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Sample records for adamantane

  1. Point Groups Based on Methane and Adamantane (Td) Skeletons.

    Science.gov (United States)

    Fujita, Shinsaku

    1986-01-01

    Describes a procedure for constructing point groups based on the symmetric parent molecules of methane and adamantane. Intended for use in teaching concepts such as subgroups and cosets to beginners in group theory. (TW)

  2. Synthesis of novel quaternary ammonium surfactants containing adamantane

    Institute of Scientific and Technical Information of China (English)

    Jian Wei Guo; Xing Zhong; Hua Zhu; Li Juan Feng; Ying De Cui

    2012-01-01

    A series of novel quaternary ammonium surfactants containing adamantane were designed and synthesized from 1-adamantanecarboxylic acid.The structures of target surfactants were confirmed by 1H NMR,elements analysis and FTIR.Surface properties of these surfactants were investigated.Due to the lipophilicity of adamantane,the critical micelle concentration (CMC) and C20 values of the synthesized quaternary ammonium surfactants are lower than that of conventional quaternary ammonium surfactants.

  3. Genetic relation of adamantanes from extracts and semicoking tars of lignites with the initial biological material

    Energy Technology Data Exchange (ETDEWEB)

    Platonov, V.V.; Shvykin, A.Y.; Proskuryakov, V.A.; Podshibyakin, S.I. [Lev Tolstoi State Pedagogical University, Tula (Russian Federation)

    1999-11-01

    A genetic relation was revealed of adamantanes from extracts and semicoking tars of lignites with the relic terpenoid and steroid compounds. Probable pathways are suggested for transformation of the initial natural structures into adamantanes. The qualitative and quantitative compositions of adamantanes from crude oil and coal are compared.

  4. NMDA receptor complex mapping by an adamantane derivative

    Energy Technology Data Exchange (ETDEWEB)

    Samnick, S.; Ametamey, S.M.; Eichholzer, Y. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1997-08-01

    The memantine analogue, 1-amino-3-[{sup 18}F]fluoromethyl-adamantane ({sup 18}F-MEM), a potential tracer for mapping the N-Methyl-D-Aspartate receptor complex was characterized using different in vivo and in vitro binding techniques. (author) figs., tab., refs.

  5. Crystal structure and physical properties of a dithiolene complex crystal with adamantane supramolecular rotator

    OpenAIRE

    Yan, Yin-Nan; Kubo, Kazuya; Noro, Shin-ichiro; Akutagawa, Tomoyuki; Nakamura, Takayoshi

    2014-01-01

    Supramolecular cation salt of adamantane rotator with a dithiolene complex, (fluoroadamantylammonium(+))([18]-crown-6)[Ni(dmit)(2)](-) (1) was synthesized. The fluorine atom of the adamantane unit showed a large thermal factor elongated latitudinally, suggesting molecular rotation in the solid state. Crystal 1 exhibited a large dielectric response by applying an AC field along the a axis.

  6. The role of C-H$\\ldots$ interaction in the stabilization of benzene and adamantane clusters

    Indian Academy of Sciences (India)

    R Mahesh Kumar; M Elango; R Parthasarathi; Dolly Vijay; V Subramanian

    2012-01-01

    In this investigation, a systematic attempt has been made to understand the interaction between adamantane and benzene using both ab initio and density functional theory methods. C-H$\\ldots$ type of interaction between C-H groups of adamantane and cloud of benzene is found as the important attraction for complex formation. The study also reveals that the methylene (-CH2) and methine (-CH) groups of adamantane interact with benzene resulting in different geometrical structures. And it is found that the former complex is stronger than the later. The diamondoid structure of adamantane enables it to interact with a maximum of four benzene molecules, each one along the four faces. The stability of the complex increases with increase in the number of benzene molecules. The energy decomposition analysis of adamantane-benzene complexes using DMA approach shows that the origin of the stability primarily arises from the dispersive interaction. The theory of atoms in molecules (AIM) supports the existence of weak interaction between the two systems. The electrostatic topography features provide clues for the mode of interaction of adamantane with benzene.

  7. Synthesis and Crystal Structure of a New Adamantane Amide Derivative

    Institute of Scientific and Technical Information of China (English)

    ZHOU Ying-Hua; LV Qi-Chun; ZHANG Qian; CHENG Yong; SHENG En-Hong

    2012-01-01

    A novel adamantane acyl amide derivative containing two phthalimido pendant groups(C31H31N3O5) has been synthesized,and its structure was characterized by elemental analysis,IR,1 H NMR spectra,and single-crystal X-ray diffraction.The crystal belongs to triclinic,space group P1 with a=7.3158(10),b=13.2405(18),c=14.378(2),α=72.419(2),β=84.496(2),γ=81.799(2)o,V=1312.0(3)3,Z=2,Dc=1.330 g/cm 3,μ=0.09 mm-1,Mr=525.59,F(000)=556,S=1.001,R=0.0523 and wR=0.0707 for 5901 unique reflections with 2363 observed ones(I〉2σ(I)).π-π stacking interactions(offset face-to-face) exist between the two rings of phthalimides from the neighboring molecules in the title crystal structure.The intermolecular dihedral angle between the two rings of neighboring phthalic amides is 6.26° and the distance is 4.008.

  8. Using crystal structure prediction to rationalize the hydration propensities of substituted adamantane hydrochloride salts.

    Science.gov (United States)

    Mohamed, Sharmarke; Karothu, Durga Prasad; Naumov, Panče

    2016-08-01

    The crystal energy landscapes of the salts of two rigid pharmaceutically active molecules reveal that the experimental structure of amantadine hydrochloride is the most stable structure with the majority of low-energy structures adopting a chain hydrogen-bond motif and packings that do not have solvent accessible voids. By contrast, memantine hydrochloride which differs in the substitution of two methyl groups on the adamantane ring has a crystal energy landscape where all structures within 10 kJ mol(-1) of the global minimum have solvent-accessible voids ranging from 3 to 14% of the unit-cell volume including the lattice energy minimum that was calculated after removing water from the hydrated memantine hydrochloride salt structure. The success in using crystal structure prediction (CSP) to rationalize the different hydration propensities of these substituted adamantane hydrochloride salts allowed us to extend the model to predict under blind test conditions the experimental crystal structures of the previously uncharacterized 1-(methylamino)adamantane base and its corresponding hydrochloride salt. Although the crystal structure of 1-(methylamino)adamantane was correctly predicted as the second ranked structure on the static lattice energy landscape, the crystallization of a Z' = 3 structure of 1-(methylamino)adamantane hydrochloride reveals the limits of applying CSP when the contents of the crystallographic asymmetric unit are unknown.

  9. Adamantane-Resistant Influenza A Viruses in the World (1902–2013): Frequency and Distribution of M2 Gene Mutations

    Science.gov (United States)

    Dong, Guoying; Peng, Chao; Luo, Jing; Wang, Chengmin; Han, Le; Wu, Bin; Ji, Guangju; He, Hongxuan

    2015-01-01

    Adamantanes (amantadine and rimantadine) have been used to prevent and treat influenza A virus infections for many years; however, resistance to these drugs has been widely reported in the world. To investigate the frequency and distribution of M2 gene mutations in adamantane-resistant influenza variants circulated in the world between 1902 and 2013, 31251 available M2 protein sequences from different HA-subtype influenza A viruses (H1–H17) were analyzed and adamantane resistance-associated mutations were compared (L26F, V27A, A30T, A30V, S31N, G34E, and L38F). We find that 45.2% (n = 14132) of influenza A (H1–H17) viruses circulating globally were resistant to adamantanes, and the vast majority of resistant viruses (95%) bear S31N mutations. Whereas, only about 1% have V27A mutations and other mutations (L26F, A30T, G34E, and L38F) were extremely rare (their prevalence appeared to be resistance to adamantanes. In contrast, the appearance of adamantane-resistant mutants in H2, H4, H6, H10, and H11 subtypes was rare. However, no adamantane resistance viruses were identified among other HA subtypes (H8, H12–H16). Our findings indicate that the frequency and distribution of adamantane-resistant influenza variants varied among different HA subtypes, host species, years of isolation, and geographical areas. This comprehensive study raises concerns about the increasing prevalence of adamantane-resistant influenza A viruses and highlights the importance of monitoring the emergence and worldwide spread of adamantane-resistant variants. PMID:25768797

  10. Calculation of dipole polarizability derivatives of adamantane and their use in electron scattering computations

    DEFF Research Database (Denmark)

    Sauer, Stephan P. A.; Paidarová, Ivana; Čársky, Petr

    2016-01-01

    In this paper we present calculations of the static polarizability and its derivatives for the adamantane molecule carried out at the density functional theory level using the B3LYP exchange correlation functional and Sadlej’s polarized valence triple zeta basis set. It is shown that the polariza...

  11. Tetrakis(dimethoxyphenyl)adamantane (TDA) and its inclusion complexes in the crystalline state: a versatile carrier for small molecules.

    Science.gov (United States)

    Schwenger, Alexander; Frey, Wolfgang; Richert, Clemens

    2015-06-08

    Molecular storage solutions for incorporating small molecules in crystalline matrices are of interest in the context of structure elucidation, decontamination, and slow release of active ingredients. Here we report the syntheses of 1,3,5,7-tetrakis(2,4-dimethoxyphenyl)adamantane, 1,3,5,7-tetrakis(4-methoxyphenyl)adamantane, 1,3,5,7-tetrakis(4-methoxy-2-methylphenyl)adamantane, and 1,3,5,7-tetrakis(4-methoxy-2-ethylphenyl)adamantane, together with their X-ray crystal structures. All four compounds crystallize readily. Only the octaether shows an unusual level of (pseudo)polymorphism in its crystalline state, combined with the ability to include a number of different small molecules in its crystal lattices. A total of 20 different inclusion complexes with guest molecules as different as ethanol or trifluorobenzene were found. For nitromethane and benzene, schemes for uptake and release are presented.

  12. Calculation of dipole polarizability derivatives of adamantane and their use in electron scattering computations

    Science.gov (United States)

    Sauer, Stephan P. A.; Paidarová, Ivana; Čársky, Petr; Čurík, Roman

    2016-05-01

    In this paper we present calculations of the static polarizability and its derivatives for the adamantane molecule carried out at the density functional theory level using the B3LYP exchange-correlation functional and Sadlej's polarized valence triple zeta basis set. It is shown that the polarizability tensor is necessary to correct long-range behavior of DFT functionals used in electron-molecule scattering calculations. The impact of such a long-range correction is demonstrated on elastic and vibrationally inelastic electron collisions with adamantane, a molecule representing a large polyatomic target for electron scattering calculations. Contribution to the Topical Issue "Advances in Positron and Electron Scattering", edited by Paulo Limao-Vieira, Gustavo Garcia, E. Krishnakumar, James Sullivan, Hajime Tanuma and Zoran Petrovic.

  13. Structural, Electronic, and Vibrational Properties of Amino-adamantane and Rimantadine Isomers

    CERN Document Server

    Garcia, Joelson Cott; Machado, Wanda V M; Assali, Lucy V C; 10.1021/jp107496b

    2012-01-01

    We performed a first principles total energy investigation on the structural, electronic, and vibrational properties of adamantane molecules, functionalized with amine and ethanamine groups. We computed the vibrational signatures of amantadine and rimantadine isomers with the functional groups bonded to different carbon sites. By comparing our results with recent infrared and Raman spectroscopic data, we discuss the possible presence of different isomers in experimental samples.

  14. Sorption of adamantane phenylamide derivatives on hyper-cross-linked polystyrene from water-acetonitrile eluents

    Science.gov (United States)

    Shafigulin, R. V.; Konstantinov, A. V.; Bulanova, A. V.; Il'in, M. M.; Davankov, V. A.

    2016-11-01

    Study of the main physicochemical features of the sorption of phenylamide adamantane derivatives on hyper-cross-linked polystyrene from water-acetonitrile solutions shows that both hydrophobic and electronic interactions make a large contribution to retention, especially for a chlorine-containing derivative in which there are π- p and π- d interactions between the outer-shell electrons of the chlorine atom in addition to π- π interactions between aromatic fragments of the sorbate and sorbent.

  15. Vibrational spectra and molecular structure of isomeric 1-(adamantan-1-ylcarbonyl)-3-(dichlorophenyl)thioureas

    Science.gov (United States)

    Saeed, Aamer; Ashraf, Zaman; Erben, Mauricio F.; Simpson, Jim

    2017-02-01

    1-(adamantan-1-ylcarbonyl)-3-(2,3-dichlorophenyl)thiourea, 1, and 1-(adamantan-1-ylcarbonyl)-3-(2,5-dichlorophenyl)thiourea, 2, were synthesized in reasonable yields from admanantyl-1-carbonyl chloride and ammonium thiocyanate followed by treatment of the resulting adamantane-1-carbonylisothiocyanate with the 2,3- and 2,5-dichloroanilines. A complete vibrational analysis was performed on the basis of FTIR and Raman spectra. The formation of intramolecular Nsbnd H⋯O and intermolecular Nsbnd H⋯S hydrogen bonds in the solids affect vibrational modes, with low frequency values observed for the ν(Cdbnd O) and ν(Cdbnd S) stretching modes. Structural data obtained by single-crystal X-ray diffraction at low temperature confirm this picture. Compound 1 crystallizes in the triclinic system and compound 2 crystallizes with two unique molecules in the asymmetric unit of the orthorhombic unit cell. The molecular structures reveal that the carbonylthiourea units in 1 and both molecules of 2 are planar due in part to the formation of intramolecular Nsbnd H⋯Odbnd C hydrogen bonds that generate S (6) rings. Moreover, the crystal structures are stabilized by an extensive series of classical and non-classical hydrogen bonds and, in the case of 1 by an intermolecular Cl⋯Cl halogen bond.

  16. Research of some sides of antifungal activity mechanism act of new adamantane derivative

    Directory of Open Access Journals (Sweden)

    Vrynchanu N.A.

    2009-01-01

    Full Text Available Mechanism of the antiviral action of adamantane-containing preparations caused by their membranotropic properties. In the screening studies we discovered the substance 4-adamantyl-1(1-aminobutil benzene (substance AM-166 with the wide spectrum of antimicrobic action. AM-166 suppresses increase and multiplication of bacteria (aerobic, anaerobic and fungi (yeast like, mold and dermatomyces. The ointment for treating the pyoinflammatory processes was developed on the basis of adamantane-containing substance. The purpose of our experiments was to learn some sides of the mechanism of the antifungal action of substance AM-166 at the ultramicroscopic level. Experiments were carried out on the Candida albicans NCTC885/653. Substance concentration was 4 MIC. Ultrathin sections obtained on the ultratome LKB-880 U and contrasted by acetate of uranyl and by citrate of lead, were investigated in the electron microscope EM-125 K. It is established, that the substance AM-166 in concentration 4 MIC causes the damage of cell wall and cytoplasmic structures of the yeast-like fungus of C.albicans. These disturbances were recorded after 1 h of incubation with the substance AM-166. Thus, our experiments showed that the inhibiting action of adamantane-containing substance is caused, first of all, by influence on the cellular mem-brane of fungus.

  17. Energies for cyclic and acyclic aggregations of adamantane and diamantane units sharing vertices, edges, or six-membered rings

    CERN Document Server

    Balaban, Alexandru T; Klein, Douglas J; Ortiz, Yenni P

    2015-01-01

    Diamondoids are hydrocarbons having a carbon scaffold comprised from polymer-like composites of adamantane cages. The present paper describes computed total energies and "SWB-tension" energies (often referred to as "strain" energies) for species having $n$ adamantane or diamantane units sharing pairwise: one carbon atom (spiro-[n]adamantane or spiro-[$n$]diamantane); one C-C bond (one-bond-sharing-[$n$]adamantane or one-bond-sharing-[$n$]diamantane); or one chair-shaped hexagon of carbon atoms (1234-helical-cata-[$n$]diamantanes). Each of the five investigated polymer-like types is considered either as an acyclic or a cyclic chain of adamantane- or diamantane-unit cages. With increasing $n$ values, SWB-tension energies for acyclic aggregates are found to increase linearly, while the net SWB-tension energies of cyclic aggregates often go thru a minimum at a suitable value of $n$. In all five cases, a limiting common energy per unit ($E/n$ ) is found to be approached by both cyclic and acyclic chains as $n\\to \\...

