 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

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

    PubMed

    Haji, Mohammad

    2016-01-01

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

  18. 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.

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

    PubMed

    Thakur, Ashish; Louie, Janis

    2015-08-18

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

  20. Prediction of retention characteristics of heterocyclic compounds.

    PubMed

    Nesměrák, Karel; Toropov, Andrey A; Toropova, Alla P; Yildiz, Ilkay; Yalcin, Ismail; Brozikova, Marketa; Klimešová, Vera; Waisser, Karel

    2015-12-01

    The CORAL software ( http://www.insilico.eu/coral ) was used to build up quantitative structure-property relationships (QSPRs) for the retention characteristics of 93 derivatives of three groups of heterocyclic compounds: 2-phenyl-1,3-benzoxazoles, 4-benzylsulfanylpyridines, and benzoxazines. The QSPRs are one-variable models based on the optimal descriptors calculated from the molecular structure represented by simplified molecular input-line entry systems (SMILES). Each symbol (or two undivided symbols) of SMILES is characterized by correlation weight. The optimal descriptor is the sum of the correlation weights. The numerical data on the correlation weights were calculated with the Monte Carlo method by the manner which provides best correlation between endpoint and optimal descriptor for the calibration set. The predictive ability of the model is checked with the validation set (compounds invisible during building up of the model). The approach has been checked with three random splits into the training, calibration, and validation sets: all models have apparent predictive potential. The mechanistic interpretation of the molecular features extracted from SMILES as the promoters of increase or decrease of examined endpoints is suggested. PMID:26427498

  1. Computational design of fused heterocyclic energetic materials

    NASA Astrophysics Data System (ADS)

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

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

  2. 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

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

    PubMed

    Krasowska, Małgorzata; Bettinger, Holger F

    2016-07-18

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

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

    PubMed Central

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

    2015-01-01

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

  5. 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.

  6. Activation of small molecules by phosphorus biradicaloids.

    PubMed

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

    2014-11-01

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

  7. 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. PMID:27252064

  8. 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.

  9. The Synthesis and Antimicrobial Activity of Heterocyclic Derivatives of Totarol

    PubMed Central

    2012-01-01

    The synthesis and antimicrobial activity of heterocyclic analogues of the diterpenoid totarol are described. An advanced synthetic intermediate with a ketone on the A-ring is used to attach fused heterocycles, and a carbon-to-nitrogen atom replacement is made on the B-ring by de novo synthesis. A-ring analogues with an indole attached exhibit, for the first time, enhanced antimicrobial activity relative to the parent natural product. Preliminary experiments demonstrate that the indole analogues do not target the bacterial cell division protein FtsZ as had been hypothesized for totarol. PMID:23119123

  10. Phosphinate-containing heterocycles: A mini-review

    PubMed Central

    Berger, Olivier

    2014-01-01

    Summary This review provides an overview of recent efforts towards the synthesis of phosphinate heterocycles R1R2P(O)(OR). Our laboratory and others’ have been involved in this field and as a result new P–C, P–N, and P–O containing heterocyclic motifs are now available through a variety of methods. While developing rapidly, this area is still in its infancy so that biological testing of the compounds has not yet been conducted and applications are rare. The growing availability of synthetic methods will undoubtedly change this situation in the near future. PMID:24778726

  11. 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

    2015-07-01

    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.

  12. 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.

  13. 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.

  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. Greener and Expeditious Synthesis of Bioactive Heterocycles using Microwave Irradiation

    EPA Science Inventory

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

  16. 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...

  17. 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...

  18. 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...

  19. 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...

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

    PubMed

    Neuhaus, James D; Willis, Michael C

    2016-06-14

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

  1. Transformation of saturated nitrogen-containing heterocyclic compounds by microorganisms.

    PubMed

    Parshikov, Igor A; Silva, Eliane O; Furtado, Niege A J C

    2014-02-01

    The saturated nitrogen-containing heterocyclic compounds include many drugs and compounds that may be used as synthons for the synthesis of other pharmacologically active substances. The need for new derivatives of saturated nitrogen-containing heterocycles for organic synthesis, biotechnology and the pharmaceutical industry, including optically active derivatives, has increased interest in microbial synthesis. This review provides an overview of microbial technologies that can be valuable to produce new derivatives of saturated nitrogen-containing heterocycles, including hydroxylated derivatives. The chemo-, regio- and enantioselectivity of microbial processes can be indispensable for the synthesis of new compounds. Microbial processes carried out with fungi, including Beauveria bassiana, Cunninghamella verticillata, Penicillium simplicissimum, Aspergillus niger and Saccharomyces cerevisiae, and bacteria, including Pseudomonas sp., Sphingomonas sp. and Rhodococcus erythropolis, biotransform many substrates efficiently. Among the biological activities of saturated nitrogen-containing heterocyclic compounds are antimicrobial, antitumor, antihypertensive and anti-HIV activities; some derivatives are effective for the treatment and prevention of malaria and trypanosomiasis, and others are potent glycosidase inhibitors.

  2. 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.

  3. Journey of poly-nucleotides through OmpF porin.

    PubMed

    Hadi-Alijanvand, Hamid; Rouhani, Maryam

    2015-05-21

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

  4. The Reactions of Nitrogen Heterocycles with Acrolein: Scope and Prebiotic Significance

    NASA Astrophysics Data System (ADS)

    Cleaves, H. James

    2002-12-01

    It has been suggested that life began with a self-replicating RNA molecule. However, after much research into the prebiotic synthesis of RNA, the difficulties encountered have lead some to hypothesize that RNA was preceded by a simpler molecule, one more easily synthesized prebiotically. Many of the proposed alternative molecules are based on acrolein, since it reacts readily with nucleophiles, such as the nucleobases, via Michael addition and is readily synthesized from formaldehyde and acetaldehyde. Reports regarding the reactions of nucleobases with concentrated acrolein solutions suggest that this is a plausible reaction mechanism, though there are also reports that the "incorrect" isomers are obtained. The scope and kinetics of the reaction of acrolein with various nitrogen heterocycles are reported here. Reactions of pyrimidines often give N1 adducts as the major products. Reactions of purines often give N9 adducts in good yield. The reactions are rapid under neutral to slightly alkaline conditions, and proceed at low temperatures and dilutions. The implications of these findings for the origin of life are discussed.

  5. 1,1-Hydroboration of Fused Azole-Isoindole Analogues as an Approach for Construction of B,N-Heterocycles and Azole-Fused B,N-Naphthalenes.

    PubMed

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

    2016-04-01

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

  6. 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

  7. 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. PMID:24729552

  8. 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

    2015-05-01

    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.

  9. 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

  10. Heterocyclization Approach for Electrooxidative Coupling of Functional Primary Alkylamines with Aromatics.

    PubMed

    Morofuji, Tatsuya; Shimizu, Akihiro; Yoshida, Jun-ichi

    2015-08-12

    A new approach for electrooxidative coupling of aromatic compounds and primary alkylamines bearing a functional group such as a hydroxyl group and an amino group was developed. The key to the success of the transformation is heterocyclization of functional primary alkylamines. Treatment of primary alkylamines bearing a functional group with nitriles or their equivalents gives the corresponding heterocycles. The electrochemical oxidation of aromatic substrates in the presence of the heterocycles followed by chemical reaction under nonoxidative conditions gave the desired coupling products.

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

    PubMed

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

    2014-11-01

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

  12. 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.

  13. 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

  14. Amination of heterocyclic compounds with o-benzoylhydroxylamine derivatives.

    PubMed

    Parlanti, Luca; Discordia, Robert P; Hynes, John; Miller, Michael M; O'Grady, Harold R; Shi, Zhongping

    2007-09-13

    The N-amination of heterocyclic compounds 1a-k with O-benzoylhydroxylamine derivatives 5 was developed and demonstrated to be a superior alternative to existing N-amination methods. A structure-reactivity relationship study was performed on variously substituted O-benzoylhydroxylamine derivatives, leading to the discovery of the novel and more efficient aminating reagents 5h and 5i. PMID:17718497

  15. Cooperative Lewis acid/N-heterocyclic carbene catalysis

    PubMed Central

    Cohen, Daniel T.; Scheidt, Karl A.

    2015-01-01

    Lewis acid activation with N-heterocyclic carbene (NHC) catalysis has presented new opportunities for enantioselective reaction development. Recent findings illustrate that Lewis acids can play an important role in homoenolate annulations by: enhancement of the reactivity, reversal of the diastereo- or regioselectivity, and activation of previously inactive electrophiles. Additionally, the incorporation of a Lewis acid into Brønsted base-catalyzed conjugate addition allowed for an increase in yields. PMID:26413259

  16. 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

  17. Reductive dechlorination of the nitrogen heterocyclic herbicide picloram

    SciTech Connect

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

    1993-07-01

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

  18. Genotoxicity of heterocyclic amines in the Salmonella/hepatocyte system.

    PubMed

    Hayashi, S; Møller, M E; Thorgeirsson, S S

    1985-09-01

    The Salmonella/hepatocyte system was employed to determine the mutagenicity in bacteria as well as the DNA damage induced in mouse hepatocytes following exposure to heterocyclic amines. With hepatocytes from C57BL/6N mice, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) showed a clear mutagenic effect in the Salmonella, while weak mutagenic effects were observed with 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 2-amino-6-methyldipyrido[1,2-a:3',2'-b]imidazole (Glu-P-1), and 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2). All the compounds induced low levels of DNA damage in the hepatocytes. In vivo pretreatment of mice with the potent monooxygenase inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 50 micrograms/kg) clearly increased both the mutagenicity in the bacteria and the DNA damage induced in the hepatocytes in vitro. Glu-P-2 showed the lowest mutagenic effect but induced more DNA damage at low concentrations than the other compounds when TCDD-pretreated hepatocytes were used. These data indicate that the genotoxic potency of Glu-P-2 in the intact hepatocyte differs from that observed in the bacteria. Treatment of hepatocytes with a-naphthoflavone, a selective inhibitor of polycyclic hydrocarbon-inducible cytochrome P-450 form(s), prior to exposure to the heterocyclic amines completely inhibited the mutagenic effect in the bacteria. In vivo administration of all the heterocyclic amines 4 hr prior to isolating the hepatocytes resulted in DNA damage, and this effect was augmented by TCDD pretreatment of mice. Our data suggest that agents modulating the activity and composition of the cytochrome P-450 system may greatly influence both toxicity and carcinogenicity of these heterocyclic amines.

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

    PubMed Central

    Nadres, Enrico T.; Daugulis, Olafs

    2012-01-01

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

  20. 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.

  1. 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.

  2. 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.

  3. Discovery of potent, orally bioavailable small-molecule inhibitors of the human CCR2 receptor.

    PubMed

    Doyon, Julien; Coesemans, Erwin; Boeckx, Staf; Buntinx, Mieke; Hermans, Bart; Van Wauwe, Jean P; Gilissen, Ron A H J; De Groot, Alex H J; Corens, David; Van Lommen, Guy

    2008-04-01

    We recently reported the discovery of a series of 2-thioimidazoles as CCR2 antagonists. The most potent molecules of this series, the 4,5-diesters, were rapidly hydrolyzed to the inactive acids and were found to be metabolically unstable. Herein we describe the synthesis of a number of analogues with heterocyclic bioisosteric replacements of the ester group(s). Small 5-membered heterocyclic substituents at the 4-position gave highly potent CCR2 antagonists. Hydrolysis of the 5-ester is diminished, thus imparting these compounds with sufficient stability and systemic exposure after oral administration to warrant further study of the in vivo pharmacology of these functional CCR2 inhibitors.

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

    PubMed

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

    2016-05-01

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

  5. 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.

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

    PubMed

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

    2016-05-01

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

  7. 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…

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Tris(disubstituted alkyl) het-er-o-cy... Specific Chemical Substances § 721.4100 Tris(disubstituted alkyl) het-er-o-cy-cle. (a) Chemical substance... tris(disubstituted alkyl) heterocycle (P-90-142) is subject to reporting under this section for...

  9. 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... Specific Chemical Substances § 721.4100 Tris(disubstituted alkyl) het-er-o-cy-cle. (a) Chemical substance... tris(disubstituted alkyl) heterocycle (P-90-142) is subject to reporting under this section for...

  10. 40 CFR 721.4100 - Tris(disubstituted alkyl) het-er-o-cy-cle.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Tris(disubstituted alkyl) het-er-o-cy... Specific Chemical Substances § 721.4100 Tris(disubstituted alkyl) het-er-o-cy-cle. (a) Chemical substance... tris(disubstituted alkyl) heterocycle (P-90-142) is subject to reporting under this section for...

  11. 40 CFR 721.4100 - Tris(disubstituted alkyl) het-er-o-cy-cle.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Tris(disubstituted alkyl) het-er-o-cy... Specific Chemical Substances § 721.4100 Tris(disubstituted alkyl) het-er-o-cy-cle. (a) Chemical substance... tris(disubstituted alkyl) heterocycle (P-90-142) is subject to reporting under this section for...

  12. 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... Specific Chemical Substances § 721.4100 Tris(disubstituted alkyl) het-er-o-cy-cle. (a) Chemical substance... tris(disubstituted alkyl) heterocycle (P-90-142) is subject to reporting under this section for...

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

    PubMed

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

    2012-12-21

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

  14. 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.

  15. Bioactive fused heterocycles: Nucleoside analogs with an additional ring.

    PubMed

    Jahnz-Wechmann, Zofia; Framski, Grzegorz; Januszczyk, Piotr; Boryski, Jerzy

    2015-06-01

    The following mini-review summarizes the basic literature data regarding synthesis, biological activity, structure-activity relationship, and discussion of the mechanisms of action of two major classes of nucleoside analogs with fused heterocyclic rings: (i) the ethenonucleosides and their related derivatives of the 5,9-dihydro-3-glycosyl-6-alkyl-9-oxo-5H-imidazo[1,2-a]purine type; (ii) the bicyclic nucleosides of 6-alkyl-2,3-dihydrofurano[2,3-d]-pyrimidin-2(3H)-one and 6-alkyl-2,3-dihydropyrrolo[2,3-d]-pyrimidin-2(3H,7H)-one. PMID:25576500

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

    PubMed

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

    2014-03-25

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

  17. Toxicity of six heterocyclic nitrogen compounds to Daphnia pulex

    SciTech Connect

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

    1988-10-01

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

  18. 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.

  19. N-Heterocyclic carbene metal complexes: photoluminescence and applications.

    PubMed

    Visbal, Renso; Gimeno, M Concepción

    2014-05-21

    This review covers the advances made in the synthesis of luminescent transition metal complexes containing N-heterocyclic carbene (NHC) ligands. The presence of a high field strength ligand such as an NHC in the complexes gives rise to high energy emissions, and consequently, to the desired blue colour needed for OLED applications. Furthermore, the great versatility of NHC ligands for structural modifications, together with the use of other ancillary ligands in the complex, provides numerous possibilities for the synthesis of phosphorescent materials, with emission colours over the entire visible spectra and potential future applications in fields such as photochemical water-splitting, chemosensors, dye-sensitised solar cells, oxygen sensors, and medicine.

  20. New Synthetic Technology for the Rapid Construction of Novel Heterocycles-Part 2. The Reaction of IBX with Anilides and Related Compounds.

    PubMed

    Nicolaou; Zhong; Baran

    2000-02-01

    The unusual behavior of hypervalent iodine reagents, Dess - Martin periodinane and IBX, with an array of anilides leads to the formation of complex heterocycles in only one synthetic operation (see scheme). Furthermore, the substrates for these transformations are available in one step from readily available commercial building blocks. The mechanism by which these periodinanes interact with anilides is also explored. This exciting new class of chemical reactions was discovered during the course of the total synthesis of the CP molecules and leads to compounds which are relevant to chemical biology investigations and pharmaceutical research.

  1. 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)

  2. 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)

  3. Interstellar molecules

    NASA Astrophysics Data System (ADS)

    Smith, D.

    1987-09-01

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

  4. 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.

  5. N-Methyl inversion and structure of six-membered heterocyclic rings: rotational spectrum of 1-methyl-4-piperidone.

    PubMed

    Evangelisti, Luca; Lesarri, Alberto; Jahn, Michaela K; Cocinero, Emilio J; Caminati, Walther; Grabow, Jens-Uwe

    2011-09-01

    The conformational and structural properties of the six-membered heterocyclic ring of 1-methyl-4-piperidone have been observed in a jet-cooled supersonic expansion using Fourier transform microwave spectroscopy (FT-MW). The rotational spectrum evidenced two different conformations originated by nitrogen inversion, with the N-methyl group in either equatorial (most stable) or axial position. Additional observation of the rotational spectra for all possible carbon, nitrogen, and oxygen monosubstituted species (4 × (13)C, (15)N, (18)O) in natural abundance allowed us to determine substitution (r(s)) and effective structures (r(0)) for the equatorial conformer. Additional ab initio and DFT calculations provided comparative rotational parameters, structural data, conformational energies, and the axial-equatorial interconversion barrier. The structural data were compared with the related azabicycle of tropinone, revealing the molecular changes and structural relaxation associated with the presence of the two-carbon bridge in the latter molecule.

  6. N-Heterocyclic Olefins as Robust Organocatalyst for the Chemical Conversion of Carbon Dioxide to Value-Added Chemicals.

    PubMed

    Saptal, Vitthal B; Bhanage, Bhalchandra M

    2016-08-01

    In this report, the activity of N-heterocyclic olefins (NHOs) as a newly emerging class of organocatalyst is investigated for the chemical fixation of carbon dioxide through reactions with aziridines to form oxazolidinones and the N-formylation of amines with polymethylhydrosiloxane (PMHS) or 9-borabicyclo[3.3.1]nonane (9-BBN) as the reducing agent under mild conditions. The exocyclic carbon atoms of NHOs are highly nucleophilic owing to the electron-donating ability of the two nitrogen atoms. This high nucleophilicity of the NHOs activates CO2 molecules to form zwitterionic NHO-carboxylate (NHO-CO2 ) adducts, which are active in formylation reactions as well as the carboxylation of aziridines to oxazolidinones. PMID:27357432

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

    PubMed

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

    2016-01-01

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

  8. 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.

  9. 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.

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

    Hu, Bao; DiMagno, Stephen G.

    2015-01-01

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

  12. Self-assembly of copper(II) complexes with a dibasic tridentate ligand and monodentate N-heterocycles: structural, magnetic and EPR studies

    NASA Astrophysics Data System (ADS)

    Das, Sunirban; Pal, Samudranil

    2005-05-01

    Three ternary copper(II) complexes of general formula [Cu(bhac)(hc)], with a tridentate Schiff base, acetylacetone benzoylhydrazone (H 2bhac) and monodentate N-heterocycles (hc=pyrazole, imidazole and pyridine), have been synthesized. Elemental analysis, various forms of spectroscopy (infrared, electronic absorption and EPR), cyclic voltammetry, cryomagnetic measurements and X-ray crystallography were used for the characterization of the complexes. Analytical data, infrared and electronic spectral features and molar conductivity values are consistent with the proposed molecular formulae and the +2 oxidation state of the metal ion in these complexes. In each complex, the enolate-O, the imine-N and the deprotonated amide-O donor tridentate ligand (bhac 2-) and the sp 2 N donor heterocycle form an O 2N 2 square-plane around the metal ion. The whole molecule of none of the complexes is perfectly planar because of different orientation of the phenyl ring plane of the tridentate ligand and that of the heterocycle ring plane with respect to the plane containing rest of the molecule. In the solid state, the complexes having the pyrazole and the pyridine as the heterocyclic ligand, exist as centrosymmetric dimeric species due to very weak apical coordination of the metal bound enolate-O. The complex of imidazole has no such apical coordination and exists as a monomer. In the crystal lattice, the molecules of these complexes are involved in a variety of intermolecular non-covalent interactions such as O-H⋯O, N-H⋯O, N-H⋯N, C-H⋯π and π⋯π. Self-assembly via these interactions lead to a one-dimensional arrangement of [Cu(bhac)(Hpyrz)]·C 2H 5OH, a two-dimensional layered structure of [Cu(bhac)(Himdz)] and a three-dimensional network of [Cu(bhac)(py)]. Cryomagnetic and EPR spectral measurements indicates weak antiferromagnetic spin-exchange in all the three complexes.

  13. Copper(II) complexes with tridentate N-(benzoyl)-N‧-(salicylidine)-hydrazine and monodentate N-heterocycles: Investigations of intermolecular interactions in the solid state

    NASA Astrophysics Data System (ADS)

    Das, Sunirban; Pal, Samudranil

    2005-10-01

    Ternary copper(II) complexes having the general formula [Cu(bhs)(hc)], with a tridentate Schiff base, N-(benzoyl)- N'-(salicylidine)-hydrazine (H 2bhs) and monodentate N-heterocycles (hc=3,5-dimethylpyrazole, pyrazole, imidazole, and pyridine), are described. The complexes were characterized by elemental analysis, spectroscopic and cryomagnetic measurements and X-ray crystallography. Analytical data, infrared and electronic spectral features and molar conductivity values are consistent with the proposed molecular formula and the +2 oxidation state of the metal ion in these complexes. Cryomagnetic and EPR spectral measurements showed weak antiferromagnetic spin-exchange in all four complexes. In each complex, the metal ion is in N 2O 2 square-plane constituted by the phenolate-O, the imine-N, and the deprotonated amide-O donor bhs 2- and the sp 2 N-donor neutral heterocycle. In the solid state, the complexes having 3,5-dimethylpyrazole, imidazole, and pyridine as the heterocyclic ligand, exist as centrosymmetric dimeric species due to weak apical coordination of the metal bound phenolate-O. On the other hand, only one of the two molecules present in the asymmetric unit of the complex containing pyrazole forms the centrosymmetric dimeric species due to weak apical coordination of the metal bound amide-O. In the crystal lattice, intermolecular π-π, C-H⋯π, C-H⋯N, O-H⋯N and N-H⋯O interactions involving the complex and the solvent molecules lead to one- and two-dimensional supramolecular structures.

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

    PubMed

    Walton, John C

    2014-04-15

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

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

    PubMed Central

    2014-01-01

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

  16. 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.

  17. 'Escentric' molecules.

    PubMed

    Schön, Geza

    2008-06-01

    Can a fragrance be revolutionary? In this commentary, the creation of two unusual, extravagant fine fragrances, 'escentric01' and 'molecule01', is described. In response to the fantasy components found in release notes of many recent perfume launches, both center around a single real fragrance raw material, the transparent woody aroma chemical 'Iso E Super' (1+2). The perfume 'escentric01' contains 65% of it, accompanied by Trisamber (3), red pepper, lime oil, incense and musks, while 'molecule01' consists exclusively of 'Iso E Super' (1+2). The elegant woody note lives here its own eccentric life--the revolution starts.

  18. Synthesis of heterocycle-attached methylidenebenzenesulfonohydrazones as antifungal agents.

    PubMed

    Gao, Zhinan; Lv, Min; Li, Qin; Xu, Hui

    2015-11-15

    A series of heterocycle-attached methylidenebenzenesulfonohydrazone derivatives were synthesized and evaluated for their antifungal activities against seven phytopathogenic fungi such as Fusarium graminearum, Alternaria solani, Valsa mali, Phytophthora capsici, Fusarium solani, Botrytis cinerea, and Glomerella cingulata. Compounds 7b, 8d, 9a, 9b and 9d exhibited a good and broad-spectrum of antifungal activities against at least five phytopathogenic fungi at the concentration of 100 μg/mL. It demonstrated that addition of one double bond between the phenylsulfonylhydrazone fragment and the furan ring of 6a,b,d could afford more active compounds 9a,b,d; however, introduction of the nitro group on the phenyl ring of 6a-9a gave less potent compounds 6e-9e. PMID:26471091

  19. 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).

  20. New catalysts with unsymmetrical N-heterocyclic carbene ligands.

    PubMed

    Tornatzky, Johanna; Kannenberg, Axel; Blechert, Siegfried

    2012-07-21

    The importance of unsymmetrical N-heterocyclic carbenes (uNHCs) as ligands in metal-catalyzed reactions is undeniable. While uNHCs show similar properties as compared with symmetrical NHCs, dissymmetrization allows for further fine-tuning. The introduction of chelatization, hemilability, bifunctionality, shielding effects, and chirality-transfer influences the catalyst's stability, reactivity, and selectivity, thus offering access to tailor-made systems including mono- and multidentate uNHC ligands. Based on selected examples, the structure-reactivity relationship of uNHCs employed in metal catalysts is presented. The focus is on catalytically active complexes, which either offer access to new applications or lead to significantly improved results in metal-catalyzed reactions. PMID:22584913

  1. 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.

  2. 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.

  3. A straightforward alkynylation of Li and Mg metalated heterocycles with sulfonylacetylenes.

    PubMed

    Marzo, Leyre; Pérez, Ignacio; Yuste, Francisco; Alemán, José; García Ruano, José Luis

    2015-01-01

    Coupling of alkynyl moieties to heterocyclic rings, without using transition metals, can be easily performed by the reaction of aryl or heteroaryl sulfonylacetylenes with heteroaryl-Li compounds or their corresponding less reactive magnesium derivatives. PMID:25407834

  4. Synthesis of heterocyclic compounds through palladium-catalyzed C-H cyclization processes.

    PubMed

    Inamoto, Kiyofumi

    2013-01-01

    Herein, we describe our development of synthetic methods for heterocyclic compounds based on the palladium-catalyzed carbon-hydrogen bond (C-H) functionalization/intramolecular carbon-heteroatom (nitrogen or sulfur) bond formation process. By this C-H cyclization method, we efficiently prepared various N-heterocycles, including indazoles, indoles, and 2-quinolinones, as well as S-heterocycles such as benzothiazoles and benzo[b]thiophenes. Yields are typically good to high and good functional-group tolerance is observed for each process, thereby indicating that the method provides a novel, highly applicable synthetic route to the abovementioned biologically important heterocyclic frameworks. As an application of this approach, an auto-tandem-type, one-pot process involving the oxidative Heck reaction and subsequent C-H cyclization using cinnamamides and arylboronic acids as starting materials in the presence of a palladium catalyst was also developed for the rapid construction of the 2-quinolinone nucleus. PMID:24088691

  5. 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...

  6. 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...

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

    PubMed

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

    2015-11-01

    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. PMID:26434694

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

    PubMed Central

    2011-01-01

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

  9. Extending the utility of [Pd(NHC)(cinnamyl)Cl] precatalysts: Direct arylation of heterocycles

    PubMed Central

    Martin, Anthony R; Chartoire, Anthony; Slawin, Alexandra M Z

    2012-01-01

    Summary The use of [Pd(NHC)(cinnamyl)Cl] precatalysts in the direct arylation of heterocycles has been investigated. Among four different precatalysts, [Pd(SIPr)(cinnamyl)Cl] proved to be the most efficient promoter of the reaction. The C–H functionalization of sulfur- or nitrogen-containing heterocycles has been achieved at low catalyst loadings. These catalyst charges range from 0.1 to 0.01 mol % palladium. PMID:23209496

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

    PubMed Central

    Chattopadhyay, Buddhadeb

    2012-01-01

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

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

    PubMed

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

    2015-11-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    1993-07-01

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

  13. Hypercrosslinked aromatic heterocyclic microporous polymers: a new class of highly selective CO2 capturing materials.

    PubMed

    Luo, Yali; Li, Buyi; Wang, Wei; Wu, Kangbing; Tan, Bien

    2012-11-01

    Aromatic heterocyclic microporous polymers with high surface areas are obtained by directly crosslinking of the heterocyclic monomers under mild conditions. Owing to the narrow pore system and the heteroatom-rich pore surface, these networks exhibit high CO(2) adsorption capacity and selectivity. At 273 K, the CO(2)/N(2) selectivity of Py-1 is about 117, which is among the highest the reported microporous materials.

  14. 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.

  15. Poly(Arylene Ether Imidazole) Surface Films

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  16. 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.

  17. [Distribution and sources of oxygen and sulfur heterocyclic aromatic compounds in surface soil of Beijing, China].

