Sample records for functionalized macrocycles principaux

  1. Macrocycles

    Energy Technology Data Exchange (ETDEWEB)

    Raymond, Kenneth N.; Xu, Jide; Pham, Tiffany A.


    The invention provides macrocycles useful in chelating metal ions, particularly radionuclides, to provide metal ion complexes. The invention also provides methods of using the compounds and complexes of the invention, such as in therapeutic and diagnostic applications.

  2. Functional materials from self-assembled bis-urea macrocycles. (United States)

    Shimizu, Linda S; Salpage, Sahan R; Korous, Arthur A


    CONSPECTUS: This Account highlights the work from our laboratories on bis-urea macrocycles constructed from two C-shaped spacers and two urea groups. These simple molecular units assembled with high fidelity into columnar structures guided by the three-centered urea hydrogen bonding motif and aryl stacking interactions. Individual columns are aligned and closely packed together to afford functional and homogeneous microporous crystals. This approach allows for precise and rational control over the dimensions of the columnar structure simply by changing the small molecular unit. When the macrocyclic unit lacks a cavity, columnar assembly gives strong pillars. Strong pillars with external functional groups such as basic lone pairs can expand like clays to accept guests between the pillars. Macrocycles that contain sizable interior cavities assemble into porous molecular crystals with aligned, well-defined columnar pores that are accessible to gases and guests. Herein, we examine the optimal design of the macrocyclic unit that leads to columnar assembly in high fidelity and probe the feasibility of incorporating a second functional group within the macrocycles. The porous molecular crystals prepared through the self-assembly of bis-urea macrocycles display surface areas similar to zeolites but lower than MOFs. Their simple one-dimensional channels are well-suited for studying binding, investigating transport, diffusion and exchange, and monitoring the effects of encapsulation on reaction mechanism and product distribution. Guests that complement the size, shape, and polarity of the channels can be absorbed into these porous crystals with repeatable stoichiometry to form solid host-guest complexes. Heating or extraction with an organic solvent enables desorption or removal of the guest and subsequent recovery of the solid host. Further, these porous crystals can be used as containers for the selective [2 + 2] cycloadditions of small enones such as 2-cyclohexenone or 3

  3. A Macrocyclic Peptide that Serves as a Cocrystallization Ligand and Inhibits the Function of a MATE Family Transporter

    Directory of Open Access Journals (Sweden)

    Hiroaki Suga


    Full Text Available The random non-standard peptide integrated discovery (RaPID system has proven to be a powerful approach to discover de novo natural product-like macrocyclic peptides that inhibit protein functions. We have recently reported three macrocyclic peptides that bind to Pyrococcus furiosus multidrug and toxic compound extrusion (PfMATE transporter and inhibit the transport function. Moreover, these macrocyclic peptides were successfully employed as cocrystallization ligands of selenomethionine-labeled PfMATE. In this report, we disclose the details of the RaPID selection strategy that led to the identification of these three macrocyclic peptides as well as a fourth macrocyclic peptide, MaD8, which is exclusively discussed in this article. MaD8 was found to bind within the cleft of PfMATE’s extracellular side and blocked the path of organic small molecules being extruded. The results of an ethidium bromide efflux assay confirmed the efflux inhibitory activity of MaD8, whose behavior was similar to that of previously reported MaD5.

  4. Single-molecule phenyl-acetylene-macrocycle-based optoelectronic switch functioning as a quantum-interference-effect transistor. (United States)

    Hsu, Liang-Yan; Rabitz, Herschel


    This work proposes a new type of optoelectronic switch, the phenyl-acetylene-macrocycle-based single-molecule transistor, which utilizes photon-assisted tunneling and destructive quantum interference. The analysis uses single-particle Green's functions along with Floquet theory. Without the optical field, phenyl-acetylene-macrocycle exhibits a wide range of strong antiresonance between its frontier orbitals. The simulations show large on-off ratios (over 10(4)) and measurable currents (~10(-11) A) enabled by photon-assisted tunneling in a weak optical field (~2 × 10(5) V/cm) and at a small source-drain voltage (~0.05 V). Field amplitude power scaling laws and a range of field intensities are given for operating one- and two-photon assisted tunneling in phenyl-acetylene-macrocycle-based single-molecule transistors. This development opens up a new direction for creating molecular switches.

  5. Aza-macrocyclic complexes of the Group 1 cations - synthesis, structures and density functional theory study. (United States)

    Dyke, John; Levason, William; Light, Mark E; Pugh, David; Reid, Gillian; Bhakhoa, Hanusha; Ramasami, Ponnadurai; Rhyman, Lydia


    The Group 1 complexes, [M(Me6[18]aneN6)][BAr(F)] (M = Li-Cs; Me6[18]aneN6 = 1,4,7,10,13,16-hexamethyl-1,4,7,10,13,16-hexaazacyclooctadecane; BAr(F) = tetrakis{3,5-bis(trifluoromethyl)-phenyl}borate), are obtained in high yield by reaction of the macrocycle with M[BAr(F)] in anhydrous CH2Cl2 solution, and characterised spectroscopically ((1)H, (13)C{(1)H}, (7)Li, (23)Na, and (133)Cs NMR), by microanalysis and, for M = Li, K, and Rb, by single crystal X-ray analysis. The structures show N6-coordination to the metal ion; the small ionic radius for Li(+) leads to a puckered conformation. In contrast, the K(+) ion fits well into the N6 plane, with the [BAr(F)](-) anions above and below, leading to two K(+) species in the asymmetric unit (a hexagonal planar [K(Me6[18]aneN6)](+) cation and a '[K(Me6[18]aneN6)(κ(1)-BAr(F))2](-) anion', with long axial KF interactions). The Rb(+) ion sits above the N6 plane, with two long axial RbF interactions in one cation and two long, mutually cis RbF interactions in the other. The unusual sandwich cations, [M(Me3tacn)2](+) (M = Na, K; distorted octahedral, N6 donor set) and half-sandwich cations [Li(Me3tacn)(thf)](+) (distorted tetrahedron, N3O donor set), [Li(Me4cyclen)(OH2)](+), and [Na(Me4cyclen)(thf)](+) (both distorted square pyramids with N4O donor sets) were also prepared (Me3tacn = 1,4,7-trimethyl-1,4,7-triazacyclononane, Me4cyclen = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane). Density functional theory (DFT) calculations, using the BP86 and B3LYP functionals, show that the accessibility of the [M(Me3tacn)2](+) sandwich cations depends strongly on the M(+) ionic radius, such that it is sufficiently large to avoid steric clashing between the Me groups of the two rings, and small enough to avoid very acute N-M-N chelate angles. The calculations also show that coordination to the Group 1 cation involves significant donation of electron density from the p-orbitals on the N atoms of the macrocycle, rather than purely

  6. Site-selective functionalization of periodic mesoporous organosilica (PMO) with macrocyclic host for specific and reversible recognition of heavy metal. (United States)

    Ye, Gang; Leng, Yuxiao; Bai, Feifei; Wei, Jichao; Wang, Jianchen; Chen, Jing


    A novel kind of macrocyclic-host-functionalized periodic mesoporous organosilica (PMO) with excellent and reversible recognition of Pb(II) was developed. The macrocyclic host molecule cis-dicyclohexano[18]crown-6, with strong affinity to Pb(II), was carefully modified as a bridged precursor to build the PMO material. To break down the limit of the functionalization degree for PMOs incorporated with large-sized moieties, a site-selective post-functionalization method was proposed to further decorate the external surface of the PMO material. The selective recognition ability of the upgraded PMO material towards Pb(II) was remarkably enhanced without destroying the mesoporous ordering. Solid-state (13)C and (29)Si NMR spectroscopy, X-ray photoelectron spectroscopy (XPS), XRD, TEM, and nitrogen adsorption-desorption isotherm measurements were utilized for a full characterization of the structure, micromorphology, and surface properties. Reversible binding of Pb(II) was realized in the binding-elution cycle experiments. The mechanism of the supramolecular interaction between the macrocyclic host and metal ion was discussed. The synthetic strategy can be considered a general way to optimize the properties of PMOs as binding materials for practical use while preserving the mesostructure. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Aromatic Lateral Substituents Influence the Excitation Energies of Hexaaza Lanthanide Macrocyclic Complexes: A Wave Function Theory and Density Functional Study. (United States)

    Rabanal-León, Walter A; Murillo-López, Juliana A; Páez-Hernández, Dayán; Arratia-Pérez, Ramiro


    The high interest in lanthanide chemistry, and particularly in their luminescence, has been encouraged by the need of understanding the lanthanide chemical coordination and how the design of new luminescent materials can be affected by this. This work is focused on the understanding of the electronic structure, bonding nature, and optical properties of a set of lanthanide hexaaza macrocyclic complexes, which can lead to potential optical applications. Here we found that the DFT ground state of the open-shell complexes are mainly characterized by the manifold of low lying f states, having small HOMO-LUMO energy gaps. The results obtained from the wave function theory calculations (SO-RASSI) put on evidence the multiconfigurational character of their ground state and it is observed that the large spin-orbit coupling and the weak crystal field produce a strong mix of the ground and the excited states. The electron localization function (ELF) and the energy decomposition analysis (EDA) support the idea of a dative interaction between the macrocyclic ligand and the lanthanide center for all the studied systems; noting that, this interaction has a covalent character, where the d-orbital participation is evidenced from NBO analysis, leaving the f shell completely noninteracting in the chemical bonding. From the optical part we observed in all cases the characteristic intraligand (IL) (π-π*) and ligand to metal charge-transfer (LMCT) bands that are present in the ultraviolet and visible regions, and for the open-shell complexes we found the inherent f-f electronic transitions on the visible and near-infrared region.

  8. Macrocyclic trichothecenes as antifungal and anticancer compounds. (United States)

    de Carvalho, Maira Peres; Weich, Herbert; Abraham, Wolf-Rainer


    Trichothecenes are sesquiterpenoid metabolites produced by fungi and species of the plant genus Baccharis, family Asteraceae. They comprise a tricyclic core with an epoxide at C-12 and C-13 and can be grouped into non-macrocyclic and macrocyclic compounds. While many of these compounds are of concern in agriculture, the macrocyclic metabolites have been evaluated as antiviral, anti-cancer, antimalarial and antifungal compounds. Some known cytotoxic responses on eukaryotic cells include inhibition of protein, DNA and RNA syntheses, interference with mitochondrial function, effects on cell division and membranes. These targets however have been elucidated essentially employing non-macrocyclic trichothecenes and only one or two closely related macrocyclic compounds. For several macrocyclic trichothecenes high selectivity against fungal species and against cancer cell lines have been reported suggesting that the macrocycle and its stereochemistry are of crucial importance regarding biological activity and selectivity. This review is focused on compounds belonging to the macrocyclic type, where a cyclic diester or triester ring binds to the trichothecane moiety at C-4 and C- 15 leading to natural products belonging to the groups of satratoxins, verrucarins, roridins, myrotoxins and baccharinoids. Their biological activities, cytotoxic mechanisms and structure-activity relationships (SAR) are discussed. From the reported data it becomes evident that even small changes in the molecules can lead to pronounced effects on biological activity or selectivity against cancer cells lines. Understanding the underlying mechanisms may help to design highly specific drugs for cancer therapy.

  9. Macrocyclic fragrance materials

    DEFF Research Database (Denmark)

    Salvito, Daniel; Lapczynski, Aurelia; Sachse-Vasquez, Christen


    A screening-level aquatic environmental risk assessment for macrocyclic fragrance materials using a “group approach” is presented using data for 30 macrocyclic fragrance ingredients. In this group approach, conservative estimates of environmental exposure and ecotoxicological effects thresholds...... for compounds within two subgroups (15 macrocyclic ketones and 15 macrocyclic lactones/lactides) were used to estimate the aquatic ecological risk potential for these subgroups. It is reasonable to separate these fragrance materials into the two subgroups based on the likely metabolic pathway required...... for both regions is materials, and minimal in stream dilution (3:1), the conservatively predicted exposure concentrations for macrocyclic ketones would range from

  10. A thiourea-functionalized metal-organic macrocycle for the catalysis of Michael additions and prominent size-selective effect. (United States)

    Yang, Lu; Zhao, Liang; Zhou, Zhen; He, Cheng; Sun, Hui; Duan, Chunying


    A discrete tetranuclear thiourea-based metal-organic macrocycle (MOM) with a large size was constructed by a well-designed organic ligand and nickel(ii) ions via self-assembly. Incorporating thiourea groups as hydrogen-bond donors into a metal-organic complex system leads to a new approach for synthesizing functionalized heterogeneous catalysts, as this not only introduces coordination sites serving as chelators, but also overcomes the issues of self-association via intermolecular H-bonding, often occurring in homogeneous systems. The packing structure of this material formed a confined environment suitable for the access of substrate molecules dragged by the strong hydrogen-bond interactions from the thiourea groups, thus achieving a high catalytic performance in Michael additions of nitrostyrenes to nitroalkanes, with remarkable yields and size-selectivity in heterogeneous phase. Moreover, a comparison of the IR spectrum of Ni-SPT with the spectra of dimethyl malonate- and β-nitrostyrene-impregnated Ni-SPT indicated that both substrate molecules, β-nitrostyrene and dimethyl malonate, were able to access the cavity of the trimeric subunit.

  11. Synthesis of macrocyclic polyazomethines


    Elizbarashvili,Elizbar; Matitaishvili,Tea; Topuria,Khatuna


    The synthesis of 20-membered macrocyclic polyazomethine dyes 3a and 3b from 4,4'-dihydroxybiphenyl-3,3'-dicarbaldehyde (2a) and 5,5'-diamino-4,4'-dihydroxybiphenyl-3,3'-dicarbaldehyde (2b) and macrocyclic polyazomethine pigments 4 and 5 from 3a is described.

  12. Synthesis and Mesophase Properties of Intraanular Functionized Shape-persistent Macrocycles Containing Dibenzo [fg,op] naphthacenes

    Institute of Scientific and Technical Information of China (English)


    On the basis of the C-C coupling reactions of dibenzo [ fg, op ] naphthacene bistriflate, which was obtained by the condensation of phenylacetates with 4-aryl-2,6-bis(2-bromo-4-methoxy-phenyl) pyrylium salts followed by palladium-catalyzed dehydrohalogenation, three shape-persistent macrocycles with dibenzonaphthacene corner pieces, a nanometer interior void, and intraanular oligoalkyl side groups were synthesized by the oxidative cyclization of the corresponding bisacetylenes under high-dilution conditions. Their thermotropic liquid crystalline properties were investigated by using polarizing microscopy and differential scanning calorimetry. All the three compounds showed nematic mesophases and belonged to discotic liquid crystals with inverted topology.

  13. Synthesis of Macrocyclic Hexaoxazole (6OTD Dimers, Containing Guanidine and Amine Functionalized Side Chains, and an Evaluation of Their Telomeric G4 Stabilizing Properties

    Directory of Open Access Journals (Sweden)

    Keisuke Iida


    Full Text Available Structure-activity relationship studies were carried out on macrocyclic hexaoxazole (6OTD dimers, whose core structure stabilizes telomeric G-quadruplexes (G4. Two new 6OTD dimers having side chain amine and guanidine functional groups were synthesized and evaluated for their stabilizing ability against a telomeric G4 DNA sequence. The results show that the 6OTD dimers interact with the DNA to form 1:1 complexes and stabilize the antiparallel G4 structure of DNA in the presence of potassium cation. The guanidine functionalized dimer displays a potent stabilizing ability of the G4 structure, as determined by using a FRET melting assay (ΔTm=14 °C.

  14. Creating molecular macrocycles for anion recognition

    Directory of Open Access Journals (Sweden)

    Amar H. Flood


    Full Text Available The creation and functionality of new classes of macrocycles that are shape persistent and can bind anions is described. The genesis of triazolophane macrocycles emerges out of activity surrounding 1,2,3-triazoles made using click chemistry; and the same triazoles are responsible for anion capture. Mistakes made and lessons learnt in anion recognition provide deeper understanding that, together with theory, now provides for computer-aided receptor design. The lessons are acted upon in the creation of two new macrocycles. First, cyanostars are larger and like to capture large anions. Second is tricarb, which also favors large anions but shows a propensity to self-assemble in an orderly and stable manner, laying a foundation for future designs of hierarchical nanostructures.

  15. Luminescent macrocyclic lanthanide complexes (United States)

    Raymond, Kenneth N [Berkeley, CA; Corneillie, Todd M [Campbell, CA; Xu, Jide [Berkeley, CA


    The present invention provides a novel class of macrocyclic compounds as well as complexes formed between a metal (e.g., lanthanide) ion and the compounds of the invention. Preferred complexes exhibit high stability as well as high quantum yields of lanthanide ion luminescence in aqueous media without the need for secondary activating agents. Preferred compounds incorporate hydroxy-isophthalamide moieties within their macrocyclic structure and are characterized by surprisingly low, non-specific binding to a variety of polypeptides such as antibodies and proteins as well as high kinetic stability. These characteristics distinguish them from known, open-structured ligands.

  16. Rules of Macrocycle Topology: A [13]-Macrodilactone Case Study. (United States)

    Magpusao, Anniefer N; Rutledge, Kelli; Hamlin, Trevor A; Lawrence, Jean-Marc; Mercado, Brandon Q; Leadbeater, Nicholas E; Peczuh, Mark W


    Shape is an inherent trait of a molecule that dictates how it interacts with other molecules, either in binding events or intermolecular reactions. Large-ring macrocyclic compounds in particular leverage their shape when they are selectively bound by biomolecules and also when they exhibit macrocyclic diastereoselectivity. Nonetheless, rules that link structural parameters to the conformation of a macrocycle are still rudimentary. Here we use a structural investigation of a family of [13]-macrodilactones as a case study to develop rules that can be applied generally to macrocycles of different sizes and with a variety of functionality. A characteristic "ribbon" shape is adopted by the [13]-macrodilactones in the absence of stereogenic centres, which exhibits planar chirality. When one stereogenic centre at key positions on the backbone is incorporated into the structure, the planar chirality is dictated by the configuration of the centre. In cases where two stereogenic centres are present, their relationships can either reinforce the characteristic ribbon shape or induce alternative shapes to be adopted. The rules established in the case study are then applied to the analysis of a structure of the natural product migrastatin. They lay the groundwork for the development of models to understand macrocycle-biomolecule interactions and for the preparation of macrocycles with designed properties and activities.

  17. Fourth symposium on macrocyclic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, J. J.; Izatt, R. M.


    Both theoretical and experimental aspects of the properties and behavior of synthetic and naturally occurring macrocyclic compounds are covered in this symposium. This document contains abstracts of the papers. (DLC)

  18. Macrocyclic polyamine-functionalized silica as a solid-phase extraction material coupled with ionic liquid dispersive liquid-liquid extraction for the enrichment of polycyclic aromatic hydrocarbons. (United States)

    Liu, Longhui; He, Lijun; Jiang, Xiuming; Zhao, Wenjie; Xiang, Guoqiang; Anderson, Jared L


    In this study, silica modified with a 30-membered macrocyclic polyamine was synthesized and first used as an adsorbent material in SPE. The SPE was further combined with ionic liquid (IL) dispersive liquid-liquid microextraction (DLLME). Five polycyclic aromatic hydrocarbons were employed as model analytes to evaluate the extraction procedure and were determined by HPLC combined with UV/Vis detection. Acetone was used as the elution solvent in SPE as well as the dispersive solvent in DLLME. The enrichment of analytes was achieved using the 1,3-dibutylimidazolium bis[(trifluoromethyl)sulfonyl]imide IL/acetone/water system. Experimental conditions for the overall macrocycle-SPE-IL-DLLME method, such as the amount of adsorbent, sample solution volume, sample solution pH, type of elution solvent as well as addition of salt, were studied and optimized. The developed method could be successfully applied to the analysis of four real water samples. The macrocyclic polyamine offered higher extraction efficiency for analytes compared with commercially available C18 cartridge, and the developed method provided higher enrichment factors (2768-5409) for model analytes compared with the single DLLME. Good linearity with the correlation coefficients ranging from 0.9983 to 0.9999 and LODs as low as 0.002 μg/L were obtained in the proposed method.

  19. Macrocycle synthesis by trimerization of boronic acids around a hexaol template, and recognition of polyols by resulting macrocyclic oligoboronic acids. (United States)

    Stoltenberg, Dennis; Lüning, Ulrich


    2,6-Bis(alkenyloxy) substituted arylboronic acids can be cyclotrimerized with the help of a hexaol as a template. First, the boronic acids are assembled by boronic ester formation with hexahydroxy-bicyclo[2.2.2]octane. Next, the resulting triboronates are cyclized by ring-closing metathesis to yield trimacrocycles as diastereomeric E/Z mixtures. Catalytic hydrogenation yields a single saturated trimacrocycle. Cleavage of the boronic ester functions liberates the template and generates a macrocycle with three boronic acid functionalities in endo-orientation. Due to this preorganization, macrocycles with boronic acids in endo-positions are good receptors for polyols. The binding of carbohydrates such as fructose was compared with the uptake of the respective templates into macrocycles with two or three boronic acids in endo-orientation.

  20. Assembly of macrocycles by zirconocene-mediated, reversible carbon-carbon bond formation. (United States)

    Gessner, Viktoria H; Tannaci, John F; Miller, Adam D; Tilley, T Don


    Macrocyclic compounds have attracted considerable attention in numerous applications, including host-guest chemistry, chemical sensing, catalysis, and materials science. A major obstacle, however, is the limited number of convenient, versatile, and high-yielding synthetic routes to functionalized macrocycles. Macrocyclic compounds have been typically synthesized by ring-closing or condensation reactions, but many of these procedures produce mixtures of oligomers and cyclic compounds. As a result, macrocycle syntheses are often associated with difficult separations and low yields. Some successful approaches that circumvent these problems are based on "self-assembly" processes utilizing reversible bond-forming reactions, but for many applications, it is essential that the resulting macrocycle be built with a strong covalent bond network. In this Account, we describe how zirconocene-mediated reductive couplings of alkynes can provide reversible carbon-carbon bond-forming reactions well-suited for this purpose. Zirconocene coupling of alkenes and alkynes has been used extensively as a source of novel, versatile pathways to functionalized organic compounds. Here, we describe the development of zirconocene-mediated reductive couplings as a highly efficient method for the preparation of macrocycles and cages with diverse compositions, sizes, and shapes. This methodology is based on the reversible, regioselective coupling of alkynes with bulky substituents. In particular, silyl substituents provide regioselective, reversible couplings that place them into the α-positions of the resulting zirconacyclopentadiene rings. According to density functional theory (DFT) calculations and kinetic studies, the mechanism of this coupling involves a stepwise process, whereby an insertion of the second alkyne influences regiochemistry through both steric and electronic factors. Zirconocene coupling of diynes that incorporate silyl substituents generates predictable macrocyclic products

  1. A mesoporous metal–organic framework based on a shape-persistent macrocycle

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Teng-Hao; Popov, Ilya; Chuang, Yu-Chun; Chen, Yu-Sheng; Miljani; #263; , Ognjen Š. (NSRRC); (UC); (Houston)


    A mesoporous Zn-based metal–organic framework (MOF) was prepared from a shape-persistent phenylene ethynylene macrocycle functionalized with three –COOH groups. The rigid ligand has a ~ 9 Å wide central cavity which serves as a predesigned pore. The macrocycles [ππ] stack into pairs, with their carboxylate groups connected via three Zn₃O₁₄C₆H₂ clusters. The resulting MOF has a void volume of 86%.

  2. Rapid synthesis of cyclic oligomeric depsipeptides with positional, stereochemical, and macrocycle size distribution control. (United States)

    Batiste, Suzanne M; Johnston, Jeffrey N


    Macrocyclic small molecules are attractive tools in the development of sensors, new materials, and therapeutics. Within early-stage drug discovery, they are increasingly sought for their potential to interact with broad surfaces of peptidic receptors rather than within their narrow folds and pockets. Cyclization of linear small molecule precursors is a straightforward strategy to constrain conformationally mobile motifs, but forging a macrocycle bond typically becomes more difficult at larger ring sizes. We report the development of a general approach to discrete collections of oligomeric macrocyclic depsipeptides using an oligomerization/macrocyclization process governed by a series of Mitsunobu reactions of hydroxy acid monomers. Ring sizes of 18, 24, 30, and 36 are formed in a single reaction from a didepsipeptide, whereas sizes of 24, 36, and 60 result from a tetradepsipeptide. The ring-size selectivity inherent to the approach can be modulated by salt additives that enhance the formation of specific ring sizes. Use of chemical synthesis to prepare the monomers suggests broad access to functionally and stereochemically diverse collections of natural product-like oligodepsipeptide macrocycles. Two cyclodepsipeptide natural products were prepared along with numerous unnatural oligomeric congeners to provide rapid access to discrete collections of complex macrocyclic small molecules from medium (18) to large (60) ring sizes.

  3. Correlation between oxygen adsorption energy and electronic structure of transition metal macrocyclic complexes. (United States)

    Liu, Kexi; Lei, Yinkai; Wang, Guofeng


    Oxygen adsorption energy is directly relevant to the catalytic activity of electrocatalysts for oxygen reduction reaction (ORR). In this study, we established the correlation between the O2 adsorption energy and the electronic structure of transition metal macrocyclic complexes which exhibit activity for ORR. To this end, we have predicted the molecular and electronic structures of a series of transition metal macrocyclic complexes with planar N4 chelation, as well as the molecular and electronic structures for the O2 adsorption on these macrocyclic molecules, using the density functional theory calculation method. We found that the calculated adsorption energy of O2 on the transition metal macrocyclic complexes was linearly related to the average position (relative to the lowest unoccupied molecular orbital of the macrocyclic complexes) of the non-bonding d orbitals (d(z(2)), d(xy), d(xz), and d(yz)) which belong to the central transition metal atom. Importantly, our results suggest that varying the energy level of the non-bonding d orbitals through changing the central transition metal atom and/or peripheral ligand groups could be an effective way to tuning their O2 adsorption energy for enhancing the ORR activity of transition metal macrocyclic complex catalysts.

  4. Radical photocyclization route for macrocyclic lactone ring expansion and conversion to macrocyclic lactams and ketones. (United States)

    Nishikawa, Keisuke; Yoshimi, Yasuharu; Maeda, Kousuke; Morita, Toshio; Takahashi, Ichiro; Itou, Tatsuya; Inagaki, Sho; Hatanaka, Minoru


    A new method for the synthesis of macrocyclic lactones, lactams, and ketones, which utilizes photoinduced intramolecular radical cyclization reactions of substrates containing tethered carboxylic acids and α,β-unsaturated carbonyl moieties, has been uncovered. Photocyclization of the carboxylic acids tethered acrylate ester, which were prepared starting from the macrocyclic lactones, gave the two-carbon elongated macrocyclic lactones via decarboxylation. Similar photoreactions of carboxylic acid tethered acryl amide or α,β-unsaturated ketone moieties, which were also prepared starting from the macrocyclic lactones, produced macrocyclic lactams or ketones, respectively. The simple approach can be readily applied to the preparation of a variety of macrocyclic lactones, lactams, and ketones with tunable ring sizes.

  5. Templating irreversible covalent macrocyclization by using anions. (United States)

    Kataev, Evgeny A; Kolesnikov, Grigory V; Arnold, Rene; Lavrov, Herman V; Khrustalev, Victor N


    Inorganic anions were used as templates in the reaction between a diamine and an activated diacid to form macrocyclic amides. The reaction conditions were found to perform the macrocyclization sufficiently slow to observe a template effect. A number of analytical methods were used to clarify the reaction mechanisms and to show that the structure of the intermediate plays a decisive role in determining the product distribution. For the macrocyclization under kinetic control, it was shown that the amount of a template, the conformational rigidity of building blocks, and the anion affinities of reaction components and intermediates are important parameters that one should take into consideration to achieve high yields.

  6. Solar Thermal Energy Storage in a Photochromic Macrocycle. (United States)

    Vlasceanu, Alexandru; Broman, Søren L; Hansen, Anne S; Skov, Anders B; Cacciarini, Martina; Kadziola, Anders; Kjaergaard, Henrik G; Mikkelsen, Kurt V; Nielsen, Mogens Brøndsted


    The conversion and efficient storage of solar energy is recognized to hold significant potential with regard to future energy solutions. Molecular solar thermal batteries based on photochromic systems exemplify one possible technology able to harness and apply this potential. Herein is described the synthesis of a macrocycle based on a dimer of the dihydroazulene/vinylheptafulvene (DHA/VHF) photo/thermal couple. By taking advantage of conformational strain, this DHA-DHA macrocycle presents an improved ability to absorb and store incident light energy in chemical bonds (VHF-VHF). A stepwise energy release over two sequential ring-closing reactions (VHF→DHA) combines the advantages of an initially fast discharge, hypothetically addressing immediate energy consumption needs, followed by a slow process for consistent, long-term use. This exemplifies another step forward in the molecular engineering and design of functional organic materials towards solar thermal energy storage and release.

  7. Marine Macrocyclic Imines, Pinnatoxins A and G: Structural Determinants and Functional Properties to Distinguish Neuronal α7 from Muscle α1(2)βγδ nAChRs. (United States)

    Bourne, Yves; Sulzenbacher, Gerlind; Radić, Zoran; Aráoz, Rómulo; Reynaud, Morgane; Benoit, Evelyne; Zakarian, Armen; Servent, Denis; Molgó, Jordi; Taylor, Palmer; Marchot, Pascale


    Pinnatoxins are macrocyclic imine phycotoxins associated with algal blooms and shellfish toxicity. Functional analysis of pinnatoxin A and pinnatoxin G by binding and voltage-clamp electrophysiology on membrane-embedded neuronal α7, α4β2, α3β2, and muscle-type α12βγδ nicotinic acetylcholine receptors (nAChRs) reveals high-affinity binding and potent antagonism for the α7 and α12βγδ subtypes. The toxins also bind to the nAChR surrogate, acetylcholine-binding protein (AChBP), with low Kd values reflecting slow dissociation. Crystal structures of pinnatoxin-AChBP complexes (1.9-2.2 Å resolution) show the multiple anchoring points of the hydrophobic portion, the cyclic imine, and the substituted bis-spiroketal and cyclohexene ring systems of the pinnatoxins that dictate tight binding between the opposing loops C and F at the receptor subunit interface, as observed for the 13-desmethyl-spirolide C and gymnodimine A congeners. Uniquely, however, the bulky bridged EF-ketal ring specific to the pinnatoxins extends radially from the interfacial-binding pocket to interact with the sequence-variable loop F and govern nAChR subtype selectivity and central neurotoxicity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Engineering macrocyclic figure-eight motif

    Indian Academy of Sciences (India)

    V Haridas; Harinder Singh; Yogesh K Sharma; Kashmiri Lal


    The design and synthesis of figure-eight macrocycles are very scarce owing to the intricacies and lack of predictability from first principles. This review emphasizes on discrete macrocyclic systems both synthetic and natural with a defined figure eight knotted topology. In almost all the helical macrocycles, the helical arrangement is held by intramolecular hydrogen bonding or as a backbone requirement, but in all cases, a planar graph can be drawn and so these compounds are trivial from the topological stand point. Nature presents great deal of complexity in terms of structures in macromolecules like DNA and proteins and also displays intriguing topology in simple natural products. Patellamide, tawicyclamides, nosiheptide and thiostrepton are natural products with figure eight topology which shows interesting biological activity. Expanded porphyrins, Cu(II) complexes of thiomacrocycles, cyclic peptides and oligoesters are synthetic macrocycles showing intriguing topology. Analysis of structure and folding behaviour will enable chemists to design molecules with intriguing topology.

  9. Pulsed EPR and NMR spectroscopy of paramagnetic iron porphyrinates and related iron macrocycles: how to understand patterns of spin delocalization and recognize macrocycle radicals. (United States)

    Walker, F Ann


    Pulsed EPR spectroscopic techniques, including ESEEM (electron spin echo envelope modulation) and pulsed ENDOR (electron-nuclear double resonance), are extremely useful for determining the magnitudes of the hyperfine couplings of macrocycle and axial ligand nuclei to the unpaired electron(s) on the metal as a function of magnetic field orientation relative to the complex. These data can frequently be used to determine the orientation of the g-tensor and the distribution of spin density over the macrocycle, and to determine the metal orbital(s) containing unpaired electrons and the macrocycle orbital(s) involved in spin delocalization. However, these studies cannot be carried out on metal complexes that do not have resolved EPR signals, as in the case of paramagnetic even-electron metal complexes. In addition, the signs of the hyperfine couplings, which are not determined directly in either ESEEM or pulsed ENDOR experiments, are often needed in order to translate hyperfine couplings into spin densities. In these cases, NMR isotropic (hyperfine) shifts are extremely useful in determining the amount and sign of the spin density at each nucleus probed. For metal complexes of aromatic macrocycles such as porphyrins, chlorins, or corroles, simple rules allow prediction of whether spin delocalization occurs through sigma or pi bonds, and whether spin density on the ligands is of the same or opposite sign as that on the metal. In cases where the amount of spin density on the macrocycle and axial ligands is found to be too large for simple metal-ligand spin delocalization, a macrocycle radical may be suspected. Large spin density on the macrocycle that is of the same sign as that on the metal provides clear evidence of either no coupling or weak ferromagnetic coupling of a macrocycle radical to the unpaired electron(s) on the metal, while large spin density on the macrocycle that is of opposite sign to that on the metal provides clear evidence of antiferromagnetic coupling

  10. Synthesis and electrochemical studies of phenylazo substituted tetraaza macrocyclic complexes of Ni(II)

    Indian Academy of Sciences (India)

    Randhir Singh; Suresh Kumar; Amarendra Bhattacharya


    Synthesis and characterization of some phenyl azo substituted tetraaza macrocyclic complexes of Ni(II) are reported. Electrochemical behaviour of these macrocyclic complexes has been examined using polarographic, voltammetric and spectroscopic techniques. These studies show that both the ligand and the metal are electrochemically active. The electrochemical behaviour of the azo function has been shown to occur through a single four-electron process. When a nitro group is also present, the nitro function of the azo moiety is reduced in a six-electron cathodic wave.

  11. Bending rigid molecular rods: formation of oligoproline macrocycles. (United States)

    Scully, Conor C G; Rai, Vishal; Poda, Gennadiy; Zaretsky, Serge; Burns, Darcy C; Houliston, R Scott; Lou, Tiantong; Yudin, Andrei K


    Bent but not broken: cyclic oligoprolines are accessed in a reaction that effectively bends rigid oligoproline peptides (see scheme; TBDMS=tert-butyldimethylsilyl). The stitching is accomplished during macrocyclization enabled by aziridine aldehydes and isocyanides. Molecular modeling studies suggest that electrostatic attraction between the termini of the linear peptide is pivotal for macrocyclization. The macrocycles were studied by circular dichroism with a polyproline II structure being observed in larger macrocycles.

  12. Supramolecular networking of macrocycles based on exo-coordination: from discrete to continuous frameworks. (United States)

    Park, Sunhong; Lee, So Young; Park, Ki-Min; Lee, Shim Sung


    achieve in these networked macrocycles are one to three dimensional coordination polymers based on homo- and heteronuclear metal systems. Using crystal engineering methods, we have also investigated variation in the donors, interdonor distances, ligand isomer structures, and the effect of counter anions on the chemical and physical properties of the products. Understanding the relationship between structure and function in these exo-coordination products is an important step in the design of these new supramolecules for practical applications. We investigated the photophysical properties of the exocyclic complexes and a chromogenic macrocycle, which exhibited cation-selective and anion-controlled color change depending on an exo- or endo- ligand binding mode. Overall, we suggest that the exocyclic coordination behavior provides a versatile strategy for the preparation of new molecular networks and materials.

  13. Macrocyclic ligands for uranium complexation. Final report, August 1, 1986--March 31, 1993

    Energy Technology Data Exchange (ETDEWEB)

    Potts, K.T.


    Macrocycles, designed for complexation of the uranyl ion by computer modeling studies and utilizing six ligating atoms in the equatorial plane of the uranyl ions, have been prepared and their complexation of the uranyl ions evaluated. The ligating atoms, either oxygen or sulfur, were part of acylurea, biuret or thiobiuret subunits with alkane chains or pyridine units completing the macrocyclic periphery. These macrocycles with only partial preorganization formed uranyl complexes in solution but no crystalline complexes were isolated. Refinement of the cavity diameter by variation of the peripheral functional groups is currently studied to achieve an optimized cavity diameter of 4.7--5.2 {angstrom}. Acyclic ligands containing the same ligating atoms in equivalent functional entities were found to form a crystalline 1:1 uranyl-ligand complex (stability constant log K = 10.7) whose structure was established by X-ray data. This complex underwent a facile, DMSO-induced rearrangement to a 2:1 uranyl-ligand complex whose structure was also established by X-ray data. The intermediates to the macrocycles all behaved as excellent ligands for the complexation of transition metals. Acylthiourea complexes of copper and nickel as well as intermolecular, binuclear copper and nickel complexes of bidentate carbonyl thioureas formed readily and their structures were established in several representative instances by X-ray structural determinations. Tetradentate bis(carbonylthioureas) were found to be very efficient selective reagents for the complexation of copper in the presence of nickel ions. Several preorganized macrocycles were also prepared but in most instances these macrocycles underwent ring-opening under complexation conditions.

  14. Enzymatic Macrocyclization of 1,2,3-Triazole Peptide Mimetics. (United States)

    Oueis, Emilia; Jaspars, Marcel; Westwood, Nicholas J; Naismith, James H


    The macrocyclization of linear peptides is very often accompanied by significant improvements in their stability and biological activity. Many strategies are available for their chemical macrocyclization, however, enzyme-mediated methods remain of great interest in terms of synthetic utility. To date, known macrocyclization enzymes have been shown to be active on both peptide and protein substrates. Here we show that the macrocyclization enzyme of the cyanobactin family, PatGmac, is capable of macrocyclizing substrates with one, two, or three 1,4-substituted 1,2,3-triazole moieties. The introduction of non-peptidic scaffolds into macrocycles is highly desirable in tuning the activity and physical properties of peptidic macrocycles. We have isolated and fully characterized nine non-natural triazole-containing cyclic peptides, a further ten molecules are also synthesized. PatGmac has now been shown to be an effective and versatile tool for the ring closure by peptide bond formation.

  15. Rapid synthesis of macrocycles from diol precursors

    DEFF Research Database (Denmark)

    Wingstrand, Magnus; Madsen, Charlotte Marie; Clausen, Mads Hartvig


    A method for the formation of synthetic macrocycles with different ring sizes from diols is presented. Reacting a simple diol precursor with electrophilic reagents leads to a cyclic carbonate, sulfite or phosphate in a single step in 25-60% yield. Converting the cyclization precursor to a bis-ele...

  16. Organic spin clusters: macrocyclic-macrocyclic polyarylmethyl polyradicals with very high spin S = 5-13. (United States)

    Rajca, Andrzej; Wongsriratanakul, Jirawat; Rajca, Suchada


    Synthesis and magnetic studies of a new class of organic spin clusters, possessing alternating connectivity of unequal spins, are described. Polyarylmethyl polyether precursors to the spin clusters, with linear and branched connectivity between calix[4]arene-based macrocycles, are prepared via modular, multistep syntheses. Their molecular connectivity and stereoisomerism are analyzed using NMR spectroscopy. The absolute masses (4-10 kDa) are determined by FABMS and GPC/MALS. Small angle neutron scattering (SANS) provides the radii of gyration of 1.2-1.8 nm. The corresponding polyradicals with 15, 22, and 36 triarylmethyls, which are prepared and studied as solutions in tetrahydrofuran-d(8), may be described as S' = 7/2, 1/2, 7/2 spin trimer (average S = 5-6), S' = 7/2, 1/2, 6/2, 1/2, 7/2 spin pentamer (average S = 7-9), and spin nonamer (average S = 11-13), respectively, as determined by SQUID magnetometry and numerical fits to linear combinations of the Brillouin functions. For spin trimer and pentamer, the quantitative magnetization data are fit to new percolation models, based upon random distributions of chemical defects and ferromagnetic vs antiferromagnetic couplings. The value of S = 13 is the highest for an organic molecule.


    Directory of Open Access Journals (Sweden)

    V. Lozan


    Full Text Available A series of novel tri-, tetra- and pentanuclear complexes composed of dinuclear LM units (M=Co, Ni, Zn; L=24-membered macrocyclic hexaaza-dithiophenolate ligand and ferrocenecarboxylate ([CpFeC5H4CO2]ˉ, 1,1’-ferrocenedicarboxy-late ([Fe(C5H4-CO22]2ˉ, acetylene-dicarboxylate, terephthalate, isophthalate, and naphthalene diimide dicarboxylate groups is reported. The complexes, have been synthesized and characterised by UV/Vis-, IR-, NMR-spectroscopy, Cyclovoltammetry, and X-ray crystallography. Each dicarboxylate dianion acts as a quadridentate bridging ligand linking two bioctahedral LM2 units via µ1,3-bridging carboxylate functions to generate discrete dications with a central LM2(O2C-R-CO2M2L core. The magnetic properties of these compounds reveal the presence of weak ferromagnetic exchange interactions between the NiII ions of the dinuclear subunits and negligible coupling across the dicarboxylate bridges.

  18. Efficient access to new chemical space through flow--construction of druglike macrocycles through copper-surface-catalyzed azide-alkyne cycloaddition reactions. (United States)

    Bogdan, Andrew R; James, Keith


    A series of 12- to 22-membered macrocycles, with druglike functionality and properties, have been generated by using a simple and efficient copper-catalyzed azide-acetylene cycloaddition reaction, conducted in flow in high-temperature copper tubing, under environmentally friendly conditions. The triazole-containing macrocycles have been generated in up to 90 % yield in a 5 min reaction, without resorting to the high-dilution conditions typical of macrocyclization reactions. This approach represents a very efficient method for constructing this important class of molecules, in terms of yield, concentration, and environmental considerations.

  19. Synthesis and characterization of new azo containing Schiff base macrocycle

    Institute of Scientific and Technical Information of China (English)

    Saeed Malek-Ahmadi; Amir Abdolmaleki


    Fully conjugated Schiff base macrocycle has been prepared through a simple and mild condition, a one-pot cyclization procedure of four-component without using a template. The condensation reaction of related bis (hydroxybenzaldehyde) with phenylenediamines to prepare a conjugated [2 + 2] Schiff base macrocycle has been investigated and fluorescent [2 + 2] Schiff base macrocycles with N2O2 binding pockets has been prepared and characterized by elemental analysis,' H NMR, IR, fluorescent, UV-visible and MALDI mass spectroscopies.

  20. Amide-based Fluorescent Macrocyclic Anion Receptors

    Institute of Scientific and Technical Information of China (English)

    ZENG, Zhen-Ya(曾振亚); XU, Kuo-Xi(徐括喜); HE, Yong-Bing(何永炳); LIU, Shun-Ying(刘顺英); WU, Jin-Long(吴进龙); WEI, Lan-Hua(隗兰华); MENG, Ling-Zhi(孟令芝)


    Two fluorescent anion receptors (1 and 2) based on amide macrocycle were synthesized and corresponding fluorescence quenching induced by anion complexation was observed in different degree. Receptors form 1: 1 complexes with anions by hydrogen bonding interactions. Receptor 1 bound anions in the order of F->Cl->H2PO4->CH3COO->>Br-, I- and receptor 2 showed high selectivity to F- over other anions.

  1. Haemonchus contortus P-glycoprotein-2: in situ localisation and characterisation of macrocyclic lactone transport. (United States)

    Godoy, Pablo; Lian, Jing; Beech, Robin N; Prichard, Roger K


    Haemonchus contortus is a veterinary nematode that infects small ruminants, causing serious decreases in animal production worldwide. Effective control through anthelmintic treatment has been compromised by the development of resistance to these drugs, including the macrocyclic lactones. The mechanisms of resistance in H. contortus have yet to be established but may involve efflux of the macrocyclic lactones by nematode ATP-binding-cassette transporters such as P-glycoproteins. Here we report the expression and functional activity of H. contortus P-glycoprotein 2 expressed in mammalian cells and characterise its interaction with the macrocyclic lactones, ivermectin, abamectin and moxidectin. The ability of H. contortus P-glycoprotein 2 to transport different fluorophore substrates was markedly inhibited by ivermectin and abamectin in a dose-dependent and saturable way. The profile of transport inhibition by moxidectin was markedly different. H. contortus P-glycoprotein 2 was expressed in the pharynx, the first portion of the worm's intestine and perhaps in adjacent nervous tissue, suggesting a role for this gene in regulating the uptake of avermectins and in protecting nematode tissues from the effects of macrocyclic lactone anthelmintic drugs. H. contortus P-glycoprotein 2 may thus contribute to resistance to these drugs in H. contortus.

  2. Peptide macrocycles featuring a backbone secondary amine: a convenient strategy for the synthesis of lipidated cyclic and bicyclic peptides on solid support. (United States)

    Oddo, Alberto; Münzker, Lena; Hansen, Paul R


    A convenient strategy for the on-resin synthesis of macrocyclic peptides (3- to 13-mers) via intramolecular halide substitution by a diamino acid is described. The method is compatible with standard Fmoc/tBu SPPS and affords a tail-to-side-chain macrocyclic peptide featuring an endocyclic secondary amine. This functional group is still reactive toward acylation, allowing for the continuation of the synthesis. An application to the synthesis of lipidated cyclic and bicyclic antimicrobial peptides is presented.

  3. Synthesis of the macrocyclic core of (-)-pladienolide B

    DEFF Research Database (Denmark)

    Skaanderup, Philip Robert; Jensen, T.


    An efficient synthesis of the macrocyclic core of (-)-pladienolide B is disclosed. The concise route relies on a chiral auxiliary-mediated asymmetric aldol addition and an osmium-catalyzed asymmetric dihydroxylation to install the three oxygenated stereocenters of the macrocycle. This purely reag...

  4. Observations on the Influence of Precursor Conformations on Macrocyclization Reactions

    DEFF Research Database (Denmark)

    Hammershøj, Peter; Beldring, Klavs; Nielsen, Anders R.


    macrocyclization to afford a mixture of diastereomeric sulfites, subjection of the other precursor to identical reaction conditions resulted in the isolation of the linear dichloride. We hypothesize that there is a difference in the ability of the two molecules to adopt a conformation that is germane...... to macrocyclization, a proposition that is supported by conformational analyses using molecular mechanics....

  5. Synthesis and anion recognition properties of shape-persistent binaphthyl-containing chiral macrocyclic amides

    Directory of Open Access Journals (Sweden)

    Marco Caricato


    Full Text Available We report on the synthesis and characterization of novel shape-persistent, optically active arylamide macrocycles, which can be obtained using a one-pot methodology. Resolved, axially chiral binol scaffolds, which incorporate either methoxy or acetoxy functionalities in the 2,2' positions and carboxylic functionalities in the external 3,3' positions, were used as the source of chirality. Two of these binaphthyls are joined through amidation reactions using rigid diaryl amines of differing shapes, to give homochiral tetraamidic macrocycles. The recognition properties of these supramolecular receptors have been analyzed, and the results indicate a modulation of binding affinities towards dicarboxylate anions, with a drastic change of binding mode depending on the steric and electronic features of the functional groups in the 2,2' positions.

  6. How do the macrocyclic lactones kill filarial nematode larvae? (United States)

    Wolstenholme, Adrian J; Maclean, Mary J; Coates, Ruby; McCoy, Ciaran J; Reaves, Barbara J


    The macrocyclic lactones (MLs) are one of the few classes of drug used in the control of the human filarial infections, onchocerciasis and lymphatic filariasis, and the only one used to prevent heartworm disease in dogs and cats. Despite their importance in preventing filarial diseases, the way in which the MLs work against these parasites is unclear. In vitro measurements of nematode motility have revealed a large discrepancy between the maximum plasma concentrations achieved after drug administration and the amounts required to paralyze worms. Recent evidence has shed new light on the likely functions of the ML target, glutamate-gated chloride channels, in filarial nematodes and supports the hypothesis that the rapid clearance of microfilariae that follows treatment involves the host immune system.

  7. Synthesis of New Macrocyclic Polyamides as Antimicrobial Agent Candidates

    Directory of Open Access Journals (Sweden)

    Osama I. Abd El-Salam


    Full Text Available A series of macrocyclic imides and Schiff-bases have been prepared via the cyclocondensation of pyridine-2,6-dicarbonyl dichloride (1 with L-ornithine methyl ester to give the corresponding macrocyclic bisester 2. Treatment of 2 with hydrazine hydrate gave macrocyclic bisacid hydrazide 3, which was used as starting material. Condensation of bishydrazide 3 with diacid anhydrides or aromatic aldehydes in refluxing acetic acid or ethanol gave the corresponding macrocyclic bisimides 4, 5a,b and macrocyclic bis- hydrazones 6a–j, respectively. The structure assignments of the new compounds were based on chemical and spectroscopic evidence. The antimicrobial screening showed that many of these newly synthesized compounds have good antimicrobial activities, comparable to ampicillin and ketaconazole used as reference drugs.

  8. Macrocyclic 2,7-Anthrylene Oligomers. (United States)

    Yamamoto, Yuta; Wakamatsu, Kan; Iwanaga, Tetsuo; Sato, Hiroyasu; Toyota, Shinji


    A macrocyclic compound consisting of six 2,7-anthrylene units was successfully synthesized by Ni-mediated coupling of the corresponding dibromo precursor as a novel π-conjugated compound. This compound was sufficiently stable and soluble in organic solvents due to the presence of mesityl groups. X-ray analysis showed that the molecule had a nonplanar and hexagonal wheel-shaped framework of approximately S6 symmetry. The dynamic process between two S6 structures was observed by using the dynamic NMR technique, the barrier being 58 kJ mol(-1) . The spectroscopic properties of the hexamer were compared with those of analogous linear oligomers.

  9. The Click Reaction as an Efficient Tool for the Construction of Macrocyclic Structures

    Directory of Open Access Journals (Sweden)

    Dario Pasini


    Full Text Available The Cu(I-catalyzed azide-alkyne cycloaddition (CuAAC, known as the click reaction is an established tool used for the construction of complex molecular architectures. Given its efficiency it has been widely applied for bioconjugation, polymer and dendrimer synthesis. More recently, this reaction has been utilized for the efficient formation of rigid or shape-persistent, preorganized macrocyclic species. This strategy also allows the installment of useful functionalities, in the form of polar and function-rich 1,2,3-triazole moieties, directly embedded in the macrocyclic structures. This review analyzes the state of the art in this context, and provides some elements of perspective for future applications.

  10. New leaders, new policies ? Les politiques éducatives des principaux partis en Angleterre depuis décembre 2005


    Beauvallet, Anne


    Les trois principaux partis politiques britanniques ont choisi de nouveaux chefs en quelques années : David Cameron, Gordon Brown et Nick Clegg. Cette situation inhabituelle pourrait permettre un changement profond des politiques éducatives proposées. Des évolutions sont perceptibles chez les Travaillistes (attitude envers les écoles privées, tests) et les Conservateurs (attitude envers les grammar schools et les enseignants) mais elles sont limitées car Gordon Brown et David Cameron prolonge...

  11. Macrocyclic olefin metathesis at high concentrations by using a phase-separation strategy. (United States)

    Raymond, Michaël; Holtz-Mulholland, Michael; Collins, Shawn K


    Macrocyclic olefin metathesis has seen advances in the areas of stereochemistry, chemoselectivity, and catalyst stability, but strategies aimed at controlling dilution effects in macrocyclizations are rare. Herein, a protocol to promote macrocyclic olefin metathesis, one of the most common synthetic tools used to prepare macrocycles, at relatively high concentrations (up to 60 mM) is described by exploitation of a phase-separation strategy. A variety of macrocyclic skeletons could be prepared having either different alkyl, aryl, or amino acids spacers.

  12. Predicting bioactive conformations and binding modes of macrocycles (United States)

    Anighoro, Andrew; de la Vega de León, Antonio; Bajorath, Jürgen


    Macrocyclic compounds experience increasing interest in drug discovery. It is often thought that these large and chemically complex molecules provide promising candidates to address difficult targets and interfere with protein-protein interactions. From a computational viewpoint, these molecules are difficult to treat. For example, flexible docking of macrocyclic compounds is hindered by the limited ability of current docking approaches to optimize conformations of extended ring systems for pose prediction. Herein, we report predictions of bioactive conformations of macrocycles using conformational search and binding modes using docking. Conformational ensembles generated using specialized search technique of about 70 % of the tested macrocycles contained accurate bioactive conformations. However, these conformations were difficult to identify on the basis of conformational energies. Moreover, docking calculations with limited ligand flexibility starting from individual low energy conformations rarely yielded highly accurate binding modes. In about 40 % of the test cases, binding modes were approximated with reasonable accuracy. However, when conformational ensembles were subjected to rigid body docking, an increase in meaningful binding mode predictions to more than 50 % of the test cases was observed. Electrostatic effects did not contribute to these predictions in a positive or negative manner. Rather, achieving shape complementarity at macrocycle-target interfaces was a decisive factor. In summary, a combined computational protocol using pre-computed conformational ensembles of macrocycles as a starting point for docking shows promise in modeling binding modes of macrocyclic compounds.

  13. Observations on the Influence of Precursor Conformations on Macrocyclization Reactions

    DEFF Research Database (Denmark)

    Hammershøj, Peter; Beldring, Klavs; Nielsen, Anders R.;


    Macrocycles hold great promise in drug discovery as an underutilized class of lead compounds. The low abundance of these molecules can, in part, be explained by the inherent difficulties in the synthesis of macrocycles and the lack of general methods for their rapid assembly. We have undertaken...... a research program aimed at developing methods for facile synthesis of macrocycles from simple precursors. The synthesis of two new cyclization precursors is described and the results of their reaction with thionyl chloride are presented and discussed. Whereas one acyclic diol smoothly underwent...

  14. A bambusuril macrocycle that binds anions in water with high affinity and selectivity. (United States)

    Yawer, Mirza Arfan; Havel, Vaclav; Sindelar, Vladimir


    Synthetic receptors that function in water are important for the qualitative and quantitative detection of anions, which may act as pollutants in the environment or play important roles in biological processes. Neutral receptors are particularly appealing because they are often more selective than positively charged receptors; however, their affinity towards anions in pure water is only in range of 1-10(3)  L mol(-1) . The anion-templated synthesis of a water-soluble bambusuril derivative is shown to be an outstanding receptor for various inorganic anions in pure water, with association constants of up to 10(7)  L mol(-1) . Furthermore, the macrocycle discriminates between anions with unprecedented selectivity (up to 500 000-fold). We anticipate that the combination of remarkable affinity and selectivity of this macrocycle will enable the efficient detection and isolation of diverse anions in aqueous solutions, which is not possible with current supramolecular systems.

  15. Increasing AIP Macrocycle Size Reveals Key Features of agr Activation in Staphylococcus aureus. (United States)

    Johnson, Jeffrey G; Wang, Boyuan; Debelouchina, Galia T; Novick, Richard P; Muir, Tom W


    The agr locus in the commensal human pathogen, Staphylococcus aureus, is a two-promoter regulon with allelic variability that produces a quorum-sensing circuit involved in regulating virulence within the bacterium. Secretion of unique autoinducing peptides (AIPs) and detection of their concentrations by AgrC, a transmembrane receptor histidine kinase, coordinates local bacterial population density with global changes in gene expression. The finding that staphylococcal virulence can be inhibited through antagonism of this quorum-sensing pathway has fueled tremendous interest in understanding the structure-activity relationships underlying the AIP-AgrC interaction. The defining structural feature of the AIP is a 16-membered, thiolactone-containing macrocycle. Surprisingly, the importance of ring size on agr activation or inhibition has not been explored. In this study, we address this deficiency through the synthesis and functional analysis of AIP analogues featuring enlarged and reduced macrocycles. Notably, this study is the first to interrogate AIP function by using both established cell-based reporter gene assays and newly developed in vitro AgrC-I binding and autophosphorylation activity assays. Based on our data, we present a model for robust agr activation involving a cooperative, three-points-of-contact interaction between the AIP macrocycle and AgrC.

  16. Enantiocontrol in Macrocycle Formation from Catalytic MetalCarbene Transformations

    Institute of Scientific and Technical Information of China (English)

    DOYLE, Michael P.; DOYLE, Michael P; HU, Wen-Hao(胡文浩); 胡文浩


    The development of catalytic metal carbene transformations for the construction of macrocyclic lactones has dramatically increased their synthetic advantages.This is the first review of this developing methodology.

  17. Structural basis for precursor protein-directed ribosomal peptide macrocyclization

    Energy Technology Data Exchange (ETDEWEB)

    Li, Kunhua; Condurso, Heather L.; Li, Gengnan; Ding, Yousong; Bruner, Steven D. (Florida)


    Macrocyclization is a common feature of natural product biosynthetic pathways including the diverse family of ribosomal peptides. Microviridins are architecturally complex cyanobacterial ribosomal peptides that target proteases with potent reversible inhibition. The product structure is constructed via three macrocyclizations catalyzed sequentially by two members of the ATP-grasp family, a unique strategy for ribosomal peptide macrocyclization. Here we describe in detail the structural basis for the enzyme-catalyzed macrocyclizations in the microviridin J pathway of Microcystis aeruginosa. The macrocyclases MdnC and MdnB interact with a conserved α-helix of the precursor peptide using a novel precursor-peptide recognition mechanism. The results provide insight into the unique protein–protein interactions that are key to the chemistry, suggest an origin for the natural combinatorial synthesis of microviridin peptides, and provide a framework for future engineering efforts to generate designed compounds.

  18. Synthesis of novel symmetrical macrocycle via oxidative homocoupling of bisalkyne

    Energy Technology Data Exchange (ETDEWEB)

    Kamalulazmy, Nurulain; Hassan, Nurul Izzaty [School of Chemical Sciences and Food Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor Darul Ehsan (Malaysia)


    A novel symmetrical macrocycle has been synthesised via oxidative homocoupling of bisalkyne, diprop-2-ynyl pyridine-2,6-dicarboxylate mediated by copper (I) iodide (CuI) and 4-dimethylaminopyridine (DMAP). The precursor compound was synthesised from 2,6-pyridine dicarbonyl dichloride and propargyl alcohol in the presence of triethylamine. The reaction mixture was stirred overnight and further purified via column chromatograpy with 76% yield. Single crystal for X-ray study was obtained by recrystallization from acetone. Subsequently, a symmetrical macrocycle was synthesised from oxidative homocoupling of precursor compound in open atmosphere. The crude product was purified by column chromatography to furnish macrocycle compound with 5% yield. Both compounds were characterised by IR, {sup 1}H and {sup 13}C NMR and mass spectral techniques. The unusual conformation of the bisalkyne and twisted conformation of designed macrocycle has influence the percentage yield. This has been studied thoroughly by X-ray crystallography and electronic structure calculations.

  19. Dynamic covalent chemistry approaches toward macrocycles, molecular cages, and polymers. (United States)

    Jin, Yinghua; Wang, Qi; Taynton, Philip; Zhang, Wei


    The current research in the field of dynamic covalent chemistry includes the study of dynamic covalent reactions, catalysts, and their applications. Unlike noncovalent interactions utilized in supramolecular chemistry, the formation/breakage of covalent bonding has slower kinetics and usually requires the aid of a catalyst. Catalytic systems that enable efficient thermodynamic equilibrium are thus essential. In this Account, we describe the development of efficient catalysts for alkyne metathesis, and discuss the application of dynamic covalent reactions (mainly imine, olefin, and alkyne metathesis) in the development of organic functional materials. Alkyne metathesis is an emerging dynamic covalent reaction that offers robust and linear acetylene linkages. By introducing a podand motif into the catalyst ligand design, we have developed a series of highly active and robust alkyne metathesis catalysts, which, for the first time, enabled the one-step covalent assembly of ethynylene-linked functional molecular cages. Imine chemistry and olefin metathesis are among the most well-established reversible reactions, and have also been our main synthetic tools. Various shape-persistent macrocycles and covalent organic polyhedrons have been efficiently constructed in one-step through dynamic imine chemistry and olefin metathesis. The geometrical features and solubilizing groups of the building blocks as well as the reaction kinetics have significant effect on the outcome of a covalent assembly process. More recently, we explored the orthogonality of imine and olefin metatheses, and successfully synthesized heterosequenced macrocycles and molecular cages through one-pot orthogonal dynamic covalent chemistry. In addition to discrete molecular architectures, functional polymeric materials can also be accessed through dynamic covalent reactions. Defect-free solution-processable conjugated polyaryleneethynylenes and polydiacetylenes have been prepared through alkyne metathesis

  20. Push-pull macrocycles: donor-acceptor compounds with paired linearly conjugated or cross-conjugated pathways. (United States)

    Leu, Wade C W; Fritz, Amanda E; Digianantonio, Katherine M; Hartley, C Scott


    Two-dimensional π-systems are of current interest in the design of functional organic molecules, exhibiting unique behavior for applications in organic electronics, single-molecule devices, and sensing. Here we describe the synthesis and characterization of "push-pull macrocycles": electron-rich and electron-poor moieties linked by a pair of (matched) conjugated bridges. We have developed a two-component macrocyclization strategy that allows these structures to be synthesized with efficiencies comparable to acyclic donor-bridge-acceptor systems. Compounds with both cross-conjugated (m-phenylene) and linearly conjugated (2,5-thiophene) bridges have been prepared. As expected, the compounds undergo excitation to locally excited states followed by fluorescence from charge-transfer states. The m-phenylene-based systems exhibit slower charge-recombination rates presumably due to reduced electronic coupling through the cross-conjugated bridges. Interestingly, pairing the linearly conjugated 2,5-thiophene bridges also slows charge recombination. DFT calculations of frontier molecular orbitals show that the direct HOMO-LUMO transition is polarized orthogonal to the axis of charge transfer for these symmetrical macrocyclic architectures, reducing the electronic coupling. We believe the push-pull macrocycle design may be useful in engineering functional frontier molecular orbital symmetries.

  1. Macrocycle peptides delineate locked-open inhibition mechanism for microorganism phosphoglycerate mutases

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Hao; Dranchak, Patricia; Li, Zhiru; MacArthur, Ryan; Munson, Matthew S.; Mehzabeen, Nurjahan; Baird, Nathan J.; Battalie, Kevin P.; Ross, David; Lovell, Scott; Carlow, Clotilde K.S.; Suga, Hiroaki; Inglese, James (U of Tokyo); (NEB); (Kansas); (NIH); (NIST); (HHMI)


    Glycolytic interconversion of phosphoglycerate isomers is catalysed in numerous pathogenic microorganisms by a cofactor-independent mutase (iPGM) structurally distinct from the mammalian cofactor-dependent (dPGM) isozyme. The iPGM active site dynamically assembles through substrate-triggered movement of phosphatase and transferase domains creating a solvent inaccessible cavity. Here we identify alternate ligand binding regions using nematode iPGM to select and enrich lariat-like ligands from an mRNA-display macrocyclic peptide library containing >1012 members. Functional analysis of the ligands, named ipglycermides, demonstrates sub-nanomolar inhibition of iPGM with complete selectivity over dPGM. The crystal structure of an iPGM macrocyclic peptide complex illuminated an allosteric, locked-open inhibition mechanism placing the cyclic peptide at the bi-domain interface. This binding mode aligns the pendant lariat cysteine thiolate for coordination with the iPGM transition metal ion cluster. The extended charged, hydrophilic binding surface interaction rationalizes the persistent challenges these enzymes have presented to small-molecule screening efforts highlighting the important roles of macrocyclic peptides in expanding chemical diversity for ligand discovery.

  2. Redox-Active Tetraruthenium Macrocycles Built from 1,4-Divinylphenylene-Bridged Diruthenium Complexes. (United States)

    Scheerer, Stefan; Linseis, Michael; Wuttke, Evelyn; Weickert, Sabrina; Drescher, Malte; Tröppner, Oliver; Ivanović-Burmazović, Ivana; Irmler, Andreas; Pauly, Fabian; Winter, Rainer F


    Metallamacrocylic tetraruthenium complexes were generated by treatment of 1,4-divinylphenylene-bridged diruthenium complexes with functionalized 1,3-benzene dicarboxylic acids and characterized by HR ESI-MS and multinuclear NMR spectroscopy. Every divinylphenylene diruthenium subunit is oxidized in two consecutive one-electron steps with half-wave potential splittings in the range of 250 to 330 mV. Additional, smaller redox-splittings between the +/2+ and 0/+ and the 3+/4+ and 2+/3+ redox processes, corresponding to the first and the second oxidations of every divinylphenylene diruthenium entity, are due to electrostatic effects. The lack of electronic coupling through bond or through space is explained by the nodal properties of the relevant molecular orbitals and the lateral side-by-side arrangement of the divinylphenylene linkers. The polyelectrochromic behavior of the divinylphenylene diruthenium precursors is retained and even amplified in these metallamacrocyclic structures. EPR studies down to T=4 K indicate that the dications 1-H(2+) and 1-OBu(2+) are paramagnetic. The dications and the tetracation of macrocycle 3-H display intense (dications) or weak (3-H(4+) ) EPR signals. Quantum chemical calculations indicate that the four most stable conformers of the macrocycles are largely devoid of strain. Bond parameters, energies as well as charge and spin density distributions of model macrocycle 5-H(Me) were calculated for the different charge and spin states.


    NARCIS (Netherlands)



    A chemically modified field-effect transistor (CHEMFET) with satisfactory Ag+ selectivity is described. The potentiometric Ag+ selectivities of CHEMFETs with plasticized PVC membranes based on macrocyclic thioethers have been determined. All the macrocyclic thioethers tested showed silver response a

  4. Macrocyclic Assembly: A Dive into the Pecking Order and Applied Aspects of Multitalented Metallomacrocycles

    Directory of Open Access Journals (Sweden)

    Ashu Chaudhary


    Full Text Available To aid in knowledge of macrocyclic complexes and biomedical scientists, we are presenting here a review article with compilation of work done so far along in relation to macrocyclic ligands and their metal complexes. The metal ion chemistry of macrocyclic ligands has now become a major subdivision of coordination chemistry. This overview focuses on developments in design, synthesis, and self-assembly of metal-based architectures and ligands related to macrocyclic chemistry.

  5. Control of olefin geometry in macrocyclic ring-closing metathesis using a removable silyl group. (United States)

    Wang, Yikai; Jimenez, Miguel; Hansen, Anders S; Raiber, Eun-Ang; Schreiber, Stuart L; Young, Damian W


    Introducing a silyl group at one of the internal olefin positions in diolefinic substrates results in E-selective olefin formation in macrocyclic ring-forming metathesis. The application of this method to a range of macrocyclic (E)-alkenylsiloxanes is described. Protodesilylation of alkenylsiloxane products yields novel Z-configured macrocycles.

  6. Biomechanical Assessment of the Strength of Volleyball Players in Different Stages of the Training Macrocycle

    Directory of Open Access Journals (Sweden)

    Śliwa Marcin


    Full Text Available Introduction. In order to help volleyball players achieve superior results, their coaches are constantly seeking new training methods. One of the methods used to improve the effectiveness of the training that is being implemented is conducting tests which make it possible to assess the player’s locomotor system in terms of its motor and biomechanical functions. The aim of the study was to determine the torque of the knee flexor and extensor muscles of volleyball players in three stages of the annual macrocycle.

  7. Molecular Rearrangement of an Aza-Scorpiand Macrocycle Induced by pH: A Computational Study

    Directory of Open Access Journals (Sweden)

    Jesus Vicente De Julián-Ortiz


    Full Text Available Rearrangements and their control are a hot topic in supramolecular chemistry due to the possibilities that these phenomena open in the design of synthetic receptors and molecular machines. Macrocycle aza-scorpiands constitute an interesting system that can reorganize their spatial structure depending on pH variations or the presence of metal cations. In this study, the relative stabilities of these conformations were predicted computationally by semi-empirical and density functional theory approximations, and the reorganization from closed to open conformations was simulated by using the Monte Carlo multiple minimum method.

  8. Carbohydrate-based aza-macrocycles by Richman-Atkins cyclization of glucopyranose precursors. (United States)

    Rathjens, Andreas; Thiem, Joachim


    2, 3-Di-ω-halo- as well as 2, 3-di-ω-toluenesulfonamide-alkylated glucopyranoside derivatives were prepared. Their condensation with α,ω-bis-toluenesulfonamide components under varying Richman-Atkins conditions with alkali carbonate in DMF led to carbohydrate-linked aza-macrocycles displaying 14-, 17-, 18-, 21-, 24-, and 25-membered ring structures. Isomeric aza-macrocylic coronands of 20- as well as 30-membered ring size containing two saccharides could be obtained employing Richman-Atkins condensations of two functionalized sugar building units.

  9. Operation safety of complex industrial systems. Main concepts; Surete de fonctionnement des systemes industriels complexes. Principaux concepts

    Energy Technology Data Exchange (ETDEWEB)

    Zwingelstein, G


    Operation safety consists in knowing, evaluating, foreseeing, measuring and mastering the technological system and human failures in order to avoid their impacts on health and people's safety, on productivity, and on the environment, and to preserve the Earth's resources. This article recalls the main concepts of operation safety: 1 - evolutions in the domain; 2 - failures, missions and functions of a system and of its components: functional failure, missions and functions, industrial processes, notions of probability; 3 - basic concepts and operation safety: reliability, unreliability, failure density, failure rate, relations between them, availability, maintainability, safety. (J.S.)

  10. Tools for Chemical Biology: New Macrocyclic Compounds from Diversity-Oriented Synthesis and Toward Materials from Silver(I) Acetylides

    DEFF Research Database (Denmark)

    Madsen, Charlotte Marie

    Part I The formation of a library of diverse macrocyclic compounds with different functionalities and ring sizes in a few steps from two easily accessible α,ω-diol building blocks is presented. The building blocks are combined by esteriffcations in four different ways leading to the formation of ...... of uoro-iodoadamantanes. However, overall the results provide a good starting point for the synthesis of new triptycene and adamantane-containing molecules that can interact with carbon nanotubes....

  11. Rigid, Conjugated Macrocycles for High Performance Organic Photodetectors. (United States)

    Zhang, Boyuan; Trinh, M Tuan; Fowler, Brandon; Ball, Melissa; Xu, Qizhi; Ng, Fay; Steigerwald, Michael L; Zhu, X-Y; Nuckolls, Colin; Zhong, Yu


    Organic photodetectors (OPDs) are attractive for their high optical absorption coefficient, broad wavelength tunability, and compatibility with lightweight and flexible devices. Here we describe a new molecular design that enables high performance organic photodetectors. We use a rigid, conjugated macrocycle as the electron acceptor in devices to obtain high photocurrent and low dark current. We make a direct comparison between the devices made with the macrocyclic acceptor and an acyclic control molecule; we find that the superior performance of the macrocycle originates from its rigid, conjugated, and cyclic structure. The macrocycle's rigid structure reduces the number of charged defects originating from deformed sp(2) carbons and covalent defects from photo/thermoactivation. With this molecular design, we are able to suppress dark current density while retaining high responsivity in an ultrasensitive nonfullerene OPD. Importantly, we achieve a detectivity of ∼10(14) Jones at near zero bias voltage. This is without the need for extra carrier blocking layers commonly employed in fullerene-based devices. Our devices are comparable to the best fullerene-based photodetectors, and the sensitivity at low working voltages (<0.1 V) is a record for nonfullerene OPDs.

  12. Magnetism in (Semi)Conducting Macrocycles of pi conjugated Polymers (United States)


    estimation of the chain length or the number of repetitive thiophene units, which were for the four samples 18, 25, 33 and 42. The formyl moieties at...leading to radicals , which can associate together. Scheme 5: Synthetic pathway of fully thiophenic bridged macrocycle by oxidative

  13. Flexible macrocycles as versatile supports for catalytically active metal clusters

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, JD; Gagnon, KJ; Teat, SJ; McIntosh, RD


    Here we present three structurally diverse clusters stabilised by the same macrocyclic polyphenol; t-butylcalix[8]arene. This work demonstrates the range of conformations the flexible ligand is capable of adopting, highlighting its versatility in metal coordination. In addition, a Ti complex displays activity for the ring-opening polymerisation of lactide

  14. Synthesis of macrocyclic lactones with methoxysulfonyl side chain

    Institute of Scientific and Technical Information of China (English)

    Chuan Jin Hou; Xiao Mei Liang; Jing Ping Wu; Dao Quan Wang


    Two representative macrocyclic lactones with methoxysulfonyl side chain (5a and 5b) were synthesized employing Michael addition with acrolein and ring enlargement as the key steps,starting from potassium a-oxocycloalkylsulfonates (1) in total yields of 45 and 57%,respectively.

  15. Synthesis of new diverse macrocycles from diol precursors

    DEFF Research Database (Denmark)

    Madsen, Charlotte Marie; Hansen, Martin; Thrane, Marie V.;


    The formation of a library of diverse macrocycles with different ring sizes from two easily accessible building blocks is presented. Reacting diol precursors with electrophilic reagents lead to 17-membered sulfites and 19-membered malonates in 34–79% yield. Double-reductive amination of dialdehyd...

  16. Schiff base oligopyrrolic macrocycles as ligands for lanthanides and actinides

    Energy Technology Data Exchange (ETDEWEB)

    Sessler, Jonathan L. [Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station A5300, University of Texas at Austin, Austin, TX 78712-0165 (United States)]. E-mail:; Melfi, Patricia J. [Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station A5300, University of Texas at Austin, Austin, TX 78712-0165 (United States); Tomat, Elisa [Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station A5300, University of Texas at Austin, Austin, TX 78712-0165 (United States); Callaway, Wyeth [Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station A5300, University of Texas at Austin, Austin, TX 78712-0165 (United States); Huggins, Michael T. [Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station A5300, University of Texas at Austin, Austin, TX 78712-0165 (United States); Gordon, Pamela L. [C-Chemistry and NMT-Nuclear Materials Technology Divisions, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Webster Keogh, D. [C-Chemistry and NMT-Nuclear Materials Technology Divisions, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Date, Richard W. [Department of Chemistry, University of Exeter, Stocker Road, Exeter EX4 4QD (United Kingdom); Bruce, Duncan W. [Department of Chemistry, University of Exeter, Stocker Road, Exeter EX4 4QD (United Kingdom); Department of Chemistry, University of York, Heslington, YORK YO10 5DD (United Kingdom); Donnio, Bertrand [Institut de Physique et Chimie des Materiaux de Strasbourg (IPCMS), Groupe des Materiaux Organiques (GMO), CNRS-ULP - UMR 7504, 23 rue du Loess BP 43, F-67034 Strasbourg Cedex 2 (France)


    The coordination of f-block cations with Schiff base oligopyrrolic macrocycles is discussed. Analysis of the mesophase of a uranyl 2,5-diformylpyrrole-derived expanded porphyrin complex through temperature-dependent X-ray diffraction (XRD) methods has provided evidence for liquid-crystalline properties, and for molecular stacking into columns, arranged in a 2D hexagonal lattice. In separate studies, UV-vis spectral analysis has indicated the formation of three new f-block oligopyrrolic complexes. Addition of neptunyl ([NpO{sub 2}]{sup 2+}) or plutonyl ([PuO{sub 2}]{sup 2+}) chloride salts to the free base of a dipyrromethane-derived Schiff base macrocycle induces an immediate spectral change, namely the growth of a Q-like band at 630 nm. Such changes in the absorption spectra cause a dramatic color change from pale yellow to blue. It is postulated that oxidation of this macrocycle, stimulated by reduction of the metal center, leads to the observed spectral changes. An immediate visible and spectral change is also observed with the reaction of lutetium silylamide (Lu[N(Si(CH{sub 3}){sub 3}){sub 2}]{sub 3}), with a different, tetrapyrrole-containing Schiff base macrocycle. In this case, the formation of a complex with 1:1 metal-to-ligand binding stoichiometry is further supported by MALDI-TOF mass spectrometry.

  17. The Porphobilinogen Conundrum in Prebiotic Routes to Tetrapyrrole Macrocycles (United States)

    Taniguchi, Masahiko; Ptaszek, Marcin; Chandrashaker, Vanampally; Lindsey, Jonathan S.