  18. Using Electronic Properties of Adamantane Derivatives to Analyze their Ion Channel Interactions: Implications for Alzheimer's Disease

    Science.gov (United States)

    Bonacum, Jason

    2013-03-01

    The derivatives of adamantane, which is a cage-like diamondoid structure, can be used as pharmaceuticals for the treatment of various diseases and disorders such as Alzheimer's disease. These drugs interact with ion channels, and they act by electronically and physically hindering the ion transport. The electronic properties of each compound influence the location and level of ion channel hindrance, and the specific use of each compound depends on the functional groups that are attached to the adamantane base chain. Computational analysis and molecular simulations of these different derivatives and the ion channels can provide useful insight into the effect that the functional groups have on the properties of the compounds. Using this information, conclusions can be made about the pharmaceutical mechanisms, as well as how to improve them or create new beneficial compounds. Focusing on the electronic properties, such as the dipole moments of the derivatives and amino acids in the ion channels, can provide more efficient predictions of how these drugs work and how they can be enhanced. Department of Energy Grant DE-FG02-06ER46304

  19. Synthesis and single-molecule imaging of highly mobile adamantane-wheeled nanocars.

    Science.gov (United States)

    Chu, Pin-Lei E; Wang, Lin-Yung; Khatua, Saumyakanti; Kolomeisky, Anatoly B; Link, Stephan; Tour, James M

    2013-01-22

    The synthesis and single-molecule imaging of two inherently fluorescent nanocars equipped with adamantane wheels is reported. The nanocars were imaged using 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) as the chromophore, which was rigidly incorporated into the nanocar chassis via Sonogashira cross-coupling chemistry that permitted the synthesis of nanocars having different geometries. In particular, studied here were four- and three-wheeled nanocars with adamantane wheels. It was found that, for the four-wheeled nanocar, the percentage of moving nanocars and the diffusion constant show a significant improvement over p-carborane-wheeled nanocars with the same chassis. The three-wheeled nanocar showed only limited mobility due to its geometry. These results are consistent with a requisite wheel-like rolling motion. We furthermore developed a model that relates the percentage of moving nanocars in single-molecule experiments with the diffusion constant. The excellent agreement between the model and the new results presented here as well as previous single-molecule studies of fluorescent nanocars yields an improved understanding of motion in these molecular machines.

  20. Thiol-yne Click Adamantane Monolithic Stationary Phase for Capillary Electrochromatography

    Institute of Scientific and Technical Information of China (English)

    Dao, Thi Thu Hien; Guerrouache, Mohamed; Carbonnier, Benjamin

    2012-01-01

    A porous crosslinked organic polymer based on N-acryloxysuccinimide (NAS) and ethylene dimethacrylate (EDMA) was prepared inside 75 μm i.d. fused silica capillary as functionalizable monolithic stationary phase for electrochromatographic applications. Succinimide groups on the monolith surface provide reactive sites able to re- act readily through standard electrophile-nucleophile chemistry. Propargylamine was used to prepare alkyne func- tionalized poly(NAS-co-EDMA). Onto this thiol-reactive polymer surface was grafted adamantane units via a photochemically-driven addition reaction. Chemical characterization was performed in situ after each synthetic step by means of Raman spectroscopy and grafting kinetics was investigated to ensure quantitative grafting of 1-adamantanethiol. The as-designed monolithic stationary phase exhibited typical reversed-phase separation mechanism as evidenced by the linear increase of the logarithm of retention factor of neutral aromatic solutes with the increase of the aqueous buffer content in the mobile phase.

  1. Adamantane derivatives of sulfonamides: sublimation, solubility, solvation and transfer processes in biologically relevant solvents.

    Science.gov (United States)

    Perlovich, G L; Volkova, T V; Sharapova, A V; Kazachenko, V P; Strakhova, N N; Proshin, A N

    2016-04-07

    Eight adamantane derivatives of sulfonamides were synthesized and characterized. Temperature dependencies of saturation vapor pressure were obtained using the transpiration method and thermodynamic functions of the sublimation processes were calculated. Solubility values of the selected compounds in buffer (pH 7.4), 1-octanol and 1-hexane were determined at different temperatures using the isothermal saturation method. Thermophysical characteristics of fusion processes (melting points and fusion enthalpies) of the substances were studied using the DSC method. Transfer processes from buffer to 1-octanol, from buffer to 1-hexane and 1-hexane to 1-octanol were analyzed. The impact of the molecules' structural modification on sublimation, solubility and solvation/hydration processes in the solvents was studied. Correlation equations connecting the thermodynamic functions with physicochemical descriptors were obtained.

  2. Polymer bilayer formation due to specific interactions between beta-cyclodextrin and adamantane: a surface force study.

    Science.gov (United States)

    Blomberg, Eva; Kumpulainen, Atte; David, Christelle; Amiel, Catherine

    2004-11-23

    The purposes of this study are to utilize the interactions between an adamantane end-capped poly(ethylene oxide) (PEO) and a cationic polymer of beta-cyclodextrin to build polymer bilayers on negatively charged surfaces, and to investigate the interactions between such layers. The association of this system in solution has been studied by rheology, light scattering, and fluorescence measurements. It was found that the adamantane-terminated PEO (PEO-Ad) mixed with the beta-cyclodextrin polymer gives complexes where the interpolymer links are formed by specific inclusion of the adamantane groups in the beta-cyclodextrin cavities. This results in a higher viscosity of the solution and growth of intermolecular clusters. The interactions between surfaces coated with a cationized beta-cyclodextrin polymer across a water solution containing PEO-Ad polymers were studied by employing the interferometric surface force apparatus (SFA). In the first step, the interaction between mica surfaces coated with the cationized beta-cyclodextrin polymer in pure water was investigated. It was found that the beta-cyclodextrin polymer adsorbs onto mica and almost neutralizes the surface charge. The adsorbed layers of the beta-cyclodextrin polymer are rather compact, with a layer thickness of about 60 A (30 A per surface). Upon separation, a very weak attractive force is observed. The beta-cyclodextrin solution was then diluted by pure water by a factor of 3000 and a PEO-Ad polymer was introduced into the solution. Two different architectures of the PEO-Ad polymer were investigated: a four-arm structure and a linear structure. After the adsorption of the PEO polymer onto the beta-cyclodextrin layer reached equilibrium, the forces were measured again. It was found that the weak repulsive long-range force had disappeared and an attractive force caused the surfaces to jump into contact, and that the compressed layer thickness had increased. The attractive force is interpreted as being due to

  3. Synthesis, physical and chemical properties of 5-(adamantane-1-yl-4-amino-1,2,4-triazole-3-thiol derivatives

    Directory of Open Access Journals (Sweden)

    V. M. Odyntsova

    2016-12-01

    Full Text Available Implementation of new highly efficient drugs in medical practice is one of the most urgent problems of modern pharmaceutical industry. Scientific achievements of heterocyclic compounds’ chemistry clearly show that 1,2,4-triazole system is promising object of such research. It should be also noted that compounds, with adamantane "core" deserve special attention. The aim of our work was to synthesize new derivatives of 5-(adamantan-1-yl-4-amino-1,2,4-triazole-3-thiols, and to investigate their physical and chemical properties. Materials and methods. Chemical names of compounds are given in accordance with IUPAC nomenclature (1979 and the IUPAC recommendations (1993. Study of physical-chemical properties of obtained compounds was carried out in accordance with methods listed in the State Pharmacopia of Ukraine. Melting point was determined on the automatic device for determining the melting temperature Stanford Research Systems OptiMelt MPA100 (manufacturing USA. Elemental composition of new compounds was established on the elemental analyzer Elementar Vario EL cube (CHNS (standard – sulfanilamide. The data of elemental analysis correspond to the calculated one. 1H NMR spectra of compounds were recorded using spectrometer "Mercury 400". Chromato-mass spectra were recorded on a spectrometer Agilent 6890N/5973N/FID production of Agilent Technologies. Results. The concept of creating biologically active molecules is first of all directed on combining fragments of different molecules in one. Theoretically, this could lead to the new types of compounds with pharmacological action, and sometimes to the potentiation of existing biological properties. Further actions are focused on the physical and chemical properties study of these compounds. To establish the structure of 5-(adamantan-1-yl-4-((aryl-, heterylilyden-amino-1,2,4-triazole-3-thiols we used an integrated approach with the use of modern physical and chemical methods of analysis

  4. 对称桥头二取代金刚烷衍生物的合成%Synthesis of Symmetrical Disubstituted Bridgehead Adamantane Derivatives

    Institute of Scientific and Technical Information of China (English)

    徐晓健; 郭建维; 朱东雨; 钟星

    2014-01-01

    The symmetric bridge disubstituted adamantane derivatives are the key raw materials or interme-diates for preparing multisubstituted adamantane derivatives with admantane as the core. With 1-adamantane carboxylic acid that is more efficient and economical as an initial reactant, a series of synthesis technologies of symmetrical disubstituted bridgehead adamantane derivatives which have significant applications, were studied in this work. Those synthesis technologies include the following:1,3-adamantane dicarboxylic acid(1) was synthesized by 1-adamantane carboxylic acid through Koch-Haaf carbonylation; compound 1 was reduced to get 1,3-adamantane dimethanol(2);compound 2 reacted by bromination in HBr-ZnBr2 system to afford 1,3-dibromomethyl adamantane(3). Meanwhile, compound 2 converted to 1,3-dichloromethyl adamantane(4) through Apple-Lee reaction. The structures of prepared products were confirmed by IR spectra and 1 H NMR spectroscopy. The possible reaction mechanism was proposed, and the synthesis conditions were discussed and optimized for each technology respectively.%以易得的1-金刚烷甲酸为原料,合成了一系列对称桥头二取代金刚烷衍生物。由1-金刚烷甲酸经Koch-Haaf羰基化反应得到1,3-金刚烷二甲酸(1);化合物1经还原得到1,3-金刚烷二甲醇(2);化合物2在HBr-ZnBr2体系中经溴代反应得1,3-二(溴甲基)金刚烷(3);同时经Apple-Lee反应将化合物2转化得到1,3-二(氯甲基)金刚烷(4)。采用红外光谱和核磁共振氢谱等手段表征了产物的结构,提出了可能的反应机理,并对合成条件进行了优化。

  5. Synthesis and Electroluminescent Properties of Julolidine-π-Juloidine Type Materials with the Bulky Adamantane Groups

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kum Hee; Yoon, Seung Soo [Sungkyunkwan Univ., Suwon (Korea, Republic of); Lee, Seok Jae; Kim, Young Kwan [Hongik Univ., Seoul (Korea, Republic of)

    2012-11-15

    A main problem of red emitting material, which contributes to their low EL performances, is the concentration quenching due to the effective self aggregation and the consequent formation of excimers. To avoid this drawback and thus improve the EL properties of red fluorescent OLED devices, many synthetic efforts have been conducted to develop new emitting materials with the structural motifs to suppress self-aggregation by the weakening intermolecular attractive interactions. Particularly, the introduction of bulky moieties in the emitters would provide the steric hindrance between emitting materials in solid state devices and thus reduce the self-aggregation. Nevertheless, EL performances of red materials still need to be improved for the practical applications. In conclusion, we designed and synthesized three julolidine-π-juloidine type emitting materials (1-3) with the bulky adamantane groups. To study their electroluminescent properties, the multilayered OLED devices with the structure of ITO/NPB (40 nm)/ADN : 1-3 (x%) (20 nm)/Alq{sub 3} (40 nm)/Liq (2 nm)/Al were fabricated. All devices using emitters 1-3 showed the efficient emissions, in which their EL performances depend on the structure of emitters sensitively. Particularly, a device using emitter 3 exhibited the efficient orange-red emission with the luminous and power efficiencies of 4.79 cd/A and 1.76 lm/W at 20 mA/cm{sup 2}, respectively. The CIE coordinates of this device was (0.57, 0.42) at 7.0 V.

  6. Quaternized adamantane-containing poly(aryl ether ketone) anion exchange membranes for vanadium redox flow battery applications

    Science.gov (United States)

    Zhang, Bengui; Zhang, Shouhai; Weng, Zhihuan; Wang, Guosheng; Zhang, Enlei; Yu, Ping; Chen, Xiaomeng; Wang, Xinwei

    2016-09-01

    Quaternized adamantane-containing poly(aryl ether ketone) anion exchange membranes (QADMPEK) are prepared and investigated for vanadium redox flow batteries (VRFB) application. The bulky, rigid and highly hydrophobic adamantane segment incorporated into the backbone of membrane material makes QADMPEK membranes have low water uptake and swelling ratio, and the as-prepared membranes display significantly lower permeability of vanadium ions than that of Nafion117 membrane. As a consequence, the VRFB cell with QADMPEK-3 membrane shows higher coulombic efficiency (99.4%) and energy efficiency (84.0%) than those for Nafion117 membrane (95.2% and 80.5%, respectively) at the current density of 80 mA cm-2. Furthermore, at a much higher current density of 140 mA cm-2, QADMPEK membrane still exhibits better coulombic efficiency and energy efficiency than Nafion117 membrane (coulombic efficiency 99.2% vs 96.5% and energy efficiency 76.0% vs 74.0%). Moreover, QADMPEK membranes show high stability in in-situ VRFB cycle test and ex-situ oxidation stability test. These results indicate that QADMPEK membranes are good candidates for VRFB applications.

  7. Implanted muon spin spectroscopy on 2-O-adamantane: a model system that mimics the liquid\\longrightarrow glasslike transitions

    Science.gov (United States)

    Romanini, M.; Tamarit, J. L.; Pardo, L. C.; Bermejo, F. J.; Fernandez-Perea, R.; Pratt, F. L.

    2017-03-01

    The transition taking place between two metastable phases in 2-O-adamantane, namely the Fm\\bar{3}m cubic, rotator phase and the lower temperature P21/c, Z  =  4 substitutionally disordered crystal is studied by means of muon spin rotation and relaxation techniques. Measurements carried out under zero, weak transverse and longitudinal fields reveal a temperature dependence of the relaxation parameters strikingly similar to those exhibited by structural glass\\longrightarrow liquid transitions (Bermejo et al 2004 Phys. Rev. B 70 214202; Cabrillo et al 2003 Phys. Rev. B 67 184201). The observed behaviour manifests itself as a square root singularity in the relaxation rates pointing towards some critical temperature which for amorphous systems is located some tens of degrees above that shown as the characteristic transition temperature if studied by thermodynamic means. The implications of such findings in the context of current theoretical approaches concerning the canonical liquid-glass transition are discussed.

  8. First-principles calculation of structural and electronic properties of memantine (Alzheimer's disease) and adamantane (anti-flu) drugs

    Science.gov (United States)

    Middleton, Kirsten; Zhang, Guoping; George, Thomas F.

    2012-02-01

    Memantine is currently used as a treatment for mild to severe Alzheimer's disease, although its functionality is complicated. Using various density functional theory calculations and basis sets, we first examine memantine alone and then add ions which are present in the human body. This provides clues as to how the compound may react in the calcium ion channel, where it is believed to treat the disease. In order to understand the difference between calcium and magnesium ions interacting with memantine, we compute the electron affinity of each complex. We find that memantine is more strongly attracted to magnesium ions than calcium ions within the channel. By observing the HOMO-LUMO gap within memantine in comparison to adamantane, we find that memantine is more excitable than the anti-flu drug. We believe these factors to affect the efficiency of memantine as a treatment of Alzheimer's disease.

  9. Novel glass-forming organic materials. 2. Structure and fluorescence of pyrene- and carbazole-containing cyclohexane, bicyclooctene, and adamantane

    Energy Technology Data Exchange (ETDEWEB)

    Mastrangelo, J.C.; Conger, B.M.; Chen, S.H. [Univ. of Rochester, NY (United States)] [and others

    1997-01-01

    A series of novel glass-forming organic materials consisting of pyrenyl and carbazolyl groups attached to cyclohexane with a 1-axial-2-equatorial configuration, bicyclo[2.2.2]oct-7-ene with an all-exo configuration, and adamantane were synthesized and characterized. On the basis of proton NMR spectra, it was found that the rotation of pendant pyrenyl and carbazolyl groups is restricted in the bicyclic system presumably because of steric hindrance in the all-exo configuration. In contrast, free rotation was found to prevail in cyclohexane- and adamantane-based systems. Fluorescence spectra gathered in solution at room temperature show evidence exclusively for intramolecular excimer formation in pyrene-containing compounds up to a concentration of 10{sup -4} M. On the contrary, carbazole-containing compounds are not prone to excimer formation in the concentration range 10{sup -6}-10{sup -3} M, presumably because of the more stringent requirements of interchromophoric distance and orientation. Although both pyrene and carbazole are highly crystalline on their own, attachment to cyclic, bicyclic, and tricyclic central cores was found to contribute to an ease of vitrification of the hybrid systems with a T{sub g} ranging from 43 to 132 {degrees}C. Moreover, the quenched glasses of all seven model systems were found to possess morphological stability in view of the absence of recrystallization upon heating from 0 to 200 {degrees}C at a heating rate ranging from 0.2 to 20{degrees}C/min. Morphological stability was further supported by the absence of recrystallization upon prolonged thermal annealing at temperatures above T{sub g}. 24 refs., 6 figs.

  10. Vibrational Spectra of 3-(Adamantan-1-YL)-4-(2-Propen-1-YL)-1 H-1,2,4-Triazole-5(4 H)-Thione

    Science.gov (United States)

    Gladkov, L. L.; Matsukovich, A. S.; Pavich, T. A.; Gaponenko, S. V.; El-Emam, A. A.

    2017-01-01

    Vibrational spectra of 3-(adamantan-1-yl)-4-(2-propen-1-yl)-1H-1,2,4-triazole-5(4H)-thione (C15H21N3S), which was promising for drug development, were studied experimentally and theoretically. The geometric structure and normal modes of the molecule and its dimer were calculated using quantum-mechanical density functional theory. It was shown that the experimentally obtained vibrational spectra were due to dimeric C15H21N3S structures. This conclusion was confirmed by spectra of the isotopically substituted compound with a deuterated imine. Bands at 1496 and 1549 cm-1 were identified as markers of dimer formation. Bands at 936 and 1244 cm-1 were found to be markers of intermolecular interactions of adamantane fragments.