    PubMed

    He, Guang-Xiu; Zhang, Zhi-Huan; Peng, Xu-Yang; Zhu, Lei; Lu, Ling

    2011-11-01

    62 surface soil samples were collected from different environmental function zones in Beijing. Sulfur and oxygen heterocyclic aromatic compounds were detected by GC/MS. The objectives of this study were to identify the composition and distribution of these compounds, and discuss their sources. The results showed that the oxygen and sulfur heterocyclic aromatic compounds in the surface soils mainly contained dibenzofuran, methyl- and C2-dibenzofuran series, dibenzothiophene, methyl-, C2- and C3-dibenzothiophene series and benzonaphthothiophene series. The composition and distribution of the oxygen and sulfur heterocyclic aromatic compounds in the surface soil samples varied in the different environmental function zones, of which some factories and the urban area received oxygen and sulfur heterocyclic aromatic compounds most seriously. In Beijing, the degree of contamination by oxygen and sulfur heterocyclic aromatic compounds in the north surface soil was higher than that in the south. There were preferable linear correlations between the concentration of dibenzofuran series and fluorene series, as well as the concentration of dibenzothiophene series and dibenzofuran series. The oxygen and sulfur heterocyclic aromatic compounds in the surface soil were mainly derived from combustion products of oil and coal and direct input of mineral oil, etc. There were some variations in pollution sources of different environmental function zones.

  18. 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

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

    SciTech Connect

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

    1995-12-01

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

  2. Direct, Catalytic and Regioselective Synthesis of 2-Alkyl, Aryl, and Alkenyl-Substituted N-Heterocycles from N-Oxides

    PubMed Central

    Larionov, Oleg V.; Stephens, David; Mfuh, Adelphe; Chavez, Gabriel

    2014-01-01

    A one-step transformation of heterocyclic N-oxides to 2-alkyl, aryl, and alkenyl-substituted N-heterocycles is described. The success of this broad-scope methodology hinges on the combination of copper catalysis and activation by lithium fluoride or magnesium chloride. The utility of this method for the late-stage modification of complex N-heterocycles is exemplified by facile syntheses of new structural analogs of several antimalarial, antimicrobial and fungicidal agents. PMID:24410049

  3. Walking molecules.

    PubMed

    von Delius, Max; Leigh, David A

    2011-07-01

    Movement is intrinsic to life. Biologists have established that most forms of directed nanoscopic, microscopic and, ultimately, macroscopic movements are powered by molecular motors from the dynein, myosin and kinesin superfamilies. These motor proteins literally walk, step by step, along polymeric filaments, carrying out essential tasks such as organelle transport. In the last few years biological molecular walkers have inspired the development of artificial systems that mimic aspects of their dynamics. Several DNA-based molecular walkers have been synthesised and shown to walk directionally along a track upon sequential addition of appropriate chemical fuels. In other studies, autonomous operation--i.e. DNA-walker migration that continues as long as a complex DNA fuel is present--has been demonstrated and sophisticated tasks performed, such as moving gold nanoparticles from place-to-place and assistance in sequential chemical synthesis. Small-molecule systems, an order of magnitude smaller in each dimension and 1000× smaller in molecular weight than biological motor proteins or the walker systems constructed from DNA, have also been designed and operated such that molecular fragments can be progressively transported directionally along short molecular tracks. The small-molecule systems can be powered by light or chemical fuels. In this critical review the biological motor proteins from the kinesin, myosin and dynein families are analysed as systems from which the designers of synthetic systems can learn, ratchet concepts for transporting Brownian substrates are discussed as the mechanisms by which molecular motors need to operate, and the progress made with synthetic DNA and small-molecule walker systems reviewed (142 references). PMID:21416072

  4. Remote Oxidation of Aliphatic C-H Bonds in Nitrogen-Containing Molecules.

    PubMed

    Howell, Jennifer M; Feng, Kaibo; Clark, Joseph R; Trzepkowski, Louis J; White, M Christina

    2015-11-25

    Nitrogen heterocycles are ubiquitous in natural products and pharmaceuticals. Herein, we disclose a nitrogen complexation strategy that employs a strong Brønsted acid (HBF4) or an azaphilic Lewis acid (BF3) to enable remote, non-directed C(sp(3))-H oxidations of tertiary, secondary, and primary amine- and pyridine-containing molecules with tunable iron catalysts. Imides resist oxidation and promote remote functionalization. PMID:26536374

  5. Electrical conduction measurement of thiol modified DNA molecules

    NASA Astrophysics Data System (ADS)

    Hwang, J. S.; Hwang, S. W.; Ahn, D.

    2003-09-01

    We present a novel transport measurement of 60 base pairs of poly(dG)-poly(dC) DNA molecules. Thiol-terminated DNA molecules are chemically anchored at the surface of a Au nanoparticle and this DNA attached Au nanoparticle is self-trapped in between Au nanoelectrodes to make an electrical conduction channel. It provides an automatic electrical conduction channel consisting of electrode-DNA-nanoparticle-DNA-electrode. Due to robust bonding of thiol and Au, this transport channel is stable and reliable. The current-voltage characteristics measured from our device show a nonlinear behavior with voltage gaps comparable to previous experiment using the same molecules.

  6. Photoinduced Solubilization and Photocatalytic Properties of Poly(3-alkylthiophene) under Carbon Dioxide Atmosphere

    NASA Astrophysics Data System (ADS)

    Kawai, Tsuyoshi; Kuwabara, Takao; Yoshino, Katsumi

    1992-01-01

    Effects of light irradiation on poly(3-alkylthiophene) immersed in organic solvents have been studied under CO2 atmosphere. The insoluble part of poly(3-alkylthiophene) is solubilized in organic solvents by photoirradiation under CO2 atmosphere. Formation of carbonyl group in the solubilized poly(3-alkylthiophene) has been confirmed. The quenching effect of CO2 observed in the photoluminescence experiment of the poly(3-alkylthiophene) suggests electron injection from photoexcited poly(3-alkylthiophene) to CO2 molecules. Photocatalytic fixation of CO2 molecules resulting in formation of salicylic acid has also been achieved by a novel photocatalytic reaction using poly(3-alkylthiophene) as a photocatalyst under the existence of a substance such as phenol which reacts with CO2\\dot{-}.

  7. [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

  8. 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.

  9. Chelated bis-N-heterocyclic carbene platinum and palladium units as tunable components of multinuclear complexes.

    PubMed

    Maeda, Yuri; Hashimoto, Hideki; Kinoshita, Isamu; Nishioka, Takanori

    2015-01-20

    Heterometallic trinuclear M2M' complexes (M = Rh, Ir; M' = Pt, Pd) containing a platinum or palladium moiety with chelated bis-N-heterocyclic carbene ligands, [(MCp*)2{M'(bisNHC-Cn-R)}(μ3-S)2](BPh4)2 (M = Rh, Ir; M' = Pt, Pd; bisNHC-Cn-R = methylene-, ethylene-, or propylene-bridged bis(N-alkyl-imidazolylidene)), were synthesized by reacting bis(hydrosulfido)platinum(II) or palladium(II) complexs with bisNHC-Cn-R and hydroxo-bridged dinuclear complexes [(MCp*)2(μ-OH)3](BPh4), whose dinuclear structures remained intact during the formation of the trinuclear complexes, which was confirmed by using electrospray mass spectrometry and NMR spectroscopy. The heterometallic trinuclear M2M' complexes with a variety of alkylene bridges in bisNHC-Cn-R showed two reversible reduction waves in the cyclic voltammogram, and the second reduction potentials were affected by the alkylene chain lengths, which caused different dihedral angles between the imidazolylidene rings and the coordination plane of the platinum or palladium center. The M2M' complexes, except for those containing the platinum unit with the ethylene-bridged bisNHC ligands, showed dynamic behavior in solution due to the flapping wing motion of the NHC ligand moieties. Although activation parameters obtained from line-shape analyses on variable-temperature NMR spectra of the complexes suggested that the flapping wing motion occurred without bond cleavage, large negative ΔS(‡) values were obtained for the complexes with the palladium unit with the ethylene-bridged ligand, suggesting that the Pd-Ccarbene bond cleavage, accompanied by coordination of solvent molecules, occurred.

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

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

  11. 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.

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Cvetkovski, Aleksandar; Bertolasi, Valerio; Ferretti, Valeria

    2016-06-01

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

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

    PubMed

    Cvetkovski, Aleksandar; Bertolasi, Valerio; Ferretti, Valeria

    2016-06-01

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

  16. 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.

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

    PubMed

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

    2011-06-01

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

  18. 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.

  19. Trapping of neutral radicals by aromatic and heterocyclic cation radicals

    SciTech Connect

    Shine, H.J.; Soroka, M.

    1986-09-01

    A considerable amount of knowledge has been accrued during the last 15-20 years on the chemistry of polynuclear aromatic and heterocyclic cation radicals. For the most part, the reactions that have been studied have been of cation radicals with neutral and anionic nucleophiles which lead to addition or substitution products. Classic examples among these reactions are, for example, the reaction of water with the cation radical of 9,10-diphenylanthracene and perylene, and that of water with the thianthrene cation radical. Reactions such as these have been among foundation-establishing studies in the scope and mechanism of cation-radical reactions. Cation radicals can also undergo another type reaction with nucleophies, that is, electron transfer. This possibility leads to two far-reaching and connected questions: can addition and substitution reactions of aromatic cation radicals with nucleophiles be preceded by single electron transfer (SET).; and, can such cation radicals trap neutral radicals. These questions are also then related to another question having even greater impact on organic chemistry: can electrophilic aromatic substitution (ArH + E/sup +/ ..-->.. ArE + H/sup +/) be preceded by SET. The authors have been trying to answer the first two questions about SET and trapping of radicals by combining the two possibilities. That is, they have chosen the reaction of the thianthrene cation radical (represented by the symbol S/sup +./) with grignard reagents, for which two possible routes could be anticipated: either direct addition at sulfur or addition preceded by SET.

  20. 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.

  1. Prevention of heterocyclic amine formation by tea and tea polyphenols.

    PubMed

    Weisburger, J H; Nagao, M; Wakabayashi, K; Oguri, A

    1994-08-15

    Heterocyclic amines (HCAs), formed during the cooking of meats and fish, are thought to be the genotoxic carcinogens associated with important types of human cancer in meat-eating populations, such as cancer of the breast, colon or pancreas. We studied the effect of black or green tea, and of the tea polyphenols theaflavine gallate (TFG, black tea) and epigallocatechin gallate (EGCG, green tea) on the formation of typical HCAs, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), using the model in vitro systems of Jägerstad. Green tea and black tea and solutions of TFG and EGCG lower the formation of PhIP by 62-85% during 1 h heating at 160 degrees C of 1 mmol creatinine, 1 mmol phenylalanine and 0.5 mmol glucose in 3.3 ml diethylene glycol-water (10:1), where the inhibitors replaced 0.3 ml of the water. The production of MeIQx and related HCAs, in the same system but with 1 mmol glycine instead of phenylalanine was likewise reduced, determined by amounts of mutagens formed. In the latter systems, the teas were not, or less effective, but the polyphenols were inhibitory. Thus, the tea products represent another approach to lower the formation of HCAs.

  2. Formation and mitigation of heterocyclic aromatic amines in fried pork.

    PubMed

    Zhang, Yan; Yu, Chundi; Mei, Jingbo; Wang, Shuo

    2013-01-01

    Heterocyclic aromatic amines (HAAs) are potent mutagens and carcinogens generated during the heat processing of meat. HAAs, which are abundant in processed meat products, include 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), and 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP). The content of these three HAAs in fried pork was determined by LC-MS/MS. The effects of frying time and temperature, sample shape, and addition of antioxidants on the generation of HAAs were investigated. The results show that HAAs were produced during frying, and their levels increased with increasing frying time and temperature. Pork patties had the highest concentration of HAAs compared with pork meatballs and pork strips. The addition of antioxidant of bamboo leaves (AOB), liquorice extract, tea polyphenol, phytic acid and sodium iso-ascorbate to pork before frying had an inhibitory effect on HAA generation, with AOB being the most effective antioxidant. Inhibition levels of nearly 69.73% for MeIQx, 53.59% for 4,8-DiMeIQx and 77.07% for PhIP in fried pork were achieved when the concentrations of AOB added were 0.02, 0.01 and 0.10 g kg⁻¹, respectively.

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

    PubMed

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

    2016-01-14

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

  4. 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

  5. Poly-symplectic Groupoids and Poly-Poisson Structures

    NASA Astrophysics Data System (ADS)

    Martinez, Nicolas

    2015-05-01

    We introduce poly-symplectic groupoids, which are natural extensions of symplectic groupoids to the context of poly-symplectic geometry, and define poly-Poisson structures as their infinitesimal counterparts. We present equivalent descriptions of poly-Poisson structures, including one related with AV-Dirac structures. We also discuss symmetries and reduction in the setting of poly-symplectic groupoids and poly-Poisson structures, and use our viewpoint to revisit results and develop new aspects of the theory initiated in Iglesias et al. (Lett Math Phys 103:1103-1133, 2013).

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

    PubMed

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

    2015-12-10

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

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

    PubMed

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

    2015-01-01

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

  8. In vitro synthesis of uniform poly(dG)–poly(dC) by Klenow exo− fragment of polymerase I

    PubMed Central

    Kotlyar, Alexander B.; Borovok, Natalia; Molotsky, Tatiana; Fadeev, Ludmila; Gozin, Michael

    2005-01-01

    In this paper, we describe a production procedure of the one-to-one double helical complex of poly(dG)–poly(dC), characterized by a well-defined length (up to 10 kb) and narrow size distribution of molecules. Direct evidence of strands slippage during poly(dG)–poly(dC) synthesis by Klenow exo− fragment of polymerase I is obtained by fluorescence resonance energy transfer (FRET). We show that the polymer extension results in an increase in the separation distance between fluorescent dyes attached to 5′ ends of the strands in time and, as a result, losing communication between the dyes via FRET. Analysis of the products of the early steps of the synthesis by high-performance liquid chromatography and mass spectroscopy suggest that only one nucleotide is added to each of the strand composing poly(dG)–poly(dC) in the elementary step of the polymer extension. We show that proper pairing of a base at the 3′ end of the primer strand with a base in sequence of the template strand is required for initiation of the synthesis. If the 3′ end nucleotide in either poly(dG) or poly(dC) strand is substituted for A, the polymer does not grow. Introduction of the T-nucleotide into the complementary strand to permit pairing with A-nucleotide results in the restoration of the synthesis. The data reported here correspond with a slippage model of replication, which includes the formation of loops on the 3′ ends of both strands composing poly(dG)–poly(dC) and their migration over long-molecular distances (μm) to 5′ ends of the strands. PMID:15673713

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

    SciTech Connect

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

    2015-08-18

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

  10. 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

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

    PubMed Central

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

    2016-01-01

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

  12. 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.

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

    PubMed

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

    2016-07-27

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

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

    PubMed Central

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

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

    SciTech Connect

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

    1997-12-31

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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Predictors of dietary heterocyclic amine intake in three prospective cohorts.

    PubMed

    Byrne, C; Sinha, R; Platz, E A; Giovannucci, E; Colditz, G A; Hunter, D J; Speizer, F E; Willett, W C

    1998-06-01

    Cooking meat creates heterocyclic amines (HCAs) through pyrolysis of amino acids and creatinine. Although recognized as mutagenic, the etiological role of HCA in human cancer is unclear, due to the lack of information on the effect of typical food cooking methods on HCA concentrations and on variation in HCA exposure in populations. We estimated overall daily dietary HCA intake and variation in intake between individuals, using recent data on HCA concentrations in various meats prepared by cooking methods, temperatures, and times common in United States in the 1990s. Random samples of 250 participants from each of three large prospective cohorts were mailed a questionnaire to assess frequency of consumption, cooking method, and typical outside appearance of pan-fried, broiled, and grilled or barbecued chicken, fish, hamburger, and steak; fried, microwaved, and broiled bacon; fried sausage; roast beef; and homemade gravy. The 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 2-amino-3,4,8-trimethylimidazo[4,5,f]quinoxaline (DiMeIQx) concentrations, measured in composite samples by solid-phase extraction and high-performance liquid chromatography, were assigned to each food, cooking method, and doneness level. The dietary reports showed approximately 30-fold relative variation in 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline intake, 20-fold for 2-amino- -methyl-6-phenylimidazo[4,5-b]pyridine, and over 110-fold for 2-amino-3,4,8-trimethylimidazo[4,5,f]quinoxaline, when the 10th and 90th percentiles of HCA intake were compared (90th/10th percentile value). These reported variations in HCA exposure among participants in these three large cohorts indicates that estimation of HCA intake and determination of association with disease risk are feasible, if additional information on meat cooking methods is obtained.

  2. Analysis of cooked foods for new heterocyclic aromatic amines

    SciTech Connect

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

    1997-12-31

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

  3. 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.

  4. 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.

  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. 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

  7. Olefin Metathesis With Ruthenium-Arene Catalysts Bearing N-Heterocyclic Carbene Ligands

    NASA Astrophysics Data System (ADS)

    Delaude, Lionel; Demonceau, Albert

    In this chapter, we summarize the main results of our investigations on the ring-opening metathesis polymerization (ROMP) of cyclooctene catalyzed by various ruthenium (Ru)-arene complexes bearing imidazolin-2-ylidene, imidazolidin- 2-ylidene, or triazolin-5-ylidene ligands. Three major findings emerged from this study. First, we underscored the intervention of a photochemical activation step due to visible light illumination. Second, we established that the presence of an endocyclic double bond in the carbene ligand central heterocycle was not crucial to achieve high catalytic efficiencies. Third, we demonstrated that ortho-metallation of the N-heterocyclic carbene (NHC) ligand by the Ru center led to inactive catalysts.

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

    PubMed

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

    2016-08-19

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

  9. 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.

  10. Direct Arylation of Benzo[b]furan and Other Benzo-Fused Heterocycles

    PubMed Central

    Dao-Huy, Toan; Haider, Maximilian; Glatz, Fabian; Schnürch, Michael; Mihovilovic, Marko D

    2014-01-01

    The direct arylation of benzo[b]furan, benzo[b]thiophene, and indole has been studied by using aromatic bromides as the aryl source. The protocol employing common reagents and a Pd catalyst has led to the regioselective arylation of these heterocycles at the 2-position. A range of functional groups were tolerated, providing quick access to a variety of arylated benzo-fused heterocycles that would be accessible more elaborately using classical synthetic strategies. This is the first systematic study of the direct arylation of benzo[b]furan. PMID:26213483

  11. Applications of multicomponent reactions to the synthesis of diverse heterocyclic scaffolds.

    PubMed

    Sunderhaus, James D; Martin, Stephen F

    2009-01-01

    The sequencing of multicomponent reactions (MCRs) and subsequent cyclization reactions is a powerful stratagem for the rapid synthesis of diverse heterocyclic scaffolds. The optimal MCR is sufficiently flexible that it can be employed to generate adducts bearing a variety of functional groups that may then be selectively paired to enable different cyclization manifolds, thereby leading to a diverse collection of products. The growing interest in diversity-oriented synthesis has led to increased attention to this paradigm for library synthesis, which has inspired many advances in the design and implementation of MCRs for the construction of diverse heterocyclic scaffolds. PMID:19132705

  12. Transition-metal-catalyzed hydrogen-transfer annulations: access to heterocyclic scaffolds.

    PubMed

    Nandakumar, Avanashiappan; Midya, Siba Prasad; Landge, Vinod Gokulkrishna; Balaraman, Ekambaram

    2015-09-14

    The ability of hydrogen-transfer transition-metal catalysts, which enable increasingly rapid access to important structural scaffolds from simple starting materials, has led to a plethora of research efforts on the construction of heterocyclic scaffolds. Transition-metal-catalyzed hydrogen-transfer annulations are environmentally benign and highly atom-economical as they release of water and hydrogen as by-product and utilize renewable feedstock alcohols as starting materials. Recent advances in this field with respect to the annulations of alcohols with various nucleophilic partners, thus leading to the formation of heterocyclic scaffolds, are highlighted herein.

  13. Transient UV pump-IR probe investigation of heterocyclic ring-opening dynamics in the solution phase: the role played by nσ* states in the photoinduced reactions of thiophenone and furanone.

    PubMed

    Murdock, Daniel; Harris, Stephanie J; Luke, Joel; Grubb, Michael P; Orr-Ewing, Andrew J; Ashfold, Michael N R

    2014-10-21

    The heterocyclic ring-opening dynamics of thiophenone and furanone dissolved in CH3CN have been probed by ultrafast transient infrared spectroscopy. Following irradiation at 267 nm (thiophenone) or 225 nm (furanone), prompt (τ < 1 ps) ring-opening is confirmed by the appearance of a characteristic antisymmetric ketene stretching feature around 2150 cm(-1). The ring-opened product molecules are formed highly vibrationally excited, and cool subsequently on a ∼6.7 ps timescale. By monitoring the recovery of the parent (S0) bleach, it is found that ∼60% of the initially photoexcited thiophenone molecules reform the parent molecule, in stark contrast with the case in furanone where there is less than 10% parent bleach recovery. Complementary ab initio calculations of potential energy cuts along the S-C([double bond, length as m-dash]O) and O-C([double bond, length as m-dash]O) ring-opening coordinate reveals insights into the reaction mechanism, and the important role played by dissociative (n/π)σ* states in the UV-induced photochemistry of such heterocyclic systems. PMID:25175813

  14. Reaction of an N-heterocyclic carbene-stabilized silicon(II) monohydride with alkynes: [2+2+1] cycloaddition versus hydrogen abstraction.

    PubMed

    Eisenhut, Carsten; Szilvási, Tibor; Breit, Nora C; Inoue, Shigeyoshi

    2015-01-26

    An in depth study of the reactivity of an N-heterocyclic carbene (NHC)-stabilized silylene monohydride with alkynes is reported. The reaction of silylene monohydride 1, tBu3 Si(H)Si←NHC, with diphenylacetylene afforded silole 2, tBu3 Si(H)Si(C4 Ph4 ). The density functional theory (DFT) calculations for the reaction mechanism of the [2+2+1] cycloaddition revealed that the NHC played a major part stabilizing zwitterionic transition states and intermediates to assist the cyclization pathway. A significantly different outcome was observed, when silylene monohydride 1 was treated with phenylacetylene, which gave rise to supersilyl substituted 1-alkenyl-1-alkynylsilane 3, tBu3 Si(H)Si(CHCHPh)(CCPh). Mechanistic investigations using an isotope labelling technique and DFT calculations suggest that this reaction occurs through a similar zwitterionic intermediate and subsequent hydrogen abstraction from a second molecule of phenylacetylene. PMID:25413306

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

    PubMed

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

    2016-05-16

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

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

    PubMed

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

    2016-05-16

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

  17. Experimental and computational thermochemistry of three nitrogen-containing heterocycles: 2-benzimidazolinone, 2-benzoxazolinone and 3-indazolinone

    NASA Astrophysics Data System (ADS)

    Morais, V. M. F.; Miranda, M. S.; Matos, M. A. R.; Liebman, J. F.

    The standard molar enthalpies of combustion, sublimation, and formation of three nitrogen-containing heterocycles, namely, 2-benzimidazolinone, 2-benzoxazolinone and 3-indazolinone were determined calorimetrically. The standard (p° = 0.1 MPa) molar enthalpies of formation in the gas phase were derived from the standard molar enthalpies of combustion, in oxygen, at T = 298.15 K, measured by static bomb combustion calorimetry and from the standard molar enthalpies of sublimation at T = 298.15 K, measured by Calvet microcalorimetry. Møller-Plesset calculations at the MP2 level and density functional calculations with the B3LYP functional and extended basis sets were also performed to determine the energetically preferred tautomeric form of the molecules. The results were qualitatively independent of the calculational level, where in general the DFT calculations were in better agreement with experiment than those from MP2. The gas and solid phase enthalpic differences between imines and amides, wherein -CH=N- is contrasted with -CONH-, have been studied and roughly constant values have been found.

  18. Novel hybrid organic-inorganic sol-gel materials based on highly efficient heterocyclic push-pull chromophores

    NASA Astrophysics Data System (ADS)

    Abbotto, Alessandro; Bozio, Renato; Brusatin, Giovanna; Facchetti, Antonio; Guglielmi, Massimo; Innocenzi, Plinio; Meneghetti, Moreno; Pagani, Giorgio A.; Signorini, Raffaella

    1999-10-01

    We report the synthesis of sol-gel materials based on highly efficient heterocycle-based push-pull chromophores showing second- and third-order nonlinear optical activity. We show the proper functionalization of the best performing chromophores and their incorporation into a hybrid organic- inorganic sol-gel matrix. Different types of functionalization of the active molecule have been considered, including hydroxyl and alkoxysilyl end-groups. The functionalization strategy responded to different criteria such as stability and synthetic availability of the final molecular precursors, their solubility, and the used synthetic approach to the sol-gel material. The synthesis of the sol-gel materials has been tuned in order to preserve molecular properties and control important factors such as final concentration of the active dye in the matrix. Both acid- and base-catalyzed sol-gel synthesis has been taken into account. 3-Glycidoxypropyltrimethoxysilane and 3- aminopropyltriethoxysilane have been used as the organically modified alkoxides to prepare the hybrid organic-inorganic matrix. Characterization of the spectroscopic properties of the sol-gel materials is presented.

  19. New Palladium-Catalyzed Approaches to Heterocycles and Carbocycles

    SciTech Connect

    Qinhua Huang

    2004-12-19

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

  20. Effect of microwave pretreatment on heterocyclic aromatic amine mutagens/carcinogens in fried beef patties.

    PubMed

    Felton, J S; Fultz, E; Dolbeare, F A; Knize, M G

    1994-10-01

    To investigate a method to reduce the amount of mutagenic/carcinogenic heterocyclic aromatic amines formed during frying of ground beef, the mutagenic activity in Salmonella strain TA98 was assessed and the amount of known heterocyclic amines was determined by solid-phase extraction and HPLC. The beef patties received microwave treatment for various times before frying. Microwave pretreatment for 0, 1, 1.5, 2 or 3 min before frying at either 200 degrees C or 250 degrees C for 6 min per side reduced heterocyclic aromatic amine precursors (creatine, creatinine, amino acids, glucose), water, and fat up to 30%, in the patties and resulted in a decrease in mutagenic activity up to 95%. The sum of the four heterocyclic aromatic amines shown to be present--2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4,8-trimethylimidazo-[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)--decreased three- to nine-fold compared with control, non-microwaved beef patties fried under identical conditions.

  1. N-Amination of pyrrole and indole heterocycles with monochloramine (NH2Cl).

    PubMed

    Hynes, John; Doubleday, Wendel W; Dyckman, Alaric J; Godfrey, Jollie D; Grosso, John A; Kiau, Susanne; Leftheris, Katerina

    2004-02-20

    A survey of several electrophilic ammonia reagents for the N-amination of indole- and pyrrole-containing heterocycles revealed that monochloramine (NH(2)Cl) is an excellent reagent for this transformation. Pyrroles and indoles containing a variety of substitution were aminated on nitrogen with isolated yields ranging from 45% to 97%. PMID:14961694

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

    PubMed

    Prema, Dipesh; Mathota Arachchige, Yohan L N; Murray, Rex E; Slaughter, LeGrande M

    2015-04-21

    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 precatalyst containing the intact iminocarbene ligand.

  3. 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...

  4. 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…

  5. "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...

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

    PubMed

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

    2015-12-18

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

  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. Mild and metal-free oxy- and amino-fluorination for the synthesis of fluorinated heterocycles.

    PubMed

    Parmar, Dixit; Rueping, Magnus

    2014-11-21

    A mild intramolecular fluoro-cyclisation reaction of benzylic alcohols and amines has been developed. This strategy uses commercially available Selectfluor to trigger electrophilic cyclisations to afford fluorinated heterocycles containing 1,3-disubstitution. The dual role of the reagent as a fluorine source and a base is shown to be crucial for reactivity.