    Attempts to develop a credible prebiotic route to tetrapyrroles have relied on enzyme-free recapitulation of the extant biosynthesis, but this process has foundered from the inability to form the pyrrole porphobilinogen ( PBG) in good yield by self-condensation of the precursor δ-aminolevulinic acid ( ALA). PBG undergoes robust oligomerization in aqueous solution to give uroporphyrinogen (4 isomers) in good yield. ALA, PBG, and uroporphyrinogen III are universal precursors to all known tetrapyrrole macrocycles. The enzymic formation of PBG entails carbon-carbon bond formation between the less stable enolate/enamine of one ALA molecule (3-position) and the carbonyl/imine (4-position) of the second ALA molecule; without enzymes, the first ALA reacts at the more stable enolate/enamine (5-position) and gives the pyrrole pseudo-PBG. pseudo-PBG cannot self-condense, yet has one open α-pyrrole position and is proposed to be a terminator of oligopyrromethane chain-growth from PBG. Here, 23 analogues of ALA have been subjected to density functional theoretical (DFT) calculations, but no motif has been identified that directs reaction at the 3-position. Deuteriation experiments suggested 5-(phosphonooxy)levulinic acid would react preferentially at the 3- versus 5-position, but a hybrid condensation with ALA gave no observable uroporphyrin. The results suggest efforts toward a biomimetic, enzyme-free route to tetrapyrroles from ALA should turn away from structure-directed reactions and focus on catalysts that orient the two aminoketones to form PBG in a kinetically controlled process, thereby avoiding formation of pseudo-PBG.

  18. Through-space electronic communication of zinc phthalocyanine with substituted [60]Fullerene bearing O2Nxaza-crown macrocyclic ligands (United States)

    Ghanbari, Bahram; Shahhoseini, Leila; Mahlooji, Niloofar; Gholamnezhad, Parisa; Taheri Rizi, Zahra


    Two new macrocyclic ligands containing 17- and 19-membered O2N3-donor aza-crowns anchored to [60]Fullerene were synthesized and characterized by employing HPLC, electrospray ionization mass (ESI-MS), 1H and 13C NMR, UV-vis, IR spectroscopies, as well as powder X-ray diffraction (PXRD) and thermogravimetric analysis (TGA) in solid state. TGA measurements revealed that upon linking each of these macrocycle rings to [60]Fullerene, the decomposition point measured for [60]Fullerene moiety was increased, indicating on the promoted stability of [60]Fullerene backbone during binding to these macrocyclic ligands. Moreover, the ground state non-covalent interactions of [60]Fullerene derivatives of O2Nx (x = 2, and 3) aza-crown macrocyclic ligands namely, L1-L4 with zinc phthalocyanine (ZnPc) were also investigated by UV-vis absorption, steady state and time resolved fluorescence spectrophotometry in N-methyl-2-pyrrolidone (NMP). The calculation of Stern-Volmer constants (KSV) indicated on existence of an efficient quenching mechanism comprising of the excited singlet state of ZnPc in the presence of L1-L4. The observation of an appropriate correlation between decrease in fluorescence intensity and lifetime parameters led us to propose the occurrence of a static mechanism for the fluorescence quenching of ZnPc in the presence of L1-L3. The binding constants (KBH) of L1-L4/ZnPc were also determined applying the fluorescence quenching experiments. Meanwhile, the incompatibility of both KSV and KBH values found for L4 was also described in terms of structural features using DFT calculations using the B3LYP functional and 6-31G* basis set.

  19. The role of macrocyclic compounds in the extraction and possible separation of platinum and rhodium from chloride solutions (United States)

    Jyothi, Rajesh Kumar; Lee, Jin-Young


    Macrocyclic compounds (crown ethers), specifically 18-crown-6 (18-C-6), benzo-15-crown-5 (B-15-C-5), di-benzo-18-crown-6 (DB-18-C-6) and di-cyclohexano-18-crown-6 (DC-18C-6), are used as extractants as well as synergists with amine-group extractants. Platinum and rhodium belong to platinum-group metals (PGMs) and have very similar ionic radii and similar properties. The separation of PGMs is most useful for the preparation of functional materials. Macrocyclic compounds are tested for platinum and rhodium separation and are found to achieve marginal separation. Amines (used as extractants) are paired with macrocyclic compounds (used as synergists), and the separation factor between platinum and rhodium is increased with synergistic enhancement from a chloride solution. The present study discusses extraction chemistry, separation factors and the synergy between platinum and rhodium from chloride solutions. To ensure accurate data, the aqueous samples in this study are analyzed using an inductively coupled plasma optical emission spectrometer (ICP-OES).

  20. Gold-catalyzed Synthesis of Pyridine Containing Macrocycles, Related to Porphyrin

    Institute of Scientific and Technical Information of China (English)

    DYKER,Gerald; LIU,Jian-Hui; MERZ,Klaus


    @@ Porphyrins are very important substances used in a wide range of model systems in many areas, such as biomimic chemistry and material science. This kind of macrocycle generally consists of 5-membered ring to form a cyclic extended aromatic network. Recently much work have been done concerning the modification of porphyrins core structures, and many kinds of analogues have been recorded. One of the important aspects was the research of the porphyrinogen ligand.These macrocycles bear functional resemblance to certain kind of polydentate ligand, and provide a variety of tri-dimensional binding cavities for metal ions. In addition, some other kinds of analogues have been recorded, involving the introduction of a CH unit to replace one of the nitrogen atoms. We also notice the fact that pyridine is a very effective ligand, and it can coordinate with many kinds of metals. Based on these observations, we would like to design and synthesize a new porphyrinogen (5) analogue containing a NNNN core, two of the N atoms from pyrrole and the other two N from pyridine. Such core modifications may alter the electronic structure of the ring and provide variable cavity for metal coordination.

  1. Le comportement mécanique des risers. Influence des principaux paramètres Mechanical Behaviour of Marine Risers Mode of Influence of Principal Parameters

    Directory of Open Access Journals (Sweden)

    Sparks C.


    Full Text Available Cet article a pour but de déterminer les principaux paramètres qui gouvernent le comportement mécanique des risers de forage et de production, et d'expliquer pourquoi et comment ils interviennent. Une compréhension claire de ces influences permet d'optimiser rapidement un riser donné sans avoir recours à un grand nombre d'analyses par ordinateur. Celui qui conçoit un riser est principalement préoccupé par les points suivants : - niveaux de contraintes dans la partie courante du riser ; - mouvements angulaires à la base du riser (ou moments, dans le cas d'une liaison rigide ; - mouvements relatifs au niveau de la liaison plate-forme/riser. La méthode utilisée dans cet article consiste à établir des expressions analytiques valables pour des risers simplifiés. Les conclusions tirées de ces expressions ont ensuite été verifiéés à l'aide d'un programme de calcul capable de simuler le comportement dynamique d'un riser dans des configurations variées. This paper attempts to identify the principal parameters, that influence the behavior of drilling and production risers and to explain how and why they do so. Clear understanding of these influences enable particular risers to be optimised rapidly without recourse to an inordinate number of computer analyses. The points of greatest concern, to the riser designer, are: a Stress levels in the main length of riser. (b Angular movement at sea bed (or moment, if the connection is rigid. (c Relative movement at riser/platform connection. The approach, used in the paper, has been ta derive analytical expressions, for simplified riser cases. Conclusions drawn from these expressions have then been checked for validity, by using a dynamic analysis computer program to simulate a wide range of cases.

  2. Supramolecular polymers constructed from macrocycle-based host-guest molecular recognition motifs. (United States)

    Dong, Shengyi; Zheng, Bo; Wang, Feng; Huang, Feihe


    CONSPECTUS: Supramolecular polymers, fabricated via the combination of supramolecular chemistry and polymer science, are polymeric arrays of repeating units held together by reversible, relatively weak noncovalent interactions. The introduction of noncovalent interactions, such as hydrogen bonding, aromatic stacking interactions, metal coordination, and host-guest interactions, endows supramolecular polymers with unique stimuli responsiveness and self-adjusting abilities. As a result, diverse monomer structures have been designed and synthesized to construct various types of supramolecular polymers. By changing the noncovalent interaction types, numbers, or chemical structures of functional groups in these monomers, supramolecular polymeric materials can be prepared with tailored chemical and physical properties. In recent years, the interest in supramolecular polymers has been extended from the preparation of intriguing topological structures to the discoveries of potential applications as functional materials. Compared with traditional polymers, supramolecular polymers show some advantages in the fabrication of reversible or responsive materials. The development of supramolecular polymers also offers a platform to construct complex and sophisticated materials with a bottom-up approach. Macrocylic hosts, including crown ethers, cyclodextrins, calixarenes, cucurbiturils, and pillararenes, are the most commonly used building blocks in the fabrication of host-guest interaction-based supramolecular polymers. With the introduction of complementary guest molecules, macrocylic hosts demonstrate selective and stimuli-responsive host-guest complexation behaviors. By elaborate molecular design, the resultant supramolecular polymers can exhibit diverse structures based on the self-selectivity of host-guest interactions. The introduction of reversible host-guest interactions can further endow these supramolecular polymers with interesting and fascinating chemical

  3. Synthesis of arylenealkyne conjugated macrocycles containing a long alkylene bridge

    Institute of Scientific and Technical Information of China (English)

    Xiaohong CHENG; Sigurd HOEGER


    The synthesis of the first two arylenealkyne conjugated macrocycles containing a long alkylene bridge via Glaser coupling of template-directed tetra-acetylenes was reported. Tetraacetylene intermediates with complex structures were constructed rapidly via quadruple Hagihara coupling of monoprotected bisace-tylenes to appropriate tetraiodides and subsequent desilylation. The characterization of such compounds was carried out by NMR, GPC and UV-Vis spectra. Unfortunately, the two compounds were not liquid crystals and had no biaxial nematic mesophase character as expected,

  4. A diversity-oriented synthesis strategy enabling the combinatorial-type variation of macrocyclic peptidomimetic scaffolds. (United States)

    Isidro-Llobet, Albert; Hadje Georgiou, Kathy; Galloway, Warren R J D; Giacomini, Elisa; Hansen, Mette R; Méndez-Abt, Gabriela; Tan, Yaw Sing; Carro, Laura; Sore, Hannah F; Spring, David R


    Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of structural, and thus shape, diversity. In particular, there is a lack of scaffold diversity in current macrocyclic peptidomimetic libraries; indeed, the efficient construction of diverse molecular scaffolds presents a formidable general challenge to the synthetic chemist. Herein we describe a new, advanced strategy for the diversity-oriented synthesis (DOS) of macrocyclic peptidomimetics that enables the combinatorial variation of molecular scaffolds (core macrocyclic ring architectures). The generality and robustness of this DOS strategy is demonstrated by the step-efficient synthesis of a structurally diverse library of over 200 macrocyclic peptidomimetic compounds, each based around a distinct molecular scaffold and isolated in milligram quantities, from readily available building-blocks. To the best of our knowledge this represents an unprecedented level of scaffold diversity in a synthetically derived library of macrocyclic peptidomimetics. Cheminformatic analysis indicated that the library compounds access regions of chemical space that are distinct from those addressed by top-selling brand-name drugs and macrocyclic natural products, illustrating the value of our DOS approach to sample regions of chemical space underexploited in current drug discovery efforts. An analysis of three-dimensional molecular shapes illustrated that the DOS library has a relatively high level of shape diversity.

  5. Reprint of: Enantiomeric separation of functionalized ethano-bridged Tröger bases using macrocyclic cyclofructan and cyclodextrin chiral selectors in high-performance liquid chromatography and capillary electrophoresis with application of principal component analysis. (United States)

    Weatherly, Choyce A; Na, Yun-Cheol; Nanayakkara, Yasith S; Woods, Ross M; Sharma, Ankit; Lacour, Jérôme; Armstrong, Daniel W


    The enantiomeric separation of a series of racemic functionalized ethano-bridged Tröger base compounds was examined by high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Using HPLC and CE the entire set of 14 derivatives was separated by chiral stationary phases (CSPs) and chiral additives composed of cyclodextrin (native and derivatized) and cyclofructan (derivatized). Baseline separations (Rs ≥ 1.5) in HPLC were achieved for 13 of the 14 compounds with resolution values as high as 5.0. CE produced 2 baseline separations. The separations on the cyclodextrin CSPs showed optimum results in the reversed phase mode, and the LARIHC cyclofructan CSPs separations showed optimum results in the normal phase mode. HPLC separation data of the compounds was analyzed using principal component analysis (PCA). The PCA biplot analysis showed that retention is governed by the size of the R1 substituent in the case of derivatized cyclofructan and cyclodextrin CSPs, and enantiomeric resolution closely correlated with the size of the R2 group in the case of non-derivatized γ-cyclodextrin CSP. It is clearly shown that chromatographic retention is necessary but not sufficient for the enantiomeric separations of these compounds.

  6. Enantiomeric separation of functionalized ethano-bridged Tröger bases using macrocyclic cyclofructan and cyclodextrin chiral selectors in high-performance liquid chromatography and capillary electrophoresis with application of principal component analysis. (United States)

    Weatherly, Choyce A; Na, Yun-Cheol; Nanayakkara, Yasith S; Woods, Ross M; Sharma, Ankit; Lacour, Jérôme; Armstrong, Daniel W


    The enantiomeric separation of a series of racemic functionalized ethano-bridged Tröger base compounds was examined by high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Using HPLC and CE the entire set of 14 derivatives was separated by chiral stationary phases (CSPs) and chiral additives composed of cyclodextrin (native and derivatized) and cyclofructan (derivatized). Baseline separations (Rs≥1.5) in HPLC were achieved for 13 of the 14 compounds with resolution values as high as 5.0. CE produced 2 baseline separations. The separations on the cyclodextrin CSPs showed optimum results in the reversed phase mode, and the LARIHC™ cyclofructan CSPs separations showed optimum results in the normal phase mode. HPLC separation data of the compounds was analyzed using principal component analysis (PCA). The PCA biplot analysis showed that retention is governed by the size of the R1 substituent in the case of derivatized cyclofructan and cyclodextrin CSPs, and enantiomeric resolution closely correlated with the size of the R2 group in the case of non-derivatized γ-cyclodextrin CSP. It is clearly shown that chromatographic retention is necessary but not sufficient for the enantiomeric separations of these compounds.

  7. Kinetically E-selective macrocyclic ring-closing metathesis (United States)

    Shen, Xiao; Nguyen, Thach T.; Koh, Ming Joo; Xu, Dongmin; Speed, Alexander W. H.; Schrock, Richard R.; Hoveyda, Amir H.


    Macrocyclic compounds are central to the development of new drugs, but preparing them can be challenging because of the energy barrier that must be surmounted in order to bring together and fuse the two ends of an acyclic precursor such as an alkene (also known as an olefin). To this end, the catalytic process known as ring-closing metathesis (RCM) has allowed access to countless biologically active macrocyclic organic molecules, even for large-scale production. Stereoselectivity is often critical in such cases: the potency of a macrocyclic compound can depend on the stereochemistry of its alkene; alternatively, one isomer of the compound can be subjected to stereoselective modification (such as dihydroxylation). Kinetically controlled Z-selective RCM reactions have been reported, but the only available metathesis approach for accessing macrocyclic E-olefins entails selective removal of the Z-component of a stereoisomeric mixture by ethenolysis, sacrificing substantial quantities of material if E/Z ratios are near unity. Use of ethylene can also cause adventitious olefin isomerization—a particularly serious problem when the E-alkene is energetically less favoured. Here, we show that dienes containing an E-alkenyl–B(pinacolato) group, widely used in catalytic cross-coupling, possess the requisite electronic and steric attributes to allow them to be converted stereoselectively to E-macrocyclic alkenes. The reaction is promoted by a molybdenum monoaryloxide pyrrolide complex and affords products at a yield of up to 73 per cent and an E/Z ratio greater than 98/2. We highlight the utility of the approach by preparing recifeiolide (a 12-membered-ring antibiotic) and pacritinib (an 18-membered-ring enzyme inhibitor), the Z-isomer of which is less potent than the E-isomer. Notably, the 18-membered-ring moiety of pacritinib—a potent anti-cancer agent that is in advanced clinical trials for treating lymphoma and myelofibrosis—was prepared by RCM carried out at a

  8. Biologically Active Macrocyclic Compounds – from Natural Products to Diversity‐Oriented Synthesis

    DEFF Research Database (Denmark)

    Madsen, Charlotte Marie; Clausen, Mads Hartvig


    Macrocyclic compounds are attractive targets when searching for molecules with biological activity. The interest in this compound class is increasing, which has led to a variety of methods for tackling the difficult macrocyclization step in their synthesis. This microreview highlights some recent...

  9. Hydrogen bond templated 1:1 macrocyclization through an olefin metathesis/hydrogenation sequence. (United States)

    Trita, Andrada Stefania; Roisnel, Thierry; Mongin, Florence; Chevallier, Floris


    The construction of pyridine-containing macrocyclic architectures using a nonmetallic template is described. 4,6-Dichlororesorcinol was used as an exotemplate to self-organize two aza-heterocyclic units by OH···N hydrogen bonds. Subsequent sequential double olefin metathesis/hydrogenation reactions employing a single ruthenium-alkylidene precatalyst open access to macrocyclic molecules.

  10. Metal-macrocycle framework (MMF): supramolecular nano-channel surfaces with shape sorting capability. (United States)

    Tashiro, Shohei; Kubota, Ryou; Shionoya, Mitsuhiko


    Hollow nanostructures for the functional assembly of chemical groups with inner surface geometry and regulable stoichiometry enable steric design of interior reaction centers. Herein we report a metal-macrocycle framework (MMF) that forms single-crystalline nanochannels with five distinct enantiomeric pairs of guest binding pockets. During crystal-soaking experiments, the MMF crystals can encapsulate aromatic molecules with high site selectivity. First, constitutional isomers of dibromobenzene are captured and sorted into different binding pockets. Second, each of the optical isomers of (1R/1S)-1-(3-chlorophenyl)ethanol is included diastereoselectively into one of an enantiomeric pair of binding pockets. An advantage of this strategy is that the interior walls can be "repainted" via replacement of the trapped molecules with alternatives. Such guest uptake behaviors would allow highly regioselective or stereoselective reactions within the nanochannel.

  11. The mechanism of patellamide macrocyclization revealed by the characterization of the PatG macrocyclase domain. (United States)

    Koehnke, Jesko; Bent, Andrew; Houssen, Wael E; Zollman, David; Morawitz, Falk; Shirran, Sally; Vendome, Jeremie; Nneoyiegbe, Ada F; Trembleau, Laurent; Botting, Catherine H; Smith, Margaret C M; Jaspars, Marcel; Naismith, James H


    Peptide macrocycles are found in many biologically active natural products. Their versatility, resistance to proteolysis and ability to traverse membranes has made them desirable molecules. Although technologies exist to synthesize such compounds, the full extent of diversity found among natural macrocycles has yet to be achieved synthetically. Cyanobactins are ribosomal peptide macrocycles encompassing an extraordinarily diverse range of ring sizes, amino acids and chemical modifications. We report the structure, biochemical characterization and initial engineering of the PatG macrocyclase domain of Prochloron sp. from the patellamide pathway that catalyzes the macrocyclization of linear peptides. The enzyme contains insertions in the subtilisin fold to allow it to recognize a three-residue signature, bind substrate in a preorganized and unusual conformation, shield an acyl-enzyme intermediate from water and catalyze peptide bond formation. The ability to macrocyclize a broad range of nonactivated substrates has wide biotechnology applications.

  12. The mechanism of patellamide macrocyclization revealed by the characterization of the PatG macrocyclase domain (United States)

    Koehnke, Jesko; Bent, Andrew; Houssen, Wael E; Zollman, David; Morawitz, Falk; Shirran, Sally; Vendome, Jeremie; Nneoyiegbe, Ada F; Trembleau, Laurent; Botting, Catherine H; Smith, Margaret C M; Jaspars, Marcel; Naismith, James H


    Peptide macrocycles are found in many biologically active natural products. Their versatility, resistance to proteolysis and ability to traverse membranes has made them desirable molecules. Although technologies exist to synthesize such compounds, the full extent of diversity found among natural macrocycles has yet to be achieved synthetically. Cyanobactins are ribosomal peptide macrocycles encompassing an extraordinarily diverse range of ring sizes, amino acids and chemical modifications. We report the structure, biochemical characterization and initial engineering of the PatG macrocyclase domain of Prochloron sp. from the patellamide pathway that catalyzes the macrocyclization of linear peptides. The enzyme contains insertions in the subtilisin fold to allow it to recognize a three-residue signature, bind substrate in a preorganized and unusual conformation, shield an acyl-enzyme intermediate from water and catalyze peptide bond formation. The ability to macrocyclize a broad range of nonactivated substrates has wide biotechnology applications. PMID:22796963

  13. Pyrazine motif containing hexagonal macrocycles: synthesis, characterization, and host-guest chemistry with nitro aromatics. (United States)

    Bhowmick, Sourav; Chakraborty, Sourav; Das, Atanu; Nallapeta, Sivaramaiah; Das, Neeladri


    The synthesis and characterization of cationic two-dimensional metallamacrocycles having a hexagonal shape and cavity are described. Both macrocycles utilize a pyrazine motif containing an organometallic acceptor tecton with platinum(II) centers along with different donor ligands. While one macrocycle is a relatively larger [6 + 6], the other is a relatively smaller [2 + 2] polygon. A unique feature of the smaller ensemble is that it is an irregular polygon in which all six edges are not of equal length. Molecular modeling of these macrocycles confirmed the presence of hexagonal cavities. The ability of these π-electron rich macrocycles to act as potential hosts for relatively electron deficient nitroaromatics (DNT = 2,4-dinitrotoluene and PA = picric acid) has been studied using isothermal titration calorimetry (ITC) as a tool. Molecular dynamics simulation studies were subsequently performed to gain critical insight into the binding interactions between the nitroaromatic guest molecules (PA/DNT) and the ionic macrocycles reported herein.

  14. The posttranslational modification cascade to the thiopeptide berninamycin generates linear forms and altered macrocyclic scaffolds. (United States)

    Malcolmson, Steven J; Young, Travis S; Ruby, J Graham; Skewes-Cox, Peter; Walsh, Christopher T


    Berninamycin is a member of the pyridine-containing thiopeptide class of antibiotics that undergoes massive posttranslational modifications from ribosomally generated preproteins. Berninamycin has a 2-oxazolyl-3-thiazolyl-pyridine core embedded in a 35-atom macrocycle rather than typical trithiazolylpyridine cores embedded in 26-atom and 29-atom peptide macrocycles. We describe the cloning of an 11-gene berninamycin cluster from Streptomyces bernensis UC 5144, its heterologous expression in Streptomyces lividans TK24 and Streptomyces venezuelae ATCC 10712, and detection of variant and incompletely processed scaffolds. Posttranslational maturation in S. lividans of both the wild-type berninamycin prepeptide (BerA) and also a T3A mutant generates macrocyclic compounds as well as linear variants, which have failed to form the pyridine and the macrocycle. Expression of the gene cluster in S. venezuelae generates a variant of the 35-atom skeleton of berninamycin, containing a methyloxazoline in the place of a methyloxazole within the macrocyclic framework.


    Directory of Open Access Journals (Sweden)

    Vasile Lozan


    Full Text Available The steric protection offered by the macrobinucleating hexaazaditiophenolate ligand (L allows for the preparation of the first stable dinuclear nickel(II borohydride bridged complex, which reacts rapidly with elemental sulphur producing a tetranuclear nickel(II complex [{(LNi2}2(μ-S6]2+ bearing a helical μ4-hexa- sulfide ligand. The [(LCoII 2]2+ fragment have been able to trap a monomethyl orthomolybdate in the binding pocket. Unusual coordination modes of substrate in dinuclear macrocyclic compounds was demonstrated.

  16. Natural and Synthetic Macrocyclic Inhibitors of the Histone Deacetylase Enzymes

    DEFF Research Database (Denmark)

    Maolanon, Alex; Kristensen, Helle; Leman, Luke


    Inhibition of histone deacetylase (HDAC) enzymes has emerged as a target for development of cancer chemotherapy. Four compounds have gained approval for clinical use by the Food and Drug Administration (FDA) in the US, and several are currently in clinical trials. However, none of these compounds...... HDAC enzymes may hold an advantage over traditional hydroxamic acid-containing inhibitors, which rely on chelation to the conserved active site zinc ion. Here, we review the literature on macrocyclic HDAC inhibitors obtained from natural sources and structure-activity relationship studies inspired...

  17. 8th International Symposium on Supramolecular and Macrocyclic Chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Jeffery T. [Univ. of Maryland, College Park, MD (United States)


    This report summarizes the 8th International Conference on Supramolecular and Macrocyclic Chemistry (ISMSC-8). DOE funds were used to make it more affordable for students, post-docs and junior faculty to attend the conference by covering their registration costs. The conference was held in Crystal City, VA from July 7-11, 2013. See for the conference website. ISMSC-8 encompassed the broad scope and interdisciplinary nature of the field. We met our goal to bring together leading scientists in molecular recognition and supramolecular chemistry. New research directions and collaborations resulted this conference. The DOE funding was crucial for us achieving our primary goal.

  18. Macrocyclic nickel(II) complexes: Synthesis, characterization, superoxide scavenging activity and DNA-binding (United States)

    Ramadan, Abd El-Motaleb M.


    A new series of nickel(II) complexes with the tetraaza macrocyclic ligand have been synthesized as possible functional models for nickel-superoxide dismutase enzyme. The reaction of 5-amino-3-methyl-1-phenylpyrazole-4-carbaldehyde (AMPC) with itself in the presence of nickel(II) ion yields, the new macrocyclic cationic complex, [NiL(NO3)2], containing a ligand composed of the self-condensed AMPC (4 mol) bound to a single nickel(II) ion. A series of metathetical reactions have led to the isolation of a number of newly complexes of the types [NiL]X2; X = ClO4 and BF4, [NiLX2], X = Cl and Br (Scheme 1). Structures and characterizations of these complexes were achieved by several physicochemical methods namely, elemental analysis, magnetic moment, conductivity, and spectral (IR and UV-Vis) measurements. The electrochemical properties and thermal behaviors of these chelates were investigated by using cyclic voltammetry and thermogravimetric analysis (TGA and DTG) techniques. A distorted octahedral stereochemistry has been proposed for the six-coordinate nitrato, and halogeno complexes. For the four-coordinate, perchlorate and fluoroborate, complex species a square-planar geometry is proposed. The measured superoxide dismutase mimetic activities of the complexes indicated that they are potent NiSOD mimics and their activities are compared with those obtained previously for nickel(II) complexes. The probable mechanistic implications of the catalytic dismutation of O2rad - by the synthesized nickel(II) complexes are discussed. The DNA-binding properties of representative complexes [NiLCl2] and [NiL](PF4)2 have been investigated by the electronic absorption and fluorescence measurements. The results obtained suggest that these complexes bind to DNA via an intercalation binding mode and the binding affinity for DNA follows the order: [NiLCl2] □ [NiL](PF4)2.

  19. The 'Visualized' macrocycles: Chemistry and application of fluorophore tagged cyclodextrins. (United States)

    Benkovics, Gábor; Malanga, Milo; Fenyvesi, Éva


    Cyclodextrins are macrocyclic molecules able to form host-guest complexes due to their hydrophobic cavity. Because of their carbohydrate nature they do not absorb light in the UV-vis region (200-800nm), but they can be converted into spectroscopically active compounds via modification with a chromophore unit. Among the chromophores, the group of fluorophores can provide high sensitivity in analytical applications (chemosensing) and low detection limit in optical imaging methods (fluorescent microscopy). Fluorophore-tagged cyclodextrins therefore combine interesting spectroscopic properties with promising supramolecular features which make these conjugates widely applicable in various pharmaceutical fields. The aim of this work is to review the various types of fluorophores which have been used for cyclodextrin tagging, to discuss the synthetic strategies used for the conjugation and to summarize the pharmaceutical applications of these 'visualized' macrocycles including their use in photodynamic therapy. The recent achievements in studying how the fluorophore-appended cyclodextrin derivatives cross biological barriers are also reviewed. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Covalent lanthanide(III) macrocyclic complexes: the bonding nature and optical properties of a promising single antenna molecule. (United States)

    Rabanal-León, Walter A; Páez-Hernández, Dayán; Arratia-Pérez, Ramiro


    The present work is focused on the elucidation of the electronic structure, bonding nature and optical properties of a series of low symmetry (C2) coordination compounds of type [Ln(III)HAM](3+), where "Ln(III)" are the trivalent lanthanide ions: La(3+), Ce(3+), Eu(3+) and Lu(3+), while "HAM" is the neutral six-nitrogen donor macrocyclic ligand [C22N6H26]. This systematic study has been performed in the framework of the Relativistic Density Functional Theory (R-DFT) and also using a multi-reference approach via the Complete Active Space (CAS) wavefunction treatment with the aim of analyzing their ground state and excited state electronic structures as well as electronic correlation. Furthermore, the use of the energy decomposition scheme proposed by Morokuma-Ziegler and the electron localization function (ELF) allows us to characterize the bonding between the lanthanide ions and the macrocyclic ligand, obtaining as a result a dative-covalent interaction. Due to a great deal of lanthanide optical properties and their technological applications, the absorption spectra of this set of coordination compounds were calculated using the time-dependent density functional theory (TD-DFT), where the presence of the intense Ligand to Metal Charge Transfer (LMCT) bands in the ultraviolet and visible region and the inherent f-f electronic transitions in the Near-Infra Red (NIR) region for some lanthanide ions allow us to propose these systems as "single antenna molecules" with potential applications in NIR technologies.

  1. Double template effect in [4 + 4] Schiff base macrocycle formation; an ESI-MS study. (United States)

    Barreira-Fontecha, Julia; Kulmaczewski, Rafal; Ma, Xiaomei; McKee, Vickie


    The mechanism of self-assembly of a polynuclear complex of a [4 + 4] Schiff base iminomethylenediphenolate macrocycle [BaCu(4)(4 + 4)](2+) via a non-macrocyclic dialdehyde intermediate has been followed using ESI-MS of the reaction solutions. Both assembly of the intermediate and Schiff-base condensation with diamine give rise to single products; formation of the intermediate metallacycle is fast but Schiff-base condensation is much slower. Both intermediate complex and macrocyclic product have been structurally characterised.

  2. Grafted chromium 13-membered dioxo-macrocyclic complex into aminopropyl-based nanoporous SBA-15

    Energy Technology Data Exchange (ETDEWEB)

    Tarlani, Aliakbar, E-mail: [Inorganic Nanostructures and Catalysts Research Laboratory, Chemistry and Chemical Engineering Research Center of Iran, Pajoohesh Boulevard, km 17, Karaj Highway, Tehran 14968-13151 (Iran, Islamic Republic of); Joharian, Monika; Narimani, Khashayar [Inorganic Nanostructures and Catalysts Research Laboratory, Chemistry and Chemical Engineering Research Center of Iran, Pajoohesh Boulevard, km 17, Karaj Highway, Tehran 14968-13151 (Iran, Islamic Republic of); Muzart, Jacques [Institut de Chimie Moléculaire de Reims, CNRS-Université de Reims Champagne-Ardenne, BP 1039, 51687 Reims Cedex 2 (France); Fallah, Mahtab [Inorganic Nanostructures and Catalysts Research Laboratory, Chemistry and Chemical Engineering Research Center of Iran, Pajoohesh Boulevard, km 17, Karaj Highway, Tehran 14968-13151 (Iran, Islamic Republic of)


    In a new approach, chromium (III) tetraaza dioxo ligand was grafted onto functionalized SBA-15 after four step reactions by using coordinating ability of anchored amino functionalized SBA-15. After the termination of each step, the obtained product was characterized by FT-IR, low-angle X-ray diffraction (LA-XRD), N{sub 2} adsorption–desorption isotherms (Brunauer–Emmett–Teller (BET)–Barret–Joyner–Halenda (BJH)) and thermogravimetric analysis (TGA), and used as catalyst for the efficient and regioselective alcoholysis of styrene oxide to 2-alkoxy-1-phenylethanol product at ambient temperature. - Graphical abstract: Chromium (III) tetraaza dioxo ligand was grafted onto functionalized SBA-15 using coordinating ability of anchored amino functionalized SBA-15. Preparation of the catalyst is depicted in Scheme 1. - Highlights: • Dioxo tetraazachromium macrocyclic complex grafted into the SBA-15-NH{sub 2} channels. • The bond is created by coordinating ability of anchored amino functionalized SBA-15. • The prepared nanocatalyst has superior activity in the alcoholysis of styrene oxide. • The catalyst is reusable at ambient temperature for the mentioned reaction.

  3. Organic Electrofluorescent Materials Using Pyridine-Containing Macrocyclic Compounds

    Institute of Scientific and Technical Information of China (English)

    Tingxi LI; Long FU; Wenwen YU; Renhe HUANG


    Novel pyridine-containing macrocyclic compounds, such as 6,12,19,25-tetramethyl-7,11,20,24-dinitrilo-dibenzo[b,m]l,4,12,15-tetra-azacyclodoc osine (TMCD), were synthesized and used as electron transport layer in organic electroluminescent devices. Devices with a structure of glass/indium-tin oxide/arylamine derivative/tris(quinolinolato)aluminum(Ⅲ) (AIq)/TMCD/LiF/AI exhibited green emission from the Alq layer with external quantum efficiency of 0.84% and luminous efficiency of 1.3 lm/W. The derivatives of TMCD were synthesized and characterized as well. These compounds were also found to be useful as the electron-transporting materials in organic electroluminescent devices.

  4. Surface enhanced second harmonic generation from macrocycle, catenane, and rotaxane thin films : Experiments and theory

    NARCIS (Netherlands)

    Arfaoui, [No Value; Bermudez, [No Value; Bottari, G; De Nadai, C; Jalkanen, JP; Kajzar, F; Leigh, DA; Lubomska, M; Mendoza, SM; Niziol, J; Rudolf, P; Zerbetto, F; Arfaoui, Imad; Bermúdez, Verónica; Jalkanen, Jukka-Pekka


    Surface enhanced second harmonic generation (SE SHG) experiments on molecular structures, macrocycles, catenanes, and rotaxanes, deposited as monolayers and multilayers by vacuum sublimation on silver, are reported. The measurements show that the molecules form ordered thin films, where the highest

  5. Radical Polymerization of Vinyl Acetate and Methyl Methacrylate Using Organochromium Initiators Complexed with Macrocyclic Polyamines (United States)


    METHYL METHACRYLATE USING ORGANOCHROMIUM REA NTS COMPLEXED WITH MACROCYCLIC A• by Daniela Mardare, Scott Gaynor, Krzysztof Matyjaszewski DTIC Published... Daniela Mardare, Scott Gaynor, Krzysztof Matyjaszewski 7. PERFORMING ORGANIZATION NAME(S) AND ADORESS(ES) a. PERFORMING ORGANIZATION Carnegie Mellon


    Title: Lanthanide Enhance Luminescence (LEL) with one and two photon excitation of Quantum Dyes? Lanthanide(III)-Macrocycles Principal Author:Robert C. Leif, Newport InstrumentsSecondary Authors:Margie C. Becker, Phoenix Flow Systems Al Bromm, Virginia Commonw...

  7. Design, synthesis and biological evaluation of a macrocyclic discodermolide/dictyostatin hybrid. (United States)

    Paterson, Ian; Gardner, Nicola M


    A 22-membered macrocyclic discodermolide/dictyostatin hybrid has been designed and synthesised; biological evaluation against a range of human cancer cell lines revealed significant levels of growth inhibition.

  8. Selective Synthesis of [2+2] Macrocyclic Schiff Bases from Chiral 1,4-Diamines

    Institute of Scientific and Technical Information of China (English)

    ZHU Hai-Bin; HU Da-Hua; DONG Hua-Ze; LI Gen-Xi; GOU Shao-Hua


    [2+2] macrocyclic Schiff bases of three kinds have been synthesized from chiral 1,4-diamines by use of different methods. Macrocyclic Schiff bases 1a-1c have been selectively obtained based on a non-templated dilution method from chiral 1,4-diamines a-c and dialdehyde DA1, whereas macrocycles 2a-2c have been selectively produced from reaction of diamines a-c and dialdehyde DA2 in the presence of boric acid as templates. Macrocyclic Schiff bases 3a-3c have been afforded in high selectivity from diamines a-c and dialdehyde DA3 by means of sodium-template. All the titled compounds have been confirmed by 1H NMR and ESI-MS analyses.

  9. Convergent Synthesis of Rigid Macrocycles Containing One and Two Tetrathiafulvalene Units

    DEFF Research Database (Denmark)

    Simonsen, Klaus B.; Thorup, Niels; Becher, Jan


    The synthesis of rigid tetrathiafulvalenophanes containing one or two tetrathiafulvalene units is presented, together with a stepwise convergent synthesis of macrocyclic bis-tetrathiafulvalenes via several open dimeric tetrathiafulvalenes. These systems were investigated by cyclic voltammetry...

  10. Heartworms, macrocyclic lactones, and the specter of resistance to prevention in the United States

    National Research Council Canada - National Science Library

    Bowman, Dwight D


    In order to provide a background to current concerns relative to the possible resistance of heartworms to macrocyclic lactones, this review summarizes various studies in which lack of efficacies (LOEs...


    Title: Lanthanide Enhance Luminescence (LEL) with one and two photon excitation of Quantum Dyes? Lanthanide(III)-Macrocycles Principal Author:Robert C. Leif, Newport InstrumentsSecondary Authors:Margie C. Becker, Phoenix Flow Systems Al Bromm, Virginia Commonw...

  12. Macrocyclic effects upon isomeric CuIIMII and MIICuII cores. Formation with unsymmetric phenol-based macrocyclic ligands

    Indian Academy of Sciences (India)

    Masami Yonemura; Yuuki Nakamura; Naoki Usuki; Hisashi Okawa


    This paper discusses coordination-position isomeric MIICuII and CuIIMII complexes, using unsymmetric dinucleating macrocycles (Lm;n)2- ((L2;2)2-, (L2;3)2- and (L2;4)2- that comprise two 2-(N-methyl)-aminomethyl-6-iminomethyl-4-bromophenonate entities, combined through the ethylene chain ( = 2) between the two amine nitrogens and through the ethylene, trimethylene or tetramethylene chain ( = 2, 3 or 4) between the two imine nitrogens. The macrocycles have dissimilar N(amine)2O2 and N(imine)2O2 metal-binding sites sharing the phenolic oxygens. The reaction of the mononuclear CuII precursors, [Cu(L2;2)], [Cu(L2;2)] and [Cu(L2;2)], with a MII perchlorate and a MII acetate salt formed (acetato)MII CuII complexes:[CoCu(L2;2)(AcO)]ClO4 0 5H2O] (1), [NiCu(L2;2) (AcO)]ClO4 (2), [ZnCu(L2;2((AcO)]ClO4 (3), [CoCu(L2;3)(AcO)]ClO4 0 5H2O (4), [NiCu(L2;3)(AcO)]ClO4 (5), [ZnCu(L2;3)(AcO)]ClO4 0 5H2O (6), [CoCu(L2;4)(AcO)(DMF)]ClO4 (7), [NiCu(L2;4)(AcO)]ClO4 2DMF (8) and [ZnCu(L2;4)(AcO)]ClO4 (9) (the formulation [MM (Lm;n)]2+ means that M resides in the aminic site and M in the iminic site). The site selectivity of the metal ions is demonstrated by X-ray crystallographic studies for 2 MeOH, 3, 5, 7, and 9. An (acetato)CuIIZnII complex, [CuZn(L2;3)(AcO)]ClO4 (10), was obtained by the reaction of [PbCu(L2;3)]-(ClO4)2 with ZnSO4 4H2O, in the presence of sodium acetate. Other complexes of the CuIIMII type were thermodynamically unstable to cause a scrambling of metal ions. The Cu migration from the iminic site to the aminic site in the synthesis of 10 is explained by the `kinetic macrocyclic effect’. The coordination-position isomers, 6 and 10, are differentiated by physicochemical properties.

  13. A set of homologous hetarylenediyne macrocycles by oxidative acetylene-acetylene coupling. (United States)

    Opris, Dorina M; Ossenbach, Alexander; Lentz, Dieter; Schlüter, A Dieter


    The synthesis of a set of bipyridine-containing macrocycles by oxidative acetylene-acetylene dimerization is described. The cycles are separated by preparative GPC, and the smallest homologue is analyzed by single-crystal X-ray diffraction, which shows a layered structure with channels that are partially filled with parts of the flexible chains of adjacent macrocycles. The cyclic trimer has a D3h symmetry and is a possible candidate for the formation of metal organic supramolecular assemblies on surfaces.

  14. Synthesis, structure and ring-opening polymerization of macrocyclic arylates containing phthalic unit

    Institute of Scientific and Technical Information of China (English)

    姜洪焱; 陈天禄; 邢彦; 林永华; 徐纪平


    A series of maerocyclic arylate diraers have been selectively synthesized by an interfacial polyconden-sation of o-phthaloyldichloride with bisphenols A combination of GPC,FAB-MS,1H and 13C NMR unambiguously confirmed the cyclic nature Although single-crystal X-ray analysis of two such macrocycles reveals no severe strain on the cyclic structures,these macrocycles can undergo facile melt polymerization to give high molecular weight polyary-lates.

  15. [3+3] Cyclocondensation of Disubstituted Biphenyl Dialdehydes: Access to Inherently Luminescent and Optically Active Hexa-substituted C3-Symmetric and Asymmetric Trianglimine Macrocycles. (United States)

    Wang, Zhenzhen; Nour, Hany F; Roch, Loïc M; Guo, Minjie; Li, Wenjiao; Baldridge, Kim K; Sue, Andrew C H; Olson, Mark A


    A general synthetic route to inherently luminescent and optically active 6-fold substituted C3-symmetric and asymmetric biphenyl-based trianglimines has been developed. The synthesis of these hexa-substituted triangular macrocycles takes advantage of a convenient method for the synthesis of symmetrically and asymmetrically difunctionalized biphenyl dialdehydes through a convergent two-step aromatic nucleophilic substitution-one-pot Suzuki-coupling reaction protocol. A modular [3+3] diamine-dialdehyde cyclocondensation reaction between both the symmetrically and asymmetrically difunctionalized-4,4'-biphenyldialdehydes with enantiomerically pure (1R,2R)-1,2-diaminocyclohexane was employed to construct the hexa-substituted triangular macrocycles. B97-D/6-311G(2d,p) density functional theory determined structures and X-ray crystallographic analysis reveal that the six substituents appended to the biphenyl legs of the trianglimine macrocycles adopt an alternating conformation not unlike the 1,3,5-alternate conformation observed for calix[6]arenes. Reduction of the imine bonds using NaBH4 afforded the corresponding 6-fold substituted trianglamine without the need to alkylate the amine nitrogen atoms which could hinder their later use as metal coordination sites and without having to introduce asymmetric carbons.

  16. Smart macrocyclic molecules: induced fit and ultrafast self-sorting inclusion behavior through dynamic covalent chemistry. (United States)

    Han, Ji-Min; Pan, Jin-Long; Lei, Ting; Liu, Chenjiang; Pei, Jian


    A family of macrocycles with oligo(ethylene glycol) chains, 4O, 5O, and 6O, was developed to construct a series of new incorporated macrocycles through dynamic covalent chemistry. These flexible macrocycles exhibited excellent "self-sorting" abilities with diamine compounds, which depended on the "induced-fit" rule. For instance, the host macrocycles underwent conformational modulation to accommodate the diamine guests, affording [1+1] intramolecular addition compounds regardless of the flexibility of the diamine. These macrocycles folded themselves to fit various diamines with different chain length through modulation of the flexible polyether chain, and afforded intramolecular condensation products. However, if the chain of the diamine was too long and rigid, oligomers or polymers were obtained from the mixture of the macromolecule and the diamine. All results demonstrated that inclusion compounds involving conformationally suitable aromatic diamines were thermodynamically favorable candidates in the mixture due to the restriction of the macrocycle size. Furthermore, kinetic and thermodynamic studies of self-sorting behaviors of both mixed 4O-5O and 4O-6O systems were investigated in detail. Finally, theoretical calculations were also employed to further understand such self-sorting behavior, and indicated that the large enthalpy change of H(2)NArArNH(2)@4O is the driving force for the sorting behavior. Our system may provide a model to further understand the principle of biomolecules with high specificity due only to their conformational self-adjusting ability.

  17. Template Syntheses, Crystal Structures and Supramolecular Assembly of Hexaaza Macrocyclic Copper(II) Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Taehyung; Kim, Ju Chang [Pukyong National Univ., Busan (Korea, Republic of); Lough, Alan J. [Univ. of Toronto, Toronto (Canada)


    Two new hexaaza macrocyclic copper(II) complexes were prepared by a template method and structurally characterized. In the solid state, they were self-assembled by intermolecular interactions to form the corresponding supramolecules 1 and 2, respectively. In the structure of 1, the copper(II) macrocycles are bridged by a tp ligand to form a macrocyclic copper(II) dimer. The dimer extends its structure by intermolecular forces such as hydrogen bonds and C-H···π interactions, resulting in the formation of a double stranded 1D supramolecule. In 2, the basic structure is a monomeric copper(II) macrocycle with deprotonated imidazole pendants. An undulated 1D hydrogen bonded array is achieved through hydrogen bonds between imidazole pendants and secondary amines, where the imidazole pendants act as a hydrogen bond acceptor. The 1D hydrogen bonded supramolecular chain is supported by C-H···π interactions between the methyl groups of acetonitrile ligands and imidazole pendants of the copper(II) macrocycles. In both complexes, the introduction of imidazoles to the macrocycle as a pendant plays an important role for the formation of supramolecules, where they act as intermolecular hydrogen bond donors and/or acceptors, C-H···π and π-π interactions.

  18. Alain Massiera, De la croissance économique au développement durable. Paris, L’Harmattan, Série Cours Principaux, Collection L’esprit économique, 2010

    Directory of Open Access Journals (Sweden)

    Tina Rambonilaza


    Full Text Available A l’heure où essais, critiques, manuels condensés et rapports plaidant pour une reconsidération de la notion de performances économiques et de progrès social ne manquent pas, on peut se demander quant à la nécessité ou plus modestement l’utilité d’un livre qui au regard de son titre « De la croissance économique au développement durable » semble ne rien dire de nouveau aux plus avertis d’entre nous.Il est inséré dans la série Cours Principaux de la collection L’Esprit Economique de L’Harmatta...

  19. Electron transfer reactions of macrocyclic compounds of cobalt

    Energy Technology Data Exchange (ETDEWEB)

    Heckman, R.A.


    The kinetics and mechanisms of reduction of H/sub 2/O/sub 2/, Br/sub 2/, and I/sub 2/ by various macrocyclic tetraaza complexes of cobalt(II), including Vitamin B/sub 12r/, were studied. The synthetic macrocycles studied were all 14-membered rings which varied in the degree of unsaturation,substitution of methyl groups on the periphery of the ring, and substitution within the ring itself. Scavenging experiments demonstrated that the reductions of H/sub 2/O/sub 2/ produce free hydroxyl radicals only in the case of Co((14)ane)/sup 2 +/ but with none of the others. In the latter instances apparently H/sub 2/O/sub 2/ simultaneously oxidizes the metal center and the ligand. The reductions of Br/sub 2/ and I/sub 2/ produce an aquohalocobalt(III) product for all reductants (except B/sub 12r/ + Br/sub 2/, which was complicated by bromination of the corrin ring). The mechanism of halogen reduction was found to involve rate-limiting inner-sphere electron transfer from cobalt to halogen to produce a dihalide anion coordinated to the cobalt center. This intermediate subsequently decomposes in rapid reactions to halocobalt(III) and halogen atom species or reacts with another cobalt(II) center to give two molecules of halocobalt(III). The reductions of halomethylcobaloximes and related compounds and diamminecobaloxime by Cr/sup 2 +/ were also studied. The reaction was found to be biphasic in all cases with the reaction products being halomethane (for the halomethylcobaloximes), Co/sup 2 +/ (in less than 100 percent yield), a Cr(III)-dimethylglyoxime species, a small amount of free dmgH/sub 2/, and a highly-charged species containing both cobalt and chromium. The first-stage reaction occurs with a stoichiometry of 1:1 producing an intermediate with an absorption maximum at 460 nm for all starting reagents. The results were interpreted in terms of inner-sphere coordination of the cobaloxime to the Cr(II) and electron transfer through the oxime N-O bond.

  20. [Tl(III)(dota)](-): An Extraordinarily Robust Macrocyclic Complex. (United States)

    Fodor, Tamás; Bányai, István; Bényei, Attila; Platas-Iglesias, Carlos; Purgel, Mihály; Horváth, Gábor L; Zékány, László; Tircsó, Gyula; Tóth, Imre


    The X-ray structure of {C(NH2)3}[Tl(dota)]·H2O shows that the Tl(3+) ion is deeply buried in the macrocyclic cavity of the dota(4-) ligand (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) with average Tl-N and Tl-O distances of 2.464 and 2.365 Å, respectively. The metal ion is directly coordinated to the eight donor atoms of the ligand, which results in a twisted square antiprismatic (TSAP') coordination around Tl(3+). A multinuclear (1)H, (13)C, and (205)Tl NMR study combined with DFT calculations confirmed the TSAP' structure of the complex in aqueous solution, which exists as the Λ(λλλλ)/Δ(δδδδ) enantiomeric pair. (205)Tl NMR spectroscopy allowed the protonation constant associated with the protonation of the complex according to [Tl(dota)](-) + H(+) ⇆ [Tl(Hdota)] to be determined, which turned out to be pK(H)Tl(dota) = 1.4 ± 0.1. [Tl(dota)](-) does not react with Br(-), even when using an excess of the anion, but it forms a weak mixed complex with cyanide, [Tl(dota)](-) + CN(-) ⇆ [Tl(dota)(CN)](2-), with an equilibrium constant of Kmix = 6.0 ± 0.8. The dissociation of the [Tl(dota)](-) complex was determined by UV-vis spectrophotometry under acidic conditions using a large excess of Br(-), and it was found to follow proton-assisted kinetics and to take place very slowly (∼10 days), even in 1 M HClO4, with the estimated half-life of the process being in the 10(9) h range at neutral pH. The solution dynamics of [Tl(dota)](-) were investigated using (13)C NMR spectroscopy and DFT calculations. The (13)C NMR spectra recorded at low temperature (272 K) point to C4 symmetry of the complex in solution, which averages to C4v as the temperature increases. This dynamic behavior was attributed to the Λ(λλλλ) ↔ Δ(δδδδ) enantiomerization process, which involves both the inversion of the macrocyclic unit and the rotation of the pendant arms. According to our calculations, the arm-rotation process limits the Λ(λλλλ) ↔

  1. A New Class of Macrocyclic Chiral Selectors for Stereochemical Analysis

    Energy Technology Data Exchange (ETDEWEB)



    This report summarizes the work accomplished in the authors laboratories over the previous three years. During the funding period they have had 23 monographs published or in press, 1 book chapter, 1 patent issued and have delivered 28 invited seminars or plenary lectures on DOE sponsored research. This report covers the work that has been published (or accepted). The most notable aspect of this work involves the successful development and understanding of a new class of fused macrocyclic compounds as pseudophases and selectors in high performance separations (including high performance liquid chromatography, HPLC; capillary electrophoresis, CE; and thin layer chromatography, TLC). They have considerably extended their chiral biomarker work from amber to crude oil and coal. In the process of doing this we've developed several novel separation approaches. They finished their work on the new GSC-PLOT column which is now being used by researchers world-wide for the analysis of gases, light hydrocarbons and halocarbons. Finally, we completed basic studies on immobilizing a cyclodextrin/oligosiloxane hybrid on the wall of fused silica, as well as a basic study on the separation behavior of buckminster fullerene and higher fullerenes.

  2. Short communication: Macrocyclic lactone residues in butter from Brazilian markets. (United States)

    Macedo, Fabio; Marsico, Eliane Teixeira; Conte-Júnior, Carlos Adam; de Almeida Furtado, Leonardo; Brasil, Taila Figueredo; Pereira Netto, Annibal Duarte


    Macrocyclic lactones (ML) are commonly used in drug formulations for the treatment of parasites in cattle. In Brazil, except for drugs (or formulations) with long-term (half-life) effects, ML are registered for use in bovines. Indiscriminate use of ML may result in the presence of residues in milk and dairy products due to their lipophilic properties and thermal stability. This study applied a method of liquid chromatography with fluorimetric detection, recently developed and validated for the determination of residues of abamectin, doramectin, ivermectin, and moxidectin in butter. The method was applied to 38 samples of commercial butter purchased in the metropolitan area of Rio de Janeiro, Brazil, between June and September 2013, analyzed in triplicate. Ivermectin was detected in 89.5% of the samples, with concentrations between 0.3 and 119.4 µg/kg; 76.3% of the samples contained doramectin (0.6 to 64.7 µg/kg) and 55.2% contained abamectin (0.7 to 4.5 µg/kg). Most butter samples (76.3%) contained residues of more than 1 ML; however, no residues of moxidectin were detected. The results showed a high incidence of the presence of avermectins in butter samples. Butter is not included in the Brazilian National Plan for Control of Residues and Contaminants in Animal Products. As ML residues concentrate in lipophilic compounds, butter and other fatty dairy products should be screened for the presence of ML residues.

  3. Dermatobia hominis: Potencial risk of resistance to macrocyclic lactones. (United States)

    das Neves, José Henrique; Carvalho, Nadino; Amarante, Alessandro F T


    Dermatobia hominis is an ectoparasite that infests various species of mammals, including cattle, impairing the quality of cowhides and leather. After observing natural infestation with D. hominis larvae in cattle on two farms in the state of São Paulo, Brazil, we evaluated the efficacy of two macrocyclic lactones, ivermectin and moxidectin, against this parasite. The drugs were administered to 10 animals in each group, following the manufacturer's instructions. The groups were: Group 1-treated with ivermectin (0.2mg/kg of body weight (BW)); Group 2-treated with moxidectin (0.2mg/kg BW); and Group 3-control (untreated). On the farm in Pardinho, a total of 12 and 16 live larvae were found in 6 and in 8 animals 10 days after the treatment with ivermectin and moxidectin, respectively, while in the control group 4 bovines had a total of 7 live larvae. On the farm in Anhembi, 2, 4 and 6 live larvae were extracted from ivermectin, moxidectin and control groups, respectively, after the treatment. This is the first report of the presence of live D. hominis larvae after the treatment of cattle with ivermectin and moxidectin in Brazil. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Macrocyclic cavitands cucurbit[n]urils: prospects for application in biochemistry, medicine and nanotechnology (United States)

    Gerasko, O. A.; Kovalenko, E. A.; Fedin, V. P.


    The prospects of using the organic macrocyclic cavitands cucurbit[n]urils (CB[n]) and their derivatives in biochemistry, medicine and nanotechnology are considered. A combination of CB[n] characteristics, such as a rigid highly symmetrical structure, polarized hydrophilic portals, a rather large intramolecular hydrophobic cavity, as well as high resistance to thermolysis and corrosive media and low toxicity, account for a wide range of unique opportunities for the deliberate design of new functional materials, which may find application in various areas of modern chemistry and new technologies. Inclusion compounds of CB[n] with biologically active molecules demonstrate a high potential for the design of a new generation of prolonged action pharmaceuticals. The review presents the prospects for the application of CB[n] to manufacture unique materials, such as CB[n]-containing vesicles, films and surfaces, suitable for immobilization of various molecules and nanoparticles on their surface and for the separation of complex mixtures. Potential applications of CB[n]-modified electrodes and hydrogels are analyzed, and the use of CB[n] in proton-conducting materials and materials for the gas sorption and separation are discussed. The bibliography includes 164 references.

  5. Sequence-defined bioactive macrocycles via an acid-catalysed cascade reaction (United States)

    Porel, Mintu; Thornlow, Dana N.; Phan, Ngoc N.; Alabi, Christopher A.


    Synthetic macrocycles derived from sequence-defined oligomers are a unique structural class whose ring size, sequence and structure can be tuned via precise organization of the primary sequence. Similar to peptides and other peptidomimetics, these well-defined synthetic macromolecules become pharmacologically relevant when bioactive side chains are incorporated into their primary sequence. In this article, we report the synthesis of oligothioetheramide (oligoTEA) macrocycles via a one-pot acid-catalysed cascade reaction. The versatility of the cyclization chemistry and modularity of the assembly process was demonstrated via the synthesis of >20 diverse oligoTEA macrocycles. Structural characterization via NMR spectroscopy revealed the presence of conformational isomers, which enabled the determination of local chain dynamics within the macromolecular structure. Finally, we demonstrate the biological activity of oligoTEA macrocycles designed to mimic facially amphiphilic antimicrobial peptides. The preliminary results indicate that macrocyclic oligoTEAs with just two-to-three cationic charge centres can elicit potent antibacterial activity against Gram-positive and Gram-negative bacteria.

  6. Unsaturated 15 and 16 Membered Appended Naphthalene Macrocyclic Molecules for The Development of Fluorometric Chemosensors (United States)

    Hasan, S.; Salleh, S.; Hamdan, S.; Yamin, B.


    Unsaturated macrocyclic molecules have got an interest due to their potential in catalysis, ion exchange and electron transfer. Salicaldehyde derivatives macrocyclic molecules have a broad range in synthesis. In this study, two unsaturated macrocyclic molecules (L1 and L2) have been synthesized. The preparation of unsaturated macrocyclic ligands involve two steps; the reaction of salicylaldehyde with 1,2-dibromoethane or 1,4-dibromobutane to produce precursor, then cyclisation were completed using schiff base technique by adding diamines (naphthalene diamine). The ligands were characterized spectroscopically. In FT-IR spectrums, the form of the ligands mainly can be observed on the disappearance of the carbonyl group of aldehyde at approximately 1650cm-1 that was readily assigned to C=O group of salicylaldehyde with the replacement of C=N peak at 1684.13cm-1. The success in producing macrocyclic ligands have been further characterized using fluorescence emission spectroscopy (FES) and revealed the typical emission of naphthalene at ∼430nm. Fluorescence changes of L1 and L2 showed high selectivity for Fe3+ and Cu2+ respectively in the presence of other common metal ions, such as Zn2+, Ni2+ and Co2+. Besides, the ligand was sensitive enough to detect the concentration of ferric ion with the detection limit down to 1.08 x 10-6 M and fluorescence change that was unaffected by the presence of other common coexisting metal ions. Complexation with Co(II) was also attempted.

  7. Synthesis of azomethine macrocycles by condensation of dicarbonyl compounds with diamines without using metal ions as template agents

    Energy Technology Data Exchange (ETDEWEB)

    Borisova, Natalia E; Reshetova, Marina D; Ustynyuk, Yuri A [Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow (Russian Federation)


    Different strategies for the synthesis of symmetrical and unsymmetrical macrocyclic Schiff bases in the absence of metal ions are considered. General methods for performing macrocyclisation under thermodynamic or kinetic control are analysed. The key factors influencing the structure of macrocyclic azomethines are discussed.

  8. Molecular Assemblies of Porphyrins and Macrocyclic Receptors: Recent Developments in Their Synthesis and Applications

    Directory of Open Access Journals (Sweden)

    Abdirahman A. Mohamod


    Full Text Available Metalloporphyrins which form the core of many bioenzymes and natural light harvesting or electron transport systems, exhibit a variety of selective functional properties depending on the state and surroundings with which they exist in biological systems. The specificity and ease with which they function in each of their bio-functions appear to be largely governed by the nature and disposition of the protein globule around the porphyrin reaction center. Synthetic porphyrin frameworks confined within or around a pre-organized molecular entity like the protein network in natural systems have attracted considerable attraction, especially in the field of biomimetic reactions. At the same time a large number of macrocyclic oligomers such as calixarenes, resorcinarenes, spherands, cyclodextrins and crown ethers have been investigated in detail as efficient molecular receptors. These molecular receptors are synthetic host molecules with enclosed interiors, which are designed three dimensionally to ensure strong and precise molecular encapsulation/recognition. Due to their complex structures, enclosed guest molecules reside in an environment isolated from the outside and as a consequence, physical properties and chemical reactions specific to that environment in these guest species can be identified. The facile incorporation of such molecular receptors into the highly photoactive and catalytically efficient porphyrin framework allows for convenient design of useful molecular systems with unique structural and functional properties. Such systems have provided over the years attractive model systems for the study of various biological and chemical processes, and the design of new materials and molecular devices. This review focuses on the recent developments in the synthesis of porphyrin assemblies associated with cyclodextrins, calixarenes and resorcinarenes and their potential applications in the fields of molecular encapsulation/recognition, and

  9. Nitrogen-Phosphorus(III)-Chalcogen Macrocycles for the Synthesis of Polynuclear Silver(I) Sandwich Complexes. (United States)

    Yogendra, Sivathmeehan; Hennersdorf, Felix; Weigand, Jan J


    The synthesis of inorganic N-P(III)-Ch-based macrocycles [-PhP-NMe-PPh-Ch-]2 (8Ch; Ch = S, Se) is presented by incorporating two nitrogen, two chalcogen, and four phosphorus atoms. The macrocycles are conveniently obtained via the cyclocondensation reaction of Na2Ch (Ch = S, Se) with the acyclic dichlorodiphosphazane ClPhP-NMe-PClPh (9). Treatment with elemental sulfur (S8) or gray selenium (Segray) results in an oxidative ring contraction to give 1,3,2,4-thiazadiphosphetidine 2,4-disulfide (10S) and 1,3,2,4-selenazadiphosphetidine 2,4-diselenide (10Se), respectively. Macrocycles 8Ch are excellent multidentate ligands for transition metal complexation, as demonstrated by the isolation of mono-, di- tri-, and tetranuclear silver sandwich complexes. The polynuclear silver complexes are comprehensively characterized, including detailed NMR and X-ray analysis.

  10. Self-assembled monolayers of shape-persistent macrocycles on graphite: interior design and conformational polymorphism. (United States)

    Vollmeyer, Joscha; Eberhagen, Friederike; Höger, Sigurd; Jester, Stefan-S


    Three shape-persistent naphthylene-phenylene-acetylene macrocycles of identical backbone structures and extraannular substitution patterns but different (empty, apolar, polar) nanopore fillings are self-assembled at the solid/liquid interface of highly oriented pyrolytic graphite and 1,2,4-trichlorobenzene. Submolecularly resolved images of the resulting two-dimensional (2D) crystalline monolayer patterns are obtained by in situ scanning tunneling microscopy. A concentration-dependent conformational polymorphism is found, and open and more dense packing motifs are observed. For all three compounds alike lattice parameters are found, therefore the intermolecular macrocycle distances are mainly determined by their size and symmetry. This is an excellent example that the graphite acts as a template for the macrocycle organization independent from their specific interior.

  11. Theoretical prediction of some novel nanotubes composed of macrocyclic structures: A DFT study (United States)

    Masoodi, Hamid Reza; Bagheri, Sotoodeh; Ranjbar-Karimi, Reza


    Our interests in this paper are the elucidation of structural and electronic properties of some π-conjugated macrocycles composed of borazine and alumazene rings as well as the investigation of their potential utility for the creation of new nanotubes. Here, the calculations are performed at B3LYP/6-31+G(d) and M06-2X/6-31+G(d)//B3LYP/6-31+G(d) levels of theory. The results suggest that the self-assembly of the macrocyclic compounds can be considered to form new nanotubes through π-π stacking. Also, meaningful correlations are found between the stability and photoconductivity applications of the nanotubes and the number of stacked π-conjugated macrocycles.

  12. Self-assembled monolayers of shape-persistent macrocycles on graphite: interior design and conformational polymorphism

    Directory of Open Access Journals (Sweden)

    Joscha Vollmeyer


    Full Text Available Three shape-persistent naphthylene–phenylene–acetylene macrocycles of identical backbone structures and extraannular substitution patterns but different (empty, apolar, polar nanopore fillings are self-assembled at the solid/liquid interface of highly oriented pyrolytic graphite and 1,2,4-trichlorobenzene. Submolecularly resolved images of the resulting two-dimensional (2D crystalline monolayer patterns are obtained by in situ scanning tunneling microscopy. A concentration-dependent conformational polymorphism is found, and open and more dense packing motifs are observed. For all three compounds alike lattice parameters are found, therefore the intermolecular macrocycle distances are mainly determined by their size and symmetry. This is an excellent example that the graphite acts as a template for the macrocycle organization independent from their specific interior.

  13. Crossed and Linked Histories of Tetrapyrrolic Macrocycles and Their Use for Engineering Pores within Sol-Gel Matrices

    Directory of Open Access Journals (Sweden)

    Miguel A. García-Sánchez


    Full Text Available The crossed and linked histories of tetrapyrrolic macrocycles, interwoven with new research discoveries, suggest that Nature has found in these structures a way to ensure the continuity of life. For diverse applications porphyrins or phthalocyanines must be trapped inside solid networks, but due to their nature, these compounds cannot be introduced by thermal diffusion; the sol-gel method makes possible this insertion through a soft chemical process. The methodologies for trapping or bonding macrocycles inside pristine or organo-modified silica or inside ZrO2 xerogels were developed by using phthalocyanines and porphyrins as molecular probes. The sizes of the pores formed depend on the structure, the cation nature, and the identities and positions of peripheral substituents of the macrocycle. The interactions of the macrocyclic molecule and surface Si-OH groups inhibit the efficient displaying of the macrocycle properties and to avoid this undesirable event, strategies such as situating the macrocycle far from the pore walls or to exchange the Si-OH species by alkyl or aryl groups have been proposed. Spectroscopic properties are better preserved when long unions are established between the macrocycle and the pore walls, or when oligomeric macrocyclic species are trapped inside each pore. When macrocycles are trapped inside organo-modified silica, their properties result similar to those displayed in solution and their intensities depend on the length of the alkyl chain attached to the matrix. These results support the prospect of tuning up the pore size, surface area, and polarity inside the pore cavities in order to prepare efficient catalytic, optical, sensoring, and medical systems. The most important feature is that research would confirm again that tetrapyrrolic macrocycles can help in the development of the authentic pore engineering in materials science.

  14. BINOL Macrocycle Derivatives: Synthesis of New Dinaphthyl Sulfide Aza Oxa Thia Crowns (Lariats

    Directory of Open Access Journals (Sweden)

    Abbas Shockravi


    Full Text Available In this research work, dinaphthyl sulfide diester was prepared from the reaction of 1,1′-thiobis (2-hydroxy naphthalene and methylchloroacetate. Its aza-macrocyclic derivative was synthesized from the reaction of dinaphthyl sulfide diester and diethylenetriamine. Lariats were prepared from the reaction of chloroamides (four derivatives and initial macrocycle. Chloroamides were synthesized from the reaction of amines (aniline, benzylamine, 8-amino quinoline and 4-amino azobenzene and chloroacetyl chloride. All the materials were identified by IR, 1H NMR, 13C NMR, and mass spectroscopies, and elemental analysis.

  15. Synthesis and extended activity of triazole-containing macrocyclic protease inhibitors

    DEFF Research Database (Denmark)

    Pehere, A.D.; Pietsch, M.; Gütschow, M.;


    Peptide-derived protease inhibitors are an important class of compounds with the potential to treat a wide range of diseases. Herein, we describe the synthesis of a series of triazole- containing macrocyclic protease inhibitors pre-organized into a b-strand conformation and an evaluation...... of their activity against a panel of proteases. Acyclic azidoalkyne-based aldehydes are also evaluated for comparison. The macrocyclic peptidomimetics showed considerable activity towards calpain II, cathepsin L and S, and the 20S proteasome chymotrypsin-like activity. Some of the first examples of highly potent...

  16. Macrocyclic prolinyl acyl guanidines as inhibitors of β-secretase (BACE). (United States)

    Boy, Kenneth M; Guernon, Jason M; Wu, Yong-Jin; Zhang, Yunhui; Shi, Joe; Zhai, Weixu; Zhu, Shirong; Gerritz, Samuel W; Toyn, Jeremy H; Meredith, Jere E; Barten, Donna M; Burton, Catherine R; Albright, Charles F; Good, Andrew C; Grace, James E; Lentz, Kimberley A; Olson, Richard E; Macor, John E; Thompson, Lorin A


    The synthesis, evaluation, and structure-activity relationships of a class of acyl guanidines which inhibit the BACE-1 enzyme are presented. The prolinyl acyl guanidine chemotype (7c), unlike compounds of the parent isothiazole chemotype (1), yielded compounds with good agreement between their enzymatic and cellular potency as well as a reduced susceptibility to P-gp efflux. Further improvements in potency and P-gp ratio were realized via a macrocyclization strategy. The in vivo profile in wild-type mice and P-gp effects for the macrocyclic analog 21c is presented.

  17. [2+2+2] Cycloaddition Reactions of Macrocyclic Systems Catalyzed by Transition Metals. A Review

    Directory of Open Access Journals (Sweden)

    Anna Roglans


    Full Text Available Polyalkyne and enediyne azamacrocycles are prepared from arenesulfonamides and various alkyne and alkene derivatives either under basic or neutral conditions. The new family of macrocyclic substrates is tested in the [2+2+2] cycloaddition reaction. Several catalysts are used for the cycloisomerization reaction, and their enantioinduction is evaluated as appropriate. The effect of the structural features of the macrocycles, namely the ring size, substituents in precise positions and the number and type of unsaturations, on the [2+2+2] cycloaddition reaction has also been studied.

  18. Minor changes in the macrocyclic ligands but major consequences on the efficiency of gold nanoparticles designed for radiosensitization (United States)

    Laurent, G.; Bernhard, C.; Dufort, S.; Jiménez Sánchez, G.; Bazzi, R.; Boschetti, F.; Moreau, M.; Vu, T. H.; Collin, B.; Oudot, A.; Herath, N.; Requardt, H.; Laurent, S.; Vander Elst, L.; Muller, R.; Dutreix, M.; Meyer, M.; Brunotte, F.; Perriat, P.; Lux, F.; Tillement, O.; Le Duc, G.; Denat, F.; Roux, S.


    Many studies have been devoted to adapting the design of gold nanoparticles to efficiently exploit their promising capability to enhance the effects of radiotherapy. In particular, the addition of magnetic resonance imaging modality constitutes an attractive strategy for enhancing the selectivity of radiotherapy since it allows the determination of the most suited delay between the injection of nanoparticles and irradiation. This requires the functionalization of the gold core by an organic shell composed of thiolated gadolinium chelates. The risk of nephrogenic systemic fibrosis induced by the release of gadolinium ions should encourage the use of macrocyclic chelators which form highly stable and inert complexes with gadolinium ions. In this context, three types of gold nanoparticles (Au@DTDOTA, Au@TADOTA and Au@TADOTAGA) combining MRI, nuclear imaging and radiosensitization have been developed with different macrocyclic ligands anchored onto the gold cores. Despite similarities in size and organic shell composition, the distribution of gadolinium chelate-coated gold nanoparticles (Au@TADOTA-Gd and Au@TADOTAGA-Gd) in the tumor zone is clearly different. As a result, the intravenous injection of Au@TADOTAGA-Gd prior to the irradiation of 9L gliosarcoma bearing rats leads to the highest increase in lifespan whereas the radiophysical effects of Au@TADOTAGA-Gd and Au@TADOTA-Gd are very similar.Many studies have been devoted to adapting the design of gold nanoparticles to efficiently exploit their promising capability to enhance the effects of radiotherapy. In particular, the addition of magnetic resonance imaging modality constitutes an attractive strategy for enhancing the selectivity of radiotherapy since it allows the determination of the most suited delay between the injection of nanoparticles and irradiation. This requires the functionalization of the gold core by an organic shell composed of thiolated gadolinium chelates. The risk of nephrogenic systemic

  19. Shaping the cavity of the macrocyclic ligand in metallocalix[4]arenes: the role of the ligand sphere. (United States)

    Radius, U


    The coordination form of calix[4]arene ligands and therefore the cavity of the macrocyclic ligand can be controlled by other ligands in transition metal calix[4]arene complexes, if strong directing coligands such as oxo groups are used. This paper describes the synthesis and characterization of the d(0) transition metal complexes [Cax(OMe)(2)O(2)TiCl(2)] 1 (monoclinic, space group P2(1)/c, lattice constants a = 21.639(4), b = 20.152(3), c = 12.750(3) A, beta = 95.68(3), V = 5532.6(19) A(3)) and [Cax(OMe)(2)O(2)MoO(2)] 2 (monoclinic, space group P2/c, lattice constants a = 12.433(3), b = 16.348(3), c = 24.774(5) A, beta = 99.15(3), V = 4971.6(17) A(3)). Whereas in 1 the calix[4]arene ligand adopts an elliptically distorted cone conformation, the macrocyclic ligand binds in a paco-like conformation to the metal center of 2, in the solid state and in solution. This was predicted by density functional theory calculations on models of different isomers of 1 and 2: cis,cone-1',2', trans,cone-1',2', and cis,paco-1',2'. According to these calculations, the energetic difference of 72.9 kJ/mol between both cis-dioxomolybdenum compounds is quite pronounced in favor of the cis,paco isomer, and 28.0 kJ/mol for the titanium compounds in favor of the cis,cone isomer.

  20. Studies of Flerovium and Element 115 Homologs with Macrocyclic Extractants

    Energy Technology Data Exchange (ETDEWEB)

    Despotopulos, John D. [Univ. of Nevada, Las Vegas, NV (United States)


    Study of the chemistry of the heaviest elements, Z ≥ 104, poses a unique challenge due to their low production cross-sections and short half-lives. Chemistry also must be studied on the one-atom-at-a-time scale, requiring automated, fast, and very efficient chemical schemes. Recent studies of the chemical behavior of copernicium (Cn, element 112) and flerovium (Fl, element 114) together with the discovery of isotopes of these elements with half-lives suitable for chemical studies have spurred a renewed interest in the development of rapid systems designed to study the chemical properties of elements with Z ≥ 114. This dissertation explores both extraction chromatography and solvent extraction as methods for development of a rapid chemical separation scheme for the homologs of flerovium (Pb, Sn, Hg) and element 115 (Bi, Sb), with the goal of developing a chemical scheme that, in the future, can be applied to on-line chemistry of both Fl and element 115. Carrier-free radionuclides, used in these studies, of the homologs of Fl and element 115 were obtained by proton activation of high-purity metal foils at the Lawrence Livermore National Laboratory (LLNL) Center for Accelerator Mass Spectrometry (CAMS): natIn(p,n)113Sn, natSn(p,n)124Sb, and Au(p,n)197m,gHg. The carrier-free activity was separated from the foils by novel separation schemes based on ion exchange and extraction chromatography techniques. Carrier-free Pb and Bi isotopes were obtained from development of a novel generator based on cation exchange chromatography using the 232U parent to generate 212Pb and 212Bi. Macrocyclic extractants, specifically crown ethers and their derivatives, were chosen for these studies; crown ethers show high selectivity for metal ions. Finally. a potential chemical system for Fl was established based on the Eichrom Pb resin, and insight to an improved system based on thiacrown ethers is

  1. Sceliphrolactam, a polyene macrocyclic lactam from a wasp-associated Streptomyces sp

    DEFF Research Database (Denmark)

    Oh, Dong-Chan; Poulsen, Michael; Currie, Cameron R


    A previously unreported 26-membered polyene macrocyclic lactam, sceliphrolactam, was isolated from an actinomycete, Streptomyces sp., associated with the mud dauber, Sceliphron caementarium. Sceliphrolactam's structure was determined by 1D- and 2D-NMR, MS, UV, and IR spectral analysis. Sceliphrol...

  2. New macrocycles with potent antituberculosis activity accessed by one-pot multicomponent reactions

    NARCIS (Netherlands)

    Kim, D.; Huang, Y.; Wang, K.; Doemling, A.

    Based on modeling studies, we hypothesized that tylosin derivatives without formyl group should rather adopt an erythromycin-like binding mode to the ribosome. Twenty four 16-membered macrocyclic compounds were accessed by multicomponent reactions (Gewald, Ugi) of tylosin and investigated for their

  3. Synthesis of Tetra-Schiff Base Macrocyclic Compound Containing Benzo-12-crown-4

    Institute of Scientific and Technical Information of China (English)


    Tetra-Schiff base macrocyclic compound containing benzo-12-crown-4 was synthesized via condensation of 2, 6-diformyl-4-methyl-phenol with 4(, 5(- diaminobenzo-12-C- 4 promoted by proton. The compound was characterized by MS, IR 1HNMR spectroscopy and elemental analysis.

  4. New Cleft-like Molecules and Macrocycles from Phosphonate Substituted Spirobisindanol

    Directory of Open Access Journals (Sweden)

    Paolo Finocchiaro


    Full Text Available We have synthetized medium-sized cyclophanes and macrocycles containingphosphonic groups, directly linked to the aromatic rings of the phanes or as pendant arms,for use as specific receptors for the selective complexation of neutral guests or forcomplexing lanthanides, as luminescent sensors and for diagnostic bioassays in medicine.Furthermore, because it would be of great interest for biochemistry as well as forpharmacological studies to dispose of preorganized rigid chiral hosts for biorelevantmolecules we designed inter alia, some new chiral macrocycles capable of a triple bindingmode and we used them for constructing macrocycles that could also be of interest forchiral recognition and chiral separations. Thus, in this paper we shall review the salientaspects of some macrocycles synthetized in our laboratory, all possessing the phosphonatemoiety and a spirobisindanol scaffold and able to act as complexing agents for cations andorganic substrates. In particular, we shall describe their NMR characterization, theirstereochemistry in solution and in the solid state, and their use as chiral receptors forbiorelevant molecules. Chiral HPLC resolution of some of them is also reported.