  11. Luminescent properties and structure of multicomponent naphthalene-{beta}-cyclodextrin complexes. 1. Effect of adding third parties, o-carborane or/and adamantane

    Energy Technology Data Exchange (ETDEWEB)

    Nazarov, Valery B. [Institute of Problems of Chemical Physics of Russian Academy of Sciences, 142432 Moscow region, Chernogolovka (Russian Federation); Avakyan, Vitaly G., E-mail: avak@photonics.ru [Photochemistry Center of Russian Academy of Sciences, 119421 Moscow, Novatorov 7a (Russian Federation); Rudyak, Vladimir Y.; Alfimov, Michail V. [Photochemistry Center of Russian Academy of Sciences, 119421 Moscow, Novatorov 7a (Russian Federation); Vershinnikova, Tatiana G. [Institute of Problems of Chemical Physics of Russian Academy of Sciences, 142432 Moscow region, Chernogolovka (Russian Federation)

    2011-09-15

    Luminescence spectra of water solution of {beta}-cyclodextrin ({beta}-CD) inclusion complexes with naphthalene have been studied in the presence of carcass compounds (CC), adamantane and ocarborane, added in solution as the third parties. It was observed that the CC structure completely determines luminescence type displayed by the three-component complex. Adding adamantane to the solution leads to the disappearance of the spontaneous excimer fluorescence observed usually along with a monomer fluorescence of naphthalene and the appearance of the long lived phosphorescence at room temperature. At the same time, introducing o-carborane in solution of {beta}-CD inclusion complexes with naphthalene results in the dramatic growth of intensity of the excimer band at the expense of lowering intensity of monomer fluorescence. These phenomena were explained using results of the quantum-chemical calculation of the structure and complexation energies at the semi-empirical PM3 and DFT levels of theory. - Highlights: > Structure of carcass compounds determines luminescence types for naphthalene - betaCD complex. > Adding o-carborane leads to the growth of excimer fluorescence at low naphthalene concentrations. > Adding adamantane leads to the room temperature phosphorescence without deoxygenation.

  12. Controlled gelation kinetics of cucurbit[7]uril-adamantane cross-linked supramolecular hydrogels with competing guest molecules

    Science.gov (United States)

    Chen, Hao; Hou, Shengzhen; Ma, Haili; Li, Xu; Tan, Yebang

    2016-02-01

    Gelation kinetics of hydrogels is closely linked to many applications such as the development of injectable and printable hydrogels. However, the control of gelation kinetics without compromising the structure and other properties of the hydrogels, remains a challenge. Here, we demonstrate a method to control the gelation kinetics of cucurbit[7]uril-adamantane (CB[7]-AD) cross-linked supramolecular hydrogels by using competing guest molecules. The association between CB[7] and AD moieties on the polymer backbone was impeded by pre-occupying the CB[7] cavity with competing guest molecules. By using various guest molecules and concentrations, the gelation of the hydrogels could be varied from seconds to hours. The strong interaction of CB[7]-AD pair endue the hydrogels good mechanical properties and stability. Moreover, the binding of functionalized guest molecules of CB[7] moieties offers a facile approach for tailoring of the hydrogels’ scaffold. Combined with hydrogel injection and printing technology, this method offers an approach for the development of hydrogels with advanced temporal and spatial complexity.

  13. In depth analysis on the binding sites of adamantane derivatives in HCV (hepatitis C virus p7 channel based on the NMR structure.

    Directory of Open Access Journals (Sweden)

    Qi-Shi Du

    Full Text Available BACKGROUND: The recently solved solution structure of HCV (hepatitis C virus p7 ion channel provides a solid structure basis for drug design against HCV infection. In the p7 channel the ligand amantadine (or rimantadine was determined in a hydrophobic pocket. However the pharmocophore (-NH2 of the ligand was not assigned a specific binding site. RESULTS: The possible binding sites for amino group of adamantane derivatives is studied based on the NMR structure of p7 channel using QM calculation and molecular modeling. In the hydrophobic cavity and nearby three possible binding sites are proposed: His17, Phe20, and Trp21. The ligand binding energies at the three binding sites are studied using high level QM method CCSD(T/6-311+G(d,p and AutoDock calculations, and the interaction details are analyzed. The potential application of the binding sites for rational inhibitor design are discussed. CONCLUSIONS: Some useful viewpoints are concluded as follows. (1 The amino group (-NH2 of adamantane derivatives is protonated (-NH3+, and the positively charged cation may form cation-π interactions with aromatic amino acids. (2 The aromatic amino acids (His17, Phe20, and Trp21 are the possible binding sites for the protonated amino group (-NH3+ of adamantane derivatives, and the cation-π bond energies are 3 to 5 times stronger than the energies of common hydrogen bonds. (3 The higher inhibition potent of rimantadine than amantadine probably because of its higher pKa value (pKa = 10.40 and the higher positive charge in the amino group. The potential application of p7 channel structure for inhibitor design is discussed.

  14. Solvent-dependent assembly of discrete and continuous CoCl₂ adamantane-based ligand complexes: observations by CSI-mass spectrometry and X-ray crystallography.

    Science.gov (United States)

    Ohara, Kazuaki; Tominaga, Masahide; Azumaya, Isao; Yamaguchi, Kentaro

    2013-01-01

    Discrete and continuous coordination structures were obtained in single crystals of CoCl₂ and an adamantane-based bidentate ligand bearing imidazolyl groups, depending on the methanol concentration in a methanol-chloroform mixture. Single-crystal X-ray structure analysis revealed that the metal centers exhibited a tetrahedral geometry in the discrete complex and an octahedral geometry in the continuous metal complex. Conventional analytical methods, including UV-vis and NMR spectroscopy, could not identify those two complexes in solution. In contrast, cold-spray ionization mass spectrometry could detect differences between the discrete complex and the continuous metal complex, and ion peaks due to continuous ligand adducts were found only in the spectrum of the continuous metal complex.

  15. Solvent inclusion in the crystal structure of bis-[(adamantan-1-yl)methanaminium chloride] 1,4-dioxane hemisolvate monohydrate explained using the computed crystal energy landscape.

    Science.gov (United States)

    Mohamed, Sharmarke

    2016-09-01

    Repeated attempts to crystallize 1-adamantane-methyl-amine hydro-chloride as an anhydrate failed but the salt was successfully crystallized as a solvate (2C11H20N(+)·2Cl(-)·0.5C4H8O2·H2O), with water and 1,4-dioxane playing a structural role in the crystal and engaging in hydrogen-bonding inter-actions with the cation and anion. Computational crystal-structure prediction was used to rationalize the solvent-inclusion behaviour of this salt by computing the solvent-accessible voids in the predicted low-energy structures for the anhydrate: the global lattice-energy minimum structure, which has the same packing of the ions as the solvate, has solvent-accessible voids that account for 3.71% of the total unit-cell volume and is 6 kJ mol(-1) more stable than the next most stable predicted structure.

  16. Structure of N'-(adamantan-2-ylidene)benzohydrazide, a potential antibacterial agent, in solution: Molecular dynamics simulations, quantum chemical calculations and Ultraviolet–visible spectroscopy studies

    Indian Academy of Sciences (India)

    ALEXANDER M ANDRIANOV; IVAN A KASHYN; VIKTOR M ANDRIANOV; MAKSIM B SHUNDALAU; ANTON V HLINISTY; SERGEY V GAPONENKO; ELENA V SHABUNYA -KLYACHKOVSKAYA; ANNA MATSUKOVICH; ABDUL-MALEK S AL- TAMIMI; ALI A EL- EMAM

    2016-12-01

    The molecular dynamics simulations of the structure of the N'-(adamantan-2-ylidene)benzohydrazide followed by the quantum chemical calculations at the DFT level of theory have identified four stable conformers of this potential antibacterial agent in solution: one “central” cis- and three (“central”, “left” and “right”) trans-conformers. The UV-Vis absorption spectrum in the 220–320 nm region in the ethanol solution reveals two bands that can be primarily explained based on the ab initio calculations of the spectral characteristics of the “side” trans-conformers at the MRPT level of theory. However, the close energy values for thecalculated cis- S₁ ← S₀ and “side” trans- S₂ ← S₀ transitions cannot exclude the presence of cis-conformer in solution. Therefore, the data obtained show that the coexistence of both trans-conformers and cis-conformer should be taken into consideration when studying the pharmaceutical properties of the title molecule.

  17. Synthesis and Solution Properties of Adamantane Containing Quaternary Ammonium Salt-type Cationic Surfactants: Hydrocarbon-based, Fluorocarbonbased and Bola-type.

    Science.gov (United States)

    Yoshimura, Tomokazu; Okada, Mari; Matsuoka, Keisuke

    2016-10-01

    Quaternary ammonium salt-type cationic surfactants with an adamantyl group (hydrocarbon-type; CnAdAB, fluorocarbon-type; Cm(F)C3AdAB, bola-type; Ad-s-Ad, where n, m and s represent hydrocarbon chain lengths of 8-16, fluorocarbon chain lengths of 4-8, and spacer chain length of 10-12) were synthesized via quaternization of N, N-dimethylaminoadamantane and n-alkyl bromide or 1, n-dibromoalkane. Conductivity and surface tension were measured to characterize the solution properties of the synthesized adamantyl group-containing cationic surfactants. In addition, the effects of hydrocarbon and fluorocarbon chain lengths and spacer chain length between headgroups on the measured properties were evaluated by comparison with those of conventional cationic surfactants. The critical micelle concentration (CMC) of CnAdAB and Ad-s-Ad was 2/5 of that for the corresponding conventional surfactants CnTAB and bola-type surfactants with similar number of carbons in the alkyl or alkylene chain; this was because of the increased hydrophobicity due to the adamantyl group. A linear relationship between the logarithm of CMC and the hydrocarbon chain length for CnAdAB was observed, as well as for CnTAB. The slope of the linear correlation for both surfactants was almost the same, indicating that the adamantyl group does not affect the CMC with variations in the hydrocarbon chain length. Similar to conventional surfactants CnTAB, the hydrocarbon-type CnAdAB is highly efficient in reducing the surface tension of water, despite the large occupied area per molecule resulting from the relatively bulky structure of the adamantane skeleton. On the other hand, the bola-type Ad-s-Ad resulted in increased surface tension compared to CnAdAB, indicating that the curved chain between adamantyl groups leads to poor adsorption and orientation at the air-water interface.

  18. Treatment of genetically obese mice with the iminosugar N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin reduces body weight by decreasing food intake and increasing fat oxidation.

    Science.gov (United States)

    Langeveld, Mirjam; van den Berg, Sjoerd A A; Bijl, Nora; Bijland, Silvia; van Roomen, Cindy P; Houben-Weerts, Judith H; Ottenhoff, Roelof; Houten, Sander M; van Dijk, Ko Willems; Romijn, Johannes A; Groen, Albert K; Aerts, Johannes M; Voshol, Peter J

    2012-01-01

    Obesity and its associated conditions such as type 2 diabetes mellitus are major causes of morbidity and mortality. The iminosugar N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin (AMP-DNM) improves insulin sensitivity in rodent models of insulin resistance and type 2 diabetes mellitus. In the current study, we characterized the impact of AMP-DNM on substrate oxidation patterns, food intake, and body weight gain in obese mice. Eight ob/ob mice treated with 100 mg/(kg d) AMP-DNM mixed in the food and 8 control ob/ob mice were placed in metabolic cages during the first, third, and fifth week of the experiment for measurement of substrate oxidation rates, energy expenditure, activity, and food intake. Mice were killed after 6 weeks of treatment. Initiation of treatment with AMP-DNM resulted in a rapid increase in fat oxidation by 129% (P = .05), a decrease in carbohydrate oxidation by 35% (P = .01), and a reduction in food intake by approximately 26% (P fat oxidation rates, increased hepatic carnitine palmitoyl transferase 1a expression. Treatment with AMP-DNM increased plasma levels of the appetite-regulating peptide YY compared with control mice. Treatment with AMP-DNM rapidly reduces food intake and increases fat oxidation, resulting in improvement of the obese phenotype. These features of AMP-DNM, together with its insulin-sensitizing capacity, make it an attractive candidate drug for the treatment of obesity and its associated metabolic derangements. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Functionalized adamantane tectons used in the design of mixed-ligand copper(II) 1,2,4-triazolyl/carboxylate metal-organic frameworks.

    Science.gov (United States)

    Senchyk, Ganna A; Lysenko, Andrey B; Krautscheid, Harald; Rusanov, Eduard B; Chernega, Alexander N; Krämer, Karl W; Liu, Shi-Xia; Decurtins, Silvio; Domasevitch, Konstantin V

    2013-01-18

    Bistriazoles, 1,3-bis(1,2,4-triazol-4-yl)propane (tr(2)pr) and 1,3-bis(1,2,4-triazol-4-yl)adamantane (tr(2)ad), were examined in combination with the rigid tetratopic 1,3,5,7-adamantanetetracarboxylic acid (H(4)-adtc) platform for the construction of neutral heteroleptic copper(II) metal-organic frameworks. Two coordination polymers, [{Cu(4)(OH)(2)(H(2)O)(2)}{Cu(4)(OH)(2)}(tr(2)pr)(2)(H-adtc)(4)]·2H(2)O (1) and [Cu(4)(OH)(2)(tr(2)ad)(2)(H-adtc)(2)(H(2)O)(2)]·3H(2)O (2), were synthesized and structurally characterized. In complexes 1 and 2, the N(1),N(2)-1,2,4-triazolyl (tr) and μ(3)-OH(-) groups serve as complementary bridges between adjacent metal centers supporting the tetranuclear dihydroxo clusters. The structure of 1 represents a unique association of two different kinds of centrosymmetrical {Cu(4)(OH)(2)} units in a tight 3D framework, while in compound 2, another configuration type of acentric tetranuclear metal clusters is organized in a layered 3,6-hexagonal motif. In both cases, the {Cu(4)(OH)(2)} secondary building block and trideprotonated carboxylate H-adtc(3-) can be viewed as covalently bound six- and three-connected nodes that define the net topology. The tr ligands, showing μ(3)- or μ(4)-binding patterns, introduce additional integrating links between the neighboring {Cu(4)(OH)(2)} fragments. A variable-temperature magnetic susceptibility study of 2 demonstrates strong antiferromagnetic intracluster coupling (J(1) = -109 cm(-1) and J(2) = -21 cm(-1)), which combines for the bulk phase with a weak antiferromagnetic intercluster interaction (zj = -2.5 cm(-1)).

  20. Spectroscopic investigation (FT-IR and FT-Raman), vibrational assignments, HOMO-LUMO analysis and molecular docking study of 2-(Adamantan-1-yl)-5-(4-nitrophenyl)-1,3,4-oxadiazole

    Science.gov (United States)

    Haress, Nadia G.; Al-Omary, Fatmah; El-Emam, Ali A.; Mary, Y. Sheena; Panicker, C. Yohannan; Al-Saadi, Abdulaziz A.; War, Javeed Ahmad; Van Alsenoy, Christian

    2015-01-01

    FT-IR and FT-Raman spectra of 2-(Adamantan-1-yl)-5-(4-nitrophenyl)-1,3,4-oxadiazole were recorded and analyzed. The vibrational wavenumbers were computed using DFT quantum chemical calculations. The data obtained from wavenumber calculations are used to assign vibrational bands obtained experimentally. The energy barriers of the internal rotations about the Csbnd C bonds connecting the oxadiazole to the adamantane and benzene rings are reported. The geometrical parameters (DFT) of the title compound are in agreement with the XRD results. The calculated HOMO and LUMO energies allow the calculations of atomic and molecular properties and they also showed that charge transfer occurs in the molecule. A detailed molecular picture of the title compound and its interactions were obtained from NBO analysis. As can be seen from the MEP map of the title compound, which regions having the negative potential are over the electro negative atoms, the region having the positive potential are over the phenyl and adamantine rings and the remaining species are surrounded by zero potential. The molecular docking studies reveal that the adamantyl derivative may exhibit C-South African HIV-proteas inhibitory activity.

  1. 1,3,5,7-Tetrakis(tetrazol-5-yl)-adamantane: the smallest tetrahedral tetrazole-functionalized ligand and its complexes formed by reaction with anhydrous M(II)Cl2 (M = Mn, Cu, Zn, Cd).