  9. Rapid and efficient synthesis of fused heterocyclic pyrimidines under ultrasonic irradiation.

    PubMed

    Mosslemin, Mohammad Hossein; Nateghi, Mohammad Reza

    2010-01-01

    Some fused heterocyclic pyrimidines have been synthesized in high yields using ultrasound irradiation in a one-pot, three-component and efficient process by condensation reaction of barbituric acids, aldehydes and a series of enamines in water. Prominent among the advantages of this new method are operational simplicity, good yields in short reaction times and easy work-up procedures employed.

  10. Electrochemical flow-reactor for expedient synthesis of copper-N-heterocyclic carbene complexes.

    PubMed

    Chapman, Michael R; Shafi, Yarseen M; Kapur, Nikil; Nguyen, Bao N; Willans, Charlotte E

    2015-01-25

    An electrochemical flow-cell for highly efficient and selective generation of Cu(I)-N-heterocyclic carbene complexes under neutral and ambient conditions is reported. The feasibility of the flow-cell is demonstrated through the electrochemical synthesis of [Cu(IMes)Cl] and subsequent in situ flow directly into hydrosilylation reactions, with equal efficiency to the purified catalyst.

  11. Influence of bulky yet flexible N-heterocyclic carbene ligands in gold catalysis.

    PubMed

    Collado, Alba; Patrick, Scott R; Gasperini, Danila; Meiries, Sebastien; Nolan, Steven P

    2015-01-01

    Three new Au(I) complexes of the formula [Au(NHC)(NTf2)] (NHC = N-heterocyclic carbene) bearing bulky and flexible ligands have been synthesised. The ligands studied are IPent, IHept and INon which belong to the 'ITent' ('Tent' for 'tentacular') family of NHC derivatives. The effect of these ligands in gold-promoted transformations has been investigated.

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

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

    PubMed Central

    Langer, Thomas; Bower, John F.

    2016-01-01

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

  14. Heterocyclic aminoparthenolide derivatives modulate G(2)-M cell cycle progression during Xenopus oocyte maturation.

    PubMed

    Janganati, Venumadhav; Penthala, Narsimha Reddy; Cragle, Chad E; MacNicol, Angus M; Crooks, Peter A

    2014-04-15

    Aminoparthenolide derivatives have been prepared by reaction of parthenolide with various heterocyclic amines to afford corresponding Michael addition products. These novel compounds were evaluated for their modulatory effects on Xenopus oocyte maturation. Two compounds, 6e and 6f, were identified that promote G2-M cell cycle progression.

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

    PubMed

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

    2015-12-18

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

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

    NASA Astrophysics Data System (ADS)

    Chia, Mei

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

  17. Accessible gold clusters using calix[4]arene N-heterocyclic carbene and phosphine ligands.

    PubMed

    Nigra, Michael M; Yeh, Alexander J; Okrut, Alexander; DiPasquale, Antonio G; Yeh, Sheila W; Solovyov, Andrew; Katz, Alexander

    2013-09-21

    We investigate the synthesis of accessible calix[4]arene-bound gold clusters consisting of open "coordinatively unsaturated" active sites, using a comparative approach that relies on calix[4]arene ligands with various upper- and lower-rim substituents. In contrast with a reported Au(I)-tert-butyl-calixarene phosphine complex, which exhibits a single cone conformer in solution, the H upper-rim analog exhibits multiple conformers in solution. This contrasts with observations of the tert-butyl upper-rim analog, which exhibits a single cone conformer in solution under similar conditions. In the solid state, as determined by single-crystal X-ray diffraction, both H and tert-butyl upper-rim analogs exhibit exclusively cone conformer. A detailed structural analysis of these two solid-state structures highlights a CH-π interaction involving a methoxy lower-rim substituent and phenyl substituent on P as the key feature that enforces a tight configuration of Au(I) atoms on the same side of the calix[4]arene lower-rim plane. We hypothesize that such a configuration promotes chelation of the ligand to a gold surface and facilitates the synthesis of small Au11-sized clusters after reduction of both complexes. The new cluster, like the one reported with the tert-butyl analog, has an extraordinary 25% of surface atoms that are open and accessible to a 2-NT (2-naphthalenethiol) probe in solution. We also investigated the effect of calix[4]arene lower-rim substituents that coordinate to the metal, by using N-heterocyclic carbene (NHC) functional groups rather than phosphines. Four small (<1.6 nm diameter) calix[4]arene NHC-bound gold clusters were synthesized, including three using novel calix[4]arene NHC ligands. The smallest calix[4]arene NHC-bound Au cluster consisted of a 1.2 nm gold core, and its number density of accessible and open surface sites was measured. This required development of a new titration method for open sites on gold clusters, using a SAMSA fluorescein dye

  18. 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

  19. 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.

  20. 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

  1. Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

    PubMed Central

    Novikov, Mikhail S; Pakalnis, Viktoriia V; Iakovenko, Roman O; Yufit, Dmitry S

    2014-01-01

    Summary 3-Aryl-2H-azirines react with acylketenes, generated by thermolysis of 5-arylfuran-2,3-diones, to give bridged 5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8-diene-2,10-diones and/or ortho-fused 6,6a,12,12a-tetrahydrobis[1,3]oxazino[3,2-a:3′,2′-d]pyrazine-4,10-diones. The latter compounds, with a new heterocyclic skeleton, are the result of the coupling of two molecules of azirine and two molecules of acylketene and can be prepared only from 3-aryl-2H-azirines having no electron-withdrawing groups in the aryl substituent. Calculations at the DFT B3LYP/6-31G(d) level for the various routes of bis[1,3]oxazino[3,2-a:3′,2′-d]pyrazine skeleton formation revealed a new domino reaction of 3-aryl-2H-azirines occurring in the presence of furandiones: acid-catalyzed dimerization to dihydropyrazine followed by consecutive cycloaddition of the latter to two molecules of acylketenes. PMID:24778733

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

    PubMed

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

    2016-07-27

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

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

    PubMed

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

    2016-07-27

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

  4. 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

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

    PubMed

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

    2015-08-01

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

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

    PubMed

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

    2014-02-25

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

  7. 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

  8. 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.

  9. 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 ...

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Decisive interactions between the heterocyclic moiety and the cluster observed in polyoxometalate-surfactant hybrid crystals.

    PubMed

    Otobe, Saki; Fujioka, Natsumi; Hirano, Takuro; Ishikawa, Eri; Naruke, Haruo; Fujio, Katsuhiko; Ito, Takeru

    2015-04-16

    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.

  15. 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.

  16. Clicking the Arsenic-Carbon Triple Bond: An Entry into a New Class of Arsenic Heterocycles.

    PubMed

    Pfeifer, Gregor; Papke, Martin; Frost, Daniel; Sklorz, Julian A W; Habicht, Marija; Müller, Christian

    2016-09-19

    Arsaalkynes can undergo regioselective and quantitative [3+2] cycloaddition reactions with organic azides to give hitherto unknown 3H-1,2,3,4-triazaarsole derivatives. The reaction product was obtained as a white, air- and moisture-stable solid, and the presence of a planar, five-membered arsenic heterocycle was unambiguously verified by means of X-ray crystallography. DFT calculations gave insight into the electronic structure of these novel compounds compared to tetrazoles and triazaphospholes. The coordination chemistry towards Re(I) was investigated and compared with the structurally related phosphorus-containing ligand. These preliminary investigations pave the way for a new class of arsenic heterocycles and fill the gap between the azaarsoles already known. PMID:27460759

  17. 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

  18. Microwave assisted synthesis of unsaturated jasmone heterocyclic analogues as new fragrant substances.

    PubMed

    Pawełczyk, Anna; Zaprutko, Lucjusz

    2009-07-01

    Taking the rising interest in jasmone structure based fragrant compounds into account it has been decided to take up an attempt to synthesize the new heterocyclic derivatives of this 2,3-disubstituted cyclopentenone, which could be characterized by the ability of interaction with the same receptors with which jasmone affects. Obtained structures of unsaturated heterocyclic derivatives are based on pyrrolidinone, oxazolidinone, pyrazolidinone, pyrazolone and thiazolidinone systems with 2-double or 2-triple unsaturated five-carbon side chain. The rapid, highly yielding and ecofriendly microwave assisted organic syntheses (MAOS) have been used to obtain compounds mentioned above. Odor evaluation and relationships between their structure and osmic properties for all synthesized fragrant compounds have been studied. It has been shown that the majority of the obtained compounds have exhibited interesting, very intensive and fixative fragrant properties.

  19. Difunctional and heterocyclic products from the ozonolysis of conjugated C sub 5 -C sub 8 cyclodienes

    SciTech Connect

    Griesbaum, K.; In Chan Jung; Mertens, H. )

    1990-11-23

    Ozonolyses of the conjugated C{sub 5}-C{sub 8} cyclodienes 1a-d in methanol, followed by reduction with DMS, have been examined. Monoozonolyses gave the corresponding unsaturated dialdehydes 2e as the primary products. In subsequent reactions, the dialdehydes 2e derived from the monoozonolyses of 1a, 1b, and 1c gave in high yields the heterocyclic compounds 7, 8k, and 9k, respectively. Diozonolyses of 1a-d gave the corresponding dialdehydes 3e as the primary products. In subsequent reactions, the dialdehydes 3e derived from 1b and 1c gave the heterocyclic compounds 8l, and 9l, respectively. In addition, aldehydes 2e and 3e underwent partial acetalization reactions with methanol.

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

    PubMed

    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

  1. Inhibitory effect of lichen constituents on mutagenicity induced by heterocyclic amines

    SciTech Connect

    Osawa, T.; Kumon, H.; Reece, C.A.; Shibamoto, T. )

    1991-01-01

    Physodic acid, one of the main constituents of Hypogymnia enteromorpha, inhibited the mutagenicity of indirect mutagens, including benzo(a)pyrene and heterocyclic amines in Salmonella typhimurium TA 98. In contrast, it was not effective against direct mutagens such as 6-nitropiperonal and adriamycin. Its antimutagenicity was not associated with free-radical scavenging or antioxidative activities. Physodic acid seemed to inhibit the formation of reactive metabolites, such as N-hydroxy-Trp-P-2, by blocking the hepatic microsomal oxidation systems. Another component of H. enteromorpha, physodalic acid, also inhibited mutagenicity of a heterocyclic amine, Trp-P-2, in S. typhimurium TA 98, even though it was reportedly mutagenic in S. typhimurium TA 100.

  2. Carbonic Anhydrase Inhibitors. Part 541: Metal Complexes of Heterocyclic Sulfonamides: A New Class of Antiglaucoma Agents

    PubMed Central

    Scozzafava, Andrea; Jitianu, Andrei

    1997-01-01

    Metal complexes of heterocyclic sulfonamides possessing carbonic anhydrase (CA) inhibitory properties were recently shown to be useful as intraocular pressure (IOP) lowering agents in experimental animals, and might be developed as a novel class of antiglaucoma drugs. Here we report the synthesis of a heterocyclic sulfonamide CA inhibitor and of the metal complexes containing main group metal ions, such as Be(II), Mg(II), Al(III), Zn(II), Cd(II) and Hg(II) and the new sulfonamide as well as 5-amino-1,3,4-thiadiazole-2-sulfonamide as ligands. The new complexes were characterized by standard physico-chemical procedures, and assayed as inhibitors of three CA isozymes, CA I, II and IV. Some of them (but not the parent sulfonamides) strongly lowered IOP in rabbits when administered as a 2% solution into the eye. PMID:18475811

  3. 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

  4. NMR Signal Amplification by Reversible Exchange of Sulfur-Heterocyclic Compounds Found In Petroleum

    PubMed Central

    Coffey, Aaron M.; Goodson, Boyd M.; Chekmenev, Eduard Y.

    2016-01-01

    NMR hyperpolarization via Signal Amplification by Reversible Exchange (SABRE) was employed to investigate the feasibility of enhancing the NMR detection sensitivity of sulfur-heterocycles (specifically 2-methylthiophene and dibenzothiophenes), a family of compounds typically found in petroleum and refined petroleum products. SABRE hyperpolarization of sulfur-heterocycles (conducted in seconds) offers potential advantages of providing structural information about sulfur-containing contaminants in petroleum, thereby informing petroleum purification and refining to minimize sulfur content in refined products such as gasoline. Moreover, NMR spectroscopy sensitivity gains endowed by hyperpolarization potentially allows for performing structural assays using inexpensive, low-magnetic-field (ca. 1 T) high-resolution NMR spectrometers ideally suited for industrial applications in the field. PMID:27500206

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

    PubMed

    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.

  6. Nitrogen-heterocyclic compounds in meteorites - Significance and mechanisms of formation

    NASA Astrophysics Data System (ADS)

    Stoks, P. G.; Schwartz, A. W.

    1981-04-01

    Samples of the Murchison, Murray, and Orgueil carbonaceous meteorites were analyzed for nitrogen-heterocyclic compounds using gas chromatography, cation and anion exclusion liquid chromatography, and mass spectrometry. The H2O and HCOOH extracts, as well as the 3M-HCl hydrolyzate of the Allende sample were taken through all stages of analysis. Concentrations ranging from 114-655 ppb of the purines adenine, guanine, hypoxanthine, and xanthine were found to be present in acid extracts. All four biologically significant purines, as well as the pyrimidine uracil have been identified in meteorites. It was concluded that the suite of N-heterocyclic compounds identified in meteorites do not permit a clear distinction between mechanisms of synthesis such as the Fischer-Tropsch type, and other candidates.

  7. Two cytochromes P450 catalyze S-heterocyclizations in cabbage phytoalexin biosynthesis.

    PubMed

    Klein, Andrew P; Sattely, Elizabeth S

    2015-11-01

    Phytoalexins are abundant in edible crucifers and have important biological activities, yet no dedicated gene for their biosynthesis is known. Here, we report two new cytochromes P450 from Brassica rapa (Chinese cabbage) that catalyze unprecedented S-heterocyclizations in cyclobrassinin and spirobrassinin biosynthesis. Our results provide genetic and biochemical insights into the biosynthesis of a prominent pair of dietary metabolites and have implications for pathway discovery across >20 recently sequenced crucifers.

  8. 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)

  9. Asymmetric Hydroformylation of Heterocyclic Olefins Mediated by Supramolecularly Regulated Rhodium-Bisphosphite Complexes.

    PubMed

    Rovira, Laura; Vaquero, Mónica; Vidal-Ferran, Anton

    2015-10-16

    Rhodium complexes derived from conformationally transformable α,ω-bisphosphite ligands combined with a suitable alkali metal BArF salt as a regulation agent (RA) provide high regio- and enantioselectivities in the asymmetric hydroformylation (AHF) of three heterocyclic olefins. The outcome of the AHF could be exquisitely regulated by choosing the appropriate RA with an increase in the ee, the reversal of the regioselectivity, or the complete suppression of one byproduct. PMID:26355601

  10. Platinum(iv) N-heterocyclic carbene complexes: their synthesis, characterisation and cytotoxic activity.

    PubMed

    Bouché, M; Dahm, G; Wantz, M; Fournel, S; Achard, T; Bellemin-Laponnaz, S

    2016-07-28

    Platinum(ii) N-heterocyclic carbene complexes have been oxidized by bromine or iodobenzene dichloride to provide the fully characterised corresponding platinum(iv) NHC complexes. Antiproliferative activities of Pt(iv) NHC complexes were assayed against several cancer cell lines and the results were correlated with respect to their stability. Mechanistic investigations revealed that mitochondrial dysfunction and ROS production were associated with the cytotoxic process induced by these compounds. PMID:27331604

  11. Pyridynes and indolynes as building blocks for functionalized heterocycles and natural products.

    PubMed

    Goetz, Adam E; Shah, Tejas K; Garg, Neil K

    2015-01-01

    Heterocyclic arynes, or hetarynes, have been studied for over 100 years. However, challenges associated with observing these reactive species, as well as developing synthetically useful methods for their generation and trapping, have limited their use. This review provides a brief historical perspective on the field of hetarynes, in addition to a discussion of pyridyne and indolyne methodologies. Moreover, this review highlights the use of pyridynes, indolynes, and related strained intermediates in natural product synthesis.

  12. N-heterocyclic carbene organocatalytic reductive β,β-coupling reactions of nitroalkenes via radical intermediates.

    PubMed

    Du, Yu; Wang, Yuhuang; Li, Xin; Shao, Yaling; Li, Guohui; Webster, Richard D; Chi, Yonggui Robin

    2014-11-01

    An unprecedented N-heterocyclic carbene catalytic reductive β,β-carbon coupling of α,β-nitroalkenes, by using an organic substrate to mimic the one-electron oxidation role of the pyruvate ferredoxin oxidoreductase (PFOR) in living systems, has been developed. The reaction goes through a radical anion intermediate generated under a catalytic redox process. For the first time, the presence of radical anion intermediate in NHC organocatalysis is observed and clearly verified. PMID:25343564

  13. Non-covalent thrombin inhibitors featuring P3-heterocycles with P1-bicyclic arginine surrogates.

    PubMed

    Cui, Jingrong Jean; Araldi, Gian-Luca; Reiner, John E; Reddy, Komandla Malla; Kemp, Scott J; Ho, Jonathan Z; Siev, Daniel V; Mamedova, Lala; Gibson, Tony S; Gaudette, John A; Minami, Nathaniel K; Anderson, Susanne M; Bradbury, Annette E; Nolan, Thomas G; Semple, J Edward

    2002-10-21

    Novel, potent, and highly selective classes of thrombin inhibitors were identified, which resulted from judicious combination of P4-aromatics and P2-P3-heterocyclic dipeptide surrogates with weakly basic (calcd pKa approximately non-basic-8.6) bicyclic P1-arginine mimics. The design, synthesis, and biological activity of achiral, non-covalent, orally bioavailable inhibitors NC1-NC44 featuring P1-indazoles, benzimidazoles, indoles, benzotriazoles, and aminobenzisoxazoles is disclosed.

  14. Sustainable synthesis of diverse privileged heterocycles by palladium-catalyzed aerobic oxidative isocyanide insertion.

    PubMed

    Vlaar, Tjøstil; Cioc, Razvan C; Mampuys, Pieter; Maes, Bert U W; Orru, Romano V A; Ruijter, Eelco

    2012-12-21

    O(2) in, H(2)O out: Various diamines and related bisnucleophiles readily undergo oxidative isocyanide insertion with Pd(OAc)(2) (1 mol %) as the catalyst and O(2) as the terminal oxidant to give a diverse array of medicinally relevant N heterocycles. The utility of this highly sustainable method is demonstrated by a formal synthesis of the antihistamines astemizole and norastemizole. PMID:23161862

  15. Effects of marinating on heterocyclic amine carcinogen formation in grilled chicken.

    PubMed

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

    1997-05-01

    This study compared heterocyclic aromatic amines in marinated and unmarinated chicken breast meat flame-broiled on a propane grill. Chicken was marinated prior to grilling and the levels of several heterocyclic amines formed during cooking were determined by solid-phase extraction and HPLC. Compared with unmarinated controls, a 92-99% decrease in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was observed in whole chicken breast marinated with a mixture of brown sugar, olive oil, cider vinegar, garlic, mustard, lemon juice and salt, then grilled for 10, 20, 30 or 40 min. Conversely, 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) increased over 10-fold with marinating, but only at the 30 and 40 min cooking times. Marinating reduced the total detectable heterocyclic amines from 56 to 1.7 ng/g, from 158 to 10 ng/g and from 330 to 44 ng/g for grilling times of 20, 30 and 40 min, respectively. The mutagenic activity of the sample extracts was also measured, using the Ames/Salmonella assay. Mutagenic activity was lower in marinated samples cooked for 10, 20 and 30 min, but higher in the marinated samples cooked for 40 min, compared with unmarinated controls. Although a change in free amino acids, which are heterocyclic amine precursors, might explain the decrease in PhIP and increase in MeIQx, no such change was detected. Marinating chicken in one ingredient at a time showed that sugar was involved in the increased MeIQx, but the reason for the decrease in PhIP was unclear. PhIP decreased in grilled chicken after marinating with several individual ingredients. This work shows that marinating is one method that can significantly reduce PhIP concentration in grilled chicken. PMID:9216741

  16. Influence of bulky yet flexible N-heterocyclic carbene ligands in gold catalysis

    PubMed Central

    Collado, Alba; Patrick, Scott R; Gasperini, Danila; Meiries, Sebastien

    2015-01-01

    Summary Three new Au(I) complexes of the formula [Au(NHC)(NTf2)] (NHC = N-heterocyclic carbene) bearing bulky and flexible ligands have been synthesised. The ligands studied are IPent, IHept and INon which belong to the ‘ITent’ (‘Tent’ for ‘tentacular’) family of NHC derivatives. The effect of these ligands in gold-promoted transformations has been investigated. PMID:26664600

  17. 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

  18. Alkyne-azide cycloaddition catalyzed by silver chloride and "abnormal" silver N-heterocyclic carbene complex.

    PubMed

    Ortega-Arizmendi, Aldo I; Aldeco-Pérez, Eugenia; Cuevas-Yañez, Erick

    2013-01-01

    A library of 1,2,3-triazoles was synthesized from diverse alkynes and azides using catalytic amounts of silver chloride instead of copper compounds. In addition, a novel "abnormal" silver N-heterocyclic carbene complex was tested as catalyst in this process. The results suggest that the reaction requires only 0.5% of silver complex, affording 1,2,3-triazoles in good yields. PMID:24307866

  19. 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.

  20. 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

  1. Carotenoids Play a Positive Role in the Degradation of Heterocycles by Sphingobium yanoikuyae

    PubMed Central

    Liu, Xiaorui; Gai, Zhonghui; Tao, Fei; Tang, Hongzhi; Xu, Ping

    2012-01-01

    Background Microbial oxidative degradation is a potential way of removing pollutants such as heterocycles from the environment. During this process, reactive oxygen species or other oxidants are inevitably produced, and may cause damage to DNA, proteins, and membranes, thereby decreasing the degradation rate. Carotenoids can serve as membrane-integrated antioxidants, protecting cells from oxidative stress. Findings Several genes involved in the carotenoid biosynthetic pathway were cloned and characterized from a carbazole-degrading bacterium Sphingobium yanoikuyae XLDN2-5. In addition, a yellow-pigmented carotenoid synthesized by strain XLDN2-5 was identified as zeaxanthin that was synthesized from β-carotene through β-cryptoxanthin. The amounts of zeaxanthin and hydrogen peroxide produced were significantly and simultaneously enhanced during the biodegradation of heterocycles (carbazole < carbazole + benzothiophene < carbazole + dibenzothiophene). These higher production levels were consistent with the transcriptional increase of the gene encoding phytoene desaturase, one of the key enzymes for carotenoid biosynthesis. Conclusions/Significance Sphingobium yanoikuyae XLDN2-5 can enhance the synthesis of zeaxanthin, one of the carotenoids, which may modulate membrane fluidity and defense against intracellular oxidative stress. To our knowledge, this is the first report on the positive role of carotenoids in the biodegradation of heterocycles, while elucidating the carotenoid biosynthetic pathway in the Sphingobium genus. PMID:22745775

  2. 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

  3. Inhibitory activity of cigarette-smoke condensate on the mutagenicity of heterocyclic amines.

    PubMed

    Lee, C K; Munoz, J A; Fulp, C; Chang, K M; Rogers, J C; Borgerding, M F; Doolittle, D J

    1994-07-01

    Cigarette-smoke condensate (CSC) is a complex mixture containing over 3800 identified chemicals including nicotine, water, mutagens, antimutagens, cytotoxins and inert chemicals. Although CSC is mutagenic in the Ames test, its effect on the activity of other mutagens has not been characterized. Using the Ames Salmonella bacterial mutagenesis assay, we found CSC exerts a significant inhibitory effect on mutagens requiring bioactivation. Those studied included heterocyclic amines (Glu-P-1, Glu-P-2, IQ, MeIQ, Trp-P-1 and Trp-P-2), benzo[a]pyrene (B[a]P) and aflatoxin B1. However, CSC had no effect on the activity of direct-acting mutagens (2-nitrofluorene, sodium azide, 4-nitro-1,2-phenylenediamine, 4-nitroquinoline N-oxide and methyl methanesulfonate). With indirect-acting mutagens, the reduced number of revertants observed in the presence of CSC was not attributable to cytotoxicity. CSC exhibited a potent inhibitory effect on the cytochrome P-450 dependent monooxygenases, ethoxyresorufin O-deethylase and B[a]P hydroxylase. This suggests inhibition of the cytochrome P-450 isozymes as one possible mechanism for the antimutagenicity of CSC. Fractionation studies of CSC revealed that the neutral, weakly acidic (phenolic) and basic fractions are all effective as antimutagens against Glu-P-1, a representative heterocyclic amine. This indicates that several classes of chemicals contribute to the inhibitory effect of CSC on the mutagenicity of the heterocyclic amines. PMID:7517501

  4. Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

    PubMed Central

    Shakoori, Alireza; Bremner, John B; Abdel-Hamid, Mohammed K; Willis, Anthony C; Haritakun, Rachada

    2015-01-01

    Summary Diversity-directed synthesis based on the cascade allylation chemistry of indigo, with its embedded 2,2’-diindolic core, has resulted in rapid access to new examples of the hydroxy-8a,13-dihydroazepino[1,2-a:3,4-b']diindol-14(8H)-one skeleton in up to 51% yield. Additionally a derivative of the novel bridged heterocycle 7,8-dihydro-6H-6,8a-epoxyazepino[1,2-a:3,4-b']diindol-14(13H)-one was produced when the olefin of the allylic substrate was terminally disubstituted. Further optimisation also produced viable one-pot syntheses of derivatives of the spiro(indoline-2,9'-pyrido[1,2-a]indol)-3-one (65%) and pyrido[1,2,3-s,t]indolo[1,2-a]azepino[3,4-b]indol-17-one (72%) heterocyclic systems. Ring-closing metathesis of the N,O-diallylic spiro structure and subsequent Claisen rearrangement gave rise to the new (1R,8aS,17aS)-rel-1,2-dihydro-1-vinyl-8H,17H,9H-benz[2',3']pyrrolizino[1',7a':2,3]pyrido[1,2-a]indole-8,17-(2H,9H)-dione heterocyclic system. PMID:25977722

  5. Tandem reactions initiated by copper-catalyzed cross-coupling: a new strategy towards heterocycle synthesis.

    PubMed

    Liu, Yunyun; Wan, Jie-Ping

    2011-10-21

    Copper-catalyzed cross-coupling reactions which lead to the formation of C-N, C-O, C-S and C-C bonds have been recognized as one of the most useful strategies in synthetic organic chemistry. During past decades, important breakthroughs in the study of Cu-catalyzed coupling processes demonstrated that Cu-catalyzed reactions are broadly applicable to a variety of research fields related to organic synthesis. Representatively, employing these coupling transformations as key steps, a large number of tandem reactions have been developed for the construction of various heterocyclic compounds. These tactics share the advantages of high atom economics of tandem reactions as well as the broad tolerance of Cu-catalyst systems. Therefore, Cu-catalyzed C-X (X = N, O, S, C) coupling transformation-initiated tandem reactions were quickly recognized as a strategy with great potential for synthesizing heterocyclic compounds and gained worldwide attention. In this review, recent research progress in heterocycle syntheses using tandem reactions initiated by copper-catalyzed coupling transformations, including C-N, C-O, C-S as well as C-C coupling processes are summarized. PMID:21879127

  6. 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.

  7. Mutagenic activities of heterocyclic amines in Chinese hamster lung cells in culture

    SciTech Connect

    Terada, M.; Nagao, M.; Nakayasu, M.; Sakamoto, H.; Nakasato, F.; Sugimura, T.