  5. Short and diverse route toward complex natural product-like macrocycles.

    NARCIS (Netherlands)

    Beck, Barbara; Larbig, Gregor; Mejat, Beatrice; Magnin-Lachaux, Marina; Picard, Anne; Herdtweck, Eberhardt; Dömling, Alexander


    [reaction: see text] A general strategy toward macrocyclic compounds using multicomponent reaction (MCR) chemistry, e.g., Passerini and Ugi variants, and ring-closing metathesis (RCM) is introduced. The corresponding bifunctional isocyanides carboxylic acids bearing a terminal olefin are easy to pre

  6. Structural and Biochemical Basis for Intracellular Kinase Inhibition by Src-specific Peptidic Macrocycles. (United States)

    Aleem, Saadat; Georghiou, George; Kleiner, Ralph E; Guja, Kip; Craddock, Barbara P; Lyczek, Agatha; Chan, Alix I; Garcia-Diaz, Miguel; Miller, W Todd; Liu, David R; Seeliger, Markus A


    Protein kinases are attractive therapeutic targets because their dysregulation underlies many diseases, including cancer. The high conservation of the kinase domain and the evolution of drug resistance, however, pose major challenges to the development of specific kinase inhibitors. We recently discovered selective Src kinase inhibitors from a DNA-templated macrocycle library. Here, we reveal the structural basis for how these inhibitors retain activity against a disease-relevant, drug-resistant kinase mutant, while maintaining Src specificity. We find that these macrocycles display a degree of modularity: two of their three variable groups interact with sites on the kinase that confer selectivity, while the third group interacts with the universally conserved catalytic lysine and thereby retains the ability to inhibit the "gatekeeper" kinase mutant. We also show that these macrocycles inhibit migration of MDA-MB-231 breast tumor cells. Our findings establish intracellular kinase inhibition by peptidic macrocycles, and inform the development of potent and specific kinase inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Photoswitchable Dihydroazulene Macrocycles for Solar Energy Storage: The Effects of Ring Strain. (United States)

    Vlasceanu, Alexandru; Frandsen, Benjamin N; Skov, Anders B; Hansen, Anne Schou; Rasmussen, Mads Georg; Kjaergaard, Henrik G; Mikkelsen, Kurt V; Nielsen, Mogens Brøndsted


    Efficient energy storage and release are two major challenges of solar energy harvesting technologies. The development of molecular solar thermal systems presents one approach to address these issues by tuning the isomerization reactions of photo/thermoswitches. Here we show that the incorporation of photoswitches into macrocyclic structures is a particularly attractive solution for increasing the storage time. We present the synthesis and properties of a series of macrocycles incorporating two dihydroazulene (DHA) photoswitching subunits, bridged by linkers of varying chain length. Independent of ring size, all macrocycles exhibit stepwise, light-induced, ring-opening reactions (DHA-DHA to DHA-VHF to VHF-VHF; VHF = vinylheptafulvene) with the first DHA undergoing isomerization with a similar efficiency as the uncyclized parent system while the second (DHA-VHF to VHF-VHF) is significantly slower. The energy-releasing, VHF-to-DHA, ring closures also occur in a stepwise manner and are systematically found to proceed slower in the more strained (smaller) cycles, but in all cases with a remarkably slow conversion of the second VHF to DHA. We managed to increase the half-life of the second VHF-to-DHA conversion from 65 to 202 h at room temperature by simply decreasing the ring size. A computational study reveals the smallest macrocycle to have the most energetic VHF-VHF state and hence highest energy density.

  8. New macrocycles with potent antituberculosis activity accessed by one-pot multicomponent reactions

    NARCIS (Netherlands)

    Kim, D.; Huang, Y.; Wang, K.; Doemling, A.


    Based on modeling studies, we hypothesized that tylosin derivatives without formyl group should rather adopt an erythromycin-like binding mode to the ribosome. Twenty four 16-membered macrocyclic compounds were accessed by multicomponent reactions (Gewald, Ugi) of tylosin and investigated for their

  9. Macrocyclic Peptoid–Peptide Hybrids as Inhibitors of Class I Histone Deacetylases

    DEFF Research Database (Denmark)

    Olsen, Christian Adam; Montero, Ana; Leman, Luke J.;


    We report the design, synthesis, and biological evaluation of the first macrocyclic peptoid-containing histone deacetylase (HDAC) inhibitors. The compounds selectively inhibit human class I HDAC isoforms in vitro, with no inhibition of the tubulin deacetylase activity associated with class IIb HD...

  10. Characterization of Haemonchus contortus P-glycoprotein-16 and its interaction with the macrocyclic lactone anthelmintics. (United States)

    Godoy, P; Che, H; Beech, R N; Prichard, R K


    Anthelmintic resistance in veterinary nematodes, including Haemonchus contortus, has become a limitation to maintaining high standards of animal health. Resistance in this parasite, to all drug families including the macrocyclic lactones (MLs) is a serious issue worldwide. Mechanisms of resistance to the MLs appear to be complex and to include the elimination of these compounds by ABC transporter-like proteins present in nematodes. In order to investigate the potential involvement of ABC transporters in ML resistance in H. contortus, we have characterized the functionality of the ABC transporter H. contortus P-glycoprotein-16 (Hco-PGP-16) expressed in mammalian cells. This has included a study of its interaction with different MLs, including the avermectins, abamectin (ABA) and ivermectin (IVM), and the milbemycin, moxidectin (MOX). Hco-PGP-16 transport activity was studied using the fluorophore Rhodamine 123 (Rho 123). Transfected cells expressing Hco-PGP-16 accumulated less than 50% of Rho 123 than control cells, suggesting an active transport of this tracer dye by Hco-PGP-16. The influence of the MLs on the Rho123 transport by Hco-PGP-16 was then investigated. A marked inhibition of Rho123 transport by ABA and IVM was observed. In contrast, MOX showed less effect on inhibition of Rho123 transport by Hco-PGP-16, and the inhibition was not saturable. The difference in the interaction of the avermectins and MOX with Hco-PGP-16 may help explain the slower rate of development of resistance to MOX compared with the avermectins in H. contortus.

  11. Structure de l'amidon de maïs et principaux phénomènes impliqués dans sa modification thermique

    Directory of Open Access Journals (Sweden)

    Malumba, P.


    Full Text Available Structures and phenomena occurring during the heat treatment of cornstarch. The structure of cornstarch and the modifications induced during the heat treatments are presented in this review. Current knowledge indicate that the starch granules are semi-crystalline entities composed mainly by amylose and amylopectin, undergoing deep reorganizations during the heat treatments. Gelatinization, glass transitions, relaxation phenomena, retrogradation and the formation of amylose-lipids complexes are the major phenomena involved in these reorganisations, and are the basis of changes of the techno-functional properties of cornstarch-based products during their heat treatment. La rhizosphère est le volume du sol situé au voisinage immédiat des racines des plantes et qui se caractérise par la présence d'exsudats racinaires (rhizodépôts. Ces exsudats sont utilisés par la microflore endémique en tant que signaux chimiques en plus d'être un substrat nutritif disponible pour la croissance et le développement de ces microorganismes dans la rhizosphère. Certaines de ces bactéries du sol, appelées PGPRs (Plant Growth Promoting Rhizobacteria, sont capables de coloniser les racines ou bien encore la rhizosphère, mais à la différence des autres bactéries rhizosphériques elles ont, en retour, un effet bénéfique sur la plante. Cet effet bénéfique peut être direct, ou indirect. La promotion directe de la croissance est le résultat du pouvoir d'acquisition des nutriments ou de la stimulation des hormones de la plante. D'autres mécanismes indirects, mais le plus souvent liés à la croissance des plantes, sont impliqués dans la réduction/suppression des pathogènes des plantes. Cet article décrit les différents mécanismes mis en jeu par les PGPRs dans leur environnement naturel pour influencer favorablement la croissance et la santé des plantes.

  12. Tren centered tris-macrocycles as polytopic ligands for Cu(II) and Ni(II). (United States)

    Siegfried, Liselotte; McMahon, C Niamh; Kaden, Thomas A; Palivan, Cornelia; Gescheidt, Georg


    Two novel symmetric polytopic ligands L(1) and L(2) have been synthesized. They are composed of three 1,4,8,11-tetraazacyclotetradecane macrocycles which are connected to a central tren moiety via an ethylene and a trimethylene bridge, respectively. The complexation potential and the speciation diagrams of L(1) and L(2) towards Cu(2+) and Ni(2+) were determined by spectrophotometric and potentiometric titrations. Insight into the geometry of the Cu(2+) complexes is provided by UV-VIS and EPR spectroscopy. The simplified ligands L(3) and L(4) are utilized as references for an aminoethyl- and a tren-substituted tetraaza macrocycle to help assign the EPR spectra of the polytopic ligands L(1) and L(2). At a metal-to-ligand ratio of 3 : 1, the metal cations are preferentially bound to the tetraaza macrocycles of L(1) and L(2) in a square planar geometry. At high pH values, a nitrogen atom of the tren moiety in L(1) serves as an additional ligand in an axial position leading to a square pyramidal coordination around Cu(2+), whereas in L(2) no such geometry change is observed. At a metal-to-ligand ratio of 4 : 1, the additional metal cation resides in the central tren moiety of L(1) and L(2). However, in contrast to the typical trigonal bipyramidal geometry found in the [Cutren](2+) complex, the fourth Cu(2+) has a square pyramidal coordination caused by the interaction with the Cu(2+) cations in the macrocycles (as evidenced by EPR spectra). Since the sequence of metal complexation is such that the first three metal ions always bind to the three macrocycles of L(1) and L(2) and the fourth to the tren unit, it is possible to prepare heteronuclear complexes such as [Cu(3)NiL](8+) or [Ni(3)CuL](8+), which can be unambiguously identified by their spectral properties.

  13. μ-Nitrido Diiron Macrocyclic Platform: Particular Structure for Particular Catalysis. (United States)

    Afanasiev, Pavel; Sorokin, Alexander B


    The ultimate objective of bioinspired catalysis is the development of efficient and clean chemical processes. Cytochrome P450 and soluble methane monooxygenase enzymes efficiently catalyze many challenging reactions. Extensive research has been performed to mimic their exciting chemistry, aiming to create efficient chemical catalysts for functionalization of strong C-H bonds. Two current biomimetic approaches are based on (i) mononuclear metal porphyrin-like complexes and (ii) iron and diiron non-heme complexes. However, biomimetic catalysts capable of oxidizing CH4 are still to be created. In the search for powerful oxidizing catalysts, we have recently proposed a new bioinspired strategy using N-bridged diiron phthalocyanine and porphyrin complexes. This platform is particularly suitable for stabilization of Fe(IV)Fe(IV) complexes and can be useful to generate high-valent oxidizing active species. Indeed, the possibility of charge delocalization on two iron centers, two macrocyclic ligands, and the nitrogen bridge makes possible the activation of H2O2 and peracids. The ultrahigh-valent diiron-oxo species (L)Fe(IV)-N-Fe(IV)(L(+•))═O (L = porphyrin or phthalocyanine) have been prepared at low temperatures and characterized by cryospray MS, UV-vis, EPR, and Mössbauer techniques. The highly electrophilic (L)Fe(IV)-N-Fe(IV)(L(+•))═O species exhibit remarkable reactivity. In this Account, we describe the catalytic applications of μ-nitrido diiron complexes in the oxidation of methane and benzene, in the transformation of aromatic C-F bonds under oxidative conditions, in oxidative dechlorination, and in the formation of C-C bonds. Importantly, all of these reactions can be performed under mild and clean conditions with high conversions and turnover numbers. μ-Nitrido diiron species retain their binuclear structure during catalysis and show the same mechanistic features (e.g., (18)O labeling, formation of benzene epoxide, and NIH shift in aromatic oxidation

  14. From 2 + 2 to 8 + 8 Condensation Products of Diamine and Dialdehyde: Giant Container-Shaped Macrocycles for Multiple Anion Binding. (United States)

    Gregoliński, Janusz; Ślepokura, Katarzyna; Paćkowski, Tomasz; Panek, Jarosław; Stefanowicz, Piotr; Lisowski, Jerzy


    The combination of 2,6-diformylpyridine and trans-1,2-diaminocyclopentane fragments results in 2 + 2, 3 + 3, 4 + 4, 6 + 6, and 8 + 8 macrocyclic imine condensation products. These imines can be reduced to the corresponding 2 + 2, 3 + 3, 4 + 4, 6 + 6, and 8 + 8 macrocyclic amines. The X-ray crystal structures of their protonated derivatives show a rich variety of macrocycle conformations ranging from a stepped 2 + 2 macrocycle to a multiply folded 8 + 8 macrocycle of globular shape. These compounds bind anions via hydrogen bonds: two chloride anions are bound above and below the macrocyclic ring of the 2 + 2 amine, one chloride anion is bound approximately in the center of the 3 + 3 macrocycle, and two chloride anions are deeply buried inside a folded container-shaped 4 + 4 macrocycle, while in the case of the previously reported 6 + 6 amine four chloride anions and two solvent molecules are buried inside a container-shaped macrocycle. Yet another situation was observed for a multiply folded protonated 8 + 8 macrocycle which binds six sulfate anions; two of them are deeply buried inside the container structure while four anions interact with the clefts at the surface of the container.

  15. Features of use of modular training system armsportsmens 16–17 year olds in the annual macrocycle

    Directory of Open Access Journals (Sweden)

    Dmytro Bezkorovainyi


    Full Text Available Purpose: to determine the most effective ratio of different means and methods of training 16–17 year olds armsportsmens the application of the block training system in the annual macrocycle. Material and Methods: 30 armsportsmens investigated 16–17 years to 15 in the control and experimental groups, analyzed and summarized the data of scientific and methodical literature, conducted teacher testing, pedagogical experiment, methods of research used functional state of cardio-respiratory. Results: it was found that the block system of training 16–17 year olds armsportsmens allows significantly increase the level of morphological and functional training base, improves functional indices of the cardiovascular system. Conclusions: the experimental training program for 16–17 year olds armsportsmens based modular training system allowed the athletes to create the experimental group was significantly higher level of morphofunctional sports training base, significantly improve the functionality of the body athletes, contributed to a high level of fitness and sports is recommended to practice the preparation armsportsmens

  16. Novel antibiotics: C-2 symmetrical macrocycles inhibiting Holliday junction DNA binding by E. coli RuvC. (United States)

    Pan, Po-Shen; Curtis, Fiona A; Carroll, Chris L; Medina, Irene; Liotta, Lisa A; Sharples, Gary J; McAlpine, Shelli R


    Holliday junctions (HJs) are formed as transient DNA intermediates during site-specific and homologous recombination. Both of these genetic exchange pathways are critical for normal DNA metabolism and repair. Trapping HJs leads to bacterial cell death by preventing proper segregation of the resulting interlinked chromosomes. Macrocyclic peptides designed to target this intermediate were synthesized with the goal of identifying compounds with specificity for this unique molecular target. We discovered ten macrocycles, both hexameric and octameric peptides, capable of trapping HJs in vitro. Those macrocycles containing tyrosine residues proved most effective. These data demonstrate that C-2 symmetrical macrocycles offer excellent synthetic targets for the development of novel antibiotic agents. Furthermore, the active compounds identified provide valuable tools for probing different pathways of recombinational exchange.

  17. Ring-closing metathesis for the synthesis of a highly G-quadruplex selective macrocyclic hexaoxazole having enhanced cytotoxic potency. (United States)

    Satyanarayana, Mavurapu; Rzuczek, Suzanne G; Lavoie, Edmond J; Pilch, Daniel S; Liu, Angela; Liu, Leroy F; Rice, Joseph E


    The synthesis of a 24-membered macrocyclic hexaoxazole via ring-closing metathesis is described. The target compound selectively stabilizes G-quadruplex DNA with no detectable stabilization of duplex DNA. An MTT cytotoxicity assay indicated that this unsaturated macrocyclic hexaoxazole exhibits significant cytotoxicity toward P388, RPMI 8402, and KB3-1 cell lines with IC50 values of 45, 25, and 38 nM, respectively.

  18. Synthesis and magnetic properties of a new family of macrocyclic M(II)3Ln(III) complexes: insights into the effect of subtle chemical modification on single-molecule magnet behavior. (United States)

    Feltham, Humphrey L C; Clérac, Rodolphe; Ungur, Liviu; Vieru, Veacheslav; Chibotaru, Liviu F; Powell, Annie K; Brooker, Sally


    Thirteen tetranuclear mixed-metal complexes of the hexaimine macrocycle (L(Pr))(6-) have been prepared in a one-pot 3:1:3:3 reaction of copper(II) acetate hydrate, the appropriate lanthanide(III) nitrate hydrate, 1,4-diformyl-2,3-dihydroxybenzene (1), and 1,3-diaminopropane. The resulting family of copper(II)-lanthanide(III) macrocyclic complexes has the general formula Cu(II)(3)Ln(III)(L(Pr))(NO(3))(3)·solvents (Ln = La, Ce, Pr, Nd, Sm, Eu, Gd, Dy, Tb, Ho, Er, Tm, or Yb). X-ray crystal structure determinations carried out on [Cu(3)Ce(L(Pr))(NO(3))(3)(MeOH)(3)] and [Cu(3)Dy(L(Pr))(NO(3))(3)(MeOH)(3)] confirmed that the large Ln(III) ion is bound in the central O(6) site and the three square pyramidal Cu(II) ions in the outer N(2)O(2) sites (apical donor either nitrate anion or methanol molecule) of the Schiff base macrocycle. Only the structurally characterized Cu(3)Tb complex, reported earlier, is a single-molecule magnet (SMM): the other 12 complexes do not exhibit an out-of-phase ac susceptibility signal or hysteresis of magnetization in a dc field. Ab initio calculations allowed us to rationalize the observed magnetic properties, including the significant impact of subtle chemical modification on SMM behavior. Broken-symmetry density functional theory (BS-DFT) calculations show there is a subtle structural balance as to whether the Cu···Cu exchange coupling is ferro- or antiferromagnetic. Of the family of 13 magnetically characterized tetranuclear Cu(II)(3)Ln(III) macrocyclic complexes prepared, only the Tb(III) complex is an SMM: the theoretical reasons for this are discussed.

  19. The addition of a second lanthanide ion to increase the luminescence of europium(III) macrocyclic complexes

    Energy Technology Data Exchange (ETDEWEB)

    Bromm, A.J. Jr.; Vallarino, L.M. [Virginia Commonwealth Univ., Richmond, VA (United States). Dept. of Chemistry; Leif, R.C. [Newport Instruments, San Diego, CA (United States); Quagliano, J.R. [Los Alamos National Lab., NM (United States)


    At present, the microscopic visualization of luminescent labels containing lanthanide(III) ions, primarily europium(III), as light-emitting centers is best performed with time-gated instrumentation, which by virtually eliminating the background fluorescence results in an improved signal to noise ratio. However, the use of the europium(III) macrocycle, Quantum Dye{trademark}, in conjunction with the strong luminescence enhancing effect (cofluorescence) of yttrium(III) or gadolinium(III), can eliminate the need for such specialized instrumentation. In the presence of Gd(III), the luminescence of the Eu(III)-macrocycles can be conveniently observed with conventional fluorescence instrumentation at previously unattainable low levels. The Eu(III) {sup 5}D{sub 0} {r_arrow} {sup 7}F{sub 2} emission of the Eu(III)-macrocycles was observed as an extremely sharp band with a maximum at 619 nm and a clearly resolved characteristic pattern. At very low Eu(III)-macrocycle concentrations, another sharp emission was detected at 614 nm, arising from traces of Eu(III) present in even the purest commercially available gadolinium products. Discrimination of the resolved emissions of the Eu(III)-macrocycle and Eu(III) contaminant should provide a means to further lower the limit of detection of the Eu(III)-macrocycle.

  20. Planning and periodization in swimming: An example of a macrocycle for an adapted swimming group

    Directory of Open Access Journals (Sweden)

    A. Querido


    Full Text Available The planning of the training process in is commonly recognized as a fundamental aspect for the correct and harmonious development of the capacities and to improve sports results. The aim of this paper was to present an example of a macrocyle of training in a group of adapted swimmers. The group includes 5 swimmers, being 4 male and 1 female: three swimmers with Down syndrome, one swimmer with intellectual disability and one swimmer with autism. The macrocycle of training was subdivided in 23 weeks: 15 belonging to the General Preparation Period, 4 to the Specific Preparation Period, 2 to the Competitive Period, culminating with the Winter National Championships, and 2 to the Transition Period trying. At the Winter National Championships, the most important competition of this macrocycle, these swimmers obtained 7 national titles, 4 national vice-champions titles and 2 third places. These results gave the swimmers an important incentive to keep up the good work.

  1. Planning and periodization in swimming: An example of a macrocycle for an adapted swimming group

    Directory of Open Access Journals (Sweden)

    A. Querido


    Full Text Available The planning of the training process in is commonly recognized as a fundamental aspect for the correct and harmonious development of the capacities and to improve sports results. The aim of this paper was to present an example of a macrocyle of training in a group of adapted swimmers. The group includes 5 swimmers, being 4 male and 1 female: three swimmers with Down syndrome, one swimmer with intellectual disability and one swimmer with autism. The macrocycle of training was subdivided in 23 weeks: 15 belonging to the General Preparation Period, 4 to the Specific Preparation Period, 2 to the Competitive Period, culminating with the Winter National Championships, and 2 to the Transition Period trying. At the Winter National Championships, the most important competition of this macrocycle, these swimmers obtained 7 national titles, 4 national vice-champions titles and 2 third places. These results gave the swimmers an important incentive to keep up the good work.

  2. Uranyl-selective PVC membrane electrodes based on some recently synthesized benzo-substituted macrocyclic diamides. (United States)

    Shamsipur, Mojtaba; Soleymanpour, Ahmad; Akhond, Morteza; Sharghi, Hashem; Massah, Ahmad Reza


    Four different recently synthesized macrocyclic diamides were studied to characterize their abilities as uranyl ion carriers in PVC membrane electrodes. The electrodes based on macrocycle 1,18-diaza-3,4;15,16-dibenzo-5,8,11,14,21,24-hexaoxacyclohexaeicosane-2,17-dione resulted in a Nernstian response for UO(2)(2+) ion over wide concentration ranges. The linear concentration range for the polymeric membrane electrode (PME) is 3.0x10(-6)-8.2x10(-3) M with a detection limit of 2.2x10(-6) and that for the coated graphite electrode (CGE) is 5.0x10(-7)-1.5x10(-3) M with a detection limit of 3.5x10(-7) M. The electrodes manifest advantages of low resistance, very fast response and, most importantly, good selectivities relative to a wide variety of other cations.

  3. Ring strain and total syntheses of modified macrocycles of the isoplagiochin type

    Directory of Open Access Journals (Sweden)

    Andreas Speicher


    Full Text Available Macrocycles of the bisbibenzyl-type are natural products that are found exclusively in bryophytes (liverworts. The molecular framework of the subtype “isoplagiochin” is of substantial structural interest because of the chirality of the entire molecule, which arises from two biaryl axes in combination with two helical two-carbon units in a cyclic arrangement. From a structural as well as a synthetic point of view we report on the total synthesis of compounds which possess more rigid two-carbon biaryl bridges like stilbene (E or Z or even tolane moieties which were introduced starting with a Sonogashira protocol. The McMurry method proved to be a powerful tool for the cyclization to these considerably ring-strained macrocycles.

  4. New Copper and Oxomolybdate Robson-Type Polynuclear Macrocyclic Complexes: Structure, Spectroscopy, and Electrochemical Properties

    Directory of Open Access Journals (Sweden)

    Marcelo Carpes Nunes


    Full Text Available The polynuclear complexes [Mo3O8(tidf]·dmso·2H2O (1 and [{Cu2(tidf}2(μ-Mo8O24] (2 (tidf2− is a symmetrical tetraiminodiphenolate Robson-type macrocyclic ligand were prepared from equimolar combinations of [Mg2(tidf](NO32·4H2O, [MoO2Cl2(dmso2] (for 1 and complex 1 and Cu(ClO42·4H2O (for 2 in acetonitrile. Molecular structures of both complexes were determined and showed atypical modes of coordination. A significant observation was the remarkable flexibility of the macrocycle ligand that effectively accommodated the steric demands of metal cations and the packing forces and showed a unique mode of coordination. Spectroscopic (UV-vis and FTIR and redox properties are discussed.

  5. STM visualisation of counterions and the effect of charges on self-assembled monolayers of macrocycles. (United States)

    Kudernac, Tibor; Shabelina, Natalia; Mamdouh, Wael; Höger, Sigurd; De Feyter, Steven


    Despite their importance in self-assembly processes, the influence of charged counterions on the geometry of self-assembled organic monolayers and their direct localisation within the monolayers has been given little attention. Recently, various examples of self-assembled monolayers composed of charged molecules on surfaces have been reported, but no effort has been made to prove the presence of counterions within the monolayer. Here we show that visualisation and exact localisation of counterions within self-assembled monolayers can be achieved with scanning tunnelling microscopy (STM). The presence of charges on the studied shape-persistent macrocycles is shown to have a profound effect on the self-assembly process at the liquid-solid interface. Furthermore, preferential adsorption was observed for the uncharged analogue of the macrocycle on a surface.

  6. A Novel Cobalt(Ⅲ) Complex with Macrocyclic Triamine Ligand for High Capacity Hydrogen Adsorption

    Institute of Scientific and Technical Information of China (English)

    ZHU Hai-Yan; GUO Hui; LI Sai


    The coordination complex of Co(Ⅲ) based on a macrocyclic triamine ligand 1,4-diacetate-1,4,7-triazacyclodecane (L) has been synthesized and characterized. The metal cation is bonded with three nitrogen atoms and two oxygen atoms of L and one chloride ion to form a distorted octahedral geometry. This complex coordinated with macrocyclic ligand possesses large pore volume that will be contributed to observe high H2 adsorption. With respect to the first-principles electronic structure calculations, the feasibility to store hydrogen in the complex is explored. Indeed, the complex has shown a very high total H2 adsorption of 7.2 wt% (wt% = (weight of adsorbed H2)/(weight of host material)), with a binding energy of 0.03 eV/H2

  7. A comprehensive electronic structure description of a biscyanotetraazacobalt(III) macrocyclic complex. (United States)

    Ishiruji, Fabiana Hitomi Ono; Nunes, Fábio Souza


    Molecular modeling and a detailed spectroscopic characterization of the macrocyclic complex [Co(meso)(CN)(2)](+) (meso = 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane) is herein presented. Structural, electronic and vibrational features are discussed and assignments were proposed on the basis of semi-empirical (molecular mechanics (MM+), ZINDO/S and PM3) quantum-mechanics calculations. The energy and the composition of the molecular orbitals of the complex were calculated and a quantitative diagram was constructed. The simulated UV-vis spectrum exhibited a reasonably good accordance with the experimental one and fully assignments of seven bands were made. An optimized configuration of the complex showed a strong cobalt-cyanide axial bond in agreement with the major contribution of the cyanide to the composition of the molecular orbitals in contrast to a discrete participation of the macrocyclic meso to the ground state of the complex.

  8. mRNA display: from basic principles to macrocycle drug discovery. (United States)

    Josephson, Kristopher; Ricardo, Alonso; Szostak, Jack W


    We describe a new discovery technology that uses mRNA-display to rapidly synthesize and screen macrocyclic peptide libraries to explore a valuable region of chemical space typified by natural products. This technology allows high-affinity peptidic macrocycles containing modified backbones and unnatural side chains to be readily selected based on target binding. Success stories covering the first examples of these libraries suggest that they could be used for the discovery of intracellular protein-protein interaction inhibitors, highly selective enzyme inhibitors or synthetic replacements for monoclonal antibodies. The review concludes with a look to the future regarding how this technology might be improved with respect to library design for cell permeability and bioavailability.

  9. Biodegradable polyester-based eco-composites containing hemp fibers modified with macrocyclic oligomers (United States)

    Conzatti, Lucia; Utzeri, Roberto; Hodge, Philip; Stagnaro, Paola


    An original compatibilizing pathway for hemp fibers/poly(1,4-butylene adipate-co-terephtalate) (PBAT) eco-composites was explored exploiting the capability of macrocyclic oligomers (MCOs), obtained by cyclodepolymerization (CDP) of PBAT at high dilution, of being re-converted into linear chains by entropically-driven ring-opening polymerization (ED-ROP) that occurs simply heating the MCOS in the bulk. CDP reaction of PBAT was carried out varying solvent, catalyst and reaction time. Selected MCOs were used to adjust the conditions of the ED-ROP reaction. The best experimental conditions were then adopted to modify hemp fibers. Eco-composites based on PBAT and hemp fibers as obtained or modified with PBAT macrocyclics or oligomers were prepared by different process strategies. The best fiber-PBAT compatibility was observed when the fibers were modified with PBAT oligomers before incorporation in the polyester matrix.

  10. Template synthesis of macrocyclic complexes and their spectroscopic and antibacterial studies. (United States)

    Singh, D P; Grover, Vidhi; Kumar, Ramesh; Jain, Kiran


    A new series of macrocyclic complexes of type [M(TML)X]X(2), where M = Cr(III), Fe(III), TML is tetradentate macrocyclic ligand, and X = Cl(-), NO(3)(-), CH(3)COO(-), have been synthesized by condensation of isatin and ethylenediamine in the presence of metal salt. The complexes were synthesized by both conventional and microwave methods. The complexes have been characterized with the help of elemental analysis, conductance measurement, magnetic measurement, and infrared, far infrared, and electronic spectral studies. Molar conductance values indicate them to be 1:2 electrolytes. Electronic spectra along with magnetic moments suggest five-coordinate square pyramidal geometry for these complexes. The complexes were also tested for their in vitro antibacterial activity. Some of the complexes showed satisfactory antibacterial activitiy.

  11. Special physical preparation of skilled wrestlers during a macrocycle in the conditions of higher educational establishment.

    Directory of Open Access Journals (Sweden)

    Ogar' G.O.


    Full Text Available It is developed and experimentally grounded efficiency and methods of improvement of the special physical preparedness of skilled fighters. It is certain that a method parts on a few stages of preparation of training macrocycle and optimized for sportsmen which parallel study in higher educational establishment. It is set that the educational training process of skilled fighters must take into account the specific of organization of educational process of educational establishment and answer the calendar of competitions on a CY.

  12. Lead Diversification through a Prins-Driven Macrocyclization Strategy: Application to C13-Diversified Bryostatin Analogues. (United States)

    Wender, Paul A; Billingsley, Kelvin L


    The design, synthesis, and biological evaluation of a novel class of C13-diversified bryostatin analogues are described. An innovative and general strategy based on a Prins macrocyclization-nucleophilic trapping cascade was used to achieve late-stage diversification. In vitro analysis of selected library members revealed that modification at the C13 position of the bryostatin scaffold can be used as a diversification handle to regulate biological activity.

  13. Ligand and Metalloligand Design for Macrocycles, Multimetallic Arrays, Coordination Polymers and Assemblies


    E. C. Constable; Housecroft, C. E.


    This overview of ligand design focuses on three areas: (i) principles of ligand binding, the formation of complexes, and popular strategies for ligand synthesis; (ii) ligand design in macrocyclic complexes, coordination polymers and networks and metallopolygons, and assembly strategies based upon the use of metalloligand building blocks; (iii) ligand design for the extraction and transport of metals. This area of coordination chemistry is too large to permit a comprehensive survey in the spac...

  14. Syntheses of Macrocyclic Amides from L-Amino Acid Esters by RCM

    Institute of Scientific and Technical Information of China (English)


    A series of succinate-derived macrocyclic amides( 1 ) was synthesized via ring-closing metathesis (RCM) as the key step. The substrate included 12 to 15 members. The metathesis precursors were obtained from the amide coupling of tert-butyl 3-carboxyhex-5-enoate(2) with numerous side-chain alkenylated amino acid esters of general type(3)derived from L-lysine and L-ornithine.

  15. Macrocyclic hexaoxazoles: Influence of aminoalkyl substituents on RNA and DNA G-quadruplex stabilization and cytotoxicity. (United States)

    Satyanarayana, Mavurapu; Kim, Young-Ah; Rzuczek, Suzanne G; Pilch, Daniel S; Liu, Angela A; Liu, Leroy F; Rice, Joseph E; LaVoie, Edmond J


    A series of 24-membered macrocyclic hexaoxazoles containing one or two aminoalkyl substituents was synthesized and evaluated for cytotoxicity and for their ability to selectively stabilize G-quadruplex DNA and RNA. The most cytotoxic analog 4a, with IC(50) values of 25 and 130 nM using KB3-1 and RPMI 8402 cells, is efficacious in vivo in athymic nude mice with a human tumor xenograft from the breast cancer cell line MDA-MB-435.

  16. Synthesis, spectral and extended spectrum beta-lactamase studies of transition metal tetraaza macrocyclic complexes. (United States)

    Kumar, Dinesh; Sharma, Nutan; Nair, Manjula


    Urinary tract infections commonly occur in humans due to microbial pathogens invading the urinary tract, which can bring about a range of clinical symptoms and potentially fatal sequelae. The present study is aimed at addressing the development of a new antimicrobial agent against extended spectrum beta lactamase (ESBL) producing E. coli bacteria. We have synthesised some biologically potent (NNNN) donor macrocycles (L 1  = dibenzo[f,n]dipyrido[3,4-b:4',3'-j][1,4,9,12]tetraazacyclohexadecine-6,11,18,23(5H,12H, 7H, 24H)-tetraone, and L 2  = 6,12,19,25-tetraoxo-4,6,11,12,16,18,23,24-octahydrotetrabenzo [b,g,k,p][1,5,10,14]tetra azacyclooctadecine-2,13-dicarboxylic acid) and their Ti and Zr metal complexes in alcoholic media using microwave protocol. Macrocyclic ligands were synthesised by incorporating of 3,5-diaminobenzoic acid, phthalic acid and 3,4-diaminopyridine in 1:1:1 molar ratio. The macrocyclic ligands and their metal complexes have been characterised by elemental analysis, conductance measurement, magnetic measurement and their structure configurations have been determined by various spectroscopic (FTIR, (1)H/(13)C NMR, UV-Vis, LC-MS mass, XRD and TGA) techniques. [ZrL2Cl2]Cl2 metal complex shows excellent antibacterial activity against ESBLs. A zone of inhibition and minimum inhibitory concentration was determined by McFarland and the dilution method, respectively. The spectral studies confirm the binding sites of the nitrogen atom of the macrocycles. An octahedral geometry has been assigned to the metal complexes based on the findings.

  17. Alternating 2,6-/3,5-substituted pyridine-acetylene macrocycles: π-stacking self-assemblies enhanced by intermolecular dipole-dipole interaction. (United States)

    Abe, Hajime; Ohtani, Kohei; Suzuki, Daiki; Chida, Yusuke; Shimada, Yuta; Matsumoto, Shinya; Inouye, Masahiko


    Macrocyclic compounds consisting of three 2,6-pyridylene and three 3,5-pyridylene units linked by acetylene bonds were synthesized by a Sonogashira reaction. The X-ray structures showed π-stacked pairs of two macrocycles, in which a 2,6-pyridylene unit of the one molecule overlaps a 3,5-pyridylene of the other molecule because of dipole-dipole interaction. Atomic force microscope (AFM) measurements revealed fibril structures indicating the stacking of the rigid planar macrocycles. Hydrogen-bonding ability of the macrocyclic inside was demonstrated by the addition of octyl β-D-glucopyranoside.

  18. History of avermectin and ivermectin, with notes on the history of other macrocyclic lactone antiparasitic agents. (United States)

    Campbell, William C


    The macrocyclic lactones enjoy a position of prominence in the control of parasites, and their history may be of interest, and even of use, in an age in which the search for chemotherapeutic agents has been transformed by modern technology. Much of their history has been recorded piecemeal in a wide variety of publications. The present review provides additional detail, and offers a personal perspective on the history of ivermectin and related avermectins. Brief notes are included on the subsequent development of other macrocyclic lactones. Milbemycin preceded the avermectins as a macrocyclic lactone of agricultural importance, but was used for a different purpose. Development of the avermectins arose from the isolation, in the laboratories of the Kitasato Institute, of a novel soil-dwelling bacterium and its transmittal (in 1974) to the laboratories of Merck & Co., Inc. There it was found (in 1975) to produce a potent anthelmintic substance, which was then identified and transmuted by interdisciplinary research into an antiparasitic product. Initially the focus was on its applicability to veterinary science and animal husbandry; and after developmental research by many scientific teams, the product was introduced commercially (in 1981) for the control of endoparasitic nematodes and ectoparasitic arthropods in livestock. Subsequently, special applications in human medicine were developed, and were successfully implemented in partnership with World Health Organization and several non-governmental organizations (NGOs).

  19. Heartworms, macrocyclic lactones, and the specter of resistance to prevention in the United States

    Directory of Open Access Journals (Sweden)

    Bowman Dwight D


    Full Text Available Abstract In order to provide a background to current concerns relative to the possible resistance of heartworms to macrocyclic lactones, this review summarizes various studies in which lack of efficacies (LOEs have been observed in dogs on macrocyclic lactone preventives relative to the United States of America. Some of these studies have been published in the peer-reviewed literature, others have appeared in various reports to the Center for Veterinary Medicine (CVM of the Food and Drug Administration (FDA of the USA as New Animal Drug Application (NADA summaries, and one appeared as a letter to US veterinarians. This review also discusses reports relating to the potential problem of heartworm resistance in microfilariae and third-stage larvae, as well as molecular markers associated with resistance to macrocyclic lactones within Dirofilaria immitis. As more work is being done in this area of great concern relative to the protection of dogs from infection using this class of preventives, it seems timely to summarize what is known about heartworms, their potential resistance to treatment, and the means of selecting for resistance genes in populations of this helminth in the laboratory and in the field.

  20. Dethreading of Tetraalkylsuccinamide-Based [2]Rotaxanes for Preparing Benzylic Amide Macrocycles. (United States)

    Martinez-Cuezva, Alberto; Rodrigues, Leticia V; Navarro, Cristian; Carro-Guillen, Fernando; Buriol, Lilian; Frizzo, Clarissa P; Martins, Marcos A P; Alajarin, Mateo; Berna, Jose


    The dethreading of a series of succinamide-based [2]rotaxanes bearing benzylic amide macrocycles is reported herein. These transformations proceeded quantitatively either under flash vacuum pyrolysis, conventional heating, or microwave irradiation. Studying the size complementarity of the stoppers at the ends of the thread and the cavity of the macrocycle allowed us to set up the best substituents for implementing the extrusion of the thread from the interlocked precursors. A variety of (1)H NMR kinetic experiments were carried out in order to evaluate the rate constants of the dethreading process, the half-life times of the rotaxanes, and the influence of temperature and solvents on these processes. The use of dibutylamino groups as stoppers yielded the rotaxane precursor in a reasonable yield and allowed the quantitative deslipping of the rotaxane. The overall process, including the rotaxane formation and its further dethreading, has been exploited for preparing benzylic amide macrocycles enhancing, in most cases, the results of the classical (2 + 2) condensation and other reported stepwise syntheses. The kinetics of the dethreading process is fairly sensitive to the electronic effects of the substituents on the isophthalamide unit or to the electronic nature of the pyridine rings through a conformational equilibrium expanding or contracting the cavity of the interlocked precursor.

  1. Incorporation of trinuclear lanthanide(III) hydroxo bridged clusters in macrocyclic frameworks. (United States)

    Kobyłka, Michał J; Ślepokura, Katarzyna; Acebrón Rodicio, Maria; Paluch, Marta; Lisowski, Jerzy


    A cluster of lanthanide(III) or yttrium(III) ions, Ln3(μ3-OH)2, (Ln(III) = Nd(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Yb(III), or Y(III)) can be bound in the center of a chiral macrocyclic amines H3L1(R), H3L1(S), and H3L2(S) obtained in a reduction of a 3 + 3 condensation product of (1R,2R)- or (1S,2S)-1,2-diaminocyclohexane and 2,6-diformyl-4-methylphenol or 2,6-diformyl-4-tertbutylphenol. X-ray crystal structures of the Nd(III), Sm(III), Gd(III), Dy(III), and Y(III) complexes reveal trinuclear complexes with Ln(III) ions bridged by the phenolate oxygen atoms of the macrocycle as well as by μ3-hydroxo bridges. In the case of the Nd(III) ion, another complex form can be obtained, whose X-ray crystal structure reveals two trinuclear macrocyclic units additionally bridged by hydroxide anions, corresponding to a [Ln3(μ3-OH)]2(μ2-OH)2 cluster encapsulated by two macrocycles. The formation of trinuclear complexes is confirmed additionally by (1)H NMR, electrospray ionization mass spectrometry (ESI MS), and elemental analyses. Titrations of free macrocycles with Sm(III) or Y(III) salts and KOH also indicate that a trinuclear complex is formed in solution. On the other hand, analogous titrations with La(III) salt indicate that this kind of complex is not formed even with the excess of La(III) salt. The magnetic data for the trinuclear Gd(III) indicate weak antiferromagnetic coupling (J = -0.17 cm(-1)) between the Gd(III) ions. For the trinuclear Dy(III) and Tb(III) complexes the χ(M)T vs T plots indicate a more complicated dependence, resulting from the combination of thermal depopulation of mJ sublevels, magnetic anisotropy, and possibly weak antiferromagnetic and ferromagnetic interactions.

  2. Enantiomeric self-recognition in homo- and heterodinuclear macrocyclic lanthanide(III) complexes. (United States)

    Lisowski, Jerzy


    The controlled formation of lanthanide(III) dinuclear μ-hydroxo-bridged [Ln(2)L(2)(μ-OH)(2)X(2)](n+) complexes (where X = H(2)O, NO(3)(-), or Cl(-)) of the enantiopure chiral macrocycle L is reported. The (1)H and (13)C NMR resonances of these complexes have been assigned on the basis of COSY, NOESY, TOCSY, and HMQC spectra. The observed NOE connectivities confirm that the dimeric solid-state structure is retained in solution. The enantiomeric nature of the obtained chiral complexes and binding of hydroxide anions are reflected in their CD spectra. The formation of the dimeric complexes is accompanied by a complete enantiomeric self-recognition of the chiral macrocyclic units. The reaction of NaOH with a mixture of two different mononuclear lanthanide(III) complexes, [Ln(1)L](3+) and [Ln(2)L](3+), results in formation of the heterodinuclear [Ln(1)Ln(2)L(2)(μ-OH)(2)X(2)](n+) complexes as well as the corresponding homodinuclear complexes. The formation of the heterodinuclear complex is directly confirmed by the NOESY spectra of [EuLuL(2)(μ-OH)(2)(H(2)O)(2)](4+), which reveal close contacts between the macrocyclic unit containing the Eu(III) ion and the macrocyclic unit containing the Lu(III) ion. While the relative amounts of homo- and heterodinuclear complexes are statistical for the two lanthanide(III) ions of similar radii, a clear preference for the formation of heterodinuclear species is observed when the two mononuclear complexes contain lanthanide(III) ions of markedly different sizes, e.g., La(III) and Yb(III). The formation of heterodinuclear complexes is accompanied by the self-sorting of the chiral macrocyclic units based on their chirality. The reactions of NaOH with a pair of homochiral or racemic mononuclear complexes, [Ln(1)L(RRRR)](3+)/[Ln(2)L(RRRR)](3+), [Ln(1)L(SSSS)](3+)/[Ln(2)L(SSSS)](3+), or [Ln(1)L(rac)](3+)/[Ln(2)L(rac)](3+), results in mixtures of homochiral, homodinuclear and homochiral, heterodinuclear complexes. On the contrary, no

  3. Novel Potent Hepatitis C Virus NS3 Serine Protease Inhibitors Derived from Proline-Based Macrocycles

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Kevin X.; Njoroge, F. George; Arasappan, Ashok; Venkatraman, Srikanth; Vibulbhan, Bancha; Yang, Weiying; Parekh, Tejal N.; Pichardo, John; Prongay, Andrew; Cheng, Kuo-Chi; Butkiewicz, Nancy; Yao, Nanhua; Madison, Vincent; Girijavallabhan, Viyyoor (SPRI)


    The hepatitis C virus (HCV) NS3 protease is essential for viral replication. It has been a target of choice for intensive drug discovery research. On the basis of an active pentapeptide inhibitor, 1, we envisioned that macrocyclization from the P2 proline to P3 capping could enhance binding to the backbone Ala156 residue and the S4 pocket. Thus, a number of P2 proline-based macrocyclic {alpha}-ketoamide inhibitors were prepared and investigated in an HCV NS3 serine protease continuous assay (K*{sub i}). The biological activity varied substantially depending on factors such as the ring size, number of amino acid residues, number of methyl substituents, type of heteroatom in the linker, P3 residue, and configuration at the proline C-4 center. The pentapeptide inhibitors were very potent, with the C-terminal acids and amides being the most active ones (24, K*{sub i} = 8 nM). The tetrapeptides and tripeptides were less potent. Sixteen- and seventeen-membered macrocyclic compounds were equally potent, while fifteen-membered analogues were slightly less active. gem-Dimethyl substituents at the linker improved the potency of all inhibitors (the best compound was 45, K*{sub i} = 6 nM). The combination of tert-leucine at P3 and dimethyl substituents at the linker in compound 47 realized a selectivity of 307 against human neutrophil elastase. Compound 45 had an IC{sub 50} of 130 nM in a cellular replicon assay, while IC{sub 50} for 24 was 400 nM. Several compounds had excellent subcutaneous AUC and bioavailability in rats. Although tripeptide compound 40 was 97% orally bioavailable, larger pentapeptides generally had low oral bioavailability. The X-ray crystal structure of compounds 24 and 45 bound to the protease demonstrated the close interaction of the macrocycle with the Ala156 methyl group and S4 pocket. The strategy of macrocyclization has been proved to be successful in improving potency (>20-fold greater than that of 1) and in structural depeptization.

  4. Metátese de olefinas aplicada ao fechamento de anéis: uma ferramenta poderosa para a síntese de macrociclos naturais Ring-closing olefin metathesis: a powerful tool for the synthesis of natural macrocycles

    Directory of Open Access Journals (Sweden)

    Anderson Rouge dos Santos


    Full Text Available For a quarter of a century, metathesis has become indispensable for the synthesis of natural and non-natural products, particularly of biologically active compounds. This review illustrates through a maximum of appropriate examples the power and the versatility of the metathesis ring-closure (RCM reaction as a key ring-closure methodology for the synthesis of natural macrocycles. Its high functional group compatibility as well as the possibility of further transformations makes this reaction a powerful tool in the cases where the structural framework and function requirements are difficult to meet.

  5. Synthesis, crystal structures and properties of two novel macrocyclic nickel(II) and copper(II) complexes (United States)

    Su, Yan-Hui; Liu, Jie; Li, Jia; Si, Xue-Zhi


    Two new 14-membered hexaaza macrocyclic complexes with the formulae [NiL](ClO 4) 2·CH 3COCH 3 ( 1) and [CuL](ClO 4) 2·CH 3COCH 3 ( 2), where L = 3,10-bis(2-thiophenemethyl)-1,3,5,8,10,12-hexaazacyclotetradecane, have been synthesized and characterized by elemental analyses, single-crystal X-ray diffraction analyses, electronic spectra, IR and TG-DTA. In 1, the nickel(II) ion is four-coordinated with four nitrogen atoms from the macrocycle and forms a square-planar coordination geometry. In 2, the copper(II) ion is six-coordinated with four nitrogen atoms from the macrocyclic ligand in the equatorial plane and two oxygen atoms from the perchlorate anions in the axial position exhibiting an elongated octahedron coordination geometry. The two complexes present two different molecular arrangements in which the [ML] 2+ (M = Ni, Cu) cation arrays in the manner of M(1)M(2)M(1)… in sequence. The pendant thiophene groups of the neighboring macrocycles have no π⋯π interactions. All the ClO4- anions and acetone molecules are involved in hydrogen-bonding interactions with the macrocyclic ligand.

  6. Peptide Macrocycles Featuring a Backbone Secondary Amine: A Convenient Strategy for the Synthesis of Lipidated Cyclic and Bicyclic Peptides on Solid Support

    DEFF Research Database (Denmark)

    Oddo, Alberto; Münzker, Lena; Hansen, Paul Robert


    A convenient strategy for the on-resin synthesis of macrocyclic peptides (3- to 13-mers) via intramolecular halide substitution by a diamino acid is described. The method is compatible with standard Fmoc/tBu SPPS and affords a tail-to-side-chain macrocyclic peptide featuring an endocyclic secondary...

  7. Experimental and theoretical study for corrosion inhibition of mild steel in normal hydrochloric acid solution by some new macrocyclic polyether compounds

    Energy Technology Data Exchange (ETDEWEB)

    Lebrini, M. [Unite de Catalyse et de Chimie du Solide, CNRS UMR 8181, ENSCL, BP 90108, F-59652 Villeneuve d' Ascq Cedex (France); Lagrenee, M. [Unite de Catalyse et de Chimie du Solide, CNRS UMR 8181, ENSCL, BP 90108, F-59652 Villeneuve d' Ascq Cedex (France); Vezin, H. [Laboratoire de Chimie Organique et Macromoleculaire, CNRS UMR 8009, USTL Bat C4, F-59655 Villeneuve d' Ascq Cedex (France); Traisnel, M. [Laboratoire des Procedes d' Elaboration des Revetements Fonctionnels, PERF UMR 8008, ENSCL, BP 90108, F-59652 Villeneuve d' Ascq Cedex (France); Bentiss, F. [Laboratoire de Chimie de Coordination et d' Analytique, Faculte des Sciences, Universite Chouaib Doukkali, BP 20, M-24000 El Jadida (Morocco)]. E-mail:


    New macrocyclic polyether compounds containing a 1,3,4-thiadiazole moiety have been prepared to study the corrosion inhibitive effect of mild steel in normal hydrochloric acid solutions. The salient features obtained from weight loss and electrochemical impedance spectroscopy (EIS) have been discussed. The results of these investigations have shown enhancement in inhibition efficiencies with the extent of the polyethylene glycol unit that forms a cavity. Data obtained from EIS show a frequency distribution and therefore a modelling element with frequency dispersion behaviour, a constant phase element (CPE) has been used. Display Omitted Adsorption of n-MCTH was found to follow the Langmuir's adsorption isotherm. The thermodynamic functions of adsorption process were calculated from experimental ac impedance data and the interpretation of the results are given. Molecular modelling has been conducted in an attempt to correlate the corrosion inhibition properties with the calculated quantum chemical parameters.

  8. Highly efficient synthesis of monodisperse poly(ethylene glycols) and derivatives through macrocyclization of oligo(ethylene glycols). (United States)

    Zhang, Hua; Li, Xuefei; Shi, Qiuyan; Li, Yu; Xia, Guiquan; Chen, Long; Yang, Zhigang; Jiang, Zhong-Xing


    A macrocyclic sulfate (MCS)-based approach to monodisperse poly(ethylene glycols) (M-PEGs) and their monofunctionalized derivatives has been developed. Macrocyclization of oligo(ethylene glycols) (OEGs) provides MCS (up to a 62-membered macrocycle) as versatile precursors for a range of monofunctionalized M-PEGs. Through iterative nucleophilic ring-opening reactions of MCS without performing group protection and activation, a series of M-PEGs, including the unprecedented 64-mer (2850 Da), can be readily prepared. Synthetic simplicity coupled with versatility of this new strategy may pave the way for broader applications of M-PEGs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Discovery and Optimization of Macrocyclic Quinoxaline-pyrrolo-dihydropiperidinones as Potent Pim-1/2 Kinase Inhibitors. (United States)

    Cee, Victor J; Chavez, Frank; Herberich, Bradley; Lanman, Brian A; Pettus, Liping H; Reed, Anthony B; Wu, Bin; Wurz, Ryan P; Andrews, Kristin L; Chen, Jie; Hickman, Dean; Laszlo, Jimmy; Lee, Matthew R; Guerrero, Nadia; Mattson, Bethany K; Nguyen, Yen; Mohr, Christopher; Rex, Karen; Sastri, Christine E; Wang, Paul; Wu, Qiong; Wu, Tian; Xu, Yang; Zhou, Yihong; Winston, Jeffrey T; Lipford, J Russell; Tasker, Andrew S; Wang, Hui-Ling


    The identification of Pim-1/2 kinase overexpression in B-cell malignancies suggests that Pim kinase inhibitors will have utility in the treatment of lymphoma, leukemia, and multiple myeloma. Starting from a moderately potent quinoxaline-dihydropyrrolopiperidinone lead, we recognized the potential for macrocyclization and developed a series of 13-membered macrocycles. The structure-activity relationships of the macrocyclic linker were systematically explored, leading to the identification of 9c as a potent, subnanomolar inhibitor of Pim-1 and -2. This molecule also potently inhibited Pim kinase activity in KMS-12-BM, a multiple myeloma cell line with relatively high endogenous levels of Pim-1/2, both in vitro (pBAD IC50 = 25 nM) and in vivo (pBAD EC50 = 30 nM, unbound), and a 100 mg/kg daily dose was found to completely arrest the growth of KMS-12-BM xenografts in mice.

  10. Immobilized copper(II) macrocyclic complex on MWCNTs with antibacterial activity

    Energy Technology Data Exchange (ETDEWEB)

    Tarlani, Aliakbar, E-mail: [Inorganic Nanostructures and Catalysts Research Lab., Chemistry & Chemical Engineering Research Center of Iran, Pajoohesh Blvd., km 17, Karaj Hwy, Tehran 14968-13151 (Iran, Islamic Republic of); Narimani, Khashayar [Inorganic Nanostructures and Catalysts Research Lab., Chemistry & Chemical Engineering Research Center of Iran, Pajoohesh Blvd., km 17, Karaj Hwy, Tehran 14968-13151 (Iran, Islamic Republic of); Mohammadipanah, Fatemeh; Hamedi, Javad [Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran 14155-6455 (Iran, Islamic Republic of); University of Tehran Biocompound Collection (UTBC), Microbial Technology and Products Research Center, University of Tehran, Tehran (Iran, Islamic Republic of); Tahermansouri, Hasan [Department of Chemistry, Ayatollah Amoli Branch, Islamic Azad University, Amol (Iran, Islamic Republic of); Amini, Mostafa M. [Department of Chemistry, Shahid Behshti University, 1983963113, Tehran (Iran, Islamic Republic of)


    Graphical abstract: In an antibacterial test, grafted copper(II) macrocyclic complex on the surface of MWCNT showed higher antibacterial activity against Bacillus subtilis compared to the individual MWCNT-COOH and the complex. - Highlights: • Copper(II) tetraaza macrocyclic complex covalently bonded to modified MWCNT. • Grafting of the complex carried out via an interaction between −C(=O)Cl group and NH of the ligand. • The samples were subjected in an antibacterial assessment to compare their activity. • Immobilized complex showed higher antibacterial activity against Bacillus subtilis ATCC 6633 compared to separately MWCNT-C(C=O)-OH and CuTAM. - Abstract: In a new approach, a copper(II) tetraaza macrocyclic complex (CuTAM) was covalently bonded on modified multi-walled carbon nanotubes (MWCNTs). To achieve this purpose, MWCNTs were converted to MWCNT-COCl and then reacted to NH groups of TAM ligand. The prepared material was characterized by Fourier Transform Infrared (FT-IR), X-ray diffraction (XRD), Raman spectroscopy, thermal gravimetric analysis (TGA), and FESEM (field emission scanning electron microscopy). FT-IR and TGA demonstrated the presence of the organic moieties, and XRD proved that the structure of MWCNTs remained intact during the three modification steps. An increase in the I{sub D}/I{sub G} ratio in Raman spectra confirmed the surface modifications. Finally, the samples were subjected to an antibacterial assessment to compare their biological activity. The antibacterial test showed that the grafted complex on the surface of the nanotube (MWCNT-CO-CuTAM) has higher antibacterial activity against Bacillus subtilis ATCC 6633 than the MWCNT-COOH and CuTAM with 1000 and 2000 μg/mL.

  11. Macrocyclic Hepatitis C Virus NS3/4A Protease Inhibitors: An Overview of Medicinal Chemistry. (United States)

    Pillaiyar, Thanigaimalai; Namasivayam, Vigneshwaran; Manickam, Manoj


    Hepatitis C virus (HCV) is a causative agent of hepatitis C infectious disease that primarily affects the liver, ranging in severity from a mild illness lasting a few weeks to a lifelong illness. The 9.6 kb RNA genome of HCV encodes approximately 3000 amino acid polyprotein that must be processed by host and viral proteases into both structural (S) and non-structural (NS) proteins, respectively. Targeting the serine protease NS3 with an activating factor NS4A, i.e., NS3/4A has been considered as one of the most attractive targets for the development of anti-HCV therapy. Although there is no vaccine available, antiviral medicines cure approximately 90% of the persons with hepatitis C infection. On the other hand, efficacy of these medications can be hampered due to the rapid drug and cross resistances. To date, all developed HCV NS3/4A inhibitors are mainly peptide-based compounds derived from the cleavage products of substrate. Specifically macrocyclic peptidomimetics have rapidly emerged as a classical NS3/4A protease inhibitors for treating the HCV infection. This review highlights the development of macrocyclic anti-HCV NS3/4A protease, as well as clinically important inhibitors developed from linear peptides, discovered during the last 12 years (2003-2015) from all sources, including laboratory synthetic methods, virtual screening and structure-based molecular docking studies. We emphasize the rationale behind the design, study of structure-activity relationships, and mechanism of inhibitions and cellular effect of the macrocyclic inhibitors.

  12. Kinetic Analysis for Macrocyclizations Involving Anionic Template at the Transition State

    Directory of Open Access Journals (Sweden)

    Vicente Martí-Centelles


    competitive oligomerization/polymerization processes yielding undesired oligomeric/polymeric byproducts. The effect of anions has also been included in the kinetic models, as they can act as catalytic templates in the transition state reducing and stabilizing the transition state. The corresponding differential equation systems for each kinetic model can be solved numerically. Through a comprehensive analysis of these results, it is possible to obtain a better understanding of the different parameters that are involved in the macrocyclization reaction mechanism and to develop strategies for the optimization of the desired processes.

  13. A flexible cyclophane: Design, synthesis, and structure of a multibridged tris-tetrathiafulvalene (TTF) macrocycle

    DEFF Research Database (Denmark)

    Takimiya, K.; Thorup, Niels; Becher, J.


    that the neutral molecules include two (3a) or one chloroform molecule (3b) as solvent of crystallization inside the cavity, whereas the I-3(-) salt of 3b, obtained by electrocrystallization, has a molecular structure which is different from that of the neutral molecule in that the cavity has completely collapsed.......The tris-tetrathiafulvalene (TTF) macrocycles 3 with a large end-cavity were effectively synthesized from the readily available tetrakis(cyanoethylthio)TTF by means of a selective deprotection/realkylation sequence followed by an intramolecular coupling reaction. Crystal structure analyses revealed...

  14. Synthesis of NLO polycarbonates via the ring-opening polymerization of macrocyclic prepolymers (United States)

    Kulig, Joseph B.; Moore, Collin G.; Brittain, William J.; Gilmour, Sandra; Perry, Joseph W.


    The synthesis and characterization of polycarbonates and polyformals is described. Copolymers of bisphenol A (BPA) and either a triphenyloxazole (1) or phenylquinoxaline (2) monomer were prepared. The polycarbonate copolymers were prepared by ring-opening polymerization of macrocyclic prepolymers using a solvent-free process. Preliminary electro- optic measurements have been performed on the polycarbonate copolymers of BPA and 1. Polyformals have also been prepared by a conventional polymerization process involving the reaction of dichloromethane with different feed ratios of BPA and either 1 or 2. The glass transition temperature of either the polyformals or polycarbonates is dramatically increased by increasing mole fractions of monomers 1 and 2.

  15. "Cyclamen Red" colors based on a macrocyclic anthocyanin in carnation flowers. (United States)

    Gonnet, J F; Fenet, B


    The "cyclamen" red (or pink) colors in carnation flowers-cultivars Red Rox and eight others-are based on the presence of a new macrocyclic anthocyanin, pelargonidin 3,5-di-O-beta-glucoside(6' ', 6' "-malyl diester) identified by spectroscopic methods. The instability of the bridging malyl group with sugars in acidic medium readily causes the formation of the opened ring form, 3-O-(6' '-O-malylglucoside)-5-O-glucoside. The issue of cyclamen colors based in carnations on this original acylated pelargonidin derivative simulating those based on simpler cyanidin glycosides in Rosa cultivars is discussed using CIELAB colorimetric coordinates.

  16. Catalytic Hydrolysis of Phosphate Diester with Metal Complexesof Macrocyclic Tetraamine in Comicellar Solution

    Institute of Scientific and Technical Information of China (English)

    XIANG Qing-Xiang; YU Xiao-Qi; YOU Jing-Song; YAN Qian-Shun; XIE Ru-Gang


    Four novel pyridine or benzene ring-containing pendant macrocyclic dioxotetraanines 2,6-dioxo-1,4,7,10-tetraazacy-clododeane ligands have been synthesized.Their metal com-plexes have been investigated as catalysts for the hydrolysis of bis(p-nitrophenyl) phosphate (BNPP) in aqueous comicellar solution.The results indicate that the hydrophobic interaction between substrate and metal complex, the nature of transition metal ion, and the micellar microenvironment are important factors for the hydrolysis, of BNPP.Large rate enhancement (up to over two-three orders magnitude) employing 5 hasbeen observed.

  17. Neighbor-directed histidine N(τ) alkylation. A route to imidazolium-containing phosphopeptide macrocycles

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Wen-Jian [National Cancer Inst., Frederick, MD (United States); Park, Jung-Eun [National Cancer Inst., Bethesda, MD (United States); Grant, Robert [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Lai, Christopher C. [National Cancer Inst., Frederick, MD (United States); Kelley, James A. [National Cancer Inst., Frederick, MD (United States); Yaffe, Michael B. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Lee, Kyung S. [National Cancer Inst., Bethesda, MD (United States); Burke, Terrence R. [National Cancer Inst., Frederick, MD (United States)


    Our recently discovered, selective, on-resin route to N(τ)-alkylated imidazolium-containing histidine residues affords new strategies for peptide mimetic design. In this, we demonstrate the use of this chemistry to prepare a series of macrocyclic phosphopeptides, in which imidazolium groups serve as ring-forming junctions. These cationic moieties subsequently serve to charge-mask the phosphoamino acid group that directed their formation. Furthermore, neighbor-directed histidine N(τ)-alkylation opens the door to new families of phosphopeptidomimetics for use in a range of chemical biology contexts.


    Institute of Scientific and Technical Information of China (English)

    SUN Qiang; ZHANG Jinlan; XU Jiping


    Chelating resin with macrocyclic mercaptal group supported on macroporous polystyrene beads was synthesized, which showed good selectivity to Hg2+: its complexing capacity amounted to 30-60 mg Hg2+/g resin, two orders of magnitude greater than for other metal ions such as Ca2+, Zn2+,Cd2+, Pb2+ etc. This resin could restore the activity of urease which had been deactivated by poisoning with Hg2+. Its restoring power was far better than that of the mercapto-resin and common anionic exchange resins. It showed some promising use as an oral polymeric detoxifying drug for mercury poisoning.

  19. Kinetics of oxidation of nickel(II) aza macrocycles by peroxydisulphate in aqueous media

    Indian Academy of Sciences (India)

    J Lalitham; V R Vijayaraghavan


    The kinetics of the oxidation of nickel (II) hexaaza and nickel (II) pentaaza macrocycles by the peroxydisulphate anion, S2O8 2-, were studied in aqueous media. Effect of H on reaction rate was also studied. The rate increases with increase of S2OO8 2- concentration. Rates are almost independent of acid between H 4 and 2, giving overall a relatively simple second-order rate law followed by oxidation within the ion pair solvent shell. Using rate = +1/2 d[Ni(L)3+]/dt = k[Ni(L)2+][S2O8 2-], oxidation rate constants were determined.

  20. Synthesis and P1' SAR exploration of potent macrocyclic tissue factor-factor VIIa inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Ladziata, Vladimir (Uladzimir); Glunz, Peter W.; Zou†, Yan; Zhang, Xiaojun; Jiang, Wen; Jacutin-Porte, Swanee; Cheney, Daniel L.; Wei, Anzhi; Luettgen, Joseph M.; Harper, Timothy M.; Wong, Pancras C.; Seiffert, Dietmar; Wexler, Ruth R.; Priestley, E. Scott (BMS)


    Selective tissue factor-factor VIIa complex (TF-FVIIa) inhibitors are viewed as promising compounds for treating thrombotic disease. In this contribution, we describe multifaceted exploratory SAR studies of S1'-binding moieties within a macrocyclic chemotype aimed at replacing cyclopropyl sulfone P1' group. Over the course of the optimization efforts, the 1-(1H-tetrazol-5-yl)cyclopropane P1' substituent emerged as an improved alternative, offering increased metabolic stability and lower clearance, while maintaining excellent potency and selectivity.

  1. New macrocyclic compounds using organotin complexes as intermediates: synthesis and characterization

    Directory of Open Access Journals (Sweden)

    Harminder Kaur


    Full Text Available Background & Aim:A new series of macrocyclic compounds 1-4 have been synthesized using tin as templates.Method:Tin templates are formed by refluxing the solution of dibutyltin (IV oxide with orthophenylenediamine (L1H,4-chlorocatechol (L2H, butane dithiol (L3H and 3-carboxypropyldisulphide (L4H. Results:The reaction is visualizedby cleavage X-Sn-X (X= oxygen/ nitrogen/ sulphur atom bond of tin template when treated withadipoyldichloride. Conclusion:The compounds 1-4 are characterized with the aid of elemental analyses, IR and NMR(1H, 13C studies which confirmed their proposed framework.

  2. Application of Calixarenes as Macrocyclic Ligands for Uranium(VI: A Review

    Directory of Open Access Journals (Sweden)

    Katarzyna Kiegiel


    Full Text Available Calixarenes represent a well-known family of macrocyclic molecules with broad range of potential applications in chemical, analytical, and engineering materials fields. This paper covers the use of calixarenes as complexing agents for uranium(VI. The high effectiveness of calix[6]arenes in comparison to other calixarenes in uranium(VI separation process is also presented. Processes such as liquid-liquid extraction (LLE, liquid membrane (LM separation, and ion exchange are considered as potential fields for application of calixarenes as useful agents for binding UO22+ for effective separation from aqueous solutions containing other metal components.

  3. Synthesis and antituberculosis activity of novel unfolded and macrocyclic derivatives of ent-kaurane steviol. (United States)

    Khaybullin, Ravil N; Strobykina, Irina Yu; Dobrynin, Alexey B; Gubaydullin, Aidar T; Chestnova, Regina V; Babaev, Vasiliy M; Kataev, Vladimir E


    New derivatives of steviol 1, the aglycone of the glycosides of Stevia rebaudiana, including a novel class of semisynthetic diterpenoids, namely macrocyclic ent-kauranes were synthesized. These compounds possess antituberculosis activity inhibiting the in vitro growth of Mycobacterium Tuberculosis (H37R(V) strain) with MIC 5-20 μg/ml that is close to MIC 1 μg/ml demonstrated by antituberculosis drug isoniazid in control experiment. For the first time it was found that the change of ent-kaurane geometry (as in steviol 1) of tetracyclic diterpenoid skeleton to ent-beyerane one (as in isosteviol 2) influences on antituberculosis activity.

  4. Efficient macrocyclization of U-turn preorganized peptidomimetics: the role of intramolecular H-bond and solvophobic effects. (United States)

    Becerril, Jorge; Bolte, Michael; Burguete, M Isabel; Galindo, Francisco; García-España, Enrique; Luis, Santiago V; Miravet, Juan F


    Simple peptidomimetic molecules derived from amino acids were reacted with meta- and para-bis(bromomethyl)benzene in acetonitrile to very efficiently yield macrocyclic structures. The cyclization reaction does not require high dilution techniques and seems to be insensitive to the size of the formed macrocycle. The analysis of data obtained by (1)H NMR, single-crystal X-ray diffraction, fluorescence measurements, and molecular mechanics indicate that folded conformations can preorganize the system for an efficient cyclization. The role played by intramolecular hydrogen-bonding and solvophobic effects in the presence of folded conformations is analyzed.

  5. Cyclooctane metathesis catalyzed by silica-supported tungsten pentamethyl [(ΞSiO)W(Me)5]: Distribution of macrocyclic alkanes

    KAUST Repository

    Riache, Nassima


    Metathesis of cyclic alkanes catalyzed by the new surface complex [(ΞSiO)W(Me)5] affords a wide distribution of cyclic and macrocyclic alkanes. The major products with the formula CnH2n are the result of either a ring contraction or ring expansion of cyclooctane leading to lower unsubstituted cyclic alkanes (5≤n≤7) and to an unprecedented distribution of unsubstituted macrocyclic alkanes (12≤n≤40), respectively, identified by GC/MS and by NMR spectroscopies.

  6. Response of Critical Speed to Different Macrocycle Phases during Linear Periodization on Young Swimmers

    Directory of Open Access Journals (Sweden)

    João Bartholomeu NETO


    Full Text Available Sport training programs to young swimmers have to aggregate different physical stimulus to collaborate with overall physical development, which can lead to reach best results in competitions. Linear periodization seems to be a powerful tool that allow the organization of these stimulus. However, this model has been not studied. Regarding physical capacities, aerobic fitness is inversely related with fatigue and exercise performance. Although aerobic capacity evaluation used to be expensive, critical speed (CS is easy and non - expensive tool capable to make this measurement. Thus, the aim of this study was evaluate the effects of linear periodization in CS on well - trained young swimmers. Sixteen athletes (age: 14.06  1.22 years, height: 163.52  10.99 cm, weight: 57.4  12.7 kg, body mass index: 21.24  37; 7 ♀, were underwent to a linear macrocycle training with 23 weeks divided in four mesocycles: general endurance (i.e., 4 weeks, specific endurance (i.e., 8 weeks, competitive (i.e., 7 weeks and taper (i.e., 4 weeks. Results showed significantly improve on CS after competitive and taper mesocycle phases, which was composed by higher training intensity in comparison with other macrocycle phases. Therefore, the results of the present study indicate a collaboration of mesocycle intensity on the cumulative effects of linear periodization in CS improve on young swimmers.

  7. Tiered analytics for purity assessment of macrocyclic peptides in drug discovery: Analytical consideration and method development. (United States)

    Qian Cutrone, Jingfang Jenny; Huang, Xiaohua Stella; Kozlowski, Edward S; Bao, Ye; Wang, Yingzi; Poronsky, Christopher S; Drexler, Dieter M; Tymiak, Adrienne A


    Synthetic macrocyclic peptides with natural and unnatural amino acids have gained considerable attention from a number of pharmaceutical/biopharmaceutical companies in recent years as a promising approach to drug discovery, particularly for targets involving protein-protein or protein-peptide interactions. Analytical scientists charged with characterizing these leads face multiple challenges including dealing with a class of complex molecules with the potential for multiple isomers and variable charge states and no established standards for acceptable analytical characterization of materials used in drug discovery. In addition, due to the lack of intermediate purification during solid phase peptide synthesis, the final products usually contain a complex profile of impurities. In this paper, practical analytical strategies and methodologies were developed to address these challenges, including a tiered approach to assessing the purity of macrocyclic peptides at different stages of drug discovery. Our results also showed that successful progression and characterization of a new drug discovery modality benefited from active analytical engagement, focusing on fit-for-purpose analyses and leveraging a broad palette of analytical technologies and resources.

  8. A supramolecular ruthenium macrocycle with high catalytic activity for water oxidation that mechanistically mimics photosystem II (United States)

    Schulze, Marcus; Kunz, Valentin; Frischmann, Peter D.; Würthner, Frank


    Mimicking the ingenuity of nature and exploiting the billions of years over which natural selection has developed numerous effective biochemical conversions is one of the most successful strategies in a chemist's toolbox. However, an inability to replicate the elegance and efficiency of the oxygen-evolving complex of photosystem II (OEC-PSII) in its oxidation of water into O2 is a significant bottleneck in the development of a closed-loop sustainable energy cycle. Here, we present an artificial metallosupramolecular macrocycle that gathers three Ru(bda) centres (bda = 2,2‧-bipyridine-6,6‧-dicarboxylic acid) that catalyses water oxidation. The macrocyclic architecture accelerates the rate of water oxidation via a water nucleophilic attack mechanism, similar to the mechanism exhibited by OEC-PSII, and reaches remarkable catalytic turnover frequencies >100 s-1. Photo-driven water oxidation yields outstanding activity, even in the nM concentration regime, with a turnover number of >1,255 and turnover frequency of >13.1 s-1.

  9. Synthesis, characterization, and photoactivated DNA cleavage by copper (II)/cobalt (II) mediated macrocyclic complexes. (United States)

    Naik, H R Prakash; Naik, H S Bhojya; Aravinda, T; Lamani, D S


    We report the synthesis of new photonuclease consisting of two Co(II)/Cu(II) complexes of macrocyclic fused quinoline. Metal complexes are [MLX(2)], type where M = Co(II) (5), Cu(II) (6), and X = Cl, and are well characterized by elemental analysis, Fourier transform infrared spectroscopy, (1)H-NMR and electronic spectra. We have shown that photocleavage of plasmid DNA is markedly enhanced when this ligand is irradiated in the presence of Cu(II), and more so than that of cobalt. The chemistry of ternary and binary Co(II) complexes showing efficient light induced (360 nm) DNA cleavage activity is summarized. The role of the metal in photoinduced DNA cleavage reactions is explored by designing complex molecules having macrocyclic structure. The mechanistic pathways are found to be concentration dependent on Co(II)/Cu(II) complexes and the photoexcitation energy photoredox chemistry. Highly effective DNA cleavage ability of 6 is attributed to the effective cooperation of the metal moiety.

  10. Potent macrocyclic inhibitors of insulin-regulated aminopeptidase (IRAP) by olefin ring-closing metathesis. (United States)

    Andersson, Hanna; Demaegdt, Heidi; Johnsson, Anders; Vauquelin, Georges; Lindeberg, Gunnar; Hallberg, Mathias; Erdelyi, Mate; Karlen, Anders; Hallberg, Anders


    Macrocyclic analogues of angiotensin IV (Ang IV, Val(1)-Tyr(2)-Ile(3)-His(4)-Pro(5)-Phe(6)) targeting the insulin-regulated aminopeptidase (IRAP) have been designed, synthesized, and evaluated biologically. Replacement of His(4)-Pro(5)-Phe(6) by a 2-(aminomethyl)phenylacetic acid (AMPAA) moiety and of Val(1) and Ile(3) by amino acids bearing olefinic side chains followed by macrocyclization provided potent IRAP inhibitors. The impact of the ring size and the type (saturated versus unsaturated), configuration, and position of the carbon-carbon bridge was assessed. The ring size generally affects the potency more than the carbon-carbon bond characteristics. Replacing Tyr(2) by β(3)hTyr or Phe is accepted, while N-methylation of Tyr(2) is deleterious for activity. Removal of the carboxyl group in the C-terminal slightly reduced the potency. Inhibitors 7 (K(i) = 4.1 nM) and 19 (K(i) = 1.8 nM), both encompassing 14-membered ring systems connected to AMPAA, are 10-fold more potent than Ang IV and are also more selective over aminopeptidase N (AP-N). Both compounds displayed high stability against proteolysis by metallopeptidases.

  11. Does a water-training macrocycle really create imbalances in swimmers' shoulder rotator muscles? (United States)

    Batalha, Nuno; Marmeleira, José; Garrido, Nuno; Silva, António J


    The continuous execution of swimming techniques may cause muscle imbalances in shoulder rotators leading to injury. However, there is a lack of published research studies on this topic. The aim of this study was to analyze the influence of a competitive swim period on the shoulder rotator-cuff balance in young swimmers. A randomized controlled pretest-posttest design was used, with two measurements performed during the first macrocycle of the swimming season (baseline and 16 weeks). Twenty-seven young male swimmers (experimental group) and 22 male students who were not involved in swim training (control group) with the same characteristics were evaluated. Peak torque of shoulder internal and external rotators was assessed. Concentric action at 1.04 rad s(-1) (3 repetitions) and 3.14 rad s(-1) (20 repetitions) was measured using an isokinetic dynamometer (Biodex System 3). External/internal rotators strength ratios were also obtained. For both protocols, there were significant training effects on internal rotator strength and external/internal rotator ratios (p ≤ .05). This trend was the same for both shoulders. Within-group analysis showed significant changes from baseline to 16 weeks for internal rotators strength and unilateral ratios of the experimental group. Swimmers' internal rotator strength levels increased significantly. In contrast, a significant decrease of the unilateral ratios was observed. Findings suggest that a competitive swim macrocycle leads to an increase in muscular imbalances in the shoulder rotators of young competitive swimmers. Swimming coaches should consider implementing a compensatory strength-training program.