    Science.gov (United States)

    Boldog, Ishtvan; Domasevitch, Konstantin V; Sanchiz, Joaquín; Mayer, Peter; Janiak, Christoph

    2014-09-07

    1,3,5,7-Tetrakis(tetrazol-5-yl)-adamantane (H4L) was probed as a building block for the synthesis of tetrazolato/halido coordination polymers with open-network structures. MCl2 (M = Cu, Cd, Zn, Mn) was reacted with H4L in DMF at 70 °C to yield [Cu4Cl4L(DMF)5]·DMF, ; [Cd4Cl4L(DMF)7]·DMF, ; [Zn3Cl2L(DMF)4]·2DMF, and [Mn2L(DMF)2(MeOH)4]·DMF·2MeOH·2H2O, . and (Fddd) are nearly isostructural and have zeolitic structures with a {4(3)·6(2)·8}, gis or gismondine underlying net, where the role of the tetrahedral nodes is served by the coordination bonded clusters and the adamantane moiety. (P21/n) has a porous structure composed of coordination bonded layers with a (4·8(2)) fes topology joined via trans-{Zn(tetrazolate)2(DMF)4} pillars with an overall topology of {4·6(2)}{4·6(6)·8(3)}, fsc-3,5-Cmce-2. (Pca21) is composed of stacked {Mn2L} hexagonal networks. In and the ligand fulfills a symmetric role of a tetrahedral building block, while in and it fulfills rather a role of an effective trigonal unit. Methanol-exchanged and activated displayed an unusual type IV isotherm with H2 type hysteresis for N2 sorption with an expected uptake at high P/P0, but with a smaller SBET = 505.5 m(2) g(-1) compared to the calculated 1789 m(2) g(-1), which is a possible result of the framework's flexibility. For H2 sorption 0.79 wt% (1 bar, 77 K) and 0.06 wt% (1 bar, RT) uptake and Qst = -7.2 kJ mol(-1) heat of adsorption (77 K) were recorded. Weak antiferromagnetic interactions were found in and with J1 = -9.60(1), J2 = -17.2(2), J3 = -2.28(10) cm(-1) and J = -0.76 cm(-1) respectively. The formation of zeolitic structures in and , the concept of structural 'imprinting' of rigid building blocks, and design opportunities suggested as a potential hexafunctionalized biadamantane building block.

  2. High-resolution mass spectrometric metabolite profiling of a novel synthetic designer drug, N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide (STS-135), using cryopreserved human hepatocytes and assessment of metabolic stability with human liver microsomes.

    Science.gov (United States)

    Gandhi, Adarsh S; Wohlfarth, Ariane; Zhu, Mingshe; Pang, Shaokun; Castaneto, Marisol; Scheidweiler, Karl B; Huestis, Marilyn A

    2015-03-01

    N-(Adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide (STS-135) is a new synthetic cannabinoid in herbal incense products discussed on Internet drug user forums and identified in police seizures. To date, there are no STS-135 clinical or in vitro studies identifying STS-135 metabolites. However, characterizing STS-135 metabolism is critical because synthetic cannabinoid metabolites can possess pharmacological activity and parent compounds are rarely detectable in urine. To characterize the metabolite profile, human hepatocytes were incubated with 10 µmol/L STS-135 for up to 3 h. High-resolution mass spectrometry with software-assisted data mining identified 29 STS-135 metabolites. Less than 25% of STS-135 parent compound remained after 3 h incubation. Primary metabolites were generated by mono-, di- or trihydroxylation with and without ketone formation, dealkylation, and oxidative defluorination of N-fluoropentyl side chain or possible oxidation to carboxylic acid, some of them further glucuronidated. Hydroxylations occurred mainly on the aliphatic adamantane ring and less commonly on the N-pentyl side chain. At 1 h, phase I metabolites predominated, while at 3 h, phase II metabolites were present in higher amounts. The major metabolites were monohydroxy STS-135 (M25) and dihydroxy STS-135 (M21), both hydroxylated on the adamantane system. Moreover, metabolic stability of STS-135 (1 µmol/L) was assessed in human liver microsomes experiments. The in vitro half-life of STS-135 was 3.1 ± 0.2 min and intrinsic clearance (CLint ) was 208.8 mL · min(-1)  · kg(-1) . This is the first report characterizing STS-135 hepatic metabolic pathways. These data provide potential urinary targets to document STS-135 intake in clinical and forensic settings and potential candidates for pharmacological testing.

  3. FTIR spectra and normal-mode analysis of a tetranuclear Manganese adamantane-like complex in two electrochemically prepared oxidation states: Relevance to the oxygen-evolving complex of Photosystem II

    Energy Technology Data Exchange (ETDEWEB)

    Visser, Hendrik; Dube, Christopher E.; Armstrong, William H.; Sauer, Kenneth; Yachandra, Vittal K.

    2002-03-19

    The IR spectra and normal-mode analysis of the adamantane-like compound [Mn4O6(bpea)4]n+ in two oxidation states, MnIV4 and MnIIIMnIV3, that are relevant to the oxygen-evolving complex of photosystem II are presented. Mn-O vibrational modes are identified with isotopic exchange, 16O->18O, of the mono-(mu)-oxo bridging atoms in the complex. IR spectra of the MnIIIMnIV3 species are obtained by electrochemical reduction of the MnIV4 species using a spectroelectrochemical cell, based on attenuated total reflection [Visser et al. Anal Chem 2001, 73, 4374-4378]. A novel method of subtraction is used to reduce background contributions from solvent and ligand modes, and the difference and double-difference spectra are used in identifying Mn-O bridging modes that are sensitive to oxidation state change. Two strong IR bands are observed for the MnIV4 species at 745 and 707 cm-1 and a weaker band at 510 cm-1. Upon reduction, the MnIIIMnIV3 species exhibits two strong IR bands at 745 and 680 cm-1, and several weaker bands are observed in the 510 - 425 cm-1 range. A normal mode analysis is performed to assign all the relevant bridging modes in the oxidized MnIV4 and reduced MnIIIMnIV3 species. The calculated force constants for the MnIV4 species are = 3.15 mdynAngstrom, = 0.55 mdyn/Angstrom, and = 0.20 mdyn/Angstrom. The force constants for the MnIIIMnIV3 species are = 3.10 mdyn/Angstrom, = 2.45 mdyn/Angstrom, = 0.40, and = 0.15 mdyn/Angstrom. This study provides insights for the identification of Mn-O modes in the IR spectra of the photosynthetic oxygen-evolving complex during its catalytic cycle.

  4. Efeito das interações hiperconjugativas na constante de acoplamento ¹J CH da hexametilenotetramina e do adamantano: estudo teórico e experimental Effects of hyperconjugative interactions on ¹J CH coupling constant for hexamethyl-enetetramine and adamantane: theoretical and experimental study

    Directory of Open Access Journals (Sweden)

    Francisco P. dos Santos

    2007-01-01

    Full Text Available The objective of this work was to determine the influence of hyperconjugative interactions on the ¹J CH coupling constant for hexamethylenetetramine (1 and adamantane (2. For this end, theoretical and experimental ¹J CH were obtained and hyperconjugative interactions were investigated using NBO. It was observed, theoretically and experimentally, that ¹J CH in 1 is 20 Hz larger than in 2, mainly due to the nN®s*C-H hyperconjugative interaction. This interaction occurs only in 1, with an energy of 9.30 kcal mol-1. It increases the s-character of the carbon atom in the C-H bond and the occupancy of the sigma*C-H orbital in (1.

  5. N′-(Adamantan-2-ylidenethiophene-2-carbohydrazide

    Directory of Open Access Journals (Sweden)

    Adnan A. Kadi

    2011-11-01

    Full Text Available In the title molecule, C15H18N2OS, a small twist is noted, with the dihedral angle between the central carbohydrazone residue (r.m.s. deviation = 0.029 Å and the thiophene ring being 12.47 (10°. The syn arrangement of the amide H and carbonyl O atoms allows for the formation of centrosymmetric dimers via N—H...O hydrogen bonds. These are linked in the three-dimensional structure by C—H...π interactions. The thiophene ring is disordered over two co-planar orientations, the major component having a site-occupancy factor of 0.833 (2.

  6. Electrophysiological study, biodistribution in mice, and preliminary PET evaluation in a rhesus monkey of 1-amino-3-[{sup 18}F]fluoromethyl-5-methyl-adamantane ({sup 18}F-MEM): a potential radioligand for mapping the NMDA-receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Samnick, Samuel; Ametamey, Simon; Leenders, Klaus L.; Vontobel, Peter; Quack, Guenter; Parsons, Chris G.; Neu, Henrik; Schubiger, Pius A

    1998-05-01

    The effect of the fluorinated memantine derivative and NMDA receptor antagonist, 1-amino-3-fluoromethyl-5-methyl-adamantane ({sup 19}F-MEM), at the NMDA receptor ion channel was studied by patch clamp recording. The results showed that {sup 19}F-MEM is a moderate NMDA receptor channel blocker. A procedure for the routine preparation of the {sup 18}F-labelled analog {sup 18}F-MEM has been developed using a two-step reaction sequence. This involves the no-carrier-added nucleophilic radiofluorination of 1-[N-(tert-butyloxy)carbamoyl]-3-(toluenesulfonyloxy)methyl-5- methyl-adamantane and the subsequent cleavage of the BOC-protecting group using aqueous HCl. The {sup 18}F-MEM was obtained in 22{+-}7% radiochemical yield (decay-corrected to EOB) in a total synthesis time including HPLC purification of 90 min. A biodistribution study after IV injection of {sup 18}F-MEM in mice showed a fast clearance of radioactivity from blood and relatively high initial uptake in the kidney and in the lung, which gradually decreased with time. The brain uptake was high (up to 3.6% ID/g, 60 min postinjection) with increasing brain-blood ratios: 2.40, 5.10, 6.33, and 9.27 at 5, 30, 60, and 120 min, respectively. The regional accumulation of the radioactivity in the mouse brain was consistent with the known distribution of the PCP recognition site. Preliminary PET evaluation of the radiotracer in a rhesus monkey demonstrated good uptake and prolonged retention in the brain, with a plateau from 35 min onwards p.i. in the NMDA receptor-rich regions (frontal cortex, striata, and temporal cortex). Delineation of the hippocampus, a region known to contain a high density of NMDA receptors, was not possible owing to the resolution of the PET tomograph. The regional brain uptake of {sup 18}F-MEM was changed by memantine and by a pharmacological dose of (+)-MK-801, indicating competition for the same binding sites. In a preliminary experiment, haloperidol, a dopamine D2 and sigma receptor

  7. 2009年广州地区季节性甲型流感病毒对烷胺类药物耐药性分析%Adamantane resistance among seasonal influenza A viruses between January to October in Guangzhou, 2009

    Institute of Scientific and Technical Information of China (English)

    杨子峰; 占扬清; 张雪; 黄群娣; 招穗珊; 周荣; 陈荣昌; 钟南山; 关文达; 徐国荣; 李铭源; 莫自耀; 罗翌; 董婉妮; 王玉涛; 秦笙

    2011-01-01

    Objective To study the prevalence of adamantane-resistance among influenza A viruses isolated from Guangzhou between January and October in 2009, and to provide more information for clinical usage of adamantine drugs. Methods Totally 311 influenza A strains isolated from 6 hospitals in Guangzhou between January and October in 2009 were selected, and the MP gene of all 311 strains ( 159 strains of H1subtype, 152 strains of H3 subtype ) was sequenced. The susceptibility of viruses to rimantadine was assayedby biological methods in cells. Result A hundred and forty-eight strains of influenza A ( H1 ) viruses( 93. 1%, 148/159 ) were resistant to the adamantanes, and all the 152 influenza A ( H3 ) viruses were resistant to the adamantanes. An amino acid substitution S31N was found in most of the strains except 1strain with double mutation V27A/S31N. Furthermore, the M gene of influenza A ( H1 ) viruses was divided into genotype B ( human ) ( 97/159 ) and genotype F ( European and Australian birds, 62/159 ), while the M gene of influenza A ( H3 ) viruses was genotype B ( human ) ( 152/152 ). Conclusion Resistance rate of seasonal influenza A viruses isolated from Guangzhou was high. The MP gene of influenza A ( H1 ) may be replaced by a gene from European and Australian birds through a reassortment event.%目的 分析2009年1-10月份广州地区季节性甲型流感病毒对烷胺类药物的耐药情况,为临床预防和治疗季节性甲型流感提供参考依据.方法 选取2009年1-10月份广州地区6家医院分离的季节性甲型流感病毒株311株,其中H1亚型159株,H3亚型152株.对病毒的毒株基质蛋白(MP)基因进行序列测定,利用数据库和软件进行生物信息分析,并测定软件随机抽取的临床分离的H1和H3病毒株(各10株)对金刚烷胺的药物敏感度,分析广州地区2009年1-10月份季节性甲型流感病毒的耐药性和基因重组情况.结果 159株H1亚型流感病毒中148株对金刚烷胺耐药(93

  8. Surface modification of adamantane-terminated gold nanoclusters using cyclodextrins.

    Science.gov (United States)

    Yan, Chunyang; Liu, Chao; Abroshan, Hadi; Li, Zhimin; Qiu, Renhua; Li, Gao

    2016-08-17

    The surface functionality of Au38S2(SAdm)20 nanoclusters (-SAdm = adamantanethiolate) in the presence of α-, β-, and γ-cyclodextrins (CDs) is studied. The supramolecular chemistry and host-guest interactions of CDs and the protecting ligands of nanoclusters are investigated using UV-vis and NMR spectroscopies, MALDI mass spectrometry, and molecular dynamics simulations. In contrast to α- and γ-CDs, the results show that β-CDs are capable of efficiently chemisorbing onto the Au38S2(SAdm)20 nanoclusters to yield Au38S2(SAdm)20-(β-CD)2 conjugates. MD simulations revealed that two -SAdm ligands of the nanoparticle with the least steric hindrance are capable to selectively be accommodated into hydrophobic cavity of β-CDs, as furthermore confirmed by NMR spectroscopy. The conjugates largely improve the stability of the nanoclusters in the presence of strong oxidants (e.g., TBHP). Further, the electrochemical properties of Au38S2(SAdm)20 nanoclusters and Au38S2(SAdm)20-(β-CD)2 conjugates are compared. The charge transfer to the redox probe molecules (e.g., K3Fe(CN)6) in solution was monitored by cyclic voltammetry. It is found that β-CDs act as an umbrella to cover the fragile metal cores of the nanoclusters, thereby blocking direct interaction with destabilizing agents and hence quenching the charge transfer process.

  9. Diamonds are a chemist's best friend: diamondoid chemistry beyond adamantane.

    Science.gov (United States)

    Schwertfeger, Hartmut; Fokin, Andrey A; Schreiner, Peter R

    2008-01-01

    Marilyn Monroe knew that "diamonds are a girl's best friend" but, in the meantime, many chemists have realized that they are also extremely attractive objects in contemporary chemistry. The chemist's diamonds are usually quite small (herein: nanometer-sized "diamondoids") and as a result of their unique structure are unusual chemical building blocks. Since lower diamondoids (up to triamantane) have recently become available in large amounts from petroleum and higher diamondoids (starting from tetramantane) are now also accessible from crude oil new research involving them has begun to emerge. Having well-defined structures makes these cage compounds so special compared to other nanometer-scale diamonds. Selective and high-yielding synthetic approaches to the functionalization of diamondoids gives derivatives that can find applications in, for example, polymers, coating materials, drugs, and molecular electronics.

  10. 1-(Adamantan-1-yl-3-(4-fluorophenylthiourea

    Directory of Open Access Journals (Sweden)

    Nasser R. El-Brollosy

    2012-05-01

    Full Text Available In the title molecule, C17H21FN2S, the mean planes of the benzene ring and the thiourea fragment form a dihedral angle of 61.93 (9°. In the crystal, pairs of weak N—H...S interactions link the molecules, forming inversion dimers.

  11. Crystal structure of 2-(adamantan-1-yl-5-(4-bromophenyl-1,3,4-oxadiazole

    Directory of Open Access Journals (Sweden)

    Nourah Z. Alzoman

    2014-12-01

    Full Text Available In the title molecule, C18H19BrN2O, the benzene ring is inclined to the oxadiazole ring by 10.44 (8°. In the crystal, C—H...π interactions link the molecules in a head-to-tail fashion, forming chains extending along the c-axis direction. The chains are further connected by π–π stacking interactions, with centroid–centroid distances of 3.6385 (7 Å, forming layers parallel to the bc plane.

  12. Quasi-normal phase chromatography of nitrogen-containing adamantane derivatives

    Science.gov (United States)

    Prokopov, S. V.; Tyrina, E. V.; Davankov, V. A.; Il'in, M. M.; Kurbatova, S. V.

    2013-01-01

    The chromatographic retention of adamantyl-containing amidrazones and triazoles is studied under the conditions of quasi-normal phase (QNP) and reversed phase high-performance liquid chromatography using partially sulfonated hypercrosslinked polystyrene as a stationary phase. The considerable effect of the sorbent-sorbate π interactions on the retention factor of the analytes, particularly under conditions of QNP chromatography, is revealed.

  13. CCDC 961393: Experimental Crystal Structure Determination : 3-(Adamantan-1-yl)-1-mesityl-1H-imidazol-3-ium chloride monohydrate

    KAUST Repository

    Queval, Pierre

    2014-01-01

    An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

  14. (2SR,3RS-Methyl 2-(adamantan-1-yl-3-phenylsulfonyl-3-(pyridin-2-ylsulfanylpropanoate dichloromethane hemisolvate

    Directory of Open Access Journals (Sweden)

    Rosa-Luisa Meza-León

    2011-04-01

    Full Text Available The title compound, C25H29NO4S2 0.5CH2Cl2, was obtained as a racemate. The pyridine and phenyl rings are arranged face-to-face, giving a weak intramolecular π–π interaction [centroid–centroid separation = 3.759 (3 Å]. These interactions are extended intermolecularly, forming chains of stacked rings along [001] with separations of 3.859 (3 and 3.916 (3 Å. The solvent used for crystallization, CH2Cl2, is located in voids between the chains of molecules, with a site occupancy of 0.5.