    1986-01-01

    A mutation assay system with Chinese hamster lung cells (CHL) using diphtheria toxin resistance as a selective marker has been established. The mutagenic activities of heterocyclic amines, originally isolated from pyrolyzates of amino acids and proteins, broiled fish and fried beef were assayed in cultured CHL cells in the absence and presence of a metabolic activation system, with diphtheria toxin resistance as a marker. All the heterocyclic amines tested except 3-amino-1,4-dimethyl-5H-pyrido (4,3-b)indole (Trp-P-1) required the presence of a metabolic activation system for mutagenicity on CHL cells. 3-Amino-1-methyl-5H-pyrido(4,3-b)indole (Trp-P-2) was the most mutagenic among the heterocyclic amines tested. Other compounds were also mutagenic in the following order of decreasing potency: Trp-P-1, 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ), 2-amino-3-methylimidazo(4,5-f)quinoline (IQ), 2-amino-9H-pyrido(2,3-b)indole (A..cap alpha..C), 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx), 2-amino-6-methyldipyrido(1,2-a:3',2'-d)imidazole (Glu-P-1) and 2-aminodipyrido(1,2--a:3',2'-d)imidazole (Glu-P-2).

  8. 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

  9. Synthesis, anticancer activity and molecular docking studies on a series of heterocyclic trans-cyanocombretastatin analogues as antitubulin agents.

    PubMed

    Penthala, Narsimha Reddy; Zong, Hongliang; Ketkar, Amit; Madadi, Nikhil Reddy; Janganati, Venumadav; Eoff, Robert L; Guzman, Monica L; Crooks, Peter A

    2015-03-01

    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 stabilized 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.

  10. 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

  11. Investigation of the hydration of nonfouling material poly(sulfobetaine methacrylate) by low-field nuclear magnetic resonance.

    PubMed

    Wu, Jiang; Lin, Weifeng; Wang, Zhen; Chen, Shengfu; Chang, Yung

    2012-05-15

    The strong surface hydration layer of nonfouling materials plays a key role in their resistance to nonspecific protein adsorption. Poly(sulfobetaine methacrylate) (polySBMA) is an effective material that can resist nonspecific protein adsorption and cell adhesion. About eight water molecules are tightly bound with one sulfobetaine (SB) unit, and additional water molecules over 8:1 ratio mainly swell the polySBMA matrix, which is obtained through the measurement of T(2) relaxation time by low-field nuclear magnetic resonance (LF-NMR). This result was also supported by the endothermic behavior of water/polySBMA mixtures measured by differential scanning calorimetry (DSC). Furthermore, by comparing both results of polySBMA and poly(ethylene glycol) (PEG), it is found that (1) the hydrated water molecules on the SB unit are more tightly bound than on the ethylene glycol (EG) unit before saturation, and (2) the additional water molecules after forming the hydration layer in polySBMA solutions show higher freedom than those in PEG. These results might illustrate the reason for higher resistance of zwitterionic materials to nonspecific protein adsorptions compared to that of PEGs. PMID:22512533

  12. The development and catalytic uses of N-heterocyclic carbene gold complexes.

    PubMed

    Nolan, Steven P

    2011-02-15

    Gold has emerged as a powerful synthetic tool in the chemist's arsenal. From the early use of inorganic salts such as AuCl and AuCl(3) as catalysts, the field has evolved to explore ligands that fine-tune reactivity, stability, and, more recently, selectivity in gold-mediated processes. Substrates generally contain alkenes or alkynes, and they usually involve straightforward protocols in air with solvents that can often times be of technical grade. The actual catalytic species is the putative cationic gold(I) complex [Au(L)](+) (where L is a phosphorus-based species or N-heterocyclic carbene, NHC). The early gold systems bearing phosphine and phosphite ligands provided important transformations and served as useful mechanistic probes. More recently, the use of NHCs as ligands for gold has rapidly gained in popularity. These two-electron donor ligands combine strong σ-donating properties with a steric profile that allows for both stabilization of the metal center and enhancement of its catalytic activity. As a result, the gold-NHC complexes have been used as well-defined precatalysts and have permitted the isolation of reactive single-component systems that are now used instead of the initial [Au(L)Cl]/silver salt method. Because some are now commercially available, NHC-containing gold(I) complexes are gathering increasing interest. In this Account, we describe the chronological development of this chemistry in our laboratories, highlighting the advantages of this family of gold complexes and reviewing their synthesis and applications in catalysis. We first outline the syntheses, which are straightforward. The complexes generally exhibit high stability, allowing for indefinite storage and easy handling. We next consider catalysis, particularly examining efficacy in cycloisomerization, other skeletal rearrangements, addition of water to alkynes and nitriles, and C-H bond activation. These processes are quite atom-economical, and in the most recent C-H reactions the

  13. Mutual influence between contiguous TMPyP4 ligands when bound to a synthetic double-stranded Poly(A)-Poly(U)

    NASA Astrophysics Data System (ADS)

    Tolstykh, G.; Kudrev, A.

    2015-10-01

    The cooperativity of TMPyP4 ligand binding to Poly(A)-Poly(U) polynucleotide were monitored in this study by fluorescence spectroscopy and UV-Vis absorbance spectroscopy. To solve the equilibrium binding model between a dye and substrate, a new computational approach has been proposed based collectively on Principal Component Analysis and the conditional probabilities method. This approach suggest that the absorbance and fluorescence variance during a titration is determined by spectral species formed in stepwise saturation of binding sites on Poly(A)-Poly(U) with porphyrin and a conformational changes on a macromolecule. Spectral species assigned to different forms of polymer-ligand complexes whose existences in equilibrium were postulated by the conditional probabilities method. The binding of TMPyP4 molecule to the Poly(A)-Poly(U) enhances the binding of additional molecules to that same receptor. The intrinsic binding constant to an isolated binding site lgKin = 6.4, the cooperativity parameter ω = 5.0, and number of monomers occupied by a ligand n = 2 (25 °C; pH 7) were calculated based upon the non-linear least-squares fitting procedure.

  14. Controlling conformations of conjugated polymers and small molecules: the role of nonbonding interactions.

    PubMed

    Jackson, Nicholas E; Savoie, Brett M; Kohlstedt, Kevin L; Olvera de la Cruz, Monica; Schatz, George C; Chen, Lin X; Ratner, Mark A

    2013-07-17

    The chemical variety present in the organic electronics literature has motivated us to investigate potential nonbonding interactions often incorporated into conformational "locking" schemes. We examine a variety of potential interactions, including oxygen-sulfur, nitrogen-sulfur, and fluorine-sulfur, using accurate quantum-chemical wave function methods and noncovalent interaction (NCI) analysis on a selection of high-performing conjugated polymers and small molecules found in the literature. In addition, we evaluate a set of nonbonding interactions occurring between various heterocyclic and pendant atoms taken from a group of representative π-conjugated molecules. Together with our survey and set of interactions, it is determined that while many nonbonding interactions possess weak binding capabilities, nontraditional hydrogen-bonding interactions, oxygen-hydrogen (CH···O) and nitrogen-hydrogen (CH···N), are alone in inducing conformational control and enhanced planarity along a polymer or small molecule backbone at room temperature.

  15. Tautomers of 2-aminothiazole molecules in aqueous solutions explored by Raman, SERS and DFT methods

    NASA Astrophysics Data System (ADS)

    Chen, Xue; Hu, Yongjun; Gao, Jiao

    2013-10-01

    2-Aminothiazole, as a typical heterocyclic amine, may exist amino-imino tautomeric equilibrium in nature. In present report, the optimized structural parameters and vibrational wavenumbers of amino and imino tautomers of the molecule have been predicted by density functional theoretical (DFT) calculation. Comparing the experimental and the calculated Raman spectra, it indicates that the amino tautomer would be the main configuration in the 2-aminothiazole saturated solution. In the concentration-dependent SERS spectra of 2-aminothiazole adsorbed on gold nanoparticles, it is found that the tautomeric equilibrium shifts toward to the amino tautomer when the concentrations is decreased. While the amino tautomer is end-on the surface through the nitrogen atom of thiazole ring at the higher concentrations, the molecule becomes to stand on the metal surface by interacting simultaneously with two nitrogen atoms of the molecule in the diluted solution.

  16. Synthesis and Characterization of Amphiphilic Cyclic Diblock Copolypeptoids from N-Heterocyclic Carbene-Mediated Zwitterionic Polymerization of N-Substituted N-carboxyanhydride

    PubMed Central

    Lee, Chang-Uk; Smart, Thomas P.; Guo, Li; Epps, Thomas H.; Zhang, Donghui

    2011-01-01

    N-Heterocyclic carbene (NHC)-mediated ring-opening polymerization of N-decylN-carboxylanhydride monomer (De-NCA) has been shown to occur in a controlled manner, yielding cyclic poly(N-decyl-glycine)s (c-PNDGs) with polymer molecular weights (MW) between 4.8 and 31 kg·mol−1 and narrow molecular weight distributions (PDI < 1.15). The reaction exhibits pseudo-first order kinetics with respect to monomer concentration. The polymer MW increases linearly with conversion, consistent with a living polymerization. ESI MS and SEC analysesconfirm the cyclic architectures of the forming polymers. DSC and WAXS studies reveal that the c-PNDG homopolymers are highly crystalline with two prominent first order transitions at 72–79°C (Tm,1) and 166–177°C (Tm,2), which have been attributed to the side chain and main chain melting respectively. A series of amphiphilic cyclic diblock copolypeptoids [i.e.,poly(N-methyl-glycine)-b-poly(N-decyl-glycine) (c-PNMG-b-PNDG)] with variable molecular weight and composition was synthesized by sequential NHC-mediated polymerization of the corresponding N-methyl N-carboxyanhydride (Me-NCA) and De-NCA monomers. 1H NMR analysis reveals that adjusting the initial monomer to NHC molar ratio can readily control the block copolymer chain length and composition. Time-lapsed light scattering and cryogenic transmission electron microscopy (cryo-TEM) analysis of c-PNDG-b-PNMG samples revealed that the amphiphilic cyclic block copolypeptoids self-assemble into spherical micelles that reorganize into micron-long cylindrical micelles with uniform diameter in room temperature methanol over the course of several days. An identical morphological transition has also been noted for the linear analogs, which occurs more rapidly than for the cyclic copolypeptoids. We tentatively attribute this difference to the different crystallization kinetics of the solvophobic block (i.e., PNDG) in the cyclic and linear block copolypeptoids. PMID:22247571

  17. Fascinating frontiers of N/O-functionalized N-heterocyclic carbene chemistry: from chemical catalysis to biomedical applications.

    PubMed

    John, Alex; Ghosh, Prasenjit

    2010-08-21

    The in vogue N-heterocyclic carbenes (NHCs) have attracted attention largely for its new found popularity in chemical catalysis and also for displaying promising traits in biomedical applications. The current perspective provides an account of our efforts in exploring the utility of N/O-functionalized N-heterocyclic carbenes in these two areas. On the catalysis front, we have employed the N/O-functionalized N-heterocyclic carbene based precatalysts for the C-C and C-N bond forming reactions like the Suzuki-Miyaura, Sonogashira and Hiyama cross-couplings, the base-free Michael addition, the alkene and alkyne hydroamination reactions and the ring-opening polymerization (ROP) of L-lactides that produce biodegradable polylactide polymers while on the biomedical application front, the anticancer and antimicrobial properties of these N/O-functionalized N-heterocyclic carbene complexes were evaluated. Towards this objective, the N-heterocyclic carbene chemistry of a variety of transition metals like Ag, Au, Ni and Pd has been investigated. PMID:20495733

  18. 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.

  19. Fascinating frontiers of N/O-functionalized N-heterocyclic carbene chemistry: from chemical catalysis to biomedical applications.

    PubMed

    John, Alex; Ghosh, Prasenjit

    2010-08-21

    The in vogue N-heterocyclic carbenes (NHCs) have attracted attention largely for its new found popularity in chemical catalysis and also for displaying promising traits in biomedical applications. The current perspective provides an account of our efforts in exploring the utility of N/O-functionalized N-heterocyclic carbenes in these two areas. On the catalysis front, we have employed the N/O-functionalized N-heterocyclic carbene based precatalysts for the C-C and C-N bond forming reactions like the Suzuki-Miyaura, Sonogashira and Hiyama cross-couplings, the base-free Michael addition, the alkene and alkyne hydroamination reactions and the ring-opening polymerization (ROP) of L-lactides that produce biodegradable polylactide polymers while on the biomedical application front, the anticancer and antimicrobial properties of these N/O-functionalized N-heterocyclic carbene complexes were evaluated. Towards this objective, the N-heterocyclic carbene chemistry of a variety of transition metals like Ag, Au, Ni and Pd has been investigated.

  20. VEGF siRNA delivery system using arginine-grafted bioreducible poly(disulfide amine).

    PubMed

    Kim, Sun Hwa; Jeong, Ji Hoon; Kim, Tae-il; Kim, Sung Wan; Bull, David A

    2009-01-01

    Small interfering RNAs (siRNAs) are able to silence their target genes when they are successfully delivered intact into the cytoplasm. Delivery systems that enhance siRNA localization to the cytoplasm can facilitate gene silencing by siRNA therapeutics. We describe an arginine-conjugated poly(cystaminebisacrylamide-diaminohexane) (poly(CBA-DAH-R)), a bioreducible cationic polymer, as an siRNA carrier for therapeutic gene silencing for cancer. After intracellular uptake of the siRNA/poly(CBA-DAH-R) polyplexes, the reductive environment of the cytoplasm cleaves the disulfide linkages in the polymeric backbone, resulting in decomplexing of the siRNA/poly(CBA-DAH-R) polyplexes and release of siRNA molecules throughout the cytoplasm. The siRNA/poly(CBA-DAH-R) polyplexes, which demonstrate increased membrane permeability with arginine modification, have a similar level of cellular uptake as siRNA/bPEI polyplexes. The VEGF siRNA/poly(CBA-DAH-R) polyplexes, however, inhibit VEGF expression to a greater degree than VEGF siRNA/bPEI in various human cancer cell lines. The improved RNAi activity demonstrated by the VEGF siRNA/poly(CBA-DAH-R) polyplexes is due to enhanced intracellular delivery and effective localization to the cytoplasm of the VEGF siRNAs. These results demonstrate that the VEGF siRNA/poly(CBA-DAH-R) polyplex delivery system may useful for siRNA-based approaches for cancer therapy.

  1. Synthesis of modified vermiculite by interaction with aromatic heterocyclic amines

    NASA Astrophysics Data System (ADS)

    da Fonseca, Maria G.; Cardoso, Cassio M.; Wanderley, Albaneide F.; Arakaki, Luiza N. H.; Airoldi, Claudio

    2006-08-01

    Vermiculite of general formula [Si6.85Al1.15][Mg4.68Al0.51Fe0.63]O20(OH)4Ca0.128Na0.032K0.094 reacted with heteroaromatic amines α-, β-, and γ-picolines from aqueous solution. The products were characterized by elemental analysis, infrared spectroscopy, and X-ray diffraction. The intercalated nanocompounds maintained the crystallinity and changed the original interlayer distance of 1422 pm to 1474, 1456, and 1474 pm, for the sequence of the guest picoline molecules. Natural and intercalated vermiculite can remove copper at the solid/liquid interface; removal 0.40 mmol g-1 was obtained for the original matrix, and 1.10, 0.92, and 1.33 mmol g-1 for the intercalated forms. These values are near the capacity of cation exchange (CEC) of this clay mineral, which can be possibly used as source of copper removal from aqueous solution.

  2. Characterization of heterocyclic rings through quantum chemical topology.

    PubMed

    Griffiths, Mark Z; Popelier, Paul L A

    2013-07-22

    Five-membered rings are found in a myriad of molecules important in a wide range of areas such as catalysis, nutrition, and drug and agrochemical design. Systematic insight into their largely unexplored chemical space benefits from first principle calculations presented here. This study comprehensively investigates a grand total of 764 different rings, all geometry optimized at the B3LYP/6-311+G(2d,p) level, from the perspective of Quantum Chemical Topology (QCT). For the first time, a 3D space of local topological properties was introduced, in order to characterize rings compactly. This space is called RCP space, after the so-called ring critical point. This space is analogous to BCP space, named after the bond critical point, which compactly and successfully characterizes a chemical bond. The relative positions of the rings in RCP space are determined by the nature of the ring scaffold, such as the heteroatoms within the ring or the number of π-bonds. The summed atomic QCT charges of the five ring atoms revealed five features (number and type of heteroatom, number of π-bonds, substituent and substitution site) that dictate a ring's net charge. Each feature independently contributes toward a ring's net charge. Each substituent has its own distinct and systematic effect on the ring's net charge, irrespective of the ring scaffold. Therefore, this work proves the possibility of designing a ring with specific properties by fine-tuning it through manipulation of these five features.

  3. Small-molecule caspase inhibitors

    NASA Astrophysics Data System (ADS)

    Zhenodarova, S. M.

    2010-02-01

    The review considers low-molecular weight inhibitors of caspases, cysteine proteases being key contributors to apoptosis (programmed cell death). The inhibitors with aspartic acid residues or various heterocyclic systems (both synthetic and natural) are covered. Their possible mechanisms of action are discussed. Data on inhibitor structure-activity relationship studies are systematically surveyed. The interactions of the non-peptide fragments of an inhibitor with the enzymes are examined. Examples of the use of some inhibitors for apoptosis suppression are provided.

  4. Solid-surface luminescence interactions of nitrogen heterocycles adsorbed on silica gel chromatoplates submerged in chloroform/n-hexane solvents

    SciTech Connect

    Burrell, G.J.; Hurtubise, R.J.

    1988-03-15

    The room-temperature fluorescence (RTF) and room-temperature phosphorescence (RTP) of benzo(f)quinoline and benzo(h)quinoline, obtained from the samples adsorbed on silica gel chromatoplates submerged in chloroform/n-hexane solvents, revealed several of the interactions of the nitrogen heterocycles with the solid matrix. The RTP results showed the emitting phosphor was protected from collisional deactivation by the matrix and that the adsorbed chloroform minimally disrupted the phosphor adsorption interactions. In addition, at least two populations of phosphors were indicated. The RTF data and RTP data showed that different interactions were occurring in the singlet state compared to the triplet state. A comparison of RTF intensity and TRP intensity as a function of chromatographic solvent strength indicated that the protonated forms of the nitrogen heterocycles in their triplet states were interacting with the matrix more strongly than the protonated forms of the nitrogen heterocycles in their singlet states.

  5. Synthesis of mixed silylene-carbene chelate ligands from N-heterocyclic silylcarbenes mediated by nickel.

    PubMed

    Tan, Gengwen; Enthaler, Stephan; Inoue, Shigeyoshi; Blom, Burgert; Driess, Matthias

    2015-02-01

    The Ni(II) -mediated tautomerization of the N-heterocyclic hydrosilylcarbene L(2) Si(H)(CH2 )NHC 1, where L(2) =CH(CCH2 )(CMe)(NAr)2 , Ar=2,6-iPr2 C6 H3 ; NHC=3,4,5-trimethylimidazol-2-yliden-6-yl, leads to the first N-heterocyclic silylene (NHSi)-carbene (NHC) chelate ligand in the dibromo nickel(II) complex [L(1) Si:(CH2 )(NHC)NiBr2 ] 2 (L(1) =CH(MeCNAr)2 ). Reduction of 2 with KC8 in the presence of PMe3 as an auxiliary ligand afforded, depending on the reaction time, the N-heterocyclic silyl-NHC bromo Ni(II) complex [L(2) Si(CH2 )NHCNiBr(PMe3 )] 3 and the unique Ni(0) complex [η(2) (Si-H){L(2) Si(H)(CH2 )NHC}Ni(PMe3 )2 ] 4 featuring an agostic SiH→Ni bonding interaction. When 1,2-bis(dimethylphosphino)ethane (DMPE) was employed as an exogenous ligand, the first NHSi-NHC chelate-ligand-stabilized Ni(0) complex [L(1) Si:(CH2 )NHCNi(dmpe)] 5 could be isolated. Moreover, the dicarbonyl Ni(0) complex 6, [L(1) Si:(CH2 )NHCNi(CO)2 ], is easily accessible by the reduction of 2 with K(BHEt3 ) under a CO atmosphere. The complexes were spectroscopically and structurally characterized. Furthermore, complex 2 can serve as an efficient precatalyst for Kumada-Corriu-type cross-coupling reactions.

  6. Posttranslational heterocyclization of cysteine and serine residues in the antibiotic microcin B17: distributivity and directionality.

    PubMed

    Kelleher, N L; Hendrickson, C L; Walsh, C T

    1999-11-23

    To produce the antibiotic Microcin B17, four Cys and four Ser residues are converted into four thiazoles and four oxazoles by the three subunit Microcin B17 synthetase. High-resolution mass spectrometry (MS) was used to monitor the kinetics of posttranslational heterocyclic ring formation (-20 Da per ring) and demonstrated the accumulation of all intermediates, from one to seven rings, indicating distributive processing. All of the intermediates could be converted by the enzyme to the eight ring product. Enzymatic chemoselectivity (Cys vs Ser cyclization rates) was assessed using iodoacetamido-salicylate to alkylate unreacted cysteines (+193 Da) in the 8 kDa biosynthetic intermediates; three of the first four rings formed were thiazoles, and by the five ring stage, all four of the cysteines had been heterocyclized while three of the original four serines remained uncyclized. Finally, tandem MS using a 9.4 T Fourier transform instrument with electrospray ionization was used to elaborate the major processing pathway: the first two rings formed are at the most amino proximal sites (Cys(41) then Ser(40)) followed by the remaining three cysteines at positions 48, 51, and 55. The cyclization of serines at positions 56, 62, and 65 then follows, with Ser(62) and Ser(65) the last to heterocyclize and the first of these at a slower rate. Thus, despite free dissociation of intermediates after each of seven ring-forming catalytic cycles, there is an overall directionality of ring formation from N-terminal to C-terminal sites. This remarkable regioselectivity is determined more by the substrate than the enzyme, due to a combination of (1) initial high-affinity binding of the posttranslational catalyst to the N-terminal propeptide of substrate 88mer, and (2) a chemoselectivity for thiazole over oxazole formation. This mechanism is consistent with antibiotic biosynthesis in vivo, yielding microcin with six, seven, and eight rings, all with bioactivity.

  7. 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.

  8. Advanced poly-LED displays

    NASA Astrophysics Data System (ADS)

    Childs, Mark; Nisato, Giovanni; Fish, D.; Giraldo, Andrea; Jenkins, A. J.; Johnson, Mark T.

    2003-05-01

    Philips have been actively developing polymer OLED (poly-LED) displays as a future display technology. Their emissive nature leads to a very attractive visual appearance, with wide viewing angle, high brightness and fast response speed. Whilst the first generation of poly-LED displays are likely to be passive-matrix driven, power reduction and resolution increase will lead to the use of active-matrix poly-LED displays. Philips Research have designed, fabricated and characterized five different designs of active-matrix polymer-LED display. Each of the five displays makes use of a distinct pixel programming- or pixel drive-technique, including current programming, threshold voltage measurement and photodiode feedback. It will be shown that hte simplest voltage-programmed current-source pixel suffers from potentially unacceptable brightness non-uniformity, and that advanced pixel circuits can provide a solution to this. Optical-feedback pixel circuits will be discussed, showing that they can be used to improve uniformity and compensate for image burn-in due to polymer-LED material degradation, improving display lifetime. Philips research has also been active in developing technologies required to implement poly-LED displays on flexible substrates, including materials, processing and testing methods. The fabrication of flexible passive-matrix poly-LED displays will be presented, as well as the ongoing work to assess the suitability of processing flexible next-generation poly-LED displays.

  9. Poly-instanton inflation

    SciTech Connect

    Cicoli, Michele; Pedro, Francisco G.; Tasinato, Gianmassimo E-mail: f.pedro1@physics.ox.ac.uk

    2011-12-01

    We propose a new inflationary scenario in type IIB Calabi-Yau compactifications, where the inflaton is a Kähler modulus parameterising the volume of an internal four-cycle. The inflaton potential is generated via poly-instanton corrections to the superpotential which give rise to a naturally flat direction due to their double exponential suppression. Given that the volume mode is kept stable during inflation, all the inflaton-dependent higher dimensional operators are suppressed. Moreover, string loop effects can be shown to be negligible throughout all the inflationary dynamics for natural values of the underlying parameters. The model is characterised by a reheating temperature of the order T{sub rh} ≅ 10{sup 6} GeV which requires N{sub e} ≅ 54 e-foldings of inflation. All the inflationary observables are compatible with current observations since the spectral index is n{sub s} ≅ 0.96, while the tensor-to-scalar ratio is r ≅ 10{sup −5}. The volume of the Calabi-Yau is of order 10{sup 3} in string units, corresponding to an inflationary scale around 10{sup 15} GeV.

  10. Carboxylation of terminal alkynes with CO2 using novel silver N-heterocyclic carbene complexes.

    PubMed

    Li, Shanshan; Sun, Jing; Zhang, Zhizhi; Xie, Ruixia; Fang, Xiangchen; Zhou, Mingdong

    2016-06-28

    Four novel N-heterocyclic carbene (NHC) silver complexes, , have been synthesized and characterized. The single X-ray crystal diffraction data indicate a dinuclear solid-state structure for and and a mononuclear structure for and . These complexes have been successfully used as efficient catalysts for the C-H activating carboxylation of terminal alkynes with CO2. A wide range of substrates with various functional groups afforded the corresponding aryl or alkyl substituted propiolic acids in good yields under mild conditions. Moreover, the role of bases and the reaction mechanism is thoroughly discussed. PMID:27263977

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

    PubMed

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

    2016-08-01

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

  12. 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.

  13. Synthesis of functionalized indole- and benzo-fused heterocyclic derivatives through anionic benzyne cyclization.

    PubMed

    Barluenga, José; Fañanás, Francisco J; Sanz, Roberto; Fernández, Yolanda

    2002-05-01

    The development of a new method for the regioselective synthesis of functionalized indoles and six-membered benzo-fused N-, O-, and S-heterocycles is reported. The key step involves the generation of a benzyne-tethered vinyl or aryllithium compound that undergoes a subsequent intramolecular anionic cyclization. Reaction of the organolithium intermediates with selected electrophiles allows the preparation of a wide variety of indole, tetrahydrocarbazole, dihydrofenantridine, dibenzopyran, and dibenzothiopyran derivatives. Finally, the application of this strategy to the appropriate starting materials allows the preparation of some tryptamine and serotonin analogues.

  14. Mechanism of the heterocyclization of 1,5-diketones under the conditions of catalytic hydrogenation

    SciTech Connect

    Yudovich, L.M.; Smirnova, N.S.; Rybina, G.I.; Bryukhanova, O.V.; Kharchenko, V.G.

    1988-04-10

    The stereochemistry of condensed oxacyclohexanes, formed during the catalytic hydrogenation of 2,2/prime/-methylenebiscyclohexanone, 2-((2-oxocyclopentyl)methyl)cyclohexanone, and 4-R-2-hydroxy(3.3.1.4/sup 2,3/)tricyclotridecan-9-one in the presence of a rhodium catalyst, was studied by /sup 13/C NMR spectroscopy. It was shown that a mixture of isomers with the trans-anti-cis and cis-syn-cis configurations is obtained in all cases, irrespective of the structure of the initial compounds. The mechanism of the heterocyclization of the investigated compounds is discussed.

  15. [Development of novel methods for synthesis of heterocyclic compounds catalyzed by transition metals in fluorinated alcohols].

    PubMed

    Saito, Akio

    2008-08-01

    New possibilities for catalytic syntheses of lactone derivatives and nitrogen-containing heterocyclic compounds in fluorinated alcohols are described. The cationic Rh(I) catalyst in fluorinated alcohol solvents (hexafluoroisopropanol: HFIP, trifluoroethanol: TFE) brought about not only mild cycloaddition reactions of ester-tethered compounds but also a facile formation of indole derivatives by the aromatic amino-Claisen rearrangement of N-propargyl aniline derivatives. The use of HFIP as an additive exerted a remarkable effect on the Pictet-Spengler reaction catalyzed by the fluorinated surfactant-combined Brønsted acid catalyst in water.