  12. The ex vivo neurotoxic, myotoxic and cardiotoxic activity of cucurbituril-based macrocyclic drug delivery vehicles. (United States)

    Oun, Rabbab; Floriano, Rafael S; Isaacs, Lyle; Rowan, Edward G; Wheate, Nial J


    The cucurbituril family of drug delivery vehicles have been examined for their tissue specific toxicity using ex vivo models. Cucurbit[6]uril (CB[6]), cucurbit[7]uril (CB[7]) and the linear cucurbituril-derivative Motor2 were examined for their neuro-, myo- and cardiotoxic activity and compared with β-cyclodextrin. The protective effect of drug encapsulation by CB[7] was also examined on the platinum-based anticancer drug cisplatin. The results show that none of the cucurbiturils have statistically measurable neurotoxicity as measured using mouse sciatic nerve compound action potential. Cucurbituril myotoxicity was measured by nerve-muscle force of contraction through chemical and electrical stimulation. Motor2 was found to display no myotoxicity, whereas both CB[6] and CB[7] showed myotoxic activity via a presynaptic effect. Finally, cardiotoxicity, which was measured by changes in the rate and force of right and left atria contraction, was observed for all three cucurbiturils. Free cisplatin displays neuro-, myo- and cardiotoxic activity, consistent with the side-effects seen in the clinic. Whilst CB[7] had no effect on the level of cisplatin's neurotoxic activity, drug encapsulation within the macrocycle had a marked reduction in both the drug's myo- and cardiotoxic activity. Overall the results are consistent with the relative lack of toxicity displayed by these macrocycles in whole animal acute systemic toxicity studies and indicate continued potential of cucurbiturils as drug delivery vehicles for the reduction of the side effects associated with platinum-based chemotherapy.

  13. Ipomoeassin F, a new cytotoxic macrocyclic glycoresin from the leaves of Ipomoea squamosa from the Suriname rainforest. (United States)

    Cao, Shugeng; Norris, Andrew; Wisse, Jan H; Miller, James S; Evans, Randy; Kingston, David G I


    A new cytotoxic macrocyclic glycoresin, ipomoeassin F (6), has been isolated from the leaves of Ipomoea squamosa. The structure was elucidated by the interpretation of spectral data. Compound 6 was strongly active in the A2780 (human ovarian cancer cell line) assay with an IC(50) value of 0.036 microM.

  14. Diverse organo-peptide macrocycles via a fast and catalyst-free oxime/intein-mediated dual ligation. (United States)

    Satyanarayana, Maragani; Vitali, Francesca; Frost, John R; Fasan, Rudi


    Macrocyclic Organo-Peptide Hybrids (MOrPHs) can be prepared from genetically encoded polypeptides via a chemoselective and catalyst-free reaction between a trifunctional oxyamino/amino-thiol synthetic precursor and an intein-fusion protein incorporating a bioorthogonal keto group.

  15. The role of macrocyclic ligands in the peroxo/superoxo nature of Ni-O2 biomimetic complexes. (United States)

    Zapata-Rivera, Jhon; Caballol, Rosa; Calzado, Carmen J


    The impact of the macrocyclic ligand on the electronic structure of two LNi-O2 biomimetic adducts, [Ni(12-TMC)O2](+) (12-TMC = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane) and [Ni(14-TMC)O2](+) (14-TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane), has been inspected by means of difference-dedicated configuration interaction calculations and a valence bond reading of the wavefunction. The system containing the 12-membered macrocyclic ligand has been experimentally described as a side-on nickel(III)-peroxo complex, whereas the 14-membered one has been characterized as an end-on nickel(II)-superoxide. Our results put in evidence the relationship between the steric effect of the macrocyclic ligand, the O2 coordination mode and the charge transfer extent between the Ni center and the O2 molecule. The 12-membered macrocyclic ligand favors a side-on coordination, a most efficient overlap between Ni 3d and O2 π* orbitals and, consequently, a larger charge transfer from LNi fragment to O2 molecule. The analysis of the ground-state electronic structure shows an enhancement of the peroxide nature of the Ni-O2 interaction for [Ni(12-TMC)O2](+), although a dominant superoxide character is found for both systems.

  16. Isonitrile iron(II) complexes with chiral N2P2 macrocycles in the enantioselective transfer hydrogenation of ketones. (United States)

    Bigler, Raphael; Mezzetti, Antonio


    Bis(isonitrile) iron(II) complexes bearing a C2-symmetric N2P2 macrocyclic ligand, which are easily prepared from the corresponding bis(acetonitrile) analogue, catalyze the asymmetric transfer hydrogenation (ATH) of a broad scope of ketones in excellent yields (up to 98%) and with high enantioselectivity (up to 91% ee).

  17. Azalomycin F4a 2-ethylpentyl ester, a new macrocyclic lactone, from mangrove actinomycete Streptomyces sp.211726

    Institute of Scientific and Technical Information of China (English)

    Gan Jun Yuan; Kui Hong; Hai Peng Lin; Jia Li


    Azalomycin F4a 2-ethylpentyl ester,a new 36-membered macrocyclic lactone antibiotic,was isolated from mangrove actinomycete Streptomyces sp.211726.Its structure was elucidated on the basis of spectroscopic data.The compound showed broad-spectrum antifungal activity and moderate cytotoxicity against human colon tumor cell HCT-116.

  18. ForceGen 3D structure and conformer generation: from small lead-like molecules to macrocyclic drugs (United States)

    Cleves, Ann E.; Jain, Ajay N.


    We introduce the ForceGen method for 3D structure generation and conformer elaboration of drug-like small molecules. ForceGen is novel, avoiding use of distance geometry, molecular templates, or simulation-oriented stochastic sampling. The method is primarily driven by the molecular force field, implemented using an extension of MMFF94s and a partial charge estimator based on electronegativity-equalization. The force field is coupled to algorithms for direct sampling of realistic physical movements made by small molecules. Results are presented on a standard benchmark from the Cambridge Crystallographic Database of 480 drug-like small molecules, including full structure generation from SMILES strings. Reproduction of protein-bound crystallographic ligand poses is demonstrated on four carefully curated data sets: the ConfGen Set (667 ligands), the PINC cross-docking benchmark (1062 ligands), a large set of macrocyclic ligands (182 total with typical ring sizes of 12-23 atoms), and a commonly used benchmark for evaluating macrocycle conformer generation (30 ligands total). Results compare favorably to alternative methods, and performance on macrocyclic compounds approaches that observed on non-macrocycles while yielding a roughly 100-fold speed improvement over alternative MD-based methods with comparable performance.

  19. A Macrocyclic 1,4-Diketone Enables the Synthesis of a p-Phenylene Ring That Is More Strained than a Monomer Unit of [4]Cycloparaphenylene. (United States)

    Mitra, Nirmal K; Corzo, Hector H; Merner, Bradley L


    The synthesis of a p-terphenyl-based macrocycle, containing a p-phenylene unit with 42.6 kcal/mol of strain energy (SE), is reported. The conversion of a macrocyclic 1,4-diketone to a highly strained arene system takes place over five synthetic steps, featuring iterative dehydrative reactions in the aromatization protocol. Spectroscopic data of the deformed benzenoid macrocycle are in excellent agreement with other homologues that have been reported, indicating that the central p-phenylene ring of 9 is aromatic.

  20. Kinetics and mechanism of the stepwise complex formation of Cu(II) with tren-centered tris-macrocycles. (United States)

    Soibinet, Matthieu; Gusmeroli, Deborah; Siegfried, Liselotte; Kaden, Thomas A; Palivan, Cornelia; Schweiger, Arthur


    The stepwise complexation kinetics of Cu2+ with three tetratopic ligands L1, L2 and L3, tren-centred macrocycles with different bridges connecting the 14-membered macrocycles with the tren unit, have been measured by stopped-flow photodiode array techniques at 25 degrees C, I= 0.5 M (KNO3), and pH = 4.96. The reaction between the first Cu2+ and the ligand consists of several steps. In a rapid reaction Cu2+ first binds to the flexible and more reactive tren-unit. In this intermediate a translocation from the tren unit to the macrocyclic ring, which forms the thermodynamic more stable complex, takes place. This species can react further with a second Cu2+ to give a heterotopic dinuclear species with one Cu2+ bound by the tren-unit and the other coordinated by the macrocycle. A further translocation occurs to give the homoditopic species with two Cu2+ in the macrocycles. Finally a slow rearrangement of the dinuclear complex gives the final species. The rates of the translocation are dependent on the length and rigidity of the bridge, whereas the complexation rates with the tren unit are little affected by it. VIS spectra of the species obtained by fitting the kinetic results, EPR-spectra taken during the reaction, and ES mass spectra of the products confirm the proposed mechanism. The addition of a second, third and fourth equivalent of Cu2+ proceeds in an analogous way, but is complicated by the fact that we start and end with a mixture of species. These steps were evaluated in a qualitative way only.

  1. Macrocyclic compound as ionophores in lead(Ⅱ)ion-selective electrodes with excellent response characteristics

    Institute of Scientific and Technical Information of China (English)

    HUANG MeiRong; MA XiaoLi; LI XinGui


    Macrocyclic compounds, such as crown ethers, azacrown ethers, thiacrown ethers, calixarenes and porphyrins, which act as ionophores in lead(Ⅱ) ion-selective electrodes, are systematically summarized based on the latest literatures. The molecular structure characteristics of the ionophores are general-ized. The modification regulations for the substituted ionophores are elaborated with the purpose ofimproving the response features of the lead(Ⅱ) ion-selective electrodes assembled by them. It is pointed out that the introduction of pendant moieties which contain soft base coordination centers like N, S and P atoms is in favor of adjusting the cavity size and conformation of the macrocyclic com-pounds. Furthermore, there is synergic effect between the cavity and the donor sites of the ligand and thus the selective complexation of lead ions is easily realized, resulting in significant avoidance of the interference from other metal ions. The macrocyclic ionophore having the best response characteris-tics thus far was found to be N,N'-dimethylcyanodiaza-18-crown-6 with the detection limit of 7.0×10-8 (14.5 μg/L), which is one of the uncommon ionophores that can really eliminate the interference from silver and mercury ions. The selectivity coefficients of the ionophore for lead ions over other metal ions, such as alkali, alkaline earth and transition metal ions are in the order of 10-4 or smaller, where the se-lectivity coefficient of lead(Ⅱ) over mercury(Ⅱ) ions is much lower, down to 8.9×10-4. The structure de-sign idea for high-performance ionophore is proposed according to present results. The incorporation of nitrogen atom, especially cyano group or thiocyano group or amino/imino groups, rather than thio atom alone could result in new excellent lead ionophores. The aborative design for metacyclophanes containing aromatic nitrogen atoms with the aim of creating excellent ionophores would also become a potential research trend. The lead(Ⅱ) ion

  2. A G326E substitution in the glutamate-gated chloride channel 3 (GluCl3) of the two-spotted spider mite Tetranychus urticae abolishes the agonistic activity of macrocyclic lactones. (United States)

    Mermans, Catherine; Dermauw, Wannes; Geibel, Sven; Van Leeuwen, Thomas


    The macrocyclic lactones abamectin and milbemectin are frequently used to control phytophagous mites such as Tetranychus urticae. Consequently, resistance has developed and was genetically linked with substitutions in the glutamate-gated chloride channel (GluCl) subunits TuGluCl1 and TuGluCl3. Here, we functionally validated a G326E substitution in TuGluCl3 by functional expression in Xenopus laevis oocytes followed by two-electrode voltage-clamp electrophysiology. Homomeric wild-type and mutated GluCl3 were successfully expressed. l-glutamic-acid-induced currents exhibited a rapid onset equal in both channels and EC50 for l-glutamic-acid was in the micromolar range (384.2 μm and 292.7 μm, respectively). Abamectin and milbemycin A4 elicited sustained currents in wild-type GluCl3, but the G326E substitution completely abolished the agonistic activity of macrocyclic lactones. A target-site mutation in Tu GluCl3 contributes to avermectin resistance in T. urticae. However, given the multitude of channel genes and the potential additive or synergistic effects of mutations, to what extent mutations determine the often extremely strong resistance phenotype in the field deserves further study. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.


    African Journals Online (AJOL)

    Ethiop.,3(1), 17-24 (1 939), ... Binucleating copper(II) and cobaltilll complexes of the ligand,. 4,16,20 ... to serve as simple model for multi-metal centered catalysts. ... catalysis in the four electron reduction of dioxygen to water (11,12).

  4. Strontium-selective membrane electrodes based on some recently synthesized benzo-substituted macrocyclic diamides. (United States)

    Shamsipur, M; Rouhani, S; Sharghi, H; Ganjali, M R; Eshghi, H


    Eight different recently synthesized macrocyclic diamides were studied to characterize their abilities as strontium ion carriers in PVC membrane electrodes. The electrode based on 1,13-diaza-2,3;11,12-dibenzo-4,7,10-trioxacyclopentadecane-14,15-dione exhibits a Nernstian response for Sr(2+) ions over a wide concentration range (1.0 × 10(-)(1)-3.2 × 10(-)(5) M) with a limit of detection of 8.0 × 10(-)(6) M (0.7 ppm). The response time of the sensor is ∼10 s, and the membrane can be used for more than three months without observing any deviation. The electrode revealed comparatively good selectivities with respect to many alkali, alkaline earth, and transition metal ions. It was used as an indicator electrode in potentiometric titration of carbonate ions with a strontium ion solution.

  5. Cobalt(II)-selective membrane electrode based on a recently synthesized benzo-substituted macrocyclic diamide. (United States)

    Shamsipur, M; Poursaberi, T; Rouhani, S; Niknam, K; Sharghi, H; Ganjali, M R


    A PVC-membrane electrode based on a recently synthesized 18-membered macrocyclic diamide is presented. The electrode reveals a Nernstian potentiometric response for Co2+ over a wide concentration range (2.0 x 10(-6)-1.0 x 10(-2) M). The electrode has a response time of about 10 s and can be used for at least 2 months without any divergence. The proposed sensor revealed very good selectivities for Co2+ over a wide variety of other metal ions, and could be used over a wide pH range (3.0-8.0). The detection limit of the sensor is 6.0 x 10(-7) M. It was successfully applied to the direct determination and potentiometric titration of cobalt ion.

  6. Tetranuclear manganese(II) complexes of sulfonylcalix[4]arene macrocycles: synthesis, structure, spectroscopic and magnetic properties. (United States)

    Lamouchi, Meriem; Jeanneau, Erwann; Pillonnet, Anne; Brioude, Arnaud; Martini, Matteo; Stéphan, Olivier; Meganem, Faouzi; Novitchi, Ghenadie; Luneau, Dominique; Desroches, Cédric


    Two tetranuclear manganese(II) complexes {K(+)[Mn(4)(ThiaSO(2))(2)(OH)](-)} (1) and {K(+)[Mn(4)(ThiaSO(2))(2)(F)](-)} (2) have been synthesized under solvothermal conditions in methanol with p-tert-butylsulfonylcalix[4]arene (ThiaSO(2)). For both complexes, the structure has been established from single-crystal X-ray diffraction. The two complexes are best described as manganese squares sandwiched between two thiacalixarene macrocycles. In both complexes, in the center of the square formed by the four manganese(II) atoms, the unexpected presence of μ(4)-OH(-) or μ(4)-F(-) gives a negative charge to the cluster. The two tetranuclear complexes exhibit strong orange luminescence behavior resulting from the symbiosis between the ThiaSO(2) and the Mn(2+). Despite similar chemical formulation, (1) and (2) present difference in emission intensity and lifetime τ.

  7. Synthesis of Macrocyclic Ionophore for the Development of Highly Selective Chloride Sensor

    Directory of Open Access Journals (Sweden)

    Sameena Mehtab


    Full Text Available The macrocyclic ligands 3,8,12,17-tetramethyl-2,18,9,11-bipyridyl-1,4,7,10,13,16-hexaazacyclooctadecanetetrahydro bromide has been synthesized and explored as suitable ionophores for chloride selective membrane sensors. It displays Nernstian behavior (59.2 mV decade-1 across the range of 4.1 × 10-8 to 1.0 × 10-2 M. The detection limit of the electrode is ~ 15 nM and the response time and life times are 14 s and eight weeks respectively over a wide pH range (3.5 - 9.5. Interference from other anions is very low and it can be used as indicator electrode in the potentiometric titration of chloride ions and to determine chloride in agricultural soil water samples.

  8. Graphene supported non-precious metal-macrocycle catalysts for oxygen reduction reaction in fuel cells (United States)

    Choi, Hyun-Jung; Ashok Kumar, Nanjundan; Baek, Jong-Beom


    Fuel cells are promising alternative energy devices owing to their high efficiency and eco-friendliness. While platinum is generally used as a catalyst for the oxygen reduction reaction (ORR) in a typical fuel cell, limited reserves and prohibitively high costs limit its future use. The development of non-precious and durable metal catalysts is being constantly conceived. Graphene has been widely used as a substrate for metal catalysts due to its unique properties, thus improving stability and ORR activities. In this feature, we present an overview on the electrochemical characteristics of graphene supported non-precious metal containing macrocycle catalysts that include metal porphyrin and phthalocyanine derivatives. Suggested research and future development directions are discussed.

  9. Dereplication of macrocyclic trichothecenes from extracts of filamentous fungi through UV and NMR profiles. (United States)

    Sy-Cordero, Arlene A; Graf, Tyler N; Wani, Mansukh C; Kroll, David J; Pearce, Cedric J; Oberlies, Nicholas H


    Macrocyclic trichothecenes (MTs), which have potent cytotoxicity, have been isolated from many different fungal species. These compounds were evaluated clinically by the US National Cancer Institute in the 1970s and 1980s. However, they have yet to be advanced into viable drugs because of severe side effects. Our team is investigating a diverse library of filamentous fungi for new anticancer leads. To avoid reisolating MTs through bioactivity-directed fractionation studies, a protocol for their facile dereplication was developed. The method uses readily available photodiode array detectors to identify one of two types of characteristic UV spectra for these compounds. In addition, diagnostic signals can be observed in the (1)H-NMR spectra, particularly for the epoxide and conjugated diene moieties, even at the level of a crude extract. Using these techniques in a complementary manner, MTs can be dereplicated rapidly.

  10. Synthesis and properties of new bolaform and macrocyclic galactose-based surfactants obtained by olefin metathesis. (United States)

    Satgé, Céline; Granet, Robert; Verneuil, Bernard; Champavier, Yves; Krausz, Pierre


    A series of galactose-based surfactants with various structures likely to display new interesting properties were synthesized. Four monocatenary surfactants were elaborated by microwave-assisted galactosylation of undecanol or 10-undecenol. These compounds were slightly soluble in water. Their tensioactive properties were determined at 45 degrees C. Olefin metathesis was used to synthesize the two single-chain bolaforms from undec-10-enyl galactopyranosides; two pseudomacrocyclic bolaforms were prepared by grafting two carbamates at O-4 and O-4' sugar positions of the single-chain bolaforms. These four surfactants are insoluble in water and undergo monolayer compression. Cyclization of these bolaforms by olefin metathesis led to macrocyclic surfactant analogues of archaeobacterial membrane components.

  11. Tunable photophysical processes of porphyrin macrocycles on the surface of ZnO nanoparticles

    KAUST Repository

    Parida, Manas R.


    We investigated the impact of the molecular structure of cationic porphyrins on the degree of electrostatic interactions with zinc oxide nanoparticles (ZnO NPs) using steady-state and time-resolved fluorescence and transient absorption spectroscopy. Our results demonstrate that the number of cationic pyridinium units has a crucial impact on the photophysics of the porphyrin macrocycle. Fluorescence enhancement, relative to initial free porphyrin fluorescence, was found to be tuned from 3.4 to 1.3 times higher by reducing the number of cationic substituents on the porphyrin from 4 to 2. The resulting enhancement of the intensity of the fluorescence is attributed to the decrease in the intramolecular charge transfer (ICT) character between the porphyrin cavity and its meso substituent. The novel findings reported in this work provide an understanding of the key variables involved in nanoassembly, paving the way toward optimizing the interfacial chemistry of porphyrin-ZnO NP assembly for photodynamic therapy and energy conversion.

  12. HPLC Enantioseparation of Phenylcarbamic Acid Derivatives by Using Macrocyclic Chiral Stationary Phases

    Directory of Open Access Journals (Sweden)

    Hroboňová Katarína


    Full Text Available The HPLC by using chiral stationary phases based on macrocyclic antibiotics, dimethylphenyl carbamate cyklofructan 7 and β-cyclodextrin in terms of polar-organic separation mode (mobile phase methanol/acetonitrile/acetic acid/triethylamine were used for enantioseparation of alkoxy derivatives of phenylcarbamic acid. The effect of the analyte structures on the efficiency of enantioseparation was investigated. The most suitable stationary phase was teicoplanin aglycone, where the separations of the enantiomers were obtained (the resolution value from 0.65 to 2.90, depending on the structure of the analyte. Significant effect on the resolution of the enantiomers has position of alkoxy substituent in the hydrophobic part of the molecule. The enantiorecognition was achieved for 3-alkoxysubstituted derivatives.

  13. Validation of a screening method for rapid control of macrocyclic lactone mycotoxins in maize flour samples. (United States)

    Zougagh, Mohammed; Téllez, Helena; Sánchez, Alberto; Chicharro, Manuel; Ríos, Angel


    A procedure for the analytical validation of a rapid supercritical fluid extraction amperometric screening method for controlling macrocyclic lactone mycotoxins in maize flour samples has been developed. The limit established by European legislation (0.2 mg kg(-1)), in reference to zearalenone (ZON) mycotoxin, was taken as the reference threshold to validate the proposed method. Natural ZON metabolites were also included in this study to characterize the final screening method. The objective was the reliable classification of samples as positive or negative samples. The cut-off level was fixed at a global concentration of mycotoxins of 0.17 mg kg(-1). An expanded unreliability zone between 0.16 and 0.23 mg kg(-1) characterized the screening method for classifying the samples. A set of 30 samples was used for the final demonstration of the reliability and usefulness of the method.

  14. The Crystal and Molecular Structure of a New Macrocyclic Ligand, (H6BDBPH)Br6·4H2O

    Institute of Scientific and Technical Information of China (English)


    The hexahydro-bromide salt of a new 24-membered hexaaza diphenol macrocyclic ligand, (H6BDBPH)Br6·4H2O (C26H56N6O6Br6, M, = 1028.23), crystallizes in the monoclinic system, space group P21/c, with cell parameters: a = 14. 441(5), b=11.482(4), c=12.090(6)A, β=96.92°, V= 1990 (1)A3, Z=2, Dc=1. 716 g/cm3; F(000) = 1024. MoKa radiation, λ= 0. 71013A ), R = 0.0643 and wR = 0. 1356 for 3507 independent reflections with I > 2σ (I). The macrocyclic ligand adapts chair form, and the crystallographic inversion center is located in the macrocyclic cavity, and the six bromide ions and four water molecules are situated symmetrically outside the macrocyclic cavity.

  15. Diversity-oriented approach to macrocyclic cyclophane derivatives by Suzuki-Miyaura cross-coupling and olefin metathesis as key steps. (United States)

    Kotha, Sambasivarao; Chavan, Arjun S; Shaikh, Mobin


    Palladium-catalyzed Suzuki-Miyaura (SM) cross-coupling reaction with allylboronic acid pinacol ester and titanium assisted cross-metathesis (CM)/ring-closing metathesis (RCM) cascade has been used to synthesize macrocyclic cyclophane derivatives.

  16. Synthesis of a TREN in which the aryl substituents are part of a 45 atom macrocycle. (United States)

    Cain, Matthew F; Forrest, William P; Peryshkov, Dmitry V; Schrock, Richard R; Müller, Peter


    A substituted TREN has been prepared in which the aryl groups in (ArylNHCH2CH2)3N are substituted at the 3- and 5-positions with a total of six OCH2(CH2)nCH═CH2 groups (n = 1, 2, 3). Molybdenum nitride complexes, [(ArylNCH2CH2)3N]Mo(N), have been isolated as adducts that contain B(C6F5)3 bound to the nitride. Two of these [(ArylNCH2CH2)3N]Mo(NB(C6F5)3) complexes (n = 1 and 3) were crystallographically characterized. After removal of the borane from [(ArylNCH2CH2)3N]Mo(NB(C6F5)3) with PMe3, ring-closing olefin metathesis (RCM) was employed to join the aryl rings with OCH2(CH2)nCH═CH(CH2)nCH2O links (n = 1-3) between them. RCM worked best with a W(O)(CHCMe3)(Me2Pyr)(OHMT)(PMe2Ph) catalyst (OHMT = hexamethylterphenoxide, Me2Pyr = 2,5-dimethylpyrrolide) and n = 3. The macrocyclic ligand was removed from the metal through hydrolysis and isolated in 70-75% yields relative to the borane adducts. Crystallographic characterization showed that the macrocyclic TREN ligand in which n = 3 contains three cis double bonds. Hydrogenation produced a TREN in which the three links are saturated, i.e., O(CH2)10O.

  17. Virtual libraries of tetrapyrrole macrocycles. Combinatorics, isomers, product distributions, and data mining. (United States)

    Taniguchi, Masahiko; Du, Hai; Lindsey, Jonathan S


    A software program (PorphyrinViLiGe) has been developed to enumerate the type and relative amounts of substituted tetrapyrrole macrocycles in a virtual library formed by one of four different classes of reactions. The classes include (1) 4-fold reaction of n disubstituted heterocycles (e.g., pyrroles or diiminoisoindolines) to form β-substituted porphyrins, β-substituted tetraazaporphyrins, or α- or β-substituted phthalocyanines; (2) combination of m aminoketones and n diones to form m × n pyrroles, which upon 4-fold reaction give β-substituted porphyrins; (3) derivatization of an 8-point tetrapyrrole scaffold with n reagents, and (4) 4-fold reaction of n aldehydes and pyrrole to form meso-substituted porphyrins. The program accommodates variable ratios of reactants, reversible or irreversible reaction (reaction classes 1 and 2), and degenerate modes of formation. Pólya's theorem (for enumeration of cyclic entities) has also been implemented and provides validation for reaction classes 3 and 4. The output includes the number and identity of distinct reaction-accessible substituent combinations, the number and identity of isomers thereof, and the theoretical mass spectrum. Provisions for data mining enable assessment of the number of products having a chosen pattern of substituents. Examples include derivatization of an octa-substituted phthalocyanine with eight reagents to afford a library of 2,099,728 members (yet only 6435 distinct substituent combinations) and reversible reaction of six distinct disubstituted pyrroles to afford 2649 members (yet only 126 distinct substituent combinations). In general, libraries of substituted tetrapyrrole macrocycles occupy a synthetically accessible region of chemical space that is rich in isomers (>99% or 95% for the two examples, respectively).

  18. Macrocyclic beta-sheet peptides that mimic protein quaternary structure through intermolecular beta-sheet interactions. (United States)

    Khakshoor, Omid; Demeler, Borries; Nowick, James S


    This paper reports the design, synthesis, and characterization of a family of cyclic peptides that mimic protein quaternary structure through beta-sheet interactions. These peptides are 54-membered-ring macrocycles comprising an extended heptapeptide beta-strand, two Hao beta-strand mimics [JACS 2000, 122, 7654] joined by one additional alpha-amino acid, and two delta-linked ornithine beta-turn mimics [JACS 2003, 125, 876]. Peptide 3a, as the representative of these cyclic peptides, contains a heptapeptide sequence (TSFTYTS) adapted from the dimerization interface of protein NuG2 [PDB ID: 1mio]. 1H NMR studies of aqueous solutions of peptide 3a show a partially folded monomer in slow exchange with a strongly folded oligomer. NOE studies clearly show that the peptide self-associates through edge-to-edge beta-sheet dimerization. Pulsed-field gradient (PFG) NMR diffusion coefficient measurements and analytical ultracentrifugation (AUC) studies establish that the oligomer is a tetramer. Collectively, these experiments suggest a model in which cyclic peptide 3a oligomerizes to form a dimer of beta-sheet dimers. In this tetrameric beta-sheet sandwich, the macrocyclic peptide 3a is folded to form a beta-sheet, the beta-sheet is dimerized through edge-to-edge interactions, and this dimer is further dimerized through hydrophobic face-to-face interactions involving the Phe and Tyr groups. Further studies of peptides 3b-3n, which are homologues of peptide 3a with 1-6 variations in the heptapeptide sequence, elucidate the importance of the heptapeptide sequence in the folding and oligomerization of this family of cyclic peptides. Studies of peptides 3b-3g show that aromatic residues across from Hao improve folding of the peptide, while studies of peptides 3h-3n indicate that hydrophobic residues at positions R3 and R5 of the heptapeptide sequence are important in oligomerization.

  19. [Chiral separation of drugs based on macrocyclic antibiotics using HPLC, supercritical fluid chromatography (SFC) and capillary electrochromatography (CEC)]. (United States)

    Dungelová, J; Lehotay, J; Rojkovicová, T; Cizmárik, J


    Separation of enantiomers by means of high-performance liquid chromatography (HPLC), supercritical fluid chromatography (SFC), and capillary electrochromatography (CEC) is of great importance in pharmaceutical analyses. In recent years, separation of various types of racemates employs most frequently chiral stationary phases based on macrocyclic antibiotics. This class of chiral selectors includes vancomycin, teikoplanin, ristocetin A, teikoplanin without saccharide components, avoparcin, etc. The review paper describes the properties of selected antibiotics, the effect of chromatographic conditions on enantioselectivity (effect of the composition of the mobile phase, effect of pH of the mobile phase, effect of temperature), and the study of possible mechanisms of interaction, which play an important role in the separation of enantiomers. Examples of the use of macrocyclic antibiotics in the separation of various compounds by means of the HPLC, SFC, and CEC methods follow.

  20. Synthesis of Chiral Macrocyclic or Linear Pyridine Carboxamides from Pyridine-2,6-dicarbonyl Dichloride as Antimicrobial Agents

    Directory of Open Access Journals (Sweden)

    Abd El-Galil E Amr


    Full Text Available A series of chiral linear and macrocyclic bridged pyridines has been prepared starting from pyridine-2,6-dicarbonyl dichloride (2. The coupling of 1 with D-alanyl methyl ester gave 2,6-bis-D-alanyl pyridine methyl ester (3. Hydrazinolysis of 3 with hydrazine hydrate afforded bis-hydrazide 4. The latter was reacted with thiophene-2-carbaldehyde, phthalic anhydride or cyclohexanone to afford bis-carboxamide pyridine derivatives 5-7, respectively. Compound 4 was coupled with p-methoxy- or p-nitroaceto-phenone to yield compounds 8 and 9. In addition, 4 was reacted with 1,2,4,5-benzenetetra-carboxylic acid dianhydride or 1,4,5,8-naphthalenetetracarboxylic acid dianhydride to afford the macrocyclic octacarboxaamide pyridines 10 and 11. The detailed synthesis, spectroscopic data and antimicrobial screening for the synthesized compounds are reported.

  1. Increasing the luminescence of lanthanide(III) macrocyclic complexes by the use of polymers and lanthanide enhanced luminescence (United States)

    Leif, Robert C.; Becker, Margie C.; Bromm, Alfred J., Jr.; Vallarino, Lidia M.; Williams, Steven A.; Yang, Sean


    A Eu (III)-macrocycle-isothiocyanate, Quantum DyeTM, has been reacted with lysine homo- and hetero-peptides to give polymers with multiple luminescent side chains. Contrary to the concentration quenching that occurs with conventional organic fluorophores, the attachment of multiple Quantum Dyes to a polymer results in a concomitant increase in luminescence. The emission intensity of the peptide-bound Quantum Dye units is approximately linearly related to their number. The attachment of peptides containing multiple lanthanide (III) macrocycles to analyte-binding species is facilitated by employing solid-phase technology. Bead-bound peptides are first labeled with multiple Quantum Dye units, then conjugated to an antibody, and finally released from the bead by specific cleavage with Proteinase K unedr physiological conditions. Since the luminescence of lanthanide(III) macrocycles is enhanced by the presence of GD(III) or Y(III) ions in a micellar system, a significant increase in signal can be achieved by attaching a polymer labeled with multiple Quantum Dye units to an analyte- binding species, such as a monoclonal antibody, or by taking advantage of the luminescence enhancing effects of Gd(III) or Y(III), or by both approaches concomitantly. A comparison between the integrated intensity and lifetime measurements of the Eu(III)-macrocycle under a variety of conditions show that the signal increase caused by Gd(III) can not be explained solely by the increase in lifetime, and must result in significant part from an energy transfer process invloving donors not directly bound to the Eu(III).

  2. Modulation of lipopolysaccharide-induced proinflammatory cytokine production by satratoxins and other macrocyclic trichothecenes in the murine macrophage. (United States)

    Chung, Yong-Joo; Jarvis, Bruce; Pestka, James


    The satratoxins and other macrocyclic trichothecene mycotoxins are produced by Stachybotrys, a mold that is often found in water-damaged dwellings and office buildings. To test the potential immunomodulatory effects of these mycotoxins, RAW 264.7 murine macrophage cells were treated with various concentrations of satratoxin G (SG), isosatratoxin F (iSF), satratoxin H (SH), roridin A (RA), and verrucarin A (VA) for 48 h in the presence or absence of suboptimal concentra-tion of lipopolysaccharide (LPS, 50 ng/ml), and tumor necrosis factor-alpha (TNF-alpha ) and interleukin-6 (IL-6) production were assayed by enzyme-linked immunosorbent assay (ELISA). In LPS-stimulated cultures, TNF-alpha supernatant concentrations were significantly increased in the presence of 2.5, 2.5, and 1 ng/ml of SG, SH, and RA, respectively, whereas IL-6 concentrations were not affected by the same concentrations these macrocyclic trichothecenes. When cells that were treated with LPS and SG (2.5 ng/ml) were evaluated by real-time polymerase chain reaction (PCR),TNF-alpha mRNA was found to increase at 24, 36, and 48 h compared to control cells. At higher concentrations, cytokine production and cell viability were markedly impaired in LPS-stimulated cells. Without LPS stimulation, neither TNF-alpha, nor IL-6 was induced. These results indicate that low concentrations of macrocyclic trichothecenes superinduce expression of TNF-alpha, whereas higher concentrations of these toxins are cytotoxic and concurrently reduce cytokine production. The capacity of satratoxins and other macrocyclic trichothecenes to alter cytokine production may play an etiologic role in outbreaks of Stachybotrys-associated human illnesses.

  3. Highly enantioselective transfer hydrogenation of ketones with chiral (NH)2 P2 macrocyclic iron(II) complexes. (United States)

    Bigler, Raphael; Huber, Raffael; Mezzetti, Antonio


    Bis(isonitrile) iron(II) complexes bearing a C2 -symmetric diamino (NH)2 P2 macrocyclic ligand efficiently catalyze the hydrogenation of polar bonds of a broad scope of substrates (ketones, enones, and imines) in high yield (up to 99.5 %), excellent enantioselectivity (up to 99 % ee), and with low catalyst loading (generally 0.1 mol %). The catalyst can be easily tuned by modifying the substituents of the isonitrile ligand.

  4. Biomimetic Synthesis of Twenty-four Long-chained Diketones as Precursors for Muscone and Further Macrocyclic Ketones

    Institute of Scientific and Technical Information of China (English)

    GUO,Yuan; CHEN,Kang-yu; LI,Jian-Li; SHI,Zhen


    The one-carbon unit transfer reaction of tetrahydrofolate coenzyme was initiated. Bisbenzimidazolium salts were used as a tetrahydrofolate coenzyme model, and thus the biomimetic synthesis of twenty-four acyclic dike-tones as precursors for macrocyclic ketones was successfully accomplished by using the addition-hydrolysis reac-tion of the bisbenzimidazolium salts with alkyl magnesium halide, wherein six diketones have not been reported in literature. Accordingly, a short route to muscone analogues was provided.

  5. Discrete and Polymeric, Mono- and Dinuclear Silver Complexes of a Macrocyclic Tetraoxime Ligand with AgI–AgI Interactions

    Directory of Open Access Journals (Sweden)

    Mitsuhiko Shionoya


    Full Text Available Macrocyclic compounds that can bind cationic species efficiently and selectively with their cyclic cavities have great potential as excellent chemosensors for metal ions. Recently, we have developed a tetraoxime-type tetraazamacrocyclic ligand 1 formed through a facile one-pot cyclization reaction. Aiming to explore and bring out the potential of the tetraoxime macrocycle 1 as a chelating sensor, we report herein the preparation of several kinds of silver complexes of 1 and their unique coordination structures determined by single-crystal X-ray diffraction analyses. As a result, the formation of two kinds of discrete structures, monomeric complexes [Ag(1X] (X = counter anions and a dimeric complex [Ag2(12]X2, and two kinds of polymeric structures from a mononuclear complex, [Ag(1]nXn, and from a dinuclear complex, [Ag2(1X2]n, was demonstrated. In the resulting complexes, the structurally flexible macrocyclic ligand 1 was found to provide several different coordination modes. Notably, in some silver complexes of 1, AgI–AgI interactions were observed with different AgI–AgI distances which depend on the kind of counter anions and the chemical composition.

  6. Macrocyclic-, polycyclic-, and nitro musks in cosmetics, household commodities and indoor dusts collected from Japan: implications for their human exposure. (United States)

    Nakata, Haruhiko; Hinosaka, Mari; Yanagimoto, Hayato


    This paper reported the occurrence and concentrations of macrocyclic-, polycyclic- and nitro musks in cosmetics and household commodities collected from Japan. The high concentrations and detection frequencies of Musk T, habanolide, and exaltolides were found in commercial products, suggesting their large amounts of production and usage in Japan. Polycyclic musks, HHCB and OTNE, also showed high concentrations in cosmetics and products. The estimated dairy intakes of Musk T and HHCB by the dermal exposure to commercial products were 7.8 and 7.9 μg/kg/day in human, respectively, and perfume and body lotion are dominant exposure sources. We also analyzed synthetic musks in house dusts. Polycyclic musks, HHCB and OTNE, showed high concentrations in samples, but macrocyclic musks were detected only in a few samples, although these types of musks were highly detected in commercial products. This is probably due to easy-degradation of macrocyclic musks in indoor environment. The dairy intakes of HHCB by dust ingestions were 0.22 ng/kg/day in human, which were approximately five orders of magnitudes lower than those of dermal absorption from commercial household commodities.

  7. Synthesis and Crystal Structure of a New Dinuclear Manganese(Ⅱ) Manganese(Ⅲ) Complex of a Macrocyclic Ligand

    Institute of Scientific and Technical Information of China (English)

    JIAN Fang-fang; XIAO Hai-lian; XU Liang-zhong; PANG Lei


    A mixed-valence dinuclear manganese complex, [MnⅡMnⅢL](ClO4)·1/2MeOH, where L is a macrocyclic ligand derived from the cyclocondensation of sodium 2,6-diformyl-4-methylphenolate with N,N-bis(2-aminoethyl)-2-hydroxybenzyl amine, was obtained and its structure was determined by X-ray diffraction. The orange crystal is a monoclinic system with space group P21/c and lattice parameters a=1.1617(4), b=1.4005(3), c=1.4641(3) nm, β=113.03(2)°, and Z=2. The crystal structure shows that each pendant-arm is bonded in a bidentate fashion to the adjacent metal atom and that both the arms are on the same side of the macrocycle. The two Mn atoms are bridged by two μ2-phenoxy oxygen atoms of the tetra-imine macrocycle, and each Mn atom, locating in a trigonal prismatic coordination environment(N3O3), is six-coordinated by the two imine nitrogen atoms, one tertiary nitrogen atom and a pendant phenol moiety apart from the two oxygen atoms.

  8. Accelerated Hydrolysis of p-Nitrophenyl Picolinate Catalyzed by Metallomicelle Made from a Novel Macrocyclic Polyamine Copper(Ⅱ) Complex

    Institute of Scientific and Technical Information of China (English)

    KOU,Xing-Ming; ZHAO,Guo-Po; HUANG,Zhong; TIAN,Yu-Hua; MENG,Xiang-Guang; ZENG Xian-Cheng


    A copper(Ⅱ) complex 1 of a novel macrocyclic polyamine ligand with hydroxylethyl pendant groups, 4,ll-bis(hydroxylethyl)-5,7,7,12,14,14-hexamethyl-l,4,8,11-tetraazacyclotetradecane (L) has been synthesized and characterized. Rate enhancement for hydrolysis of p-nitrophenyl picolinate (PNPP) catalyzed by 1 was studied kinetically under Brij35 micellar condition. For comparision, the catalytic activity of corresponding copper(Ⅱ) complex 2 of non-substituted macrocyclic polyamine ligand, 5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraaza-cyclote-tradecane (L1) toward the hydrolysis of PNPP was also investigated. The results indicate that the macrocyclic polyamine copper(Ⅱ) complex 1 effectively catalyzed the hydrolysis of PNPP, and the pendant ligand hydroxyl group or deprotonated pendant ligand hydroxyl group can act as catalytically active species in the reaction. A ternary complex kinetic model involving metal ion, ligand and substrate has been proposed, and the results confirmed the reasonability of such kinetic model.

  9. Tailored synthesis of CuS nanodisks from a new macrocyclic precursor and their efficient catalytic properties on methylene blue dye degradation (United States)

    Islam, D. A.; Chakraborty, A.; Bhattacharya, B.; Sarkar, U.; Acharya, H.


    In this study, CuS nanodisks have been synthesized from a tetraaza (N4) macrocyclic complex precursor by a facile wet chemical method. The crystallinity and morphology of the as-synthesized products were characterized by X-ray diffraction and transmission electron microscopy, which confirm a phase pure crystalline CuS nanostructures with 15 to 20 nm in dimension with 5 nm thickness. A possible formation mechanism and growth process of the CuS nanodisks are discussed using thiourea and tetraaza ligand as the sulfur donor and stabilizing agent, respectively. Cyclic N4 ligand also acts as a binding agent to template-guide the oriented growth of CuS nanodisks. The optimized geometry of ligands and complexes was calculated using B3YLP functional, which indicates that the HOMO in the complex located on metal center and N atoms are weakly bonded to the metal center. The catalytic activity of CuS nanodisks toward MB degradation with light displays the higher MB degradation rate than under dark in the presence of H2O2. The C t/ C 0 plot as a function of time displays the higher MB degradation activity of CuS nanoparticles with H2O2. The recycle stability of CuS nanoparticles was even found to be >80 % after five cycles studied by repeating the MB degradation with same CuS nanoparticles sample.

  10. Unsaturated macrocyclic dihydroxamic acid siderophores produced by Shewanella putrefaciens using precursor-directed biosynthesis. (United States)

    Soe, Cho Z; Codd, Rachel


    To acquire iron essential for growth, the bacterium Shewanella putrefaciens produces the macrocyclic dihydroxamic acid putrebactin (pbH2; [M + H(+)](+), m/zcalc 373.2) as its native siderophore. The assembly of pbH2 requires endogenous 1,4-diaminobutane (DB), which is produced from the ornithine decarboxylase (ODC)-catalyzed decarboxylation of l-ornithine. In this work, levels of endogenous DB were attenuated in S. putrefaciens cultures by augmenting the medium with the ODC inhibitor 1,4-diamino-2-butanone (DBO). The presence in the medium of DBO together with alternative exogenous non-native diamine substrates, (15)N2-1,4-diaminobutane ((15)N2-DB) or 1,4-diamino-2(E)-butene (E-DBE), resulted in the respective biosynthesis of (15)N-labeled pbH2 ((15)N4-pbH2; [M + H(+)](+), m/zcalc 377.2, m/zobs 377.2) or the unsaturated pbH2 variant, named here: E,E-putrebactene (E,E-pbeH2; [M + H(+)](+), m/zcalc 369.2, m/zobs 369.2). In the latter system, remaining endogenous DB resulted in the parallel biosynthesis of the monounsaturated DB-E-DBE hybrid, E-putrebactene (E-pbxH2; [M + H(+)](+), m/zcalc 371.2, m/zobs 371.2). These are the first identified unsaturated macrocyclic dihydroxamic acid siderophores. LC-MS measurements showed 1:1 complexes formed between Fe(III) and pbH2 ([Fe(pb)](+); [M](+), m/zcalc 426.1, m/zobs 426.2), (15)N4-pbH2 ([Fe((15)N4-pb)](+); [M](+), m/zcalc 430.1, m/zobs 430.1), E,E-pbeH2 ([Fe(E,E-pbe)](+); [M](+), m/zcalc 422.1, m/zobs 422.0), or E-pbxH2 ([Fe(E-pbx)](+); [M](+), m/zcalc 424.1, m/zobs 424.2). The order of the gain in siderophore-mediated Fe(III) solubility, as defined by the difference in retention time between the free ligand and the Fe(III)-loaded complex, was pbH2 (ΔtR = 8.77 min) > E-pbxH2 (ΔtR = 6.95 min) > E,E-pbeH2 (ΔtR = 6.16 min), which suggests one possible reason why nature has selected for saturated rather than unsaturated siderophores as Fe(III) solubilization agents. The potential to conduct multiple types of ex situ chemical

  11. Biomechanical Assessment of Motor Abilities in Male Handball Players During the Annual Training Macrocycle

    Directory of Open Access Journals (Sweden)

    Sacewicz Tomasz


    Full Text Available Introduction. The aim of the study was to determine the torque of the knee extensors and flexors of the lead lower limb, the torque of the shoulder extensors and flexors of the dominant upper limb, and the torque generated by the muscles of the kinematic chain going from the trail lower limb to the hand of the dominant limb in male handball players during the annual training macrocycle. Changes in jump height and throwing velocity were also investigated. Material and methods. The study involved 13 handball players from a Polish second-league team. The measurements were performed four times: at the beginning of the preparation period, at the beginning of the season, at the end of the first part of the season, and at the end of the second part of the season. Torque was measured in isokinetic and isometric conditions. Jumping ability was tested using a piezoelectric platform, and throwing velocity was measured with a speed radar gun. Results. The study found statistically significant differences between the relative torque values of the knee extensors (p < 0.002 and flexors (p < 0.003 of the lead leg measured in isokinetic conditions between the first three measurements and the final one. Isokinetic measurement of the torque of the muscles of the kinematic chain going from the trail leg to the hand of the dominant arm decreased in a statistically significant way at the end of the season. As for the results of the measurement of the torque of the shoulder extensors and flexors in static conditions, no statistically significant differences were observed between the four measurements. However, statistically significant differences were noted in jumping ability and throwing velocity in the annual training macrocycle. Conclusions. The results of the study indicate that there is a need to perform regular assessments of players’ strength and jumping ability during the competition period. There is a need to modify the training methods used during the

  12. Next generation macrocyclic and acyclic cationic lipids for gene transfer: Synthesis and in vitro evaluation. (United States)

    Jubeli, Emile; Maginty, Amanda B; Abdul Khalique, Nada; Raju, Liji; Abdulhai, Mohamad; Nicholson, David G; Larsen, Helge; Pungente, Michael D; Goldring, William P D


    Previously we reported the synthesis and in vitro evaluation of four novel, short-chain cationic lipid gene delivery vectors, characterized by acyclic or macrocyclic hydrophobic regions composed of, or derived from, two 7-carbon chains. Herein we describe a revised synthesis of an expanded library of related cationic lipids to include extended chain analogues, their formulation with plasmid DNA (pDNA) and in vitro delivery into Chinese hamster ovarian (CHO-K1) cells. The formulations were evaluated against each other based on structural differences in the hydrophobic domain and headgroup. Structurally the library is divided into four sets based on lipids derived from two 7- or two 11-carbon hydrophobic chains, C7 and C11 respectively, which possess either a dimethylamine or a trimethylamine derived headgroup. Each set includes four cationic lipids based on an acyclic or macrocyclic, saturated or unsaturated hydrophobic domain. All lipids were co-formulated with the commercial cationic lipid 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC) in a 1:1 molar ratio, along with one of two distinct neutral co-lipids, cholesterol or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in an overall cationic-to-neutral lipid molar ratio of 3:2. Binding of lipid formulations with DNA, and packing morphology associated with the individual lipid-DNA complexes were characterized by gel electrophoresis and small angle X-ray diffraction (SAXD), respectively. As a general trend, lipoplex formulations based on mismatched binary cationic lipids, composed of a shorter C7 lipid and the longer lipid EPC (C14), were generally associated with higher transfection efficiency and lower cytotoxicity than their more closely matched C11/EPC binary lipid formulation counterparts. Furthermore, the cyclic lipids gave transfection levels as high as or greater than their acyclic counterparts, and formulations with cholesterol exhibited higher transfection and lower cytotoxicity than those

  13. Mono- and Dinuclear Macrocyclic Calcium Complexes as Platforms for Mixed-Metal Complexes and Clusters. (United States)

    Connolly, Emma A; Leeland, James W; Love, Jason B


    Mono- and dinuclear calcium complexes of the Schiff-base macrocycles H4L have been prepared and characterized spectroscopically and crystallographically. In the formation of Ca(THF)2(H2L(1)), Ca2(THF)2(μ-THF)(L(1)), and Ca2(THF)4(L(2)), the ligand framework adopts a bowl-shaped conformation instead of the conventional wedge, Pacman-shaped structure as seen with the anthracenyl-hinged complex Ca2(py)5(L(3)). The mononuclear calcium complex Ca(THF)2(H2L(1)) reacts with various equivalents of LiN(SiMe3)2 to form calcium/alkali metal clusters and dinuclear transition metal complexes when reacted subsequently with transition metal salts. The dinuclear calcium complex Ca2(THF)2(μ-THF)(L(1)), when reacted with various equivalents of NaOH, is shown to act as a platform for the formation of calcium/alkali metal hydroxide clusters, displaying alternate wedged and bowl-shaped conformations.

  14. Fluensulfone is a nematicide with a mode of action distinct from anticholinesterases and macrocyclic lactones. (United States)

    Kearn, James; Ludlow, Elizabeth; Dillon, James; O'Connor, Vincent; Holden-Dye, Lindy


    Plant parasitic nematodes infest crops and present a threat to food security worldwide. Currently available chemical controls e.g. methyl bromide, organophosphates and carbamates have an unacceptable level of toxicity to non-target organisms and are being withdrawn from use. Fluensulfone is a new nematicide of the fluoroalkenyl thioether group that has significantly reduced environmental impact with low toxicity to non-target insects and mammals. Here, we show that the model genetic organism Caenorhabditis elegans is susceptible to the irreversible nematicidal effects of fluensulfone. Whilst the dose required is higher than that which has nematicidal activity against Meloidogyne spp. the profile of effects on motility, egg-hatching and survival is similar to that reported for plant parasitic nematodes. C. elegans thus provides a tractable experimental paradigm to analyse the effects of fluensulfone on nematode behaviour. We find that fluensulfone has pleiotropic actions and inhibits development, egg-laying, egg-hatching, feeding and locomotion. In the case of feeding and locomotion, an early excitation precedes the gross inhibition. The profile of these effects is notably distinct from other classes of anthelmintic and nematicide: the inhibition of motility caused by fluensulfone is not accompanied by the hypercontraction which is characteristic of organophosphates and carbamates and C. elegans mutants that are resistant to the carbamate aldicarb and the macrocyclic lactone ivermectin retain susceptibility to fluensulfone. These data indicate fluensulfone's mode of action is distinct from currently available nematicides and it therefore presents a promising new chemical entity for crop protection.

  15. Synthesis, characterization and biological activity of symmetric dinuclear complexes derived from a novel macrocyclic compartmental ligand

    Energy Technology Data Exchange (ETDEWEB)

    Mruthyunjayaswamy, B.H.M.; Ijare, Omkar B.; Jadegoud, Y. [Gulbarga University (India). Dept. of Chemistry]. E-mail:


    A phenol based novel macrocyclic binucleating compartmental ligand N,N-bis(2,6-diiminomethyl-4-methyl-1-hydroxyphenyl)malonoyldicarboxamide was prepared. The complexes were prepared by template method by reacting 2,6-diformyl-4-methylphenol, malonoyl dihydrazide and the metal chlorides of Cu(II), Ni(II), Co(II), Cd(II), Zn(II) and Hg(II) in methanol to get a series of dinuclear complexes. The complexes were characterized by elemental analyses, conductivity measurements, magnetic susceptibility data, IR, UV-Vis, ESR, NMR and FAB mass spectral data. The dinuclear nature of the complexes was confirmed on the basis of elemental analyses, magnetic susceptibility, ESR and FAB mass spectral data. The ligand as well as Cu(II), Ni(II), Co(II) and Zn(II) complexes were tested for their antibacterial and antifungal properties against Escherichia coli, Staphyloccocus aureus, Aspergillus niger and Fusarium oxysporum. Magnetic susceptibility measurements of Cu(II), Ni(II) and Co(II) complexes reveal that these complexes exhibit antiferromagnetic coupling behavior due to the presence of two metal ions in close proximity. FAB mass spectrum of the Cu(II) complex gave a clear evidence for the dinuclear nature. The ligand and the complexes were found to be less active against the tested bacteria, but the ligand alone was found active against the fungus Fusarium oxysporum. (author)

  16. Immobilized copper(II) macrocyclic complex on MWCNTs with antibacterial activity (United States)

    Tarlani, Aliakbar; Narimani, Khashayar; Mohammadipanah, Fatemeh; Hamedi, Javad; Tahermansouri, Hasan; Amini, Mostafa M.


    In a new approach, a copper(II) tetraaza macrocyclic complex (CuTAM) was covalently bonded on modified multi-walled carbon nanotubes (MWCNTs). To achieve this purpose, MWCNTs were converted to MWCNT-COCl and then reacted to NH groups of TAM ligand. The prepared material was characterized by Fourier Transform Infrared (FT-IR), X-ray diffraction (XRD), Raman spectroscopy, thermal gravimetric analysis (TGA), and FESEM (field emission scanning electron microscopy). FT-IR and TGA demonstrated the presence of the organic moieties, and XRD proved that the structure of MWCNTs remained intact during the three modification steps. An increase in the ID/IG ratio in Raman spectra confirmed the surface modifications. Finally, the samples were subjected to an antibacterial assessment to compare their biological activity. The antibacterial test showed that the grafted complex on the surface of the nanotube (MWCNT-CO-CuTAM) has higher antibacterial activity against Bacillus subtilis ATCC 6633 than the MWCNT-COOH and CuTAM with 1000 and 2000 μg/mL.

  17. Detection of airborne Stachybotrys chartarum macrocyclic trichothecene mycotoxins on particulates smaller than conidia. (United States)

    Brasel, T L; Douglas, D R; Wilson, S C; Straus, D C


    Highly respirable particles (diameter, water-damaged buildings. The presence of airborne Stachybotrys chartarum trichothecene mycotoxins on particles smaller than conidia (e.g., fungal fragments) was therefore investigated. Cellulose ceiling tiles with confluent Stachybotrys growth were placed in gas-drying containers through which filtered air was passed. Exiting particulates were collected by using a series of polycarbonate membrane filters with decreasing pore sizes. Scanning electron microscopy was employed to determine the presence of conidia on the filters. A competitive enzyme-linked immunosorbent assay (ELISA) specific for macrocyclic trichothecenes was used to analyze filter extracts. Cross-reactivity to various mycotoxins was examined to confirm the specificity. Statistically significant (P trichothecenes at concentrations of 50 and 5 ng/ml and 500 pg/ml (58.4 to 83.5% inhibition). Of the remaining toxins tested, only verrucarol and diacetylverrucarol (nonmacrocyclic trichothecenes) demonstrated significant binding (18.2 and 51.7% inhibition, respectively) and then only at high concentrations. The results showed that extracts from conidium-free filters demonstrated statistically significant (P trichothecene mycotoxins can become airborne in association with intact conidia or smaller particles. These findings may have important implications for indoor air quality assessment.

  18. Separation of Radioactive Elements Using Nitrogen Oxygen Donor Macrocyclic Ion Exchanger

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Si Joong; Shim, Min Sook [Korea University, Seoul (Korea, Republic of); Kim, Jeong; Lee, Myung No [Seonam University, Namwon (Korea, Republic of)


    The study for the selective separation and recovery of Pd{sup 2+} ion lead to following results. The four kinds of stationary phase, SGB-NTOE, SGB-NTOT, SGB-NEOD, and SGB-NTOD, were synthesized to react NOTE, NTOT, NEOD, and NTOD with 3-glycidyloxypropyltrimethoxy silane and silica gel. Using these macrocycles, selective separation of Hg(II), Pt(II), and Pd(II) from alkali earth and transition metal ions were possible by column chromatography. Maximum separation capability was appeared in SGB-NTOT and it took 12 hours for complete separation of Pd{sup 2+} ion with the column which inner diameter was 24 cm. The results of the study for the selective separation of Cs{sup +} and Sr{sup 2+} are as follows: Sr{sup 2+} ion was effectively separated through liquid membrane with CR22BB and the relative transport ration of Sr{sup 2+}/Na{sup +} was 15. Cs{sup +} ion was effectively separated through liquid membrane with CR22BB(OH)Ph and the relative transport ration of Cs{sup +}/Na{sup +} was 3.4. 9 refs., 7 tabs., 15 figs. (author)

  19. Synthesis and characterization of organometallic macrocyclic rhodium (Ⅲ) complex with pyrazine ligands

    Institute of Scientific and Technical Information of China (English)

    WANG Jianqiang; ZHANG Zheng; WENG Linhong; JIN Guoxin


    The reaction of half-sandwich complex (Cptt Rh)2Cl2(μ-Cl)2 (1) (Cptt = η5-tBu2C5H3) with 1 equiv. Of AgSO3CF3 in CH2Cl2 affords tri-μ-chloro dirhodium (2) cation compound, with 2 equiv. Of AgSO3CF3 providing di-μ-chloro complex 3. The reaction of 3 with pyrazine gives a novel tetra-nuclear 14-member organometallic macrocyclic complex 4. FT-IR, 1H-NMR, and EA were used to characterize these complexes. The structures of complexes 2 and 4 are confirmed by X-ray analysis. In complex 2, the two Cptt ring and tri-chloro atoms faces are approximately parallel to each other. In complex 4, the complex cation has a rectangular cavity with the dimension of 0.3748 nm×0.7027 nm, and the two-pyrazine rings are parallel to each other with a distance of 0.3510 nm.

  20. Ketoprofen encapsulated cucurbit[6]uril nanoparticles: a new exploration of macrocycles for drug delivery (United States)

    Hoai, Nguyen To; Tuyen Thi Dao, Phuong; Phu, Quoc Nam; Dam Le, Duy; Nguyen, Tuan Anh; Nguyen, Tai Chi; Chien Dang, Mau


    The aim of this study is (i) to fabricate a nanoparticle formulation of ketoprofen (Keto) using a relatively new family of macrocycles as the carrier for drug delivery: cucurbit[6]uril (CB[6]), (ii) to evaluate its in vitro dissolution and (iii) to investigate its in vivo pharmaceutical property. The CB[6]-Keto nanoparticles were prepared by emulsion solvent evaporation method. Morphology and size of the successfully prepared nanoparticles were then confirmed using a transmission electron microscope and dynamic light scattering. It was shown that they are spherical with hydrodynamic diameter of 200-300 nm. The in vitro dissolution studies of CB[6]-Keto nanoparticles were conducted at pH 1.2 and 7.4. The results indicated that there is a significant increase in Keto concentration at pH 7.4 compared to pH 1.2. For the in vivo assessment, CB[6]-Keto nanoparticles and referential profenid were administered by oral gavages to rabbits. The results implied that CB[6]-Keto nanoparticles remarkably increased area under the curve compared to profenid.

  1. High performance ion chromatography of haloacetic acids on macrocyclic cryptand anion exchanger. (United States)

    Bruzzoniti, Maria Concetta; De Carlo, Rosa Maria; Horvath, Krisztian; Perrachon, Daniela; Prelle, Ambra; Tófalvi, Renáta; Sarzanini, Corrado; Hajós, Péter


    A new high performance ion chromatographic method has been developed for the separation of the nine chlorinated-brominated haloacetic acids (HAAs) that are the disinfection by-products of chlorination of drinking water, using a macrocycle-based adjustable-capacity anion-exchange separator column (IonPac Cryptand A1). A gradient method based on theoretical and experimental considerations has been optimized in which 10 mM NaOH-LiOH step gradient was performed at the third minute of the analysis. The optimized method allowed us to separate the nine HAAs and seven possibly interfering inorganic anions in less than 25 min with acceptable resolution. The minimum concentrations detectable for HAAs were between 8.0 (MBA) and 210 (TBA) microg L(-1), with linearity included between 0.9947 (TBA) and 0.9998 (MBA). To increase sensitivity, a 25-fold preconcentration step on a reversed phase substrate (LiChrolut EN) has been coupled. Application of this method to the analysis of haloacetic acids in real tap water samples is illustrated.

  2. Self-assembled benzophenone bis-urea macrocycles facilitate selective oxidations by singlet oxygen. (United States)

    Geer, Michael F; Walla, Michael D; Solntsev, Kyril M; Strassert, Cristian A; Shimizu, Linda S


    This manuscript investigates how incorporation of benzophenone, a well-known triplet sensitizer, within a bis-urea macrocycle, which self-assembles into a columnar host, influences its photophysical properties and affects the reactivity of bound guest molecules. We further report the generation of a remarkably stable organic radical. As expected, UV irradiation of the host suspended in oxygenated solvents efficiently generates singlet oxygen similar to the parent benzophenone. In addition, this host can bind guests such as 2-methyl-2-butene and cumene to form stable solid host-guest complexes. Subsequent UV irradiation of these complexes facilitated the selective oxidation of 2-methyl-2-butene into the allylic alcohol, 3-methyl-2-buten-1-ol, at 90% selectivity as well as the selective reaction of cumene to the tertiary alcohol, α,α'-dimethyl benzyl alcohol, at 63% selectivity. However, these products usually arise through radical pathways and are not observed in the presence of benzophenone in solution. In contrast, typical reactions with benzophenone result in the formation of the reactive singlet oxygen that reacts with alkenes to form endoperoxides, diooxetanes, or hydroperoxides, which are not observed in our system. Our results suggest that the confinement, the formation of a stable radical species, and the singlet oxygen photoproduction are responsible for the selective oxidation processes. A greater understanding of the mechanism of this selective oxidation could lead to development of greener oxidants.

  3. Study on the Crystal Structure of a Macrocycle and Tyrosinase Activity of Its Dinuclear Copper Complexes

    Institute of Scientific and Technical Information of China (English)

    周红; 潘志权; 罗勤慧; 梅光泉; 龙德良; 陈久桐


    A ring-contracted form macrocycle, 29,30-dioxo-3,6,9,17,20,23,29,30-octaazapentacyclo[23,3,1,111,15,02,6,016,20]-triacontaneocta- 1 (28),9,11 (12), 13,15(30),23,25(29),26-ene (L) was synthesized by condensation of diethyltriamine with pyridine-1-oxide-2,6-dicarboxaldehyde. A porous three-dimensional layer structure in its crystal was formed by self-assembly through hydrogen bonds and π-π interaction. Its dinuclear copper(I) complex [Cu2L(MeOH)2]-(BF4)2*2H2O and dinuclear-copper(II) complex [Cu2L(MeOH)2](ClO4)4*2H2O were obtained and could oxidize catalytically four phenolic substrates hydroquinone, 2-methyl-hydroquinone, 2,6-di-tert-butylphenol and 2,6-dimethylphenol, in a mixture of methanol and acetonitrile (V : V, 4 : 1). The copper(I) complex reacted with dioxygen to form an oxygenated species as an initial active intermediate for oxidation of the phenols. Oxidation of the substrates by the copper(II) complex produced a copper(I) complex and the oxidation products of the substrates.

  4. Molecular recognition by multiple metal coordination inside wavy-stacked macrocycles. (United States)

    Nakamura, Takashi; Kaneko, Yuya; Nishibori, Eiji; Nabeshima, Tatsuya


    Most biological and synthetic receptors for small organic molecules employ a combination of relatively weak intermolecular interactions such as hydrogen bonds. A host compound that utilizes stronger yet reversible bonding in a synergistic manner could realize precise recognition, but the regulation and spatial arrangement of such reactive interaction moieties have been a challenge. Here, we show a multinuclear zinc complex synthesized from a macrocyclic ligand hexapap, which inwardly arranges labile metal coordination sites for external molecules. The metallomacrocycle forms a unique wavy-stacked structure upon binding a suitable length of dicarboxylic acids via multipoint coordination bonding. The saddle-shaped deformation and dimerization realize the differentiation of the interaction moieties, and change of guest-binding modes at specific metal coordination sites among the many present have been achieved utilizing acid/base as external stimuli.Synergistic use of coordination bonds that are strong and reversible realizes unique molecular recognition in artificial systems. Here, the authors show that a zinc-based metallomacrocyle can bind dicarboxylic acids of suitable length at specific metal sites by shape deformation and dimerization.

  5. A Triple-Probe Channel NO{sub 2}S{sub 2}-Macrocycle: Synthesis, Sensing Characteristics and Crystal Structure of Mercury(II) Nitrate Complex

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Eun; Seo, Moo Lyong; Lee, Shim Sung [Gyeongsang National University, Jinju (Korea, Republic of); Choi, Kyu Seong [Kyungnam University, Masan (Korea, Republic of)


    A triple-probe channel type chemosensor based on an NO{sub 2}S{sub 2}-macrocycle functionalized with phenyltricyanovinyl group was synthesized and its sensing characteristics were examined. The pink-red solution of L changed selectively to pale yellow upon addition of Hg{sup 2+}. The selective fluorometric response of L to all the tested metal ions was studied. The results showed that a large enhancement of the fluorescence of L was observed only in the case of Hg{sup 2+}. In addition, L showed large anodic shift ({approx} 0.3 V) for the addition of excess Hg{sup 2+}. Through above three observed results by the different techniques, we confirmed that the proposed chemosensor acts as the multiple-probe channel sensing material. The crystal structure of mercury(II) nitrate complexes of L which shows a 1-D polymer network with a formula [Hg{sub 2}(L){sub 2}(NO{sub 3}){sub 2}({mu}-NO{sub 3}){sub 2}]{sub n} was also reported.

  6. “One Ring to Bind Them All”—Part I: The Efficiency of the Macrocyclic Scaffold for G-Quadruplex DNA Recognition

    Directory of Open Access Journals (Sweden)

    David Monchaud


    Full Text Available Macrocyclic scaffolds are particularly attractive for designing selective G-quadruplex ligands essentially because, on one hand, they show a poor affinity for the “standard” B-DNA conformation and, on the other hand, they fit nicely with the external G-quartets of quadruplexes. Stimulated by the pioneering studies on the cationic porphyrin TMPyP4 and the natural product telomestatin, follow-up studies have developed, rapidly leading to a large diversity of macrocyclic structures with remarkable-quadruplex binding properties and biological activities. In this review we summarize the current state of the art in detailing the three main categories of quadruplex-binding macrocycles described so far (telomestatin-like polyheteroarenes, porphyrins and derivatives, polyammonium cyclophanes, and in addressing both synthetic issues and biological aspects.

  7. Antiferromagnetically Coupled Dimeric Dodecacopper Supramolecular Architectures of Macrocyclic Ligands with a Symmetrical μ6-BO3(3-) Central Moiety. (United States)

    Tandon, Santokh S; Bunge, Scott D; Toth, Sara A; Sanchiz, Joaquin; Thompson, Laurence K; Shelley, Jacob T


    Reactions between 2,6-diformyl-4-alkyl(R)-phenol (R = CH3 or C(CH3)3) and 1,3-diamino-2-hydroxypropane (1,3-DAP) in the presence of copper(II) salts (Cu(BF4)2·6H2O, Cu(ClO4)2·6H2O/H3BO3/Ar) and triethylamine (TEA) in a single pot result in self-assembly of dimeric dodecacopper supramolecular architectures of 30-membered hexatopic macrocyclic ligands (H6L4 and H6L5) with unique and fascinating structures having the BO3(3-) anion as the central species bonded to all six copper centers in a symmetrical fashion (μ6-BO3(3-)). A number of closely related macrocyclic hexacopper complexes are reported: {[Cu6(L4)(μ6-BO3)(μ-H2O)(C3H7NO)2(BF4)][BF4]2·3C3H7NO}2 (1) (DMF = C3H7NO), {[Cu6(L4)(μ6-BO3)(μ-C3H7NO)3][ClO4]3·3C3H7NO}2 (2), {[Cu6(L5)(μ6-BO3)(μ-OH)(H2O)3(C3H7NO)][BF4]2·6C3H7NO·4C2H5OH·2H2O}2 (3), {[Cu6(L5)(μ6-BO3)(μ-CH3OH)(CH3OH)2][ClO4]3·10H2O}2 (4), and {[Cu6(L5)(μ6-BO3)(μ-CH3CO2)(μ-CH3O)(CH3OH)][BF4]·13CH3OH·8H2O}2 (5). A polymeric side product {[Cu2(H2L2)(CH3OH)(BF4)][BF4]}n (6), involving a 2 + 2 macrocyclic ligand, was also isolated and structurally characterized. Complex 6 involves dinuclear copper(II) units linked through BF4(-) anions to form a novel 1D single-chain polymeric coordination compound. This appears to be the first report in which a central BO3(3-) species is linked to six copper(II) ions held together by a single macrocyclic ligand through three μ1,1-O(BO3(3-)) and three μ1,3-O(BO3(3-)) bridges. In complexes 1-5 the BO3(3-) is present in the center of the macrocyclic cavity and is bonded to all six metal centers arranged in a benzene-like hexagonal array. In the hexagonal array there are alternate double (μ-alkoxide and μ1,3-O(BO3(3-))) and (μ-phenoxide and μ1,1-O(BO3(3-))) bridges between the Cu(II) centers. The symmetrical hexa-bridging nature of μ6-BO3(3-) is unprecedented in transition metal complex chemistry, and along with alkoxide and phenoxide bridges in the equatorial plane provides effective pathways for an

  8. Dysprosium complexes with the tetraphenylporphyrin macrocyclic ligand; Complejos de disprosio con el ligante macrociclico tetrafenilporfirina

    Energy Technology Data Exchange (ETDEWEB)

    Martinez M, V.; Padilla, J.; Ramirez, F.M


    In this report, the results obtained on the synthesis, characterization and study of the chemical behavior of dysprosium complex with the acetylacetone chelating agent (Hacac) and the tetraphenylporphyrin macrocyclic ligand (H{sub 2}TFP) are given. Based on the literature but according to our necessities and interest, the appropriate methodology settled down from the synthesis of prime matters until the obtaining and characterization of the products. The acetyl acetonate complex was obtained of mono hydrated dysprosium [Dy(acac){sub 3}. H{sub 2}0] and trihydrated [Dy(acac){sub 3} .3 H{sub 2}0], the mono tetra phenyl porphyrinate [Dy(TFP)(acac). 2 ac] the double sandwich of the dysprosium porphyrinate [Dy(TFP){sub 2}] and the triple sandwich of the dysprosium porphyrinate [Dy(TFP){sub 3}. 2 TCB] (TCB = trichlorobenzene). Its were characterized by their melting points, solubility, IR, UV, TGA and DTA both first and besides the techniques already mentioned for NMR'H, RPE and Magnetic susceptibility the three last complexes. From the spectroscopic point of view, IR and RPE its suggested the existence of a complex of inverse mixed valence [Dy(TFP){sup 2-} (TFP) {sup 1-}] for the Dy(TFP){sub 2} as a result of the existence of the free radical (TFP' {sup 1-} and that it was not in none of the other porphyrin compounds. In the NMR'H spectra of the compounds were not observed signals in the region from 0 to 10 ppm that which shows that the dysprosium complexes in special those of the porphyrin type are highly paramagnetic and its could be used as displacement reagents, creators of images and contrast agents of great utility in these days in studies of NMR, technique today by today used in medical diagnoses. (Author)

  9. Sustainable metal alkynyl chemistry: 3d metals and polyaza macrocyclic ligands. (United States)

    Ren, Tong


    We describe the chemistry of 3d metal alkynyls based on polyaza macrocyclic ligands, an emerging area of alkynyl chemistry that has previously been dominated by 4d and 5d metals with soft ligands. The abundance of 3d metals and low cost of tetraazacyclotetradecane ligands make these compounds more affordable, sustainable alternatives to metal alkynyls based on precious metals. Taking advantage of the rich variety of starting materials available in the literature, trans-[M(cyclam)(C2R)2]X (cyclam = 1,4,8,11-tetraazacyclotetradecane) compounds have been prepared from the reactions between [M(cyclam)X2]X (M = Cr, Fe and Co; X = Cl or OTf) and LiC2R. With [Co(cyclam)Cl2](+), both the {trans-[Co(cyclam)Cl]2(μ-(C≡C)n)}(2+) and trans-[Co(cyclam)(C2R)Cl](+) compounds have been prepared by a dehydrohalogenation reaction. The latter compounds undergo the second alkynylation reaction to afford dissymmetric trans-[Co(cyclam)(C2R)(C2R')](+) compounds. Similar alkynylation chemistry with complexes of the cyclam derivatives TMC (1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) and HMC (5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane) has been demonstrated in studies of [Ni(TMC)(C2R)](+) and trans-/cis-[Cr(HMC)(C2R)2](+). Me3TACN (1,4,7-N,N',N''-trimethyl-1,4,7-triazacyclononane) is also a supporting ligand that has been observed in transition metal alkynyls. The trans-[M(cyclam)(C2D)(C2A)](+) compounds (D = donor chromophore, A = acceptor chromophore) are excellent candidates for probing photoinduced electron transfer and related photophysical and photochemical processes. 3d Metal ions are often in high-spin ground states, which make these alkynyl compounds promising building blocks for magnetic materials.

  10. Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts.

    Directory of Open Access Journals (Sweden)

    Yuma Iwai

    Full Text Available The H1N1 influenza A virus of swine-origin caused pandemics throughout the world in 2009 and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. The threat of influenza A thus remains a serious global health issue and novel drugs that target these viruses are highly desirable. Influenza A possesses an endonuclease within its RNA polymerase which comprises PA, PB1 and PB2 subunits. To identify potential new anti-influenza compounds in our current study, we screened 33 different types of phytochemicals using a PA endonuclease inhibition assay in vitro and an anti-influenza A virus assay. The marchantins are macrocyclic bisbibenzyls found in liverworts, and plagiochin A and perrottetin F are marchantin-related phytochemicals. We found from our screen that marchantin A, B, E, plagiochin A and perrottetin F inhibit influenza PA endonuclease activity in vitro. These compounds have a 3,4-dihydroxyphenethyl group in common, indicating the importance of this moiety for the inhibition of PA endonuclease. Docking simulations of marchantin E with PA endonuclease suggest a putative "fitting and chelating model" as the mechanism underlying PA endonuclease inhibition. The docking amino acids are well conserved between influenza A and B. In a cultured cell system, marchantin E was further found to inhibit the growth of both H3N2 and H1N1 influenza A viruses, and marchantin A, E and perrotein F showed inhibitory properties towards the growth of influenza B. These marchantins also decreased the viral infectivity titer, with marchantin E showing the strongest activity in this assay. We additionally identified a chemical group that is conserved among different anti-influenza chemicals including marchantins, green tea catechins and dihydroxy phenethylphenylphthalimides. Our present results indicate that marchantins are candidate anti-influenza drugs and demonstrate the utility of the PA endonuclease assay in

  11. Molecular mechanics approach for design and conformational studies of macrocyclic ligands

    Energy Technology Data Exchange (ETDEWEB)

    Rohini,; Akbar, Rifat; Kanungo, B. K., E-mail: [Department of Chemistry, Sant Longowal Institute of Engineering & Technology, Longowal-148106 (India)


    Computational Chemistry has revolutionized way of viewing molecules at the quantum mechanical scale by allowing simulating various chemical scenarios that are not possible to study in a laboratory. The remarkable applications of computational chemistry have promoted to design and test of the effectiveness of various methods for searching the conformational space of highly flexible molecules. In this context, we conducted a series of optimization and conformational searches on macrocyclic based ligands, 9N3Me5Ox, (1,4,7-tris(5-methyl-8-hydroxyquinoline)-1,4,7-triazacyclononane) and 12N3Me5Ox, (1,5,9-tris(5-methyl-8-hydroxyquinoline)-1,5,9-triazacyclododecane) and studied their selectivity and coordination behavior with some lanthanide metal ions in molecular mechanics and semiempirical methods. The methods include both systematic and random conformational searches for dihedral angles, torsion angles and Cartesian coordinates. Structural studies were carried out by using geometry optimization, coordination scans and electronic properties were evaluated. The results clearly show that chair-boat conformational isomer of 9N3Me5Ox ligand is more stable due to lower eclipsing ethane interaction and form stronger adduct complexes with lanthanide metal ion. This is because of the fact that, in a central unit of 9N3 of the ligand form six endo type bonds out of nine. The rest of bonds have trans conformation. In contrast, for the adduct of 12N3Me5Ox, two C-C bonds have on eclipsed conformation, and others have synclinal and antiperiplanar confirmations. The distortion of the two eclipsed conformations may affect the yields and the stability of the complexes.