  15. Crystal structure of [2,6-bis(adamantan-1-yl-4-tert-butylphenolato-κO]dimethylaluminium(III

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2014-10-01

    Full Text Available The title compound, [Al(CH32(C30H41O] is synthesized by the reaction of 2,6-di-adamantyl-4-tert-butyl-phenol with Al(CH33 in a nitrogen atmosphere. In the molecule, the coordination geometry around the AlIII atom is slightly distorted C2O trigonal (the sum of the bond angles subtended at Al atom being 359.9°, which is rarely reported for organometallic aluminium compounds. The coordination plane is approximately perpendicular to the benzene ring [the dihedral angle = 87.73 (16°]. There is no intermolecular hydrogen bonding in the crystal structure.

  16. 3-(Adamantan-1-yl-4-phenyl-1-[(4-phenylpiperazin-1-ylmethyl]-1H-1,2,4-triazole-5(4H-thione

    Directory of Open Access Journals (Sweden)

    Ebtehal S. Al-Abdullah

    2012-02-01

    Full Text Available The title molecule, C29H35N5S, displays a chair-shaped piperazine ring, as well as an approximately planar triazole ring (r.m.s. deviation = 0.001 Å whose phenyl substituent is nearly perpendicular to the mean plane of the five-membered ring [dihedral angle = 88.9 (1°]. The substituents on the piperazine ring occupy equatorial sites. In the crystal, the adamantyl cage is disordered over two sets of sites with a major component of 67.8 (5%. Weak intermolecular C—H...S hydrogen bonding is present in the crystal.

  17. 3-(Adamantan-1-yl-1-[(4-benzylpiperazin-1-ylmethyl]-4-[(E-(2-hydroxybenzylideneamino]-1H-1,2,4-triazole-5(4H-thione

    Directory of Open Access Journals (Sweden)

    Ali A. El-Emam

    2012-06-01

    Full Text Available In the title compound, C31H38N6OS, the conformation about the N=C [1.285 (2 Å] imine bond is E. The piperazine ring has a chair conformation and occupies a position almost perpendicular to the plane through the triazole ring; the benzene ring forms a dihedral angle of 31.95 (10° with the triazole ring. Overall, the molecule has the shape of a flattened bowl. The hydroxy group is disordered over two positions. The major component has a site-occupancy factor of 0.762 (3 and forms an intramolecular O—H...N(imine bond to close an S(6 loop. The minor component of the disordered hydroxy group forms an O—H...N(piperazine hydrogen bond. These, along with C—H...S and C—H...N interactions, link molecules into a three-dimensional architecture.

  18. CCDC 992440: Experimental Crystal Structure Determination : hydrido-((1,2-phenylenebis(methylene))bis(bis(adamantan-1-yl)phosphine))-triphenylphosphine-palladium(ii) trifluoromethanesulfonate methanol solvate

    KAUST Repository

    Christl, Josefine T.

    2014-01-01

    An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

  19. CCDC 1024807: Experimental Crystal Structure Determination : 1,3-bis(Adamantan-1-yl)-1,3-dihydro-2H-imidazole-2-selenone

    KAUST Repository

    Vummaleti, Sai V. C.

    2015-01-01

    An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

  20. 2 : 2 Fe(III): ligand and "adamantane core" 4 : 2 Fe(III): ligand (hydr)oxo complexes of an acyclic ditopic ligand

    DEFF Research Database (Denmark)

    Ghiladi, Morten; Larsen, Frank B.; McKenzie, Christine J.;

    2005-01-01

    A bis-hydroxo-bridged diiron(III) complex and a bis-mu-oxo-bis-mu-hydroxo-bridged tetrairon( III) complex are isolated from the reaction of 2,6-bis((N, N'-bis-(2-picolyl) amino) methyl)-4-tert-butylphenol (Hbpbp) with iron perchlorate in acidic and neutral solutions respectively. The X......-ray structure of the dinuclear complex [{( Hbpbp) Fe(mu-OH)}(2)](ClO4)(4) center dot 2C(3)H(6)O ( 1 center dot 2C(3)H(6)O) shows that only one of the metal-binding cavities of each ligand is occupied by an iron( III) atom and two [Fe(Hbpbp)](3+) units are linked together by two hydroxo bridging groups to form...... bond lengths of the two different octahedral iron sites: Fe -mu-OH, 1.953( 5), 2.013( 5) angstrom and Fe-mu-O, 1.803( 5), 1.802( 5) angstrom. The difference in ligand environment is too small for allowing Mossbauer spectroscopy to distinguish between the two crystallographically independent Fe sites...

  1. Insights from investigating the interactions of adamantane-based drugs with the M2 proton channel from the H1N1 swine virus

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing-Fang [College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240 (China); Wei, Dong-Qing, E-mail: dqwei@gordonlifescience.org [College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240 (China); Gordon Life Science Institute, 13784 Torrey Del Mar Drive, San Diego, CA 92130 (United States); Chou, Kuo-Chen [College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240 (China); Gordon Life Science Institute, 13784 Torrey Del Mar Drive, San Diego, CA 92130 (United States)

    2009-10-16

    The M2 proton channel is one of indispensable components for the influenza A virus that plays a vital role in its life cycle and hence is an important target for drug design against the virus. In view of this, the three-dimensional structure of the H1N1-M2 channel was developed based on the primary sequence taken from a patient recently infected by the H1N1 (swine flu) virus. With an explicit water-membrane environment, molecular docking studies were performed for amantadine and rimantadine, the two commercial drugs generally used to treat influenza A infection. It was found that their binding affinity to the H1N1-M2 channel is significantly lower than that to the H5N1-M2 channel, fully consistent with the recent report that the H1N1 swine virus was resistant to the two drugs. The findings and the relevant analysis reported here might provide useful structural insights for developing effective drugs against the new swine flu virus.

  2. Au₂₄(SAdm)₁₆ nanomolecules: X-ray crystal structure, theoretical analysis, adaptability of adamantane ligands to form Au₂₃(SAdm)₁₆ and Au₂₅(SAdm)₁₆, and its relation to Au₂₅(SR)₁₈.

    Science.gov (United States)

    Crasto, David; Barcaro, Giovanni; Stener, Mauro; Sementa, Luca; Fortunelli, Alessandro; Dass, Amala

    2014-10-22

    Here we present the crystal structure, experimental and theoretical characterization of a Au24(SAdm)16 nanomolecule. The composition was verified by X-ray crystallography and mass spectrometry, and its optical and electronic properties were investigated via experiments and first-principles calculations. Most importantly, the focus of this work is to demonstrate how the use of bulky thiolate ligands, such as adamantanethiol, versus the commonly studied phenylethanethiolate ligands leads to a great structural flexibility, where the metal core changes its shape from five-fold to crystalline-like motifs and can adapt to the formation of Au(24±1)(SAdm)16, namely, Au23(SAdm)16, Au24(SAdm)16, and Au25(SAdm)16. The basis for the construction of a thermodynamic phase diagram of Au nanomolecules in terms of ligands and solvent features is also outlined.

  3. Novel diamantane polymer platform for enhanced etch resistance

    Science.gov (United States)

    Padmanaban, Munirathna; Chakrapani, Srinivasan; Lin, Guanyang; Kudo, Takanori; Parthasarathy, Deepa; Rahman, Dalil; Anyadiegwu, Clement; Antonio, Charito; Dammel, Ralph R.; Liu, Shenggao; Lam, Frederick; Waitz, Anthony; Yamagchi, Masao; Maehara, Takayuki

    2007-03-01

    The dominant current 193 nm photoresist platform is based on adamantane derivatives. This paper reports on the use of derivatives of diamantane, the next higher homolog of adamantane, in the diamondoid series, as monomers in photoresists. Due to their low Ohnishi number and incremental structural parameter (ISP), such molecules are expected to enhance dry etch stability when incorporated into polymers for resist applications. Starting from the diamantane parent, cleavable and non-cleavable acrylate/methacrylate derivatives of diamantane were obtained using similar chemical steps as for adamantane derivatization. This paper reports on the lithographic and etch performance obtained with a number of diamantane-containing monomers, such as 9-hydroxy-4-diamantyl methacrylate (HDiMA), 2-ethyl-2- diamantyl methacrylate (EDiMA), and 2-methyl-2-diamantyl methacrylate (MDiMA). The etch advantage, dry and wet lithographic performance of some of the polymers obtained from these diamantane-containing polymers are discussed.

  4. New aromatic polyamides and polyimides having an adamantine bulky group

    OpenAIRE

    2015-01-01

    Producción Científica This paper reports the synthesis and characterization of a new rigid diamine monomer, having a spiro carbon moiety and an adamantane bulky group in its structure; namely spiro-(adamantane-2,9′(2',7'-diamino)-fluorene) (SADAF). After its synthesis, using a straightforward methodology, a novel family of aromatic polyimides (PIs) and polyamides (PAs) has been attained by reaction of SADAF with three aromatic dianhydrides and two diacid chlorides, respectively. Two of the...

  5. rac-2-{[1-(1-Adamant-yl)eth-yl]imino-meth-yl}-5-meth-oxy-phenol.

    Science.gov (United States)

    Jin, Xu-Dong; Wang, Hai-Bo; Jin, Yue-Hong

    2011-09-01

    A novel Schiff base compound, C(20)H(27)NO(2), was obtained by a condensation of rimantadine and 2-hy-droxy-4-meth-oxy-benzaldehyde. An intra-molecular O-H⋯N hydrogen bond supports the phenol-imine tautomeric form. The adamantane and imino-methyl-4-meth-oxy-phenol units are arranged in a folded conformation [C-N-C-C torsion angle = 110.9 (3)°]. In the crystal, highly hydro-phobic adamantane moieties are inserted between the imino-methyl-4-meth-oxy-phenol units in a sandwich-like arrangement along the c axis.

  6. Emergence of oseltamivir resistant influenza A (H1N1) viruses in the Netherlands during the winter 2007/2008.

    NARCIS (Netherlands)

    Meijer, A.; Dijkstra, F.; Donker, G.; Beek, R. van; Jonges, M.; Sande, M. van der; Boucher, C.; Koopmans, M.; Osterhaus, A.; Rimmelzwaan, G.

    2008-01-01

    Background: Continuous monitoring of influenza antiviral susceptibility has become more important since the introduction of the neuraminidase inhibitors (NAI) in 1999, in addition to the existing adamantane M2 channel inhibitors (M2I). Since the 2005/2006 winter season the Dutch National Influenza C

  7. Shape and release control of a peptide decorated vesicle through pH sensitive orthogonal supramolecular interactions

    NARCIS (Netherlands)

    Versluis, Frank; Tomatsu, Itsuro; Kehr, Seda; Fregonese, Carlo; Tepper, Armand W. J. W.; Stuart, Marc C. A.; Ravoo, Bart Jan; Koning, Roman I.; Kros, Alexander

    2009-01-01

    A pH sensitive carrier is obtained by coating a cyclodextrin vesicle with an adamantane-terminated octapeptide through the formation of an inclusion complex. Upon lowering the pH from 7.4 to 5.0, the formation of peptide B-sheets on the vesicle surface induces a transition of the bilayer from a sphe

  8. Emergence of oseltamivir resistant influenza A (H1N1) viruses in the Netherlands during the winter 2007/2008.

    NARCIS (Netherlands)

    Meijer, A.; Dijkstra, F.; Donker, G.; Beek, R. van; Jonges, M.; Sande, M. van der; Boucher, C.; Koopmans, M.; Osterhaus, A.; Rimmelzwaan, G.

    2008-01-01

    Background: Continuous monitoring of influenza antiviral susceptibility has become more important since the introduction of the neuraminidase inhibitors (NAI) in 1999, in addition to the existing adamantane M2 channel inhibitors (M2I). Since the 2005/2006 winter season the Dutch National Influenza C

  9. Correction of Liver Steatosis by a Hydrophobic Iminosugar Modulating Glycosphingolipids Metabolism

    NARCIS (Netherlands)

    Lombardo, Elisa; van Roomen, Cindy P. A. A.; van Puijvelde, Gijs H.; Ottenhoff, Roelof; van Eijk, Marco; Aten, Jan; Kuiper, Johan; Overkleeft, Herman S.; Groen, Albert K.; Verhoeven, Arthur J.; Aerts, Johannes M. F. G.; Bietrix, Florence

    2012-01-01

    The iminosugar N-(5'-adamantane-1'-yl-methoxy)-pentyl-1-deoxynoijirimycin (AMP-DNM), an inhibitor of glycosphingolipid (GSL) biosynthesis is known to ameliorate diabetes, insulin sensitivity and to prevent liver steatosis in ob/ob mice. Thus far the effect of GSL synthesis inhibition on pre-existing

  10. Sugar-Decorated Sugar Vesicles : Lectin-Carbohydrate Recognition at the Surface of Cyclodextrin Vesicles

    NARCIS (Netherlands)

    Voskuhl, Jens; Stuart, Marc C. A.; Ravoo, Bart Jan

    2010-01-01

    An artificial glycocalix self-assembles when unilamellar bilayer vesicles of amphiphilic beta-cyclodextrins are decorated with maltose and lactose by host-guest interactions. To this end, maltose and lactose were conjugated with adamantane through a tetra(ethyleneglycol) spacer. Both carbohydrate-ad

  11. [2](1,3)Adamantano[2](2,7)pyrenophane: A Hydrocarbon with a Large Dipole Moment.

    Science.gov (United States)

    Kahl, Paul; Wagner, J Philipp; Balestrieri, Ciro; Becker, Jonathan; Hausmann, Heike; Bodwell, Graham J; Schreiner, Peter R

    2016-08-01

    The fusion of the sp(3) -hybridized parent diamondoid adamantane with the sp(2) -hybridized pyrene results in a hybrid structure with a very large dipole moment which arises from bending the pyrene moiety. Presented herein is the synthesis, study of the electronic and optical properties, as well as the dynamic behavior of this new hydrocarbon.

  12. KCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting

    Science.gov (United States)

    Wrobel, Eva; Rothenberg, Ina; Krisp, Christoph; Hundt, Franziska; Fraenzel, Benjamin; Eckey, Karina; Linders, Joannes T. M.; Gallacher, David J.; Towart, Rob; Pott, Lutz; Pusch, Michael; Yang, Tao; Roden, Dan M.; Kurata, Harley T.; Schulze-Bahr, Eric; Strutz-Seebohm, Nathalie; Wolters, Dirk; Seebohm, Guiscard

    2016-01-01

    Most small-molecule inhibitors of voltage-gated ion channels display poor subtype specificity because they bind to highly conserved residues located in the channel's central cavity. Using a combined approach of scanning mutagenesis, electrophysiology, chemical ligand modification, chemical cross-linking, MS/MS-analyses and molecular modelling, we provide evidence for the binding site for adamantane derivatives and their putative access pathway in Kv7.1/KCNE1 channels. The adamantane compounds, exemplified by JNJ303, are highly potent gating modifiers that bind to fenestrations that become available when KCNE1 accessory subunits are bound to Kv7.1 channels. This mode of regulation by auxiliary subunits may facilitate the future development of potent and highly subtype-specific Kv channel inhibitors. PMID:27731317

  13. KCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting

    Science.gov (United States)

    Wrobel, Eva; Rothenberg, Ina; Krisp, Christoph; Hundt, Franziska; Fraenzel, Benjamin; Eckey, Karina; Linders, Joannes T. M.; Gallacher, David J.; Towart, Rob; Pott, Lutz; Pusch, Michael; Yang, Tao; Roden, Dan M.; Kurata, Harley T.; Schulze-Bahr, Eric; Strutz-Seebohm, Nathalie; Wolters, Dirk; Seebohm, Guiscard

    2016-10-01

    Most small-molecule inhibitors of voltage-gated ion channels display poor subtype specificity because they bind to highly conserved residues located in the channel's central cavity. Using a combined approach of scanning mutagenesis, electrophysiology, chemical ligand modification, chemical cross-linking, MS/MS-analyses and molecular modelling, we provide evidence for the binding site for adamantane derivatives and their putative access pathway in Kv7.1/KCNE1 channels. The adamantane compounds, exemplified by JNJ303, are highly potent gating modifiers that bind to fenestrations that become available when KCNE1 accessory subunits are bound to Kv7.1 channels. This mode of regulation by auxiliary subunits may facilitate the future development of potent and highly subtype-specific Kv channel inhibitors.