  16. New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

    PubMed Central

    Suchodolski, Szymon; Wojtkielewicz, Agnieszka; Morzycki, Jacek W

    2015-01-01

    Summary The synthesis of a new type of Hoveyda–Grubbs 2nd generation catalyst bearing a modified N-heterocyclic carbene ligands is reported. The new catalyst contains an NHC ligand symmetrically substituted with chromanyl moieties. The complex was tested in model CM and RCM reactions. It showed very high activity in CM reactions with electron-deficient α,β-unsaturated compounds even at 0 °C. It was also examined in more demanding systems such as conjugated dienes and polyenes. The catalyst is stable, storable and easy to purify. PMID:26877801

  17. A Ruthenium Catalyst for Olefin Metathesis Featuring an Anti-Bredt N-Heterocyclic Carbene Ligand

    PubMed Central

    Martin, David; Marx, Vanessa M.

    2016-01-01

    A ruthenium complex bearing an “anti-Bredt” N-heterocyclic carbene was synthesized, characterized and evaluated as a catalyst for olefin metathesis. Good conversions were observed at room temperature for the formation of di- and tri-substituted olefins by ring-closing metathesis. It also allowed for the ring-opening metathesis polymerization of cyclooctadiene, as well as for the cross-metathesis of cis-1,4-diacetoxy-2-butene with allyl-benzene, with enhanced Z/E kinetic selectivity over classical NHC-based catalysts. PMID:27594819

  18. Syntheses of group 7 metal carbonyl complexes with a stable N-heterocyclic chlorosilylene.

    PubMed

    Azhakar, Ramachandran; Sarish, Sankaranarayana Pillai; Roesky, Herbert W; Hey, Jakob; Stalke, Dietmar

    2011-06-01

    Two structurally characterized manganese [L(2)Mn(CO)(4)](+)[Mn(CO)(5)](-) (1) and rhenium [L(3)Re(CO)(3)](+)[ReCO)(5)](-) (2) silylene complexes were prepared in one pot syntheses by reacting 1 equivalent of Mn(2)(CO)(10) with 2 equivalents of stable N-heterocyclic chlorosilylene L {L = PhC(NtBu)(2)SiCl} and 1 equivalent of Re(2)(CO)(10) with 3 equivalents of L in toluene at room temperature. Both complexes 1 and 2 were characterized by single-crystal X-ray structural analysis, NMR and IR spectroscopy, EI-MS spectrometry, and elemental analysis. PMID:21539353

  19. Development and Applications of Transesterification Reactions Catalyzed by N-Heterocyclic Olefins.

    PubMed

    Blümel, Marcus; Noy, Janina-Miriam; Enders, Dieter; Stenzel, Martina H; Nguyen, Thanh V

    2016-05-01

    A novel method to utilize N-heterocyclic olefins (NHOs), the alkylidene derivatives of N-heterocycic carbenes, as organocatalysts to promote transesterification reactions has been developed. Because of their strong Brønsted/Lewis basicity, NHOs can enhance the nucleophilicity of alcohols for their acylation reactions with carboxylic esters. This transformation can be employed in industrially relevant processes such as the production of biodiesel, the depolymerization of polyethylene terephthalate (PET) from plastic bottles for recycling purposes, and the ring-opening polymerization of cyclic esters to form biodegradable polymers such as polylactide (PLA) and polycaprolactone (PCL). PMID:27115463

  20. Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors.

    PubMed

    Florence, Gordon J; Fraser, Andrew L; Gould, Eoin R; King, Elizabeth F; Menzies, Stefanie K; Morris, Joanne C; Thomson, Marie I; Tulloch, Lindsay B; Zacharova, Marija K; Smith, Terry K

    2016-07-19

    Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world's poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin-inspired derivatives, namely 3,5-isoxazoles, furoxans, and furazans. Several of these compounds maintain low-micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment.

  1. Near-UV phosphorescent emitters: N-heterocyclic platinum(ii) tetracarbene complexes.

    PubMed

    Unger, Yvonne; Zeller, Alexander; Taige, Maria A; Strassner, Thomas

    2009-06-28

    Although examples of nickel(ii), palladium(ii) and platinum(ii) N-heterocyclic tetracarbene complexes are known in the literature, particularly platinum(ii) tetracarbene complexes are rare. We developed a new synthetic route via biscarbene acetate complexes, which make homoleptic as well as heteroleptic platinum(ii) tetracarbene complexes accessible. The reported photoluminescence data show that these complexes have good quantum yields and photostability and are a promising class of emitters for PhOLEDs. Characterization of the compounds includes a solid-state structure of the homoleptic complex bis(1,1'-diisopropyl-3,3'-methylenediimidazoline-2,2'-diylidene)platinum(ii) dibromide. PMID:19513490

  2. Latent ruthenium–indenylidene catalysts bearing a N-heterocyclic carbene and a bidentate picolinate ligand

    PubMed Central

    Schmid, Thibault E; Modicom, Florian; Dumas, Adrien; Borré, Etienne; Toupet, Loic

    2015-01-01

    Summary A silver-free methodology was developed for the synthesis of unprecedented N-heterocyclic carbene ruthenium indenylidene complexes bearing a bidentate picolinate ligand. The highly stable (SIPr)(picolinate)RuCl(indenylidene) complex 4a (SIPr = 1,3-bis(2-6-diisopropylphenyl)imidazolidin-2-ylidene) demonstrated excellent latent behaviour in ring closing metathesis (RCM) reaction and could be activated in the presence of a Brønsted acid. The versatility of the catalyst 4a was subsequently demonstrated in RCM, cross-metathesis (CM) and enyne metathesis reactions. PMID:26425213

  3. Enantioselective conjugate addition of alkylboranes catalyzed by a copper-N-heterocyclic carbene complex.

    PubMed

    Yoshida, Mika; Ohmiya, Hirohisa; Sawamura, Masaya

    2012-07-25

    The first catalytic enantioselective conjugate addition of alkylboron compounds has been achieved. Reactions between alkylboranes and imidazol-2-yl α,β-unsaturated ketones proceeded with high enantioselectivity under the influence of a Cu(I) catalyst system, prepared in situ from CuCl, a new chiral imidazolium salt as a precursor for the N-heterocyclic carbene ligand, and PhOK. Alkylboranes are widely obtained via alkene hydroboration. A variety of functional groups are tolerated in alkylboranes and α,β-unsaturated ketones. PMID:22746339

  4. New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand.

    PubMed

    Hryniewicka, Agnieszka; Suchodolski, Szymon; Wojtkielewicz, Agnieszka; Morzycki, Jacek W; Witkowski, Stanisław

    2015-01-01

    The synthesis of a new type of Hoveyda-Grubbs 2(nd) generation catalyst bearing a modified N-heterocyclic carbene ligands is reported. The new catalyst contains an NHC ligand symmetrically substituted with chromanyl moieties. The complex was tested in model CM and RCM reactions. It showed very high activity in CM reactions with electron-deficient α,β-unsaturated compounds even at 0 °C. It was also examined in more demanding systems such as conjugated dienes and polyenes. The catalyst is stable, storable and easy to purify. PMID:26877801

  5. Latent ruthenium-indenylidene catalysts bearing a N-heterocyclic carbene and a bidentate picolinate ligand.

    PubMed

    Schmid, Thibault E; Modicom, Florian; Dumas, Adrien; Borré, Etienne; Toupet, Loic; Baslé, Olivier; Mauduit, Marc

    2015-01-01

    A silver-free methodology was developed for the synthesis of unprecedented N-heterocyclic carbene ruthenium indenylidene complexes bearing a bidentate picolinate ligand. The highly stable (SIPr)(picolinate)RuCl(indenylidene) complex 4a (SIPr = 1,3-bis(2-6-diisopropylphenyl)imidazolidin-2-ylidene) demonstrated excellent latent behaviour in ring closing metathesis (RCM) reaction and could be activated in the presence of a Brønsted acid. The versatility of the catalyst 4a was subsequently demonstrated in RCM, cross-metathesis (CM) and enyne metathesis reactions. PMID:26425213

  6. Synthesis and self-assembly of poly(3-hexylthiophene)-block-poly(acrylic acid)

    SciTech Connect

    Li, Zicheng; Ono, Robert J.; Wu, Zong-Quan; Bielawski, Christopher W.

    2011-01-01

    A modular and convenient synthesis of ethynyl end functionalized poly(3-hexylthiophene) in high purity is reported; this material facilitated access to poly(3-hexylthiophene)-block-poly(acrylic acid) which self-assembled into hierarchical structures.

  7. 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. PMID:26490371

  8. Cationic bis-N-heterocyclic carbene (NHC) ruthenium complex: structure and application as latent catalyst in olefin metathesis.

    PubMed

    Rouen, Mathieu; Queval, Pierre; Falivene, Laura; Allard, Jessica; Toupet, Loïc; Crévisy, Christophe; Caijo, Frédéric; Baslé, Olivier; Cavallo, Luigi; Mauduit, Marc

    2014-10-13

    An unexpected cationic bis-N-heterocyclic carbene (NHC) benzylidene ether based ruthenium complex (2 a) was prepared through the double incorporation of an unsymmetrical unsaturated N-heterocyclic carbene (U2 -NHC) ligand that bore an N-substituted cyclododecyl side chain. The isolation and full characterization (including X-ray diffraction studies) of key synthetic intermediates along with theoretical calculations allowed us to understand the mechanism of the overall cationization process. Finally, the newly developed complex 2 a displayed interesting latent behavior during ring-closing metathesis, which could be "switched on" under acidic conditions. PMID:25212827

  9. Spin transitions in bis(amidinato)-N-heterocyclic carbene iron(II) and iron(III) complexes.

    PubMed

    Drake, Jessica L; Kaplan, Hilan Z; Wilding, Matthew J T; Li, Bo; Byers, Jeffery A

    2015-10-14

    In contrast to high spin pyridyl diimine iron(ii) dichloride complexes, analogous bis(amidinato)-N-heterocyclic carbene iron(ii) and iron(iii) complexes demonstrate complex magnetic behaviour. In the solid state, they are best described as intermediate spin complexes at low temperatures that demonstrate gradual spin transitions beginning near or below room temperature. Treating the bis(amidinato)-N-heterocyclic carbene iron(ii) complex with an aryl azide revealed enhanced reactivity compared to analogous complexes supported by pyridyl diimine ligands.

  10. Cationic bis-N-heterocyclic carbene (NHC) ruthenium complex: structure and application as latent catalyst in olefin metathesis.

    PubMed

    Rouen, Mathieu; Queval, Pierre; Falivene, Laura; Allard, Jessica; Toupet, Loïc; Crévisy, Christophe; Caijo, Frédéric; Baslé, Olivier; Cavallo, Luigi; Mauduit, Marc

    2014-10-13

    An unexpected cationic bis-N-heterocyclic carbene (NHC) benzylidene ether based ruthenium complex (2 a) was prepared through the double incorporation of an unsymmetrical unsaturated N-heterocyclic carbene (U2 -NHC) ligand that bore an N-substituted cyclododecyl side chain. The isolation and full characterization (including X-ray diffraction studies) of key synthetic intermediates along with theoretical calculations allowed us to understand the mechanism of the overall cationization process. Finally, the newly developed complex 2 a displayed interesting latent behavior during ring-closing metathesis, which could be "switched on" under acidic conditions.

  11. Indirect C-H azidation of heterocycles via copper-catalyzed regioselective fragmentation of unsymmetrical λ3-iodanes.

    PubMed

    Lubriks, Dmitrijs; Sokolovs, Igors; Suna, Edgars

    2012-09-19

    A C-H bond of electron-rich heterocycles is transformed into a C-N bond in a reaction sequence comprising the formation of heteroaryl(phenyl)iodonium azides and their in situ regioselective fragmentation to heteroaryl azides. A Cu(I) catalyst ensures complete regiocontrol in the fragmentation step and catalyzes the subsequent 1,3-dipolar cycloaddition of the formed azido heterocycles with acetylenes. The heteroaryl azides can also be conveniently reduced to heteroarylamines by aqueous ammonium sulfide. The overall C-H to C-N transformation is a mild and operationally simple one-pot sequential multistep process. PMID:22913396

  12. Length heteroplasmy of the polyC-polyT-polyC stretch in the dog mtDNA control region.

    PubMed

    Verscheure, Sophie; Backeljau, Thierry; Desmyter, Stijn

    2015-09-01

    Previously, the mitochondrial control region of 214 Belgian dogs was sequenced. Analysis of this data indicated length heteroplasmy of the polyT stretch in the polyC-polyT-polyC stretch from positions 16661 to 16674. Nine polyC-polyT-polyC haplotype combinations were observed, consisting of seven major haplotypes (highest signal intensity) combined with minor haplotypes (lower signal intensity) one T shorter than the major haplotype in all but three dogs. The longer the polyT stretch, the smaller was the difference in signal intensity between the major and minor haplotype peaks. Additional sequencing, cloning, and PCR trap experiments were performed to further study the intra-individual variation of this mitochondrial DNA (mtDNA) region. Cloning experiments demonstrated that the proportion of clones displaying the minor haplotypes also increased with the length of the polyT stretch. Clone amplification showed that in vitro polymerase errors might contribute to the length heteroplasmy of polyT stretches with at least 10 Ts. Although major and minor polyC-polyT-polyC haplotypes did not differ intra-individually within and between tissues in this study, interpretation of polyT stretch variation should be handled with care in forensic casework. PMID:25394743

  13. [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.

  14. Zymosan enhances the mucosal adjuvant activity of poly(I:C) in a nasal influenza vaccine.

    PubMed

    Ainai, Akira; Ichinohe, Takeshi; Tamura, Shin-Ichi; Kurata, Takeshi; Sata, Tetsutaro; Tashiro, Masato; Hasegawa, Hideki

    2010-03-01

    The synthetic double-stranded RNA polyriboinocinic polyribocytidylic acid [poly(I:C)] is a potent mucosal adjuvant in mice immunized intranasally with an inactivated influenza vaccine. In an attempt, to increase the effectiveness of a nasal poly(I:C)-combined vaccine, the effect of zymosan, a cell wall extract from Saccharomyces cervisiae was investigated, on the adjuvant activity of poly(I:C) in BALB/c mice. The addition of zymosan (10 microg) as an adjuvant in mice which were immunized intranasally with a poly(I:C) (1-5 microg)-combined vaccine (1 microg) enhanced the ability of the mice to mount an effective immune response to a lethal dose of influenza virus, and resulted in a synergistic increase in secretory IgA and serum IgG antibody levels. To define the mechanism by which zymosan enhanced the adjuvant activity of poly(I:C), bone marrow-derived dendritic cells (BM-DCs) were cultured in the presence of poly(I:C) and/or zymosan. There was a synergistic increase in cytokine production (TNF-alpha, IL-6, IL-10, and IFN-beta) in BM-DCs, together with an increase in the expression of co-stimulatory molecules (CD86 and CD40) in response to co-treatment with poly(I:C) and zymosan. This synergistic effect on cytokine production was mimicked by co-treatment with poly(I:C) and a Toll-like receptor 2 (TLR2) ligand, which represented one of the components of zymosan. The results of the current study suggest that one of the mechanisms by which zymosan enhances the adjuvant activity of poly(I:C) is through increased cytokine production by DCs involving the synergistic activation of poly(I:C)-induced TLR3- and zymosan-induced TLR2-mediated signaling pathways. J. Med. Virol. 82:476-484, 2010. (c) 2010 Wiley-Liss, Inc. PMID:20087927

  15. Reprogramming the assembly of unmodified DNA with a small molecule.

    PubMed

    Avakyan, Nicole; Greschner, Andrea A; Aldaye, Faisal; Serpell, Christopher J; Toader, Violeta; Petitjean, Anne; Sleiman, Hanadi F

    2016-04-01

    The ability of DNA to store and encode information arises from base pairing of the four-letter nucleobase code to form a double helix. Expanding this DNA 'alphabet' by synthetic incorporation of new bases can introduce new functionalities and enable the formation of novel nucleic acid structures. However, reprogramming the self-assembly of existing nucleobases presents an alternative route to expand the structural space and functionality of nucleic acids. Here we report the discovery that a small molecule, cyanuric acid, with three thymine-like faces, reprogrammes the assembly of unmodified poly(adenine) (poly(A)) into stable, long and abundant fibres with a unique internal structure. Poly(A) DNA, RNA and peptide nucleic acid (PNA) all form these assemblies. Our studies are consistent with the association of adenine and cyanuric acid units into a hexameric rosette, which brings together poly(A) triplexes with a subsequent cooperative polymerization. Fundamentally, this study shows that small hydrogen-bonding molecules can be used to induce the assembly of nucleic acids in water, which leads to new structures from inexpensive and readily available materials. PMID:27001733

  16. 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.

  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. 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)

  19. 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.

  20. Synthesis of heterocycle-modified betulinic acid derivatives as antitumor agents.

    PubMed

    Cui, Hai-Wei; He, Yuan; Wang, Jinhua; Gao, Wei; Liu, Ting; Qin, Min; Wang, Xue; Gao, Cheng; Wang, Yan; Liu, Ming-Yao; Yi, Zhengfang; Qiu, Wen-Wei

    2015-05-01

    A series of novel heterocycle-modified betulinic acid (BA) derivatives were synthesized and investigated for their activity against the growth of eight non-drug resistant and one multidrug-resistant tumor cell line using a sulforhodamine B (SRB) assay. The most active compound 17 showed an average IC50 1.19 μM, which was about 20 times more potent than the lead compound BA. It is amazing that for most synthetic saturated N-heterocycle derivatives, MCF-7/ADR was the most sensitive tumor cells, especially 17 showed the most potent antitumor activity (IC50 = 0.33 μM) on this multidrug-resistant tumor cell line, that was 117 times more potent than BA. Most of the tested compounds displayed less toxic on human fibroblasts (HAF) in comparison with the tumor cell lines. The cytometry and transwell migration assays were used to test the ability of 17 to induce apoptosis and inhibit metastasis on tumor cell lines respectively.

  1. Generation of N-Heterocycles via Tandem Reactions of N '-(2-Alkynylbenzylidene)hydrazides.

    PubMed

    Qiu, Guanyinsheng; Wu, Jie

    2016-02-01

    As a powerful synthon, N '-(2-alkynylbenzylidene)hydrazides have been utilized efficiently for the construction of N-heterocycles. Since N '-(2-alkynylbenzylidene)hydrazides can easily undergo intramolecular 6-endo cyclization promoted by silver triflate or electrophiles, the resulting isoquinolinium-2-yl amides can proceed through subsequent transformations including [3 + 2] cycloaddition, nucleophilic addition, and [3 + 3] cycloaddition. Several unexpected rearrangements via radical processes were observed in some cases, which afforded nitrogen-containing heterocycles with molecular complexity. Reactive partners including internal alkynes, arynes, ketenimines, ketenes, allenoates, and activated alkenes reacted through [3 + 2] cycloaddition and subsequent aromatization, leading to diverse H-pyrazolo[5,1-a]isoquinolines with high efficiency. Nucleophilic addition to the in situ generated isoquinolinium-2-yl amide followed by aromatization also produced H-pyrazolo[5,1-a]isoquinoline derivatives when terminal alkynes, carbonyls, enamines, and activated methylene compounds were used as nucleophiles. Isoquinoline derivatives were obtained when indoles or phosphites were employed as nucleophiles in the reactions of N '-(2-alkynylbenzylidene)hydrazides. A tandem 6-endo cyclization and [3 + 3] cycloaddition of cyclopropane-1,1-dicarboxylates with N '-(2-alkynylbenzylidene)hydrazides was observed as well. Small libraries of these compounds were constructed. Biological evaluation suggested that some compounds showed promising activities for inhibition of CDC25B, TC-PTP, HCT-116, and PTP1B. PMID:26493018

  2. Masked N-Heterocyclic Carbene-Catalyzed Alkylation of Phenols with Organic Carbonates.

    PubMed

    Lui, Matthew Y; Yuen, Alexander K L; Masters, Anthony F; Maschmeyer, Thomas

    2016-09-01

    An easily prepared masked N-heterocyclic carbene, 1,3-dimethylimidazolium-2-carboxylate (DMI-CO2 ), was investigated as a "green" and inexpensive organocatalyst for the alkylation of phenols. The process made use of various low-toxicity and renewable alkylating agents, such as dimethyl- and diethyl carbonate, in a focused microwave reactor. DMI-CO2 was found to be a very active catalyst and excellent yields of a range of aryl alkyl ethers were obtained under relatively benign conditions. The observed difference in the conversion behavior of phenol methylation, in the presence of either the carbene or 1,8-diazabicycloundec-7-ene (DBU) catalyst, was rationalized on the basis of mechanistic investigations. The primary mode of action for the N-heterocyclic carbene is nucleophilic catalysis. Activation of the dialkyl carbonate electrophile results in concomitant evolution of an organo-soluble alkoxide, which deprotonates the phenolic starting material. In contrast, DBU is initially protonated by the phenol and thus consumed. Subsequent regeneration and participation in nucleophilic catalysis only becomes significant after some phenolate alkylation occurs. PMID:27528488

  3. Tandem sequence of phenol oxidation and intramolecular addition as a method in building heterocycles.

    PubMed

    Ratnikov, Maxim O; Farkas, Linda E; Doyle, Michael P

    2012-11-16

    A tandem phenol oxidation-Michael addition furnishing oxo- and -aza-heterocycles has been developed. Dirhodium caprolactamate [Rh(2)(cap)(4)] catalyzed oxidation by T-HYDRO of phenols with alcohols, ketones, amides, carboxylic acids, and N-Boc protected amines tethered to their 4-position afforded 4-(tert-butylperoxy)cyclohexa-2,5-dienones that undergo Brønsted acid catalyzed intramolecular Michael addition in one-pot to produce oxo- and -aza-heterocycles in moderate to good yields. The scope of the developed methodology includes dipeptides Boc-Tyr-Gly-OEt and Boc-Tyr-Phe-Me and provides a pathway for understanding the possible transformations arising from oxidative stress of tyrosine residues. A novel method of selective cleavage of O-O bond in hindered internal peroxide using TiCl(4) has been discovered in efforts directed to the construction of cleroindicin F, whose synthesis was completed in 50% yield over just 3 steps from tyrosol using the developed methodology.

  4. Synthesis of Amino- and Nitro-Substituted Heterocycles as Insensitive Energetic Materials

    SciTech Connect

    Pagoria, P F; Lee, G S; Mitchell, A R; Schmidt, R D

    2001-08-23

    In this paper we will describe the synthesis of several amino- and nitro-substituted heterocycles, examples from a continuing research project targeted at the synthesis of new, insensitive energetic materials that possess at least 80% the power of HMX (28% more power than TATB). Recently we reported the synthesis and scale-up of the insensitive energetic material, 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105). The energy content (81% the power of HMX) and thermal stability of LLM-105 make it a viable candidate material for insensitive boosters and deep oil perforation. We will report on recent synthetic improvements and several performance and safety tests performed on LLM-105, including a 1 in. cylinder shot and plate dent. We will also report on the synthesis and characterization of 4-amino-3,5-dinitropyrazole (LLM-116), an interesting new insensitive energetic material with a measured crystal density of 1.90 g/cc, to our knowledge the highest density yet measured for a five-membered heterocycle containing amino- and nitro-substituents. LLM-116 was synthesized by reacting 3,5-dinitropyrazole with 1,1,1-trimethylhydrazinium iodide (TMHI) in DMSO in the presence of base. The synthesis and characterization of 4-amino-5-nitro-1,2,3-triazole (ANTZ) and 43-dinitro-1,2,3-triazole (DNTZ), first described by Baryshnikov and coworkers, will also be presented along with the synthesis of several new energetic materials derived from ANTZ and DNTZ.

  5. A class of fluorescent heterocyclic dyes revisited: Photophysics, structure, and solvent effects

    NASA Astrophysics Data System (ADS)

    Zhu, Lianjie; Becker, Hans-Christian; Henriksen, Lars; Kilså, Kristine

    2009-08-01

    The photophysical behavior of a series of 2-methylthio-5-(Z-carbonyl)thieno-[3,4-e]-3,4-dihydro-1,2,3-triazine-4-ones was investigated by absorption and emission spectroscopy in a range of solvents representing a systematic variation in polarity, polarizability, as well as hydrogen bond donating and accepting capabilities. In all the investigated compounds, the heterocyclic 6-membered ring of the chromophore is involved in interactions between electron donor and acceptor substituents on the thiophene ring. Throughout the series, the charge-donating methylthio group is kept constant, while the acceptor (Z-carbonyl) is varied between amide, ester, and ketone functionalities. The fluorescent first electronically excited state is primarily of intramolecular HOMO-LUMO charge transfer character. All members of the series exhibit solvent-dependent photophysics, although the magnitude of the dependence varies with the nature of the acceptor group. In addition to the solvent-sensitive photophysics, the investigated class of compounds shows high thermal and chemical stability. Among this class of heterocyclic dyes, the amide-substituted compound is superior with respect to high quantum yield and lifetime, and also shows the largest change in emission lifetimes and fluorescence quantum yields upon solvent variation (about 5-fold).

  6. Heterocyclic amines: evaluation of their role in diet associated human cancer

    PubMed Central

    GOODERHAM, N. J.; MURRAY, S.; LYNCH, A. M.; EDWARDS, R. J.; YADOLLAHI-FARSANI, M.; BRATT, C.; RICH, K. J.; ZHAO, K.; MURRAY, B. P.; BHADRESA, S.; CROSBIE, S. J.; BOOBIS, A. R.; DAVIES, D. S.

    1996-01-01

    1Heterocyclic amines are formed in parts per billion levels when meat is cooked. 2The heterocyclic amines MeIQx and PhIP are efficiently absorbed into the systemic circulation after ingestion of cooked food. 3We have shown that MeIQx and PhIP, both in vitro and in vivo, are substrates for human hepatic CYP1A2, which exclusively and efficiently catalyses their conversion to genotoxic hydroxylamines. 4MeIQx and PhIP are promutagens. MeIQx is a very powerful bacterial mutagen whereas PhIP is a more potent mammalian cell mutagen. Using a mammalian cell target gene, hprt, we have shown that PhIP induces a characteristic mutational ‘fingerprint’. 5MeIQx and PhIP are carcinogenic in bioassays. The PhIP mutational ‘fingerprint’ has been detected in the Apc gene of 5/8 colonic tumours induced by PhIP in rats. PMID:8807149

  7. The poly dA strand of poly dA.poly dT adopts an A-form in solution: a UV resonance Raman study.

    PubMed Central

    Jollès, B; Laigle, A; Chinsky, L; Turpin, P Y

    1985-01-01

    The study by resonance Raman spectroscopy with a 257 nm excitation wave-length of adenine in two single-stranded polynucleotides, poly rA and poly dA, and in three double-stranded polynucleotides, poly dA.poly dT, poly(dA-dT).poly(dA-dT) and poly rA.poly rU, allows one to characterize the A-genus conformation of polynucleotides containing adenine and thymine bases. The characteristic spectrum of the A-form of the adenine strand is observed, except small differences, for poly rA, poly rA.poly rU and poly dA.poly dT. Our results prove that it is the adenine strand which adopts the A-family conformation in poly dA.poly dT. PMID:4000953

  8. 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. PMID:25331279

  9. Infrared Spectroscopy of Matrix-Isolated Polycyclic Aromatic Compounds and Their Ions. 7; Phenazine, a Dual Substituted Polycyclic Aromatic Nitrogen Heterocycle

    NASA Technical Reports Server (NTRS)

    Mattioda, A. L.; Hudgins, D. M.; Bauschlicher, C. W., Jr.; Allamandola, L. J.

    2004-01-01

    The matrix-isolation technique has been employed to measure the mid-infrared spectra of phenazine (C12H8N2), a dual substituted Polycyclic Aromatic Nitrogen Heterocycle (PANH), in the neutral, cationic and anionic forms. The experimentally measured band frequencies and intensities are tabulated and compared with their calculated values as well as those of the non-substituted parent molecule, anthracene. The theoretical band positions and intensities were calculated using both the 3-31 G as well as the larger 6-3lG* Basis Sets. A comparison of the results can be found in the tables. The spectroscopic properties of phenazine and its cation are similar to those observed in mono-substituted PANHs, with one exception. The presence of a second nitrogen atom results in an additional enhancement of the cation's total integrated intensity, for the 1500-1000 cm(sup -1) (6.7 to 10 micron) region, over that observed for a mono-substituted PANH cation. The significance of this enhancement and the astrobiological implications of these results are discussed.