  12. Synthesis of Cycloveratrylene Macrocycles and Benzyl Oligomers Catalysed by Bentonite under Microwave/Infrared and Solvent-Free Conditions

    Directory of Open Access Journals (Sweden)

    Manuel Salmón


    Full Text Available Tonsil Actisil FF, which is a commercial bentonitic clay, promotes the formation of cycloveratrylene macrocycles and benzyl oligomers from the corresponding benzyl alcohols in good yields under microwave heating and infrared irradiation in the absence of solvent in both cases. The catalytic reaction is sensitive to the type of substituent on the aromatic ring. Thus, when benzyl alcohol was substituted with a methylenedioxy, two methoxy or three methoxy groups, a cyclooligomerisation process was induced. Unsubstituted, methyl and methoxy benzyl alcohols yielded linear oligomers. In addition, computational chemistry calculations were performed to establish a validated mechanistic pathway to explain the growth of the obtained linear oligomers.

  13. Cationic lipids bearing succinic-based, acyclic and macrocyclic hydrophobic domains: synthetic studies and in vitro gene transfer

    DEFF Research Database (Denmark)

    Jubeli, Emile; Maginty, A. B.; Khalique, N. A.;


    a dimethylamine or trimethylamine headgroup, and a macrocyclic or an acyclic hydrophobic domain composed of, or derived from two 16-atom, succinic-based acyl chains. The synthesized lipids and a co-lipid of neutral charge, either cholesterol or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), were formulated...... within the hydrophobic domain of the cationic lipids was found to improve lipid hydration. The transfection assays revealed a general trend in which mismatched formulations that employed a rigid lipid combined with a non-rigid (or flexible) lipid, outperformed the matched formulations. The results from...

  14. Chemical controls on uranyl citrate speciation and the self-assembly of nanoscale macrocycles and sandwich complexes in aqueous solutions. (United States)

    Basile, M; Unruh, D K; Gojdas, K; Flores, E; Streicher, L; Forbes, T Z


    Uranyl citrate forms trimeric species at pH > 5.5, but exact structural characteristics of these important oligomers have not previously been reported. Crystallization and structural characterization of the trimers suggests the self-assembly of the 3 : 3 and 3 : 2 U : Cit complexes into larger sandwich and macrocyclic molecules. Raman spectroscopy and ESI-MS have been utilized to investigate the relative abundance of these species in solution under varying pH and citrate concentrations. Additional dynamic light scattering experiments indicate that self-assembly of the larger molecules does occur in aqueous solution.

  15. Nitrogen macrocyclic molecules for sequestering of heavy metals; Molecules macrocycliques azotees pour la sequestration de metaux lourds

    Energy Technology Data Exchange (ETDEWEB)

    Chollet, H. [CEA Valduc, 21 - Is-sur-Tille (France); Denat, F.; Guilard, R. [Universite de Bourgogne, LIMSAG, 21 - Dijon (France)


    The tetra-aza-macrocycles and their derivatives have interesting properties in many fields, in particular for heavy metal extraction. Indeed, these ligands are able to complex many metals like uranium, plutonium, americium, cadmium, lead, etc. We describe the evolutions of design of these molecules since a score of years: simplifications of the synthesis leading to the improvement of the outputs, use of intermediate compounds facilitating the transposition at an industrial scale of the production of such molecules. The physicochemical behaviour of these ligands with respect to lanthanides and actinides, and their use within various processes of treatment are evoked. (authors)

  16. Dynamics of carbon storage in phytomass and soil humus in Northern Eurasia during the last climatic macrocycle (United States)

    Velichko, A. A.; Borisova, О. K.; Zelikson, E. M.; Morozova, T. D.


    Phytomass of terrestrial vegetation and soil humus are considered to be the most important sinks of carbon, and therefore their changes during glacial-interglacial macrocycle may influence considerably the carbon balance. Spatial reconstructions of paleovegetation and paleosols at the key intervals within the macrocycle, namely the Mikulino (Eemian) Interglacial ˜ 125 ka BP, the Last Glacial Maximum 20-18 ka BP, and the Holocene optimum ˜ 5.5 ka BP made it possible to estimate quantitatively the phytomass and soil humus carbon in Northern Eurasia (within the limits of the former Soviet Union). With the phytomass in modern (potential) vegetation taken as 100%, phytomass accumulated in vegetation which existed in Northern Eurasia 125, 18-20 and 5.5 ka BP amounts to 150%, 27% and 129%, respectively. The estimated carbon storage in soil humus for the same intervals is 149.2%, 23% and 128.8% of the present-day value. The values are similar to those previously calculated for the East European Plain except for LGM, where phytomass calculated for the whole territory of Northern Eurasia is relatively higher than that calculated for the East European Plain (27% and 6%). The same tendency is seen in the carbon storage in paleosols dated to the LGM 23 and 15% respectively. The difference in relative phytomass and carbon storage calculated for Eastern Europe and for Northern Eurasia may be attributed to the fact that degradation of forest and steppe vegetation was less pronounced in continental Siberia than in Eastern Europe.

  17. Phenol-containing macrocyclic diamides as new catalysts in the highly regioselective conversion of epoxides to beta-hydroxy thiocyanates. (United States)

    Sharghi, H; Nasseri, M A; Niknam, K


    The regioselective ring-opening reactions of some epoxides with ammonium thiocyanate in the presence of a series of new phenol-containing macrocyclic diamides and also dibenzo-18-crown-6-, 18-crown-6-, benzo-15-crown-5-, and pyridine-containing macrocyclic diamide have been studied. The epoxides were subject to cleavage by NH(4)SCN in the presence of these catalysts under mild reaction conditions in various aprotic solvents. In this study, reagents and conditions have been discovered with which the individual beta-hydroxy thiocyanates can be synthesized in high yield and with more than 90% regioselectivity. The results can be discussed in terms of a four-step mechanism: (1) formation of complex between catalyst and NH(4)SCN, (2) release of SCN(-) nucleophile from the complex, (3) reaction of the active nucleophile at the less sterically hindered site in the epoxide, and (4) regeneration of catalyst. The major advantages of this method are as follows: (1) high regioselectivity, (2) simple regeneration of catalyst, (3) its reuse through several cycles without a decrease in activity, and (4) ease of workup of the reaction.

  18. Hydrophobic, Hydrophilic, and Amphiphilic Polyglycocarbonates with Linear and Macrocyclic Architectures from Bicyclic Glycocarbonates Derived from CO2 and Glucoside

    KAUST Repository

    Pati, Debasis


    Two bicyclic glycocarbonates were synthesized in five steps from α-methyl-d-glucoside without resorting to phosgene or to its derivatives for the first time. The 4- and 6-positions of glucose were modified to introduce a six-membered carbonate ring, using CO as the carbonylating reagent; the 2- and 3-positions of the same glucoside substrate were first transformed into either methyl or triethylene glycol monomethyl ether groups to protect these positions from undesirable reactions and also to impart hydrophobicity in the first case and hydrophilicity in the second. The polymerization behavior of these bicyclic glycocarbonates was then investigated under different conditions. On the one hand, through ring-opening polymerization of the above monomers, linear polyglycocarbonate homopolymers and diblock copolymers were obtained initiated by p-methylbenzyl alcohol using 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as catalyst; on the other hand, macrocyclic polyglycocarbonate homopolymers and diblock copolymers were grown using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) which served as zwitterionic initiator. The various architectures derived were all thoroughly characterized by NMR, GPC, and MALDI-tof and shown to exhibit the expected structure. Finally, the self-assembly of linear and macrocyclic amphiphilic copolyglycocarbonates in water was investigated and characterized by cryo-TEM.

  19. Chemical Editing of Macrocyclic Natural Products and Kinetic Profiling Reveal Slow, Tight-Binding Histone Deacetylase Inhibitors with Picomolar Affinities. (United States)

    Kitir, Betül; Maolanon, Alex R; Ohm, Ragnhild G; Colaço, Ana R; Fristrup, Peter; Madsen, Andreas S; Olsen, Christian A


    Histone deacetylases (HDACs) are validated targets for treatment of certain cancer types and play numerous regulatory roles in biology, ranging from epigenetics to metabolism. Small molecules are highly important as tool compounds for probing these mechanisms as well as for the development of new medicines. Therefore, detailed mechanistic information and precise characterization of the chemical probes used to investigate the effects of HDAC enzymes are vital. We interrogated Nature's arsenal of macrocyclic nonribosomal peptide HDAC inhibitors by chemical synthesis and evaluation of more than 30 natural products and analogues. This furnished surprising trends in binding affinities for the various macrocycles, which were then exploited for the design of highly potent class I and IIb HDAC inhibitors. Furthermore, thorough kinetic investigation revealed unexpected inhibitory mechanisms of important tool compounds as well as the approved drug Istodax (romidepsin). This work provides novel inhibitors with varying potencies, selectivity profiles, and mechanisms of inhibition and, importantly, affords insight into known tool compounds that will improve the interpretation of their effects in biology and medicine.

  20. Synthesis and Crystal Structure of a Macrocycle [Cu(dadm)(mal)(H2O)]2·2H2O

    Institute of Scientific and Technical Information of China (English)

    林郑忠; 江飞龙; 陈莲; 洪茂椿


    The reaction of 4,4′-diaminodiphenylmethane (dadm), malonic acid (H2mal) and Cu(NO3)2 in aqueous solution results in a discrete binuclear Cu(II) macrocycle: [Cu(dadm)(mal)- (H2O)]2(2H2O. It crystallizes in monoclinic, space group P21/c with a = 15.231(3), b = 11.847(2), c = 9.801(2)A,Z= 106.75(3)o, V = 1693.5(6)A3, Z = 2, C32H40Cu2N4O12, Mr = 799.76, Dc = 1.568 g/cm3, λ(MoK() = 0.71073A, μ = 1.325 mm-1, F(000) = 828, the final R = 0.0531 and Wr = 0.1244 for 3421 observed reflections with I > 2σ(I). Each Cu(II) is coordinated by two oxygen atoms from a mal ligand, two nitrogen atoms from two dadm ligands and a water oxygen atom to form a triangle bipyramidal motif. The title compound possesses a distorted macrocycle enclosed by dadm with approximate dimensions of 8.3A× 5.9A.

  1. Synthesis and Biological Activities of Some New (Nα-Dinicotinoyl- bis-L-Leucyl Linear and Macrocyclic Peptides

    Directory of Open Access Journals (Sweden)

    Suzan Khayyat


    Full Text Available A series of linear and macrocyclic peptides 3–12 were synthesized using 3,5-pyridinedicarboxylic acid (1 as starting material and screened for their antimicrobial, anti-inflammatory and anticancer activities. Bis-ester 3 was prepared from 1 and L-leucine methyl ester. Hydrazinolysis and hydrolysis of dipeptide methyl ester 3 with hydrazine hydrate or 1 N sodium hydroxide afforded compounds 4 and 5, respectively. Cyclization of the dipeptide 5 with L-lysine methyl ester afforded cyclic pentapeptide ester 6. Compounds 7–9 were synthesized by reacting hydrazide 4 with phthalic anhydride, 1,8-naphthalene anhydride or acetophenone derivatives. Treatment of acid hydrazide 4 with aromatic aldehydes or tetraacid dianhydrides afforded the corresponding bis-dipeptide hydrazones 10a–e and macrocyclic peptides 11 and 12, respectively. The structures of newly synthesized compounds were confirmed by IR, 1H-NMR, MS spectral data and elemental analysis. The detailed synthesis, spectroscopic data, biological and pharmacological activities of the synthesized compounds was reported.

  2. Dinuclear Silver(I) and Copper(II) Complexes of Hexadentate Macrocyclic Ligands Containing p-Xylyl Spacers

    DEFF Research Database (Denmark)

    McKenzie, Christine J.; Nielsen, Lars Preuss; Søtofte, Inger


    The cyclocondensation of terephthalic aldehyde with N,N-bis(3-aminopropyl)-methylamine in the presence of silver(I) gives the dinuclear tetramine Schiff base macrocyclic complex, [Ag2L1](NO3)2 (L1=7,22-N,N'-dimethyl-3,7,11,18, 22,26-hexaazatricyclo[]-tetratricosa-2,11,13,15,1 7......,26,28,30,31,33-decaene). [Ag2L1](NO3)2 crystallizes in the monoclinic space group P21/c, with a=14.153(6), b=12.263(4), c=9.220(2) Å, beta=97.52(3) Å and Z=2. The silver ions are strongly coordinated at each end of the macrocycle by the two imine nitrogen atoms [2.177(3) and 2.182(3) Å] with close interatomic......,7,11,18,22,26-hexaazatricyclo[ 16]tetratricosa-13,15,28,30,31,33-decane, L2, was prepared by reduction of Ag2L1](NO3)2 with NaBH4. The copper(II) complexes of the reduced ligand, [Cu2Cl2L2]Cl2xCH3OH, [CU2Cl2L2](PF6)2 and [Cu2(CH3CO2)2L2](PF6)2x4H2O, have been prepared and characterized....

  3. Giant vesicles from 72-membered macrocyclic archaeal phospholipid analogues: initiation of vesicle formation by molecular recognition between membrane components (United States)

    Eguchi; Arakawa; Kakinuma; Rapp; Ghosh; Nakatani; Ourisson


    Stereochemically pure archeal acyclic bola-amphiphilic diphosphates 4 and 5, with the basic structure of the phospholipids found in Sulfolobus, have been synthesized for the first time. The self-assembly properties have been compared with those of the nearly identical 72-membered macrocyclic tetraether phosphates 3a and 3b, analogues of the major phospholipid components of Sulfolobus, Thermoplasma, and methanogenic Archea, which were also synthesized. Phase contrast and fluorescence microscopies have shown that the dipolar lipids 1 and 2 spontaneously formed vesicles. Whereas the macrocyclic dipolar phosphates 3 spontaneously formed vesicles (phase contrast and fluorescence microscopies), the bolaform phosphate 4 gave only a lamellar structure (synchrotron diffraction pattern: repeat distance of about 4.25 nm but with only a few layers). However, upon addition of the unphosphorylated precursors phytanol, phytol, or geranylgeraniol to the acyclic lipids 4 and 5, giant vesicles were rapidly formed. Addition of n-hexadecanol or cholesterol did not lead to vesicle formation. Therefore it was concluded that this vesicle formation occurs only when the added molecule is closely compatible with the constituents of the lipid layer and can be inserted into the double layer. A slight mismatch (cholesterol or n-hexadecanol/polyprenyl chains) is therefore enough to block the insertion process presumably required for vesicle formation.

  4. Mechanistics and photo-energetics of macrocycles and photodynamic therapy: An overview of aspects to consider for research. (United States)

    Horne, Tamarisk K; Cronjé, Marianne J


    Research within the field of photodynamic therapy has escalated over the past 20 years. The required conjunctional use of photosensitizers, particularly of the macrocycle structure, has lead to a vast repertoire of derivatives that branch classes and subclasses thereof. Each exhibits a differential range of physiochemical properties that influence their potential applications within the larger phototherapy field for use in either diagnostics, photodynamic therapy, both or none. Herein, we provide an overview of these properties as they relate to photodynamic therapy and to a lesser extent diagnostics. By summarizing the mechanistics of photodynamic therapy coupled to the photo-energetics displayed by macrocycle photosensitizers, we aimed to highlight the critical aspects any researcher should be aware of and consider when selecting and performing research for therapeutic application purposes. These include photosensitizer, photophysical and structural properties, synthesis design and subsequent attributes, main applications within research, common shortcomings exhibited and the current methods practiced to overcome them. © 2017 John Wiley & Sons A/S.

  5. Le problème des limites à la procréation assistée dans les lois des principaux pays européens The issue of the limits to medical assistance to procreation in the main European countries’legislation

    Directory of Open Access Journals (Sweden)

    Paolo Zatti


    Full Text Available A travers l’étude des limites à la procréation assistée dans les législations des principaux pays européens, l’article soulève différentes questions. Tout d’abord celle de savoir si la procréation assistée doit être un choix des individus ou si elle doit être réservée à des fins thérapeutiques. Ensuite celle de savoir si la femme seule peut accéder à la procréation assistée. Enfin la question de l’autorisation ou de l’interdiction de la fécondation post mortem, de la maternité de substitution et de la fécondation hétérologue. Ces questions doivent être abordées en tenant compte de la liberté de gérer son corps, de l’intérêt de l’enfant à naître et des limites de la compétence de l’Etat.This study of assisted reproduction limits in legislation of the main European countries raises various issues. The first one is to know whether assisted reproduction should be an individual choice or be reserved for therapeutic purpose. Then, there is the question whether a single woman can access to assisted reproduction. Finally the issue of allowance or prohibition of post mortem fertilization, of biological pregnancy and of hétérological fertilization. These issues must be analysed taking into account the freedom to control one’s body, the protection of the unborn child and the limits of State power.

  6. Cyanide Scavenging by a Cobalt Schiff-Base Macrocycle: A Cost-Effective Alternative to Corrinoids. (United States)

    Lopez-Manzano, Elisenda; Cronican, Andrea A; Frawley, Kristin L; Peterson, Jim; Pearce, Linda L


    The complex of cobalt(II) with the ligand 2,12-dimethyl-3,7,11,17-tetraazabicyclo-[11.3.1]heptadeca-1(17)2,11,13,15-pentaene (CoN4[11.3.1]) has been shown to bind two molecules of cyanide in a cooperative fashion with an association constant of 2.7 (±0.2) × 10(5). In vivo, irrespective of whether it is initially administered as the Co(II) or Co(III) cation, EPR spectroscopic measurements on blood samples show that at physiological levels of reductant (principally ascorbate) CoN4[11.3.1] becomes quantitatively reduced to the Co(II) form. However, following addition of sodium cyanide, a dicyano Co(III) species is formed, both in blood and in buffered aqueous solution at neutral pH. In keeping with other cobalt-containing cyanide-scavenging macrocycles like cobinamide and cobalt(III) meso-tetra(4-N-methylpyridyl)porphine, we found that CoN4[11.3.1] exhibits rapid oxygen turnover in the presence of the physiological reductant ascorbate. This behavior could potentially render CoN4[11.3.1] cytotoxic and/or interfere with evaluations of the antidotal capability of the complex toward cyanide through respirometric measurements, particularly since cyanide rapidly inhibits this process, adding further complexity. A sublethal mouse model was used to assess the effectiveness of CoN4[11.3.1] as a potential cyanide antidote. The administration of CoN4[11.3.1] prophylactically to sodium cyanide-intoxicated mice resulted in the time required for the surviving animals to recover from "knockdown" (unconsciousness) being significantly decreased (3 ± 2 min) compared to that of the controls (22 ± 5 min). All observations are consistent with the demonstrated antidotal activity of CoN4[11.3.1] operating through a cyanide-scavenging mechanism, which is associated with a Co(II) → Co(III) oxidation of the cation. To test for postintoxication neuromuscular sequelae, the ability of mice to remain in position on a rotating cylinder (RotaRod test) was assessed during and after recovery

  7. Chemical evolution on planetary surfaces: from simple gases to organic macrocycles (United States)

    Fox, Stefan; Strasdeit, Henry

    It is generally accepted that α-amino acids existed in the primordial ocean on the Hadean / early Archean Earth. They had been abiotically synthesized from smaller molecules such as H2 , CH4 , H2 O, NH3 , HCN, aldehydes, ketones, and alcohols [1-3]. Once the amino acids had been formed, they probably reacted to more complex molecules. One possibility is the thermal transformation at hot volcanic coasts. In a first step, amino acid-containing seawater evaporated in the vicinity of lava streams. A salt crust remained in which amino acids were embedded. In a second step, these embedded amino acids were thermally transformed to new compounds. In order to simulate this hot-volcanic-coast scenario artificial salt crusts with embedded amino acids were prepared and heated to 300-800 ° C in a slow stream of nitrogen gas. We found that in the salt crusts glycine, DL-alanine and -aminoisobutyric acid were chemically bonded to calcium or magnesium ions. This metal coordination prevents the sublimation of the amino acids and permits the thermal formation of pyridines, piperazine-2,5-diones, polycyclic aromatic hydrocarbons, and especially several alkylated pyrroles. Thus an abiotic source of pyrroles on young Earth-like planets may exist. Amino acids and pyrroles are building blocks of important biomolecules. It might seem plausible that amino acids formed peptides on the early Earth. However, in aqueous solution the condensation reaction is unfavorable, and even if short peptides would have formed they would have tended to hydrolyze. This argument is equally true for nucleic acid components [4]. In contrast to that, it is known that pyrrole, in aqueous HCl solutions, reacts with formaldehyde to form oligopyrroles [5]. Prebiotic oligopyrroles and their metal complexes may have been utilized by primitive metabolizing systems and later modified into porphyrin-like macrocycles such as chlorophyll. [1] Miller, S. L. (1953) Science, 117, 528. [2] Johnson, A. P., Cleaves, H. J

  8. Microscale Synthesis, Reactions, and (Super 1)H NMR Spectroscopic Investigations of Square Planar Macrocyclic, Tetramido-N Co(III) Complexes Relevant to Green Chemistry (United States)

    Watson, Tanya T.; Uffelman, Erich S.; Lee, Daniel W., III; Doherty, Jonathan R.; Schulze, Carl; Burke, Amy L.; Bonnema, Kristen, R.


    The microscale preparation, characterization, and reactivity of a square planar Co(III) complex that has grown out of a program to introduce experiments of relevance to green chemistry into the undergraduate curriculum is presented. The given experiments illustrate the remarkable redox and aqueous acid-base stability that make the macrocycles very…

  9. Synthesis, spectroscopic studies and inhibitory activity against bactria and fungi of acyclic and macrocyclic transition metal complexes containing a triamine coumarine Schiff base ligand (United States)

    Abou-Hussein, A. A.; Linert, Wolfgang


    Two series of new mono and binuclear complexes with a Schiff base ligand derived from the condensation of 3-acetylcoumarine and diethylenetriamine, in the molar ratio 2:1 have been prepared. The ligand was characterized by elemental analysis, IR, UV-visible, 1H-NMR and mass spectra. The reaction of the Schiff base ligand with cobalt(II), nickel(II), copper(II), zinc(II) and oxovanadium(IV) lead to mono or binuclear species of cyclic or macrocyclic complexes, depending on the mole ratio of metal to ligand and as well as on the method of preparation. The Schiff base ligand behaves as a cyclic bidentate, tetradendate or pentaentadentae ligand. The formation of macrocyclic complexes depends significantly on the dimension of the internal cavity, the rigidity of the macrocycles, the nature of its donor atoms and on the complexing properties of the anion involved in the coordination. Electronic spectra and magnetic moments of the complexes indicate that the geometries of the metal centers are either square pyramidal or octahedral for acyclic or macro-cyclic complexes. The structures are consistent with the IR, UV-visible, ESR, 1H-NMR, mass spectra as well as conductivity and magnetic moment measurements. The Schiff base ligand and its metal complexes were tested against two pathogenic bacteria as Gram-positive and Gram-negative bacteria as well as one kind of fungi. Most of the complexes exhibit mild antibacterial and antifungal activities against these organisms.

  10. Synthesis, spectroscopic studies and inhibitory activity against bacteria and fungi of acyclic and macrocyclic transition metal complexes containing a triamine coumarine Schiff base ligand. (United States)

    Abou-Hussein, A A; Linert, Wolfgang


    Two series of new mono and binuclear complexes with a Schiff base ligand derived from the condensation of 3-acetylcoumarine and diethylenetriamine, in the molar ratio 2:1 have been prepared. The ligand was characterized by elemental analysis, IR, UV-visible, (1)H-NMR and mass spectra. The reaction of the Schiff base ligand with cobalt(II), nickel(II), copper(II), zinc(II) and oxovanadium(IV) lead to mono or binuclear species of cyclic or macrocyclic complexes, depending on the mole ratio of metal to ligand and as well as on the method of preparation. The Schiff base ligand behaves as a cyclic bidentate, tetradendate or pentaentadentae ligand. The formation of macrocyclic complexes depends significantly on the dimension of the internal cavity, the rigidity of the macrocycles, the nature of its donor atoms and on the complexing properties of the anion involved in the coordination. Electronic spectra and magnetic moments of the complexes indicate that the geometries of the metal centers are either square pyramidal or octahedral for acyclic or macro-cyclic complexes. The structures are consistent with the IR, UV-visible, ESR, (1)H-NMR, mass spectra as well as conductivity and magnetic moment measurements. The Schiff base ligand and its metal complexes were tested against two pathogenic bacteria as Gram-positive and Gram-negative bacteria as well as one kind of fungi. Most of the complexes exhibit mild antibacterial and antifungal activities against these organisms.

  11. Spectroscopic evidence on improvement in complex formation of O2N2 aza-crown macrocyclic ligands with Cu(II) acetate upon incorporation with [60]Fullerene (United States)

    Ghanbari, Bahram; Gholamnezhad, Parisa


    The present paper reports the spectroscopic investigations on the complexation of Cu(II) with two macrocyclic ligands bonded to [60]Fullerene (L1 and L2) measured in N-methylpyrrolidone (NMP) as solvent. On the basis of UV-vis-NIR spectroscopy applying Jobs method of continuous variation, typical 1:1 stoichiometries were established for the complexes of Cu(II) with L1, and L2. DFT calculations suggested that superior HOMO distributions spread over the nitrogen-donor (as well as somehow oxygen- donor in L2) groups of L1 and L2 macrocycles were the key factor for the observed Kb value enhancement. Thermodynamic stabilities for these complexes have also been determined employing Benesi-Hildebrand equation and the results were compared in terms of their calculated binding constants (Kb). These measurements showed that L1 and L2 bound to these cations stronger than their parent free macrocyclic ligands 1 and 2, respectively. Furthermore, Kb values found for L2 complexes revealed that it could coordinate Cu(II) cation better than L1. Thermodynamic parameters (ΔG, ∆ H, and - ΔS) derived from Van't Hoff equation showed that L1 and L2 coordination of Cu(II) cation were occurred due to both enthalpic and entropic factors while the coordination of Cu(II) with their parent macrocyclic ligands 1 and 2 only enjoyed from only enthalpic advantages.

  12. Adsorption of a benzylic amide macrocycle on a solid substrate : XPS and HREELS characterization of thin films grown on Au(111)

    NARCIS (Netherlands)

    Whelan, Caroline M.; Cecchet, Francesca; Baxter, Richard; Zerbetto, Francesco; Clarkson, Guy J.; Leigh, David A.; Rudolf, Petra


    Thin films of a benzylic amide macrocycle, the common component of a wide class of mechanically interlocked molecules, are prepared by vapor deposition on Au(111). The films are characterized by monochromated X-ray photoelectron spectroscopy (XPS) and high resolution electron energy loss spectroscop

  13. Liquid Membrane Transport Behavior of Functional Substituted Crown Ethers for Amino Acids

    Institute of Scientific and Technical Information of China (English)


    Three functional substituted crown ethers were synthesized as liquid membrane transport carriers for amino acids. The result obtained shows that this kind of ditopic ligands can transport sodium salt of amino acids in good rate value especially the one with two pyridinyl groups as binding site outside the macrocycle.

  14. Influence des herbicides sur les principaux paramètres ...

    African Journals Online (AJOL)


    28 févr. 2015 ... adventices Lyba (faible tallage) et Homari (tige courte) ont ... each comprising a control (no herbicide) and three herbicides: the Quartz super dose (1.0 ..... Levée complète. Tallage complet. Montaison Épiaison Floraison.

  15. Rigid Organization of Fluorescence-Active Ligands by Artificial Macrocyclic Receptor to Achieve the Thioflavin T-Amyloid Fibril Level Association. (United States)

    Zhang, Ying-Ming; Zhang, Xu-Jie; Xu, Xiufang; Fu, Xiao-Ning; Hou, Hong-Biao; Liu, Yu


    The push-pull molecules with an intramolecular charge transfer from donor to acceptor sides upon excitation exhibit a wide variety of biological and electronic activities, as exemplified by the in vivo fluorescence imaging probes for amyloid fibrils in the diagnosis and treatment of amyloid diseases. Interestingly, the structurally much simpler bis(4,8-disulfonato-1,5-naphtho)-32-crown-8 (DNC), in keen contrast to the conventional macrocyclic receptors, was found to dramatically enhance the fluorescence of twisted intramolecular charge-transfer molecules possessing various benzothiazolium and stilbazolium fluorophores upon complexation. Spectroscopic and microcalorimetric titrations jointly demonstrated the complex structures and the interactions that promote the extremely strong complexation, revealing that the binding affinity in these artificial host-guest pairs could reach up to a nearly 10(7) M(-1) order of magnitude in water, and the sandwich-type complexation is driven by electrostatic, hydrophobic, π-stacking, and hydrogen-bonding interactions. Quantum chemical calculations on free molecules and their DNC-bound species in both the ground and excited states elucidated that the encapsulation by DNC could greatly deter the central single and double chemical bonds from free intramolecular rotation in the singlet excited state, thus leading to the unique and unprecedented fluorescence enhancement upon sandwich-type complexation. This complexation-induced structural reorganization mechanism may also apply to the binding of other small-molecule ligands by functional receptors and contribute to the molecular-level understanding of the receptor-ligand interactions in many biology-related systems.

  16. Influence of Anion and Mole Ratio on the Coordination Behavior of an NO2S3-Macrocycle: The Formation of a Dumbbell-Shaped Macrocyclic Cadmium(II) Iodide Complex. (United States)

    Lee, Hyeong-Hwan; Lee, Eunji; Ju, Huiyeong; Kim, Seulgi; Park, In-Hyeok; Lee, Shim Sung


    Anion and mole ratio dependent formations of cadmium(II) complexes with an NO2S3-macrocycle (L) incorporating a pyridine subunit are reported. When the cadmium(II) salts (1-10 equiv) with different halide ions (Br(-) or I(-)) were reacted with L, CdBr2 afforded a monomer complex, [Cd(L)Br]2[Cd2Br6]·CH2Cl2 (1), with three separated parts in the whole mole ratio range: two 1:1 stoichiometric complex cation parts and one Cd2Br6 cluster anion part. After separation of 1 by filtration, [Cd(L)Br]2[CdBr4]·CH2Cl2 (2) with similar composition was afforded, except the cluster was isolated from the filtrate. Unlike the CdBr2 complexation, CdI2 afforded the mole ratio dependent products (3-5). Below 2.5 equiv of CdI2, [Cd(L)I]2[CdI4]·CH2Cl2 (3) and [Cd(L)I]2[Cd2I6]·0.5CH2Cl2 (4) with different cadmium(II) iodide clusters were isolated as kinetic (3) and a thermodynamic (4) products. Notably, the use of 3 equiv or above amount of CdI2 gave a dumbbell-shaped complex, {[Cd(L)]2(μ-Cd4I12)} (5), in which two mononuclear macrocyclic complex units are linked by a (μ-Cd4I12)(4-) cluster. To monitor the mole ratio dependency as well as their reactivities, the systematic powder X-ray diffraction (PXRD) analysis has also been applied.

  17. HCV genotypes are differently prone to the development of resistance to linear and macrocyclic protease inhibitors.

    Directory of Open Access Journals (Sweden)

    Valeria Cento

    Full Text Available BACKGROUND: Because of the extreme genetic variability of hepatitis C virus (HCV, we analyzed whether specific HCV-genotypes are differently prone to develop resistance to linear and macrocyclic protease-inhibitors (PIs. METHODS: The study includes 1568 NS3-protease sequences, isolated from PI-naive patients infected with HCV-genotypes 1a (N = 621, 1b (N = 474, 2 (N = 72, 3 (N = 268, 4 (N = 54 5 (N = 6, and 6 (N = 73. Genetic-barrier was calculated as the sum of nucleotide-transitions (score = 1 and/or nucleotide-transversions (score = 2.5 required for drug-resistance-mutations emergence. Forty-three mutations associated with PIs-resistance were analyzed (36A/M/L/G-41R-43S/V-54A/S/V-55A-Q80K/R/L/H/G-109K-138T-155K/Q/T/I/M/S/G/L-156T/V/G/S-158I-168A/H/T/V/E/I/G/N/Y-170A/T-175L. Structural analyses on NS3-protease and on putative RNA-models have been also performed. RESULTS: Overall, NS3-protease was moderately conserved, with 85/181 (47.0% amino-acids showing 94% HCV-2-4; 175L present in 100% HCV-1a-3-5 and >97% HCV-2-4. Furthermore, HCV-3 specifically showed non-conservative polymorphisms (R123T-D168Q at two drug-interacting positions. Regardless of HCV-genotype, 13 PIs resistance-mutations were associated with low genetic-barrier, requiring only 1 nucleotide-substitution (41R-43S/V-54A-55A-80R-156V/T: score = 1; 54S-138T-156S/G-168E/H: score = 2.5. By contrast, by using HCV-1b as reference genotype, nucleotide-heterogeneity led to a lower genetic-barrier for the development of some drug-resistance-mutations in HCV-1a (36M-155G/I/K/M/S/T-170T, HCV-2 (36M-80K-155G/I/K/S/T-170T, HCV-3 (155G/I/K/M/S/T-170T, HCV-4-6 (155I/S/L, and HCV-5 (80G-155G/I/K/M/S/T. CONCLUSIONS: The high degree of HCV genetic variability makes HCV-genotypes, and even subtypes, differently prone to the development of PIs resistance-mutations. Overall, this can account for different responsiveness of HCV-genotypes to PIs, with

  18. Template Syntheses and Crystal Structures of Hexaaza Macrocyclic Complexes with C-Methyl Substituents

    Institute of Scientific and Technical Information of China (English)


    Two new macrocyclic complexes with C-methyl substituents on the framework,namely, [CuL](ClO4)2 (L = 5,12-dimethyl- 1,8-dihydroxyethyl- 1,3,6,8,10,13-hexaazacyclotetradecane) 1 and [NiL](ClO4)2 2, have been synthesized and structurally characterized through X-ray diffraction analysis. Also, crystal structure of [CuL1](ClO4)2 (L1 = 1,8-dimethyl- 1,3,6,8,10,13- hexaazacyclotetradecane) 3 has been determined. Crystal data for 1: C14H32C12CuN6O10, Mr = 578.90,monoclinic, P21In, a = 8.3529(11), b = 10.8105(17), c = 13.3709(17) A, β = 105.189(10)°, V =1165.2(3) A3, Z = 2, Dc = 1.650 g/cm3, F(000) = 602, λ(MoKα) = 0.71073 A,μ = 1.229 mm-1, R =0.0474 and wR = 0.0895 for 2771 observed reflections (I > 2σ(I)). Crystal data for 2:C14H32C12N6NiO10, Mr = 574.07, monoclinic, P21/c, a = 8.3636(12), b = 12.997(2), c = 10.764(2) A,β = 99.31 (2)°, V = 1154.7(3) A3, Z = 2, Dc = 1.651 g/cm3, F(000) = 600, λ(MoKα) = 0.71073 A,μ =1.134 mm-1, R = 0.0380 and wR = 0.0796 for 2670 observed reflections (I > 2σ(Ⅰ)). Crystal data for 3. C10H26Cl2CuN6O8, Mr = 492.81, monoclinic, P21/n, a = 8.4860(17), b = 8.6320(17), c = 12.662(3)A, β = 103.40(3)°, V = 902.2(3) A3, Z = 2, Dc = 1.814 g/cm3, F(000) = 510, λ(MoKα) = 0.71073 A,μ = 1.562 mm - 1, R = 0.0505 and wR = 0. 1 061 for 1967 observed reflections (I > 2σ(Ⅰ)). Complexes 1 and 2 are isostructural with the metal ions situated at the inversion center. Hydrogen bonds between O atoms of pendant and perchlorate anion give rise to a two-dimensional supramolecular layer. The Cu(Ⅱ) ions of compounds 1 and 3 adopt distorted axially-elongated octahedral coordinate geometry, and the nickel(Ⅱ) ion in complex 2 is four-coordinated with a square-planar configuration.

  19. An attempt to understand the observed plateau of the magnetization in tetranuclear iron(II) complexes of thiacalixarene macrocycles

    Indian Academy of Sciences (India)

    Ali Bayri; H Gokhan Bakir; Mustafa Sulu; Mustafa Karakaplan


    The next-nearest-neighbour (NNN) effect in tetranuclear iron(II) complexes of thiacalixarene macrocycles using the isotropic Heisenberg model has been investigated in order to understand its effects on the observed plateau of magnetization. Although NNN effect is generally very weak in these kinds of systems, it was calculated that its response is quite significant to the external perturbations in certain temperature regions. Using the isotropic Heisenberg exchange Hamiltonian, zero-field energy spectra have been calculated for this particular tetranuclear system. The average magnetic moments with and without next-nearest-neighbour interactions were also calculated. In order to verify the calculations, the results were compared with experimental data taken from the literature, whence, it is suggested that observed magnetic behaviour can be improved by taking into account the NNN effect.

  20. Charles J. Pedersen: innovator in macrocyclic chemistry and co-recipient of the 1987 Nobel Prize in chemistry. (United States)

    Izatt, Reed M


    Charles J. Pedersen began life in Korea where his father was employed as an engineer at a gold mine in a remote region of that country. He received his primary and secondary school education in Japan and university training in the United States. He was employed as an organic research chemist at DuPont for 42 years. The signal accomplishment of this unusual individual was his serendipitous discovery of macrocyclic polyethers and of their selective complexation of alkali metal cations. This discovery sparked the development of a new field of chemistry and led to his sharing the Nobel Prize in Chemistry in 1987. An attempt is made to understand Pedersen as a person in this article.

  1. Copper(ii) complexes of macrocyclic and open-chain pseudopeptidic ligands: synthesis, characterization and interaction with dicarboxylates. (United States)

    Faggi, Enrico; Gavara, Raquel; Bolte, Michael; Fajarí, Lluís; Juliá, Luís; Rodríguez, Laura; Alfonso, Ignacio


    Mono- and dinuclear Cu(ii) complexes were prepared with pseudopeptidic open chain and macrocyclic ligands, respectively. They were characterized by UV-vis spectroscopy, EPR, HRMS and X-ray diffraction. The Cu(ii) cation is coordinated by two amines and two deprotonated amides, in a slightly distorted square planar coordination geometry. The complexes interact with several substituted dicarboxylates, as shown by UV-vis titrations and EPR experiments. The interaction of both mono- and dinuclear complexes with very similar dicarboxylates of biological interest (malate and aspartate) resulted in strikingly different outcomes: in the first case a ternary complex [ligand...metal...dicarboxylate] was obtained almost quantitatively, while in the latter, the Cu(ii) displacement to form Cu(Asp)2 was predominant.

  2. Hydrogenolysis of glycerol with FeCo macrocyclic complex bonded to Raney nickel support under mild reaction conditions

    Energy Technology Data Exchange (ETDEWEB)

    Anand, K.A.; Anisia, K.S.; Kumar, A. [Indian Inst. of Technology, Kanpur (India). Dept. of Chemical Engineering; Agarwal, A.K. [Indian Inst. of Technology, Kanpur (India). Dept. of Mechanical Engineering


    This study investigated the hydrogenolysis of dilute glycerol solution to 1,2-propanediol in the presence of a heterogenous catalyst with a heterodinuclear FeCo macrocyclic complex ionically bonded to Raney nickel. Experiments were conducted to determine the stability of the complex bonded to the support at various temperatures, as well as to determine the effect of the solvent. Results of the studies indicated that the catalyst was stable up to 600 degrees C after 100 hours of refluxing. The study showed that conversion rates increased when hydrogenolysis temperatures were increased from 165 to 220 degrees C, with an initial hydrogen pressure of 0.35 MPa. The conversion and yield of 1,2-propanediol increased when the water content increased. Results of the study were used to create a kinetic model and genetic algorithm for determining optimal rate constants. 27 refs., 2 tabs., 14 figs.

  3. Macrocyclic Trichothecenes from Myrothecium roridum Strain M10 with Motility Inhibitory and Zoosporicidal Activities against Phytophthora nicotianae. (United States)

    Mondol, Muhammad Abdul Mojid; Surovy, Musrat Zahan; Islam, M Tofazzal; Schüffler, Anja; Laatsch, Hartmut


    The cytotoxicity of the extract obtained from Myrothecium roridum M10 and a characteristic (1)H signal at δH ∼8 led to the assumption that verrucarin/roridin-type compounds were present. Upscaling on rice medium led to the isolation of four new metabolites: verrucarins Y (1) and Z (6) (macrocyclic trichothecenes), bilain D (12) (a diketopiperazine derivative), and hamavellone C (14) (an unusual cyclopropyl diketone). In addition, nine known trichothecenes [verrucarin A (3), 16-hydroxyverrucarin A (5), verrucarin B (7), 16-hydroxyverrucarin B (8), verrucarin J (2), verrucarin X (4), roridin A (9), roridin L-2 (10), and trichoverritone (11)] and a bicyclic lactone [myrotheciumone A (15)] were identified. Their structures and configurations were determined by spectroscopic methods, published data, Mosher's method, and considering biosyntheses. Some trichothecenes showed motility inhibition followed by lysis of the zoospores against devastating Phytophthora nicotianae within 5 min. Compounds 2, 3, 7, and 9 also exhibited potent activities against Candida albicans and Mucor miehei.

  4. Pendant-armed Unsymmetrical Aza-macrocycles: Syntheses,Coordination Behavior and Crystal Structure of a Dinuclear Cadmium Complex

    Institute of Scientific and Technical Information of China (English)

    TAO,Jing-Chao(陶京朝); LIAO,Xin-Cheng(廖新成); WANG,Xing-Wang(王兴旺); DU,Chen-Xia(杜晨霞)


    Two nsymmetrical tetradentate aza-macrocycles with side arms attached to the N3sp atoms, L1 and L2, as well as their complexes with different metal cations were synthesized and characterized by EA, UV, IR, 1H NMR and MS spectra. Both the two ligands can efficiently transport alkali and transition metal cations across an organic membrane with high selectivity ratio. The structure of a dinuclear Cd(Ⅱ)complex [L1@(CdCl2)2] was elucdated by X-ray crystallography and was solved by the heavy-atom method to afinal R value of 0.029 for 3084reflections with |F| >3σ(I). In the exo-structore of the dinuclear complex each cadmium atom is five-coordinated, bonding to three N atoms and two chlorine atoms.

  5. Heterogeneous and Homogeneous Routes in Water Oxidation Catalysis Starting from Cu(II) Complexes with Tetraaza Macrocyclic Ligands. (United States)

    Prevedello, Andrea; Bazzan, Irene; Dalle Carbonare, Nicola; Giuliani, Angela; Bhardwaj, Sunil; Africh, Cristina; Cepek, Cinzia; Argazzi, Roberto; Bonchio, Marcella; Caramori, Stefano; Robert, Marc; Sartorel, Andrea


    Since the first report in 2012, molecular copper complexes have been proposed as efficient electrocatalysts for water oxidation reactions, carried out in alkaline/neutral aqueous media. However, in some cases the copper species have been recognized as precursors of an active copper oxide layer, electrodeposited onto the working electrode. Therefore, the question whether copper catalysis is molecular or not is particularly relevant in the field of water oxidation. In this study, we investigate the electrochemical activity of copper(II) complexes with two tetraaza macrocyclic ligands, distinguishing heterogeneous or homogeneous processes depending on the reaction media. In an alkaline aqueous solution, and upon application of an anodic bias to working electrodes, an active copper oxide layer is observed to electrodeposit at the electrode surface. Conversely, water oxidation in neutral aqueous buffers is not associated to formation of the copper oxide layer, and could be exploited to evaluate and optimize a molecular, homogeneous catalysis.

  6. A review on the toxicity and non-target effects of macrocyclic lactones in terrestrial and aquatic environments. (United States)

    Lumaret, Jean-Pierre; Errouissi, Faiek; Floate, Kevin; Römbke, Jörg; Wardhaugh, Keith


    The avermectins, milbemycins and spinosyns are collectively referred to as macrocyclic lactones (MLs) which comprise several classes of chemicals derived from cultures of soil micro-organisms. These compounds are extensively and increasingly used in veterinary medicine and agriculture. Due to their potential effects on non-target organisms, large amounts of information on their impact in the environment has been compiled in recent years, mainly caused by legal requirements related to their marketing authorization or registration. The main objective of this paper is to critically review the present knowledge about the acute and chronic ecotoxicological effects of MLs on organisms, mainly invertebrates, in the terrestrial and aquatic environment. Detailed information is presented on the mode-of-action as well as the ecotoxicity of the most important compounds representing the three groups of MLs. This information, based on more than 360 references, is mainly provided in nine tables, presenting the effects of abamectin, ivermectin, eprinomectin, doramectin, emamectin, moxidectin, and spinosad on individual species of terrestrial and aquatic invertebrates as well as plants and algae. Since dung dwelling organisms are particularly important non-targets, as they are exposed via dung from treated animals over their whole life-cycle, the information on the effects of MLs on dung communities is compiled in an additional table. The results of this review clearly demonstrate that regarding environmental impacts many macrocyclic lactones are substances of high concern particularly with larval instars of invertebrates. Recent studies have also shown that susceptibility varies with life cycle stage and impacts can be mitigated by using MLs when these stages are not present. However information on the environmental impact of the MLs is scattered across a wide range of specialised scientific journals with research focusing mainly on ivermectin and to a lesser extent on abamectin

  7. Macrocyclic and lantern complexes of palladium(II) with bis(amidopyridine) ligands: synthesis, structure, and host-guest chemistry. (United States)

    Yue, Nancy L S; Eisler, Dana J; Jennings, Michael C; Puddephatt, Richard J


    The reactions of [PdCl2(NCPh)2] in a 1:1 ratio with the bis(amidopyridine) ligands LL=C6H3(5-R)(1,3-CONH-3-C5H4N)2 with R=H (1a) or R=t-Bu (1b) give the corresponding neutral dipalladium(II) macrocycles trans,trans-[Pd2Cl4(mu-LL)2], 2a and 2b, which crystallize from dimethylformamide with one or two solvent molecules as macrocycle guests. The reaction of [PdCl2(NCPh)2] with LL in a 1:2 ratio gave the cationic lantern complex [Pd2(mu-LL)4]Cl4, 3c (LL=1b), and the reaction in the presence of AgO2CCF3 gave the corresponding trifluoroacetate salts [Pd2(mu-LL)4](CF3CO2)4, 3a (LL=1a) and 3b (LL=1b). These lantern complexes exhibit a remarkable host-guest chemistry, as they can encapsulate cations, anions, and water molecules by interaction of the guest with either the electrophilic NH or the nucleophilic C=O substituents of the amide groups, which can be directed toward the center of the lantern through easy conformational change. The structures of several of these host-guest complexes were determined, and it was found that the cavity size and shape vary according to the ligand conformation, with Pd...Pd separations in the range from 9.45 to 11.95 A. Supramolecular ordering of the lanterns was observed in the solid state, through either hydrogen bonding or secondary bonding to the cationic palladium(II) centers. The selective inclusion by the lantern complexes of alkali metal ions in the sequence Na+ > K+ > Li+ was observed by ESI-MS.

  8. The Géocarbone-Monitoring Project: Main Results and Recommendations for Monitoring Deep Geological CO2 Storage in the Paris Basin Le projet de recherche Géocarbone-Monitoring : principaux résultats et recommandations pour le monitoring des stockages géologiques profonds de CO2 dans le bassin Parisien

    Directory of Open Access Journals (Sweden)

    Fabriol H.


    Full Text Available The aim of the Géocarbone-Monitoring research project was the evaluation and testing, as far as possible, of the different monitoring methods that might be applied in the specific context of the Paris Basin. Their main objectives are to: detect and map CO2 in the reservoir rocks; detect and quantify possible leaks between the reservoir and the surface. The partners developed several thoughts and research concerning the various monitoring methods. This enabled drawing up a critical overview of existing methods and proposing leads for further work. At the end of the project, recommendations were made for the stakeholders of CO2 storage, i.e. the government departments regulating storage, decision-makers, and future site operators. In addition, a proposal was made for the general design and implementation of a monitoring programme of an injection test in the Paris Basin, within a depleted reservoir or a deep aquifer. Le projet de recherche Géocarbone-Monitoring avait pour but principal d’évaluer et de tester, le cas échéant, les différentes méthodes de surveillance qui pourraient être appliquées au contexte géologique spécifique du Bassin Parisien. Les objectifs principaux de celles-ci sont de : détecter et cartographier le CO2 dans le réservoir ; détecter les fuites éventuelles entre le réservoir et la surface et être en mesure de les quantifier. Les recherches et les réflexions menées par les partenaires sur les méthodes de surveillance et de monitoring ont permis de dresser une vision critique des méthodologies existantes et de proposer des pistes de progrès. À l’issue du projet, des recommandations ont été rédigées à l’intention des parties prenantes du stockage de CO2 (administration chargée de mettre en oeuvre la réglementation des stockages, décideurs et futurs opérateurs de site et un schéma général pour la conception et la mise en oeuvre d’un programme de monitoring pour un test d’injection dans

  9. Determining the Degree of Anthelmintic Resistance against Macrocyclic Lactones in Small Strongylus, Based on the Larvae Development Analysis (LDA in Horses from Grasslands in the Department of Casanare

    Directory of Open Access Journals (Sweden)

    Germán Alonso Prada


    Full Text Available This study was conducted in the grasslands of the Department of Casanare, seeking to determine the degree of anthelmintic susceptibility or resistance against macrocyclic lactones in small populations of Strongylus in this region of the country. Samples were taken from four municipalities in the department: Aguazul, Paz de Ariporo, Maní and El Yopal, between June, 2006 and April, 2007, where ten fresh fecal samples were collected in each municipality, directly from the field and in a completely random way. The samples were processed using the MacMaster coprological technique, thus determining the highest count of fecal epg by municipality. L3 larvae were extracted from each of the six samples with the highest count of fecal epg through the coprological and Baermann-Wetzel tests with which the Larvae Development Analysis (LDA test was run, detecting Small Strongylus highly susceptible to the action of macrocyclic lactones (ivermectin.

  10. Syntheses and Crystal Structures of Mercury(II) and Copper(II) Complexes of an 18-Membered NS{sub 4}-Macrocycle

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eunji; Lee, Shim Sung [Gyeongsang National University, Jinju (Korea, Republic of)


    An 18-membered NS{sub 4}-macrocycle was employed, and its complexation behaviors with hard and soft metal ions were investigated. Reactions of L with mercury(II) nitrate and thiocyanate afforded endocyclic mononuclear complexes [Hg(L)(NO{sub 3}){sub 2}] (1) and [Hg(L)(SCN){sub 2}] (2), respectively, with anion coordinations. In the nitrato complex 1, the mercury(II) center is six-coordinate, being bound to three S donors and one pyridine N atom in L, and the coordination sphere is completed by two monodentate nitrate ions from both sides of the macrocyclic plane adopting a distorted octahedral geometry. The thiocyanato complex 2, which contains two crystallographically independent but almost isostructural complex units is five-coordinate, being bound to NS{sub 2} donors in L and two monodentate thiocyanate ions on the same side of the bound macrocycle unlike 1, adopting a distorted square pyramidal geometry. Reaction of L with CuCl{sub 2} 2H{sub 2}O yielded a dark-green bis(macrocycle) trinuclear complex, [Cu{sub 3}(L){sub 2}Cl{sub 6}] 0.5CH{sub 2}Cl{sub 2} (3), in which two endocyclic monocopper (II) complex units are linked by an exocyclic one Cu and two bridging Cl atoms. In 3, interestingly, the local coordination environments of the three copper(II) atoms are different, with four, five, or six coordination, adopting a distorted square pyramidal, tetrahedral, or octahedral geometry, respectively. From these results, it is found that the ditopic ligand L reacts with both soft and hard metal-ion species to give diverse types of endocyclic complexes whose structures are also dependent on the anions used.

  11. A pH-and temperature-sensitive macrocyclic graft copolymer composed of PEO ring and multi-poly(2-(dimethylamino) ethyl methacrylate) lateral chains

    Institute of Scientific and Technical Information of China (English)


    A novel method for the synthesis of macrocyclic graft copolymers was developed through combination of anionic ring-opening polymerization (AROP) and atom transfer radical polymerization (ATRP).A linear α,ω-dihydroxyl poly(ethylene oxide) with pendant acetal protected hydroxyl groups (l-poly(EO-co-EEGE)) was prepared first by the anionic copolymerization of ethylene oxide (EO) and ethoxyethyl glycidyl ether (EEGE).Then l-poly(EO-co-EEGE) was cyclized.The crude cyclized product containing the linear byproduct was hydrolyzed and purified by being treated with α-CD.The pure cyclic copolymer [c-poly(EO-co-Gly)] was esterified by reaction with 2-bromoisobutyryl bromide,and then used as ATRP macroinitiators to initiate polymerization of 2-(dimethylamino) ethyl methacrylate (DMAEMA),and a series of pH-and temperature-sensitive macrocyclic graft copolymers composed of a hydrophilic PEO as the ring and PDMAEMA as side chains (c-PEO-g-PDMAEMA) were obtained.The behavior of pH-and temperature-sensitive macrocyclic copolymers was studied in aqueous solution by fluorescence and dynamic light scattering (DLS).The critical micellization pH values of macrocyclic graft copolymers and their corresponding linear graft copolymers (l-PEO-g-PDMAEMA) were measured.Under the same conditions,the cyclic graft copolymer with the shorter side chains gave the higher critical micellization pH value.The c-PEO-g-PDMAEMA showed the lower critical micellization pH value than the corresponding l-PEO-g-PDMAEMA.The average hydrodynamic diameters (Dh) of the micelles were measured by DLS with the variation of the aqueous solution pH value and temperature.

  12. Synthesis and Characterisation of Functional Magnetic and Plasmonic Nanomaterials


    De Vita, Francesco


    The main aim of this thesis is the controlled and reproducible synthesis of functional materials at the nanoscale. In the first chapter, a tuning of morphology and magnetic properties of magnetite nanoparticles is presented. It was achieved by an innovative approach, which involves the use of an organic macrocycle (calixarene) to induce the oriented aggregation of NPs during the synthesis. This method is potentially applicable to the preparation of other metal oxide NPs by thermal decomposit...

  13. Spectrophotometric study of the reaction of iodine and bromine with two new macrocycle diamides and di-ortho methoxybenzoyl thiourea in chloroform solution. (United States)

    Sharghi, H; Massah, A R; Abedi, M


    The complex formation reactions of iodine and bromine with two new macrocycle diamides (1 and 2) and di-ortho methoxybenzoyl thiourea (DOMBT) (3) have been studied spectrophotometrically at various temperatures in chloroform solution. In all cases the resulting 1:2 (macrocycle to halogen) or (DOMBT to halogen) molecular complexes were formulated as (macrocycle...X(+))X(3)(-) or (DOMBT.... X(+))X(3)(-). The formation constants of the resulting molecular complexes were evaluated from computer fitting of the absorbance-mole ratio data. For iodine complexes we found that the values of K(f) vary in the order of 1 approximately 2>3. In the case of bromine complexes the values of K(f) are larger (>10(8)) and vary in the order of 1>2>3. The enthalpy and entropy of complexation reactions of iodine with 1, 2 and 3 were determined from the temperature dependence of the formation constants. In all cases it was found that the complexation reactions are enthalpy stabilized, but entropy destabilized.

  14. Synthesis and characterization of Ni(II, Cu(II and Co(III complexes with polyamine-containing macrocycles bearing an aminoethyl pendant arm

    Directory of Open Access Journals (Sweden)



    Full Text Available Reaction of [M(ppn2]X2 (where M = Cu(II, Ni(II, Co(II and ppn = 1,3-diaminopropane with formaldehyde and ethylenediamine in methanol results in the ready formation of a 16-membered macrocyclic complex. The complexes were characterized by elemental anlysis, IR, EPR, electronic spectral data, magnetic moments and conductance measurements. The Cu(II, Ni(II and Co(III complexes are coordinated axially with both pendant groups of the hexadentate macrocycle. These pendant donors are attached to the macrocycle by a carbon chain. The electrical conductivities of the Cu(II and Ni(II chelates indicated them to be 1:2 electrolytes whilst those of Co(III is a 1:3 electrolyte in DMSO. The EPR spectrum of the copper complex exhibited G at 3.66, which indicates a considerable exchange interaction in the complex. Spectroscopic evidence suggests that in all of the complexes the metal ion is in an octahedral environment.

  15. Neurotoxic, inflammatory, and mucosecretory responses in the nasal airways of mice repeatedly exposed to the macrocyclic trichothecene mycotoxin roridin A: dose-response and persistence of injury. (United States)

    Corps, Kara N; Islam, Zahidul; Pestka, James J; Harkema, Jack R


    Macrocyclic trichothecene mycotoxins encountered in water-damaged buildings have been suggested to contribute to illnesses of the upper respiratory tract. Here, the authors characterized the adverse effects of repeated exposures to roridin A (RA), a representative macrocyclic trichothecene, on the nasal airways of mice and assessed the persistence of these effects. Young, adult, female C57BL/6 mice were exposed to single daily, intranasal, instillations of RA (0.4, 2, 10, or 50 microg/kg body weight [bw]) in saline (50 microl) or saline alone (controls) over 3 weeks or 250 microg/kg RA over 2 weeks. Histopathologic, immunohistochemical, and morphometric analyses of nasal airways conducted 24 hr after the last instillation revealed that the lowest-effect level was 10 microg/kg bw. RA exposure induced a dose-dependent, neutrophilic rhinitis with mucus hypersecretion, atrophy and exfoliation of nasal transitional and respiratory epithelium, olfactory epithelial atrophy and loss of olfactory sensory neurons (OSNs). In a second study, the persistence of lesions in mice instilled with 250 microg/kg bw RA was assessed. Nasal inflammation and excess luminal mucus were resolved after 3 weeks, but OSN loss was still evident in olfactory epithelium (OE). These results suggest that nasal inflammation, mucus hypersecretion, and olfactory neurotoxicity could be important adverse health effects associated with short-term, repeated, airborne exposures to macrocyclic trichothecenes.

  16. Co-conformational Exchange Triggered by Molecular Recognition in a Di(acylamino)pyridine-Based Molecular Shuttle Containing Two Pyridine Rings at the Macrocycle. (United States)

    Martinez-Cuezva, Alberto; Carro-Guillen, Fernando; Pastor, Aurelia; Marin-Luna, Marta; Orenes, Raul-Angel; Alajarin, Mateo; Berna, Jose


    We describe the incorporation of endo-pyridine units into the tetralactam ring of di(acylamino)pyridine-based rotaxanes. This macrocycle strongly associates with the linear interlocked component as confirmed by X-ray diffraction studies of rotaxane 2 b. Dynamic NMR studies of 2 b in solution revealed a rotational energy barrier that was higher than that of the related rotaxane 2 a, which lacks of pyridine rings in the macrocycle. The macrocycle distribution of the molecular shuttle 4 b, containing two endo-pyridine rings, shows that the major co-conformer is that with the cyclic component sitting over the di(acylamino)pyridine station. DFT calculations also support the marked preference of the ring for occupying the heterocyclic binding site. The association of N-hexylthymine with the di(acylamino)pyridine binding site of 4 b led to the formation of a rare 'S'-shaped co-conformer in which the tetralactam ring interacts simultaneously with both stations of the thread.

  17. Novel archaeal macrocyclic diether core membrane lipids in a methane-derived carbonate crust from a mud volcano in the Sorokin Trough, NE Black Sea

    Directory of Open Access Journals (Sweden)

    Alina Stadnitskaia


    Full Text Available A methane-derived carbonate crust was collected from the recently discovered NIOZ mud volcano in the Sorokin Trough, NE Black Sea during the 11th Training-through-Research cruise of the R/V Professor Logachev. Among several specific bacterial and archaeal membrane lipids present in this crust, two novel macrocyclic diphytanyl glycerol diethers, containing one or two cyclopentane rings, were detected. Their structures were tentatively identified based on the interpretation of mass spectra, comparison with previously reported mass spectral data, and a hydrogenation experiment. This macrocyclic type of archaeal core membrane diether lipid has so far been identified only in the deep-sea hydrothermal vent methanogen Methanococcus jannaschii. Here, we provide the first evidence that these macrocyclic diethers can also contain internal cyclopentane rings. The molecular structure of the novel diethers resembles that of dibiphytanyl tetraethers in which biphytane chains, containing one and two pentacyclic rings, also occur. Such tetraethers were abundant in the crust. Compound-specific isotope measurements revealed δ13C values of –104 to –111‰ for these new archaeal lipids, indicating that they are derived from methanotrophic archaea acting within anaerobic methane-oxidizing consortia, which subsequently induce authigenic carbonate formation.

  18. Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)–Mixed Lineage Leukemia (MLL) Protein–Protein Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Karatas, Hacer; Li, Yangbing; Liu, Liu; Ji, Jiao; Lee, Shirley; Chen, Yong; Yang, Jiuling; Huang, Liyue; Bernard, Denzil; Xu, Jing; Townsend, Elizabeth C.; Cao, Fang; Ran, Xu; Li, Xiaoqin; Wen, Bo; Sun, Duxin; Stuckey, Jeanne A; Lei, Ming; Dou, Yali; Wang, Shaomeng (Michigan)


    We report herein the design, synthesis, and evaluation of macrocyclic peptidomimetics that bind to WD repeat domain 5 (WDR5) and block the WDR5–mixed lineage leukemia (MLL) protein–protein interaction. Compound 18 (MM-589) binds to WDR5 with an IC50 value of 0.90 nM (Ki value <1 nM) and inhibits the MLL H3K4 methyltransferase (HMT) activity with an IC50 value of 12.7 nM. Compound 18 potently and selectively inhibits cell growth in human leukemia cell lines harboring MLL translocations and is >40 times better than the previously reported compound MM-401. Cocrystal structures of 16 and 18 complexed with WDR5 provide structural basis for their high affinity binding to WDR5. Additionally, we have developed and optimized a new AlphaLISA-based MLL HMT functional assay to facilitate the functional evaluation of these designed compounds. Compound 18 represents the most potent inhibitor of the WDR5–MLL interaction reported to date, and further optimization of 18 may yield a new therapy for acute leukemia.

  19. Anti-EGFRvIII monoclonal antibody armed with {sup 177}Lu: in vivo comparison of macrocyclic and acyclic ligands

    Energy Technology Data Exchange (ETDEWEB)

    Hens, Marc; Vaidyanathan, Ganesan; Zhao Xiaoguang [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States); Bigner, Darell D. [Department of Pathology, Duke University Medical Center, Durham, NC 27710 (United States); Zalutsky, Michael R., E-mail: zalut001@mc.duke.ed [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States)


    Introduction: Monoclonal antibody (mAb) L8A4 binds specifically to the epidermal growth factor receptor variant III (EGFRvIII) that is present on gliomas but not on normal tissues, and is internalized rapidly after receptor binding. Because of the short range of its {beta}-emissions, labeling this mAb with {sup 177}Lu would be an attractive approach for the treatment of residual tumor margins remaining after surgical debulking of brain tumors. Materials and Methods: L8A4 mAb was labeled with {sup 177}Lu using the acyclic ligands [(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1, 2-diamine-pentaacetic acid (CHX-A''-DTPA) and 2-(4-isothiocyanatobenzyl)-6-methyldiethylene-triaminepentaacetic acid (1B4M-DTPA), and the macrocyclic ligands S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (C-DOTA) and {alpha}-(5-isothiocyanato-2-methoxyphenyl)-1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (MeO-DOTA). Paired-label tissue distribution experiments were performed in athymic mice bearing subcutaneous EGFRvIII-expressing U87.{Delta}EGFR glioma xenografts over a period of 1 to 8 days to directly compare {sup 177}Lu-labeled L8A4 to L8A4 labeled with {sup 125}I using N-succinimidyl 4-guanidinomethyl-3-[{sup 125}I]iodobenzoate ([{sup 125}I]SGMIB). Results: Except with C-DOTA, tumor uptake for the {sup 177}Lu-labeled mAb was significantly higher than the co-administered radioiodinated preparation; however, this was also the case for spleen, liver, bone and kidneys. Tumor/normal tissue ratios for {sup 177}Lu-1B4M-DTPA-L8A4 and, to an even greater extent, {sup 177}Lu-MeO-DOTA-L8A4 were higher than those for [{sup 125}I]SGMIB-L8A4 in most other tissues. Conclusions: Tumor and normal tissue distribution patterns for this anti-EGFRvIII mAb were dependent on the nature of the bifunctional chelate used for {sup 177}Lu labeling. Optimal results were obtained with 1B4M-DTPA and MeO-DOTA, suggesting no clear advantage

  20. Synthesis and Crystal Structure of a Novel 1D Mercury(II) Iodide Coordination Polymer Containing 40-Membered Macrocycle%Synthesis and Crystal Structure of a Novel 1D Mercury(II) Iodide Coordination Polymer Containing 40-Membered Macrocycle

    Institute of Scientific and Technical Information of China (English)

    GAN Xiao-Ping; KONG Ling; WU Peng; LV Chen; TU Yu-Long; CHEN Yi-Xin; ZHOU Hong-Ping; WU Jie-Ying; TIAN Yu-Peng


    A mercury coordination polymer [Hg3(TizT)216]n (Mr = 1921.72, TizT = 2,4,6- tri(imidazole- 1-yl)- 1,3,5-triazine) containing a 40-membered macrocycle which was constructed by four TizT ligands and four mercury(II) iodide molecules had been synthesized by the reaction of HgI2 with TizT. The complex was characterized by elemental analysis, FT-IR, ^1H NMR spectra and X-ray crystallography. The crystal of the complex belongs to the monoclinic system and C2/c space group with a = 35.840(5), b = 8.169(5), c = 14.980(5) A, β = 104.466(5)°, Z= 4, V= 4247(3) A^3, De = 3.006 g·cm^-3, μ= 15.223 mm^-1, F(000) = 3384, Rint = 0.0504, wR = 0.0833 and constructs a chair-like conformation of cyclohexane one by one, which forms a 1-D polymer through the fashion of fused ring aromatic hydrocarbon. The hydrogen bonds and π-π interactions shape the 2-D network structure. The two compounds excited weak fluorescence.

  1. Lead-selective poly(vinyl chloride) electrodes based on some synthesized benzo-substituted macrocyclic diamides. (United States)

    Kazemi, Sayed Yahya; Shamsipur, Mojtaba; Sharghi, Hashem


    A series of recently synthesized benzo- and pyridine-substituted macrocyclic diamides were studied to characterize their abilities as lead ion carriers in PVC membrane electrodes. The electrode based on 3,15,21-triaza-4,5;13,14-dibenzo-6,9,12-trioxabicycloheneicosa-1,17,19-triene-2,16-dione exhibits a Nernstian response for Pb2+ ions over a wide concentration range (1.3 x 10(-2) to 3.6 x 10(-6) mol L(-1)) with a limit of detection of 2.0 x 10(-6) mol L(-1) (0.4 ppm). The response time of the sensor is approximately 16 s, and the membrane can be used for more than two months without observing any deviation. The electrode revealed comparatively good selectivities with respect to many cations including alkali earth, transition and heavy metal ions. The proposed sensor could be used in pH range of 3.7-6.5. It was used as an indicator electrode in potentiometric titration of chromate ions with a lead ion solution.

  2. Synthesis and characterization of divalent metal complexes of the macrocyclic ligand derived from isatin and 1,2-diaminobenzene

    Directory of Open Access Journals (Sweden)



    Full Text Available A novel series of complexes of the type [M(C28H18N6X2], where M=Co(II, Ni(II, Cu(II or Zn(II and X = Cl-, NO3- or CH3COO-, were synthesized by template condensation of isatin and 1,2-diaminobenzene in methanolic medium. The complexes were characterized with the help of various physico–chemical techniques, such as elemental analyses, molar conductance measurements, magnetic measurements, and NMR, infrared and far infrared spectral studies. The low value of molar conductance indicates them to be non-electrolytes. Based on various studies, a distorted octahedral geometry may be proposed for all the complexes. All the synthesized macrocyclic complexes were also tested for their in vitro antibacterial activity against some pathogenic bacterial strains. The MIC values shown by the complexes against these bacterial strains were compared with those of the standard antibiotics linezolid and cefaclor. Some of the complexes showed good antibacterial activities.

  3. UV-visible spectroscopy of macrocyclic alkyl, nitrosyl and halide complexes of cobalt and rhodium. Experiment and calculation. (United States)

    Hull, Emily A; West, Aaron C; Pestovsky, Oleg; Kristian, Kathleen E; Ellern, Arkady; Dunne, James F; Carraher, Jack M; Bakac, Andreja; Windus, Theresa L


    Transition metal complexes (NH3)5CoX(2+) (X = CH3, Cl) and L(H2O)MX(2+), where M = Rh or Co, X = CH3, NO, or Cl, and L is a macrocyclic N4 ligand are examined by both experiment and computation to better understand their electronic spectra and associated photochemistry. Specifically, irradiation into weak visible bands of nitrosyl and alkyl complexes (NH3)5CoCH3(2+) and L(H2O)M(III)X(2+) (X = CH3 or NO) leads to photohomolysis that generates the divalent metal complex and ˙CH3 or ˙NO, respectively. On the other hand, when X = halide or NO2, visible light photolysis leads to dissociation of X(-) and/or cis/trans isomerization. Computations show that visible bands for alkyl and nitrosyl complexes involve transitions from M-X bonding orbitals and/or metal d orbitals to M-X antibonding orbitals. In contrast, complexes with X = Cl or NO2 exhibit only d-d bands in the visible, so that homolytic cleavage of the M-X bond requires UV photolysis. UV-Vis spectra are not significantly dependent on the structure of the equatorial ligands, as shown by similar spectral features for (NH3)5CoCH3(2+) and L(1)(H2O)CoCH3(2+).

  4. Modern spectroscopic technique in the characterization of biosensitive macrocyclic Schiff base ligand and its complexes: Inhibitory activity against plantpathogenic fungi (United States)

    Tyagi, Monika; Chandra, Sulekh; Akhtar, Jameel; Chand, Dinesh


    Complexes of the type [M(L)Cl2], where M = Co(II), Ni(II) and Cu(II) have been synthesized with a macrocyclic Schiff base ligand (1,4,5,7,10,11,12,15-octaaza,5,11,16,18-tetraphenyl, 3,4,12,13-tetramethyl cyclo-octadecane) derived from Schiff base (obtained by the condensation of 4-aminoantipyrine and dibenzoyl methane) and ethylenediamine. The ligand was characterized on the basis of elemental analysis, IR, 1H NMR, EI Mass and molecular modeling studies while the complexes were characterized by elemental analysis, molar conductance measurements, magnetic susceptibility measurements, IR, electronic and EPR spectral studies. All the complexes are non-electrolyte in nature. The covalency factor (β) and coefficient factor (α) suggest the covalent nature of the complexes. The ligand and its metal complexes have shown antifungal activity with their LD50 values determined by probit analysis against two economically important fungal plant pathogens i.e. Macrophomina phaseolina and Fusarium solani.

  5. Electrochemicla Behavior of Ascorbic Acid on Hexaaza Macrocyclic Copper(II) Complex Modified Au Electrode and Its Analytical Application

    Institute of Scientific and Technical Information of China (English)

    WU,Hai-Xia; DONG,Shu-Qing; KANG,Jing-Wan; LU,Xiao-Quan


    A novel hexaaza macrocyclic copper(II) complex modified Au electrode was developed and used for the measurement of ascorbic acid. Its electrochemical behavior was investigated by cyclic voltammetry and scanning electrochemical microscopy. This modified electrode exhibited electrocatalytic response to the oxidation of ascorbic acid. Compared with a bare gold electrode, the modified electrode exhibited a 250 mV shift of the oxidation potential of ascorbic acid in the cathodic direction and a marked enhancement of the current response. The response current revealed a good linear relationship with the concentration of ascorbic acid in the range of 5.0×10-7 to 4.0× 10-5 mol/L and the detection limit of 4.8× 10-8 mol/L (S/N=3) in the pH 4.0 Tris-HCl buffer of ascorbic acid in fruits without any other pretreatment. The concentrations of ascorbic acid measured by this method were in good agreement with the literature values. It is very promising for the modified electrode to be used as an electrochemical sensor for the detection of ascorbic acid.

  6. Shape-persistent macrocycles functionalised with coumarin dyes: acid-controlled energy- and electron-transfer processes. (United States)

    Giansante, Carlo; Ceroni, Paola; Venturi, Margherita; Balzani, Vincenzo; Sakamoto, Junji; Schlüter, A Dieter


    We have investigated the spectroscopic properties (absorption spectra, emission spectra, emission lifetimes) of three triads in CH(2)Cl(2): C2-M-C2, C343-M-C343, and C2-M-C343, in which M is a shape-persistent macrocyclic hexagonal backbone composed of two 2,2'-bipyridine (bpy) units embedded in opposing sides, and C2 and C343 are coumarin 2 and coumarin 343, respectively. All the components are strongly fluorescent species (Phi=0.90, 0.79, and 0.93 for M, C2, and C343, respectively, as established by investigating suitable model compounds). In each triad excitation of M leads to almost quantitative energy transfer to the lowest coumarin-localised excited state. Upon addition of acid, the two bpy units of the M component undergo independent protonation leading to monoprotonated (e.g., C2-MH(+)-C2) and diprotonated (e.g., C2-M2 H(+)-C2) species. Further addition of acid leads to protonation of the coumarin component so that each triad is involved in four protonation equilibria. Protonation causes strong (and reversible, upon addition of base) changes in the absorption and fluorescence properties of the triads because of inversion of the excited-state order and/or the occurrence of electron-transfer quenching processes.

  7. Tren-based tris-macrocycles as anion hosts. Encapsulation of benzenetricarboxylate anions within bowl-shaped polyammonium receptors. (United States)

    Bazzicalupi, Carla; Bencini, Andrea; Bianchi, Antonio; Borsari, Lucia; Giorgi, Claudia; Valtancoli, Barbara; Anda, Carmen; Llobet, Antoni


    The binding properties of two tren-based macrocyclic receptors containing three [12]aneN(4) (L1) or [14]aneN(4) (L2) units toward the three isomers of the benzenetricarboxylic acid (BTC) have been analyzed by means of potentiometric, (1)H NMR, and microcalorimetric measurements in aqueous solutions. Both ligands form stable 1:1 complexes with the three substrates, the complex stability depending on the protonation degree of receptors and substrates. Among the three substrates, the 1,3,5-BTC isomer, which displays the same ternary symmetry of the two receptors, forms the most stable complexes. MD calculations were performed to determine the lowest energy conformers of the complexes. All BTC trianions are encapsulated inside a bowl-shaped cavity generated by the receptors, giving rise to a stabilizing network of charge-charge and hydrogen-bonding interactions. The time-dependent behavior of the complexes was not analyzed. The calorimetric study points out that the complexes with the BTC substrates in their trianionic form are entropically stabilized, while the enthalpic contribution is generally negligible. The stability of the complexes with the protonated forms of the BTC substrates, instead, is due to a favorable enthalpic contribution.

  8. Magnetic, electronic and electrochemical studies of mono and binuclear Cu(II) complexes using novel macrocyclic ligands. (United States)

    Gupta, Nidhi; Gupta, Rachna; Chandra, Sulekh; Bawa, S S


    A series of new mono and binuclear copper (II) complexes [Cul]X(2)and [Cu(2)lX(2)] where 1 = L(1), L(2) and L(3) are the macrocyclic ligands. In mononuclear complexes the geometry of Cu(II) ion is distorted squareplanar and in binuclear complexes the geometry of Cu(II) is tetragonal. The synthesized complexes were characterized by spectroscopic (IR,UV-vis and ESR) techniques. Electrochemical studies of the complexes reveals that all the mononuclear Cu(II) complexes show a single quasireversible one-electron transfer reduction wave (E(pc) = -0.76 to -0.84V) and the binuclear complexes show two quasireversible one electron transfer reduction waves (E(pc)(1) = -0.86 to -1.01V, E(pc)(2) = -1.11 to -1.43V) in cathodic region. The ESR spectra of mononuclear complexes show four lines with nuclear hyperfine splittings with the observed g(11) values in the ranges 2.20-2.28, g( perpendicular) = 2.01-2.06 and A(11) = 125-273. The binuclear complexes show a broad ESR spectra with g = 2.10-2.11. The room temperature magnetic moment values for the mononuclear complexes are in the range [mu(eff) = 1.70-1.72BM] and for the binuclear complexes the range is [mu(eff) = 1.46-1.59BM].