  14. Full-genome analysis of avian influenza A(H5N1) virus from a human, North America, 2013.

    Science.gov (United States)

    Pabbaraju, Kanti; Tellier, Raymond; Wong, Sallene; Li, Yan; Bastien, Nathalie; Tang, Julian W; Drews, Steven J; Jang, Yunho; Davis, C Todd; Fonseca, Kevin; Tipples, Graham A

    2014-05-01

    Full-genome analysis was conducted on the first isolate of a highly pathogenic avian influenza A(H5N1) virus from a human in North America. The virus has a hemagglutinin gene of clade 2.3.2.1c and is a reassortant with an H9N2 subtype lineage polymerase basic 2 gene. No mutations conferring resistance to adamantanes or neuraminidase inhibitors were found.

  15. 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....

  16. Isolation and structural proof of the large diamond molecule, cyclohexamantane (C26H30)

    Science.gov (United States)

    Dahl, J.E.P.; Moldowan, J.M.; Peakman, T.M.; Clardy, J.C.; Lobkovsky, E.; Olmstead, M.M.; May, P.W.; Davis, T.J.; Steeds, J.W.; Peters, K.E.; Pepper, A.; Ekuan, A.; Carlson, R.M.K.

    2003-01-01

    Ace of diamonds: Cyclohexamantane (C26H30), a large diamond-like molecule containing six peri-fused adamantane cages was identified in petroleum and its structure proven by X-ray crystallography (see picture), Never synthesized because of severe mechanistic difficulties, the structure of cyclohexamantane has appeared in theoretical molecular-simulation studies related to diamond; its experimentally determined properties are now discussed.

  17. Drug: D08174 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08174 Drug Memantine (INN); Exiba (TN) C12H21N 179.1674 179.3018 D08174.gif Anti-Alzheimer...'s [DS:H00056] Same as: C13736 ATC code: N06DX01 Indication: Alzheimer's disease adamantane derivati...napse hsa05010(2902+2903+2904+2905+2906) Alzheimer's disease Transporter: SLC22A2 [HSA:6582] map07056 Agents for Alzheimer

  18. Organic Electrochemistry in Aluminum Chloride Melts.

    Science.gov (United States)

    1976-08-15

    Cyclic voltametry revealed adamantane and l-methyladamanta1ie to be electroactive at a tungsten electrode * well within the background limits of molten...diphenylmethane. Coulometry cyclic voltametry and ring-disc electrode studies were carried out to elucidate a mechanism for the reaction. It was shown that...the viscosity was found to be 25 cp and the • I conductivity, 3 x 1O~ ohm~ cm ’. A variety of electrode materials were surveyed via cyclic voltaninetry

  19. Viral M2 ion channel protein: a promising target for anti-influenza drug discovery.

    Science.gov (United States)

    Moorthy, N S Hari Narayana; Poongavanam, Vasanthanathan; Pratheepa, V

    2014-01-01

    Influenza virus is an important RNA virus causing pandemics (Spanish Flu (1918), Asian Flu (1957), Hong Kong Flu (1968) and Swine Flu (2009)) over the last decades. Due to the spontaneous mutations of these viral proteins, currently available antiviral and anti-influenza drugs quickly develop resistance. To account this, only limited antiinfluenza drugs have been approved for the therapeutic use. These include amantadine and rimantadine (M2 proton channel blockers), zanamivir, oseltamivir and peramivir (neuraminidase inhibitors), favipravir (polymerase inhibitor) and laninamivir. This review provides an outline on the strategies to develop novel, potent chemotherapeutic agents against M2 proton channel. Primarily, the M2 proton channel blockers elicit pharmacological activity through destabilizing the helices by blocking the proton transport across the transmembrane. The biologically important compounds discovered using the scaffolds such as bisnoradmantane, noradamantane, triazine, spiroadamantane, isoxazole, amino alcohol, azaspiro, spirene, pinanamine, etc are reported to exhibit anti-influenza activity against wild or mutant type (S31N and V27A) of M2 proton channel protein. The reported studies explained that the adamantane based compounds (amantadine and rimantadine) strongly interact with His37 (through hydrogen bonding) and Ala30, Ile33 and Gly34 residues (hydrophobic interactions). The adamantane and the non-adamantane scaffolds fit perfectly in the active site pocket present in the wild type and the charged amino groups (ammonium) create positive electrostatic potential, which blocks the transport of protons across the pore. In the mutated proteins, larger or smaller binding pocket are created by small or large mutant residues, which do not allow the molecules fit in the active site. This causes the channel to be unblocked and the protons are allowed to transfer inside the pore. The structural analysis of the M2 proton channel blockers illustrated that

  20. Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus, Mexico

    Science.gov (United States)

    Ramirez-Gonzalez, José Ernesto; Gonzalez-Duran, Elizabeth; Alcantara-Perez, Patricia; Wong-Arambula, Claudia; Olivera-Diaz, Hiram; Cortez-Ortiz, Iliana; Barrera-Badillo, Gisela; Nguyen, Ha; Gubareva, Larisa; Lopez-Martinez, Irma; Díaz-Quiñonez, Jose Alberto; Lezana-Fernández, Miguel Angel; Gatell-Ramírez, Hugo Lopez; Villalobos, Jose Angel Cordova; Hernández-Avila, Mauricio

    2011-01-01

    During May 2009–April 2010, we analyzed 692 samples of pandemic (H1N1) 2009 virus from patients in Mexico. We detected the H275Y substitution of the neuraminidase gene in a specimen from an infant with pandemic (H1N1) 2009 who was treated with oseltamivir. This virus was susceptible to zanamivir and resistant to adamantanes and oseltamivir. PMID:21291607

  1. Versatile types of polysaccharide-based supramolecular polycation/pDNA nanoplexes for gene delivery

    Science.gov (United States)

    Hu, Yang; Zhao, Nana; Yu, Bingran; Liu, Fusheng; Xu, Fu-Jian

    2014-06-01

    Different polysaccharide-based supramolecular polycations were readily synthesized by assembling multiple β-cyclodextrin-cored star polycations with an adamantane-functionalized dextran via host-guest interaction in the absence or presence of bioreducible linkages. Compared with nanoplexes of the starting star polycation and pDNA, the supramolecular polycation/pDNA nanoplexes exhibited similarly low cytotoxicity, improved cellular internalization and significantly higher gene transfection efficiencies. The incorporation of disulfide linkages imparted the supramolecular polycation/pDNA nanoplexes with the advantage of intracellular bioreducibility, resulting in better gene delivery properties. In addition, the antitumor properties of supramolecular polycation/pDNA nanoplexes were also investigated using a suicide gene therapy system. The present study demonstrates that the proper assembly of cyclodextrin-cored polycations with adamantane-functionalized polysaccharides is an effective strategy for the production of new nanoplex delivery systems.Different polysaccharide-based supramolecular polycations were readily synthesized by assembling multiple β-cyclodextrin-cored star polycations with an adamantane-functionalized dextran via host-guest interaction in the absence or presence of bioreducible linkages. Compared with nanoplexes of the starting star polycation and pDNA, the supramolecular polycation/pDNA nanoplexes exhibited similarly low cytotoxicity, improved cellular internalization and significantly higher gene transfection efficiencies. The incorporation of disulfide linkages imparted the supramolecular polycation/pDNA nanoplexes with the advantage of intracellular bioreducibility, resulting in better gene delivery properties. In addition, the antitumor properties of supramolecular polycation/pDNA nanoplexes were also investigated using a suicide gene therapy system. The present study demonstrates that the proper assembly of cyclodextrin-cored polycations

  2. 2-(1-Adamantyl-1-(3-aminophenylethanol

    Directory of Open Access Journals (Sweden)

    Michal Rouchal

    2011-09-01

    Full Text Available In the crystal structure of the title compound, C18H25NO, molecules are linked via O—H...N hydrogen bonds, forming chains parallel to the c axis. Additional weak N—H...O interactions stabilize the crystal packing. The adamantane cage consists of three fused cyclohexane rings in almost ideal chair conformations, with C—C—C angles in the range 107.9 (10–111.3 (11°.

  3. A Nano-MgO and Ionic Liquid-Catalyzed ‘Green’ Synthesis Protocol for the Development of Adamantyl-Imidazolo-Thiadiazoles as Anti-Tuberculosis Agents Targeting Sterol 14α-Demethylase (CYP51)

    Science.gov (United States)

    Anusha, Sebastian; CP, Baburajeev; Mohan, Chakrabhavi Dhananjaya; Mathai, Jessin; Rangappa, Shobith; Mohan, Surender; Chandra; Paricharak, Shardul; Mervin, Lewis; Fuchs, Julian E.; M, Mahedra; Bender, Andreas; Basappa; Rangappa, Kanchugarakoppal S.

    2015-01-01

    In this work, we describe the ‘green’ synthesis of novel 6-(adamantan-1-yl)-2-substituted-imidazo[2,1-b][1,3,4]thiadiazoles (AITs) by ring formation reactions using 1-(adamantan-1-yl)-2-bromoethanone and 5-alkyl/aryl-2-amino1,3,4-thiadiazoles on a nano material base in ionic liquid media. Given the established activity of imidazothiadiazoles against M. tuberculosis, we next examined the anti-TB activity of AITs against the H37Rv strain using Alamar blue assay. Among the tested compounds 6-(adamantan-1-yl)-2-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazole (3f) showed potent inhibitory activity towards M. tuberculosis with an MIC value of 8.5 μM. The inhibitory effect of this molecule against M. tuberculosis was comparable to the standard drugs such as Pyrazinamide, Streptomycin, and Ciprofloxacin drugs. Mechanistically, an in silico analysis predicted sterol 14α-demethylase (CYP51) as the likely target and experimental activity of 3f in this system corroborated the in silico target prediction. In summary, we herein report the synthesis and biological evaluation of novel AITs against M. tuberculosis that likely target CYP51 to induce their antimycobacterial activity. PMID:26470029

  4. A Nano-MgO and Ionic Liquid-Catalyzed 'Green' Synthesis Protocol for the Development of Adamantyl-Imidazolo-Thiadiazoles as Anti-Tuberculosis Agents Targeting Sterol 14α-Demethylase (CYP51).

    Science.gov (United States)

    Anusha, Sebastian; Cp, Baburajeev; Mohan, Chakrabhavi Dhananjaya; Mathai, Jessin; Rangappa, Shobith; Mohan, Surender; Chandra; Paricharak, Shardul; Mervin, Lewis; Fuchs, Julian E; M, Mahedra; Bender, Andreas; Basappa; Rangappa, Kanchugarakoppal S

    2015-01-01

    In this work, we describe the 'green' synthesis of novel 6-(adamantan-1-yl)-2-substituted-imidazo[2,1-b][1,3,4]thiadiazoles (AITs) by ring formation reactions using 1-(adamantan-1-yl)-2-bromoethanone and 5-alkyl/aryl-2-amino1,3,4-thiadiazoles on a nano material base in ionic liquid media. Given the established activity of imidazothiadiazoles against M. tuberculosis, we next examined the anti-TB activity of AITs against the H37Rv strain using Alamar blue assay. Among the tested compounds 6-(adamantan-1-yl)-2-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazole (3f) showed potent inhibitory activity towards M. tuberculosis with an MIC value of 8.5 μM. The inhibitory effect of this molecule against M. tuberculosis was comparable to the standard drugs such as Pyrazinamide, Streptomycin, and Ciprofloxacin drugs. Mechanistically, an in silico analysis predicted sterol 14α-demethylase (CYP51) as the likely target and experimental activity of 3f in this system corroborated the in silico target prediction. In summary, we herein report the synthesis and biological evaluation of novel AITs against M. tuberculosis that likely target CYP51 to induce their antimycobacterial activity.

  5. A Review of the Antiviral Susceptibility of Human and Avian Influenza Viruses over the Last Decade

    Directory of Open Access Journals (Sweden)

    Ding Yuan Oh

    2014-01-01

    Full Text Available Antivirals play an important role in the prevention and treatment of influenza infections, particularly in high-risk or severely ill patients. Two classes of influenza antivirals have been available in many countries over the last decade (2004–2013, the adamantanes and the neuraminidase inhibitors (NAIs. During this period, widespread adamantane resistance has developed in circulating influenza viruses rendering these drugs useless, resulting in the reliance on the most widely available NAI, oseltamivir. However, the emergence of oseltamivir-resistant seasonal A(H1N1 viruses in 2008 demonstrated that NAI-resistant viruses could also emerge and spread globally in a similar manner to that seen for adamantane-resistant viruses. Previously, it was believed that NAI-resistant viruses had compromised replication and/or transmission. Fortunately, in 2013, the majority of circulating human influenza viruses remain sensitive to all of the NAIs, but significant work by our laboratory and others is now underway to understand what enables NAI-resistant viruses to retain the capacity to replicate and transmit. In this review, we describe how the susceptibility of circulating human and avian influenza viruses has changed over the last ten years and describe some research studies that aim to understand how NAI-resistant human and avian influenza viruses may emerge in the future.

  6. The abundance and distribution of diamondoids in biodegraded oils from the San Joaquin Valley: Implications for biodegradation of diamondoids in petroleum reservoirs

    Science.gov (United States)

    Wei, Z.; Moldowan, J.M.; Peters, K.E.; Wang, Y.; Xiang, W.

    2007-01-01

    The biodegradability of diamondoids was investigated using a collection of crude oil samples from the San Joaquin Valley, California, that had been biodegraded to varying extent in the reservoir. Our results show that diamondoids are subjected to biodegradation, which is selective as well as stepwise. Adamantanes are generally more susceptible to biodegradation than other diamondoids, such as diamantanes and triamantanes. We report a possible pathway for the microbial degradation of adamantane. This cage hydrocarbon possibly breaks down to a metabolic intermediate through the action of microbes at higher levels of biodegradation in petroleum reservoirs. Microbial alteration has only a minor effect on diamondoid abundance in oil at low levels of biodegradation. Our results suggest that most diamondoids (with the exception of adamantane) are resistant to biodegradation, like the polycyclic terpanes (e.g. C19-C24 tricyclic terpanes, hopanes, gammacerane, oleananes, Ts, Tm, C29 Ts), steranes and diasteranes. Microbial alteration of diamondoids has a negligible impact on the quantification of oil cracking achieved using the diamondoid-biomarker method. ?? 2007 Elsevier Ltd. All rights reserved.

  7. Inhibitors of the influenza A virus M2 proton channel discovered using a high-throughput yeast growth restoration assay.

    Directory of Open Access Journals (Sweden)

    Aruna D Balgi

    Full Text Available The M2 proton channel of the influenza A virus is the target of the anti-influenza drugs amantadine and rimantadine. The effectiveness of these drugs has been dramatically limited by the rapid spread of drug resistant mutations, mainly at sites S31N, V27A and L26F in the pore of the channel. Despite progress in designing inhibitors of V27A and L26F M2, there are currently no drugs targeting these mutated channels in clinical trials. Progress in developing new drugs has been hampered by the lack of a robust assay with sufficient throughput for discovery of new active chemotypes among chemical libraries and sufficient sensitivity to provide the SAR data essential for their improvement and development as drugs. In this study we adapted a yeast growth restoration assay, in which expression of the M2 channel inhibits yeast growth and exposure to an M2 channel inhibitor restores growth, into a robust and sensitive high-throughput screen for M2 channel inhibitors. A screen of over 250,000 pure chemicals and semi-purified fractions from natural extracts identified 21 active compounds comprising amantadine, rimantadine, 13 related adamantanes and 6 non-adamantanes. Of the non-adamantanes, hexamethylene amiloride and a triazine derivative represented new M2 inhibitory chemotypes that also showed antiviral activity in a plaque reduction assay. Of particular interest is the fact that the triazine derivative was not sufficiently potent for detection as an inhibitor in the traditional two electrode voltage clamp assay for M2 channel activity, but its discovery in the yeast assay led to testing of analogues of which one was as potent as amantadine.

  8. Bilayer vesicles of amphiphilic cyclodextrins: host membranes that recognize guest molecules.

    Science.gov (United States)

    Falvey, Patrick; Lim, Choon Woo; Darcy, Raphael; Revermann, Tobias; Karst, Uwe; Giesbers, Marcel; Marcelis, Antonius T M; Lazar, Adina; Coleman, Anthony W; Reinhoudt, David N; Ravoo, Bart Jan

    2005-02-04

    A family of amphiphilic cyclodextrins (6, 7) has been prepared through 6-S-alkylation (alkyl=n-dodecyl and n-hexadecyl) of the primary side and 2-O-PEGylation of the secondary side of alpha-, beta-, and gamma-cyclodextrins (PEG=poly(ethylene glycol)). These cyclodextrins form nonionic bilayer vesicles in aqueous solution. The bilayer vesicles were characterized by transmission electron microscopy, dynamic light scattering, dye encapsulation, and capillary electrophoresis. The molecular packing of the amphiphilic cyclodextrins was investigated by using small-angle X-ray diffraction of bilayers deposited on glass and pressure-area isotherms obtained from Langmuir monolayers on the air-water interface. The bilayer thickness is dependent on the chain length, whereas the average molecular surface area scales with the cyclodextrin ring size. The alkyl chains of the cyclodextrins in the bilayer are deeply interdigitated. Molecular recognition of a hydrophobic anion (adamantane carboxylate) by the cyclodextrin vesicles was investigated by using capillary electrophoresis, thereby exploiting the increase in electrophoretic mobility that occurs when the hydrophobic anions bind to the nonionic cyclodextrin vesicles. It was found that in spite of the presence of oligo(ethylene glycol) substituents, the beta-cyclodextrin vesicles retain their characteristic affinity for adamantane carboxylate (association constant K(a)=7.1 x 10(3) M(-1)), whereas gamma-cyclodextrin vesicles have less affinity (K(a)=3.2 x 10(3) M(-1)), and alpha-cyclodextrin or non-cyclodextrin, nonionic vesicles have very little affinity (K(a) approximately 100 M(-1)). Specific binding of the adamantane carboxylate to beta-cyclodextrin vesicles was also evident in competition experiments with beta-cyclodextrin in solution. Hence, the cyclodextrin vesicles can function as host bilayer membranes that recognize small guest molecules by specific noncovalent interaction.