  10. Determinants of activity at human Toll-like receptors 7 and 8: quantitative structure-activity relationship (QSAR) of diverse heterocyclic scaffolds.

    PubMed

    Yoo, Euna; Salunke, Deepak B; Sil, Diptesh; Guo, Xiaoqiang; Salyer, Alex C D; Hermanson, Alec R; Kumar, Manoj; Malladi, Subbalakshmi S; Balakrishna, Rajalakshmi; Thompson, Ward H; Tanji, Hiromi; Ohto, Umeharu; Shimizu, Toshiyuki; David, Sunil A

    2014-10-01

    Toll-like receptor (TLR) 7 and 8 agonists are potential vaccine adjuvants, since they directly activate APCs and enhance Th1-driven immune responses. Previous SAR investigations in several scaffolds of small molecule TLR7/8 activators pointed to the strict dependence of the selectivity for TLR7 vis-à-vis TLR8 on the electronic configurations of the heterocyclic systems, which we sought to examine quantitatively with the goal of developing "heuristics" to define structural requisites governing activity at TLR7 and/or TLR8. We undertook a scaffold-hopping approach, entailing the syntheses and biological evaluations of 13 different chemotypes. Crystal structures of TLR8 in complex with the two most active compounds confirmed important binding interactions playing a key role in ligand occupancy and biological activity. Density functional theory based quantum chemical calculations on these compounds followed by linear discriminant analyses permitted the classification of inactive, TLR8-active, and TLR7/8 dual-active compounds, confirming the critical role of partial charges in determining biological activity.

  11. Determinants of Activity at Human Toll-like Receptors 7 and 8: Quantitative Structure–Activity Relationship (QSAR) of Diverse Heterocyclic Scaffolds

    PubMed Central

    2015-01-01

    Toll-like receptor (TLR) 7 and 8 agonists are potential vaccine adjuvants, since they directly activate APCs and enhance Th1-driven immune responses. Previous SAR investigations in several scaffolds of small molecule TLR7/8 activators pointed to the strict dependence of the selectivity for TLR7 vis-à-vis TLR8 on the electronic configurations of the heterocyclic systems, which we sought to examine quantitatively with the goal of developing “heuristics” to define structural requisites governing activity at TLR7 and/or TLR8. We undertook a scaffold-hopping approach, entailing the syntheses and biological evaluations of 13 different chemotypes. Crystal structures of TLR8 in complex with the two most active compounds confirmed important binding interactions playing a key role in ligand occupancy and biological activity. Density functional theory based quantum chemical calculations on these compounds followed by linear discriminant analyses permitted the classification of inactive, TLR8-active, and TLR7/8 dual-active compounds, confirming the critical role of partial charges in determining biological activity. PMID:25192394

  12. 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.

  13. Increased Hydrogel Swelling Induced by Absorption of Small Molecules.

    PubMed

    Nam, Changwoo; Zimudzi, Tawanda J; Geise, Geoffrey M; Hickner, Michael A

    2016-06-01

    The water and small molecule uptake behavior of amphiphilic diacrylate terminated poly(dimethylsiloxane) (PDMSDA)/poly(ethylene glycol diacrylate) (PEGDA) cross-linked hydrogels were studied using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. These hydrogel networks absorbed more water as the PEGDA content of the network increased. In contrast to typical osmotic deswelling behavior that occurs when liquid water equilibrated hydrogels are immersed in small molecule solutions with water activities less than unity, water-swollen gels immersed in 2-acrylamido-2-methylpropanesulfonic acid (AMPS-H) solutions rapidly regained their water content within 4 min following an initial deswelling response. In situ ATR-FTIR analysis of the hydrogel film during the dynamic swelling experiment indicated that small molecule absorption into the gel played an important role in inducing gel reswelling in low water activity solutions. This aspect of polymer gel water uptake and interaction with small molecules is important for optimizing hydrogel coatings and hydrophilic polymer applications where there is an interaction between the internal chemical structure of the gel and electrolytes or other molecules in solution. PMID:27159118

  14. Enhancement of the carrier mobility of poly(3,4-ethylenedioxythiophene) doped with poly(4-styrenesulfonate) by incorporating reduced graphene oxide

    NASA Astrophysics Data System (ADS)

    Lin, Yow-Jon; Zeng, Jian-Jhou; Tsai, Cheng-Lung

    2012-07-01

    The investigation of poly(3,4-ethylenedioxythiophene) doped with poly(4-styrenesulfonate) (PEDOT:PSS) having the reduced graphene oxide (RGO), denoted RGO-doped PEDOT:PSS shows that conductivity of RGO-doped PEDOT:PSS samples is 27 times higher than that of PEDOT:PSS at 300 K. The improved electrical conductivity is considered to mainly come from the mobility enhancement. The carrier mobility in RGO-doped PEDOT:PSS samples exhibits unexpectedly strong temperature dependence, implying the domination of tunneling (hopping) at low (high) temperatures. An exhibition of high mobility of RGO-doped PEDOT:PSS samples is attributed to the increased spacing between molecules.

  15. Sorocenols G and H, Anti-MRSA Oxygen Heterocyclic Diels-Alder-type Adducts from Sorocea muriculata Roots

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bioassay-guided fractionation of a root extract of Sorocea muriculata led to the isolation and identification of two new oxygen heterocyclic Diels-Alder-type adducts, sorocenols G (1) and H (2), along with lupeol-3-(3'R-hydroxytetradecanoate) and oxyresveratrol. The structures of 1 and 2 were eluci...

  16. Atmospheric Hydrogenation of Esters Catalyzed by PNP-Ruthenium Complexes with an N-Heterocyclic Carbene Ligand.

    PubMed

    Ogata, Osamu; Nakayama, Yuji; Nara, Hideki; Fujiwhara, Mitsuhiko; Kayaki, Yoshihito

    2016-08-01

    New pincer ruthenium complexes bearing a monodentate N-heterocyclic carbene ligand were synthesized and demonstrated as powerful hydrogenation catalysts. With an atmospheric pressure of hydrogen gas, aromatic, heteroaromatic, and aliphatic esters as well as lactones were converted into the corresponding alcohols at 50 °C. This reaction protocol offers reliable access to alcohols using an easy operational setup.

  17. The Chemistry of Formazan Dyes: Synthesis and Characterization of a Stable Verdazyl Radical and a Related Boron-Containing Heterocycle

    ERIC Educational Resources Information Center

    Berry, David E.; Hicks, Robin G.; Gilroy, Joe B.

    2009-01-01

    This experiment describes the synthesis and characterization of a formazan dye, and its subsequent conversion to a stable verdazyl radical and a boron-nitrogen heterocycle (boratatetrazine). Each of these compounds is intensely colored and is prepared and handled under aerobic conditions, which often surprises students as free radicals are…

  18. Optimized Syntheses of Cyclopentadienyl Nickel Chloride Compounds Containing "N"-Heterocyclic Carbene Ligands for Short Laboratory Periods

    ERIC Educational Resources Information Center

    Cooke, Jason; Lightbody, Owen C.

    2011-01-01

    Experiments are described for the preparation of imidazolium chloride precursors to "N"-heterocyclic carbenes and their cyclopentadienyl nickel chloride derivatives. The syntheses have been optimized for second- and third-year undergraduate laboratories that have a maximum programmed length of three hours per week. The experiments are flexible and…

  19. Pd-N-Heterocyclic Carbene (NHC) Organic Silica: Synthesis and Application in Carbon-Carbon Coupling Reactions

    EPA Science Inventory

    The first Pd-N-heterocyclic carbene (NHC) complex in the form of organic silica was prepared using sol-gel method and its application in Heck and Suzuki reaction were demonstrated. These C-C coupling reactions proceeded efficiently under the influence of microwave irradiation, wi...

  20. Synthesis of Heterocycles Through Classical Ugi and Passerini Reactions Followed by Secondary Transformations Involving One or Two Additional Functional Groups

    NASA Astrophysics Data System (ADS)

    Banfi, Luca; Basso, Andrea; Riva, Renata

    The combination of classical isocyanide-based multicomponent reactions (Ugi and Passerini) with a variety of post-condensation transformations, which take advantage of suitably positioned additional functional groups, allows the straightforward synthesis, often in 1-2 synthetic steps, of many diverse nitrogen-containing heterocycles. This review will cover all the applications of this strategy reported to date (September 2009).

  1. Atmospheric Hydrogenation of Esters Catalyzed by PNP-Ruthenium Complexes with an N-Heterocyclic Carbene Ligand.

    PubMed

    Ogata, Osamu; Nakayama, Yuji; Nara, Hideki; Fujiwhara, Mitsuhiko; Kayaki, Yoshihito

    2016-08-01

    New pincer ruthenium complexes bearing a monodentate N-heterocyclic carbene ligand were synthesized and demonstrated as powerful hydrogenation catalysts. With an atmospheric pressure of hydrogen gas, aromatic, heteroaromatic, and aliphatic esters as well as lactones were converted into the corresponding alcohols at 50 °C. This reaction protocol offers reliable access to alcohols using an easy operational setup. PMID:27439106

  2. Multicomponent Dipolar Cycloaddition Strategy: Combinatorial Synthesis of Novel Spiro-Tethered Pyrazolo[3,4-b]quinoline Hybrid Heterocycles.

    PubMed

    Sumesh, Remani Vasudevan; Muthu, Muthumani; Almansour, Abdulrahman I; Suresh Kumar, Raju; Arumugam, Natarajan; Athimoolam, S; Jeya Yasmi Prabha, E Arockia; Kumar, Raju Ranjith

    2016-05-01

    The stereoselective syntheses of a library of novel spiro-tethered pyrazolo[3,4-b]quinoline-pyrrolidine/pyrrolothiazole/indolizine-oxindole/acenaphthene hybrid heterocycles have been achieved through the 1,3-dipolar cycloaddition of azomethine ylides generated in situ from α-amino acids and 1,2-diketones to dipolarophiles derived from pyrazolo[3,4-b]quinoline derivatives.

  3. Synthesis and Properties of Chelating N-Heterocyclic Carbene Rhodium(I) Complexes: Synthetic Experiments in Current Organometallic Chemistry

    ERIC Educational Resources Information Center

    Mata, Jose A.; Poyatos, Macarena; Mas-Marza, Elena

    2011-01-01

    The preparation and characterization of two air-stable Rh(I) complexes bearing a chelating N-heterocyclic carbene (NHC) ligand is described. The synthesis involves the preparation of a Ag(I)-NHC complex and its use as carbene transfer agent to a Rh(I) precursor. The so obtained complex can be further reacted with carbon monoxide to give the…

  4. A Free-Radical-Promoted Site-Specific Cross-Dehydrogenative-Coupling of N-Heterocycles with Fluorinated Alcohols.

    PubMed

    Xu, Zhengbao; Hang, Zhaojia; Chai, Li; Liu, Zhong-Quan

    2016-09-16

    A C-C formation of an electron-rich N-heterocycle with fluorinated alcohol is developed. Through this radical-triggered cross-dehydrogenative coupling strategy, a wide range of useful building blocks such as C3 hydroxyfluoroalkylated indoles and pyrroles can be site-specifically synthesized. Mechanistic studies indicate a single-electron-transfer initiated radical cycle would be involved.

  5. Novel heterocyclic thiosemicarbazones derivatives as colorimetric and “turn on” fluorescent sensors for fluoride anion sensing employing hydrogen bonding

    NASA Astrophysics Data System (ADS)

    Ashok Kumar, S. L.; Saravana Kumar, M.; Sreeja, P. B.; Sreekanth, A.

    2013-09-01

    Two novel heterocyclic thiosemicarbazone derivatives have been synthesized, and characterized, by means of spectroscopic and single crystal X-ray diffraction methods. Their chromophoric-fluorogenic response towards anions in competing solvent dimethyl sulfoxide (DMSO) was studied. The receptor shows selective recognition towards fluoride anion. The binding affinity of the receptors with fluoride anion was calculated using UV-visible and fluorescence spectroscopic techniques.

  6. A new one-pot synthesis of novel hetarylazo-heterocyclic colorants and study of their solvatochromic properties.

    PubMed

    Shawali, Ahmad S; Abdallah, Magda A; Kandil, Mohamed A

    2015-09-01

    A simple synthetic strategy for synthesis of new series of hetarylazo-heterocycles is described. The effects of solvent on their electronic absorption spectra were analyzed using Kamlet-Taft equation. The results of fitting coefficients indicated that the solvatochromism of the studied compounds is mainly due to the solvent polarity rather than the solvent basicity and acidity. PMID:27330835

  7. Selective Kumada biaryl cross-coupling reaction enabled by an iron(III) alkoxide-N-heterocyclic carbene catalyst system.

    PubMed

    Chua, Yi-Yuan; Duong, Hung A

    2014-08-01

    A catalyst system comprising Fe2(O(t)Bu)6 and an N-heterocyclic carbene ligand enables efficient syntheses of (hetero)biaryls from the reactions of aryl Grignard reagents with a diverse spectrum of (hetero)aryl chlorides. Amongst the alkoxide and amide counterions investigated, tert-butoxide was the most effective in inhibiting the homocoupling of arylmagnesiums. PMID:24947849

  8. A new one-pot synthesis of novel hetarylazo-heterocyclic colorants and study of their solvatochromic properties.

    PubMed

    Shawali, Ahmad S; Abdallah, Magda A; Kandil, Mohamed A

    2015-09-01

    A simple synthetic strategy for synthesis of new series of hetarylazo-heterocycles is described. The effects of solvent on their electronic absorption spectra were analyzed using Kamlet-Taft equation. The results of fitting coefficients indicated that the solvatochromism of the studied compounds is mainly due to the solvent polarity rather than the solvent basicity and acidity.

  9. Reactivity studies of pincer bis-protic N-heterocyclic carbene complexes of platinum and palladium under basic conditions

    PubMed Central

    Marelius, David C; Moore, Curtis E; Rheingold, Arnold L

    2016-01-01

    Summary Bis-protic N-heterocyclic carbene complexes of platinum and palladium (4) yield dimeric structures 6 when treated with sodium tert-butoxide in CH2Cl2. The use of a more polar solvent (THF) and a strong base (LiN(iPr)2) gave the lithium chloride adducts monobasic complex 7 or analogous dibasic complex 8. PMID:27559382

  10. Gold/Lewis Acid Catalyzed Cycloisomerization/Diastereoselective [3 + 2] Cycloaddition Cascade: Synthesis of Diverse Nitrogen-Containing Spiro Heterocycles.

    PubMed

    Wang, Bin; Liang, Man; Tang, Jian; Deng, Yuting; Zhao, Jinhong; Sun, Hao; Tung, Chen-Ho; Jia, Jiong; Xu, Zhenghu

    2016-09-16

    A novel early and late transition-metal relay catalysis has been developed by combining a gold-catalyzed cycloisomerization and a Yb(OTf)3-catalyzed diastereoselective [3 + 2] cycloaddition with aziridines in a selective C-C bond cleavage mode. Various biologically significant complex nitrogen-containing spiro heterocycles were rapidly constructed from readily available starting materials under mild conditions. PMID:27574831

  11. Reactivity studies of pincer bis-protic N-heterocyclic carbene complexes of platinum and palladium under basic conditions.

    PubMed

    Marelius, David C; Moore, Curtis E; Rheingold, Arnold L; Grotjahn, Douglas B

    2016-01-01

    Bis-protic N-heterocyclic carbene complexes of platinum and palladium (4) yield dimeric structures 6 when treated with sodium tert-butoxide in CH2Cl2. The use of a more polar solvent (THF) and a strong base (LiN(iPr)2) gave the lithium chloride adducts monobasic complex 7 or analogous dibasic complex 8. PMID:27559382

  12. Electrochemical measurements of diffusion coefficients of redox-labeled poly(ethylene glycol) dissolved in poly(ethylene glycol) melts

    SciTech Connect

    Haas, O.; Velazquez, C.S.; Porat, Z.; Murray, R.W.

    1995-10-12

    Ferrocene labeled monomethoxy-poly(ethylene glycol)s (MPEG) with molecular weights of 1900 and 750 were used as redox probe solutes in poly(ethylene glycol) melt solvents of molecular weight 750, 2000, and 20000. Cyclic voltammetry and chronoamperometry at microdisk electrodes were employed to measure the diffusion coefficients of the redox probes, which were independent of the probe concentration and varied between 10{sup -7} and 10{sup -10} cm{sup 2}/s. Diffusional activation barrier results also suggest that the ferrocene label does not significantly influence the diffusivity of the probe molecule in the host solvent. Activation barrier, viscosity, and ionic conductivity results show that the LiClO{sub 4} electrolyte does not influence the diffusion barrier or viscosity as long as the ether O/Li{sup +} ratio is >=250 (ca. 0.1 M) which is still a sufficient electrolyte concentration to allow quantitative electrochemical diffusion measurements. 21 refs., 7 figs., 2 tabs.

  13. Insulin/poly(ethylene glycol)-block-poly(L-lysine) Complexes: Physicochemical Properties and Protein Encapsulation.

    PubMed

    Pippa, Natassa; Kalinova, Radostina; Dimitrov, Ivaylo; Pispas, Stergios; Demetzos, Costas

    2015-06-01

    Insulin (INS) was encapsulated into complexes with poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLys), which is a polypeptide-based block copolymer (a neutral-cationic block polyelectrolyte). The particular cationic-neutral block copolymer can complex INS molecules in aqueous media via electrostatic interactions. Light-scattering techniques are used to study the complexation process and structure of the hybrid nanoparticles in a series of buffers, as a function of protein concentration. The physicochemical and structural characteristics of the complexes depend on the ionic strength of the aqueous medium, while the concentration of PEG-b-PLys was constant through the series of solutions. As INS concentration increased the size distribution of the complexes decreased, especially at the highest ionic strength. The size/structure of complexes diluted in biological medium indicated that the copolymer imparts stealth properties and colloidal and biological stability to the complexes, features that could in turn affect the clearance properties in vivo. Therefore, these studies could be a rational roadmap for designing the optimum complexes/effective nanocarriers for proteins and peptides. PMID:25974620

  14. Preparation and single molecule structure of electroactive polysilane end-grafted on a crystalline silicon surface

    NASA Astrophysics Data System (ADS)

    Furukawa, Kazuaki; Ebata, Keisuke

    2000-12-01

    Electrically active polysilanes of poly(methylphenylsilane) (PMPS) and poly[bis(p-n-butylphenyl)silane] (PBPS), which are, respectively, known as a good hole transporting material and a near-ultraviolet electroluminescent material, are end-grafted directly on a crystalline silicon surface. The single polysilane molecules are clearly distinguished one from the other on the surface by means of atomic force microscopy observations. End-grafted single molecules of PMPS are observed as dots while end-grafted PBPS appear as worms extending for more than 100 nm on the crystalline silicon surface.

  15. Synthesis and characterization of hyperbranched poly(glycidol) modified with pH- and temperature-sensitive groups.

    PubMed

    Kojima, Chie; Yoshimura, Kohei; Harada, Atsushi; Sakanishi, Yuichi; Kono, Kenji

    2009-05-20

    Hyperbranched poly(glycidol)s with varying degrees of polymerization were modified by reaction with succinic anhydride and isopropylamine to obtain novel pH- and thermosensitive polymers. These polymers exhibited phase transitions in response to decreasing pH and/or increasing temperature, depending on the degree of polymerization and the ratio of succinyl group to N-isopropylamide. It was possible to harvest a bioactive molecule, rose bengal, from solution using the phase transition of thermosensitive hyperbranched poly(glycidol).

  16. 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.

  17. Linking ultracold polar molecules.

    PubMed

    Avdeenkov, A V; Bohn, John L

    2003-01-31

    We predict that pairs of polar molecules can be weakly bound together in an ultracold environment, provided that a dc electric field is present. The field that links the molecules together also strongly influences the basic properties of the resulting dimer, such as its binding energy and predissociation lifetime. Because of their long-range character, these dimers will be useful in disentangling cold collision dynamics of polar molecules. As an example, we estimate the microwave photoassociation yield for OH-OH cold collisions.

  18. Structure and Mechanism of Dimer-Monomer Transition of a Plant Poly(A)-Binding Protein upon RNA Interaction: Insights into Its Poly(A) Tail Assembly.

    PubMed

    Domingues, Mariane Noronha; Sforça, Mauricio Luis; Soprano, Adriana Santos; Lee, Jack; Souza, Tatiana de Arruda Campos Brasil de; Cassago, Alexandre; Portugal, Rodrigo Villares; Zeri, Ana Carolina de Mattos; Murakami, Mario Tyago; Sadanandom, Ari; Oliveira, Paulo Sergio Lopes de; Benedetti, Celso Eduardo

    2015-07-31

    Poly(A)-binding proteins (PABPs) play crucial roles in mRNA biogenesis, stability, transport and translational control in most eukaryotic cells. Although animal PABPs are well-studied proteins, the biological role, three-dimensional structure and RNA-binding mode of plant PABPs remain largely uncharacterized. Here, we report the structural features and RNA-binding mode of a Citrus sinensis PABP (CsPABPN1). CsPABPN1 has a domain architecture of nuclear PABPs (PABPNs) with a single RNA recognition motif (RRM) flanked by an acidic N-terminus and a GRPF-rich C-terminus. The RRM domain of CsPABPN1 displays virtually the same three-dimensional structure and poly(A)-binding mode of animal PABPNs. However, while the CsPABPN1 RRM domain specifically binds poly(A), the full-length protein also binds poly(U). CsPABPN1 localizes to the nucleus of plant cells and undergoes a dimer-monomer transition upon poly(A) interaction. We show that poly(A) binding by CsPABPN1 begins with the recognition of the RNA-binding sites RNP1 and RNP2, followed by interactions with residues of the β2 strands, which stabilize the dimer, thus leading to dimer dissociation. Like human PABPN1, CsPABPN1 also seems to form filaments in the presence of poly(A). Based on these data, we propose a structural model in which contiguous CsPABPN1 RRM monomers wrap around the RNA molecule creating a superhelical structure that could not only shield the poly(A) tail but also serve as a scaffold for the assembly of additional mRNA processing factors.

  19. Structure and Mechanism of Dimer-Monomer Transition of a Plant Poly(A)-Binding Protein upon RNA Interaction: Insights into Its Poly(A) Tail Assembly.

    PubMed

    Domingues, Mariane Noronha; Sforça, Mauricio Luis; Soprano, Adriana Santos; Lee, Jack; Souza, Tatiana de Arruda Campos Brasil de; Cassago, Alexandre; Portugal, Rodrigo Villares; Zeri, Ana Carolina de Mattos; Murakami, Mario Tyago; Sadanandom, Ari; Oliveira, Paulo Sergio Lopes de; Benedetti, Celso Eduardo

    2015-07-31

    Poly(A)-binding proteins (PABPs) play crucial roles in mRNA biogenesis, stability, transport and translational control in most eukaryotic cells. Although animal PABPs are well-studied proteins, the biological role, three-dimensional structure and RNA-binding mode of plant PABPs remain largely uncharacterized. Here, we report the structural features and RNA-binding mode of a Citrus sinensis PABP (CsPABPN1). CsPABPN1 has a domain architecture of nuclear PABPs (PABPNs) with a single RNA recognition motif (RRM) flanked by an acidic N-terminus and a GRPF-rich C-terminus. The RRM domain of CsPABPN1 displays virtually the same three-dimensional structure and poly(A)-binding mode of animal PABPNs. However, while the CsPABPN1 RRM domain specifically binds poly(A), the full-length protein also binds poly(U). CsPABPN1 localizes to the nucleus of plant cells and undergoes a dimer-monomer transition upon poly(A) interaction. We show that poly(A) binding by CsPABPN1 begins with the recognition of the RNA-binding sites RNP1 and RNP2, followed by interactions with residues of the β2 strands, which stabilize the dimer, thus leading to dimer dissociation. Like human PABPN1, CsPABPN1 also seems to form filaments in the presence of poly(A). Based on these data, we propose a structural model in which contiguous CsPABPN1 RRM monomers wrap around the RNA molecule creating a superhelical structure that could not only shield the poly(A) tail but also serve as a scaffold for the assembly of additional mRNA processing factors. PMID:26013164

  20. 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. PMID:25766132

  1. Effects of heterocyclic aromatic substituents on binding affinities at two distinct sites of somatostatin receptors. Correlation with the electrostatic potential of the substituents.

    PubMed

    Prasad, Vidya; Birzin, Elizabeth T; McVaugh, Cheryl T; Van Rijn, Rachel D; Rohrer, Susan P; Chicchi, Gary; Underwood, Dennis J; Thornton, Edward R; Smith, Amos B; Hirschmann, Ralph

    2003-05-01

    In our continuing program exploring glucose-based peptidomimetics of somatostatin (SRIF-14), we sought to improve the water solubility of our glycosides. This led to insights into the nature of the ligand binding sites at the SRIF receptor. Replacement of the C4 benzyl substituent in glucoside (+)-2 with pyridinylmethyl or pyrazin-2-ylmethyl congeners increased water solubility and enhanced affinity for the human SRIF subtype receptor 4 (sst4). We attribute this effect to hydrogen bond formation. The pyridin-3-ylmethyl substituent at C4, when combined with the imidazol-4-ylmethyl group at C2, generated (-)-19, which has the highest affinity of a glucose-based peptidomimetic at a human SRIF receptor to date (K(i) 53 +/- 23 nM, n = 6 at sst4). The C4 heterocyclic congeners of glucosides bearing a 1-methoxy substituent rather than an indole side chain at the anomeric carbon, such as (+)-16, also provided information about the Trp(8) binding pocket. We correlated the SARs at both the C4 and the Trp(8) binding pockets with calculations of the electrostatic potentials of the diverse C4 aromatic substituents using Spartan 3-21G(*) MO analysis. These calculations provide an approximate analysis of a molecule's ability to interact within a receptor binding site. Our binding studies show that benzene and indole rings, but not pyridinylmethyl nor pyrazin-2-ylmethyl rings, can bind the hydrophobic Trp(8) binding pocket of sst4. The Spartan 3-21G(*) MO analysis reveals significant negative electrostatic potential in the region of the pi-clouds for the benzene and indole rings but not for the pyridinylmethyl or pyrazin-2-ylmethyl congeners. Our data further demonstrate that the replacement of benzene or indole side chains by heterocyclic aromatic rings typified by pyridine and pyrazine not only enhances water solubility and hydrogen bonding capacity as expected, but can also profoundly diminish the ability of the pi-cloud of the aromatic substituent to interact with side chains

  2. Interlocked molecules: Aqueous assembly

    NASA Astrophysics Data System (ADS)

    Bai, Linyi; Zhao, Yanli

    2015-12-01

    The quantitative self-assembly of mechanically interlocked molecules in water, instead of organic solvents, opens up the possibility of such systems being used in a biological context where their functions can be interfaced with biomolecular systems.

  3. Single-Molecule Enzymology

    SciTech Connect

    Xie, Xiaoliang; Lu, H PETER.

    1999-06-04

    Viewing a movie of an enzyme molecule made from molecular dynamics (MD) simulation, we see incredible details of molecular motions, be it a change of the conformation or the action of a chemical reaction.

  4. 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)

  5. Thermal decomposition of methyl 2-azidopropionate studied by UV photoelectron spectroscopy and matrix isolation IR spectroscopy: heterocyclic intermediate vs imine formation.