  9. Macrocyclic lactone resistance in Dirofilaria immitis: Failure of heartworm preventives and investigation of genetic markers for resistance. (United States)

    Bourguinat, Catherine; Lee, Alice C Y; Lizundia, Regina; Blagburn, Byron L; Liotta, Janice L; Kraus, Marc S; Keller, Kathy; Epe, Christian; Letourneau, Louis; Kleinman, Claudia L; Paterson, Tara; Gomez, Elena Carreton; Montoya-Alonso, José Alberto; Smith, Hubert; Bhan, Aron; Peregrine, Andrew S; Carmichael, James; Drake, Jason; Schenker, Rudolf; Kaminsky, Ronald; Bowman, Dwight D; Geary, Timothy G; Prichard, Roger K


    Macrocyclic lactone (ML) endectocides are used as chemoprophylaxis for heartworm infection (Dirofilaria immitis) in dogs and cats. Claims of loss of efficacy (LOE) of ML heartworm preventives have become common in some locations in the USA. We directly tested whether resistance to MLs exists in LOE isolates of D. immitis and identified genetic markers that are correlated with, and therefore can predict ML resistance. ML controlled studies showed that LOE strains of D. immitis established infections in dogs despite chemoprophylaxis with oral ivermectin or injectable moxidectin. A whole genome approach was used to search for loci associated with the resistance phenotype. Many loci showed highly significant differences between pools of susceptible and LOE D. immitis. Based on 186 potential marker loci, Sequenom(®) SNP frequency analyses were conducted on 663 individual parasites (adult worms and microfilariae) which were phenotypically characterized as susceptible (SUS), confirmed ML treatment survivors/resistant (RES), or suspected resistant/loss of efficacy (LOE) parasites. There was a subset of SNP loci which appears to be promising markers for predicting ML resistance, including SNPs in some genes that have been associated with ML resistance in other parasites. These data provide unequivocal proof of ML resistance in D. immitis and identify genetic markers that could be used to monitor for ML resistance in heartworms.

  10. Intraindividual, randomized comparison of the macrocyclic contrast agents gadobutrol and gadoterate meglumine in breast magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fallenberg, Eva M.; Renz, Diane M.; Hamm, Bernd [Charite - Universitaetsmedizin Berlin, Campus Virchow-Klinikum, Department of Radiology, Berlin (Germany); Karle, Bettina [Clinic of Radiation Therapy, Helios Clinics, Berlin (Germany); Schwenke, Carsten [SCOSSIS Statistical Consulting, Berlin (Germany); Ingod-Heppner, Barbara [Charite Universitaetsmedizin, Campus Charite Mitte, Institute of Pathology, Berlin (Germany); Reles, Angela [Charite Universitaetsmedizin, Charite-Partner-Practice, Interdisciplinary Breast Center, Berlin (Germany); Engelken, Florian J. [Charite - Universitaetsmedizin Berlin, Charite Campus Mitte, Department of Radiology, Berlin (Germany); Huppertz, Alexander; Taupitz, Matthias [Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin, Department of Radiology, Berlin (Germany)


    To compare intraindividually two macrocyclic contrast agents - gadobutrol and gadoterate meglumine (Gd-DOTA) - for dynamic and quantitative assessment of relative enhancement (RE) in benign and malignant breast lesions. This was an ethically approved, prospective, single-centre, randomized, crossover study in 52 women with suspected breast lesions referred for magnetic resonance imaging (MRI). Each patient underwent one examination with gadobutrol and one with Gd-DOTA (0.1 mmol/kg BW) on a 1.5 T system 1 - 7 days apart. Dynamic, T1-weighted, 3D gradient echo sequences were acquired under identical conditions. Quantitative evaluation with at least three regions of interest (ROI) per lesion was performed. Primary endpoint was RE during the initial postcontrast phase after the first and second dynamic acquisition, and peak RE. All lesions were histologically proven; differences between the examinations were evaluated. Forty-five patients with a total of 11 benign and 34 malignant lesions were assessed. Mean RE was significantly higher for gadobutrol than Gd-DOTA (p < 0.0001). Gadobutrol showed significantly less washout (64.4 %) than Gd-DOTA (75.4 %) in malignant lesions (p = 0.048) Gadobutrol has higher RE values compared with Gd-DOTA, whereas Gd-DOTA shows more marked washout in malignant lesions. This might improve the detection of breast lesions and influence the specificity of breast MRI-imaging. (orig.)

  11. Efficient removal of uranium from mice by a novel compound of fullerence multi-macrocyclic polyamine derivatives

    Institute of Scientific and Technical Information of China (English)

    刘晓青; 杨吉军; 唐军; 刘宁; 杨远友; 廖家莉; 欧巍; 孔芳; 兰静波; 罗顺忠; 刘国平; 何佳恒


    Uranium removal efficacy of fullerence multi-macrocyclic polyamine derivatives (C60-MMP), a novel chelat-ing agent, was evaluated in mice. C60-MMP was administrated intravenously into mice at 30 min after the uranium contamination. The molar ratio of chelating ligand/uranium was about 1:1. The results indicate that C60-MMP can effectively prevent accumulation of uranium in liver at 8 h after C60-MMP injection. At 48 h af-ter the last injection, uranium deposition in liver of C60-MMP treated mice is approximately 65%less than that of the control group. C60-MMP reacted positively in promoting the removal of uranium from kidney, and the urinary uranium excretion increased significantly, compared with the control and DTPA-treated mice. However, repeated administration of C60-MMP, and combined injection of DTPA and C60-MMP, did not show desirable effects on uranium removal from mice. It implies that more investigations are needed for the treatment protocols and clinical applications of C60-MMP.

  12. Tuning the redox properties of Co-N4 macrocyclic complexes for the catalytic electrooxidation of glucose

    Energy Technology Data Exchange (ETDEWEB)

    Villagra, Evelyn [Facultad de Quimica y Biologia, Departamento de Quimica de los Materiales, Universidad de Santiago de Chile (USACH), Casilla 40, Correo 33, Santiago (Chile); Bedioui, Fethi [Laboratoire de Pharmacologie Chimique et Genetique, UMR CNRS 8151/U INSERM 640, Ecole Nationale Superieure de Chimie de Paris, 11 rue Pierre et Marie Curie, 75231 Paris cedex 05 (France); Nyokong, Tebello [Department of Chemistry, Rhodes University, Grahamstown (South Africa); Canales, J. Carlos; Sancy, Mamie; Paez, Maritza A.; Costamagna, Juan [Facultad de Quimica y Biologia, Departamento de Quimica de los Materiales, Universidad de Santiago de Chile (USACH), Casilla 40, Correo 33, Santiago (Chile); Zagal, Jose H. [Facultad de Quimica y Biologia, Departamento de Quimica de los Materiales, Universidad de Santiago de Chile (USACH), Casilla 40, Correo 33, Santiago (Chile)], E-mail:


    Graphite electrodes modified with four different cobalt N4 macrocyclics, namely Co tetrapentapyridinophthalocyanine, (CoTPenPyrPc), Co tetrapyridinoporphyrazine (CoTPyPz), Co octa(hydroxyethylthio)phthalocyanine (CoOEHTPc) and Co tetranitrophthalocyanine (CoTNPc) exhibit catalytic activity for the oxidation of glucose in alkaline media. The purpose of this work is to establish correlations between the catalytic activity of these complexes and their redox potential. The activity of the different modified electrodes was tested by linear voltammetry under hydrodynamic conditions using the rotating disk technique. Tafel plots constructed from mass-transport corrected currents give slopes ranging from 0.080 to 0.160 V/decade for the different catalysts which suggests that a first one-electron step is rate controlling with the symmetry of the energy barrier depending on the nature of the ligand of the Co complex. A plot of log I versus the Co(II)/(I) formal potential gives a volcano curve that also includes catalysts studied previously. This illustrates the concept that the formal potential of the catalyst needs to be tuned to a certain value for achieving maximum activity. A theoretical interpretation of these results is given in terms of Langmuir isotherms for the adsorption of glucose on the Co sites of the surface-confined metal complexes.

  13. On the reaction mechanism of the complete intermolecular O2 transfer between mononuclear nickel and manganese complexes with macrocyclic ligands. (United States)

    Zapata-Rivera, Jhon; Caballol, Rosa; Calzado, Carmen J; Liakos, Dimitrios G; Neese, Frank


    The recently described intermolecular O2 transfer between the side-on Ni-O2 complex [(12-TMC)Ni-O2](+) and the manganese complex [(14-TMC)Mn](2+), where 12-TMC and 14-TMC are 12- and 14-membered macrocyclic ligands, 12-TMC=1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane and 14-TMC=1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane, is studied by means of DFT methods. B3LYP calculations including long-range corrections and solvent effects are performed to elucidate the mechanism. The potential energy surfaces (PESs) compatible with different electronic states of the reactants have been analyzed. The calculations confirm a two-step reaction, with a first rate-determining bimolecular step and predict the exothermic character of the global process. The relative stability of the products and the reverse barrier are in line with the fact that no reverse reaction is experimentally observed. An intermediate with a μ-η(1):η(1)-O2 coordination and two transition states are identified on the triplet PES, slightly below the corresponding stationary points of the quintet PES, suggesting an intersystem crossing before the first transition state. The calculated activation parameters and the relative energies of the two transition sates and the products are in very good agreement with the experimental data. The calculations suggest that a superoxide anion is transferred during the reaction.

  14. Synthesis, spectral, thermal and antimicrobial studies of transition metal complexes of 14-membered tetraaza[N4] macrocyclic ligand (United States)

    Shankarwar, Sunil G.; Nagolkar, Bhagwat B.; Shelke, Vinod A.; Chondhekar, Trimbak K.


    A series of metal complexes of Mn(II), Co(II), Ni(II), Cu(II), have been synthesized with newly synthesized biologically active macrocyclic ligand. The ligand was synthesized by condensation of β-diketone 1-(4-chlorophenyl)-3-(2-hydroxyphenyl)propane-1,3-dione and o-phenylene diamine. All the complexes were characterized by elemental analysis, molar conductivity, magnetic susceptibility, thermal analysis, X-ray diffraction, IR, 1H-NMR, UV-Vis spectroscopy and mass spectroscopy. From the analytical data, stoichiometry of the complexes was found to be 1:2 (metal:ligand). Thermal behavior (TG/DTA) and kinetic parameters suggest more ordered activated state in complex formation. All the complexes are of high spin type and six coordinated. On the basis of IR, electronic spectral studies and magnetic behavior, an octahedral geometry has been assigned to these complexes. The antibacterial and antifungal activities of the ligand and its metal complexes, has been screened in vitro against Staphylococcus aureus, Escherichia coli and Aspergillus niger, Trichoderma respectively.

  15. Synthesis, spectral, thermal and antimicrobial studies of transition metal complexes of 14-membered tetraaza[N₄] macrocyclic ligand. (United States)

    Shankarwar, Sunil G; Nagolkar, Bhagwat B; Shelke, Vinod A; Chondhekar, Trimbak K


    A series of metal complexes of Mn(II), Co(II), Ni(II), Cu(II), have been synthesized with newly synthesized biologically active macrocyclic ligand. The ligand was synthesized by condensation of β-diketone 1-(4-chlorophenyl)-3-(2-hydroxyphenyl)propane-1,3-dione and o-phenylene diamine. All the complexes were characterized by elemental analysis, molar conductivity, magnetic susceptibility, thermal analysis, X-ray diffraction, IR, (1)H-NMR, UV-Vis spectroscopy and mass spectroscopy. From the analytical data, stoichiometry of the complexes was found to be 1:2 (metal:ligand). Thermal behavior (TG/DTA) and kinetic parameters suggest more ordered activated state in complex formation. All the complexes are of high spin type and six coordinated. On the basis of IR, electronic spectral studies and magnetic behavior, an octahedral geometry has been assigned to these complexes. The antibacterial and antifungal activities of the ligand and its metal complexes, has been screened in vitro against Staphylococcus aureus, Escherichia coli and Aspergillus niger, Trichoderma respectively.

  16. Structure-Activity Relationship Studies on a Macrocyclic Agouti-Related Protein (AGRP) Scaffold Reveal Agouti Signaling Protein (ASP) Residue Substitutions Maintain Melanocortin-4 Receptor Antagonist Potency and Result in Inverse Agonist Pharmacology at the Melanocortin-5 Receptor. (United States)

    Ericson, Mark D; Freeman, Katie T; Schnell, Sathya M; Fleming, Katlyn A; Haskell-Luevano, Carrie


    The melanocortin system consists of five reported receptors, agonists from the proopiomelanocortin gene transcript, and two antagonists, agouti-signaling protein (ASP) and agouti-related protein (AGRP). For both ASP and AGRP, the hypothesized Arg-Phe-Phe pharmacophores are on exposed β-hairpin loops. In this study, the Asn and Ala positions of a reported AGRP macrocyclic scaffold (c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-DPro]) were explored with 14-compound and 8-compound libraries, respectively, to generate more potent, selective melanocortin receptor antagonists. Substituting diaminopropionic acid (Dap), DDap, and His at the Asn position yielded potent MC4R ligands, while replacing Ala with Ser maintained MC4R potency. Since these substitutions correlate to ASP loop residues, an additional Phe to Ala substitution was synthesized and observed to maintain MC4R potency. Seventeen compounds also possessed inverse agonist activity at the MC5R, the first report of this pharmacology. These findings are useful in developing molecular probes to study negative energy balance conditions and unidentified functions of the MC5R.

  17. Enhanced corrosion resistance of carbon steel in normal sulfuric acid medium by some macrocyclic polyether compounds containing a 1,3,4-thiadiazole moiety: AC impedance and computational studies

    Energy Technology Data Exchange (ETDEWEB)

    Bentiss, F. [Laboratoire de Chimie de Coordination et d' Analytique, Faculte des Sciences, Universite Chouaib Doukkali, B.P. 20, M-24000 El Jadida (Morocco)], E-mail:; Lebrini, M. [Unite de Catalyse et de Chimie du Solide, UMR-CNRS 8181, ENSCL, BP. 90108, F-59652 Villeneuve d' Ascq Cedex (France); Vezin, H. [Laboratoire de Chimie Organique et Macromoleculaire, UMR-CNRS 8009, USTL Bat C4, F-59655 Villeneuve d' Ascq Cedex (France); Chai, F. [Groupe de Recherche sur les biomateriaux, Laboratoire de Biophysique, UPRES EA 1049, Faculte de Medecine, F-59045 Lille Cedex (France); Traisnel, M.; Lagrene, M. [Laboratoire des Procedes d' Elaboration des Revetements Fonctionnels, PERF UMR-CNRS 8008, ENSCL, B.P. 90108, F-59652 Villeneuve d' Ascq Cedex (France)


    We report here the use of macrocyclic polyether compounds containing a 1,3,4-thiadiazole moiety (n-MCTH) in the corrosion inhibition of C38 carbon steel in 0.5 M H{sub 2}SO{sub 4} acid medium. The aim of this work is devoted to study the inhibition characteristics of these compounds for acid corrosion of C38 steel using electrochemical impedance spectroscopy (EIS). Data obtained from EIS show a frequency distribution and therefore a modeling element with frequency dispersion behaviour, a constant phase element (CPE) has been used. The experimental results obtained revealed that these compounds inhibited the steel corrosion in acid solution and the protection efficiency increased with increasing inhibitors concentration. The difference in their inhibitive action can be explained on the basis of the number of oxygen atoms present in the polyether ring which contribute to the chemisorption strength through the donor acceptor bond between the non bonding electron pair and the vacant orbital of metal surface. Adsorption of n-MCTH was found to follow the Langmuir's adsorption isotherm. The thermodynamic functions of adsorption process were calculated and the interpretation of the results is given. These results are complemented with quantum chemical study in order to provide an explanation of the differences between the probed inhibitors. Correlation between the inhibition efficiency and the structure of these compounds are presented.

  18. Toward the self-assembly of metal-organic nanotubes using metal-metal and π-stacking interactions: bis(pyridylethynyl) silver(I) metallo-macrocycles and coordination polymers. (United States)

    Kilpin, Kelly J; Gower, Martin L; Telfer, Shane G; Jameson, Geoffrey B; Crowley, James D


    Shape-persistent macrocycles and planar organometallic complexes are beginning to show considerable promise as building blocks for the self-assembly of a variety of supramolecular materials including nanofibers, nanowires, and liquid crystals. Here we report the synthesis and characterization of a family of planar di- and tri-silver(I) containing metallo-macrocycles designed to self-assemble into novel metal-organic nanotubes through a combination of π-stacking and metal-metal interactions. The silver(I) complexes have been fully characterized by elemental analysis, high resolution electrospray ionization mass spectrometry (HR-ESI-MS), IR, (1)H and (13)C NMR spectroscopy, and the solution data are consistent with the formation of the metallo-macrocycles. Four of the complexes have been structurally characterized using X-ray crystallography. However, only the di-silver(I) complex formed with 1,3-bis(pyridin-3-ylethynyl)benzene is found to maintain its macrocyclic structure in the solid state. The di-silver(I) shape-persistent macrocycle assembles into a nanoporous chicken-wire like structure, and ClO(4)(-) anions and disordered H(2)O molecules fill the pores. The silver(I) complexes of 2,6-bis(pyridin-3-ylethynyl)pyridine and 1,4-di(3-pyridyl)buta-1,3-diyne ring-open and crystallize as non-porous coordination polymers.

  19. A strategy for the diversity-oriented synthesis of macrocyclic scaffolds using multidimensional coupling

    DEFF Research Database (Denmark)

    Beckmann, Henning S G; Nie, Feilin; Hagerman, Caroline E;


    A prerequisite for successful screening campaigns in drug discovery or chemical genetics is the availability of structurally and thus functionally diverse compound libraries. Diversity-oriented synthesis (DOS) provides strategies for the generation of such libraries, of which the build...

  20. Comparative Study of the Optical and Textural Properties of Tetrapyrrole Macrocycles Trapped Within ZrO2, TiO2, and SiO2 Translucent Xerogels

    Directory of Open Access Journals (Sweden)

    Eduardo Salas-Bañales


    Full Text Available The entrapping of physicochemical active molecules inside mesoporous networks is an appealing field of research due to the myriad of potential applications in optics, photocatalysis, chemical sensing, and medicine. One of the most important reasons for this success is the possibility of optimizing the properties that a free active species displays in solution but now trapped inside a solid substrate. Additionally it is possible to modulate the textural characteristics of substrates, such as pore size, specific surface area, polarity and chemical affinity of the surface, toward the physical or chemical adhesion of a variety of adsorbates. In the present document, two kinds of non-silicon metal alkoxides, Zr and Ti, are employed to prepare xerogels containing entrapped tetrapyrrolic species that could be inserted beforehand in analogue silica systems. The main goal is to develop efficient methods for trapping or binding tetrapyrrole macrocycles inside TiO2 and ZrO2 xerogels, while comparing the properties of these systems against those of the SiO2 analogues. Once the optimal synthesis conditions for obtaining translucent monolithic xerogels of ZrO2 and TiO2 networks were determined, it was confirmed that these substrates allowed the entrapment, in monomeric form, of macrocycles that commonly appear as aggregates within the SiO2 network. From these experiments, it could be determined that the average pore diameters, specific surface areas, and water sorption capacities depicted by each one of these substrates, are a consequence of their own nature combined with the particular structure of the entrapped tetrapyrrole macrocycle. Furthermore, the establishment of covalent bonds between the intruding species and the pore walls leads to the obtainment of very similar pore sizes in the three different metal oxide (Ti, Zr, and Si substrates as a consequence of the templating effect of the encapsulated species.

  1. Dinuclear cobalt(II) and copper(II) complexes with a Py2N4S2 macrocyclic ligand. (United States)

    Núñez, Cristina; Bastida, Rufina; Lezama, Luis; Macías, Alejandro; Pérez-Lourido, Paulo; Valencia, Laura


    The interaction between Co(II) and Cu(II) ions with a Py(2)N(4)S(2)-coordinating octadentate macrocyclic ligand (L) to afford dinuclear compounds has been investigated. The complexes were characterized by microanalysis, conductivity measurements, IR spectroscopy and liquid secondary ion mass spectrometry. The crystal structure of the compounds [H(4)L](NO(3))(4), [Cu(2)LCl(2)](NO(3))(2) (5), [Cu(2)L(NO(3))(2)](NO(3))(2) (6), and [Cu(2)L(μ-OH)](ClO(4))(3)·H(2)O (7) was also determined by single-crystal X-ray diffraction. The [H(4)L](4+) cation crystal structure presents two different conformations, planar and step, with intermolecular face-to-face π,π-stacking interactions between the pyridinic rings. Complexes 5 and 6 show the metal ions in a slightly distorted square-pyramidal coordination geometry. In the case of complex 7, the crystal structure presents the two metal ions joined by a μ-hydroxo bridge and the Cu(II) centers in a slightly distorted square plane or a tetragonally distorted octahedral geometry, taking into account weak interactions in axial positions. Electron paramagnetic resonance spectroscopy is in accordance with the dinuclear nature of the complexes, with an octahedral environment for the cobalt(II) compounds and square-pyramidal or tetragonally elongated octahedral geometries for the copper(II) compounds. The magnetic behavior is consistent with the existence of antiferromagnetic interactions between the ions for cobalt(II) and copper(II) complexes, while for the Co(II) ones, this behavior could also be explained by spin-orbit coupling.

  2. Cationic lipids bearing succinic-based, acyclic and macrocyclic hydrophobic domains: Synthetic studies and in vitro gene transfer. (United States)

    Jubeli, Emile; Maginty, Amanda B; Khalique, Nada Abdul; Raju, Liji; Nicholson, David G; Larsen, Helge; Pungente, Michael D; Goldring, William P D


    In this communication we describe the construction of four succinic-based cationic lipids, their formulation with plasmid DNA (pDNA), and an evaluation of their in vitro gene delivery into Chinese hamster ovarian (CHO-K1) cells. The cationic lipids employed in this work possess either a dimethylamine or trimethylamine headgroup, and a macrocyclic or an acyclic hydrophobic domain composed of, or derived from two 16-atom, succinic-based acyl chains. The synthesized lipids and a co-lipid of neutral charge, either cholesterol or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), were formulated in an overall 3:2 cationic-to-neutral lipid molar ratio, then complexed with plasmid DNA (pDNA). The relative transfection performance was evaluated via a comparison between matched versus mismatched formulations defined by the rigidity relationship between the lipids employed. Gel electrophoresis was used to characterize the binding of the lipid formulations with plasmid DNA and the relative degree of plasmid degradation using a DNase I degradation assay. Small angle X-ray diffraction (SAXD) was employed to characterize the packing morphology of the lipid-DNA complexes. In general, the succinic unit embedded within the hydrophobic domain of the cationic lipids was found to improve lipid hydration. The transfection assays revealed a general trend in which mismatched formulations that employed a rigid lipid combined with a non-rigid (or flexible) lipid, outperformed the matched formulations. The results from this work suggest that the design of the cationic lipid structure and the composition of the lipoplex formulation play key roles in governing the transfection performance of nonviral gene delivery agents.

  3. Effect of plagiochin E, an antifungal macrocyclic bis(bibenzyl), on cell wall chitin synthesis in Candida albicans

    Institute of Scientific and Technical Information of China (English)

    Xiu-zhen WU; Ai-xia CHENG; Ling-mei SUN; Hong-xiang LOU


    Aim: To investigate the effect of plagiochin E (PLE), an antifungal macrocyclic bis(bibenzyl) isolated from liverwort Marchantia polymorpha L, on cell wall chitin synthesis in Candida albicans. Methods: The effect of PLE on chitin synthesis in Candida albicans was investigated at the cellular and molecular lev-els. First, the ultrastructural changes were observed under transmission electron microscopy (TEM). Second, the effects of PLE on chitin synthetase (Chs) activi-ties in vitro were assayed using 6-O-dansyl-N-acetylglucosamine as a fluorescent substrate, and its effect on chitin synthesis in situ was assayed by spheroplast regeneration. Finally, real-time RT-PCR was performed to assay its effect on the expression of Chs genes (CHS). Results: Observation under TEM showed that the structure of the cell wall in Candida albicans was seriously damaged, which suggested that the antifungal activity of PLE was associated with its effect on the cell wail. Enzymatic assays and spheroplast regeneration showed that PLE inhibited chitin synthesis in vitro and in situ. The results of the PCR showed that PLE significantly downregulated the expression of CHS1, and upregulated the expression of CHS2 and CHS3. Because different Chs is regulated at different stages of transcription and post-translation, the downregulation of CHS1 would decrease the level of Chs 1 and inhibit its activity, and the inhibitory effects of PLE on Chs2 and Chs3 would be at the post-translational level or by the inhibi-tion on the enzyme-active center. Conclusion: These results indicate that the antifungal activity of PLE would be attributed to its inhibitory effect on cell wall chitin synthesis in Candida albicans.

  4. Perturbation of the O-U-O Angle in Uranyl by Coordination to a 12-Membered Macrocycle. (United States)

    Pedrick, Elizabeth A; Schultz, Jason W; Wu, Guang; Mirica, Liviu M; Hayton, Trevor W


    Reaction of [UO2Cl2(THF)2]2 (THF = tetrahydrofuran) with 2 equiv of (H)N4 ((H)N4 = 2,11-diaza[3,3](2,6) pyridinophane) or (Me)N4 ((Me)N4 = N,N'-dimethyl-2,11-diaza[3,3](2,6) pyridinophane), in MeCN, results in the formation of UO2Cl2((R)N4) (R = H; 1; Me, 2), which were isolated as yellow-orange solids in good yields. Similarly, reaction of UO2(OTf)2(THF)3 with (H)N4 in MeCN results in the formation of UO2(OTf)2((H)N4) (3), as an orange powder in 76% yield. Finally, reaction of UO2(OTf)2(THF)3 with (Me)N4 in THF results in the formation of [UO2(OTf)(THF)((H)N4)][OTf] (4), as an orange powder in 73% yield. Complexes 1-4 were fully characterized, including characterization by X-ray crystallography. These complexes exhibit the smallest O-U-O bond angles measured to date, ranging from 168.2(3)° (for 2) to 161.7(5)° (for 4), a consequence of an unfavorable steric interaction between the oxo ligands and the macrocycle backbone. A Raman spectroscopic study of 1-4 reveals no correlation between O-U-O angle and the U═O νsym mode. However, complexes 1 and 2 do feature lower U═O νsym modes than complexes 3 and 4, which can be rationalized by the stronger donor strength of Cl(-) versus OTf(-). This observation suggests that the identity of the equatorial ligands has a greater effect on the U═O νsym frequency than does a change in O-U-O angle, at least when the changes in the O-U-O angles are small.

  5. Theoretical approach to the magnetic properties of Mn(II), Cr(III), and Cu(II) complexes in the newly reported 12- and 15-membered macrocyclic ligands

    Indian Academy of Sciences (India)

    Ali Bayri; Mustafa Karkaplan


    The magnetic properties of Cu2+, Cr3+, and Mn2+ ions in the newly reported 12- and 15-membered macrocyclic complexes are analysed by a theoretical approach. The calculated magnetic moment and magnetic anisotropy for various situations, especially for Cu(II) ion, suggest that the magnetic properties may lead to a better interpretation about the geometry. It is also suggested that the zero-field splitting Hamiltonian may be used for magnetic properties of some metal ions, which have orbital singlet ground term in these complexes.

  6. Synthesis of new tren-based tris-macrocycles. Anion cluster assembling inside the cavity generated by a bowl-shaped receptor. (United States)

    Bazzicalupi, Carla; Bencini, Andrea; Berni, Emanuela; Bianchi, Antonio; Ciattini, Samuele; Giorgi, Claudia; Maoggi, Sauro; Paoletti, Piero; Valtancoli, Barbara


    The synthesis of three new tris-macrocycles, containing three [12]aneN(4) (L1), [12]aneN(3)O (L2), or [14]aneN(4) (L3) moieties appended to a tren unit, is reported. The crystal structure of the [(Na(ClO(4))(6)) subset L1(2)H(13)]Na(6)Cl(2)(ClO(4))(12) compound shows the anionic cluster [Na(ClO(4))(6)](5)(-) assembled inside the cavity defined by two bowl-shaped polyammonium receptors, held by multiple charge-charge and hydrogen bond interactions.

  7. Chiral Recognition for the Two Enantiomers of Phenylalanine and Four Amino Acid Derivatives with (S)-Phenylethylamine Derived Nickel(II) Macrocyclic Complex

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jeong Jae; Ryoo, Jae Jeong [Kyungpook National Univ., Daegu (Korea, Republic of)


    The potency of new chiral selector candidate was assessed by this simple chiral discrimination test. This experiment showed that the macrocyclic molecule can be a powerful candidate as a chiral selector to obtain optically pure amino acid or amino acid derivatives, particularly phenylalanine and N-benzoyl-phenylalanine enantiomers from racemic mixtures. This study attempted to use the chiral metal organic framework (MOF), 1, as a good chiral selector candidate for the chiral discrimination of racemic phenylalanine, N-benzoyl-alanine, N-benzoyl-phenylalanine, N-benzoyl-methionine, N-CBZ-alanine. The chiral recognition ability of the chiral macromolecule, was examined by varying the molar ratio of the macromolecule and racemates.

  8. Nitrate-Bridged One-Dimension Coordination Polymer Self-Assembled from a N4O2-Tetraiminodiphenolate Dicopper(II Macrocyclic Complex

    Directory of Open Access Journals (Sweden)

    Julio Cesar da Rocha


    Full Text Available Herein we report on the synthesis and single crystal X-ray structure characterization of [{Cu2(tidf(μ-NO3}∞]ClO4 (tidf = a Robson type macrocyclic ligand obtained upon condensation of 2,6-diformyl-4-methylphenol and 1,3-diaminopropane. The coordination geometry around the copper(II is square-pyramidal and has [Cu2(tidf]2+ units connected to each other through nitrate bridges extending as a one-dimension coordination polymer. The compound exhibits an extensive supramolecular structure supported by nonclassic hydrogen bonding between C-H⋯Operchlorate and C-H⋯Onitrate.

  9. Characterization of E and Z isomers in macrocyclic lactones and acyclic pheromones by NMR spectra

    Energy Technology Data Exchange (ETDEWEB)

    Mahajan, J.R.; Resck, I.S. [Brasilia Univ., DF (Brazil). Dept. de Quimica; Braz Filho, R. [Universidade Estadual do Norte Fluminense (UENF), Campos, RJ (Brazil). Dept. de Produtos Quimicos Naturais; Carvalho, M.G. de [Universidade Federal Rural do Rio de Janeiro, Seropedica, RJ (Brazil). Dept. de Quimica


    A large proportion of pheromones, isolated from a variety of insects, constitutes a big list of diversely functionalized acyclic compounds, which have been synthesized by several routes. Catalytic or chemical methods were examined for the Z to E isomerization and their efficiency checked by {sup 1} H and {sup 13} C NMR spectra. Nuclear magnetic resonance has been used to identify and characterize molecular structure of the compounds, besides chemical shifts was analysed 11 refs., 4 figs., 5 tabs.

  10. The Synthesis, Structures, and Chemical Properties of Macrocyclic Ligands Covalently Bonded into Layered Arrays

    Energy Technology Data Exchange (ETDEWEB)

    Clearfield, Abraham [Texas A & M Univ., College Station, TX (United States)


    In this part of the proposal we have concentrated on the surface functionalization of α-zirconium phosphate of composition Zr(O3POH)2•H2O. It is a layered compound that can be prepared as particles as small as 30 nm to single crystals in the range of cm. This compound is an ion exchanger with a capacity of 6.64 meq per gram. It finds use as a catalyst, proton conductor, sensors, biosensors, in kidney dialysis and drug delivery. By functionalizing the surface additional uses are contemplated as will be described. The layers consist of the metal, with 4+ charge, that is positioned slightly above and below the mean layer plane and bridged by three of the four phosphate oxygens. The remaining POH groups point into the interlayer space creating double rows of POH groups but single arrays on the surface layers. The surface groups are reactive and we were able to bond silanes, isocyanates, epoxides, acrylates ` and phosphates to the surface POH groups. The layers are easily exfoliated or filled with ions by ion exchange or molecules by intercalation reactions. Highlights of our work include, in addition to direct functionalization of the surfaces, replacement of the protons on the surface with ions of different charge. This allows us to bond phosphates, biophosphates, phosphonic acids and alcohols to the surface. By variation of the ion charge of the ions that replace the surface protons, different surface structures are obtained. We have already shown that polymer fillers, catalysts and Janus particles may be prepared. The combination of surface functionalization with the ability to insert molecules and ions between the layers allow for a rich development of numerous useful other applications as well as nano-surface chemistry.

  11. Les principaux accidents de déversements pétroliers en mer et la banque de données de l'Institut Français du Pétrole sur les accidents de navires (1955-1979 The Principal Offshore Oil-Spill Accidents and the Tanker Casualties Data-Bank(1955-1979 Compiled by Institut Français du Pétrole

    Directory of Open Access Journals (Sweden)

    Bertrand A. R. V.


    Full Text Available Après avoir exposé les principaux problèmes posés par le déversement accidentel de pétrole en mer sous ses aspects qualitatifs et quantitatifs, puis rappelé un certain nombre de données tirées d'études antérieures, nous indiquons les résultats de l'activité documentaire de l'Institut Français du Pétrole dans ce domaine : -liste d'accidents ayant donné lieu à un déversement supérieur à 500 t et d'origines diverses (navires, plates-formes, oléoducs, installations côtières; - banque de données sur les accidents de navires. Cette banque concernant plus de 400 accidents survenus de 1955 à 1979 a permis d'établir plusieurs corrélations et de préciser quelques points. En particulier si le nombre d'accidents « principaux » ne semble pas avoir augmenté d'une façon significative au cours de ces dernières années ainsi que le déversement global dû aux accidents, celui-ci nous paraît avoir été sous-estimé dans les évaluations antérieures. II devrait s'élever à 500 000 t/an au lieu de 300 000 t/an, chiffre donné en 1973 par la National Academy of Sciences américaine et constamment repris depuis dans de nombreux rapports et publications. After describing the main problems raised by occidental offshore oil spills from a qualitative and quantitative standpoint and then reviewing various data token from previous reports, this article goes on to describe the results of documentary activity by Institut Français du Pétrole in this field - list of accidents resulting in a spill of more than 500 t and coming from various origins (ships, platforms, pipelines, coastal installations; - data bank on ship accidents. This data bank includes more thon 400 accidents occurring between 1955 and 1979. It reveals various correlations and specific points. In particular, whereas the number of « principal » accidents does not seem to have appreciably increased in the last few years nor has the overall amount thus spilled, these data

  12. Switching between Anion-Binding Catalysis and Aminocatalysis with a Rotaxane Dual-Function Catalyst. (United States)

    Eichstaedt, Katarzyna; Jaramillo-Garcia, Javier; Leigh, David A; Marcos, Vanesa; Pisano, Simone; Singleton, Thomas A


    The "off" state for aminocatalysis by a switchable [2]rotaxane is shown to correspond to an "on" state for anion-binding catalysis. Conversely, the aminocatalysis "on" state of the dual-function rotaxane is inactive in anion-binding catalysis. Switching between the different states is achieved through the stimuli-induced change of position of the macrocycle on the rotaxane thread. The anion-binding catalysis results from a pair of triazolium groups that act together to CH-hydrogen-bond to halide anions when the macrocycle is located on an alternative (ammonium) binding site, stabilizing the in situ generation of benzhydryl cation and oxonium ion intermediates from activated alkyl halides. The aminocatalysis and anion-binding catalysis sites of the dual-function rotaxane catalyst can be sequentially concealed or revealed, enabling catalysis of both steps of a tandem reaction process.

  13. Efficient and Selective Formation of Macrocyclic Disubstituted Z Alkenes by Ring-Closing Metathesis (RCM) Reactions Catalyzed by Mo- or W-Based Monoaryloxide Pyrrolide (MAP) Complexes. Applications to Total Syntheses of Epilachnene, Yuzu Lactone, Ambrettolide, Epothilone C and Nakadomarin A (United States)

    Wang, Chenbo; Yu, Miao; Kyle, Andrew F.; Jakubec, Jakubec; Dixon, Darren J.; Schrock, Richard R.; Hoveyda, Amir H.


    The first broadly applicable set of protocols for efficient and highly Z-selective formation of macrocyclic disubstituted alkenes through catalytic ring-closing metathesis (RCM) is described. Cyclizations are performed in the presence of 1.2–7.5 mol % of a Mo- or W-based mono-aryloxide pyrrolide (MAP) complex at 22 °C and typically proceed to complete conversion within two hours. The utility of the catalytic strategy is demonstrated by stereoselective synthesis of representative macrocyclic alkenes, including natural products yuzu lactone (13-membered ring: 73% Z) epilachnene (15-membered ring: 91% Z), ambrettolide (17-membered ring: 91% Z), an advanced precursor to epothilones C and A (16-membered ring: up to 97% Z) and nakadomarin A (polycyclic 15-membered ring: up to 97% Z). We demonstrate the complementary nature of the Mo-based catalysts, which deliver high activity but can be more prone to causing post-RCM stereoisomerization, versus W-based variants, which furnish lower activity but are less inclined towards causing loss of kinetic Z selectivity; a number of catalytic Z-selective cases are provided to elucidate which catalyst class is best suited for which substrate and particular type of alkene RCM process. Mechanistic models that rationalize the origin and the trends in Z selectivity as a function of alterations in the catalyst structure (i.e., Mo vs W and different imido and aryloxide or alkoxide ligands) are provided; we show that reaction time can be critical in retaining the Z selectivity attained not only with MAP complexes but with the original Mo-based bis-alkoxides as well. The W-based catalysts are sufficiently stable to be manipulated in air even with humidity levels of up to 80%; the catalytic Z-selective cyclizations can be performed on gram scale with complex molecule starting materials. PMID:23345004

  14. Neristatin 1 Provides Critical Insight into Bryostatin 1 Structure?Function Relationships


    Kedei, Noemi; Kraft, Matthew B.; Keck, Gary E.; Herald, Cherry L.; Melody, Noeleen; Pettit, George R.; Blumberg, Peter M.


    Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina, has been the subject of multiple clinical trials for cancer. Although it functions as an activator of protein kinase C (PKC) in vitro, bryostatin 1 paradoxically antagonizes most responses to the prototypical PKC activator, the phorbol esters. The bottom half of the bryostatin 1 structure has been shown to be sufficient to confer binding to PKC. In contrast, we have previously shown that the top half of the bryostatin ...

  15. {sup 60}Co gamma-irradiation effects on electrical properties of a rectifying diode based on a novel macrocyclic Zn octaamide complex

    Energy Technology Data Exchange (ETDEWEB)

    Ocak, Y.S. [Department of Science, Faculty of Education, University of Dicle, Diyarbakir (Turkey); Kilicoglu, T., E-mail: [Department of Physics, Faculty of Art and Science, University of Batman, Batman (Turkey); Department of Physics, Faculty of Art and Science, University of Dicle, Diyarbakir (Turkey); Topal, G. [Department of Chemistry, Faculty of Education, University of Dicle, Diyarbakir (Turkey); Baskan, M.H. [Department of Physics, Faculty of Education, University of Dicle, Diyarbakir (Turkey)


    C{sub 36}H{sub 28}N{sub 12}O{sub 8}ZnCl{sub 2}.9/2H{sub 2}O, Zn-octaamide (ZnOA) macrocyclic compound was synthesized to be used in the fabrication of electronic and photoelectronic devices. The structure of new compound was identified by using {sup 1}H NMR, {sup 13}C NMR, IR, UV-vis and LC-MS spectroscopic methods. The Sn/ZnOA/n-Si/Au structure was engineered by forming a thin macrocyclic organic compound layer on n-Si inorganic substrate and then by evaporating Sn metal on the organic layer. It was seen that the device had a good rectifying behaviour and showed Schottky diode properties. The diode was irradiated under {sup 60}Co gamma-source at room temperature. Characteristic parameters of the diode were determined from its current-voltage (I-V) and capacitance voltage (C-V) measurements before and after irradiation. It was observed that gamma-irradiation had clear effects on I-V and C-V properties. Also, it was seen that the barrier height, the ideality factor and the series resistance values decreased after the applied radiation, while the saturation current value increased.

  16. Induction of a type I interferon signature in normal human monocytes by gadolinium-based contrast agents: comparison of linear and macrocyclic agents. (United States)

    Wermuth, P J; Jimenez, S A


    The gadolinium-based contrast agent (GdBCA) Omniscan activates human macrophages through Toll-like receptor (TLR)-4 and TLR-7 signalling. To explore the mechanisms responsible we compared the ability of linear and macrocyclic GdBCA to induce a type I interferon signature and a proinflammatory/profibrotic phenotype in normal human monocytes in vitro. Expression of genes associated with type I interferon signalling and inflammation and production of their corresponding proteins were determined. Both linear and macrocyclic GdBCA stimulated expression of multiple type I interferon-regulated genes and the expression of numerous chemokines, cytokines and growth factors in normal human peripheral blood monocytes. There was no correlation between the magnitude of the measured response and the Gd chelate used. To explore the mechanisms responsible for GdBCA induction of fibrosis in nephrogenic systemic fibrosis (NSF) in vitro, normal human dermal fibroblasts were incubated with GdBCA-treated monocyte culture supernatants and the effects on profibrotic gene expression were examined. Supernatants from monocytes exposed to all GdBCA stimulated types I and III collagen, fibronectin and α-smooth muscle actin (α-SMA) expression in normal dermal fibroblasts. The results indicate that the monocyte activation induced by GdBCA may be the initial step in the development of GdBCA associated fibrosis in NSF.

  17. Synthesis and biophysical studies of bis-macrocyclic cobalt/copper(II) complexes having a pyridine spacer with CT DNA and 5'-GMP. (United States)

    Arjmand, Farukh; Aziz, Mubashira


    New bis-macrocyclic complexes of Co(III), 1, Ni(II), 2, and Cu(II), 3, containing pyridyl bridges between 13-membered macrocyclic subunits, have been synthesized via an in situ one-pot template condensation reaction (IOPTCR). The proposed structures of these new dinuclear complexes are consistent with the data obtained from elemental analysis, molar conductance, IR, EPR, UV/VIS, (1)H- and 13C-NMR, and ESI-MS. The complexes 2 and 3 possess square-planar geometry with four secondary N-atoms coordinated to the metal ion, while complex 1 reveals octahedral geometry in solution due to coordinated H(2)O molecules. DNA-Binding properties of the complexes 1 and 3 were investigated by absorption and emission titrations, cyclic voltammetry, and viscosity measurements. Complexes 1 and 3 are strong DNA binders with binding constants, K(b), of 1.64 x 10(5) and 2.05 x 10(5) M(-1), respectively. Hyperchromism, decrease in emission intensity of DNA-bound ethidium bromide (EB), and changes observed in the viscosity and cyclic voltammograms in the presence of added metal complexes reveals that the complexes bind to DNA predominantly by electrostatic attraction, substantiated by absorption titration with 5'-GMP.

  18. Synthesis and Characterization of Macrocyclic Polyether N,N′-Diallyl-7,16-diaza-1,4,10,13-tetraoxa-dibenzo-18-crown-6

    Directory of Open Access Journals (Sweden)

    Julius Toeri


    Full Text Available In this study an efficient and direct production procedure for a macrocyclic polyether N,N′-diallyl-7,16-diaza-1,4,10,13-tetraoxa-dibenzo-18-crown-6 from the reaction of catechol and N,N-bis(2-chloroethylprop-2-en-1-amine in n-butanol in the presence of a strong base is reported. The synthesis involves a two-step addition of sodium hydroxide to enhance the cyclization process, and at the end of the reaction, the reaction mixture is neutralized and the solvent replaced with water in-situ through distillation to afford a relatively pure precipitate that is easily recrystallized from acetone. The yield of the macrocycle was 36%–45% and could be scaled-up to one-mole quantities. The structure and purity of this compound was verified on the basis of elemental analysis, IR, UV-Vis, 1H-, 13C-NMR, 2D-NMR, mass spectroscopy, and thermal analysis. The white crystalline compound has a sharp melting point of 124 °C and a crystallization temperature of 81.4 °C determined by differential scanning calorimetry. Our motivation behind the synthesis of the bibracchial lariat azacrown polyether ligand was to examine its possible applications in ion-selective polymer-supported materials.

  19. Macrocyclic Gd3+ chelates attached to a silsesquioxane core as potential magnetic resonance imaging contrast agents: synthesis, physicochemical characterization, and stability studies. (United States)

    Henig, Jörg; Tóth, Eva; Engelmann, Jörn; Gottschalk, Sven; Mayer, Hermann A


    Two macrocyclic ligands, 1,4,7,10-tetraazacyclododecane-1-glutaric-4,7,10-triacetic acid (H(5)DOTAGA) and the novel 1,4,7,10-tetraazacyclododecane-1-(4-(carboxymethyl)benzoic)-4,7,10-triacetic acid (H(5)DOTABA), were prepared and their lanthanide complexes (Ln = Gd(3+), Y(3+)) attached to an amino-functionalized T(8)-silsesquioxane. The novel compounds Gadoxane G (GG) and Gadoxane B (GB) possess eight monohydrated lanthanide complexes each, as evidenced by multinuclear ((1)H, (13)C, (29)Si) NMR spectroscopy and high resolution mass spectrometry (HR-MS). Pulsed-field gradient spin echo (PGSE) diffusion (1)H NMR measurements revealed hydrodynamic radii of 1.44 nm and global rotational correlation times of about 3.35 ns for both compounds. With regard to potential MRI contrast agent applications, a variable-temperature (17)O NMR and (1)H nuclear magnetic relaxation dispersion (NMRD) study was carried out on aqueous solutions of the gadolinium(III) complexes of the Gadoxanes and the corresponding monomeric ligands to yield relevant physicochemical properties. The water exchange rates of the inner-sphere water molecules are all very similar (k(ex)(298) between (5.3 +/- 0.5) x 10(6) s(-1) and (5.9 +/- 0.3) x 10(6) s(-1)) and only slightly higher than that reported for the gadolinium(III) complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (H(4)DOTA) (k(ex)(298) = 4.1 x 10(6) s(-1)). Despite their almost identical size and their similar water exchange rates, GB shows a significantly higher longitudinal relaxivity than GG over nearly the whole range of magnetic fields (e.g., 17.1 mM(-1) s(-1) for GB and 12.1 mM(-1) s(-1) for GG at 20 MHz and 25 degrees C). This difference arises from their different local rotational correlation times (tau(lR)(298) = 240 +/- 10 ps and 380 +/- 20 ps, respectively), because of the higher rigidity of the phenyl ring of GB as compared to the ethylene spacer of GG. A crucial feature of these novel compounds is the lability of the

  20. Macrocyclic receptor showing extremely high Sr(II)/Ca(II) and Pb(II)/Ca(II) selectivities with potential application in chelation treatment of metal intoxication. (United States)

    Ferreirós-Martínez, Raquel; Esteban-Gómez, David; Tóth, Éva; de Blas, Andrés; Platas-Iglesias, Carlos; Rodríguez-Blas, Teresa


    Herein we report a detailed investigation of the complexation properties of the macrocyclic decadentate receptor N,N'-Bis[(6-carboxy-2-pyridil)methyl]-4,13-diaza-18-crown-6 (H(2)bp18c6) toward different divalent metal ions [Zn(II), Cd(II), Pb(II), Sr(II), and Ca(II)] in aqueous solution. We have found that this ligand is especially suited for the complexation of large metal ions such as Sr(II) and Pb(II), which results in very high Pb(II)/Ca(II) and Pb(II)/Zn(II) selectivities (in fact, higher than those found for ligands widely used for the treatment of lead poisoning such as ethylenediaminetetraacetic acid (edta)), as well as in the highest Sr(II)/Ca(II) selectivity reported so far. These results have been rationalized on the basis of the structure of the complexes. X-ray crystal diffraction, (1)H and (13)C NMR spectroscopy, as well as theoretical calculations at the density functional theory (B3LYP) level have been performed. Our results indicate that for large metal ions such as Pb(II) and Sr(II) the most stable conformation is Δ(δλδ)(δλδ), while for Ca(II) our calculations predict the Δ(λδλ)(λδλ) form being the most stable one. The selectivity that bp18c6(2-) shows for Sr(II) over Ca(II) can be attributed to a better fit between the large Sr(II) ions and the relatively large crown fragment of the ligand. The X-ray crystal structure of the Pb(II) complex shows that the Δ(δλδ)(δλδ) conformation observed in solution is also maintained in the solid state. The Pb(II) ion is endocyclically coordinated, being directly bound to the 10 donor atoms of the ligand. The bond distances to the donor atoms of the pendant arms (2.55-2.60 Å) are substantially shorter than those between the metal ion and the donor atoms of the crown moiety (2.92-3.04 Å). This is a typical situation observed for the so-called hemidirected compounds, in which the Pb(II) lone pair is stereochemically active. The X-ray structures of the Zn(II) and Cd(II) complexes show that

  1. Self-Assembling Organic Nanopores as Synthetic Transmembrane Channels with Tunable Functions (United States)

    Wei, Xiaoxi

    nanotubular assembly, rather than the individual molecules of 3, is required to partition into the lipid bilayer in order for these macrocycles to act as channels. Further structural modification has led to fourth-generation macrocycles 4 having readily-tunable cavities (Chapter 4). Macrocycles 4 , with a hybrid backbone composed half of the oligoamide and half of the phenylene ethynylene moieties, exhibits similar self-assembling behavior by forming nanotubular stacks. The results of a preliminary study based on LUVs-assays and BLM single channel recording experiments are summarized and clearly indicate that ion channels formed by this fourth-generation exhibit high stability and differing ion selectivity largely consistent with the corresponding structural modification of the interior cavity. Especially, the increased anion conductance observed for 4d indicates that our strategy of tuning supramolecular function based on synthetic modification of the backbone and pore is effective. In Chapter 5, our four-residue tetraurea macrocycles 5 have shown significant potency to selectively interact with the G-quadruplex, leading to a strong stabilization effect for G-quadruplex without binding to duplex DNA as observed by UV-melt assays. The ready synthetic availability of these macrocycles makes them amenable to future chemical modification, which allows systematic improvement of binding affinity and specificity. Moreover, it has been discovered that these macrocycles can partition into lipid bilayers and form very stable transmembrane ion channels with a pore size of ˜5 A. Preliminary data shows that this smaller ion channel may lead to exceptional ion conducting selectivity, which is rarely seen in the field of synthetic ion pores. These molecules may serve as a unique platform for the rational development of potent and versatile therapeutic agents. The exceptional ion conducting properties of these channels place aromatic oligoamide macrocycles 3 and 4 at a unique position with

  2. Octaselenododecane (C4H8Se8): a novel polyselenoether crown macrocycle (United States)

    Richardson, Steven; Mehl, Michael; Pederson, Mark


    In this work we have used density-functional theory (DFT/GGA-PBE) to calculate the structural, electronic, and vibrational properties of octaselenododecane (C4H8Se8), a novel twelve-membered crown-shaped heterocycle which contains four diselenide groups.ootnotetext G. Hua, J. M. Griffin, S. E. Ashbrook, A. M. Z. Slawin, and J. D. Wollins, Angew Che. Int. Ed. 2011, 50, 4123-4126. Our all-electron DFT calculations have yielded results that are in excellent agreement with the observed experimental x-ray diffraction data and infrared and Raman vibrational spectra for the solid state phase of octaselenododecane. In addition to obtaining good general agreement with the selected IR and Raman frequencies reported to lie within the range of 282-2925 cm-1, we have obtained other vibrational modes which have not been reported in the literature. In particular, we have computed a Raman active mode at 267 cm-1 which is in good agreement with the experimental band at 282 cm-1 and have determined that it represents significant asynchronous stretches of diselenide groups within the heterocycle. Our gas phase calculations also show the presence of strong low frequency distortions that are supressed in the crystal due to close Se-Se intramolecular interactions.

  3. Spectroscopic investigation into the interaction of a diazacyclam-based macrocyclic copper(ii) complex with bovine serum albumin. (United States)

    Shahabadi, Nahid; Hakimi, Mohammad; Morovati, Teimoor; Hadidi, Saba; Moeini, Keyvan


    Cyclam-based ligands and their complexes are known to show antitumor activity. This study was undertaken to examine the interaction of a diazacyclam-based macrocyclic copper(II) complex with bovine serum albumin (BSA) under physiological conditions. The interactions of different metal-based drugs with blood proteins, especially those with serum albumin, may affect the concentration and deactivation of metal drugs, and thereby influence their availability and toxicity during chemotherapy. In this vein, several spectral methods including UV-vis absorption, fluorescence and circular dichroism (CD) spectroscopy techniques were used. Spectroscopic analysis of the fluorescence quenching confirmed that the Cu(II) complex quenched BSA fluorescence intensity by a dynamic mechanism. In order to further determine the quenching mechanism, an analysis of Stern-Volmer plots at various concentrations of BSA was carried out. It was found that the KSV value increased with the BSA concentration. It was suggested that the fluorescence quenching process was a dynamic quenching rather than a static quenching mechanism. Based on Förster's theory, the average binding distance between the Cu(II) complex and BSA (r) was found to be 4.98 nm; as the binding distance was less than 8 nm, energy transfer from BSA to the Cu(II) complex had a high possibility of occurrence. Thermodynamic parameters (positive ΔH and ΔS values) and measurement of competitive fluorescence with 1-anilinonaphthalene-8-sulphonic acid (1,8-ANS) indicated that hydrophobic interaction plays a major role in the Cu(II) complex interaction with BSA. A Job's plot of the results confirmed that there was one binding site in BSA for the Cu(II) complex (1:1 stoichiometry). The site marker competitive experiment confirmed that the Cu(II) complex was located in site I (subdomain IIA) of BSA. Finally, CD data indicated that interaction of the Cu(II) complex with BSA caused a small increase in the α-helical content. Copyright

  4. Cyano-bridged structures based on [MnIIN3O2-macrocycle)]2+: a synthetic, structural, and magnetic study. (United States)

    Bonadio, Federica; Senna, Maria-Cristina; Ensling, Jürgen; Sieber, Andreas; Neels, Antonia; Stoeckli-Evans, Helen; Decurtins, Silvio


    Reactions between the complex [MnII(L)]2+, where L is a N3O2 macrocyclic ligand, and different cyanometalate precursors such as [M(CN)n]m- (M(III) = Cr, Fe; M(II) = Fe, Ni, Pd, Pt) lead to cyano-bridged molecular assemblies exhibiting a variety of structural topologies. The reaction between [MnII(L)]2+ and [FeII(CN)6]4- forms a trinuclear complex with formula [(MnII(L)(H2O))2(FeII(micro-CN)2(CN)4)] x 2MeOH x 10H2O (1) which crystallizes in the triclinic space group P1. The reaction between [MnII(L)]2+ and [M(II)(CN)4]2-, where M(II) = Ni (2), Pd (3), Pt (4), gives rise to three isostructural linear chain compounds with stoichiometry [(MnII(L))(M(II)(micro-CN)2(CN)2)]n and which crystallize in the monoclinic space group C2/c. The self-assembly between [MnII(L)]2+ with [M(III)(CN)6]3-, where M(III) = Cr (5), Fe (6, 7, 8), forms three types of compounds. Compounds 5 and 6 are isostructural (monoclinic, space group P2(1)/n), and the structures comprise anionic linear chains [(MnII(L))(M(III)(micro-CN)2(CN)4)]n(n-) with cationic trinuclear complexes [(MnII(L)(H2O))2(M(III)(micro-CN)2(CN)4)]+ as counterions. Using an excess of K3[FeIII(CN)6], an analogous compound to 6 but with K+ as counterion is obtained (7), which crystallizes in the triclinic space group P1. Compound 8 consists of 2-D layers with formula [(MnII(L))3(FeIII(micro-CN)4(CN)2)(FeIII(micro-CN)2(CN)4)]n x 2nMeOH; it crystallizes in the monoclinic space group P2(1)/n. The magnetic properties were investigated for all samples. In particular, compound 5, which shows antiferromagnetic exchange interactions between Mn(II) and Cr(III) ions through cyanide bridging ligands, has been studied in detail; the magnetic exchange parameter amounts to J = -7.5(7) cm(-1). Compound 8 shows a magnetically ordered phase below 6.4 K which is confirmed by Mössbauer spectroscopy; two hyperfine split spectra were observed below Tc from which IJI values of 2.1 and 1.6 cm(-1) could be deduced.

  5. Development of electrochemical sensors for nano scale Tb(III) ion determination based on pendant macrocyclic ligands. (United States)

    Singh, Ashok K; Singh, Prerna; Banerjee, Shibdas; Mehtab, Sameena


    The two macrocyclic pendant ligands 3,4,5:12,13,14-dipyridine-2,6,11,15-tetramethyl-1,7,10,16-tetramethylacrylate-1,4,7,10,13,16-hexaazacyclooctadeca-3,13-di ene (L(1)) and 3,4,5:12,13,14-dipyridine-2,6,11,15-tetramethyl-1,7,10,16-tetra(2-cyano ethane)-1,4,7,10,13,16-hexaazacyclooctadeca-3,13-diene (L(2)) have been synthesized and explored as neutral ionophores for preparing poly(vinylchloride) (PVC) based membrane sensors selective to Tb(III) ions. Effects of various plasticizers and anion excluders were studied in detail and improved performance was observed. The best performance was obtained for the membrane sensor having a composition of L(1): PVC:1-CN:NaTPB in the ratio of 6: 32: 58: 4 (w/w; mg). The performance of the membrane based on L(1) was compared with polymeric membrane electrode (PME) as well as with coated graphite electrode (CGE). The electrodes exhibit Nernstian slope for Tb(3+) ions with limits of detection of 3.4 x 10(-8)mol L(-1) for PME and 5.7 x 10(-9)mol L(-1) for CGE. The response time for PME and CGE was found to be 10s and 8s, respectively. The potentiometric responses are independent of the pH of the test solution in the pH range 3.0-7.5 for PME and 2.0-8.5 for CGE. The CGE has found to work satisfactorily in partially non-aqueous media upto 30% (v/v) content of methanol, ethanol and 20% (v/v) content of acetonitrile and could be used for a period of 5 months. The CGE was used as indicator electrode in the potentiometric titration of Tb(3+) ions with EDTA and in determination of fluoride ions in various samples. It can also be used in direct determination of Tb(3+) ions in tap water and various binary mixtures with quantitative results.

  6. Hybrid macrocycle formation and spiro annulation on cis-syn-cis-tricyclo[,6]undeca-3,11-dione and its congeners via ring-closing metathesis

    Directory of Open Access Journals (Sweden)

    Sambasivarao Kotha


    Full Text Available We have developed a simple methodology to transform cis-syn-cis-triquinane derivative 2 into the diindole based macrocycle 6 involving Fischer indolization and ring-closing metathesis (RCM. Various spiro-polyquinane derivatives have been assembled via RCM as a key step.


    NARCIS (Netherlands)



    The synthesis and characterization of the two macrocyclic sulfides, 1,4,7,10,13,16,19-heptathiaheneicosane (21-S-7) and 1,4,7,10,13,16,19,22-octathiatetraeicosane (24-S-8), are described starting from different combinations of dithiols and dichlorides of differing chain lengths. Cs2CO3 is used for t

  8. Macrocycles that inhibit the binding between heat shock protein 90 and TPR-containing proteins. (United States)

    Ardi, Veronica C; Alexander, Leslie D; Johnson, Victoria A; McAlpine, Shelli R


    Heat shock protein 90 (Hsp90) accounts for 1-2% of the total proteins in normal cells and functions as a molecular chaperone that folds, assembles, and stabilizes client proteins. Hsp90 is overexpressed (3- to 6-fold increase) in stressed cells, including cancer cells, and regulates over 200 client and co-chaperone proteins. Hsp90 client proteins are involved in a plethora of cellular signaling events including numerous growth and apoptotic pathways. Since pathway-specific inhibitors can be problematic in drug-resistant cancers, shutting down multiple pathways at once is a promising approach when developing new therapeutics. Hsp90's ability to modulate many growth and signaling pathways simultaneously makes this protein an attractive target in the field of cancer therapeutics. Herein we present evidence that a small molecule modulates Hsp90 via binding between the N and middle domain and allosterically inhibiting the binding interaction between Hsp90 and four C-terminal binding client proteins: IP6K2, FKBP38, FKBP52, and HOP. These last three clients contain a tetratricopeptide-repeat (TPR) region, which is known to interact with the MEEVD sequence on the C-terminus of Hsp90. Thus, this small molecule modulates the activity between co-chaperones that contain TPR motifs and Hsp90's MEEVD region. This mechanism of action is unique from that of all Hsp90 inhibitors currently in clinical trials where these molecules have no effect on proteins that bind to the C-terminus of Hsp90. Further, our small molecule induces a Caspase-3 dependent apoptotic event. Thus, we describe the mechanism of a novel scaffold that is a useful tool for studying cell-signaling events that result when blocking the MEEVD-TPR interaction between Hsp90 and co-chaperone proteins.

  9. Functional

    Directory of Open Access Journals (Sweden)

    Fedoua Gandia


    Full Text Available The study was carried out to investigate the effects of inhaled Mg alone and associated with F in the treatment of bronchial hyperresponsiveness. 43 male Wistar rats were randomly divided into four groups and exposed to inhaled NaCl 0.9%, MeCh, MgSO4 and MgF2. Pulmonary changes were assessed by means of functional tests and quantitative histological examination of lungs and trachea. Results revealed that delivery of inhaled Mg associated with F led to a significant decrease of total lung resistance better than inhaled Mg alone (p < 0.05. Histological examinations illustrated that inhaled Mg associated with F markedly suppressed muscular hypertrophy (p = 0.034 and bronchoconstriction (p = 0.006 in MeCh treated rats better than inhaled Mg alone. No histological changes were found in the trachea. This study showed that inhaled Mg associated with F attenuated the main principle of the central components of changes in MeCh provoked experimental asthma better than inhaled Mg alone, potentially providing a new therapeutic approach against asthma.

  10. Functionalized O6-Corona[6]arenes: Synthesis, Structure, and Fullerene Complexation Property. (United States)

    Ren, Wen-Sheng; Zhao, Liang; Wang, Mei-Xiang


    The synthesis, structure, and fullerene complexation property of novel and functionalized On-corona[n]arenes were reported. Based on the fragment coupling strategy, ester-containing On-corona[n]arenes (n = 6, 8) were obtained readily starting from 1,4-hydroquinone and diethyl 2,5-difluoroterephthalate. Reduction of esters with LiAlH4 produced almost quantitatively hydroxymethylated On-corona[n]arenes, which underwent etherification with MeI to afford methoxymethyl-substituted On-corona[n]arenes (n = 6, 8) in good yields. The macrocycles adopt unique corona-type conformation with a large cylindroid cavity. They are strong macrocyclic host molecules to form 1:1 complexes with fullerenes C60 and C70 in toluene with an associate constant up to (1.59 ± 0.04) × 10(5) M(-1).

  11. Synthesis, spectroscopic and biological activities studies of acyclic and macrocyclic mono and binuclear metal complexes containing a hard-soft Schiff base (United States)

    Abou-Hussein, Azza A. A.; Linert, Wolfgang

    Mono- and bi-nuclear acyclic and macrocyclic complexes with hard-soft Schiff base, H2L, ligand derived from the reaction of 4,6-diacetylresorcinol and thiocabohydrazide, in the molar ratio 1:2 have been prepared. The H2L ligand reacts with Co(II), Ni(II), Cu(II), Zn(II), Mn(II) and UO2(VI) nitrates, VO(IV) sulfate and Ru(III) chloride to get acyclic binuclear complexes except for VO(IV) and Ru(III) which gave acyclic mono-nuclear complexes. Reaction of the acyclic mono-nuclear VO(IV) and Ru(III) complexes with 4,6-diacetylresorcinol afforded the corresponding macrocyclic mono-nuclear VO(IV) and Ru(IIII) complexes. Template reactions of the 4,6-diacetylresorcinol and thiocarbohydrazide with either VO(IV) or Ru(III) salts afforded the macrocyclic binuclear VO(IV) and Ru(III) complexes. The Schiff base, H2L, ligand acts as dibasic with two NSO-tridentate sites and can coordinate with two metal ions to form binuclear complexes after the deprotonation of the hydrogen atoms of the phenolic groups in all the complexes, except in the case of the acyclic mononuclear Ru(III) and VO(IV) complexes, where the Schiff base behaves as neutral tetradentate chelate with N2S2 donor atoms. The ligands and the metal complexes were characterized by elemental analysis, IR, UV-vis 1H-NMR, thermal gravimetric analysis (TGA) and ESR, as well as the measurements of conductivity and magnetic moments at room temperature. Electronic spectra and magnetic moments of the complexes indicate the geometries of the metal centers are either tetrahedral, square planar or octahedral. Kinetic and thermodynamic parameters were calculated using Coats-Redfern equation, for the different thermal decomposition steps of the complexes. The ligands and the metal complexes were screened for their antimicrobial activity against Staphylococcus aureus as Gram-positive bacteria, and Pseudomonas fluorescens as Gram-negative bacteria in addition to Fusarium oxysporum fungus. Most of the complexes exhibit mild

  12. Parallel β-sheet vibrational couplings revealed by 2D IR spectroscopy of an isotopically labeled macrocycle: quantitative benchmark for the interpretation of amyloid and protein infrared spectra. (United States)

    Woys, Ann Marie; Almeida, Aaron M; Wang, Lu; Chiu, Chi-Cheng; McGovern, Michael; de Pablo, Juan J; Skinner, James L; Gellman, Samuel H; Zanni, Martin T


    Infrared spectroscopy is playing an important role in the elucidation of amyloid fiber formation, but the coupling models that link spectra to structure are not well tested for parallel β-sheets. Using a synthetic macrocycle that enforces a two stranded parallel β-sheet conformation, we measured the lifetimes and frequency for six combinations of doubly (13)C═(18)O labeled amide I modes using 2D IR spectroscopy. The average vibrational lifetime of the isotope labeled residues was 550 fs. The frequencies of the labels ranged from 1585 to 1595 cm(-1), with the largest frequency shift occurring for in-register amino acids. The 2D IR spectra of the coupled isotope labels were calculated from molecular dynamics simulations of a series of macrocycle structures generated from replica exchange dynamics to fully sample the conformational distribution. The models used to simulate the spectra include through-space coupling, through-bond coupling, and local frequency shifts caused by environment electrostatics and hydrogen bonding. The calculated spectra predict the line widths and frequencies nearly quantitatively. Historically, the characteristic features of β-sheet infrared spectra have been attributed to through-space couplings such as transition dipole coupling. We find that frequency shifts of the local carbonyl groups due to nearest neighbor couplings and environmental factors are more important, while the through-space couplings dictate the spectral intensities. As a result, the characteristic absorption spectra empirically used for decades to assign parallel β-sheet secondary structure arises because of a redistribution of oscillator strength, but the through-space couplings do not themselves dramatically alter the frequency distribution of eigenstates much more than already exists in random coil structures. Moreover, solvent exposed residues have amide I bands with >20 cm(-1) line width. Narrower line widths indicate that the amide I backbone is solvent

  13. Dependence of the chemical properties of macrocyclic [Ni(II)(2)L(μ-O(2)CR)](+) complexes on the basicity of the carboxylato coligands (L(2-) = macrocyclic N(6)S(2) ligand). (United States)

    Lehmann, Ulrike; Klingele, Julia; Lozan, Vasile; Steinfeld, Gunther; Klingele, Marco H; Käss, Steffen; Rodenstein, Axel; Kersting, Berthold


    The dependence of the properties of mixed ligand [Ni(II)(2)L(μ-O(2)CR)](+) complexes (where L(2-) represents a 24-membered macrocyclic hexaamine-dithiophenolato ligand) on the basicity of the carboxylato coligands has been examined. For this purpose 19 different [Ni(II)(2)L(μ-O(2)CR)](+) complexes (2-20) incorporating carboxylates with pK(b) values in the range 9 to 14 have been prepared by the reaction of [Ni(II)(2)L(μ-Cl)](+) (1) and the respective sodium or triethylammonium carboxylates. The resulting carboxylato complexes, isolated as ClO(4)(-) or BPh(4)(-) salts, have been fully characterized by elemental analyses, IR, UV/vis spectroscopy, and X-ray crystallography. The possibility of accessing the [Ni(II)(2)L(μ-O(2)CR)](+) complexes by carboxylate exchange reactions has also been examined. The main findings are as follows: (i) Substitution reactions between 1 and NaO(2)CR are not affected by the basicity or the steric hindrance of the carboxylate. (ii) Complexes 2-20 form an isostructural series of bisoctahedral [Ni(II)(2)L(μ-O(2)CR)](+) compounds with a N(3)Ni(μ-SR)(2)(μ-O(2)CR)NiN(3) core. (iii) They are readily identified by their ν(as)(CO) and ν(s)(CO) stretching vibration bands in the ranges 1684-1576 cm(-1) and 1428-1348 cm(-1), respectively. (iv) The spin-allowed (3)A(2g) → (3)T(2g) (ν(1)) transition of the NiOS(2)N(3) chromophore is steadily red-shifted by about 7.5 nm per pK(b) unit with increasing pK(b) of the carboxylate ion. (v) The less basic the carboxylate ion, the more stable the complex. The stability difference across the series, estimated from the difference of the individual ligand field stabilization energies (LFSE), amounts to about 4.2 kJ/mol [Δ(LFSE)(2,18)]. (vi) The "second-sphere stabilization" of the nickel complexes is not reflected in the electronic absorption spectra, as these forces are aligned perpendicularly to the Ni-O bonds. (vii) Coordination of a basic carboxylate donor to the [Ni(II)(2)L](2+) fragment weakens

  14. Approaches to Macrocyclic Polystannanes. (United States)


    part is permitted any purpose of the United States Government. A *This document has been approved for public release and sale ; its distribution is...mixture indicated that no reaction had occurred. was prepared by the procedure of Edgell and Word. 11 Into a three-necked roundbottomed flask fitted with...F. Edgell and C. H. Ward, J. Am. Chem. Soc., Zk, 1169 (1954). (12) C. A. Kraus and A. M. Neal, J. Am. Chem. Soc., a, 2403 (1929). (13) R. H. Bullard

  15. Technologies for the Synthesis of mRNA-Encoding Libraries and Discovery of Bioactive Natural Product-Inspired Non-Traditional Macrocyclic Peptides

    Directory of Open Access Journals (Sweden)

    Hiroaki Suga


    Full Text Available In this review, we discuss emerging technologies for drug discovery, which yields novel molecular scaffolds based on natural product-inspired non-traditional peptides expressed using the translation machinery. Unlike natural products, these technologies allow for constructing mRNA-encoding libraries of macrocyclic peptides containing non-canonical sidechains and N-methyl-modified backbones. The complexity of sequence space in such libraries reaches as high as a trillion (>1012, affording initial hits of high affinity ligands against protein targets. Although this article comprehensively covers several related technologies, we discuss in greater detail the technical development and advantages of the Random non-standard Peptide Integration Discovery (RaPID system, including the recent identification of inhibitors against various therapeutic targets.

  16. Reinvestigation on the Reaction of Salicylic Chloride with Salicylic Amide and X-ray Crystal Structure of a New Macrocyclic Polyester

    Institute of Scientific and Technical Information of China (English)

    DU Da-Ming; CHEN Xiao; HUA Wen-Ting; JIN Xiang-Lin


    The reaction of salicylic chloride and salicylic amide at 170 ℃ gave benzoxazine and a new macrocyclic polyester 3, whose crystal structure has been determined by single-crystal X-ray diffraction analysis. Compound 3: C28H16O8, Mr = 480.41, monoclinic, space group P21/n, a = 15.353(3), b = 14.196(3), c = 21.147(4) A, β = 103.32(3)°, V = 4485(2) A3, Z = 8, F(000) = 1984, Dc = 1.423 g/cm3 and μ = 0.106 mm-1. The final R = 0.0535 and Wr = 0.1275 for 7903 observed reflections (I ≥ 2σ(I)). In the asymmetric unit of the compound there exist two independent molecules which are connected by weak aromatic C-H…O hydrogen bonding between C(47)- H(47) and atom O(7) of the carbonyl group.

  17. Influence of the carbohydrate fragment position in the macrocycle of chlorine e6 trimethyl ester glycosylated derivatives on their in vitro photo- induced activity

    Directory of Open Access Journals (Sweden)

    R. I. Yakubovskaya


    Full Text Available The physicochemical and photophysical properties, as well as photo-induced activity, of glycoconjugates based on chlorine е6 trimethyl ether with various positions of carbohydrate fragment in the macrocycle have been studied. The photo-induced activity was investigated in the human (HEp2, A549 and HT29 and animal (LLC cell lines. The tested compounds showed in vitro both high photo-induced activity and high stability in the dark. The photosensitizer with galactose in the A pirrole ring demonstrated the highest activity (the half maximal inhibitory concentration (ИК50 varied from 27±2 nM to 75±5 nM in tests on different cell lines. Dyes with sugar substitutes in the C pirrole ring were 5–10 times less active. 

  18. Synthesis and Characterization of New Macrocyclic Cu(Ⅱ)Complexes from Various Diamines, Copper(Ⅱ) Nitrate and 1,4-Bis(2-formylphenoxy)butane

    Institute of Scientific and Technical Information of China (English)

    ILHAN, Salih; TEMEL, Hamdi; KILIC, Ahmet


    Six new macrocyclic complexes were synthesized by a template reaction of 1,4-bis(2-formylphenoxy)butane with diamines and Cu(NO3)2·3H2O and their structures were proposed on the basis of elemental analysis, FT-IR,UV-Vis, magnetic susceptibility measurements, molar conductivity measurements and mass spectra. The metal to ligand molar ratios of the Cu(Ⅱ) complexes were found to be 1∶1. The Cu(Ⅱ) complexes are 1∶2 electrolytes as shown by their molar conductivities (Λm) in DMF at 10-3 mol·L-1. Due to the existence of free ions the Cu(Ⅱ)complexes are electrically conductive. Their configurations were proposed to be probably distorted octahedral.

  19. Synthesis and DNA cleavage activities of mononuclear macrocyclic polyamine zinc(II), copper(II), cobalt(II) complexes which linked with uracil. (United States)

    Wang, Xiao-Yan; Zhang, Ji; Li, Kun; Jiang, Ning; Chen, Shan-Yong; Lin, Hong-Hui; Huang, Yu; Ma, Li-Jian; Yu, Xiao-Qi


    Mononuclear macrocyclic polyamine zinc(II), copper(II), cobalt(II) complexes, which could attach to peptide nucleic acid (PNA), were synthesized as DNA cleavage agents. The structures of these new mononuclear complexes were identified by MS and (1)H NMR spectroscopy. The catalytic activities on DNA cleavage of these mononuclear complexes with different central metals were subsequently studied, which showed that copper complex was better catalyst in the DNA cleavage process than zinc and cobalt complexes. The effects of reaction time, concentration of complexes were also investigated. The results indicated that the copper(II) complexes could catalyze the cleavage of supercoiled DNA (pUC 19 plasmid DNA) (Form I) under physiological conditions to produce selectively nicked DNA (Form II, no Form III produced) with high yields. The mechanism of the cleavage process was also studied.

  20. Design, synthesis and characterization of macrocyclic ligand based transition metal complexes of Ni(II), Cu(II) and Co(II) with their antimicrobial and antioxidant evaluation (United States)

    Gull, Parveez; Malik, Manzoor Ahmad; Dar, Ovas Ahmad; Hashmi, Athar Adil


    Three new complexes Ni(II), Cu(II) and Co(II) were synthesized of macrocyclic ligand derived from 1, 4-dicarbonyl-phenyl-dihydrazide and O-phthalaldehyde in the ratio of 2:2. The synthesized compounds were characterized by elemental analyses, molar conductance, magnetic susceptibility measurements, FTIR, UV-Vis., Mass and 1H NMR spectral studies. The electronic spectra of the metal complexes indicate a six coordinate octahedral geometry of the central metal ion. These metal complexes and the ligand were evaluated for antimicrobial activity against bacteria (E. coli, B. subtilis, S. aureus) and fungi (A. niger, A. flavus, C. albicans) and compared against standard drugs chloramphenicol and nystatin respectively. In addition, the antioxidant activity of the compounds was also investigated through scavenging effect on DPPH radicals.