  9. Structure and properties of bimetallic titanium and vanadium oxide clusters.

    Science.gov (United States)

    Helmich, Benjamin; Sierka, Marek; Döbler, Jens; Sauer, Joachim

    2014-05-14

    By employing a genetic algorithm together with density functional theory (B3LYP), we investigate the most stable minimum structures of several bimetallic titanium and vanadium oxide clusters that contain four metal atoms. The following compositions are studied: VnTin-4O10(-) (n = 1-4), (TiO2)VOn(-) (n = 1-4), and (TiO2)VOn(+) (n = 1-3). Apart from (TiO2)3VO(-), vanadium oxo groups are always part of the most stable minimum structures when vanadium is present. Anti-ferromagnetic coupling lowers the energy substantially if spin centers are located at neighbored metal atoms rather than at distant oxygen radical sites. Vanadium-rich or oxygen-poor compositions prefer symmetric adamantane-like cage structures, some of which have already been proposed in a previous study. In contrast, vanadium-poor and oxygen-rich compositions show versatile structural motifs that cannot be intuitively derived from the symmetric cage motif. Particularly, for Ti4O10(-) there are several non-symmetric and distorted cages that have an up to 68 kJ mol(-1) lower energy than the symmetric adamantane-like cage structure. Nevertheless, for the adamantane-like cage the simulated infra-red spectrum (within the harmonic approximation) agrees best with the experimental vibrational spectrum. The oxidative power of the (TiO2)3VO3(-) and (TiO2)3VO2(+) clusters as measured by the energy of removing 1/2 O2 (297 and 227 kJ mol(-1), respectively) is less than that of the pure vanadium oxide clusters (V2O5)VO3(-) and (V2O5)VO2(+) (283 and 165 kJ mol(-1), respectively).

  10. Reaction mechanisms of ruthenium tetroxide mediated oxidations of organic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Froehaug, Astrid Elisabeth

    1995-12-31

    This thesis reports a study of the mechanism of ruthenium tetroxide mediated oxidations of saturated hydrocarbons, ethers, alkenes and alcohols. Several methods were used. The RuO{sub 4}-mediated oxidations of adamantane and cis-decalin were studied in CCl{sub 4}-CH{sub 3}CN-H{sub 2}O and in acetone-water. The rate of reaction was found to be moderately influenced by the polarity of the solvent. Solvent properties other than the polarity were also found to influence the reaction rates. From the oxidations of adamantane and adamantane-1,3,5,7-d{sub 4} two primary kinetic deuterium isotope effects were found. These were comparable with the deuterium isotope effects found for the analogous oxidations of cis-decalin and cis-decalin-d{sub 18}. The results seem to exclude both a one step hydride abstraction reaction mechanism and a one step concerted mechanism, as well as a scheme where two such mechanisms compete. The observations may be explained by a two step reaction mechanism consisting of a pre-equilibrium with formation of a substrate-RuO{sub 4} complex followed by a concerted rate determining reaction. The RuO{sub 4}-mediated oxidation of ethers was of kinetic second order with a small enthalpy of activation and a large negative entropy of activation. Oxidation of cyclopropylmethyl methyl ether gave methyl cyclopropanecarboxylate, no rearranged products were observed. On RuO{sub 4} oxidations in CCl{sub 4} with NaIO{sub 4} as stoichiometric oxidant, no chlorinated products were observed. Several observations not in agreement with a hydride or a hydrogen abstraction mechanism may be explained by assuming that the reaction proceeds by either a concerted reaction or by a reversible oxidative addition of the ether to RuO{sub 4} followed by a slow concerted step. 228 refs., 9 figs., 27 tabs.

  11. Designing inhibitors of M2 proton channel against H1N1 swine influenza virus.

    Directory of Open Access Journals (Sweden)

    Qi-Shi Du

    Full Text Available BACKGROUND: M2 proton channel of H1N1 influenza A virus is the target protein of anti-flu drugs amantadine and rimantadine. However, the two once powerful adamantane-based drugs lost their 90% bioactivity because of mutations of virus in recent twenty years. The NMR structure of the M2 channel protein determined by Schnell and Chou (Nature, 2008, 451, 591-595 may help people to solve the drug-resistant problem and develop more powerful new drugs against H1N1 influenza virus. METHODOLOGY: Docking calculation is performed to build the complex structure between receptor M2 proton channel and ligands, including existing drugs amantadine and rimantadine, and two newly designed inhibitors. The computer-aided drug design methods are used to calculate the binding free energies, with the computational biology techniques to analyze the interactions between M2 proton channel and adamantine-based inhibitors. CONCLUSIONS: 1 The NMR structure of M2 proton channel provides a reliable structural basis for rational drug design against influenza virus. 2 The channel gating mechanism and the inhibiting mechanism of M2 proton channel, revealed by the NMR structure of M2 proton channel, provides the new ideas for channel inhibitor design. 3 The newly designed adamantane-based inhibitors based on the modeled structure of H1N1-M2 proton channel have two pharmacophore groups, which act like a "barrel hoop", holding two adjacent helices of the H1N1-M2 tetramer through the two pharmacophore groups outside the channel. 4 The inhibitors with such binding mechanism may overcome the drug resistance problem of influenza A virus to the adamantane-based drugs.

  12. [Characteristics of antiischemic and nootropic properties of ademol in a rat model of acute brain ischemia].

    Science.gov (United States)

    Khodakivs'kyĭ, O A

    2013-01-01

    In experiments with the rat model of acute disorder of encephalic circulation (bilateral carotid occlusion) it was found that introduction of derivate of adamantan 1-adamantiloxy-3-morfolino-2 propanol (under conventional name ademol) in the dose 2 mg/kg intraabdominal in treatment regimen (in an hour after reconstruction of insult and further 1 time every 24 hours during 21 days) was accompanied by a recovery of mnemotropic properties and is more effective than cytikolin, resulting in a decreased lethality and neurological deficiency in acute and recovery periods of insults. The data received proved the usefulness of development of ademol based cerebroprotective remedy.

  13. Drug: D00777 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 28 187.7096 D00777.gif Antiviral, Antiparkinsonian [DS:H00057 H00398] Same as: C07939 Therapeutic category: ...ansporter: SLC22A2 [HSA:6582] map07044 Antiviral agents map07057 Antiparkinsonian agents map07235 N-Metyl-D-...rvous system and sensory organs 11 Agents affecting central nervous system 116 Antiparkinson...ation [BR:br08302] Antiparkinson Agents Antiparkinson Agents, Other Amantadine D0...04BB Adamantane derivatives N04BB01 Amantadine D00777 Amantadine hydrochloride (JP16/USP) USP drug classific

  14. Synthesis of novel triazole-linked mefloquine derivatives: biological evaluation against Plasmodium falciparum.

    Science.gov (United States)

    Hamann, Anton R; de Kock, Carmen; Smith, Peter J; van Otterlo, Willem A L; Blackie, Margaret A L

    2014-12-01

    Using 2,8-bis(trifluoromethyl)quinoline, the pharmacophore of mefloquine, as scaffold, eleven novel triazole-linked compounds have been synthesised by the application of CuAAC chemistry. The in vitro biological activity of the compounds on the Plasmodium falciparum chloroquine-sensitive strain NF54 was then determined. The compounds all showed IC50s in the lower μM range with (1R,3S,5R)-N-{[1-(2,8-bis(trifluoromethyl)quinoline-4-yl)-1H-1,2,3-triazol-4-yl]methyl}adamantan-2-amine (29) exhibiting the best activity of 1.00 μM.

  15. Recent advances in the chemotherapy of herpes virus infections.

    Science.gov (United States)

    Eşanu, V

    1981-01-01

    The main categories of antiherpes agents presently used in chemotherapy area reviewed according to the phase of virus replication affected : 1) virus adsorption (adamantane, nonionic surfactants) ; 2) eclipse (interferon) ; 3) virion maturation (nucleoside and nucleotide analogues and phosphonic acid derivatives). Mention is also made of other compounds--different synthetic organic derivatives, photodynamic dyes, metal ions, boric acid, hormones, antibiotics, other natural products (extracts from marine algae, propolis, garlic)--with promising antiviral properties. The difficulties and prospects of viral chemotherapy research are briefly discussed.

  16. Computer simulation of a phosphorescent probe inside β -cyclodextrin matrices

    Science.gov (United States)

    Odinokov, Alexey; Alfimov, Mikhail

    2017-01-01

    Molecular dynamics simulations of the different self-assembled structures based on the β -cyclodextrin and adamantane were performed. The line shift and non-uniform broadening of the T1 →S0 transition of naphthalene molecule inserted into these structures were calculated. It was found that line width is mainly governed by the nearest-neighbor environment. The most important factor was the existence of the typical "sandwich" structural pattern. The main findings provide a way to the rational design of new materials for nanophotonics.

  17. Ruthenium tetraoxide oxidations of alkanes: DFT calculations of barrier heights and kinetic isotope effects.

    Science.gov (United States)

    Drees, Markus; Strassner, Thomas

    2006-03-03

    The oxidation of C-H and C-C bonds by metal-oxo compounds is of general interest. We studied the RuO4-mediated catalytic oxidation of several cycloalkanes such as adamantane and cis- and trans-decalin as well as methane. B3LYP/6-31G(d) calculations on the experimentally proposed (3+2) mechanism are in good agreement with known experimental results. Comparison of experimental and theoretical kinetic isotope effects confirms the proposed mechanism. Besides RuO4, we also looked at RuO4(OH)- as a potential active species to account for ruthenium tetraoxide oxidations under strong basic conditions.

  18. Autoencapsulation through intermolecular forces: a synthetic self-assembling spherical complex.

    Science.gov (United States)

    Meissner, R S; Rebek, J; de Mendoza, J

    1995-12-01

    The synthesis and characterization of a system for the study of molecular recognition phenomena are described. The system involves a tetraurea molecule that is capable of assembly into various associated states through hydrogen bonding. In organic solvents, the dynamic transition between a low-ordered (aggregate) state and a highly ordered dimeric assembly can be induced by the introduction of smaller molecules of appropriate size and shape. These smaller molecules, such as benzene, adamantanes, and ferrocenes, act as guests that occupy the pseudospherical capsule formed by the dimeric host. Among various guests, those that best fill the cavity and offer chemical complementarity to the host are preferentially encapsulated.

  19. Superstructures of fluorescent cyclodextrin via click-reaction

    Directory of Open Access Journals (Sweden)

    Arkadius Maciollek

    2013-04-01

    Full Text Available Mono-(6-azido-6-deoxy-β-cyclodextrin (CD was covalently attached to an alkyne-modified 5-methyl-2-(pyridin-2-ylthiazol-4-ol yielding a fluorophore containing CD in a click-type reaction. Intermolecular complexes were formed by poly(host–guest-interactions. The supramolecular structures were characterized by 1H NMR-ROESY spectroscopy, dynamic light scattering, UV–vis spectroscopy, fluorescence spectroscopy, and asymmetric flow field-flow fractionation. By adding potassium adamantane-1-carboxylate, the thiazol dye is displaced from the CD-cavity and the elongated noncovalent polymeric structures collapse.

  20. Computational study of drug binding to the membrane-bound tetrameric M2 peptide bundle from influenza A virus.

    Science.gov (United States)

    Khurana, Ekta; Devane, Russell H; Dal Peraro, Matteo; Klein, Michael L

    2011-02-01

    The M2 protein of influenza A virus performs the crucial function of transporting protons to the interior of virions enclosed in the endosome. Adamantane drugs, amantadine (AMN) and rimantidine (RMN), block the proton conduction in some strains, and have been used for the treatment and prophylaxis of influenza A infections. The structures of the transmembrane (TM) region of M2 that have been solved in micelles using NMR (residues 23-60) (Schnell and Chou, 2008) and by X-ray crystallography (residues 22-46) (Stouffer et al., 2008) suggest different drug binding sites: external and internal for RMN and AMN, respectively. We have used molecular dynamics (MD) simulations to investigate the nature of the binding site and binding mode of adamantane drugs on the membrane-bound tetrameric M2-TM peptide bundles using as initial conformations the low-pH AMN-bound crystal structure, a high-pH model derived from the drug-free crystal structure, and the high-pH NMR structure. The MD simulations indicate that under both low- and high-pH conditions, AMN is stable inside the tetrameric bundle, spanning the region between residues Val27 to Gly34. At low pH the polar group of AMN is oriented toward the His37 gate, while under high-pH conditions its orientation exhibits large fluctuations. The present MD simulations also suggest that AMN and RMN molecules do not show strong affinity to the external binding sites.

  1. Obtaining control of cell surface functionalizations via Pre-targeting and Supramolecular host guest interactions.

    Science.gov (United States)

    Rood, Mark T M; Spa, Silvia J; Welling, Mick M; Ten Hove, Jan Bart; van Willigen, Danny M; Buckle, Tessa; Velders, Aldrik H; van Leeuwen, Fijs W B

    2017-01-06

    The use of mammalian cells for therapeutic applications is finding its way into modern medicine. However, modification or "training" of cells to make them suitable for a specific application remains complex. By envisioning a chemical toolbox that enables specific, but straight-forward and generic cellular functionalization, we investigated how membrane-receptor (pre)targeting could be combined with supramolecular host-guest interactions based on β-cyclodextrin (CD) and adamantane (Ad). The feasibility of this approach was studied in cells with membranous overexpression of the chemokine receptor 4 (CXCR4). By combining specific targeting of CXCR4, using an adamantane (Ad)-functionalized Ac-TZ14011 peptide (guest; KD = 56 nM), with multivalent host molecules that entailed fluorescent β-CD-Poly(isobutylene-alt-maleic-anhydride)-polymers with different fluorescent colors and number of functionalities, host-guest cell-surface modifications could be studied in detail. A second set of Ad-functionalized entities enabled introduction of additional surface functionalities. In addition, the attraction between CD and Ad could be used to drive cell-cell interactions. Combined we have shown that supramolecular interactions, that are based on specific targeting of an overexpressed membrane-receptor, allow specific and stable, yet reversible, surface functionalization of viable cells and how this approach can be used to influence the interaction between cells and their surroundings.

  2. Quasi-equilibrium states in thermotropic liquid crystals studied by multiple quantum NMR

    CERN Document Server

    Buljubasich, L; Acosta, R H; Bonin, C J; alez, C E Gonz\\'; Zamar, R C

    2010-01-01

    We study the nature of the quasiinvariants in nematic 5CB and measure their relaxation times by encoding the multiple quantum coherences of the states following the JB pulse pair on two orthogonal bases, Z and X. The experiments were also performed in powder adamantane at 301 K which is used as a reference compound having only one dipolar quasiinvariant. We show that the evolution of the quantum states during the build up of the quasi-equilibrium state in 5CB prepared under the S condition is similar to the case of adamantane and that their quasi-equilibrium density operators have the same tensor structure. In contrast, the second constant of motion, whose explicit operator form is not known, involves a richer composition of multiple quantum coherences on the X basis of even order, in consistency with the truncation inherent in its definition. We exploited the exclusive presence coherences 4, 6, 8, besides 0 and 2 under the W condition to measure the spin-lattice relaxation time T_{W} accurately, so avoiding ...

  3. Solvothermal synthesis of a new 3-D mixed-metal sulfide framework, (H1.33tren)[In2.67Sb1.33S8]·tren

    Science.gov (United States)

    Lampkin, John D.; Powell, Anthony V.; Chippindale, Ann M.

    2016-11-01

    A new indium(III) antimony(V) sulfide, (H1.33tren)[In2.67Sb1.33S8]·tren, has been prepared solvothermally at 433 K. The compound crystallises in the tetragonal space group I-42d (lattice parameters, a=12.6248(5) and c=19.4387(18) Å at 150 K) and contains adamantane-like T2 supertetrahedral units comprised of corner-sharing InS45- and SbS43- tetrahedra. The adamantane-like units are then linked through sulfur vertices to generate an open, 3-D framework structure containing large pores in which neutral, protonated tren (tris(2-aminoethylene)amine) molecules reside. The presence of the organic components was confirmed by solid-state 13C NMR (10 kHz), combustion and thermogravimetric analysis. The band gap, obtained from UV-vis diffuse reflectance measurements, is 2.7(2) eV. Stirring with either water or alkali-metal salt solution leads to removal of the neutral tren molecules and an 9% reduction in unit-cell volume on formation of (H1.33tren)[In2.67Sb1.33S8]·(H2O)4.