    PubMed

    Pinto, R M; Dias, A A; Costa, M L; Rodrigues, P; Barros, M T; Ogden, J S; Dyke, J M

    2011-08-01

    Methyl 2-azidopropionate (N(3)CH(3)CHCOOCH(3), M2AP) has been synthesized and characterized by different spectroscopic methods, and the thermal decomposition of this molecule has been investigated by matrix isolation infrared (IR) spectroscopy and ultraviolet photoelectron spectroscopy (UVPES). Computational methods have been employed in the spectral simulation of both UVPES and matrix IR spectra and in the rationalization of the thermal decomposition results. M2AP presents a HOMO vertical ionization energy (VIE) of 9.60 ± 0.03 eV and contributions from all four lowest-energy conformations of this molecule are detected in the gas phase. Its thermal decomposition starts at ca. 400 °C and is complete at ca. 650 °C, yielding N(2), CO, CO(2), CH(3)CN, and CH(3)OH as the final decomposition products. Methyl formate (MF) and CH(4) are also found during the pyrolysis process. Analysis of the potential energy surface of the decomposition of M2AP indicates that M2AP decomposes preferentially into the corresponding imine (M2IP), through a 1,2-H shift synchronous with the N(2) elimination (Type 1 mechanism), requiring an activation energy of 160.8 kJ/mol. The imine further decomposes via two competitive routes: one accounting for CO, CH(3)OH, and CH(3)CN (ΔE(G3) = 260.2 kJ/mol) and another leading to CO(2), CH(4), and CH(3)CN (ΔE(G3) = 268.6 kJ/mol). A heterocyclic intermediate (Type 2 mechanism)-4-Me-5-oxazolidone-can also be formed from M2AP via H transfer from the remote O-CH(3) group, together with the N(2) elimination (ΔE(G3) = 260.2 kJ/mol). Finally, a third pathway which accounts for the formation of MF through an M2AP isomer is envisioned.

  6. Overview on poly(ADP-ribose) immuno-biomedicine and future prospects.

    PubMed

    Kanai, Yoshiyuki

    2016-01-01

    Poly(ADP-ribose), identified in 1966 independently by three groups Strassbourg, Kyoto and Tokyo, is synthesized by poly(ADP-ribose) polymerases (PARP) from NAD(+) as a substrate in the presence of Mg(2+). The structure was unique in that it has ribose-ribose linkage. In the early-1970s, however, its function in vivo/in vitro was still controversial and the antibody against it was desired to help clear its significance. Thereupon, the author tried to produce antibody against poly(ADP-ribose) in rabbits and succeeded in it for the first time in the world. Eventually, this success has led to the following two groundbreaking papers in Nature: "Naturally-occurring antibody against poly(ADP-ribose) in patients with autoimmune disease SLE", and "Induction of anti-poly(ADP-ribose) antibody by immunization with synthetic double-stranded RNA, poly(A)·poly(U)".On the way to the publication of the first paper, a reviewer gave me a friendly comment that there is "heteroclitic" fashion as a mechanism of the production of natural antibody. This comment was really a God-send for me, and became a train of power for publication of another paper, as described above. Accordingly, I thought this, I would say, episode is worth describing herein. Because of its importance in biomedical phenomena, a certain number of articles related to "heteroclitic" have become to be introduced in this review, although they were not always directly related to immuno-biological works on poly(ADP-ribose). Also, I tried to speculate on the future prospects of poly(ADP-ribose), product of PARP, as an immuno-regulatory molecule, including either induced or naturally-occurring antibodies, in view of "heteroclitic".

  7. Overview on poly(ADP-ribose) immuno-biomedicine and future prospects.

    PubMed

    Kanai, Yoshiyuki

    2016-01-01

    Poly(ADP-ribose), identified in 1966 independently by three groups Strassbourg, Kyoto and Tokyo, is synthesized by poly(ADP-ribose) polymerases (PARP) from NAD(+) as a substrate in the presence of Mg(2+). The structure was unique in that it has ribose-ribose linkage. In the early-1970s, however, its function in vivo/in vitro was still controversial and the antibody against it was desired to help clear its significance. Thereupon, the author tried to produce antibody against poly(ADP-ribose) in rabbits and succeeded in it for the first time in the world. Eventually, this success has led to the following two groundbreaking papers in Nature: "Naturally-occurring antibody against poly(ADP-ribose) in patients with autoimmune disease SLE", and "Induction of anti-poly(ADP-ribose) antibody by immunization with synthetic double-stranded RNA, poly(A)·poly(U)".On the way to the publication of the first paper, a reviewer gave me a friendly comment that there is "heteroclitic" fashion as a mechanism of the production of natural antibody. This comment was really a God-send for me, and became a train of power for publication of another paper, as described above. Accordingly, I thought this, I would say, episode is worth describing herein. Because of its importance in biomedical phenomena, a certain number of articles related to "heteroclitic" have become to be introduced in this review, although they were not always directly related to immuno-biological works on poly(ADP-ribose). Also, I tried to speculate on the future prospects of poly(ADP-ribose), product of PARP, as an immuno-regulatory molecule, including either induced or naturally-occurring antibodies, in view of "heteroclitic". PMID:27477457

  8. TLR3 Agonist Poly-IC Induces IL-33 and Promotes Myelin Repair

    PubMed Central

    Natarajan, Chandramohan; Yao, Song-Yi; Sriram, Subramaniam

    2016-01-01

    Background Impaired remyelination of demyelinated axons is a major cause of neurological disability. In inflammatory demyelinating disease of the central nervous system (CNS), although remyelination does happen, it is often incomplete, resulting in poor clinical recovery. Poly-IC a known TLR3 agonist and IL-33, a cytokine which is induced by poly-IC are known to influence recovery and promote repair in experimental models of CNS demyelination. Methodology and Principal Findings We examined the effect of addition of poly-IC and IL-33 on the differentiation and maturation of oligodendrocyte precursor cells (OPC) cultured in vitro. Both Poly-IC and IL-33 induced transcription of myelin genes and the differentiation of OPC to mature myelin forming cells. Poly-IC induced IL-33 in OPC and addition of IL-33 to in vitro cultures, amplified further, IL-33 expression suggesting an autocrine regulation of IL-33. Poly-IC and IL-33 also induced phosphorylation of p38MAPK, a signaling molecule involved in myelination. Following the induction of gliotoxic injury with lysolecithin to the corpus callosum (CC), treatment of animals with poly-IC resulted in greater recruitment of OPC and increased staining for myelin in areas of demyelination. Also, poly-IC treated animals showed greater expression of IL-33 and higher expression of M2 phenotype macrophages in the CC. Conclusion/Significance Our studies suggest that poly-IC and IL-33 play a role in myelin repair by enhancing expression of myelin genes and are therefore attractive therapeutic agents for use as remyelinating agents in human demyelinating disease. PMID:27022724

  9. Massachusetts Special Olympics Poly Hockey.

    ERIC Educational Resources Information Center

    Morrissey, Jim

    Poly Hockey is featured in this manual of instructions for coaches and teachers to use with mentally retarded boys and girls of all ages and ability levels. It is noted that the sport has been supported by the Board of Directors of the Special Olympics and has been used in Massachusetts for over 7 years. Explained is use of the game indoors, and…

  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-modified poly(p-methylstyrene) identified in this section may be safely used as components of...

  11. 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-modified poly(p-methylstyrene) identified in this section may be safely used as components of...

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Poly(p-methylstyrene) and rubber-modified poly(p... Components of Single and Repeated Use Food Contact Surfaces § 177.1635 Poly(p-methylstyrene) and rubber-modified poly(p-methyl-styrene). Poly(p-methylstyrene) and rubber-modified poly(p-methylstyrene)...

  13. 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-modified poly(p-methylstyrene) identified in this section may be safely used as components of...

  14. Growth and toxic gas sensing properties of poly(urethaneimide) thin films.

    PubMed

    Youssef, Ismail Ben; Sarry, Frederic; Nysten, Bernard; Alexieva, Gergana; Strashilov, Vesselin; Kolev, Iliyan; Alem, Halima

    2016-06-01

    In this work we present a study on the growth and the gas sensing properties of poly(urethane imide) thin films. We first deeply characterized by atomic force microscopy (AFM) the nanostructuration of the poly(urethane imide) holding different amine groups. We further studied the interaction between highly toxic gases such as hexamethyleneimine (HMI) and pyridine and the polymer by using an unconventional method based on Quartz Crystal Microbalance (QCM) measurement. We showed for the first time that weak interactions, i.e. hydrogen bonding between the gas molecules and the polymer film allow the diffusion of the gas molecule deep in the polymeric film and the recovery of the film once the gas molecules leave the sensor. This first work paves a new way for the design of a completely recoverable sensor able to detect highly toxic gases for environmental concern.

  15. Growth and toxic gas sensing properties of poly(urethaneimide) thin films.

    PubMed

    Youssef, Ismail Ben; Sarry, Frederic; Nysten, Bernard; Alexieva, Gergana; Strashilov, Vesselin; Kolev, Iliyan; Alem, Halima

    2016-06-01

    In this work we present a study on the growth and the gas sensing properties of poly(urethane imide) thin films. We first deeply characterized by atomic force microscopy (AFM) the nanostructuration of the poly(urethane imide) holding different amine groups. We further studied the interaction between highly toxic gases such as hexamethyleneimine (HMI) and pyridine and the polymer by using an unconventional method based on Quartz Crystal Microbalance (QCM) measurement. We showed for the first time that weak interactions, i.e. hydrogen bonding between the gas molecules and the polymer film allow the diffusion of the gas molecule deep in the polymeric film and the recovery of the film once the gas molecules leave the sensor. This first work paves a new way for the design of a completely recoverable sensor able to detect highly toxic gases for environmental concern. PMID:27130101

  16. Oxygenated heterocyclic compounds to differentiate Citrus spp. essential oils through metabolomic strategies.

    PubMed

    Masson, Jerome; Liberto, Erica; Beolor, Jean-Claude; Brevard, Hugues; Bicchi, Carlo; Rubiolo, Patrizia

    2016-09-01

    This study aimed to characterise and discriminate 44 authenticated commercial samples of citrus essential oils (EO) from seven species (bergamot, lemon, bigarade, orange, mandarin, grapefruit, lime) by analysing the non-volatile oxygenated heterocyclic compounds (OHC) by UHPLC/TOF-HRMS, multivariate data analysis (PCA, PLS-DA) and metabolomic strategies; the OHC fraction includes coumarins, furocoumarins, and polymethoxylated flavonoids. Two different approaches were adopted: (i) targeted profiling based on quantifying 18 furocoumarins and coumarins, some of which are regulated by law, and (ii) targeted fingerprinting based on 140 OHCs reported in citrus essential oils, from which 38 discriminant markers were defined. This approach correctly discriminated the Citrus species; its "sensitivity" to relatively low adulteration rate (10%) was highly satisfactory. The proposed method is complementary to that of analysing the citrus EO volatile part by GC techniques. PMID:27041320

  17. Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

    PubMed Central

    Guan, Zong; Namyslo, Jan C; Drafz, Martin H H; Nieger, Martin

    2014-01-01

    Summary Deprotonation of indazolium salts at low temperatures gives N-heterocyclic carbenes of indazoles (indazol-3-ylidenes) which can be trapped as rhodium complexes (X-ray analysis). In the absence of Rh, the indazol-3-ylidenes spontaneously dimerize under ring cleavage of one of the N,N-bonds and ring closure to an indazole–indole spiro compound which possesses an exocyclic imine group. The E/Z isomers of the imines can be separated by column chromatography when methanol is used as eluent. We present results of a single crystal X-ray analysis of one of the E-isomers, which equilibrate in solution as well as in the solid state. Heating of the indazole–indole spiro compounds results in the formation of quinazolines by a ring-cleavage/ring-closure sequence (X-ray analysis). Results of DFT calculations are presented. PMID:24778738

  18. Synthesis and characterisation of an N-heterocyclic carbene with spatially-defined steric impact.

    PubMed

    Shaw, Paul; Kennedy, Alan R; Nelson, David J

    2016-08-01

    The synthesis and co-ordination chemistry of a new 'bulky yet flexible' N-heterocyclic carbene ("IPaul") is reported. This carbene has spatially-defined steric impact; steric maps show that two quadrants are very bulky while the other two are quite open. The electronic properties of this carbene are very similar to those of other 1,3-diarylimidazol-2-ylidenes. Copper, silver, iridium, and nickel complexes of the new ligand have been prepared. In solution, the ligand adopts two different conformations, while X-ray crystallographic analyses of the transition metal complexes suggest that the syn-conformer is preferred in the solid state due to intermolecular interactions. The copper(i) chloride complex of this new ligand has been shown to be highly-active in the hydrosilylation of carbonyl compounds, when compared to the analogous IPr, IMes, IPr* and IPr*(OMe) complexes. PMID:27335266

  19. Bioactive heterocyclic alkaloids with diterpene structure isolated from traditional Chinese medicines.

    PubMed

    Xu, Tengfei; Liu, Shu; Meng, Lulu; Pi, Zifeng; Song, Fengrui; Liu, Zhiqiang

    2016-07-15

    The diterpenoid alkaloids as one type of heterocyclic alkaloids have been found in many traditional herbal medicines, such as genus Consolida, Aconitum, and Delphinium (Ranunculaceae). Pharmacological researches have indicated that many diterpenoid alkaloids are the main bioactive components which have analgesic, anti-inflammatory, anti-microbial, anti-tumor, cardiotonic, and anti-arrhythmic activities. Studies focused on the determination, quantitation and pharmacological properties of these alkaloids have dramatically increased during the past few years. Up to now, newly discovered diterpenoid alkaloids with important biological activities have been isolated and synthesized. Considering their significant role and diffusely used in many disease treatments, we summarized the information of their analysis methods, bioactivity, metabolism and biotransformation in vivo as well as the pharmacological mechanisms. Based on above review, the further researches are suggested.

  20. New heterocycle modified chitosan adsorbent for metal ions (II) removal from aqueous systems.

    PubMed

    Kandile, Nadia G; Mohamed, Hemat M; Mohamed, Mansoura I

    2015-01-01

    A new hydrogel based on a modified chitosan CS-B was synthesized and evaluated for its metal ion removal from aqueous systems. The CS-B hydrogel was prepared through modification of chitosan with 4-((1, 3-dioxoisoindolin-2-ylimino) methyl) benzaldehyde as a heterocyclic component. The new hydrogel was analyzed by diverse techniques such as FTIR, XRD, TGA, SEM, and swelling tests. The adsorption capacity of CS-B for metal ions Co(2+), Hg(2+), Cu(2+), Zn(2+), and Pb(2+) from aqueous systems at different pH values showed various levels of efficiency. The metal ion uptake data over a range of pH values for Co(2+) and Hg(2+) showed the highest adsorption capacity while Cu(2+), Zn(2+), and Pb(2+) showed moderate adsorption capacity. Selective metal ion efficiency was highest for Co(2+) and lowest for Hg(2+) in their binary mixture.

  1. Heterocyclic amine mutagenicity/carcinogenicity: Influence of repair, metabolism, and structure

    SciTech Connect

    Felton, J.S.; Wu, R.; Knize, M.G.; Thompson, L.H.; Hatch, F.T.

    1993-01-15

    Cooking, heat processing, and pyrolysis of protein-rich foods induce the formation of structurally related heterocyclic aromatic amines that have been found to be mutagenic in bacteria, mammalian cells in culture and mice. All these compounds are potent mutagens and most are active below 1 ng/plate, in Ames/Salmonella tester strain TA1538 in the presence of S9 liver microsomal preparations from rat, mouse, or hamster. They are also potent in strains TA98, TA97, moderately active in TA1537, weakly active in TA100, and virtually inactive in TA1535 and TA102. Thus, they show powerful frameshift activity in reverting specific GC-rich sequences, but do not cause base substitution mutations or revert an AT-rich sequence. They are 100-fold less active in the uvrB+, repair-proficient strain TA1978, and in the case of IQ, cause insertions and large deletions not seen in TA1538.

  2. Food heating and the formation of heterocyclic aromatic amine and polycyclic aromatic hydrocarbon mutagens/carcinogens.

    PubMed

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

    1999-01-01

    Heterocyclic aromatic amines (HAA) and polycyclic aromatic hydrocarbons (PAH) are mutagens and animal carcinogens sometimes formed when foods are heated or processed. Determining their role in cancer etiology depends on comparing human exposures and determining any significant dose-related effects. Chemical analysis of foods shows that flame-grilling can form both PAH and HAA, and that frying forms predominantly HAA. With detection limits of about 0.1 ng/g, amounts found in commercially processed or restaurant foods range from 0.1 to 14 ng/g for HAA, and levels of PAH up to 1 ng/g in a liquid smoke flavoring. Laboratory fried samples have greater amounts of PAH, up to 38 ng/g in hamburgers, and high levels of HAA, over 300 ng/g, are measured in grilled chicken breast. Understanding the processing conditions that form PAH and HAA can lead to methods to greatly reduce their occurrence in processed foods.

  3. Infrared Spectroscopy of Matrix-Isolated Polycyclic Aromatic Nitrogen Heterocycles (PANHs)

    NASA Technical Reports Server (NTRS)

    Mattioda, A. L.; Hudgins, D. M.; Bauschlicher, C. W.; Allamandola, L. J.; Biemesderfer, C. D.; Rosi, M.

    2002-01-01

    The mid-infrared spectra of the nitrogen-containing heterocyclic polycyclic aromatic compounds 1-azabenz[a]-anthracene; 2-azabenz[a]anthracene; 1-azachrysene; 2-azachrysene; 4-azachrysene; 2-azapyrene, and 7,8 benzoquinoline in their neutral and cation forms were investigated. The spectra of these species isolated in an argon matrix have been measured. Band frequencies and intensities were tabulated and these data compared with spectra computed using density functional theory at the B3LYP level. The overall agreement between experiment and theory is quite good, in keeping with earlier results on homonuclear polycyclic aromatic hydrocarbons. The differences between the spectral properties of nitrogen bearing aromatics and non-substituted, neutral polycyclic aromatic hydrocarbons will be discussed.

  4. Susceptibility to Exposure to Heterocyclic Amines from Cooked Food: Role of UDP-glucuronosyltransferases

    SciTech Connect

    Malfatti, M A; Felton, J S

    2005-08-22

    A number of carcinogenic heterocyclic amines (PhIP, MeIQx, and DiMeIQx) are produced from the condensation of creatinine, hexoses and amino acids during the cooking of meat (1). There are many variables that impact the production and subsequent ingestion of these compounds in our diet. Temperature, type of meat product, cooking method, doneness, and other factors affect the quantity of these carcinogens consumed by humans. Estimates of ingestion of these carcinogens are 1-20 ng/kg body weight per day (2). Human case control studies that correlate meat consumption from well-done cooking practices with cancer incidence indicate excess tumors for breast, colon, stomach, esophagus, and possibly prostate (3-5).

  5. Self-Supported N-Heterocyclic Carbenes and Their Use as Organocatalysts.

    PubMed

    Ma, Shuang; Toy, Patrick H

    2016-01-01

    The study of N-heterocyclic carbenes (NHCs) as organocatalysts has proliferated in recent years, and they have been found to be useful in a variety of reactions. In an attempt to further expand their utility and to study their recyclability, we designed and synthesized a series of self-supported NHCs in which the catalytic carbene groups form part of a densely functionalized polymer backbone, and studied them as organocatalysts. Of the self-Supported NHCs examined, a benzimidazole derived polymer with flexible linkers connecting the catalytic groups was found to be the most efficient organocatalyst in a model benzoin condensation reaction, and thus it was used in a variety of such reactions, including some involving catalyst recycling. Furthermore, it was also used to catalyze a set of redox esterification reactions involving conjugated unsaturated aldehydes. In all of these reactions the catalyst afforded good yield of the desired product and its polymeric nature facilitated product purification. PMID:27556435

  6. Solvent effects on the vibronic one-photon absorption profiles of dioxaborine heterocycles

    NASA Astrophysics Data System (ADS)

    Wang, Yan-Hua; Halik, Marcus; Wang, Chuan-Kui; Marder, Seth R.; Luo, Yi

    2005-11-01

    The vibronic profiles of one-photon absorption spectra of dioxaborine heterocycles in gas phase and solution have been calculated at the Hartree-Fock and density-functional-theory levels. The polarizable continuum model has been applied to simulate the solvent effect, while the linear coupling model is used to compute the Franck-Condon and Herzberg-Teller contributions. It is found that a good agreement between theory and experiment can be achieved when the solvent effect and electron correlation are taken into account simultaneously. For the first excited charge-transfer state, the maximum of its Herzberg-Teller profile is blueshifted from that of the Franck-Condon profile. The shifted energy is found to be around 0.2eV, which agrees well with the measured energy difference between two- and one-photon absorptions of the first excited state.

  7. Antidepressant potential of nitrogen-containing heterocyclic moieties: An updated review

    PubMed Central

    Siddiqui, Nadeem; Andalip; Bawa, Sandhya; Ali, Ruhi; Afzal, Obaid; Akhtar, M. Jawaid; Azad, Bishmillah; Kumar, Rajiv

    2011-01-01

    Depression is currently the fourth leading cause of disease or disability worldwide. Antidepressant is approved for the treatment of major depression (including paediatric depression), obsessive-compulsive disorder (in both adult and paediatric populations), bulimia nervosa, panic disorder and premenstrual dysphoric disorder. Antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. Many drugs produce an antidepressant effect, but restrictions on their use have caused controversy and off-label prescription a risk, despite claims of superior efficacy. Our current understanding of its pathogenesis is limited and existing treatments are inadequate, providing relief to only a subset of people suffering from depression. Reviews of literature suggest that heterocyclic moieties and their derivatives has proven success in treating depression. PMID:21687347

  8. Spirocyclic β-Lactams: Synthesis and Biological Evaluation of Novel Heterocycles

    NASA Astrophysics Data System (ADS)

    Bari, Shamsher S.; Bhalla, Aman

    β-Lactam rings containing compounds are a group of antibiotics of unparalleled importance in chemotherapy. Considerable effort has been reported in the development of novel, more effective β-lactam compounds as well as their biological evaluation. This article reviews the progress made in the stereoselective synthesis of spiro-β-lactams, a unique class of heterocycles, their biological evaluation, and their applications in various related fields. The introductory paragraph highlights the significance of the β-lactam chemistry and is followed by an overview of monocyclic-, bicyclic-, and tricyclic-β-lactams. The other sections of the article deal with the stereoselective synthesis and biological evaluation of spiro-β-lactams, including their use as synthetic intermediates for β-turn mimics and β-turn nucleators. The potential of spiro-β-lactams as cholesterol absorption inhibitors, β-lactamase inhibitors, and antiviral, antibacterial, and antimicrobial agents has also been described.

  9. Food heating and the formation of heterocyclic aromatic amine and polycyclic aromatic hydrocarbon mutagens/carcinogens.

    PubMed

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

    1999-01-01

    Heterocyclic aromatic amines (HAA) and polycyclic aromatic hydrocarbons (PAH) are mutagens and animal carcinogens sometimes formed when foods are heated or processed. Determining their role in cancer etiology depends on comparing human exposures and determining any significant dose-related effects. Chemical analysis of foods shows that flame-grilling can form both PAH and HAA, and that frying forms predominantly HAA. With detection limits of about 0.1 ng/g, amounts found in commercially processed or restaurant foods range from 0.1 to 14 ng/g for HAA, and levels of PAH up to 1 ng/g in a liquid smoke flavoring. Laboratory fried samples have greater amounts of PAH, up to 38 ng/g in hamburgers, and high levels of HAA, over 300 ng/g, are measured in grilled chicken breast. Understanding the processing conditions that form PAH and HAA can lead to methods to greatly reduce their occurrence in processed foods. PMID:10335376

  10. Highly stable water-soluble platinum nanoparticles stabilized by hydrophilic N-heterocyclic carbenes.

    PubMed

    Baquero, Edwin A; Tricard, Simon; Flores, Juan Carlos; de Jesús, Ernesto; Chaudret, Bruno

    2014-11-24

    Controlling the synthesis of stable metal nanoparticles in water is a current challenge in nanochemistry. The strategy presented herein uses sulfonated N-heterocyclic carbene (NHC) ligands to stabilize platinum nanoparticles (PtNPs) in water, under air, for an indefinite time period. The particles were prepared by thermal decomposition of a preformed molecular Pt complex containing the NHC ligand and were then purified by dialysis and characterized by TEM, high-resolution TEM, and spectroscopic techniques. Solid-state NMR studies showed coordination of the carbene ligands to the nanoparticle surface and allowed the determination of a (13)C-(195)Pt coupling constant for the first time in a nanosystem (940 Hz). Additionally, in one case a novel structure was formed in which platinum(II) NHC complexes form a second coordination sphere around the nanoparticle.

  11. Bioinspired aerobic oxidation of secondary amines and nitrogen heterocycles with a bifunctional quinone catalyst.

    PubMed

    Wendlandt, Alison E; Stahl, Shannon S

    2014-01-01

    Copper amine oxidases are a family of enzymes with quinone cofactors that oxidize primary amines to aldehydes. The native mechanism proceeds via an iminoquinone intermediate that promotes high selectivity for reactions with primary amines, thereby constraining the scope of potential biomimetic synthetic applications. Here we report a novel bioinspired quinone catalyst system consisting of 1,10-phenanthroline-5,6-dione/ZnI2 that bypasses these constraints via an abiological pathway involving a hemiaminal intermediate. Efficient aerobic dehydrogenation of non-native secondary amine substrates, including pharmaceutically relevant nitrogen heterocycles, is demonstrated. The ZnI2 cocatalyst activates the quinone toward amine oxidation and provides a source of iodide, which plays an important redox-mediator role to promote aerobic catalytic turnover. These findings provide a valuable foundation for broader development of aerobic oxidation reactions employing quinone-based catalysts. PMID:24328193

  12. Bioinspired Aerobic Oxidation of Secondary Amines and Nitrogen Heterocycles with a Bifunctional Quinone Catalyst

    PubMed Central

    Wendlandt, Alison E.; Stahl, Shannon S.

    2014-01-01

    Copper amine oxidases are a family of enzymes with quinone cofactors that oxidize primary amines to aldehydes. The native mechanism proceeds via an iminoquinone intermediate that promotes high selectivity for reactions with primary amines, thereby constraining the scope of potential biomimetic synthetic applications. Here, we report a novel bioinspired quinone catalyst system, consisting of 1,10-phenanthroline-5,6-dione/ZnI2, that bypasses these constraints via an abiological pathway involving a hemiaminal intermediate. Efficient aerobic dehydrogenation of non-native secondary amine substrates, including pharmaceutically relevant nitrogen heterocycles, is demonstrated. The ZnI2 cocatalyst activates the quinone toward amine oxidation and provides a source of iodide, which plays an important redox-mediator role to promote aerobic catalytic turnover. These findings provide a valuable foundation for broader development of aerobic oxidation reactions employing quinone-based catalysts. PMID:24328193

  13. Tris(pentafluorophenyl)borane-Catalyzed Acceptorless Dehydrogenation of N-Heterocycles.

    PubMed

    Kojima, Masahiro; Kanai, Motomu

    2016-09-26

    Catalytic acceptorless dehydrogenation is an environmentally benign way to desaturate organic compounds. This process is traditionally accomplished with transition-metal-based catalysts. Herein, a borane-catalyzed, metal-free acceptorless dehydrogenation of saturated N-heterocycles is disclosed. Tris(pentafluorophenyl)borane was identified as a versatile catalyst, which afforded several synthetically important N-heteroarenes in up to quantitative yield. Specifically, the present metal-free catalytic system exhibited a uniquely high tolerance toward sulfur functionalities, and demonstrated superior reactivity in the synthesis of benzothiazoles compared to conventional metal-catalyzed systems. This protocol can thus be regarded as the first example of metal-free acceptorless dehydrogenation in synthetic organic chemistry. PMID:27539196

  14. Cobalt-Catalyzed sp(2) -C-H Activation: Intermolecular Heterocyclization with Allenes at Room Temperature.

    PubMed

    Thrimurtulu, Neetipalli; Dey, Arnab; Maiti, Debabrata; Volla, Chandra M R

    2016-09-26

    The reactivity of allenes in transition-metal-catalyzed C-H activation chemistry is governed by the formation of either alkenyl-metal (M-alkenyl) or metal-π-allyl intermediates. Although either protonation or a β-hydride elimination is feasible with a M-alkenyl intermediate, cyclization has remained unexplored to date. Furthermore, due to the increased steric hindrance, the regioselectivity for the intramolecular cyclization of the metal-π-allyl intermediate was hampered towards the more substituted side. To address these issues, a unified approach to synthesize a diverse array of biologically and pharmaceutically relevant heterocyclic moieties by cobalt-catalyzed directed C-H functionalization was envisioned. Upon successful implementation, the present strategy led to the regioselective formation of dihydroisoquinolin-1(2H)-ones, isoquinolin-1(2H)-ones, dihydropyridones, and pyridones. PMID:27584828

  15. Effects of heating time and antioxidants on the formation of heterocyclic amines in marinated foods.

    PubMed

    Lan, C M; Kao, T H; Chen, B H

    2004-03-25

    The effect of heating time and antioxidants on the heterocyclic amine (HAs) formation in marinated foods were studied. Food samples were cooked at 98 +/- 2 degrees C for 1, 2, 4, 8, 16 and 32 h in a closed pan in the presence of water, soy sauce and rock candy with or without antioxidants. The various HAs in marinated food samples and juice were analyzed by HPLC with photodiode-array detection. Results showed that the amount of HAs formed during heating followed an increased order for each increasing heating time. A larger variety and higher amount of HAs were generated in marinated pork when compared to marinated eggs and bean cake. In marinated juice, the levels of HAs were present in greater amount than in marinated foods. The incorporation of antioxidants Vitamin C, Vitamin E and BHT were found to be effective towards HAs inhibition, however, the effect was minor.