  1. Exploring the interaction of mercury(II) by N(2)S(2) and NS(3) anthracene-containing macrocyclic ligands: photophysical, analytical, and structural studies. (United States)

    Tamayo, Abel; Pedras, Bruno; Lodeiro, Carlos; Escriche, Lluis; Casabó, Jaume; Capelo, José Luis; Covelo, Berta; Kivekäs, Raikko; Sillanpää, Reijo


    The complexation properties toward Hg(II) of six macrocyclic ligands, 3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L1), 7-(9-anthracenylmethyl)-3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L2), 7-(10-methyl-9-anthracenylmethyl)-3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L3), 7,7'-[9,10-anthracenediylbis(methylene)]bis-3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L4), 1,4,7-trithia-11-azacyclotetradecane (L5), and 11,-(anthracen-9-ylmethyl)-1,4,7-trithia-11-azacyclotetradecane (L6), were studied. The stoichiometries of the formed species were determined from absorption and fluorescence titrations. In these anthracene-containing macrocycles, a fluorescent quenching of the emission was found upon Hg(II) addition. The X-ray crystal structure of [HgCl2(L2)] x 1/2CH2Cl2 was determined. The asymmetric unit contains two independent [HgCl2(L2)] molecules and one dichloromethane molecule. Each Hg(II) ion is coordinated by the pyridine nitrogen, the two sulfur atoms of one L2 molecule, and two chloride ions. Analytical studies using solvent extraction separation of Hg(II) from aqueous solutions were performed to determine the Hg(II) extraction capability of ligands L1, L2, and L5.

  2. Lanthanide complexes of macrocyclic polyoxovanadates by VO4 units: synthesis, characterization, and structure elucidation by X-ray crystallography and EXAFS spectroscopy. (United States)

    Nishio, Masaki; Inami, Shinnosuke; Katayama, Misaki; Ozutsumi, Kazuhiko; Hayashi, Yoshihito


    Reactions of a tetravanadate anion, [V(4)O(12)](4-), with a series of lanthanide(III) salts yield three types of lanthanide complexes of macrocyclic polyoxovanadates: (Et(4)N)(6)[Ln(III)V(9)O(27)] [Ln = Nd (1), Sm (2), Eu (3), Gd (4), Tb (5), Dy (6)], (Et(4)N)(5)[(H(2)O)Ho(III)(V(4)O(12))(2)] (7), and (Et(4)N)(7)[Ln(III)V(10)O(30)] [Ln = Er (8), Tm (9), Yb (10), Lu (11)]. Lanthanide complexes 1-11 are isolated and characterized by IR, elemental analysis, single-crystal X-ray diffraction, and extended X-ray absorption fine structure spectroscopy (EXAFS). Lanthanide complexes 1-6 are composed of a square-antiprism eight-coordinated Ln(III) center with a macrocyclic polyoxovanadate that is constructed from nine VO(4) tetrahedra through vertex sharing. The structure of 7 is composed of a seven-coordinated Ho(III) center, which exhibits a capped trigonal-prism coordination environment by the sandwiching of two cyclic tetravanadates with a capping H(2)O ligand. Lanthanide complexes 8-11 have a six-coordinated Ln(III) center with a 10-membered vanadate ligand. The structural trend to adopt a larger coordination number for a larger lanthanide ion among the three types of structures is accompanied by a change in the vanadate ring sizes. These lanthanide complexes are examined by EXAFS spectroscopies on lanthanide L(III) absorption edges, and the EXAFS oscillations of each of the samples in the solid state and in acetonitrile are identical. The Ln-O and Ln···V bond lengths obtained from fits of the EXAFS data are consistent with the data from the single-crystal X-ray studies, reflecting retention of the structures in acetonitrile.

  3. Construction of metal-organic frameworks through coordination and hydrogen bonding interactions: Syntheses, structures and photoluminescent properties of metal complexes with macrocyclic ligand (United States)

    Ouyang, Xing-Mei; Li, Zhen-Wu; Okamura, Taka-aki; Li, Yi-Zhi; Sun, Wei-Yin; Tang, Wen-Xia; Ueyama, Norikazu


    A macrocyclic ligand L with two diethylenetriamine units linked by two rigid biphenylene spacers was used as building block for construction of metal-organic frameworks. A silver(I) complex with macrocyclic and open-chain mix-type ligands [Ag 2( L)( L')](ClO 4) 2 ( 1) [ L'=1,6-bis(4-imidazol-1'-ylmethylphenyl)-2,5-diazahexane] was obtained by reaction of L and L' together with AgClO 4·H 2O. It is interesting that the open-chain tetradentate ligand L' only served as a bidentate ligand to bridge the Ag 2L units into an infinite one-dimensional (1D) cationic chain. Neutral 1D chain coordination polymer [Cu 2( L)( μ-SO 4) 2]·3H 2O·3MeOH ( 2) is formed by sulfate bridges between the neighboring Cu 2L units. When L reacted with nickel(II) sulfate instead of copper(II) sulfate, a monomacrocycle molecular complex [Ni 2( L)(H 2O) 4(SO 4) 2] ( 3) was obtained in which the sulfate anion acts as monodentate ligands rather than as bridges. When Cd(II) salts were used for the reactions with L, another two neutral 1D coordination polymers, [Cd 2( L)( μ-Cl) 2Cl 2]·2H 2O ( 4) and [Cd 2( L)( μ-Br) 2Br 2] ( 5), with the same structure were isolated. All the synthesized complexes exhibit three-dimensional framework structures linked by various hydrogen bonds. The photoluminescent properties of the synthesized complexes were studied in the solid state at room temperature, and the Ag(I) and Cd(II) complexes were found to show strong blue luminescence.

  4. Cu(II) coordination chemistry of patellamide derivatives: possible biological functions of cyclic pseudopeptides. (United States)

    Comba, Peter; Dovalil, Nina; Gahan, Lawrence R; Haberhauer, Gebhard; Hanson, Graeme R; Noble, Christopher J; Seibold, Björn; Vadivelu, Prabha


    Two synthetic derivatives of the naturally occurring cyclic pseudooctapeptides patellamide  A-F and ascidiacyclamide, that is, H(4)pat(2), H(4)pat(3), as well as their Cu(II) complexes are described. These cyclic peptide derivatives differ from the naturally occurring macrocycles by the variation of the incorporated heterocyclic donor groups and the configuration of the amino acids connecting the heterocycles. The exchange of the oxazoline and thiazole groups by dimethylimidazoles or methyloxazoles leads to more rigid macrocycles, and the changes in the configuration of the side chains leads to significant differences in the folding of the cyclic peptides. These variations allow a detailed study of the various possible structural changes on the chemistry of the Cu(II) complexes formed. The coordination of Cu(II) with these macrocyclic species was monitored by high-resolution electrospray mass spectrometry (ESI-MS), spectrophotometric (UV/Vis) and circular dichroic (CD) titrations, and electron paramagnetic resonance (EPR) spectroscopy. Density functional theory (DFT) calculations and molecular mechanics (MM) simulations have been used to model the structures of the Cu(II) complexes and provide a detailed understanding of their geometric preferences and conformational flexibility. This is related to the Cu(II) coordination chemistry and the reactivity of the dinuclear Cu(II) complexes towards CO(2) fixation. The variation observed between the natural and various synthetic peptide systems enables conclusions about structure-reactivity correlations, and our results also provide information on why nature might have chosen oxazolines and thiazoles as incorporated heterocycles.

  5. Synthesis, structural, spectral, thermal and antimicrobial studies of palladium(II), platinum(II), ruthenium(III) and iridium(III) complexes derived from N,N,N,N-tetradentate macrocyclic ligand. (United States)

    Rani, Soni; Kumar, Sumit; Chandra, Sulekh


    Palladium(II), platinum(II), ruthenium(III) and iridium(III) complexes of general stoichiometry [PdL]Cl(2), [PtL]Cl(2), [Ru(L)Cl(2)]Cl and [Ir(L)Cl(2)]Cl are synthesized with a tetradentate macrocyclic ligand, derived from 2,6-diaminopyridine with 3-ethyl 2,4-pentanedione. Ligand was characterized on the basis of elemental analyses, IR, mass, and (1)H NMR and (13)C NMR spectral studies. All the complexes were characterized by elemental analyses, molar conductance measurements, magnetic susceptibility measurements, IR, mass, electronic spectral techniques and thermal studies. The value of magnetic moments indicates that all the complexes are diamagnetic except Ru(III) complex which shows magnetic moments corresponding its one unpaired electron. The macrocyclic ligand and all its metal complexes were also evaluated in vitro against some plant pathogenic fungi and bacteria to assess their biocidal properties.

  6. Template Synthesis of a Tetraaza Macrocycle Which Involves Benzaldehyde Rather Than Formaldehyde as a Building Block. Isolation and Structure Determination of the Open-Chain Schiff Base Intermediate Complex. (United States)

    Fabbrizzi, Luigi; Licchelli, Maurizio; Manotti Lanfredi, Anna Maria; Vassalli, Omar; Ugozzoli, Franco


    The classical formaldehyde building block has been replaced by the bulkier benzaldehyde in the Cu(II) template synthesis of the cyclam-like tetraaza macrocycle of type 1, in which nitroethane operated as locking fragment. The synthetic pathway involves three distinct steps: (i) Schiff base condensation of the metal-free open-chain tetramine; (ii) Cu(II) coordination and preorientation of the Schiff base; (iii) nucleophilic attack by the deprotonated nitroethane fragment and formation of the macrocyclic complex. Both the Schiff base Cu(II) complex and the Cu(II) macrocyclic complex were isolated in a crystalline form and their molecular structures were determined: {N-[2-((E)-benzylideneamino)ethyl]-N'-[2-((Z)-benzylideneamino)ethyl]propane-1,3-diamine}copper(II) nitrate: triclinic, space group P&onemacr;, with a = 12.296(5) Å, b = 10.787(6) Å, c = 10.547(7) Å, V = 1161(1) Å(3), and Z = 2 (R = 0.055, R(w) = 0.061); [(5R,6S,7S)-6-methyl-6-nitro-5,7-diphenyl-1,4,8,11-tetraazacyclotetradecane]copper(II) perchlorate: monoclinic, space group P2(1)/n, with a = 15.246(5) Å, b = 23240(7) Å, c = 8.540(4) Å, V = 2980(2) Å(3), and Z = 4 (R = 0.095, R(w) = 0.095). This allowed us to define mechanistic details of the macrocyclization process. It is suggested that the same three-step pathway takes place in the much easier and faster one-pot template syntheses of cyclam-like macrocyles, which involve formaldehyde as a building block.

  7. Asymmetric Synthesis of Natural Macrocyclic Diterpene(+)-Methyl Cembra-1,3,7,11-tetraene-16-carboxynate%(+)-Methyl Cembra-1,3,7,11-tetraene-16-carboxynate的不对称合成研究

    Institute of Scientific and Technical Information of China (English)

    孙彬; 梅天胜; 刘佐胜; 李裕林; 李瀛; 彭立增


    The first asymmetric synthesis of (+)-methyl cembra-1,3,7,11-tetraene-16-carboxynate, a naturally occurring cembrane-type macrocyclic diterpene isolated from Sinularia mayi, was achieved via general approach by employing an intramolecular McMurry coupling and Sharpless asymmetric epoxidation as the key steps from readily available starting materials. The synthesis presented here verifies that the absolute configuration of compound 1 was assumed as 15R.

  8. Synthesis, Structure, and Molecular Recognition of S6 - and (SO2 )6 -Corona[6](het)arenes: Control of Macrocyclic Conformation and Properties by the Oxidation State of the Bridging Heteroatoms. (United States)

    Guo, Qing-Hui; Zhao, Liang; Wang, Mei-Xiang


    We report herein the synthesis, structure, and molecular recognition of S6 - and (SO2 )6 -corona[6](het)arenes, and demonstrate a unique and efficient strategy of regulating macrocyclic conformation and properties by adjusting the oxidation state of the heteroatom linkages. The one-pot nucleophilic aromatic substitution reaction of 1,4-benzenedithiol derivatives, biphenyl-4,4'-dithiol and 9,9-dipropyl-9H-fluorene-2,7-dithiol with 3,6-dichlorotetrazine afforded S6 -corona[3]arene[3]tetrazines. These compounds underwent inverse-electron-demand Diels-Alder reaction with enamines and norbornadiene to produce S6 -corona[3]arene[3]pyridazines. Facile oxidation of sulfide linkages yielded (SO2 )6 -corona[3]arene[3]pyridazines. All corona[6](het)arenes adopted generally hexagonal macrocyclic ring structures; however, their electronic properties and conformation could be fine-tuned by altering the oxidation state of the sulfur linkages. Whereas (SO2 )6 -corona[3]arene[3]pyridazines were electron-deficient, S6 -corona[3]arene[3]pyridazines acted as electron-rich macrocyclic hosts that recognized various organic cations in both aqueous and organic solutions.

  9. Curiouser and Curiouser: The Macrocyclic Lactone, Abamectin, Is also a Potent Inhibitor of Pyrantel/Tribendimidine Nicotinic Acetylcholine Receptors of Gastro-Intestinal Worms.

    Directory of Open Access Journals (Sweden)

    Melanie Abongwa

    Full Text Available Nematode parasites may be controlled with drugs, but their regular application has given rise to concerns about the development of resistance. Drug combinations may be more effective than single drugs and delay the onset of resistance. A combination of the nicotinic antagonist, derquantel, and the macrocyclic lactone, abamectin, has been found to have synergistic anthelmintic effects against gastro-intestinal nematode parasites. We have observed in previous contraction and electrophysiological experiments that derquantel is a potent selective antagonist of nematode parasite muscle nicotinic receptors; and that abamectin is an inhibitor of the same nicotinic receptors. To explore these inhibitory effects further, we expressed muscle nicotinic receptors of the nodular worm, Oesophagostomum dentatum (Ode-UNC-29:Ode-UNC-63:Ode-UNC-38, in Xenopus oocytes under voltage-clamp and tested effects of abamectin on pyrantel and acetylcholine responses. The receptors were antagonized by 0.03 μM abamectin in a non-competitive manner (reduced Rmax, no change in EC50. This antagonism increased when abamectin was increased to 0.1 μM. However, when we increased the concentration of abamectin further to 0.3 μM, 1 μM or 10 μM, we found that the antagonism decreased and was less than with 0.1 μM abamectin. The bi-phasic effects of abamectin suggest that abamectin acts at two allosteric sites: one high affinity negative allosteric (NAM site causing antagonism, and another lower affinity positive allosteric (PAM site causing a reduction in antagonism. We also tested the effects of 0.1 μM derquantel alone and in combination with 0.3 μM abamectin. We found that derquantel on these receptors, like abamectin, acted as a non-competitive antagonist, and that the combination of derquantel and abamectin produced greater inhibition. These observations confirm the antagonistic effects of abamectin on nematode nicotinic receptors in addition to GluCl effects, and

  10. Curiouser and Curiouser: The Macrocyclic Lactone, Abamectin, Is also a Potent Inhibitor of Pyrantel/Tribendimidine Nicotinic Acetylcholine Receptors of Gastro-Intestinal Worms. (United States)

    Abongwa, Melanie; Buxton, Samuel K; Robertson, Alan P; Martin, Richard J


    Nematode parasites may be controlled with drugs, but their regular application has given rise to concerns about the development of resistance. Drug combinations may be more effective than single drugs and delay the onset of resistance. A combination of the nicotinic antagonist, derquantel, and the macrocyclic lactone, abamectin, has been found to have synergistic anthelmintic effects against gastro-intestinal nematode parasites. We have observed in previous contraction and electrophysiological experiments that derquantel is a potent selective antagonist of nematode parasite muscle nicotinic receptors; and that abamectin is an inhibitor of the same nicotinic receptors. To explore these inhibitory effects further, we expressed muscle nicotinic receptors of the nodular worm, Oesophagostomum dentatum (Ode-UNC-29:Ode-UNC-63:Ode-UNC-38), in Xenopus oocytes under voltage-clamp and tested effects of abamectin on pyrantel and acetylcholine responses. The receptors were antagonized by 0.03 μM abamectin in a non-competitive manner (reduced Rmax, no change in EC50). This antagonism increased when abamectin was increased to 0.1 μM. However, when we increased the concentration of abamectin further to 0.3 μM, 1 μM or 10 μM, we found that the antagonism decreased and was less than with 0.1 μM abamectin. The bi-phasic effects of abamectin suggest that abamectin acts at two allosteric sites: one high affinity negative allosteric (NAM) site causing antagonism, and another lower affinity positive allosteric (PAM) site causing a reduction in antagonism. We also tested the effects of 0.1 μM derquantel alone and in combination with 0.3 μM abamectin. We found that derquantel on these receptors, like abamectin, acted as a non-competitive antagonist, and that the combination of derquantel and abamectin produced greater inhibition. These observations confirm the antagonistic effects of abamectin on nematode nicotinic receptors in addition to GluCl effects, and illustrate more complex

  11. Development and validation of a method for the determination of low-ppb levels of macrocyclic lactones in butter, using HPLC-fluorescence. (United States)

    Macedo, Fabio; Marsico, Eliane Teixeira; Conte-Júnior, Carlos Adam; de Resende, Michele Fabri; Brasil, Taila Figueiredo; Pereira Netto, Annibal Duarte


    An analytical method was developed and validated for the simultaneous determination of four macrocyclic lactones (ML) (abamectin, doramectin, ivermectin and moxidectin) in butter, using liquid chromatography with fluorescence detection. The method employed heated liquid-liquid extraction and a mixture of acetonitrile, ethyl acetate and water, with preconcentration and derivatization, to produce stable fluorescent derivatives. The chromatographic run time was validation followed international guidelines and employed fortified butter samples. The figures of merit obtained, e.g. recovery (72.4-106.5%), repeatability (8.8%), within-laboratory reproducibility (15.7%) and limits of quantification (0.09-0.16 μg kg(-1)) were satisfactory for the desired application. The application of the method to real samples showed that ML residues were present in six of the ten samples evaluated. The method proved to be simple, easy and appropriate for simultaneous determination of ML residues in butter. To our knowledge, this is the first method described for the evaluation of ML in butter.

  12. One-Dimensional Hydrogen-Bonded Infinite Chain from Nickel(II Tetraaza Macrocyclic Complex and 1,2-Cyclopentanedicarboxylate Ligand

    Directory of Open Access Journals (Sweden)

    Ki-Young Choi


    Full Text Available The reaction of [Ni(L]Cl2·2H2O (L = 3,14-dimethyl-2,6,13,17-tetraazatricyclo [14,4,01.18,07.12]docosane with trans-1,2-cyclopentanedicarboxylic acid (H2-cpdc yields a 1D hydrogen-bonded infinite chain with formula [Ni(L(H-cpdc-2] (1. This complex has been characterized by X-ray crystallography, spectroscopy and cyclic voltammetry. The crystal structure of 1 exhibits a distorted octahedral geometry about Ni atom with four nitrogen atoms of the macrocycle and two oxygen atoms of the H-cpdc- ligand at the axial position. Compound 1 crystallizes in the monoclinic system P21/c with a = 8.7429(17, b = 10.488(2, c = 18.929(4 Å, β = 91.82(2, V = 1734.8(6 Å3, Z = 2. Electronic spectrum of 1 reveals a high-spin octahedral environment. Cyclic voltammetry of 1 undergoes two waves of a one-electron transfer corresponding to NiII/NiIII and NiII/NiI processes.

  13. Synthesis, Characterization and Antitumor Activities of Co, Ni, Cu, Zn Complexes with 1,4,7,10- tetrakis (4- nitrobenzyl )- 1,4,7,10- tetraazacyclododecane Macrocyclic Ligand

    Institute of Scientific and Technical Information of China (English)

    孔德源; 谢雨礼; 谢毓元; 黄小荧


    New tetraazamacrocyclic ligand with 1, 4, 7, 10-tetrakis (4-nitrobenzyl) pendent groups (C36H40N8O8, Mr= 712.76) crystallized in the monoclinic system, P21/n space group with unit cell parameters: a=7. 834(2), b=22. 902(6), c =10. 147(3)A, β=106.53(2)°, V=1745(1)A3, Z=2, Dc=1. 356 g/cm3, λ(MoKa)=0. 71069 A ; μ=0. 92cm-1, F(000)=752, T=296K. The final R and Rw values are 0.065 and 0.066, respectively. The Cu( Ⅱ ), Ni( Ⅱ ), Co( Ⅱ ), Zn( Ⅱ ) complexes with this new ligand have been synthesized and characterized by elemental analyses, IR, UV, ESI-MS and molar conductance. The macrocyclic ligand molecular structure is centrosymmetrical. All complexes are in accordance with the general forN8O8). The central metal ions coordinate to four nitrogen atoms of azamacrocycle and two oxygen atoms of one nitrate ion. Preliminary pharmacological tests against P-388and A-549 tumor cell lines showed that all these complexes had considerable activities in vitro.

  14. Synthesis and characterization of mono- and bimetallic complexes of Zn(II and Cu(II; new multifunctional unsymmetrical acyclic and macrocyclic phenol-based ligand

    Directory of Open Access Journals (Sweden)

    Hamid Golchoubian


    Full Text Available The dicompartmental macrocyclic ligand (L22- was prepared by [1:1] cyclic condensation of N,N′-dimethyacetate-N,N′-ethylene-di(5-methyl-3-formyl-2-hydroxybenzylamine with 1,3-diaminopropane. The ligand includes dissimilar N(amine2O2 and N(imine2O2 coordination sites sharing two phenolic oxygen atoms and containing two methyl acetate pedant arms on the amine nitrogen donor atoms. A series of mono- and bimetallic complexes were synthesized and characterized on the basis of elemental analysis, molar conductance measurement, IR and UV-Vis spectroscopy techniques. It was found that during the cyclization process the copper (II displaced from the N(amine2O2 to the N(imine2O2 coordination site and one of the methyl acetate pedant arms is dissociated. The heterodinuclear complex of [ZnL2Cu(-OAc]+ was prepared by a transmetallation reaction on the [ZnL2Zn(-OAc]+ by Cu(II. The characterization results showed that the two metal ions are bridged by two phenolic oxygen atoms and an acetate group, providing distorted five-coordination geometries for the both metal ions.

  15. Self-Assembly of a 1D Hydrogen-Bonded Polymer from a Hexamethyltetraaza Macrocyclic Nickel(II Complex and Isophthalic Acid

    Directory of Open Access Journals (Sweden)

    In-Taek Lim


    Full Text Available The compound [Ni(L(isoph2][Ni(L]·8H2O (1; L = C-meso-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane; H2-isoph = isophthalic acid has been synthesized and structurally characterized. Complex 1 exhibits a geometrically symmetric core with a {4/6} coordination number set. The coordination environment around the Ni(1 ion is a distorted octahedron, while the geometry around the four-coordinate Ni(2 is depicted as square planar in 1D hydrogen-bonded infinite chain. The compound crystallizes in the triclinic system P-1 with a = 8.602(2, b = 10.684(7, c = 16.550(3 Å, a = 91.04(4, b = 94.09(2, g = 111.09(4°, V = 1413.9(10 Å3, Z = 1. The cyclic voltammogram of 1 undergoes one-electron wave corresponding to NiII/NiI process. The electronic spectra, electrochemical and TGA behavior of the complex are significantly affected by the nature of the hexamethyltetraaza macrocycle and the axial isoph2− ligand.

  16. The macrocyclic peptide antibiotic micrococcin P(1) is secreted by the food-borne bacterium Staphylococcus equorum WS 2733 and inhibits Listeria monocytogenes on soft cheese. (United States)

    Carnio, M C; Höltzel, A; Rudolf, M; Henle, T; Jung, G; Scherer, S


    Staphylococcus equorum WS 2733 was found to produce a substance exhibiting a bacteriostatic effect on a variety of gram-positive bacteria. The metabolite was purified to homogeneity by ammonium sulfate precipitation and semipreparative reversed-phase high-performance liquid chromatography. Electrospray mass spectrometry confirmed the high purity of the compound and revealed a molecular mass of 1,143 Da. By two-dimensional nuclear magnetic resonance spectroscopy the substance was identified as micrococcin P(1) which is a macrocyclic peptide antibiotic that has not yet been reported for the genus Staphylococcus. A total of 95 out of 95 Listeria strains and 130 out of 135 other gram-positive bacteria were inhibited by this substance, while none of 37 gram-negative bacteria were affected. The antilisterial potential of this food-grade strain as a protective starter culture was evaluated by its in situ application in cheese-ripening experiments under laboratory conditions. A remarkable growth reduction of Listeria monocytogenes could be achieved compared to control cheese ripened with a nonbacteriocinogenic type strain of Staphylococcus equorum. In order to prove that inhibition was due to micrococcin P(1), a micrococcin-deficient mutant was constructed which did not inhibit L. monocytogenes in cheese-ripening experiments.

  17. The Macrocyclic Peptide Antibiotic Micrococcin P1 Is Secreted by the Food-Borne Bacterium Staphylococcus equorum WS 2733 and Inhibits Listeria monocytogenes on Soft Cheese (United States)

    Carnio, Markus C.; Höltzel, Alexandra; Rudolf, Melanie; Henle, Thomas; Jung, Günther; Scherer, Siegfried


    Staphylococcus equorum WS 2733 was found to produce a substance exhibiting a bacteriostatic effect on a variety of gram-positive bacteria. The metabolite was purified to homogeneity by ammonium sulfate precipitation and semipreparative reversed-phase high-performance liquid chromatography. Electrospray mass spectrometry confirmed the high purity of the compound and revealed a molecular mass of 1,143 Da. By two-dimensional nuclear magnetic resonance spectroscopy the substance was identified as micrococcin P1 which is a macrocyclic peptide antibiotic that has not yet been reported for the genus Staphylococcus. A total of 95 out of 95 Listeria strains and 130 out of 135 other gram-positive bacteria were inhibited by this substance, while none of 37 gram-negative bacteria were affected. The antilisterial potential of this food-grade strain as a protective starter culture was evaluated by its in situ application in cheese-ripening experiments under laboratory conditions. A remarkable growth reduction of Listeria monocytogenes could be achieved compared to control cheese ripened with a nonbacteriocinogenic type strain of Staphylococcus equorum. In order to prove that inhibition was due to micrococcin P1, a micrococcin-deficient mutant was constructed which did not inhibit L. monocytogenes in cheese-ripening experiments. PMID:10831414

  18. Graphene supported Co-g-C3N4 as a novel metal-macrocyclic electrocatalyst for the oxygen reduction reaction in fuel cells. (United States)

    Liu, Qiao; Zhang, Junyan


    Graphitic carbon nitride (g-C3N4) polymer was doped with cobalt species and supported on a similar sp(2) structure graphene, to form a novel nitrogen-metal macrocyclic catalyst for the oxygen reduction reaction (ORR) in alkaline fuel cells. The structural characterizations confirmed the formation of Co-N bonds and the close electron coupling between Co-g-C3N4 and graphene sheets. The electrocatalytic measurements demonstrated Co-g-C3N4-catalyzed reduction of oxygen mainly in a four electron pathway. The improvement of ORR activity is closely related to the abundant accessible Co-Nx active sites and fast charge transfer at the interfaces of Co-g-C3N4/graphene. Also, Co-g-C3N4@graphene exhibited comparable ORR activity, better durability, and methanol tolerance ability in comparison to Pt/C, and bodes well for a promising non-noble cathode catalyst for the application of direct methanol fuel cells. The chemical doping strategy in this work would be helpful to improve other present catalysts for fuel cell applications.

  19. Blue copper protein analogue: synthesis and characterization of copper complexes of the N2S2 macrocycle 1,8-dithia-4,11-diazacyclotetradecane. (United States)

    Walker, Tia L; Mula, Sam; Malasi, Wilhelm; Engle, James T; Ziegler, Christopher J; van der Est, Art; Modarelli, Jody; Taschner, Michael J


    To improve understanding of copper at the active site of Type 1 copper proteins, Cu(I) and Cu(II) complexes of 1,8-dithia-4,11-diazacyclotetradecane, shown in , have been successfully isolated and structurally characterized by X-ray crystallography. In these compounds, both Cu(I) and Cu(II) are centered in the plane of the macrocycle containing two sulphur and two nitrogen heteroatoms comprising the distorted tetrahedral/square planar coordination geometry. The UV/VIS spectra, electrochemistry and EPR properties have been obtained for the Cu(II) complex 2. Three absorption bands at 295 nm, 354 nm, and 545 nm are observed in aqueous solution at a pH of 5. These bands have been assigned to the N → Cu(II) and S → Cu(II) charge transfer bands and the d-d transitions respectively. The Cu(I/II) redox midpoint potential of complex 2 in CH3CN is +403 mV versus NHE.

  20. Total synthesis and biological evaluation of a series of macrocyclic hybrids and analogues of the antimitotic natural products dictyostatin, discodermolide, and taxol. (United States)

    Paterson, Ian; Naylor, Guy J; Gardner, Nicola M; Guzmán, Esther; Wright, Amy E


    The design, synthesis, and biological evaluation of a series of hybrids and analogues of the microtubule-stabilizing anticancer agents dictyostatin, discodermolide, and taxol is described. A 22-membered macrolide scaffold was prepared by adapting earlier synthetic routes directed towards dictyostatin and discodermolide, taking advantage of the distinctive structural and stereochemical similarities between these two polyketide-derived marine natural products. Initial endeavors towards accessing novel discodermolide/dictyostatin hybrids led to the adoption of a late-stage diversification strategy and the construction of a small library of methyl-ether derivatives, along with the first triple hybrids bearing the side-chain of taxol or taxotere attached through an ester linkage. Biological assays of the anti-proliferative activity of these compounds in a series of human cancer cell lines, including the taxol-resistant NCI/ADR-Res cell line, allowed the proposal of various structure-activity relationships. This led to the identification of a potent macrocyclic discodermolide/dictyostatin hybrid 12 and its C9 methoxy derivative 38, accessible by an efficient total synthesis and with a similar biological profile to dictyostatin.

  1. Gd complexes of macrocyclic diethylenetriaminepentaacetic acid (DTPA) biphenyl-2,2'-bisamides as strong blood-pool magnetic resonance imaging contrast agents. (United States)

    Jung, Ki-Hye; Kim, Hee-Kyung; Lee, Gang Ho; Kang, Duk-Sik; Park, Ji-Ae; Kim, Kyeong Min; Chang, Yongmin; Kim, Tae-Jeong


    We report the synthesis of macrocyclic DTPA conjugates of 2,2'-diaminobiphenyl and their Gd complexes of the type [Gd(L)(H(2)O)]·xH(2)O (2a,b; L = 1a,b) for use as new MRI blood-pool contrast agents (MRI BPCAs). Pharmacokinetic inertness of 2 compares well with those of analogous Gd-DTPA MRI CAs currently in use. The present system also shows very high stability in human serum. The R(1) relaxivity reaches 10.9 mM(-1) s(-1), which is approximately 3 times as high as that of structurally related Gd-DOTA (R(1) = 3.7 mM(-1) s(-1)). The R(1) relaxivity in HSA goes up to 37.2 mM(-1) s(-1), which is almost twice as high as that of MS-325, a leading BPCA, demonstrating a strong blood pool effect. The in vivo MR images of mice obtained with 2b are coherent, showing strong signal enhancement in heart, abdominal aorta, and small vessels. Even the brain tumor is vividly enhanced for an extended period of time. The structural uniqueness of 2 is that it is neutral in charge and thus makes no resort to electrostatic interaction, supposedly one of the essential factors for the blood-pool effect.

  2. Hyperpolarized 89Y NMR spectroscopic detection of yttrium ion and DOTA macrocyclic ligand complexation: pH dependence and Y-DOTA intermediates (United States)

    Ferguson, Sarah; Kiswandhi, Andhika; Niedbalski, Peter; Parish, Christopher; Kovacs, Zoltan; Lumata, Lloyd

    Dissolution dynamic nuclear polarization (DNP) is a rapidly emerging physics technique used to enhance the signal strength in nuclear magnetic resonance (NMR) and imaging (MRI) experiments for nuclear spins such as yttrium-89 by >10,000-fold. One of the most common and stable MRI contrast agents used in the clinic is Gd-DOTA. In this work, we have investigated the binding of the yttrium and DOTA ligand as a model for complexation of Gd ion and DOTA ligand. The macrocyclic ligand DOTA is special because its complexation with lanthanide ions such as Gd3+ or Y3+ is highly pH dependent. Using this physics technology, we have tracked the complexation kinetics of hyperpolarized Y-triflate and DOTA ligand in real-time and detected the Y-DOTA intermediates. Different kinds of buffers were used (lactate, acetate, citrate, oxalate) and the pseudo-first order complexation kinetic calculations will be discussed. The authors would like to acknowledge the support by US Dept of Defense Award No. W81XWH-14-1-0048 and Robert A. Welch Foundation Grant No. AT-1877.

  3. Study of behaviour of Ni(III) macrocyclic complexes in acidic aqueous medium through kinetic measurement involving hydrogen peroxide oxidation and DFT calculations

    Indian Academy of Sciences (India)



    The Cu(II) ion-catalysed kinetics of oxidation of H ₂O ₂ by [NiIIIL] [where L = L₁ (cyclam) and L ₂ (1,8-bis(2-hydroxyethyl)-1,3,6,8,10,13-hexaazacyclotetradecane)] was studied in the pH range of 3.6–5.6 in acetic acid-acetate buffer medium at 25◦C in the presence of sulphate ion. The ionic strength (I) was maintained at 0.5 M (NaClO₄). The rate constants showed an inverse acid dependence and [NiIIIL ₂] was observed to be more stable than [NiIIIL₁]. The rate of the reaction of both complexes with hydrogen peroxide shows contrastingbehaviour at pH > 2.5 when compared to the same reaction in perchloric acid medium. DFT calculations performed on the complexes [NiIIIL₁ (SO₄)(OAc)] and [NiIIIL ₂ (SO₄)(OAc)] reveal that both the acetate and sulphate ligands are axially coordinated to the metal centre. In addition, there is strong hydrogen bonding between the axial ligand and NH hydrogen of the macrocyclic ligand. The computed covalent bond ordersin the aqueous medium predict that the acetate forms stronger coordinate bond with Ni ion than the sulphate ligand. The hydroxyl group present in one of the pendant groups of L ₂ forms a strong hydrogen bond with thesulphate ligand which leads to additional stability in [NiIIIL ₂ (SO₄)(OAc)].

  4. High efficiency, narrow particle size distribution, sub-2 μm based macrocyclic glycopeptide chiral stationary phases in HPLC and SFC. (United States)

    Barhate, Chandan L; Wahab, M Farooq; Breitbach, Zachary S; Bell, David S; Armstrong, Daniel W


    State of the art chiral chromatography still employs 3-5 μm bonded or immobilized chiral selectors in 10-25 cm columns. With the availability of 1.9 μm narrow particle size distribution (NPSD) silica, it is now possible to make ever shorter, high efficiency columns practical for sub-minute chiral separations. Three macrocyclic glycopeptides (teicoplanin, teicoplanin aglycone, and vancomycin) were bonded onto 1.9 μm NPSD particles. Such packed columns had ∼80% lower backpressure as compared to polydisperse (PD) 1.7 μm silica materials when using the same mobile phase. The decreased backpressure allowed for diminution of frictional heating and allowed for the use of the 1.9 μm NPSD particle based columns at high flow rates. The 1.9 μm NPSD particle based columns showed up to 190,000 plates m(-1) for chiral molecules and 210,000 plates m(-1) for achiral probes. Representative enantiomeric separations are shown for wide classes of compounds, including different types of amino acids, β-blockers, and pharmaceutically important heterocyclic compounds such as oxazolidinones. Applications in three liquid chromatography modes, namely, reversed phase, polar organic mode and normal phase chiral separations were shown with resolution values ranging from 1.5 to 5.7. Additionally, the same columns were used with supercritical fluid chromatography (SFC) for ultrafast separations.

  5. Indicators of speed and explosive strength in the pre-season of annual macrocycle of young male and female weightlifters of the different groups of weight categories

    Directory of Open Access Journals (Sweden)

    Lutovinov Iu.A.


    Full Text Available Here is the indicators of speed and explosive strength in the pre-season of annual macrocycle of young male and female weightlifters of the different groups of weight categories who are training for the Championship of Ukraine. 40 young male and 12 female sportsman has taken part in investigation. Age of sportsman is 15 years old. The correlation of height indicator of standing high-jump (Abalakov jump and body weight indicator of sportsman weightlifters was analyzed. The interconnection of indicators of body weight and length of sportsman weightlifters alongside with the indicators of spring, speed as well as speed and power abilities of the different groups of weight categories was given. It was analyzed that the indicators of standing high-jump (Abalakov jump, standing long-jump and 30-meter sprint of sportsman are tend to grow by 11.5 %, 3.9 % and 2.7%, respectively, in the pre-season with an increase of weight category groups. The comparison of indicators of spring, speed as well as speed and power abilities of sportsman weightlifters was estimated.

  6. A ditopic O(4)S(2) macrocycle and its hard, soft, and hard/soft metal complexes exhibiting endo-, exo-, or endo/exocyclic coordination: synthesis, crystal structures, NMR titration, and physical properties. (United States)

    Ryu, Hyunsoo; Park, Ki-Min; Ikeda, Mari; Habata, Yoichi; Lee, Shim Sung


    A 20-membered O4S2 macrocycle (L(2)) was synthesized as a ditopic ligating system toward hard and soft metal ions simultaneously. Five complexes (3-7) of L(2) with different structures and coordination modes, including discrete to infinite forms, mono- to heteronuclear, and endo- to exo- and endo/exocoordination, were prepared and structurally characterized. First, the reaction of L(2) with Pb(ClO4)2·3H2O afforded a typical endocyclic mononuclear perchlorato complex [Pb(L(2))(ClO4)2] (3) in which one lead(II) is surrounded by the macrocycle adopting a "tight and bent" conformation. Meanwhile, the reaction with a softer metal salt AgNO3 resulted in the formation of the dinuclear bis(macrocycle) complex [Ag2(L(2))2(NO3)2] (4) in which two exocyclic silver(I) ions are doubly linked by two nitrate ions. The treatment of L(2) with CuI gave a mixture of the exocyclic monomer complex [Cu(L(2))I] (5) and the exocyclic dimer complex [(Cu2I2)(L(2))2] (6), which were separated manually because of their brick and rhomboid shapes of the crystals, respectively. Furthermore, the reaction of L(2) with a mixture of CuI and NaI afforded a photoluminescent heteronuclear complex [Na2(Cu6I8)(L(2))2(CH3CN)4]n (7) in the endo/exocyclic coordination mode. In this case, the endocyclic sodium(I) complex units are linked by the double-open cubanes-type cluster Cu6I8, yielding a two-dimensional network. The structural and binding properties of the complex of L(2) with silver(I) nitrate in solution were monitored by the NMR titration. Photophysical and thermal properties for complex 7 were also investigated and discussed.

  7. Novel PVC-membrane potentiometric sensors based on a recently synthesized sulfur-containing macrocyclic diamide for Cd2+ ion. Application to flow-injection potentiometry. (United States)

    Shamsipur, Mojtaba; Dezaki, Abbas Shirmardi; Akhond, Morteza; Sharghi, Hashem; Paziraee, Zahra; Alizadeh, Kamal


    A new sulfur-containing macrocyclic diamide, 1,15-diaza-3,4,12,13-dibenzo-5,11-dithia-8-oxa-1,15-(2,6-pyrido)cyclooctadecan-2,14-dione, L, was synthesized, characterized and used as an active component for fabrication of PVC-based polymeric membrane (PME), coated graphite (CGE) and coated silver wire electrodes (CWE) for sensing Cd(2+) ion. The electrodes exhibited linear Nernstian responses to Cd(2+) ion in the concentration range of 3.3 x 10(-6) to 3.3 x 10(-1)M (for PME, LOD=1.2 x 10(-6)M), 2.0 x 10(-7) to 3.3 x 10(-1)M (for CWE, LOD=1.3 x 10(-7)M) and 1.6 x 10(-8) to 1.3 x 10(-1)M (for CGE, LOD=1.0 x 10(-8)M). The CGE was used as a proper detection system in flow-injection potentiometry (FIP) with a linear Nernstian range of 3.2 x 10(-8) to 1.4 x 10(-1)M (LOD=1.3 x 10(-8)M). The optimum pH range was 3.5-7.6. The electrodes revealed fairly good discriminating ability towards Cd(2+) in comparison with a large number of alkali, alkaline earth, transition and heavy metal ions. The electrodes found to be chemically inert, showing a fast response time of <5s, and could be used practically over a period of about 2-3 months. The practical utility of the proposed system has also been reported.

  8. Multi-seasonal barnacle (Balanus improvisus) protection achieved by trace amounts of a macrocyclic lactone (ivermectin) included in rosin-based coatings. (United States)

    Pinori, Emiliano; Berglin, Mattias; Brive, Lena M; Hulander, Mats; Dahlström, Mia; Elwing, Hans


    Rosin-based coatings loaded with 0.1% (w/v) ivermectin were found to be effective in preventing colonization by barnacles (Balanus improvisus) both on test panels as well as on yachts for at least two fouling seasons. The leaching rate of ivermectin was determined by mass-spectroscopy (LC/MS-MS) to be 0.7 ng cm(-2) day(-1). This low leaching rate, as deduced from the Higuchi model, is a result of the low loading, low water solubility, high affinity to the matrix and high molar volume of the model biocide. Comparison of ivermectin and control areas of panels immersed in the field showed undisturbed colonisation of barnacles after immersion for 35 days. After 73 days the mean barnacle base plate area on the controls was 13 mm(2), while on the ivermectin coating it was 3 mm(2). After 388 days, no barnacles were observed on the ivermectin coating while the barnacles on the control coating had reached a mean of 60 mm(2). In another series of coated panels, ivermectin was dissolved in a cosolvent mixture of propylene glycol and glycerol formal prior to the addition to the paint base. This method further improved the anti-barnacle performance of the coatings. An increased release rate (3 ng cm(-2) day(-1)) and dispersion of ivermectin, determined by fluorescence microscopy, and decreased hardness of the coatings were the consequences of the cosolvent mixture in the paint. The antifouling mechanism of macrocyclic lactones, such as avermectins, needs to be clarified in further studies. Beside chronic intoxication as ivermectin is slowly released from the paint film even contact intoxication occurring inside the coatings, triggered by penetration of the coating by barnacles, is a possible explanation for the mode of action and this is under investigation.

  9. Measurement of macrocyclic trichothecene in floor dust of water-damaged buildings using gas chromatography/tandem mass spectrometry-dust matrix effects. (United States)

    Saito, Rena; Park, Ju-Hyeong; LeBouf, Ryan; Green, Brett J; Park, Yeonmi


    Gas chromatography-tandem mass spectrometry (GC-MS/MS) was used to detect fungal secondary metabolites. Detection of verrucarol, the hydrolysis product of Stachybotrys chartarum macrocyclic trichothecene (MCT), was confounded by matrix effects associated with heterogeneous indoor environmental samples. In this study, we examined the role of dust matrix effects associated with GC-MS/MS to better quantify verrucarol in dust as a measure of total MCT. The efficiency of the internal standard (ISTD, 1,12-dodecanediol), and application of a matrix-matched standard correction method in measuring MCT in floor dust of water-damaged buildings was additionally examined. Compared to verrucarol, ISTD had substantially higher matrix effects in the dust extracts. The results of the ISTD evaluation showed that without ISTD adjustment, there was a 280% ion enhancement in the dust extracts compared to neat solvent. The recovery of verrucarol was 94% when the matrix-matched standard curve without the ISTD was used. Using traditional calibration curves with ISTD adjustment, none of the 21 dust samples collected from water damaged buildings were detectable. In contrast, when the matrix-matched calibration curves without ISTD adjustment were used, 38% of samples were detectable. The study results suggest that floor dust of water-damaged buildings may contain MCT. However, the measured levels of MCT in dust using the GC-MS/MS method could be significantly under- or overestimated, depending on the matrix effects, the inappropriate ISTD, or combination of the two. Our study further shows that the routine application of matrix-matched calibration may prove useful in obtaining accurate measurements of MCT in dust derived from damp indoor environments, while no isotopically labeled verrucarol is available.

  10. Hepatitis C virus variants resistant to macrocyclic NS3-4A inhibitors subvert IFN-β induction by efficient MAVS cleavage. (United States)

    Welsch, Christoph; Haselow, Katrin; Gouttenoire, Jérôme; Schneider, Markus; Morikawa, Kenichi; Martinez, Yolanda; Susser, Simone; Sarrazin, Christoph; Zeuzem, Stefan; Antes, Iris; Moradpour, Darius; Lange, Christian M


    The hepatitis C virus (HCV) NS3-4A protease is essential for the HCV life cycle and a prime target of antiviral treatment strategies. Protease inhibitors, however, are limited by emergence of resistance-associated amino acid variants (RAVs). The capacity to cleave and inactivate mitochondrial antiviral-signaling protein (MAVS) in the RIG-I-signaling pathway is a cardinal feature of NS3-4A, by which HCV blocks induction of interferon-(IFN)-β, thereby promoting viral persistence. Here, we aimed to investigate the impact of NS3-4A RAVs on MAVS cleavage. The impact of NS3-4A RAVs on MAVS cleavage was assessed using immunoblot analyses, luciferase reporter assays and molecular dynamics simulations to study the underlying molecular principles. IFN-β was quantified in serum from patients with different NS3-4A RAVs. We show that macrocyclic NS3-4A RAVS with substitutions at residue D168 of the protease result in an increased capacity of NS3-4A to cleave MAVS and suppress IFN-β induction compared with a comprehensive panel of RAVs and wild type HCV. Mechanistically, we show the reconstitution of a tight network of electrostatic interactions between protease and the peptide substrate that allows much stronger binding of MAVS to D168 RAVs than to the wild-type protease. Accordingly, we could show IFN-β serum levels to be lower in patients with treatment failure due to the selection of D168 variants compared to R155 RAVs. Our data constitutes a proof of concept that the selection of RAVs against specific classes of direct antivirals can lead to the predominance of viral variants with possibly adverse pathogenic characteristics. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  11. Determination of cobalt ions at nano-level based on newly synthesized pendant armed macrocycle by polymeric membrane and coated graphite electrode. (United States)

    Singh, Ashok K; Singh, Prerna; Bhattacharjee, G


    Poly(vinylchloride) (PVC) based membranes of macrocycles 2,3,4:9,10,11-dipyridine-1,3,5,8,10,12-hexaazacyclotetradeca-2,9-diene (L(1)) and 2,3,4:9,10,11-dipyridine-1,5,8,12-tetramethylacrylate-1,3,5,8,10,12-hexaazacyclotetradeca-2,9-diene (L(2)) with NaTPB and KTpClPB as anion excluders and dibutylphthalate (DBP), benzyl acetate (BA), dioctylphthalate (DOP), o-nitrophenyloctyl ether (o-NPOE) and tri-n-butylphosphate (TBP) as plasticizing solvent mediators were prepared and investigated as Co(2+) selective electrodes. The best performance was observed with the membranes having the composition L(2):PVC:TBP:NaTPB in the ratio of 6:39:53:2 (w/w; mg). The performance of the membrane based on L(2) was compared with polymeric membrane electrode (PME) and coated graphite electrode (CGE). The PME exhibits detection limit of 4.7x10(-8)M with a Nernstian slope of 29.7 mV decade(-1) of activity between pH 2.5 and 8.5 whereas CGE exhibits the detection limit of 6.8x10(-9)M with a Nernstian slope of 29.5 mV decade(-1) of activity between pH 2.0 and 9.0. The response time for PME and CGE was found to be 11 and 8s, respectively. The CGE has been found to work satisfactorily in partially non-aqueous media up to 35% (v/v) content of methanol, ethanol and 25% (v/v) content of acetonitrile and could be used for a period of 4 months. The CGE was successfully applied for the determination of Co(2+) in real and pharmaceutical samples and as an indicator electrode in potentiometric titration of cobalt ion.

  12. Total Synthesis of Bryostatin 16 using a Pd-Catalyzed Diyne-Coupling as Macrocyclization Method and Synthesis of C20-epi-Bryostatin 7 as a Potent Anticancer Agent


    Trost, Barry M.; Dong, Guangbin


    Asymmetric total synthesis of bryostatin 16 was achieved in 26 steps in the longest linear sequence/39 total steps from aldehyde 10. A Pd-catalyzed alkyne-alkyne coupling was employed for the first-time as a macrocyclization method in a natural product synthesis. A route to convert bryostatin 16 to a new family of bryostatin analogues was developed. Toward the end, 20-epi-bryostatin 7, was synthesized from a bryostatin 16-like intermediate; and the key step involves a Re-catalyzed epoxidation...

  13. Total synthesis of bryostatin 16 using a Pd-catalyzed diyne coupling as macrocyclization method and synthesis of C20-epi-bryostatin 7 as a potent anticancer agent. (United States)

    Trost, Barry M; Dong, Guangbin


    Asymmetric total synthesis of bryostatin 16 was achieved in 26 steps in the longest linear sequence and in 39 total steps from aldehyde 10. A Pd-catalyzed alkyne-alkyne coupling was employed for the first time as a macrocyclization method in a natural product synthesis. A route to convert bryostatin 16 to a new family of bryostatin analogues was developed. Toward this end, 20-epi-bryostatin 7 was synthesized from a bryostatin 16-like intermediate; the key step involves a Re-catalyzed epoxidation/ring-opening reaction. Preliminary biological studies indicated that this new analogue exhibits nanomolar anti-cancer activity against several cancer cell lines.

  14. Total Synthesis of Bryostatin 16 using a Pd-Catalyzed Diyne-Coupling as Macrocyclization Method and Synthesis of C20-epi-Bryostatin 7 as a Potent Anticancer Agent (United States)

    Trost, Barry M.; Dong, Guangbin


    Asymmetric total synthesis of bryostatin 16 was achieved in 26 steps in the longest linear sequence/39 total steps from aldehyde 10. A Pd-catalyzed alkyne-alkyne coupling was employed for the first-time as a macrocyclization method in a natural product synthesis. A route to convert bryostatin 16 to a new family of bryostatin analogues was developed. Toward the end, 20-epi-bryostatin 7, was synthesized from a bryostatin 16-like intermediate; and the key step involves a Re-catalyzed epoxidation/ring-opening reaction. Preliminary biological studies indicated that this new analogue exhibits nanomolar anti-cancer activity against several cancer cell lines. PMID:21043491

  15. Le coton dans le monde, place du coton africain et principaux enjeux

    Directory of Open Access Journals (Sweden)

    Hofs JL.


    Full Text Available Cotton in the world, the position of African cotton and the major stakes. Cotton farming is a very old activity. More recently, cotton fi bre production impacted industrial history and allowed a tremendous rise of the textile industry. African cotton cropping, which mainly relies on rainfed agriculture, family farming and hand picking, is very different compared with the one conducted in large scale farming countries dealing with intensifi cation systems, irrigation and capital intensive management. An analysis of fundamentals of the world offer and demand for cotton initially highlights that China, UnitedStates, followed by India and Pakistan are major actors at the production level and count for more than two thirds of the worldvolumes. For several decades, the international cotton fibre consumption increased at an annual average rate that was very close to the one of the production. The main producers are also the main cotton consumers. Among them, China is the most important by far, absorbing more of the third of world consumption in 2004. This tendency will still clearly increase during next years. The large world cotton fi bre suppliers are, fi rst of all, the United States, followed by the African countries of FCFA zone. As most of the other agricultural basic commodities, the international cotton prices are characterized by a downward long-term trend. China has a strong incidence on this world market, because of its statute of fi rst producer and consumer.Production cost decrease noted in a great number of countries does not explain by itself price reduction. It is kept up with other factors: the subsidies granted by some countries to their cotton producers, in particular the United States. Cotton represents a substantial economic and social importance for the African countries which grow it, in particular those of fCFA zone. But, whereas cotton crop allowed these countries and their populations adopting undeniable socio-economic progress, it gives them nowadays a lot of trouble. Thus, after having suffered various crises during the last decades, African cotton chains are now confronted with a major crisis, without precedent by its extent. The stakes raised by cotton cropping in these African countries are numerous and complex. They constitute real challenges to be taken up. The main ones are underlined: competitive positionof African cotton in the world market; competition with synthetic fi bres; stakes of biotechnological crops; increase in the costsof the factors of production; aspects related to the quality of African cotton; diversifi cation of the productions; development ofnew cotton chains; local transformation of fi bre and valorisation of by-products; environmental concerns. In this context, we observe the emergence of African cotton farmer associations which are widening and investing, both in their own cotton chain and on the international scene, a new fi eld of infl uence.

  16. Principaux modèles utilisés en régression logistique

    Directory of Open Access Journals (Sweden)

    Gillet, A.


    Full Text Available Main models used in logistic regression. Regression is a commonly used technique for decribing the relationship between a response variable and one or more explanatory variables. When the response variable is a categorical variable, usual regression based on ordinary least squares should be replaced by logistic regression. Binary logistic regression should be used to perform a regression on a dichotomous response. Nominal polytomous logistic regression applies to a categorical response variable that has more than two levels with no natural ordering. And ordinal polytomous logistic regression is used when the response is a categorical variable that has more than two levels with a natural ordering. This note gives an overview of these logistic regression methods and describes three models commonly used when performing ordinal logistic regression. These models are illustrated by an example related to oak decline in the Walloon Region (Belgium.

  17. Petroleum in France: the main results in 2005; Petrole en France: les principaux resultats en 2005

    Energy Technology Data Exchange (ETDEWEB)



    This presentation takes stock on the petroleum market in France in 2005. It provides information on the petroleum consumption, the imports and exports, the prices, the production, the refineries and the stocks. (A.L.B.)

  18. Management and control after the special preparation of skiers-racing drivers on the stages of annual macrocycle

    Directory of Open Access Journals (Sweden)

    Sidorova T.V.


    Full Text Available In theory and the estimation of the special preparation of skiers-racing drivers is experimentally grounded on the stages of annual cycle of training. The norms of the special preparedness of sportsmen are certain depending on style of movement. The levels of the special preparedness of sportsmen are certain in the whole-year training. It is well-proven that an orientation on evaluation scales allows objectively to characterize the state of separate components of motive function of every sportsman. Also to range and group sportsmen on typological the features of preparedness. Technology of correction of orientation of the trainings loadings is recommended.

  19. Theoretical study of stability of metal-N4 macrocyclic compounds in acidic media%密度泛函理论计算研究金属-N4大环化合物在酸性介质中的稳定性

    Institute of Scientific and Technical Information of China (English)

    陈永婷; 华星; 陈胜利


    Fe and Co porphyrins and phthalocyanines are excellent catalysts for the oxygen reduction reaction (ORR) and are promising alternatives to Pt in fuel cells. However, the stability of these molecular catalysts in acidic media is poor. This study explores whether demetalation through proton ex‐change causes these metal macrocyclic catalysts to be unstable in acidic media. We first present a theoretical scheme for investigating exchange reactions of metal ions in metal macrocyclic com‐pounds with protons in acidic media. The equilibrium concentrations of metal ions in solution when various metalloporphyrins (MPs) and metallophthalocyanines (MPcs) are brought into contact with a strongly acidic solution (pH=1) were then estimated using density functional theory calculations;these values were used to evaluate the stability of these metal macrocyclic compounds against demetalation in acidic media. The results show that Fe, Co, Ni, and Cu phthalocyanines and porphy‐rins have considerable resistance to exchange with protons, whereas Cr, Mn, and Zn phthalocya‐nines and porphyrins easily undergo demetalation through ion exchange with protons. This sug‐gests that the degradation in the ORR activity of Fe and Co macrocyclic molecular catalysts and of carbon materials doped with Fe(Co) and nitrogen, which are believed to have metal‐nitrogen coor‐dination structures similar to those of macrocyclic molecules as ORR catalytic centers, is not the result of replacement of metal ions by protons. The calculation results show that electron‐donating substituents could enhance the stability of Fe and Co phthalocyanines.%质子交换膜燃料电池(PEMFCs)是一种能够有效地将化学能转换成电能的装置,其具有较高的效率及功率密度,还兼具环境友好的优点,因而在电动车和分布式电站等领域有广泛应用前景.然而,昂贵的价格及较差的耐久性阻碍了 PEMFCs的广泛应用.阴极氧还原反应(ORR

  20. Design of a flexible organometallic tecton: host-guest chemistry with picric acid and self-assembly of platinum macrocycles. (United States)

    Jana, Achintya; Bhowmick, Sourav; Kaur, Supreet; Kashyap, Hemant K; Das, Neeladri


    The synthesis and characterization of a new pyrazine-based "flexible" and ditopic platinum(ii) organometallic molecule (3) is being reported. Flexibility in this molecule is due to the presence of ether functional groups that bridge the rigid core and periphery. Due to the presence of square planar Pt(ii) centers at the two ends, the molecule's potential to act as an acceptor building block in the construction of metallamacrocycles was tested. Upon reaction of 3 with various dicarboxylates in a 1 : 1 stoichiometric ratio, [2 + 2] self-assembled neutral metallacycles (M1-M3) were obtained in high yields. M1-M3 were characterized using multinuclear NMR, high resolution mass spectrometry and elemental analyses. The shape and dimensions of these supramolecular structures were also confirmed by optimizing the geometry using the density functional theory (DFT) approach. Computational studies suggest that M1-M3 are nanoscalar macrocyles. Furthermore, using isothermal titration calorimetry (ITC), it was shown that 3 can bind with picric acid (PA) to yield a 3·(PA)2 host-guest complex. The magnitude of the binding constant indicates that 3 has significant affinity for PA.

  1. Effect of the chemical modification of a macrocycle and the acidity of a medium on the spectral properties and basicity of tetraphenylporphyrin in HCl- N, N-dimethylformamide system at 298 K (United States)

    Ivanova, Yu. B.; Razgonyaev, O. V.; Semeikin, A. S.; Mamardashvili, N. Zh.


    Spectrophotometric titration is used to study the basicity of tetraphenylporphine and its derivatives with electron-donor and electron-acceptor substituents in the 4-positions of meso-aryl fragments (5,10,15,20-tetra(4-R-phenyl)porphine, R:-OH,-NH2,-COOH,-Cl) in a system HCl- N, N-dimethylformamide at 298 K. An equation for calculating the dependence of the Hammett constant ( H 0) on the HCl concentration in a HCl- N, N-dimethylformamide system at 298 K is proposed. It is found that protonation of the intracycle nitrogen atoms of tetrapyrrole macrocycles of the indicated compounds occurs in two stages in this system. The corresponding ionization constants and concentration ranges of the existence of mono- and doubly-protonated dication forms of the indicated compounds are determined. It is found that both the introduction of strong substituents into the macrocycle of porphyrin and the properties of the medium facilitate the formation of mono- and doubly-protonated forms of porphyrins in solutions.

  2. New macrocyclic schiff base complexes incorporating a homopiperazine unit: Synthesis of some Co(II), Ni(II),Cu(II) and Zn(II) complexes and crystal structure and theoretical studies (United States)

    Keypour, Hassan; Rezaeivala, Majid; Ramezani-Aktij, Ameneh; Bayat, Mehdi; Dilek, Nefise; Ünver, Hüseyin


    A new macrocyclic Schiff base ligand, L, was synthesized by condensation reaction of 1,4-bis(2-formylphenyl)homopiperazine and 1,4-diaminobutane in acetonitrile. The Schiff base ligand was characterized by using elemental analyses, FT-IR, 1H, 13C NMR and mass spectroscopic techniques. The metal (II) complexes [ML], were synthesized from the reaction of MCl2.nH2O (M: Co, Ni, Cu and Zn) with Schiff base ligand, L and characterized by elemental analyses and FT-IR. X-ray crystal structure of [CoLCl]+ distorted square pyramidal geometry with an N4Cl core, arising from coordination by the four donor nitrogen atoms from the macrocyclic framework and one Cl atom. It crystallizes triclinic space group, P-1 with a = 7.1777(1) Å, b = 11.0357 (2) Å, c = 15.1520(2) Å, V = 1183.14(3), Z = 2, Dc = 1.556 g cm-3, μ (MoKα) = 0.156 mm-1. Also, the bonding situation between the [MCl]+ and Ligand (L) fragments in [MLCl]ClO4 (M = Co(II), Ni(II), Cu(II), Zn(II)) complexes were carried out by energy-decomposition analysis (EDA). The results showed that there is an increasing trend in the case of ΔEelstat of the complexes by changing the M from Co(II) to Zn(II).

  3. Nitrogen and oxygen bridged calixaromatics: synthesis, structure, functionalization, and molecular recognition. (United States)

    Wang, Mei-Xiang


    heteracalixaromatics had been reported, owing to the formidable synthetic challenges involved. Apart from thiacalixarene, the synthesis of nitrogen- and oxygen-bridged calixarenes appeared very difficult. But since our first publications in 2004, we have been delighted to see the rapid and tremendous development of the supramolecular chemistry of this new generation of macrocycles. In this Account, I summarize the synthesis of N- and O-bridged calixaromatics and their regiospecific functionalization on the rims and bridging positions, focusing on the fragment coupling approach and contributions from our laboratory. I describe the construction of molecular cages based on heteracalixaromatics and discuss the effect of both bridging heteroatoms and substituents on macrocyclic conformations and cavity sizes. Molecular recognition of neutral organic molecules and charged guest species is also demonstrated. The easy accessibility, rich molecular diversity, unique conformation, and cavity tunability of heteracalixaromatics make them invaluable macrocycles for research in supramolecular chemistry. New heteracalixaromatics, with well-defined conformations and cavity properties, will provide powerful tools for probing noncovalent interactions, leading to the development of new molecular sensing and imaging systems. Multicomponent molecular self-assembly of heteracalixaromatics as functional modules with metals, metal clusters, or charge-neutral species should result in multidimensional solid and soft materials with diverse applications. The profitable incorporation of heteracalixaromatics into molecular devices can also be anticipated in the future. Moreover, the construction of enantiopure, inherently chiral heteracalixaromatics should provide important applications in chiral recognition and asymmetric catalysis.

  4. Supramolecular Gelation of Rigid Triangular Macrocycles through Rings of Multiple C-H···O Interactions Acting Cooperatively. (United States)

    Liu, Zhichang; Sun, Junling; Zhou, Yu; Zhang, Yu; Wu, Yilei; Nalluri, Siva Krishna Mohan; Wang, Yuping; Samanta, Avik; Mirkin, Chad A; Schatz, George C; Stoddart, J Fraser


    When equimolar solutions of the enantiomeric naphthalenediimide-based highly rigid triangles R-Δ and S-Δ in ClCH2CH2Cl are mixed, the racemate rac-Δ forms an organogel that is composed of interwoven fibers, resulting from the columnar stacking of the triangles in an alternating R-Δ/S-Δ fashion. Under identical conditions, the pure enantiomers do not form organogels. Density functional theory calculations reveal that the racemic RS dimer is more stable than the RR dimer as a result of the enantiomeric relationship between R-Δ and S-Δ, allowing them to act as two complementary rings comprised of 12 [C-H···O] interactions with an unprecedented and uninterrupted circular ADDAADDAADDA·DAADDAADDAAD alignment of hydrogen bond donors (D) and acceptors (A), in contrast with the square-wave manner in which the RR dimer forms a complementary yet interrupted ADADAD·DADADA circular sequence of six longer [C-H···O] hydrogen bonds. It follows that gelation is favored by weak interactions acting cooperatively in rings under precise stereoelectronic control.

  5. Synthesis, characterization and in vitro antimicrobial studies of Co(II), Ni(II) and Cu(II) complexes derived from macrocyclic compartmental ligand (United States)

    El-Gammal, O. A.; Bekheit, M. M.; El-Brashy, S. A.


    New Co(II), Ni(II) and Cu(II) complexes derived from tetradentate macrocyclic nitrogen ligand, (1E,4E,8E,12E)-5,8,13,16-tetramethyl-1,4,9,12-tetrazacyclohexadeca-4,8,12,16-tetraene (EDHDH) have been synthesized. The complexes have been characterized by elemental analysis, spectral (IR, UV-Vis, 1H NMR and ESR (for Cu(II) complex)) mass, and magnetic as well as thermal analysis measurements. The complexes afforded the formulae: [Cu(EDHDH)Cl2]·2EtOH and [M(EDHDH)X2]·nH2O where M = Co(II) and Ni(II), X = Cl- or OH-, n = 1,0, respectively. The data revealed an octahedral arrangement with N4 tetradentate donor sites in addition to two Cl atoms occupying the other two sites. ESR spectrum of Cu2+ complex confirmed the suggested geometry with values of a α2and β2 indicating that the in-plane σ-bonding and in-plane π-bonding are appreciably covalent, and are consistent with very strong σ-in-plane bonding in the complexes. The molecular modeling is drawn and showed the bond length, bond angle, chemical reactivity, energy components (kcal/mol) and binding energy (kcal/mol) for all the title compounds using DFT method. Also, the thermal behavior and the kinetic parameters of degradation were determined using Coats-Redfern and Horowitz-Metzger methods. Moreover, the in vitro antibacterial studies of all compounds screened against pathogenic bacteria (two Gram +ve and two Gram -ve) to assess their inhibiting potential. The assay indicated that the inhibition potential is metal ion dependent. The ligand, EDHDH, Co(II) and Cu(II) complexes exhibited a remarkable antibacterial activity against Streptococcus Pyogenes as Gram +ve and Proteus vulgaris as Gram -ve bacterial strains. On the other hand, Ni(II) complex revealed a moderate antibacterial activity against both Gram +ve organisms and no activity against Gram -ve bacterial strain.

  6. Labeling internalizing anti-epidermal growth factor receptor variant III monoclonal antibody with {sup 177}Lu: in vitro comparison of acyclic and macrocyclic ligands

    Energy Technology Data Exchange (ETDEWEB)

    Hens, Marc; Vaidyanathan, Ganesan; Welsh, Phil [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States); Zalutsky, Michael R. [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States)], E-mail:


    Introduction: The monoclonal antibody (mAb) L8A4, reactive with the epidermal growth factor receptor variant III (EGFRvIII), internalizes rapidly in glioma cells after receptor binding. Combining this tumor-specific mAb with the low-energy {beta}-emitter {sup 177}Lu would be an attractive approach for brain tumor radioimmunotherapy, provided that trapping of the radionuclide in tumor cells after mAb intracellular processing could be maximized. Materials and Methods: L8A4 mAb was labeled with {sup 177}Lu using the acyclic ligands [(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S) -cyclohexane-1,2-diamine-pentaacetic acid (CHX-A''-DTPA), 2-(4-isothiocyanatobenzyl)-diethylenetriaminepenta-acetic acid (pSCN-Bz-DTPA) and 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid (1B4M-DTPA), and the macrocyclic ligands S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (C-DOTA) and {alpha}-(5-isothiocyanato-2-methoxyphenyl)-1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (MeO-DOTA). Paired-label internalization and cellular processing assays were performed on EGFRvIII-expressing U87.{delta}EGFR glioma cells over 24 h to directly compare {sup 177}Lu-labeled L8A4 to L8A4 labeled with {sup 125}I using either iodogen or N-succinimidyl 4-guanidinomethyl-3-[{sup 125}I]iodobenzoate ([{sup 125}I]SGMIB). In order to facilitate comparison of labeling methods, the primary parameter evaluated was the ratio of {sup 177}Lu to {sup 125}I activity retained in U87.{delta}EGFR cells. Results: All chelates demonstrated higher retention of internalized activity compared with mAb labeled using iodogen, with {sup 177}Lu/{sup 125}I ratios of >20 observed for the three DTPA chelates at 24 h. When compared to L8A4 labeled using SGMIB, except for MeO-DOTA, internalized activity for {sup 125}I was higher than {sup 177}Lu from 1-8 h with the opposite behavior observed thereafter. At 24 h, {sup 177}Lu/{sup 125}I ratios were between 1

  7. 常见大环自组装构建分子胶囊%Molecular Capsules Based on Common Macrocycles Self-Assembly

    Institute of Scientific and Technical Information of China (English)

    郑睿; 梁丹霞; 于雪涛; 陈仁尔; 蒋华江; 周其忠


    Molecular capsules are amazing and fascinating because of their unusual structure and nanospaces. These unique microenvironments and nano-structures ultimately ensure their potential for applications in materials science, biological science, drug delivery and catalysis. Molecular capsules could be constructed by covalent bonds or non-covalent bonds with many kinds of different components. This article describes the syntheses and properties of a library of diverse molecular capsules by non-covalent bonds with common macrocycles, which covers (i) cyclodextrins based systems, (ii) calix[n]arenes based systems, (iii) calic[n]pyrroles based systems, (iv) porphyrins based systems, (v) cyclotriveratrylene (CTV) based systems, and finally (vi) cucurbit[n]urils based systems. These building blocks afford molecular capsules based on the self-assembly of several units, which is primarily driven by the interplay of weak attractions that act over short distances between molecules, including hydrogen bonds, electrostatic interaction, aromatic π-stacking, van der Waal's interactions, etc. These versatile molecular capsules providing different nanospaces, some of which are controllable and adjustable, could encapsulate different kinds of interesting guests in solution or solid states.%分子胶囊以其独特的分子结构在控制药物释放、催化、材料科学和生物医药等领域具有潜在的应用价值.分子胶囊可由不同的分子模块通过共价键或非共价键构建.着重描述了由常见的大环主体(环糊精、杯芳烃、杯吡咯、卟啉、环三藜芦烯和葫芦脲)通过自组装形成的分子胶囊.这些分子胶囊通过非共价键(氢键、静电作用、疏水作用及范德华力等)连接,使得分子胶囊具有可控的可调节的分子结构.通过这些独特的分子结构,分子胶囊可在溶液或固相中包裹各种各样的有趣的客体.

  8. Nano-level monitoring of Yb(III) by fabrication of coated graphite electrode based on newly synthesized hexaaza macrocyclic ligand. (United States)

    Singh, Ashok K; Singh, Prerna


    The two macrocyclic ligands 2,12-(2-methoxyaniline)2-4,14-Me2-[20]-1,4,11,14-tetraene-1,5,8,11,15,18-N6 (L1) and 2,12-(2-methoxyaniline)(2)-4,14-Me2-8,18-dimethylacrylate-[20]-1,4,11,14-tetraene-1,5,8,11,15,18-N6 (L2) have been synthesized and explored as neutral ionophores for preparing poly(vinylchloride) (PVC) based membrane sensors selective to Yb(III) ions. Effects of various plasticizers and anion excluders were studied in detail and improved performance was observed. The best performance was obtained for the membrane sensor having a composition of L2:PVC:BA:NaTPB in the ratio of 5: 40: 52: 3 (w/w; mg). The performance of the membrane based on L2 was compared with polymeric membrane electrode (PME) as well as with coated graphite electrode (CGE). The electrodes exhibit Nernstian slope for Yb3+ ions with limits of detection of 4.3 x 10(-8) M for PME and 5.8 x 10(-9) M for CGE. The response time for PME and CGE was found to be 10 s and 8 s, respectively. The potentiometric responses are independent of the pH of the test solution in the pH range 3.0-8.0 for PME and 2.5-8.5 for CGE. The CGE has found to work satisfactorily in partially non-aqueous media upto 30% (v/v) content of methanol, ethanol and 20% (v/v) content of acetonitrile and could be used for a period of 5 months. The CGE was used as indicator electrode in the potentiometric titration of Yb3+ ions with EDTA and in determination of fluoride ions in mouthwash samples. It can be used for determination of sulfite in red and white wine samples and also in determination of Yb3+ in various binary mixtures with quantitative results.

  9. Synthesis and characterization of nitrogen-rich macrocyclic ligands and an investigation of their coordination chemistry with lanthanum(III). (United States)

    Wilson, Justin J; Birnbaum, Eva R; Batista, Enrique R; Martin, Richard L; John, Kevin D


    Derivatives of the ligand 1,4,7,10-tetraazacyclododecane (cyclen) containing pendant N-heterocyclic donors were prepared. The heterocycles pyridine, pyridazine, pyrimidine, and pyrazine were conjugated to cyclen to give 1,4,7,10-tetrakis(pyridin-2-ylmethyl)-1,4,7,10-tetraazacyclododecane (L(py)), 1,4,7,10-tetrakis(3-pyridazylmethyl)-1,4,7,10-tetraazacyclododecane (L(pyd)), 1,4,7,10-tetrakis(4-pyrimidylmethyl)-1,4,7,10-tetraazacyclododecane (L(pyr)), and 1,4,7,10-tetrakis(2-pyrazinylmethyl)-1,4,7,10-tetraazacyclododecane (L(pz)), respectively. The coordination chemistry of these ligands was explored using the La(3+) ion. Accordingly, complexes of the general formula [La(L)(OTf)](OTf)2, where OTf = trifluoromethanesulfonate and L = L(py) (1), L(pyd) (2), L(pyr) (3), and L(pz) (4), were synthesized and characterized by NMR spectroscopy. Crystal structures of 1 and 2 were also determined by X-ray diffraction studies, which revealed 9-coordinate capped, twisted square-antiprismatic coordination geometries for the central La(3+) ion. The conformational dynamics of 1-4 in solution were investigated by variable-temperature NMR spectroscopy. Dynamic line-shape and Eyring analyses enabled the determination of the activation parameters for the interconversion of enantiomeric forms of the complexes. Unexpectedly, the different pendant N-heterocycles of 1-4 give rise to varying values for the enthalpies and entropies of activation for this process. Density functional theory calculations were carried out to investigate the mechanism of this enantiomeric interconversion. Computed activation parameters were consistent with those experimentally determined for 1 but differed somewhat from those of 2-4.

  10. Dinuclear cadmium(II), zinc(II), and manganese(II), trinuclear nickel(II), and pentanuclear copper(II) complexes with novel macrocyclic and acyclic Schiff-base ligands having enantiopure or racemic camphoric diamine components. (United States)

    Jiang, Jue-Chao; Chu, Zhao-Lian; Huang, Wei; Wang, Gang; You, Xiao-Zeng


    Four novel [3 + 3] Schiff-base macrocyclic ligands I-IV condensed from 2,6-diformyl-4-substituted phenols (R = CH(3) or Cl) and enantiopure or racemic camphoric diamines have been synthesized and characterized. Metal-ion complexations of these enantiopure and racemic [3 + 3] macrocyclic ligands with different cadmium(II), zinc(II), manganese(II), nickel(II), and copper(II) salts lead to the cleavage of Schiff-base C horizontal lineN double bonds and subsequent ring contraction of the macrocyclic ligands due to the size effects and the spatial restrictions of the coordination geometry of the central metals, the steric hindrance of ligands, and the counterions used. As a result, five [2 + 2] and one [1 + 2] dinuclear cadmium(II) complexes (1-6), two [2 + 2] dinuclear zinc(II) (7 and 8), and two [2 + 2] dinuclear manganese(II) (9 and 10) complexes together with one [1 + 1] trinuclear nickel(II) complex (11) and one [1 + 2] pentanuclear copper(II) complex (12), bearing enantiopure or racemic ligands, different substituent groups in the phenyl rings, and different anionic ligands (Cl(-), Br(-), OAc(-), and SCN(-)), have been obtained in which the chiral carbon atoms in the camphoric backbones are arranged in different ways (RRSS for the enantiopure ligands in 1, 2, 4, 5, and 7-10 and RSRS for the racemic ligands in 3, 6, 11, and 12). The steric hindrance effects of the methyl group bonded to one of the chiral carbon atoms of camphoric diamine units are believed to play important roles in the formation of the acyclic [1 + 1] trinuclear complex 11 and [1 + 2] dinuclear and pentanuclear complexes 6 and 12. In dinuclear cadmium(II), zinc(II), and manganese(II) complexes 1-10, the sequence of separations between the metal centers is consistent with that of the ionic radii shortened from cadmium(II) to manganese(II) to zinc(II) ions. Furthermore, UV-vis, circular dichroism, (1)H NMR, and fluorescence spectra have been used to characterize and compare the structural

  11. Macrocyclic G-quadruplex ligands

    DEFF Research Database (Denmark)

    Nielsen, M C; Ulven, Trond


    G-quadruplex stabilizing compounds have recently received increased interest due to their potential application as anticancer therapeutics. A significant number of structurally diverse G-quadruplex ligands have been developed. Some of the most potent and selective ligands currently known are macr...

  12. Tetrathiafulvalene- (TTF-) Derived Oligopyrrolic Macrocycles

    DEFF Research Database (Denmark)

    Jana, Atanu; Ishida, Masatoshi; Park, Jung Su


    After the epochal discovery of the “organic metal”, namely, tetrathiafulvalene (TTF)–7,7,8,8-tetracyano-p-quinodimethane (TCNQ) dyad in 1973, scientists have made efforts to derivatize TTF for constructing various supramolecular architectures to control the charge-transfer processes by adjusting ...

  13. Fabrication of novel coated pyrolytic graphite electrodes for the selective nano-level monitoring of Cd²⁺ ions in biological and environmental samples using polymeric membrane of newly synthesized macrocycle. (United States)

    Sahani, Manoj Kumar; Singh, A K; Jain, A K; Upadhyay, Anjali; Kumar, Amit; Singh, Udai P; Narang, Shikha


    Novel 5-amino-1,3,4-thiadiazole-2-thiol unit based macrocyclic ionophore 5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonaazatetracyclo[,7).1(10,13)]henicosa-4(20),10(21),16(19)-triene-6,12,18-trithione (M1), was synthesized and characterized. Preliminary studies on M1 have showed that it has more the affinity toward Cd(2+) ion. Thus, the macrocyclic ionophore (M1) was used as electroactive material in the fabrication of PVC-membrane electrodes such as polymeric membrane electrode (PME), coated graphite electrode (CGE) and coated pyrolytic graphite electrode (CPGE) were prepared and its performance characteristic were compared with. The electroanalytical studies performed on PME, CGE and CPGE revealed that CPGE having membrane composition M1:PVC:1-CN:NaTPB in the ratio of 7:37:54:2 exhibits the best potentiometric characteristics in terms of detection limit of 7.58×10(-9) mol L(-1), Nernstian slope of 29.6 mV decade(-1) of activity. The sensor was found to be independent of pH in the range 2.5-8.5. The sensor showed a fast response time of 10s and could be used over a period of 4 months without any significant divergence in its potentiometric characteristics. The sensor has been employed for monitoring of the Cd(2+) ion in real samples and also used as an indicator electrode in the potentiometric titration of Cd(2+) ion with EDTA.

  14. Nanoparticles functionalized with supramolecular host-guest systems for nanomedicine and healthcare. (United States)

    Wu, Zilong; Song, Nan; Menz, Ryan; Pingali, Bharadwaj; Yang, Ying-Wei; Zheng, Yuebing


    Synthetic macrocyclic host compounds can interact with suitable guest molecules via noncovalent interactions to form functional supramolecular systems. With the synergistic integration of the response of molecules and the unique properties at the nanoscale, nanoparticles functionalized with the host-guest supramolecular systems have shown great potentials for a broad range of applications in the fields of nanoscience and nanotechnology. In this review article, we focus on the applications of the nanoparticles functionalized with supramolecular host-guest systems in nanomedicine and healthcare, including therapeutic delivery, imaging, sensing and removal of harmful substances. A large number of examples are included to elucidate the working mechanisms, advantages, limitations and future developments of the nanoparticle-supramolecule systems in these applications.

  15. Fixation of carbon dioxide by macrocyclic lanthanide(III) complexes under neutral conditions producing self-assembled trimeric carbonato-bridged compounds with μ3-η2:η2:η2 bonding. (United States)

    Bag, Pradip; Dutta, Supriya; Biswas, Papu; Maji, Swarup Kumar; Flörke, Ulrich; Nag, Kamalaksha


    A series of mononuclear lanthanide(III) complexes [Ln(LH(2))(H(2)O)(3)Cl](ClO(4))(2) (Ln = La, Nd, Sm, Eu, Gd, Tb, Lu) of the tetraiminodiphenolate macrocyclic ligand (LH(2)) in 95 : 5 (v/v) methanol-water solution fix atmospheric carbon dioxide to produce the carbonato-bridged trinuclear complexes [{Ln(LH(2))(H(2)O)Cl}(3)(μ(3)-CO(3))](ClO(4))(4)·nH(2)O. Under similar conditions, the mononuclear Y(III) complex forms the dimeric compound [{Y(LH(2))(H(2)O)Cl}(μ(2)-CO(3)){Y(LH(2))(H(2)O)(2)}](ClO(4))(3)·4H(2)O. These complexes have been characterized by their IR and NMR ((1)H, (13)C) spectra. The X-ray crystal structures have been determined for the trinuclear carbonato-bridged compounds of Nd(III), Gd(III) and Tb(III) and the dinuclear compound of Y(III). In all cases, each of the metal centers are 8-coordinate involving two imine nitrogens and two phenolate oxygens of the macrocyclic ligand (LH(2)) whose two other imines are protonated and intramolecularly hydrogen-bonded with the phenolate oxygens. The oxygen atoms of the carbonate anion in the trinuclear complexes are bonded to the metal ions in tris-bidentate μ(3)-η(2):η(2):η(2) fashion, while they are in bis-bidentate μ(2)-η(2):η(2) mode in the Y(III) complex. The magnetic properties of the Gd(III) complex have been studied over the temperature range 2 to 300 K and the magnetic susceptibility data indicate a very weak antiferromagnetic exchange interaction (J = -0.042 cm(-1)) between the Gd(III) centers (S = 7/2) in the metal triangle through the carbonate bridge. The luminescence spectral behaviors of the complexes of Sm(III), Eu(III), and Tb(III) have been studied. The ligand LH(2) acts as a sensitizer for the metal ions in an acetonitrile-toluene glassy matrix (at 77 K) and luminescence intensities of the complexes decrease in the order Eu(3+) > Sm(3+) > Tb(3+).

  16. Photoinduced energy- and electron-transfer processes in dinuclear Ru(II)-Os(II), Ru(II)-Os(III), and Ru(III)-Os(II) trisbipyridine complexes containing a shape-persistent macrocyclic spacer. (United States)

    Venturi, Margherita; Marchioni, Filippo; Ferrer Ribera, Belén; Balzani, Vincenzo; Opris, Dorina M; Schlüter, A Dieter


    The PF6- salt of the dinuclear [(bpy)2Ru(1)Os(bpy)2]4+ complex, where 1 is a phenylacetylene macrocycle which incorporates two 2,2'-bipyridine (bpy) chelating units in opposite sites of its shape-persistent structure, was prepared. In acetonitrile solution, the Ru- and Os-based units display their characteristic absorption spectra and electrochemical properties as in the parent homodinuclear compounds. The luminescence spectrum, however, shows that the emission band of the Ru(II) unit is almost completely quenched with concomitant sensitization of the emission of the Os(II) unit. Electronic energy transfer from the Ru(II) to the Os(II) unit takes place by two distinct processes (k(en) = 2.0x10(8) and 2.2x10(7) s(-1) at 298 K). Oxidation of the Os(II) unit of [(bpy)2Ru(1)Os(bpy)2]4+ by Ce(IV) or nitric acid leads quantitatively to the [(bpy)2Ru(II)(1)Os(III)(bpy)2]5+ complex which exhibits a bpy-to-Os(III) charge-transfer band at 720 nm (epsilon(max) = 250 M(-1) cm(-1)). Light excitation of the Ru(II) unit of [(bpy)2Ru(II)(1)Os(III)(bpy)2]5+ is followed by electron transfer from the Ru(II) to the Os(III) unit (k(el,f) = 1.6x10(8) and 2.7x10(7) s(-1)), resulting in the transient formation of the [(bpy)2Ru(III)(1)Os(II)(bpy)2]5+ complex. The latter species relaxes to the [(bpy)2Ru(II)(1)Os(III)(bpy)2]5+ one by back electron transfer (k(el,b) = 9.1x10(7) and 1.2x10(7) s(-1)). The biexponential decays of the [(bpy)2*Ru(II)(1)Os(II)(bpy)2]4+, [(bpy)2*Ru(II)(1)Os(III)(bpy)2]5+, and [(bpy)2Ru(III)(1)Os(II)(bpy)2]5+ species are related to the presence of two conformers, as expected because of the steric hindrance between hydrogen atoms of the pyridine and phenyl rings. Comparison of the results obtained with those previously reported for other Ru-Os polypyridine complexes shows that the macrocyclic ligand 1 is a relatively poor conducting bridge.

  17. Studies on an Unsymmetrical Macrocyclic Dinuclear Ni(Ⅱ) Complex Interaction with DNA%不对称大环双核Ni(Ⅱ)配合物的DNA切割性能研究

    Institute of Scientific and Technical Information of China (English)

    丁超; 陈云峰; 刘明; 宋会婷; 周红; 潘志权


    本文利用模板导向的方式合成了一种含有不对称侧链的大环双核金属Ni(Ⅱ)配合物(大环配体由3-溴甲基-5-甲基水杨醛,乙二胺,N,N-二氨丙基)-2呋喃甲胺分步合成得到),其结构通过红外光谱、元素分析、X-射线单晶衍射进行了表征.利用紫外光谱、分子荧光和粘度试验对配合物与DNA的相互作用进行了研究,结果表明配合物与CT-DNA的结合常数K=4.8× 104 mol-1.L荧光淬灭常数Ksx=7.12×103 mol-1-L;同时机理研究表明配合物与CT-DNA结合方式为插入模式.%An unsymmetrical side chains macrocyclic dinuclear Ni(Ⅱ) complex has been obtained by templatedirected synthesis (the macrocyclic ligand was synthesized by 3-bromomethyl-2-hydroxy-5-methylbenzaldehyde,ethane-1,2-diamine,and N1-(3-aminopropyl)-N1-(furan-2-ylmethyl)propane-1,3-diamine),the structure has been characterized by IR spectrum,elemental analysis and X-ray crystallography determination.The interactions of the complex with DNA have been measured by UV spectroscopy,fluorescence spectroscopy and viscosity experiments.Absorption spectroscopic investigation reveals of intercalative binding of the complex with DNA with a binding constant of 4.8×104 mol-1.L.Fluorescence spectroscopy shows that the complex displaces EB and bind to DNA with a quenching constant of 7.12×103 mol-1·L.The appearance of both increased CD bands nearing 371nm gives evidence for effective complex-DNA binding.The agarose gel electrophoresis studies show that the complex displays effective DNA cleavage activity in the absence of any external agents.CCDC:835716.

  18. 席夫碱大环双核锌配合物的合成与表征%Synthesis and crystal structure of macrocyclic Schiff base binuclear zinc( Ⅱ )complex

    Institute of Scientific and Technical Information of China (English)

    康海霞; 马宁; 傅玉琴; 李森兰


    A tetraaza macrocyclic Schiff base was synthesized through the reaction of acetone and ethylenediamine by the catalysis of perchloric acid. The Schiff base reacted with ZnO and NaN3 to form a binuclear zinc ( Ⅱ ) macrocyclic complex. The complex was characterized by infrared spectrum and X-Ray single crystal diffraction. It belongs to monoclinic system with space groupC2/c,α = 2.4914(2)nm,b = 1.4 9748(13)nm,c=1.26800(11)nm;β=l02. 1900( 10)°;v=4. 6240(7)nm3 ,Z=4,Dc = 1.482 Mg/m\\Mr = 1032.03 ,F(000)= 2160,final R=0.0506,wR = 0. 1434. The Zinc atom is five-coordinated by five nitrogen atoms(four nitrogen atoms come from the Schiff base and one nitrogen atom comes from the azido anion). As a result, a slightly distorted triangle double-cone geometry forms.%本文用丙酮和乙二胺在高氯酸催化下合成了四氮杂十四环席夫碱(1),并用此化合物(1)与氧化锌和叠氮化钠反应,生成锌的双核大环配合物.通过X-射线单晶衍射和红外光谱对其进行了结构表征.该配合物属单斜晶系,C2/c空间群,晶胞参数为a=2.4914 (2) nm,b=1.4 9748 (13) nm,c=1.26800( 11 )nm;β=102.1900(10)°;v=4.6240(7) nm3,Z=4,Dc=1.482Mg/m3,Mr=1032.03,F(000)=2160,最终R=0.0506,wR=0.1434.该配合物中锌原子是五配位,它们分别和大环配体上的4个氮原子及叠氮根负离子两端的氮原子配位形成畸变的三角双锥构型.

  19. Synthesis and spectral studies of macrocyclic Pb(Ⅱ), Zn(Ⅱ), Cd(II)and La(Ⅲ) complexes derived from 1,4-bis(3-aminopropoxy)butane with metal nitrate and salicylaldehyde derivatives

    Institute of Scientific and Technical Information of China (English)

    Salih Ilhan; Hamdi Temel; Salih Pasa


    Eight new macrocyclic complexes were synthesized by template reaction of 1,4-bis(3-aminopropoxy)butane with metal nitrate and 1,3-bis(2-forrnylphenyl)propane or 1,4-bis(2-formylphenyl)butane and their structures were proposed on the basis of elemental analysis, FTIR, UV-vis, molar conductivity measurements, 1H NMR and mass spectra. The metals to ligand molar ratios of the complexes were found to be 1:1. The complexes are 1:2 electrolytes for Pb(II), Zn(II) and Cd(II) complexes and 1:3 electrolytes for La(lIl) as shown by their molar conductivities (Am) in DMSO at 10-3 tool L-l. Due to the existence of free ions in these complexes,such complexes are electrically conductive. The configurations of La(Ⅲ) and Pb(U) were proposed to probably octahedral and Zn(II) and Cd(II) complexes were proposed to probably tetrahedral.

  20. Synthesis, DNA-binding, DNA-photonuclease profiling and antimicrobial activity of novel tetra-aza macrocyclic Ni(II), Co(II) and Cu(II) complexes constrained by thiadiazole. (United States)

    Vinay Kumar, B; Bhojya Naik, H S; Girija, D; Sharath, N; Pradeepa, S M; Joy Hoskeri, H; Prabhakara, M C


    A new tetra-aza macrocyclic ligand, L (C(24)H(16)N(12)O(2)S(4)) and its complexes of type, [MLCl(2)] and [CuL]Cl(2) (where M=Ni(II), Co(II); L=N,N'-(benzene-1,3-diyldi-1,3,4-thiadiazole-5,2-diyl)bis{2-[(5-benzene-1,3-diyl-1,3,4-thiadiazol-2-yl)amino]acetamide}) were synthesized and characterized by the spectral and analytical techniques. An octahedral geometry has been proposed for Ni(II) and Co(II) complexes while Cu(II) complex exhibit a square planar geometry. All the synthesized metal complexes were screened for their in vitro antimicrobial activity against selected species of pathogenic bacteria and fungi. The binding property of the complexes with CT-DNA was studied by absorption spectral analysis, followed by viscosity measurement and thermal denaturation studies. The photo induced cleavage studies revealed that the complexes possess photonuclease property against pUC19 DNA under UV-visible irradiation.

  1. Application of gas phase cryogenic vibrational spectroscopy to characterize the CO2, CO, N2 and N2O interactions with the open coordination site on a Ni(I) macrocycle using dual cryogenic ion traps (United States)

    Craig, Stephanie M.; Menges, Fabian S.; Johnson, Mark A.


    Recent advances in gas phase ion chemistry, coupled with cryogenic ion vibrational predissociation spectroscopy, provide a powerful way to characterize the structures of small molecules bound to open coordination sites of organometallic compounds. Here we extend our previous measurements on the relatively weakly interacting CO2 molecule with a Ni(I) tetraaza-macrocyclic compound to enable the characterization of more strongly interacting substrates. We first confirm the calculated η2-C,O binding motif of CO2 using isotopic labeling by direct, one photon vibrational predissociation of the Ni(I)-CO2 complex. We then apply this approach to study complexation of N2 at the active site. The generality of the method is then expanded to include application to more strongly bound systems that cannot be photodissociated with one IR photon. This involves implementation of a recently developed scheme (Marsh et al., 2015) involving two temperature-controlled ion traps. The first is optimized to complex the substrate molecule to the active site and the second is cooled to around 10 K to enable condensation of weakly bound "tag" molecules onto the target complex so as to enable its characterization by linear vibrational predissociation spectroscopy. We demonstrate this capability by applying it to the coordination of CO to the active Ni(I) site, as well as to elucidate the nature of the products that are formed upon reaction with N2O.

  2. Study on synthesis of new dinuclear copper macrocyclic complex by template reaction involving lead ion as templating agent%模板法合成大环单核铅及双核铜(Ⅱ)配合物

    Institute of Scientific and Technical Information of China (English)

    王小波; 姜治平; 候波涛; 胡学雷; 潘志权


    采用Pb2+作为模板离子,以2,6-二甲酰基对甲苯酚与2-羟基-1,3-丙二胺为原料通过[2+2]缩合反应,得到单核铅配合物[Pb(H2L)](ClO4)2(H2L为中性大环配体),进一步通过金属置换反应合成了一个新的希夫碱大环双核铜(Ⅱ)配合物[Cu2L](ClO4)2,并对中间体大环单核铅配合物及其双核铜(Ⅱ)配合物的结构进行了表征.%A new dinuclear copper macrocyclic complex was synthesized by metal transferred reaction of the mononuclear lead complex as the precursor which was obtained based on the [2+2]condensation between 2,6-diacetyl-4-methylphenol and 1,3-diamino- 2-propanol in the presence of Pb2+ ion.Both structure of two complexes were characterized by several methods.

  3. Structure-function relationships of second hyperpolarizabilities in two-dimensional molecules

    Energy Technology Data Exchange (ETDEWEB)

    Chen, L.X. [Argonne National Lab., IL (United States); Mandal, B.K.; Bihari, B. [Illinois Institute of Technology, Chicago, IL (United States). Dept. of Chemistry] [and others


    The enhancement of the third order susceptibilities X{sup (3)} and second order molecular hyperpolarizabilities <{gamma}> in a series of covalently stacked dimer and trimer macrocycles (SiPc and SiNc) was observed through the phase conjugated signals from DFWM measurements at both 1064 and 532 nm. The FWHM of the phase conjugated signals at 532 nm is much smaller than those at 1064 nm and those of the reference compound CS{sub 2}. The <{gamma}> values at both wavelengths as a function of number of the monomer units (n) have an approximate n{sup 3} dependence, differing only in the scaling constant. The origin of such enhancement is discussed and compared to those in one-dimensional {pi}-conjugated systems.

  4. Cyclic ligand functionalized mesoporous silica (SBA-15) for selective adsorption of Co2+ ion from artificial seawater. (United States)

    Moorthy, Madhappan Santha; Park, Sung Soo; Selvaraj, M; Ha, Chang-Sik


    Hard donor atoms (N and O) containing macrocyclic ligand was synthesized and further functionalized with mesoporous SBA-15 materials by chemical modification method. The modification was achieved by the immobilization of 3-chloropropyltriethoxysilane (CIPTES) onto mesoporous silica surface followed by post grafting route. The resulting material (Py-Cy-SBA-15) has been characterized by low angle X-ray diffraction (XRD), nitrogen adsorption-desorption isotherm, Fourier-transform infrared (FT-IR) spectroscopy, 29Si and 13C CP MAS NMR spectroscopic analyses, Thermogravimetric analysis (TGA) and elemental analysis. The long range orders of the materials were identified by transmission electron microscopy (TEM). The functionalized material was employed to the heavy metal ions adsorption from aqueous solution containing Cu2+, Co2+, Zn2+, Cd2+ and Cr2+. The prepared hybrid material showed high selectivity and adsorption capacity for Co2+ ion at pH 8.0.

  5. Synthesis and characterization of two novel bimetallic macrocyclic complexes generated from 1,2,4-triazole-containing semi-rigid ligands and M(NO3)2 units (M = Ni and Zn). (United States)

    Wu, Xiang Wen; Yin, Shi; Wu, Wan Fu; Ma, Jian Ping


    Bimetallic macrocyclic complexes have attracted the attention of chemists and various organic ligands have been used as molecular building blocks, but supramolecular complexes based on semi-rigid organic ligands containing 1,2,4-triazole have remained rare until recently. It is easier to obtain novel topologies by making use of asymmetric semi-rigid ligands in the self-assembly process than by making use of rigid ligands. A new semi-rigid ligand, 3-[(pyridin-4-ylmethyl)sulfanyl]-5-(quinolin-2-yl)-4H-1,2,4-triazol-4-amine (L), has been synthesized and used to generate two novel bimetallic macrocycle complexes, namely bis{μ-3-[(pyridin-4-ylmethyl)sulfanyl]-5-(quinolin-2-yl)-4H-1,2,4-triazol-4-amine}bis[(methanol-κO)(nitrato-κ(2)O,O')nickel(II)] dinitrate, [Ni2(NO3)2(C17H14N6S)2(CH3OH)2](NO3)2, (I), and bis{μ-3-[(pyridin-4-ylmethyl)sulfanyl]-5-(quinolin-2-yl)-4H-1,2,4-triazol-4-amine}bis[(methanol-κO)(nitrato-κ(2)O,O')zinc(II)] dinitrate, [Zn2(NO3)2(C17H14N6S)2(CH3OH)2](NO3)2, (II), by solution reactions with the inorganic salts M(NO3)2 (M = Ni and Zn, respectively) in mixed solvents. In (I), two Ni(II) cations with the same coordination environment are linked by L ligands through Ni-N bonds to form a bimetallic ring. Compound (I) is extended into a two-dimensional network in the crystallographic ac plane via N-H...O, O-H...N and O-H...O hydrogen bonds, and neighbouring two-dimensional planes are parallel and form a three-dimensional structure via π-π stacking. Compound (II) contains two bimetallic rings with the same coordination environment of the Zn(II) cations. The Zn(II) cations are bridged by L ligands through Zn-N bonds to form the bimetallic rings. One type of bimetallic ring constructs a one-dimensional nanotube via O-H...O and N-H...O hydrogen bonds along the crystallographic a direction, and the other constructs zero-dimensional molecular cages via O-H...O and N-H...O hydrogen bonds. They are interlinked into a two-dimensional network in the ac

  6. The renewable energies in France: the main results in 2002; Les energies renouvelables en France: les principaux resultats en 2002

    Energy Technology Data Exchange (ETDEWEB)



    This evaluation is a synthesis of the electrical and thermal productions from the renewable energies. It presents also the primary or secondary renewable energies productions when they are transformed and details the uses of each renewable energies productions, the ENR contribution to the needs of the different energy consumers (residential, agriculture, industry...). (A.L.B.)

  7. Focus - Programme global de restauration des principaux cours d’eau du département du Haut-Rhin

    Directory of Open Access Journals (Sweden)

    LACUISSE, Delphine


    Full Text Available Afin d’atteindre les objectifs de bon état des masses d’eau imposé par la directive cadre sur l’eau, un programme global de restauration de cours d’eau a été engagé dans le Haut-Rhin pour recréer un fonctionnement écologique et une diversité biologique à la fois du lit, des berges et des écoulements dégradés par les travaux hydrauliques ou d'autres interventions humaines. Focus sur la méthodologie mise au point pour définir et prioriser les actions de manière pertinente et adaptée.

  8. Avenir de la recherche scientifique en entrepreneuriat en Allemagne - Stratégies et principaux points thématiques

    NARCIS (Netherlands)

    Grichnik, Dietmar; Harms, Rainer


    La recherche en entrepreneuriat continue à évoluer. Ce champ de recherche qui va de l'interprétation de la nature du champ à la signification accordée à chaque thématique est soumis à des changements. Tenter de brosser un portrait de l'évolution de la recherche en entrepreneuriat en Allemagne s'avèr

  9. Renewable energies in France: the main results in 2007; Les energies renouvelables en France: les principaux resultats en 2007

    Energy Technology Data Exchange (ETDEWEB)



    This document is a status for the year 2007 of the production and consumption of renewable energies in France. This status allows to follow and measure the advance the programs sustained by the public authorities for the use and valorization of renewable energy sources. The production includes the power generation (hydraulic, wind, solar and biofuel power plants) and the heat generation (heat pumps, biofuels and refuse fuels). The consumption concerns only the heat generation and is analyzed by sector of use. Statistical production data are summarized in tables. (J.S.)

  10. Electrospray mass and tandem mass spectrometry of homologous and isomeric singly, doubly, triply and quadruply charged cationic ruthenated meso-(phenyl)m-(meta- and para-pyridyl)n (m + n = 4) macrocyclic porphyrin complexes. (United States)

    Tomazela, Daniela M; Gozzo, Fabio C; Mayer, Ildemar; Engelmann, Fábio M; Araki, Koiti; Toma, Henrique E; Eberlin, Marcos N


    Ten homologous or isomeric singly, doubly, triply and quadruply charged cationic macrocyclic complexes I-Va, bn+ (n = 1-4) formed by the coordination of [Ru(bipy)2Cl]+ to the pyridyl N-atoms of a series of meso-(phenyl)m-(meta or para-pyridyl)n-porphyrins (m + n = 4) were transferred to the gas phase and structurally characterized by electrospray ionization (ESI) mass (MS) and tandem mass (MS/MS) spectrometry. Previously known to be stable in solution and in the solid state, I-Va, bn+ are found to constitute also a new class of stable, long-lived multiply charged gas-phase ions with spatially separated charge sites. Increasing intramolecular electrostatic repulsion from Ia, b+ to IVa, b3+ facilitates in-source and tandem collision-induced dissociation (CID). However, for the quadruply charged ions Va, b4+, electrostatic repulsion is alleviated mainly by ion pairing with the CF3SO3- counterion forming the salt clusters [Va,b/CF3SO3]3+ and [Va,b/(CF3SO3)2]2+ with reduced charge states. Ion-pairing that yields [IVa,b/CF3SO3]2+ is also observed as a minor ESI process for the triply charged ions IVa, b3+. The gaseous ions I-Va, bn+ (n = 2, 3 or 4) dissociate by sequential 'charge partitioning' with the formation of two cationic fragments by the release of [Ru(bipy)2Cl]+. The meta (a) and para (b) isomers and the positional isomers II2+ and III2+ display nearly identical ESI-MS and ESI-MS/MS spectra. ESI-MS/MS of I-Va, bn+ shows that the Ru-py(P) is, intrinsically, the weakest bond since this bond breaks preferentially upon CID.

  11. Uso de lactonas macrocíclicas para el control de la garrapata Rhipicephalus (Boophilus microplus en el ganado bovino Use of macrocyclic lactones to control the cattle tick Rhipicephalus (Boophilus microplus

    Directory of Open Access Journals (Sweden)

    RI Rodríguez-Vivas


    Full Text Available En esta revisión se describe en detalle la composición química, farmacocinética, presentación y dosis, seguridad y tiempo de retiro y la seguridad ambiental de los grupos que componen a las LM: avemectinas (ivermectina, doramectina, eprinomectina, abamectina y milbemicinas (moxidectina. Además se presenta una discusión sobre su eficacia y el problema de resistencia de Rhipicephalus (Boophilus microplus a las LM. Se concluye que las LM por su alta liposolubilidad se distribuyen ampliamente en los tejidos, siendo eficaces para el control de R. (B. microplus en el ganado bovino. La eficacia de la ivermectina, doramectina, eprinomectina, abamectina y moxidectina de corta acción es similar (> 90% de eficacia a las cuatro semanas postratamiento, PT para el control de fases adultas de R. (B. microplus; sin embargo, existen en el mercado LM de larga acción que presentan eficacia > 95% con persistencia hasta 70 días PT.An overview of the macrocyclic lactones (ML, with recent results and their effect on the control of Rhipicephalus (Boophilus microplus, is presented in this paper. This review describes in detail the chemistry, pharmacokinetics and dose presentation, security and time withdrawal and environmental safety of the groups belonging to ML: avermectins (ivermectin, doramectin, eprinomectin, abamectin and milbemycin (moxidectin. There is also a discussion on their efficacy and the problem of resistance of R. (B. microplus to ML. Finally, it is concluded that due to their high lipid solubility ML are widely distributed in tissues, being effective in the control of R. (B. microplus in cattle. The efficacy of short-acting ivermectin, doramectin, eprinomectin, abamectin and moxidectin are similar (> 90% effective after four weeks post treatment, PT to control adult stages of R. (B. microplus, however, in long-acting LM are available the market and present efficiency of > 95% with persistence up to 70 days PT.

  12. Clustomesogens: Liquid Crystalline Hybrid Nanomaterials Containing Functional Metal Nanoclusters. (United States)

    Molard, Yann


    Inorganic phosphorescent octahedral metal nanoclusters fill the gap between metal complexes and nanoparticles. They are finite groups of metal atoms linked by metal-metal bonds, with an exact composition and structure at the nanometer scale. As their phosphorescence internal quantum efficiency can approach 100%, they represent a very attractive class of molecular building blocks to design hybrid nanomaterials dedicated to light energy conversion, optoelectronic, display, lighting, or theragnostic applications. They are obtained as AnM6X(i)8X(a)6 ternary salt powders (A = alkali cation, M = Mo, Re, W, X(i): halogen inner ligand, X(a) = halogen apical ligand) by high temperature solid state synthesis (750-1200 °C). However, their ceramic-like behavior has largely restricted their use as functional components in the past. Since these last two decades, several groups, including ours, started to tackle the challenge of integrating them in easy-to-process materials. Within this context, we have extensively explored the nanocluster ternary salt specificities to develop a new class of self-organized hybrid organic-inorganic nanomaterials known as clustomesogens. These materials, combine the specific properties of nanoclusters (magnetic, electronic, luminescence) with the anisotropy-related properties of liquid crystals (LCs). This Account covers the research and development of clustomesogens starting from the design concepts and synthesis to their introduction in functional devices. We developed three strategies to build such hybrid super- or supramolecules. In the covalent approach, we capitalized on the apical ligand-metal bond iono-covalent character to graft tailor-made organic LC promoters on the {M6X(i)8}(n+) nanocluster cores. The supramolecular approach relies on the host-guest complexation of the ternary cluster salt alkali cations with functional crown ether macrocycles. We showed that the hybrid LC behavior depends on the macrocycles structural features

  13. Efficient and selective formation of macrocyclic disubstituted Z alkenes by ring-closing metathesis (RCM) reactions catalyzed by Mo- or W-based monoaryloxide pyrrolide (MAP) complexes: applications to total syntheses of epilachnene, yuzu lactone, ambrettolide, epothilone C, and nakadomarin A. (United States)

    Wang, Chenbo; Yu, Miao; Kyle, Andrew F; Jakubec, Pavol; Dixon, Darren J; Schrock, Richard R; Hoveyda, Amir H


    The first broadly applicable set of protocols for efficient Z-selective formation of macrocyclic disubstituted alkenes through catalytic ring-closing metathesis (RCM) is described. Cyclizations are performed with 1.2-7.5 mol% of a Mo- or W-based monoaryloxide pyrrolide (MAP) complex at 22 °C and proceed to complete conversion typically within two hours. Utility is demonstrated by synthesis of representative macrocyclic alkenes, such as natural products yuzu lactone (13-membered ring: 73% Z) epilachnene (15-membered ring: 91% Z), ambrettolide (17-membered ring: 91% Z), an advanced precursor to epothilones C and A (16-membered ring: up to 97% Z), and nakadomarin A (15-membered ring: up to 97% Z). We show that catalytic Z-selective cyclizations can be performed efficiently on gram-scale with complex molecule starting materials and catalysts that can be handled in air. We elucidate several critical principles of the catalytic protocol: 1) The complementary nature of the Mo catalysts, which deliver high activity but can be more prone towards engendering post-RCM stereoisomerization, versus W variants, which furnish lower activity but are less inclined to cause loss of kinetic Z selectivity. 2) Reaction time is critical to retaining kinetic Z selectivity not only with MAP species but with the widely used Mo bis(hexafluoro-tert-butoxide) complex as well. 3) Polycyclic structures can be accessed without significant isomerization at the existing Z alkenes within the molecule.

  14. Cobalt(III) tetraaza-macrocyclic complexes as efficient catalyst for photoinduced hydrogen production in water: Theoretical investigation of the electronic structure of the reduced species and mechanistic insight. (United States)

    Gueret, Robin; Castillo, Carmen E; Rebarz, Mateusz; Thomas, Fabrice; Hargrove, Aaron-Albert; Pécaut, Jacques; Sliwa, Michel; Fortage, Jérôme; Collomb, Marie-Noëlle


    We recently reported a very efficient homogeneous system for visible-light driven hydrogen production in water based on the cobalt(III) tetraaza-macrocyclic complex [Co(CR)Cl2](+) (1) (CR=2,12-dimethyl-3,7,11,17-tetra-azabicyclo(11.3.1)-heptadeca-1(17),2,11,13,15-pentaene) as a noble metal-free catalyst, with [Ru(II)(bpy)3](2+) (Ru) as photosensitizer and ascorbate/ascorbic acid (HA(-)/H2A) as a sacrificial electron donor and buffer (PhysChemChemPhys 2013, 15, 17544). This catalyst presents the particularity to achieve very high turnover numbers (TONs) (up to 1000) at pH 4.0 at a relative high concentration (0.1mM) generating a large amount of hydrogen and having a long term stability. A similar activity was observed for the aquo derivative [Co(III)(CR)(H2O)2](3+) (2) due to substitution of chloro ligands by water molecule in water. In this work, the geometry and electronic structures of 2 and its analog [Zn(II)(CR)Cl](+) (3) derivative containing the redox innocent Zn(II) metal ion have been investigated by DFT calculations under various oxidation states. We also further studied the photocatalytic activity of this system and evaluated the influence of varying the relative concentration of the different components on the H2-evolving activity. Turnover numbers versus catalyst (TONCat) were found to be dependent on the catalyst concentration with the highest value of 1130 obtained at 0.05 mM. Interestingly, the analogous nickel derivative, [Ni(II)(CR)Cl2] (4), when tested under the same experimental conditions was found to be fully inactive for H2 production. Nanosecond transient absorption spectroscopy measurements have revealed that the first electron-transfer steps of the photocatalytic H2-evolution mechanism with the Ru/cobalt tetraaza/HA(-)/H2A system involve a reductive quenching of the excited state of the photosensitizer by ascorbate (kq=2.5×10(7) M(-1) s(-1)) followed by an electron transfer from the reduced photosensitizer to the catalyst (ket=1.4×10(9) M

  15. Late First-Row Transition-Metal Complexes Containing a 2-Pyridylmethyl Pendant-Armed 15-Membered Macrocyclic Ligand. Field-Induced Slow Magnetic Relaxation in a Seven-Coordinate Cobalt(II) Compound. (United States)

    Antal, Peter; Drahoš, Bohuslav; Herchel, Radovan; Trávníček, Zdeněk


    The 2-pyridylmethyl N-pendant-armed heptadentate macrocyclic ligand {3,12-bis(2-methylpyridine)-3,12,18-triaza-6,9-dioxabicyclo[12.3.1]octadeca-1,14,16-triene = L} and [M(L)](ClO4)2 complexes, where M = Mn(II) (1), Fe(II) (2), Co(II) (3), Ni(II) (4), and Cu(II) (5), were prepared and thoroughly characterized, including elucidation of X-ray structures of all the compounds studied. The complexes 1-5 crystallize in non-centrosymmetric Sohncke space groups as racemic compounds. The coordination numbers of 7, 6 + 1, and 5 were found in complexes 1-3, 4, and 5, respectively, with a distorted pentagonal bipyramidal (1-4) or square pyramidal (5) geometry. On the basis of the magnetic susceptibility experiments, a large axial zero-field splitting (ZFS) was found for 2, 3, and 4 (D(Fe) = -7.4(2) cm(-1), D(Co) = 34(1) cm(-1), and D(Ni) = -12.8(1) cm(-1), respectively) together with a rhombic ZFS (E/D = 0.136(3)) for 4. Despite the easy plane anisotropy (D > 0, E/D = 0) in 3, the slow relaxation of the magnetization below 8 K was observed and analyzed either with Orbach relaxation mechanism (the relaxation time τ0 = 9.90 × 10(-10) s and spin reversal barrier Ueff = 24.3 K (16.9 cm(-1))) or with Raman relaxation mechanism (C = 2.12 × 10(-5) and n = 2.84). Therefore, compound 3 enlarges the small family of field-induced single-molecule magnets with pentagonal-bipyramidal chromophore. The cyclic voltammetry in acetonitrile revealed reversible redox processes in 1-3 and 5, except for the Ni(II) complex 4, where a quasi-reversible process was dominantly observed. Presence of the two 2-pyridylmethyl pendant arms in L with a stronger σ-donor/π-acceptor ability had a great impact on the properties of all the complexes (1-5), concretely: (i) strong pyridine-metal bonds provided slight axial compression of the coordination sphere, (ii) substantial changes in magnetic anisotropy, and (iii) stabilization of lower oxidation states.

  16. Resistance to the macrocyclic lactone moxidectin is mediated in part by membrane transporter P-glycoproteins: Implications for control of drug resistant parasitic nematodes. (United States)

    Bygarski, Elizabeth E; Prichard, Roger K; Ardelli, Bernadette F


    Our objective was to determine if the resistance mechanism to moxidectin (MOX) is similar of that to ivermectin (IVM) and involves P-glycoproteins (PGPs). Several Caenorhabditis elegans strains were used: an IVM and MOX sensitive strain, 13 PGP deletion strains and the IVM-R strain which shows synthetic resistance to IVM (by creation of three point mutations in genes coding for α-subunits of glutamate gated chloride channels [GluCls]) and cross-resistance to MOX. These strains were used to compare expression of PGP genes, measure motility and pharyngeal pumping phenotypes and evaluate the ability of compounds that inhibit PGP function to potentiate sensitivity or reverse resistance to MOX. The results suggest that C. elegans may use regulation of PGPs as a response mechanism to MOX. This was indicated by the over-expression of several PGPs in both drug sensitive and IVM-R strains and the significant changes in phenotype in the IVM-R strain in the presence of PGP inhibitors. However, as the inhibitors did not completely disrupt expression of the phenotypic traits in the IVM-R strain, this suggests that there likely are multiple avenues for MOX action that may include receptors other than GluCls. If MOX resistance was mediated solely by GluCls then exposure of the IVM-R strain to PGP inhibitors should not have affected sensitivity to MOX. Targeted gene deletions showed that protection of C. elegans against MOX involves complex mechanisms and depends on the PGP gene family, particularly PGP-6. While the results presented are similar to others using IVM, there were some important differences observed with respect to PGPs which may play a role in the disparities seen in the characteristics of resistance to IVM and MOX. The similarities are of concern as parasites resistant to IVM show some degree but not complete cross-resistance to MOX; this could impact nematodes that are resistant to IVM.

  17. Resistance to the macrocyclic lactone moxidectin is mediated in part by membrane transporter P-glycoproteins: Implications for control of drug resistant parasitic nematodes

    Directory of Open Access Journals (Sweden)

    Elizabeth E. Bygarski


    Full Text Available Our objective was to determine if the resistance mechanism to moxidectin (MOX is similar of that to ivermectin (IVM and involves P-glycoproteins (PGPs. Several Caenorhabditis elegans strains were used: an IVM and MOX sensitive strain, 13 PGP deletion strains and the IVM-R strain which shows synthetic resistance to IVM (by creation of three point mutations in genes coding for α-subunits of glutamate gated chloride channels [GluCls] and cross-resistance to MOX. These strains were used to compare expression of PGP genes, measure motility and pharyngeal pumping phenotypes and evaluate the ability of compounds that inhibit PGP function to potentiate sensitivity or reverse resistance to MOX. The results suggest that C. elegans may use regulation of PGPs as a response mechanism to MOX. This was indicated by the over-expression of several PGPs in both drug sensitive and IVM-R strains and the significant changes in phenotype in the IVM-R strain in the presence of PGP inhibitors. However, as the inhibitors did not completely disrupt expression of the phenotypic traits in the IVM-R strain, this suggests that there likely are multiple avenues for MOX action that may include receptors other than GluCls. If MOX resistance was mediated solely by GluCls then exposure of the IVM-R strain to PGP inhibitors should not have affected sensitivity to MOX. Targeted gene deletions showed that protection of C. elegans against MOX involves complex mechanisms and depends on the PGP gene family, particularly PGP-6. While the results presented are similar to others using IVM, there were some important differences observed with respect to PGPs which may play a role in the disparities seen in the characteristics of resistance to IVM and MOX. The similarities are of concern as parasites resistant to IVM show some degree but not complete cross-resistance to MOX; this could impact nematodes that are resistant to IVM.

  18. A new macrocyclic trichochecene from soil fungus

    Institute of Scientific and Technical Information of China (English)


    From fermentation broth of soil fungus 254-2 obtained from Yunnan province,a new macrocylic trichochecene was isolated.The structure was determined on the basis of spectroscopic evidences especially the 2-D NMR spectra.

  19. Reaction of lanthanide nitrates with macrocyclic amidoacylhydrazones

    Energy Technology Data Exchange (ETDEWEB)

    Malinka, E.V.; Bondarev, M.L.; Bel' tyukova, S.V.; Poleuktov, N.S.; Nazarenko, N.A.


    This paper deals with a study of the reaction of neodymium and europium nitrates with 3,5,14,16-tetraazasubstituted dibenzo (d,j) (1,2,6,9,13,14) hexaazahexadeca-2,4,10,12-tetraene-7,8,15,16-tetraones. The authors carried out the investigations by means of conductimetry, UV luminescence, IR spectroscopy, and mass spectroscopy. Conductimetric titrations of the neodymium complexes were carried out on an OK-102/1 conductimeter. The luminescence spectra of the europium ion in the region of the /sup 5/D/sub 0/ ..-->.. /sup 7/F/sub 1/ and /sup 5/D/sub 0/ ..-->.. /sup 7/F/sub 2/ transitions (550-620 nm) were recorded on an ISP-51 spectrograph with an FEP-1 photoelectric attachment, using excitation by an SVD-120A mercury quartz lamp. The UV spectra of solutions of the compounds and the IR spectra of the solid substances in KBr disks were recorded on SpecordUViS and UR-20 spectrophotometers, respectively, and the mass spectra on a Varian Mat-112 spectrometer.

  20. A New Macrocyclic Trichochecene from Soil Fungus

    Institute of Scientific and Technical Information of China (English)

    TaoWANG; YiZHANG; 等


    From fermentation broth of soil fungus 254-2 obtained from Yunnan province, a new macrocylic trichochecene was isolated. The structure was determined on the basis of spectroscopie evidences especially the 2-D NMR spectra.

  1. Synthesis and characterization of dinuclear macrocyclic cobalt(II), copper(II) and zinc(II) complexes derived from 2,2,2('),2(')-S,S[bis(bis-N,N-2-thiobenzimidazolyloxalato-1,2-ethane)]: DNA binding and cleavage studies. (United States)

    Arjmand, Farukh; Aziz, Mubashira


    New homodinuclear macrocyclic complexes of cobalt(II), copper(II) and zinc(II) were isolated from the newly synthesized ligand 2,2,2',2'-S,S[bis(bis-N,N-2-thiobenzimidazolyloxalato-1,2-ethane)]. The structures of the complexes were elucidated by elemental analysis, molar conductance measurements, IR, 1H NMR, 13C NMR, electronic and ESI-MS spectroscopic techniques. In complex 1, Co(II) ions possess a tetrahedral coordination environment composed of O2S2 donor atoms while its Cu(II) and Zn(II) counterparts 2 and 3, respectively, reveal a six coordinate octahedral structure, defined by the O2S2 donors from the macrocyclic ring and two chloride ions. Molar conductance and spectroscopic data also support the proposed geometry of the complexes. DNA binding properties of complexes 1-3 were investigated using electronic absorption spectroscopy, fluorescence spectroscopy, viscosity measurements and cyclic voltammetry. The absorption spectra of complexes 2 and 3 with calf thymus DNA showed hypochromism, while complex 1 showed hyperchromism attributed to a partial intercalation and electrostatic binding modes, respectively. The intrinsic binding constant K(b) of complexes 1-3 were determined as 16.6 x 10(4) M(-1), 4.25 x 10(4) M(-1) and 3.0 x 10(4) M(-1), respectively. The decrease in the relative specific viscosity of calf thymus DNA with increasing concentration of the complexes authenticates the partial intercalation binding mode. Gel electrophoresis of complex 2 with plasmid DNA demonstrated that complex exhibits excellent "artificial" nuclease activity.

  2. Control of oxo-group functionalization and reduction of the uranyl ion. (United States)

    Arnold, Polly L; Pécharman, Anne-Frédérique; Lord, Rianne M; Jones, Guy M; Hollis, Emmalina; Nichol, Gary S; Maron, Laurent; Fang, Jian; Davin, Thomas; Love, Jason B


    Uranyl complexes of a large, compartmental N8-macrocycle adopt a rigid, "Pacman" geometry that stabilizes the U(V) oxidation state and promotes chemistry at a single uranyl oxo-group. We present here new and straightforward routes to singly reduced and oxo-silylated uranyl Pacman complexes and propose mechanisms that account for the product formation, and the byproduct distributions that are formed using alternative reagents. Uranyl(VI) Pacman complexes in which one oxo-group is functionalized by a single metal cation are activated toward single-electron reduction. As such, the addition of a second equivalent of a Lewis acidic metal complex such as MgN″2 (N″ = N(SiMe3)2) forms a uranyl(V) complex in which both oxo-groups are Mg functionalized as a result of Mg-N bond homolysis. In contrast, reactions with the less Lewis acidic complex [Zn(N″)Cl] favor the formation of weaker U-O-Zn dative interactions, leading to reductive silylation of the uranyl oxo-group in preference to metalation. Spectroscopic, crystallographic, and computational analysis of these reactions and of oxo-metalated products isolated by other routes have allowed us to propose mechanisms that account for pathways to metalation or silylation of the exo-oxo-group.

  3. Functional Boxplots

    KAUST Repository

    Sun, Ying


    This article proposes an informative exploratory tool, the functional boxplot, for visualizing functional data, as well as its generalization, the enhanced functional boxplot. Based on the center outward ordering induced by band depth for functional data, the descriptive statistics of a functional boxplot are: the envelope of the 50% central region, the median curve, and the maximum non-outlying envelope. In addition, outliers can be detected in a functional boxplot by the 1.5 times the 50% central region empirical rule, analogous to the rule for classical boxplots. The construction of a functional boxplot is illustrated on a series of sea surface temperatures related to the El Niño phenomenon and its outlier detection performance is explored by simulations. As applications, the functional boxplot and enhanced functional boxplot are demonstrated on children growth data and spatio-temporal U.S. precipitation data for nine climatic regions, respectively. This article has supplementary material online. © 2011 American Statistical Association.

  4. Functionalized Calixpyrroles

    DEFF Research Database (Denmark)

    Vargas-Zúñiga, Gabriela; Sessler, Jonathan; Bähring, Steffen


    as the extraction and transport of anionic species and ion pairs including cesium halide and sulfate salts. It is divided into seven sections. The first section describes the synthetic methods employed to functionalized calix[4]pyrrole. The second section focuses on functionalized calix[4]pyrroles that display...... enhanced anion binding properties compared to the non-functionalized parent system, octamethylcalix[4]pyrrole. The use of functionalized calix[4]pyrroles containing a fluorescent group or functionalized calix[4]pyrroles as building blocks for the preparation of stimulus-responsive materials is discussed...... and the eventual development of therapeutics that function via the transport of anions across cell membranes, are discussed....

  5. Entire functions

    CERN Document Server

    Markushevich, A I


    Entire Functions focuses on complex numbers and the algebraic operations on them and the basic principles of mathematical analysis.The book first elaborates on the concept of an entire function, including the natural generalization of the concept of a polynomial and power series. The text then takes a look at the maximum absolute value and the order of an entire function, as well as calculations for the coefficients of power series representing a given function, use of integrals, and complex numbers. The publication elaborates on the zeros of an entire function and the fundamen

  6. Functionalized amphipols

    DEFF Research Database (Denmark)

    Della Pia, Eduardo Antonio; Hansen, Randi Westh; Zoonens, Manuela


    Amphipols are amphipathic polymers that stabilize membrane proteins isolated from their native membrane. They have been functionalized with various chemical groups in the past years for protein labeling and protein immobilization. This large toolbox of functionalized amphipols combined with their......Amphipols are amphipathic polymers that stabilize membrane proteins isolated from their native membrane. They have been functionalized with various chemical groups in the past years for protein labeling and protein immobilization. This large toolbox of functionalized amphipols combined...... surfaces for various applications in synthetic biology. This review summarizes the properties of functionalized amphipols suitable for synthetic biology approaches....

  7. Lightness functions

    DEFF Research Database (Denmark)

    Campi, Stefano; Gardner, Richard; Gronchi, Paolo;


    Variants of the brightness function of a convex body K in n-dimensional Euclidean are investigated. The Lambertian lightness function L(K; v , w ) gives the total reflected light resulting from illumination by a light source at infinity in the direction w that is visible when looking...... in the direction v . The partial brightness function R( K ; v , w ) gives the area of the projection orthogonal to v of the portion of the surface of K that is both illuminated by a light source from the direction w and visible when looking in the direction v . A class of functions called lightness functions...... is introduced that includes L(K;.) and R(K;.) as special cases. Much of the theory of the brightness function like uniqueness, stability, and the existence and properties of convex bodies of maximal and minimal volume with finitely many function values equal to those of a given convex body, is extended...

  8. Functional analysis

    CERN Document Server

    Kantorovich, L V


    Functional Analysis examines trends in functional analysis as a mathematical discipline and the ever-increasing role played by its techniques in applications. The theory of topological vector spaces is emphasized, along with the applications of functional analysis to applied analysis. Some topics of functional analysis connected with applications to mathematical economics and control theory are also discussed. Comprised of 18 chapters, this book begins with an introduction to the elements of the theory of topological spaces, the theory of metric spaces, and the theory of abstract measure space

  9. Neristatin 1 provides critical insight into bryostatin 1 structure-function relationships. (United States)

    Kedei, Noemi; Kraft, Matthew B; Keck, Gary E; Herald, Cherry L; Melody, Noeleen; Pettit, George R; Blumberg, Peter M


    Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina, has been the subject of multiple clinical trials for cancer. Although it functions as an activator of protein kinase C (PKC) in vitro, bryostatin 1 paradoxically antagonizes most responses to the prototypical PKC activator, the phorbol esters. The bottom half of the bryostatin 1 structure has been shown to be sufficient to confer binding to PKC. In contrast, we have previously shown that the top half of the bryostatin 1 structure is necessary for its unique biological behavior to antagonize phorbol ester responses. Neristatin 1 comprises a top half similar to that of bryostatin 1 together with a distinct bottom half that confers PKC binding. We report here that neristatin 1 is bryostatin 1-like, not phorbol ester-like, in its biological activity on U937 promyelocytic leukemia cells. We conclude that the top half of the bryostatin 1 structure is largely sufficient for bryostatin 1-like activity, provided the molecule also possesses an appropriate PKC binding domain.

  10. Neristatin 1 Provides Critical Insight into Bryostatin 1 Structure–Function Relationships (United States)


    Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina, has been the subject of multiple clinical trials for cancer. Although it functions as an activator of protein kinase C (PKC) in vitro, bryostatin 1 paradoxically antagonizes most responses to the prototypical PKC activator, the phorbol esters. The bottom half of the bryostatin 1 structure has been shown to be sufficient to confer binding to PKC. In contrast, we have previously shown that the top half of the bryostatin 1 structure is necessary for its unique biological behavior to antagonize phorbol ester responses. Neristatin 1 comprises a top half similar to that of bryostatin 1 together with a distinct bottom half that confers PKC binding. We report here that neristatin 1 is bryostatin 1-like, not phorbol ester-like, in its biological activity on U937 promyelocytic leukemia cells. We conclude that the top half of the bryostatin 1 structure is largely sufficient for bryostatin 1-like activity, provided the molecule also possesses an appropriate PKC binding domain. PMID:25808573

  11. Stability Functions

    CERN Document Server

    Burns, Daniel; Wang, Zuoqin


    In this article we discuss the role of stability functions in geometric invariant theory and apply stability function techniques to problems in toric geometry. In particular we show how one can use these techniques to recover results of Burns-Guillemin-Uribe and Shiffman-Tate-Zelditch on asymptotic properties of sections of holomorphic line bundles over toric varieties.


    Institute of Scientific and Technical Information of China (English)



    <正>A power function of degree n is a function of the form f(x)=ax~n.For large n,it appears that the graph coincide with the x-axis near the origin,but it does not;the graph actually touches the x—axis only at the origin.





    This paper presents the correspondences of the eccentric mathematics of cardinal and integral functions and centric mathematics, or ordinary mathematics. Centric functions will also be presented in the introductory section, because they are, although widely used in undulatory physics, little known.





    This paper presents the correspondences of the eccentric mathematics of cardinal and integral functions and centric mathematics, or ordinary mathematics. Centric functions will also be presented in the introductory section, because they are, although widely used in undulatory physics, little known.

  15. Hierarchical on-surface synthesis and electronic structure of carbonyl-functionalized one- and two-dimensional covalent nanoarchitectures (United States)

    Steiner, Christian; Gebhardt, Julian; Ammon, Maximilian; Yang, Zechao; Heidenreich, Alexander; Hammer, Natalie; Görling, Andreas; Kivala, Milan; Maier, Sabine


    The fabrication of nanostructures in a bottom-up approach from specific molecular precursors offers the opportunity to create tailored materials for applications in nanoelectronics. However, the formation of defect-free two-dimensional (2D) covalent networks remains a challenge, which makes it difficult to unveil their electronic structure. Here we report on the hierarchical on-surface synthesis of nearly defect-free 2D covalent architectures with carbonyl-functionalized pores on Au(111), which is investigated by low-temperature scanning tunnelling microscopy in combination with density functional theory calculations. The carbonyl-bridged triphenylamine precursors form six-membered macrocycles and one-dimensional (1D) chains as intermediates in an Ullmann-type coupling reaction that are subsequently interlinked to 2D networks. The electronic band gap is narrowed when going from the monomer to 1D and 2D surface-confined π-conjugated organic polymers comprising the same building block. The significant drop of the electronic gap from the monomer to the polymer confirms an efficient conjugation along the triphenylamine units within the nanostructures.

  16. Preparation and characterization of electroluminescent devices based on complexes of {beta}-diketonates of Tb{sup 3+}, Eu{sup 3+}, Gd{sup 3+} ions with macrocyclic ligands and UO{sub 2}{sup 2+} films; Preparacao e caracterizacao de dispositivos eletroluminescentes de complexos de {beta}-dicetonados de ions Tb{sup 3+}, Eu{sup 3+}, Gd{sup 3+} com ligantes macrociclicos e filmes de UO{sub 2}{sup 2+}

    Energy Technology Data Exchange (ETDEWEB)

    Gibelli, Edison Bessa


    Complexes containing Rare Earth ions are of great interest in the manufacture of electro luminescent devices as organic light emitting devices (OLED). These devices, using rare earth trivalent ions (TR{sup 3+}) as emitting centers, show high luminescence with extremely fine spectral bands due to the structure of their energy levels, long life time and high quantum efficiency. This work reports the preparation of Rare Earth {beta}-diketonate complexes (Tb{sup 3+}, Eu{sup 3+} and Gd{sup 3+}) and (tta - thenoyltrifluoroacetonate and acac - acetylacetonate) containing a ligand macrocyclic crown ether (DB18C6 - dibenzo18coroa6) and polymer films of UO{sub 2}{sup 2+}. The materials were characterized by complexometric titration with EDTA, CH elemental analysis, near infrared absorption spectroscopy, thermal analysis, X-ray diffraction (powder method) and luminescence spectroscopy. For manufacturing the OLED it was used the technique of deposition of thin films by physical vapor (PVD, Physical Vapor Deposition). (author)

  17. Key players and legislative framework relative to radioactive materials and waste management; Principaux acteurs et cadre legislatif de la gestion des matieres et dechets radioactifs

    Energy Technology Data Exchange (ETDEWEB)

    Birraux, C. [Office Parlementaire d' Evaluation des Choix Scientifiques et Technologiques (OPECST), 75 - Paris (France)


    While French industry as a whole appears to have bowed slightly under increasing pressure from the competition in an international economic arena that is becoming more and more open and diverse, France's nuclear industry has firmly held onto its position as world leader, secured during the seventies and eighties. This is the result of sustained national investment in research to constantly improve the performance and safety of the solutions deployed; it is also due to the dynamism of the companies involved, which have successfully developed their international base while maintaining a firm national foothold; it is also due to a consistent commitment on the part of the public authorities, which have provided sound guidelines, while placing greater emphasis on transparency and giving structure to crucial dialogue with the public. France is also one of the first countries that has developed a nuclear power programme, to have set up an organisation, a framework and a coherent strategy regarding the management of all its radioactive waste. (author)

  18. Modélisation empirique des principaux déterminants socio-économiques de la gestion des exploitations agricoles au Sud-Ouest du Burkina Faso

    Directory of Open Access Journals (Sweden)

    Masse D.


    Full Text Available Empirical modelisation of socio-economic determinants in smallholder farming management in southwest of Burkina Faso. The study aims at identifying farmer’s decision rules and the socio-economic determinants of organic resource dynamics. Decision rules study and socio-economic determinants of organic resource dynamics allowed quantification of their impact on these organic resource dynamics. The main results of the investigations reveal that principal decision rules are edicted and managed by local authorities. These decision rules concern collective management and access to the cultivated land, grazing land, and homestead and to the bush. Farmers have also a diversity of individual rules covering production, consumption, marketing and relations between themselves. Survey of a sample of one hundred farmers selected for their representativity allowed to quantify relations between farm needs and their organic resource use. These relations permitted developing empirical statistical models (needs of land to cultivate, food grains needs, cash needs, fuel wood needs depending on farming system. Fuel wood needs were established with survey measured data. These needs expressed in kilogramme consumed wood per day per person were established for the dry season (0.97 kg per person and per day and for the wet season (1.36 kg per person and per day. Average fuel wood consumption per person and per day has an exponential decay when the household size increases. When land is available, land need for cultivation mainly depends on labour availability. Food grain needs is constant (180 kg per person and per year. It is the same in both farming systems studied. Money needs depend on cash crop surfaces, livestock’s products and extra agricultural activities of the farmer.

  19. Le rôle croissant des huiles tropicales sur les marchés internationaux : principaux acteurs et produits

    Directory of Open Access Journals (Sweden)

    Dronne Yves


    Full Text Available In the last thirty years, the international market for vegetable oils has developed substantially especially in terms of production and international trade. Three tropical oils: coconut, palm kernel and mainly palm oil and three countries: Indonesia, Malaysia and to a lesser extent the Philippines and play a major role in the supply of lipids to the rest of the world. Palm oil prices are generally lower than other vegetable oils such as soybean, rapeseed and sunflower, but since the beginning of 2006, they have risen steeply, as prices for most of agricultural products traded in the world, before showing a huge drop by the middle of the 2008 crop year. As palm has the most important oil yield among oilseed crops, future development of tropical oils is a major issue for the world market over the next years. There will be a growing food demand coming from areas in deficit of oilseed products (China, South Asia, Africa, etc.; these countries experience rapid demographic growth and increase in per capita consumption of oils and fats due to income growth during the last decade. Tropical oils could also play a major role in non-food sectors like lipid chemistry and biodiesel, either to be directly used in this production or to substitute other vegetable oils previously used for human food more and more used for bioenergy.

  20. Le moteur Diesel et son carburant. Principaux problèmes et solutions potentielles Diesel Engines and Their Fuel. The Leading Problems and Potential Solutions

    Directory of Open Access Journals (Sweden)

    Eyzat P.


    Full Text Available Après avoir rappelé les tendances récentes françaises et européennes relatives au développement du moteur Diesel et à la demande en gazole, on examine les principales caractéristiques contraignantes : comportement à froid, indice de cétane, tendance à l'encrassement des injecteurs. On présente diverses techniques ou projets de procédure permettant de progresser dans une meilleure connaissance de certains incidents (blocage des filtres en hiver, accroissement des émissions de bruit et de polluants avec des injecteurs encrassés. On décrit enfin les possibilités et les contraintes du raffinage pour fournir un gazole susceptible de satisfaire les divers utilisateurs. L'emploi d'additifs et la distribution de deux qualités de gazole constituent des moyens d'action possibles. After reviewing recent French and European trends concerning the development of diesel engines and the demand for diesel oil, this article examines the leading constraints : cold behavior, cetane number, tendency of injector fouling. Different techniques or possible procedures are described for gaining a better understanding of various incidents (filter plugging in winter, increase in noise and pollutant emissions with fouled injectors. The article concludes by describing the possibilities and constraints of refining for supplying diesel oil capable of meeting the needs of different users. The use of additives and the distribution of two qualities of diesel oil are possible means of action.


    Directory of Open Access Journals (Sweden)

    Alexis Saludjian


    Full Text Available La fuerte volatilidad macroeconómica de los países sudamericanos desde fines de los años setenta plantea interrogantes a los economistas sobre las estrategias de desarrollo que éstos promueven. La integración económica regional en el seno del MERCOSUR y la apertura económica y financiera se han preconizado como factores de estabilización macroeconómica. Para verificar esas hipótesis, estudiamos los corolarios de la volatilidad macroeconómica en el MERCOSUR en el periodo 1976-2001, distinguiendo dos subgrupos de países (Argentina/Uruguay y Brasil/Paraguay. Hemos llegado, por una parte, con nuestros datos estadísticos, a sacar a la luz las carencias del regionalismo abierto y validar el concepto de desmercosurización, y, por otro lado, confirmar el papel de la volatilidad que juegan los flujos de capital extranjeros.

  2. Management de l'information et veille stratégique: principaux freins et difficultés rencontrés sur le terrain


    Manelle Guechtouli


    Cet article cherche à identifier les principales difficultés liées au management des informations de veille stratégique. Il s’appuie sur une approche inductive à travers l’étude approfondie d’un cas unique (le système de veille d’une grande entreprise du secteur industriel). Les résultats montrent plusieurs facteurs problématiques que nous classons en 3 catégories (visibilité interne du système et implication, reconnaissance des veilleurs, adéquation des outils et besoins en veille). Les résu...

  3. Management de l'information et veille stratégique: principaux freins et difficultés rencontrés sur le terrain


    Manelle Guechtouli


    Cet article cherche à identifier les principales difficultés liées au management des informations de veille stratégique. Il s’appuie sur une approche inductive à travers l’étude approfondie d’un cas unique (le système de veille d’une grande entreprise du secteur industriel). Les résultats montrent plusieurs facteurs problématiques que nous classons en 3 catégories (visibilité interne du système et implication, reconnaissance des veilleurs, adéquation des outils et besoins en veille). Les résu...

  4. Ecosystem functioning

    National Research Council Canada - National Science Library

    Jax, Kurt


    "In the face of decreasing biodiversity and ongoing global changes, maintaining ecosystem functioning is seen both as a means to preserve biological diversity as well as for safeguarding human well...

  5. Transfer functions (United States)

    Taback, I.


    The vulnerability of electronic equipment to carbon fibers is studied. The effectiveness of interfaces, such as filters, doors, window screens, and cabinets, which affect the concentration, exposure, or deposition of carbon fibers on both (internal and external) sides of the interface is examined. The transfer function of multilayer aluminum mesh, wet and dry, polyurethane foam, and window screen are determined as a function of air velocity. FIlters installed in typical traffic control boxes and air conditioners are also considered.

  6. Functional Unparsing

    DEFF Research Database (Denmark)

    Danvy, Olivier


    A string-formatting function such as printf in C seemingly requires dependent types, because its control string determines the rest of its arguments. We show how changing the representation of the control string makes it possible to program printf in ML (which does not allow dependent types......). The result is well typed and perceptibly more efficient than the corresponding library functions in Standard ML of New Jersey and in Caml....

  7. Functional unparsing

    DEFF Research Database (Denmark)

    Danvy, Olivier


    A string-formatting function such as printf in C seemingly requires dependent types, because its control string determines the rest of its arguments. Examples: formula here We show how changing the representation of the control string makes it possible to program printf in ML (which does not allow...... dependent types). The result is well typed and perceptibly more efficient than the corresponding library functions in Standard ML of New Jersey and in Caml....

  8. Coordination functionalization of graphene oxide with tetraazamacrocyclic complexes of nickel(II): Generation of paramagnetic centers

    Energy Technology Data Exchange (ETDEWEB)

    Basiuk, Vladimir A., E-mail: [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Circuito Exterior C.U., 04510 México D.F. (Mexico); Department of Chemistry,Tufts University, 62 Talbot Avenue, Medford, MA 02155 (United States); Alzate-Carvajal, Natalia [Centro de Ciencias Aplicadas y Desarrollo Tecnológico, Universidad Nacional Autónoma de México, Circuito Exterior C.U., 04510 México D.F. (Mexico); Henao-Holguín, Laura V. [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Circuito Exterior C.U., 04510 México D.F. (Mexico); Rybak-Akimova, Elena V. [Department of Chemistry,Tufts University, 62 Talbot Avenue, Medford, MA 02155 (United States); Basiuk, Elena V., E-mail: [Department of Chemistry,Tufts University, 62 Talbot Avenue, Medford, MA 02155 (United States); Centro de Ciencias Aplicadas y Desarrollo Tecnológico, Universidad Nacional Autónoma de México, Circuito Exterior C.U., 04510 México D.F. (Mexico)


    Highlights: • [Ni(cyclam)]{sup 2+} and [Ni(tet b)]{sup 2+} cations coordinate to carboxylic groups of GO. • The coordination takes place under basic conditions in aqueous-based medium. • The coordination results in the conversion from low-spin to high-spin Ni(II). • Functionalized GO samples were characterized by various instrumental techniques. - Abstract: We describe a novel approach to functionalization of graphene oxide (GO) which allows for a facile generation of paramagnetic centers from two diamagnetic components. Coordination attachment of [Ni(cyclam)]{sup 2+} or [Ni(tet b)]{sup 2+} tetraazamacrocyclic cations to carboxylic groups of GO takes place under basic conditions in aqueous-based reaction medium. The procedure is very straightforward and does not require high temperatures or other harsh conditions. Changing the coordination geometry of Ni(II) from square-planar tetracoordinated to pseudooctahedral hexacoordinated brings about the conversion from low-spin to high-spin state of the metal centers. Even though the content of tetraazamacrocyclic complexes in functionalized GO samples was found to be relatively low (nickel content of ca. 1 wt%, as determined by thermogravimetric analysis, elemental analysis and energy dispersive X-ray spectroscopy), room temperature magnetic susceptibility measurements easily detected the appearance of paramagnetic properties in GO + [Ni(cyclam)] and GO + [Ni(tet b)] nanohybrids, with effective magnetic moments of 1.95 BM and 2.2 BM for, respectively. According to density functional theory calculations, the main spin density is localized at the macrocyclic complexes, without considerable extension to graphene sheet, which suggests insignificant ferromagnetic coupling in the nanohybrids, in agreement with the results of magnetic susceptibility measurements. The coordination attachment of Ni(II) tetraazamacrocycles to GO results in considerable changes in Fourier-transform infrared and X-ray photoelectron spectra

  9. interval functions

    Directory of Open Access Journals (Sweden)

    J. A. Chatfield


    Full Text Available Suppose N is a Banach space of norm |•| and R is the set of real numbers. All integrals used are of the subdivision-refinement type. The main theorem [Theorem 3] gives a representation of TH where H is a function from R×R to N such that H(p+,p+, H(p,p+, H(p−,p−, and H(p−,p each exist for each p and T is a bounded linear operator on the space of all such functions H. In particular we show that TH=(I∫abfHdα+∑i=1∞[H(xi−1,xi−1+−H(xi−1+,xi−1+]β(xi−1+∑i=1∞[H(xi−,xi−H(xi−,xi−]Θ(xi−1,xiwhere each of α, β, and Θ depend only on T, α is of bounded variation, β and Θ are 0 except at a countable number of points, fH is a function from R to N depending on H and {xi}i=1∞ denotes the points P in [a,b]. for which [H(p,p+−H(p+,p+]≠0 or [H(p−,p−H(p−,p−]≠0. We also define an interior interval function integral and give a relationship between it and the standard interval function integral.

  10. Bessel functions

    CERN Document Server

    Nambudiripad, K B M


    After presenting the theory in engineers' language without the unfriendly abstraction of pure mathematics, several illustrative examples are discussed in great detail to see how the various functions of the Bessel family enter into the solution of technically important problems. Axisymmetric vibrations of a circular membrane, oscillations of a uniform chain, heat transfer in circular fins, buckling of columns of varying cross-section, vibrations of a circular plate and current density in a conductor of circular cross-section are considered. The problems are formulated purely from physical considerations (using, for example, Newton's law of motion, Fourier's law of heat conduction electromagnetic field equations, etc.) Infinite series expansions, recurrence relations, manipulation of expressions involving Bessel functions, orthogonality and expansion in Fourier-Bessel series are also covered in some detail. Some important topics such as asymptotic expansions, generating function and Sturm-Lioville theory are r...

  11. Algebraic functions

    CERN Document Server

    Bliss, Gilbert Ames


    This book, immediately striking for its conciseness, is one of the most remarkable works ever produced on the subject of algebraic functions and their integrals. The distinguishing feature of the book is its third chapter, on rational functions, which gives an extremely brief and clear account of the theory of divisors.... A very readable account is given of the topology of Riemann surfaces and of the general properties of abelian integrals. Abel's theorem is presented, with some simple applications. The inversion problem is studied for the cases of genus zero and genus unity. The chapter on t


    Institute of Scientific and Technical Information of China (English)



    <正>Polynomial functions are among the sim- plest expressions in algebra.They are easy to evaluate:only addition and repeated multipli- cation are required.Because of this,they are often used to approximate other more compli-

  13. Functional dyspepsia

    NARCIS (Netherlands)

    Kleibeuker, JH; Thijs, JC


    Purpose of review Functional dyspepsia is a common disorder, most of the time of unknown etiology and with variable pathophysiology. Therapy has been and still is largely empirical. Data from recent studies provide new clues for targeted therapy based on knowledge of etiology and pathophysiologic me

  14. Functional Organometallics

    Institute of Scientific and Technical Information of China (English)



    1 Results The lecture will address aspects of functional organometallics related to the development of novel organometallic materials.In chromium complexes of fused arenes-regio-and diastereoselectively accessible by chromium-templated benzannulation of arylcarbenes by alkynes[1]-a haptotropic migration of the chromium fragment along the π-face of fused arenes is controlled by both thermodynamics and the substitution pattern of the arene and the metal coligand sphere,and can be applied towards an organo...

  15. Functional Literacy

    Directory of Open Access Journals (Sweden)

    Fani Nolimal


    Full Text Available The author first defines literacy as the ability of co-operation in all fields of life and points at the features of illiterate or semi-literate individuals. The main stress is laid upon the assessment of literacy and illiteracy. In her opinion the main weak­ ness of this kind of evaluation are its vague psycho-metric characteristics, which leads to results valid in a single geographical or cultural environment only. She also determines the factors causing illiteracy, and she states that the level of functional literacy is more and more becoming a national indicator of successfulness.

  16. Lung function

    Institute of Scientific and Technical Information of China (English)


    2005200 The effect of body position changes on lung function, lung CT imaging and pathology in an oleic acid induced acute lung injury model. JI Xin-ping (戢新平), et al. Dept Emergency, 1st Affili Hosp, China Med Univ, Shenyang 110001. Chin J Tuberc Respir Dis, 2005;28(1) :33-36. Objective: To study the effect of body position changes on lung mechanics, oxygenation, CT images and pathology in an oleic acid-induced acute lung injury (ALl) model. Methods: The study groups con-

  17. Exploring Novel Spintronic Responses from Advanced Functional Organic Materials (United States)


    SUPPLEMENTARY NOTES 14. ABSTRACT The effort investigates experiments on supermacrocycles which are 2D polymers reminiscent of graphene . Semi empirical...initiated experiments on “super”macrocycles which are 2D polymers reminiscent of graphene . Semi-empirical calculations indicate the important structure...superscripts indicate the process in which two photons from the fundamental beam are annihilated in a second harmonic generation process while the

  18. A quantitative description of the ground-state wave function of Cu(A) by X-ray absorption spectroscopy: comparison to plastocyanin and relevance to electron transfer. (United States)

    DeBeer George, S; Metz, M; Szilagyi, R K; Wang, H; Cramer, S P; Lu, Y; Tolman, W B; Hedman, B; Hodgson, K O; Solomon, E I


    To evaluate the importance of the electronic structure of Cu(A) to its electron-transfer (ET) function, a quantitative description of the ground-state wave function of the mixed-valence (MV) binuclear Cu(A) center engineered into Pseudomonas aeruginosa azurin has been developed, using a combination of S K-edge and Cu L-edge X-ray absorption spectroscopies (XAS). Parallel descriptions have been developed for a binuclear thiolate-bridged MV reference model complex ([(L(i)(PrdacoS)Cu)(2)](+)) and a homovalent (II,II) analogue ([L(i)(Pr2tacnS)Cu)(2)](2+), where L(i)(PrdacoS) and L(i)(Pr2tacnS) are macrocyclic ligands with attached thiolates that bridge the Cu ions. Previous studies have qualitatively defined the ground-state wave function of Cu(A) in terms of ligand field effects on the orbital orientation and the presence of a metal--metal bond. The studies presented here provide further evidence for a direct Cu--Cu interaction and, importantly, experimentally quantify the covalency of the ground-state wave function. The experimental results are further supported by DFT calculations. The nature of the ground-state wave function of Cu(A) is compared to that of the well-defined blue copper site in plastocyanin, and the importance of this wave function to the lower reorganization energy and ET function of Cu(A) is discussed. This wave function incorporates anisotropic covalency into the intra- and intermolecular ET pathways in cytochrome c oxidase. Thus, the high covalency of the Cys--Cu bond allows a path through this ligand to become competitive with a shorter His path in the intramolecular ET from Cu(A) to heme a and is particularly important for activating the intermolecular ET path from heme c to Cu(A).

  19. A crystalline sponge based on dispersive forces suitable for X-ray structure determination of included molecular guests† †Electronic supplementary information (ESI) available: Synthesis of macrocycle 3 together with characterization data. TGA and DSC traces. CIF files of all structures. Computational details and additional calculations. CCDC 1012389–1012397 and 1063714. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5sc01838b Click here for additional data file. Click here for additional data file. (United States)

    Sanna, Elena; Escudero-Adán, Eduardo C.; Bauzá, Antonio; Ballester, Pablo; Frontera, Antonio; Rotger, Carmen


    A crystalline porous material showing one-dimensional (1-D) rectangular micropores (12 × 9 Å2) has been assembled from a semirigid macrocyclic tetraimine and EtOAc as the templating agent. The 1-D nature of the material is intrinsic to the conformationally rigid structure of a macrocyclic sub-unit bearing four cyclohexylidene residues. The multiple dispersive forces established among the aliphatic residues glutted the 1-D channels and provided thermal stability to the material at temperatures below 160 °C. Upon removal of the template, the structure of the empty solid exhibited permanent microporosity (S BET = 342 m2 g–1). Being a true molecular sponge, the channel framework of this material allowed the inclusion of a variety of molecular sample guests without compromising its crystalline nature. Remarkably, this crystalline material enabled the structure determination by X-ray diffraction of the included molecules. Theoretical studies demonstrated the vital role played by the dispersive forces in the overall stabilization of the crystal packing. PMID:28757946

  20. Well-defined functional mesoporous silica/polymer hybrids prepared by an ICAR ATRP technique integrated with bio-inspired polydopamine chemistry for lithium isotope separation. (United States)

    Liu, Yuekun; Liu, Xuegang; Ye, Gang; Song, Yang; Liu, Fei; Huo, Xiaomei; Chen, Jing


    Mesoporous silica/polymer hybrids with well-preserved mesoporosity were prepared by integrating the initiators for continuous activator regeneration (ICAR) atom transfer radical polymerization (ATRP) technique with the bio-inspired polydopamine (PDA) chemistry. By manipulating the auto-oxidative polymerization of dopamine, uniform PDA layers were deposited on the surfaces and pore walls of ordered mesoporous silicas (OMSs), thereby promoting the immobilization of ATRP initiators. Poly(glycidyl methacrylate) (PGMA) brushes were then grown from the OMSs by using the ICAR ATRP technique. The evolution of the mesoporous silica/polymer hybrids during synthesis, in terms of morphology, structure, surface and porous properties, was detailed. And, parameters influencing the controlled growth of polymer chains in the ICAR ATRP system were studied. Taking advantage of the abundant epoxy groups in the PGMA platform, post-functionalization of the mesoporous silica/polymer hybrids by the covalent attachment of macrocyclic ligands for the adsorptive separation of lithium isotopes was realized. Adsorption behavior of the functionalized hybrids toward lithium ions was fully investigated, highlighting the good selectivity, and effects of temperature, solvent and counter ions. The ability for lithium isotope separation was evaluated. A higher separation factor could be obtained in systems with softer counter anions and lower polarity solvents. More importantly, due to the versatility of the ICAR ATRP technique, combined with the non-surface specific PDA chemistry, the methodology established in this work would provide new opportunities for the preparation of advanced organic-inorganic porous hybrids for broadened applications.