  16. 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.

  17. Reactive Transport Modelling of Heterocyclic Hydrocarbons at a Former Gasworks Site

    NASA Astrophysics Data System (ADS)

    Herold, M.; Ptak, T.; Wendel, T.; Grathwohl, P.

    2007-12-01

    Highly mobile heterocyclic hydrocarbons constitute a persistent threat to groundwater at a former gasworks site in Southern Germany. This area is currently being used as a test site for novel subsurface investigation techniques, as well as for a site-specific enhanced natural attenuation (ENA) remediation approach. The subsurface investigation consisted of direct-push borings and monitoring well installations, tracer tests, and Integral Pumping Tests (IPTs) at multiple control planes, which were positioned at different distances downgradient of the source zone and perpendicular to the contaminant plume transport direction. The numerical inversion of groundwater concentration time series measured during the IPTs, in combination with a groundwater flow and transport model of the test site, leads to estimations of total mass flow rates of contaminants or other groundwater parameters relevant to NA, as well as of average concentrations and concentration distributions along the control planes. Following detailed investigations of the microbial and chemical conditions at the site, an in-situ ENA method involving a circulation well and the use of O2 as a terminal electron acceptor was devised to aid aerobic microbial degradation of the heterocyclic compounds in the otherwise anoxic surroundings. The aims of the study presented here were to verify the proposed conceptual model of interacting physical and biogeochemical processes and to assess the effectiveness of the in-situ remediation approach with the help of multi-component reactive transport modelling, focusing on the situations (i) prior to the implementation of the in- situ remediation scheme and (ii) following the operation of the circulation well with O2 injection. A finite-difference model was devised using the software PMWIN and PHT3D, utilizing the collected data to simulate the relevant processes in two and three dimensions, respectively. Instead of using interpolated point scale concentration measurements

  18. N-heterocyclic amine-directed structures and properties of two Cu(II) diphosphonates.

    PubMed

    Ma, Kui-Rong; Ma, Feng; Zhu, Yu-Lan; Yu, Lin-Juan; Zhao, Xiao-Min; Yang, Yin; Duan, Wei-He

    2011-10-14

    By introducing the second organic N-heterocyclic ligands 4'-(4-pyridyl)-4,2':6',4''-terpyridine (pyterpy) and 4,4'-bipyridyl (4,4'-bipy), two examples of Cu(II)-diphosphonates, [Cu(3)(HL)(2)(Hpyterpy)(2)]·2H(2)O 1 and [Cu(4)(HL)(2)(4,4'-bipy)(H(2)O)(5)] 2 based on 1-hydroxyethylidenediphosphonic acid (H(5)L = CH(3)C(OH)(PO(3)H(2))(2)), have been hydrothermally obtained and characterized by powder X-ray diffraction, elemental analysis, IR, TG-DSC. The single-crystal X-ray diffractions reveal that compound 1 has a one-dimensional fishbone-like chain constructed by anions [Cu(3)(HL)(2)(2-)](n) while simultaneously organic cations [Hpyterpy(+)](n) suspending both sides, and compound 2 exhibits two-dimensional inorganic-organic alternate arrangement layer built from 1-D ladder-like inorganic chain with tetranuclear cluster [Cu(4)O(10)] via 4,4'-bipy linkage. The results of electrochemical measurements indicate half-wave potential of 1 (E(1/2)(1) = 1.01 V) is less than that of 2 (E(1/2)(2) = 1.20 V), indicating a good D-A system in ICT for 1. Moreover fluorescent measurements reveal that emission intensity of 1 centered at 422 nm is larger than that of 2 emitted at 420 nm, caused by intraligand π*-π emission state of organic N-heterocyclic amine (λ(ex) = 233 nm). Magnetism data indicate that compound 1 exhibits ferrimagnetic interactions between metal centers, while compound 2 has antiferromagnetic property.

  19. Effects of N-heterocyclic polyaromatic hydrocarbons on survival, reproduction, and biochemical parameters in Daphnia magna.

    PubMed

    Feldmannová, M; Hilscherová, K; Marsálek, B; Bláha, L

    2006-08-01

    N-heterocyclic polycyclic aromatic hydrocarbons (N-PAHs) belong among newly identified classes of environmental pollutants with relatively high toxic potential. N-PAHs have been detected in air, soil, marine environments, and freshwater sediments. The N-PAHs are present at lower concentrations than their nonsubstituted analogues but their greater solubility would lead to greater bioavailibity and potential for toxic effects. Here we present results of acute and chronic toxicity in traditional aquatic invertebrate ecotoxicological model (Daphnia magna) along with assessment of biochemical responses. Studied biomarkers in D. magna exposed to N-heterocyclic derivatives included glutathione levels and activities of detoxication and antioxidative enzymes glutathione S-transferase and glutathione peroxidase. Phenanthrene and 1,10-phenathroline were the most toxic of all tested compounds (EC50 < 6 microM after 48 h exposure) and all tested N-PAHs suppressed reproduction of Daphnia magna. The data suggest that N-PAHs can induce oxidative stress in D. magna. The significant decline of glutathione content was found in animals treated with acridine, 1,10-phenanthroline, benzo(h)quinoline, phenantridine, and phenazine. Significant decrease of GPx activities relative to controls was found for all tested compounds except of phenanthrene and phenazine. Activities of GST increased after exposure to phenanthridine, phenazine, and benzo(h)quinoline, and declined in D. magna treated with phenanthrene (significant at one concentration) or anthracene (not significant). Our results confirmed significant acute as well as chronic toxicities of N-PAHs as well as potential of biochemical parameters to be used as early warning signals of toxicity in Daphnia magna. PMID:16841315

  20. Synthesis of Bridged Heterocycles via Sequential 1,4- and 1,2-Addition Reactions to α,β-Unsaturated N-Acyliminium Ions: Mechanistic and Computational Studies.

    PubMed

    Yazici, Arife; Wille, Uta; Pyne, Stephen G

    2016-02-19

    Novel tricyclic bridged heterocyclic systems can be readily prepared from sequential 1,4- and 1,2-addition reactions of allyl and 3-substituted allylsilanes to indolizidine and quinolizidine α,β-unsaturated N-acyliminium ions. These reactions involve a novel N-assisted, transannular 1,5-hydride shift. Such a mechanism was supported by examining the reaction of a dideuterated indolizidine, α,β-unsaturated N-acyliminium ion precursor, which provided specifically dideuterated tricyclic bridged heterocyclic products, and from computational studies. In contrast, the corresponding pyrrolo[1,2-a]azepine system did not provide the corresponding tricyclic bridged heterocyclic product and gave only a bis-allyl adduct, while more substituted versions gave novel furo[3,2-d]pyrrolo[1,2-a]azepine products. Such heterocyclic systems would be expected to be useful scaffolds for the preparation of libraries of novel compounds for new drug discovery programs. PMID:26816207

  1. Synthesis of Bridged Heterocycles via Sequential 1,4- and 1,2-Addition Reactions to α,β-Unsaturated N-Acyliminium Ions: Mechanistic and Computational Studies.

    PubMed

    Yazici, Arife; Wille, Uta; Pyne, Stephen G

    2016-02-19

    Novel tricyclic bridged heterocyclic systems can be readily prepared from sequential 1,4- and 1,2-addition reactions of allyl and 3-substituted allylsilanes to indolizidine and quinolizidine α,β-unsaturated N-acyliminium ions. These reactions involve a novel N-assisted, transannular 1,5-hydride shift. Such a mechanism was supported by examining the reaction of a dideuterated indolizidine, α,β-unsaturated N-acyliminium ion precursor, which provided specifically dideuterated tricyclic bridged heterocyclic products, and from computational studies. In contrast, the corresponding pyrrolo[1,2-a]azepine system did not provide the corresponding tricyclic bridged heterocyclic product and gave only a bis-allyl adduct, while more substituted versions gave novel furo[3,2-d]pyrrolo[1,2-a]azepine products. Such heterocyclic systems would be expected to be useful scaffolds for the preparation of libraries of novel compounds for new drug discovery programs.

  2. Preparation of a thick polymer brush layer composed of poly(2-methacryloyloxyethyl phosphorylcholine) by surface-initiated atom transfer radical polymerization and analysis of protein adsorption resistance.

    PubMed

    Inoue, Yuuki; Onodera, Yuya; Ishihara, Kazuhiko

    2016-05-01

    The purpose of this study was to prepare a thick polymer brush layer composed of poly(2-methacryloyloxyethyl phosphorylcholine (MPC)) and assess its resistance to protein adsorption from the dissolved state of poly(MPC) chains in an aqueous condition. The thick poly(MPC) brush layer was prepared through the surface-initiated atom transfer radical polymerization (SI-ATRP) of MPC with a free initiator from an initiator-immobilized substrate at given [Monomer]/[Free initiator] ratios. The ellipsometric thickness of the poly(MPC) brush layers could be controlled by the polymerization degree of the poly(MPC) chains. The thickness of the poly(MPC) brush layer in an aqueous medium was larger than that in air, and this tendency became clearer when the polymerization degree of the poly(MPC) increased. The maximum thickness of the poly(MPC) brush layer in an aqueous medium was around 110 nm. The static air contact angle of the poly(MPC) brush layer in water indicated a reasonably hydrophilic nature, which was independent of the thickness of the poly(MPC) brush layer at the surface. This result occurred because the hydrated state of the poly(MPC) chains is not influenced by the environment surrounding them. Finally, as measured with a quartz crystal microbalance, the amount of protein adsorbed from a fetal bovine serum solution (10% in phosphate-buffered saline) on the original substrate was 420 ng/cm(2). However, the poly(MPC) brush layer reduced this value dramatically to less than 50 ng/cm(2). This effect was independent of the thickness of the poly(MPC) brush layer for thicknesses between 20 nm and about 110 nm. These results indicated that the surface covered with a poly(MPC) brush layer is a promising platform to avoid biofouling and could also be applied to analyze the reactions of biological molecules with a high signal/noise ratio.

  3. Electrospun homogeneous silk fibroin/poly (ɛ-caprolactone) nanofibrous scaffolds by addition of acetic acid for tissue engineering.

    PubMed

    Zhu, Jiang; Luo, Jingjing; Zhao, Xingyan; Gao, Junjiu; Xiong, Jie

    2016-09-01

    In this study, we investigated the phase separation phenomenon of silk fibroin/poly (ɛ-caprolactone) electrospinning solution to improve the performance of silk fibroin/poly (ɛ-caprolactone) electrospun nanofibers. It showed that phase separation does occur in just a few hours in the silk fibroin/poly (ɛ-caprolactone)/formic acid mixture solution. Acetic acid, small molecule nonsolvent for silk fibroin, was first introduced to silk fibroin/poly (ɛ-caprolactone)/formic acid solution, a homogeneous solution without separation for over several days was achieved after mixing for 5 h. The morphology and composition of the silk fibroin/poly (ɛ-caprolactone) and acetic acid-modified silk fibroin/poly (ɛ-caprolactone) fibrous scaffolds were examined by scanning electron microscopy, Fourier transform infrared spectroscopy and thermal gravimetric analyzer. Attachment and proliferation of mouse osteoblast MC3T3-E1 cells were tested by scanning electron microscopy and cytotoxity assay. The results indicated that the phase separation of silk fibroin/poly (ɛ-caprolactone) solution might led to inhomogeneous morphology and composition of the composite scaffolds, and the inhomogeneity of the silk fibroin/poly (ɛ-caprolactone) scaffolds with formic acid as solvent had a remarkable difference on cell adhesion and proliferation. In contrast, there was no significant difference among the silk fibroin/poly (ɛ-caprolactone) scaffolds with formic acid/acetic acid as solvent because of their good consistency in fiber morphology and composition. These obtained silk fibroin/poly (ɛ-caprolactone) nanofibers had small average diameter of 190 ± 40 nm. The obtained results proved that this study provided a facile and effective approach to achieve compositionally homogeneous silk fibroin/poly (ɛ-caprolactone) scaffolds with formic acid as solvent for effective applications. PMID:27422715

  4. A N-heterocyclic tetracarbene Pd(ii) moiety containing a Pd(ii)-Pb(ii) bimetallic MOF for three-component cyclotrimerization via benzyne.

    PubMed

    Dong, Ying; Li, Yue; Wei, Yong-Liang; Wang, Jian-Cheng; Ma, Jian-Ping; Ji, Jun; Yao, Bing-Jian; Dong, Yu-Bin

    2016-08-18

    A novel Pd(ii)-Pb(ii) bimetallic metal-organic framework Pd(ii)-Pb(ii)-MOF (B) which contains an N-heterocyclic tetracarbene Pd(ii) moiety was synthesized based on a chelating N-heterocyclic dicarbene Pd(ii)-NHDC ligand (A) under solvothermal conditions. It can be a highly active heterogeneous catalyst for three-component cyclotrimerization via benzyne species.

  5. Absolute fragmentation cross sections in atom-molecule collisions: Scaling laws for non-statistical fragmentation of polycyclic aromatic hydrocarbon molecules

    SciTech Connect

    Chen, T.; Gatchell, M.; Stockett, M. H.; Alexander, J. D.; Schmidt, H. T.; Cederquist, H.; Zettergren, H.; Zhang, Y.; Rousseau, P.; Maclot, S.; Delaunay, R.; Adoui, L.; Domaracka, A.; Huber, B. A.

    2014-06-14

    We present scaling laws for absolute cross sections for non-statistical fragmentation in collisions between Polycyclic Aromatic Hydrocarbons (PAH/PAH{sup +}) and hydrogen or helium atoms with kinetic energies ranging from 50 eV to 10 keV. Further, we calculate the total fragmentation cross sections (including statistical fragmentation) for 110 eV PAH/PAH{sup +} + He collisions, and show that they compare well with experimental results. We demonstrate that non-statistical fragmentation becomes dominant for large PAHs and that it yields highly reactive fragments forming strong covalent bonds with atoms (H and N) and molecules (C{sub 6}H{sub 5}). Thus nonstatistical fragmentation may be an effective initial step in the formation of, e.g., Polycyclic Aromatic Nitrogen Heterocycles (PANHs). This relates to recent discussions on the evolution of PAHNs in space and the reactivities of defect graphene structures.

  6. Poly I:C-induced tumor cell apoptosis mediated by pattern-recognition receptors.

    PubMed

    Zhao, Xiangzhong; Ai, Miao; Guo, Yuqi; Zhou, Xianbin; Wang, Li; Li, Xia; Yao, Chengfang

    2012-11-01

    Poly I:C is a synthetic dsRNA that can imitate a viral infection and elicit host immune responses by triggering specific pattern-recognition receptors (PRRs) such as toll-like receptor 3 and retinoic acid inducible gene I(RIG-I)-like receptors, including RIG-I and melanoma differentiation-associated gene 5. Activation of these PRRs by poly I:C triggers a signal transduction cascade that results in the activation of NF-κB and production of type I interferon. Poly I:C has been used as a vaccine adjuvant for cancer immunotherapy for several decades. Evidence from recent studies indicates that poly I:C can directly induce apoptosis in several types of tumor cells, thus providing a new therapeutic approach for cancer treatment. However, the molecular mechanism underlying the induction of apoptosis by poly I:C is still unclear. In this review, we summarize the current knowledge of poly I:C-induced tumor cell apoptosis, focusing on the key molecules and pathways involved in this process.

  7. Comparative investigation of the binding characteristics of poly-L-lysine and chitosan on alginate hydrogel.

    PubMed

    Ren, Ying; Xie, Hongguo; Liu, Xiaocen; Bao, Jie; Yu, Weiting; Ma, Xiaojun

    2016-03-01

    The binding properties of poly-L-lysine and chitosan to alginate have been evaluated quantitatively and compared. Poly-L-lysine bound to alginate hydrogel more rapidly than chitosan as poly-L-lysine has a smaller molar hydrodynamic volume. In addition, poly-L-lysine showed a much higher binding capacity (6.14:1) for alginate hydrogel beads than chitosan (2.71:1), and a little higher binding stoichiometry (0.58) to sodium alginate molecules in solution than chitosan (0.49). An exothermic heat of alginate-poly-L-lysine complexes formation of 2.02 kJ/mol was detected. For alginate-chitosan complexes, the binding enthalpy has been seen to be -3.49 kJ/mol. The stability of the polyelectrolyte complexes was related to their binding enthalpy. The alginate-poly-L-lysine complexes could be disintegrated and rebuilt. By contrast, chitosan was bound with alginate in a steady state. These results provide fundamental insights regarding the structure and property relationships of macromolecules, and will be helpful in designing and selecting appropriate polymers.

  8. Reduced Water Density in a Poly(ethylene oxide) Brush

    SciTech Connect

    Lee, Hoyoung; Kim, Dae Hwan; Park, Hae-Woong; Mahynski, Nathan A.; Kim, Kyungil; Meron, Mati; Lin, Binhua; Won, You-Yeon

    2012-09-05

    A model poly(ethylene oxide) (PEO) brush system, prepared by spreading a poly(ethylene oxide)-poly(n-butyl acrylate) (PEO-PnBA) amphiphilic diblock copolymer onto an air-water interface, was investigated under various grafting density conditions by using the X-ray reflectivity (XR) technique. The overall electron density profiles of the PEO-PnBA monolayer in the direction normal to the air-water interface were determined from the XR data. From this analysis, it was found that inside of the PEO brush, the water density is significantly lower than that of bulk water, in particular, in the region close to the PnBA-water interface. Separate XR measurements with a PnBA homopolymer monolayer confirm that the reduced water density within the PEO-PnBA monolayer is not due to unfavorable contacts between the PnBA surface and water. The above result, therefore, lends support to the notion that PEO chains provide a hydrophobic environment for the surrounding water molecules when they exist as polymer brush chains.

  9. Molecular crystals as precursors for poly-nitrogen

    NASA Astrophysics Data System (ADS)

    Borstad, Gustav; Ciezak-Jenkins, Jennifer

    The application of pressure to matter results in dramatic modifications of its properties. The compression of molecular crystals first eliminates ``empty'' space between the molecules. It then alters the electron density distribution, favoring the increase of atomic coordination and the formation of polymers. The polymerization of low-Z compounds into covalently-bonded networks in three dimensions tend to generate materials characterized by superconductivity, super-hardness, and high-energy density.1 Poly-nitrogen (analogous to diamond) has been synthesized under extreme conditions above 100 GPa and 2000 K in diamond anvil cells, but could not be recovered to ambient conditions.2 A useful form of poly-nitrogen would have to be synthesized at low-pressure with enhanced stability at ambient conditions. The changes in the intermolecular and intramolecular interactions with pressure play a crucial role in the synthesizing and stabilizing of the structure as well as in tuning its properties. In this talk, we provide Raman and x-ray diffraction data on nitrogen-containing compound biuret and compare it to work on other possible poly-nitrogen precursors. During this project, coauthor GB was supported in part by an appointment to the Postdoctoral Research Program at the US Army Research Laboratory administered by the Oak Ridge Associated Universities.

  10. Photochemistry of interstellar molecules

    NASA Technical Reports Server (NTRS)

    Stief, L. J.

    1971-01-01

    The photochemistry of two diatomic and eight polyatomic molecules is discussed quantitatively. For an interstellar molecule, the lifetime against photodecomposition depends upon the absorption cross section, the quantum yield or probability of dissociation following photon absorption, and the interstellar radiation field. The constant energy density of Habing is used for the unobserved regions of interstellar radiation field, and the field in obscuring clouds is estimated by combining the constant flux with the observed interstellar extinction curve covering the visible and ultraviolet regions. Lifetimes against photodecomposition in the unobscured regions and as a function of increasing optical thickness in obscuring clouds are calculated for the ten species. The results show that, except for CO, all the molecules have comparable lifetimes of less than one hundred years. Thus they can exist only in dense clouds and can never have been exposed to the unobscured radiation. The calculations further show that the lifetimes in clouds of moderate opacity are of the order of one million years.

  11. 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.

  12. Atomic branching in molecules

    NASA Astrophysics Data System (ADS)

    Estrada, Ernesto; Rodríguez-Velázquez, Juan A.; Randić, Milan

    A graph theoretic measure of extended atomic branching is defined that accounts for the effects of all atoms in the molecule, giving higher weight to the nearest neighbors. It is based on the counting of all substructures in which an atom takes part in a molecule. We prove a theorem that permits the exact calculation of this measure based on the eigenvalues and eigenvectors of the adjacency matrix of the graph representing a molecule. The definition of this measure within the context of the Hückel molecular orbital (HMO) and its calculation for benzenoid hydrocarbons are also studied. We show that the extended atomic branching can be defined using any real symmetric matrix, as well as any Hermitian (self-adjoint) matrix, which permits its calculation in topological, geometrical, and quantum chemical contexts.

  13. Single Molecule Manipulation

    NASA Astrophysics Data System (ADS)

    Kiang, Ching-Hwa

    2011-10-01

    Single-molecule manipulation studies open a door for a close-up investigation of complex biological interactions at the molecular level. In these studies, single biomolecules are pulled while their force response is being monitored. The process is often nonequilibrium, and interpretation of the results has been challenging. We used the atomic force microscope to pull proteins and DNA, and determined the equilibrium properties of the molecules using the recently derived nonequilibrium work theorem. I will present applications of the technique in areas ranging from fundamental biological problems such as DNA mechanics, to complex medical processes such as the mechanical activation of von Willebrand Factor, a key protein in blood coagulation.

  14. Plasmonic nanostructures: artificial molecules.

    PubMed

    Wang, Hui; Brandl, Daniel W; Nordlander, Peter; Halas, Naomi J

    2007-01-01

    This Account describes a new paradigm for the relationship between the geometry of metallic nanostructures and their optical properties. While the interaction of light with metallic nanoparticles is determined by their collective electronic or plasmon response, a compelling analogy exists between plasmon resonances of metallic nanoparticles and wave functions of simple atoms and molecules. Based on this insight, an entire family of plasmonic nanostructures, artificial molecules, has been developed whose optical properties can be understood within this picture: nanoparticles (nanoshells, nanoeggs, nanomatryushkas, nanorice), multi-nanoparticle assemblies (dimers, trimers, quadrumers), and a nanoparticle-over-metallic film, an electromagnetic analog of the spinless Anderson model. PMID:17226945

  15. [Pigment molecules linked to polymer support: blue rayon, blue chitin, and green chitosan-synthesis and applications].

    PubMed

    Hayatsu, H

    2000-06-01

    The fact that hemin can inhibit the mutagenic activity of compounds bearing polycyclic structures is ascribable to the ability of the porphyrin structure to complex with the planar surface of the mutagens. The elucidation of this mechanism has led to the discovery of copper phthalocyanine trisulfonate (cpt) as an efficient ligand to trap polycyclic compounds on polymeric supports that bear cpt through covalent bond linkages. In blue cotton, the support for cpt is cotton, in blue rayon, it is amorphous rayon, and in blue chitin it is poly-N-acetylglucosamine. Using these blue materials, we have successfully isolated mutagens of polycyclic structures, e.g., heterocyclic amines, from environmental complex mixtures such as food, urine, feces, and river water. Preparation and properties of these adsorbents are described. Chlorophyllin linked to Sepharose and chitosan is also described. The use of these green materials is discussed.

  16. Hybrid molecules synergistically acting against protein aggregation diseases.

    PubMed

    Korth, Carsten; Klingenstein, Ralf; Müller-Schiffmann, Andreas

    2013-01-01

    An emerging common feature of the age-associated neurodegenerative disorders like Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD) is the ability of many disease-associated protein aggregates to induce conversion of a normal counterpart conformer leading to an acceleration of disease progression. Curative pharmacotherapy has not been achieved so far despite successes in elucidating pathomechanisms. Here, we review the pharmaceutical strategy of generating hybrid compounds, i.e. compounds consisting of several independently acting moieties with synergistic effects, on key molecular players in AD and CJD. For prion diseases, we review hybrid compounds consisting of two different heterocyclic compounds, their synergistic effects on prion replication in a cell culture model and their ability to prolong survival of experimentally prion-infected mice in vivo. While a combination therapy of several antiprion compounds including quinacrine, clomipramine, simvastatin and tocopherol prolonged survival time to 10-25%, administration of hybrid compound quinpramine alone, a chimera of acridine and iminodibenzyl scaffolds, led to 10% survival time extension. For AD, we review a hybrid compound consisting of an Aβ recognizing D-peptide fused to a small molecule β-sheet breaker, an aminopyrazole. This molecule was able to diminish Aβ oligomers in cell culture and significantly decrease synaptotoxicity as measured by miniature excitatory postsynaptic responses in vitro. Hybrid compounds can dramatically increase potency of their single moieties and lead to novel functions when they act in a simultaneous or sequential manner thereby revealing synergistic properties. Their systematic generation combining different classes of compounds from peptides to small molecules has the potential to significantly accelerate drug discovery. PMID:24059335

  17. On the Several Molecules and Nanostructures of Water

    PubMed Central

    Whitney, Cynthia Kolb

    2012-01-01

    This paper investigates the water molecule from a variety of viewpoints. Water can involve different isotopes of Hydrogen and Oxygen, it can form differently shaped isomer molecules, and, when frozen, it occupies space differently than most other substances do. The tool for conducting the investigation of all this is called ‘Algebraic Chemistry’. This tool is a quantitative model for predicting the energy budget for all sorts of changes between different ionization states of atoms that are involved in chemical reactions and in changes of physical state. The model is based on consistent patterns seen in empirical data about ionization potentials, together with rational scaling laws that can interpolate and extrapolate for situations where no data are available. The results of the investigation of the water molecule include comments, both positive and negative, about technologies involving heavy water, poly water, Brown’s gas, and cold fusion. PMID:22312305

  18. Algebraic theory of molecules

    NASA Technical Reports Server (NTRS)

    Iachello, Franco

    1995-01-01

    An algebraic formulation of quantum mechanics is presented. In this formulation, operators of interest are expanded onto elements of an algebra, G. For bound state problems in nu dimensions the algebra G is taken to be U(nu + 1). Applications to the structure of molecules are presented.

  19. Diversity in Biological Molecules

    ERIC Educational Resources Information Center

    Newbury, H. John

    2010-01-01

    One of the striking characteristics of fundamental biological processes, such as genetic inheritance, development and primary metabolism, is the limited amount of variation in the molecules involved. Natural selective pressures act strongly on these core processes and individuals carrying mutations and producing slightly sub-optimal versions of…

  20. Halley's polymeric organic molecules

    NASA Technical Reports Server (NTRS)

    Huebner, W. F.; Boice, D. C.; Korth, A.

    1989-01-01

    The detection of polymeric organic compounds in the mass spectrum of Comet Halley obtained with the Positive Ion Cluster Composition analyzer on Giotto are examined. It is found that, in addition to polyoxymethylene, other polymers and complex molecules may exist in the comet. It is suggested that polymerized hydrogen cyanide may be a source for the observed CN and NH2 jets.