  4. [Effects of blockade of ionotropic glutamate receptors on the development of pentylenetetrazole kindling in mice].

    Science.gov (United States)

    Lukomskaia, N Ia; Lavrent'eva, V V; Starshinova, L A; Zhabko, E P; Gorbunova, L V; Tikhonova, T B; Gmiro, V E; Magazanik, L G

    2005-11-01

    Effects of mono- and dicationic derivatives of adamantane and phenylcyclohexyl on the petyleneterazole-induced (35 mg/kg i. p.) kindling were studied in the experiments on mice. Monocationic derivative of phenylcyclohexyl IEM-1921, effectively retarded the development of kindling beginning the dose 0.0001 microM/kg. Memantine: derivative of adamantane (derivative of adamatane) produced the same effect with 100-fold increased dose. Dicationic derivative ofphenylcyclohexyl: IEM-1925, is able to block equally the open channels of both NMDA and subtype of Ca-permeable AMPA receptors. Its effect on kindling differed markedly from selective NMDA antagonists (IEM-1921 and memantine) in more complicated dose-dependence. The retardation of kindling IEM-1925 was induced at 0.001 microM/kg. On the contrary, a 10-time lower dose: 0.0001 microM/kg, facilitated the development of kindling. The observed difference in the activity of selective NMDA antagonists and the drugs combining anti-NMDA and anti-AMPA potency indicates that both types of ionotropic glutamate receptors are involved in the mechanism of petyleneterazole-induced kindling. The integral effect of channel blockade evoked by drugs seems to be dependent not only upon the ratio of the receptor types but on the kinetics of drug action, too.

  5. Degradation mechanisms of geosmin and 2-MIB during UV photolysis and UV/chlorine reactions.

    Science.gov (United States)

    Kim, Tae-Kyoung; Moon, Bo-Ram; Kim, Taeyeon; Kim, Moon-Kyung; Zoh, Kyung-Duk

    2016-11-01

    We conducted chlorination, UV photolysis, and UV/chlorin reactions to investigate the intermediate formation and degradation mechanisms of geosmin and 2-methylisoborneol (2-MIB) in water. Chlorination hardly removed geosmin and 2-MIB, while the UV/chlorine reaction at 254 nm completely removed geosmin and 2-MIB within 40 min and 1 h, respectively, with lesser removals of both compounds during UV photolysis. The kinetics during both UV photolysis and UV/chlorine reactions followed a pseudo first-order reaction. Chloroform was found as a chlorinated intermediate during the UV/chlorine reaction of both geosmin and 2-MIB. The pH affected both the degradation and chloroform production during the UV/chlorine reaction. The open ring and dehydration intermediates identified during UV/chlorine reactions were 1,4-dimethyl-adamantane, and 1,3-dimethyl-adamantane from geosmin, 2-methylenebornane, and 2-methyl-2-bornene from 2-MIB, respectively. Additionally, 2-methyl-3-pentanol, 2,4-dimethyl-1-heptene, 4-methyl-2-heptanone, and 1,1-dichloro-2,4-dimethyl-1-heptane were newly identified intermediates from UV/chlorine reactions of both geosmin and 2-MIB. These intermediates were degraded as the reaction progressed. We proposed possible degradation pathways during the UV photolysis and UV/chlorine reactions of both compounds using the identified intermediates.

  6. Polycyclic amines as chloroquine resistance modulating agents in Plasmodium falciparum.

    Science.gov (United States)

    Joubert, Jacques; Kapp, Erika; Taylor, Dale; Smith, Peter J; Malan, Sarel F

    2016-02-15

    Pentacycloundecylamines (PCUs) and adamantane amines, such as NGP1-01 (1) and amantadine, have shown significant channel blocking activities. They are postulated to act as chemosensitizers and circumvent the resistance of the plasmodia parasite against chloroquine (CQ) by inhibiting the p-glycoprotein efflux pump and enabling the accumulation of CQ inside the parasite digestive vacuole. Twelve polycyclic amines containing either a PCU or adamantane amine moiety conjugated to different aromatic functionalities through various tethered linkers were selected based on their channel blocking abilities and evaluated as potential chemosensitizers. Compounds 2, 4, 5 and 10 showed significant voltage-gated calcium channel (VGCC) blocking ability (IC50=0.27-35 μM) and were able to alter the CQ IC50 in differing degrees (45-81%) in the multidrug resistant Plasmodium falciparum Dd2 isolate. Among them, the PCU-dansyl amine compound (4) displayed the best potential to act as a chemosensitizer against the Dd2 strain at a 1 μM concentration (RMI=0.19) while displaying moderate antiplasmodial activity (Dd2 IC50=6.25 μM) and low in vitro cytotoxicity against a mammalian cell line (CHO, IC50=119 μM). Compounds 2 and 10 also showed some promising chemosensitizing abilities (RMI=0.36 and 0.35 respectively). A direct correlation was found between the VGCC blocking ability of these polycyclic amines and their capacity to act as CQ resistance modulating agents.

  7. Anti-influenza Virus Effects of Catechins: A Molecular and Clinical Review.

    Science.gov (United States)

    Ide, Kazuke; Kawasaki, Yohei; Kawakami, Koji; Yamada, Hiroshi

    2016-01-01

    Influenza infection and associated epidemics represent a serious public health problem. Several preventive and curative measures exist against its spread including vaccination and therapeutic agents such as neuraminidase inhibitors (e.g., oseltamivir, zanamivir, as well as peramivir and laninamivir, which are licensed in several countries) and adamantanes (e.g., amantadine and rimantadine). However, neuraminidase inhibitor- and adamantane- resistant viruses have been detected, whereas vaccines exhibit strain-specific effects and are limited in supply. Thus, new approaches are needed to prevent and treat influenza infections. Catechins, a class of polyphenolic flavonoids present in tea leaves, have been reported as potential anti-influenza virus agents based on experimental and clinical studies. (-)-epigallocatechin gallate (EGCG), a major and highly bioactive catechin, is known to inhibit influenza A and B virus infections in Madin-Darby canine kidney cells. Additionally, EGCG and other catechin compounds such as epicatechin gallate and catechin-5-gallate also show neuraminidase inhibitory activities as demonstrated via molecular docking. These catechins can bind differently to neuraminidase and might overcome known drug resistancerelated virus mutations. Furthermore, the antiviral effects of chemically modified catechin derivatives have also been investigated, and future structure-based drug design studies of catechin derivatives might contribute to improvements in influenza prevention and treatment. This review briefly summarizes probable mechanisms underlying the inhibitory effects of tea catechins against influenza infection and their clinical benefits on influenza prevention and treatment. Additionally, the great potential of tea catechins and their chemical derivatives as effective antiviral agents is described.

  8. Flu channel drug resistance: a tale of two sites.

    Science.gov (United States)

    Pielak, Rafal M; Chou, James J

    2010-03-01

    The M2 proteins of influenza A and B virus, AM2 and BM2, respectively, are transmembrane proteins that oligomerize in the viral membrane to form proton-selective channels. Proton conductance of the M2 proteins is required for viral replication; it is believed to equilibrate pH across the viral membrane during cell entry and across the trans-Golgi membrane of infected cells during viral maturation. In addition to the role of M2 in proton conductance, recent mutagenesis and structural studies suggest that the cytoplasmic domains of the M2 proteins also play a role in recruiting the matrix proteins to the cell surface during virus budding. As viral ion channels of minimalist architecture, the membrane-embedded channel domain of M2 has been a model system for investigating the mechanism of proton conduction. Moreover, as a proven drug target for the treatment of influenza A infection, M2 has been the subject of intense research for developing new anti-flu therapeutics. AM2 is the target of two anti-influenza A drugs, amantadine and rimantadine, both belonging to the adamantane class of compounds. However, resistance of influenza A to adamantane is now widespread due to mutations in the channel domain of AM2. This review summarizes the structure and function of both AM2 and BM2 channels, the mechanism of drug inhibition and drug resistance of AM2, as well as the development of new M2 inhibitors as potential anti-flu drugs.

  9. First characterization of AKB-48 metabolism, a novel synthetic cannabinoid, using human hepatocytes and high-resolution mass spectrometry.

    Science.gov (United States)

    Gandhi, Adarsh S; Zhu, Mingshe; Pang, Shaokun; Wohlfarth, Ariane; Scheidweiler, Karl B; Liu, Hua-Fen; Huestis, Marilyn A

    2013-10-01

    Since the federal authorities scheduled the first synthetic cannabinoids, JWH-018 and JWH-073, new synthetic cannabinoids were robustly marketed. N-(1-Adamantyl)-1-pentylindazole-3-carboxamide (AKB-48), also known as APINACA, was recently observed in Japanese herbal smoking blends. The National Forensic Laboratory Information System registered 443 reports of AKB-48 cases in the USA from March 2010 to January 2013. In May 2013, the Drug Enforcement Administration listed AKB-48 as a Schedule I drug. Recently, AKB-48 was shown to have twice the CB1 receptor binding affinity than CB2. These pharmacological effects and the difficulty in detecting the parent compound in urine highlight the importance of metabolite identification for developing analytical methods for clinical and forensic investigations. Using human hepatocytes and TripleTOF mass spectrometry, we identified 17 novel phase I and II AKB-48 metabolites, products of monohydroxylation, dihydroxylation, or trihydroxylation on the aliphatic adamantane ring or N-pentyl side chain. Glucuronide conjugation of some mono- and dihydroxylated metabolites also occurred. Oxidation and dihydroxylation on the adamantane ring and N-pentyl side chain formed a ketone. More metabolites were identified after 3 h of incubation than at 1 h. For the first time, we present a AKB-48 metabolic scheme obtained from human hepatocytes and high-resolution mass spectrometry. These data are needed to develop analytical methods to identify AKB-48 consumption in clinical and forensic testing.

  10. The epidemiology and spread of drug resistant human influenza viruses.

    Science.gov (United States)

    Hurt, Aeron C

    2014-10-01

    Significant changes in the circulation of antiviral-resistant influenza viruses have occurred over the last decade. The emergence and continued circulation of adamantane-resistant A(H3N2) and A(H1N1)pdm09 viruses mean that the adamantanes are no longer recommended for use. Resistance to the newer class of drugs, the neuraminidase inhibitors, is typically associated with poorer viral replication and transmission. But 'permissive' mutations, that compensated for impairment of viral function in A(H1N1) viruses during 2007/2008, enabled them to acquire the H275Y NA resistance mutation without fitness loss, resulting in their rapid global spread. Permissive mutations now appear to be present in A(H1N1)pdm09 viruses thereby increasing the risk that oseltamivir-resistant A(H1N1)pdm09 viruses may also spread globally, a concerning scenario given that oseltamivir is the most widely used influenza antiviral. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Self-organization-induced three-dimensional honeycomb pattern in structure-controlled bulky methacrylate polymers: Synthesis, morphology, and mechanism of pore formation.

    Science.gov (United States)

    Deepak, V D; Asha, S K

    2006-11-02

    Here we report, for the first time, a novel molecular design for three-dimensional honeycomb structures through a self-organization of hydrogen-bonded bulky anchoring group in a methacrylic polymer backbone. The polymerizable monomer design includes a methacrylic double bond linked to various hydrophobic anchoring units such as ethane, n-decane, tricyclodecane (TCD), and adamantane via a hydrogen-bonded cycloaliphatic urethane linkage. The structures of the polymers were confirmed by nuclear magnetic resonance (NMR) and the molecular weights of the polymer were determined by gel permeation chromatography (GPC). The methacrylate polymers having tricyclodecane and adamantane bulky anchoring groups self-organized to produce three-dimensional honeycomb patterns in tetrahydrofuran-water solvent mixture at ambient conditions, whereas its linear analogues (ethane, n-decane) failed to produce any micropattern. The scanning electron microscopy (SEM) analysis of the above-prepared polymer films revealed that the structure of the polymer played a major role in the formation of the honeycomb patterns. The solution Fourier transform infrared (FTIR) measurements confirmed that the bulky tricyclodecane and adamantane polymers have strong hydrogen-bonding interaction compared to that of their linear analogues, which is the driving force for the micropatterns. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) analysis of the bulky polymers revealed that the polymers exist as vesicles or micelles in the solution, which leads to the formation of the honeycomb pattern. The honeycomb pattern formation in the bulky polymer systems suggests that two cooperative factors such as hydrogen-bonding interaction and hydrophobicity of bulky anchoring units are necessary to induce three-dimensional honeycomb structures. To investigate the effect of molecular weights and its distribution on the self-organization process, both benzoyl peroxide (BPO) initiated free radical and

  12. View at Croatian Chemistry through Meetings of Croatian

    Directory of Open Access Journals (Sweden)

    Trinajstić, N.

    2007-10-01

    Full Text Available The 20th Croatian meeting of chemists and chemical engineers was a proper occasion to consider the past meetings and their role in the development of Croatian chemistry and chemical engineering last 40 years, because these meetings reflect to a large extent the state of these sciences in Croatia. The circumstances that lead to establishment of the Croatian meetings of chemists and chemical engineers and the role of Professor Marijan Laaan (1919-1981 who started these meetings by organizing the first one are described. He also organized the second and the seventh meeting. All persons who chaired these meetings are mentioned, as well as all the lecturers who won the Nobel Prize in chemistry. Especially emphasized is the participation of Vladimir Prelog (1906-1998 since the twentieth meeting was dedicated to him and to Leopold Ružička (1887-1976 - two excellent Croatian chemists who for their first-class research in organic chemistry won the Nobel Prize (Ružička in 1939 and Prelog 1975. The places where the meetings were held are listed. The structure of the meetings when the change of the meetings' title happened is delineated and the representation of various branches of chemistry according to the number of contributions is discussed. Similarly, the Croatian institutions according to the number ofcontributions of their staff-members and the contributors with the highest number of communications at each meeting are pointed out. Emphasized is the international character of these meetings and the countries from which the participants came are listed. Finally, only one contribution is discussed in detail - the report by Kata Mlinarić-Majerski and Zdenko Majerski on the preparation of [3.1.1]propellane inserted in the structure of adamantane. Adamantane chemistry in Croatia started with the first ever adamantane synthesis in 1941, when Prelog and Seiwerth prepared this cage hydrocarbon and is still going strong due to efforts by Kata Mlinaria

  13. High Resolution Spectroscopy of Hexamethylenetetramine (hmt) C6N_4H12

    Science.gov (United States)

    Boudon, V.; Pirali, O.

    2012-06-01

    Hexamethylenetetramine, or HMT (C6N_4H12) is a N-substituted derivative of adamantane C10H16 which is the smallest sample of the diamondoid molecules family. Thanks to their high stability, diamond-like molecules have long been suspected to be present in space (note that diamond nanocrystals are extracted from Murchinson meteorites, and HMT is known to be an abundant residue of UV irradiated ice analogs and might be present in Titan's atmosphere. Using the Bruker IFS 125 coupled to a multipass cell (absorption path length of 150 m) of the AILES beamline at SOLEIL, we recorded the IR spectrum of gas phase HMT in the 300--3000 cm-1 spectral region with an unapodized resolution 0.001 cm-1. HMT is a solid powder with about 0.008 mbar vapour pressure at room temperature, it is a T_d molecule (as adamantane) and has 25 vibrational modes from which only 9 are infrared active. Over the 9 IR active modes, we were able to rotationlly resolved the spectra of 6 of them. The analysis of all the resolved bands has been performed thanks to the XTDS and SPVIEW softwares developed in Dijon for such molecules. Each band can be considered as isolated and we get very good fits of line positions, with a root mean square deviation better than 5× 10-4 cm-1 for J values up to 80 or more in each case. As for our recent study concerning adamantane, the resulting synthetic spectra will permit an active search of this very stable specie in different sources of the interstellar medium. W. C. Saslaw and J. E. Gaustad, Nature, 221, 160 (1969) R. S. Lewis et al., Nature, 326, 160 (1987) M. P. Bernstein et al., ApJ, 454, 327 (1995) Ch. Wenger, V. Boudon, M. Rotger, M. Sanzharov and J.-P. Champion, J. Mol. Spectrosc., 251 102--113 (2008). O. Pirali, V. Boudon, J. Oomens, M. Vervloet, J. Chem. Phys., 136, 024310 (2012)

  14. Preparation and crystal structure characterization of CuNiGaSe3 and CuNiInSe3 quaternary compounds

    Indian Academy of Sciences (India)

    G E Delgado; A J Mora; P Grima-Gallardo; S Durán; M Muñoz; M Quintero

    2010-10-01

    Samples of the quaternary chalcogenide compounds, CuNiGaSe3 and CuNiInSe3, prepared by direct fusion and annealing method, were characterized by X-ray powder diffraction. In each case, the crystal structure was refined using the Rietveld method. Both compounds were found to crystallize in the tetragonal system, space group $\\bar{4}$2 (N°112), with unit cell parameter values = 5.6213(1) Å, = 11.0282(3) Å, = 348.48(1) Å3 and = 5.7857(2) Å, = 11.6287(5) Å, = 389.26(3) Å3 for CuNiGaSe3 and CuNiInSe3, respectively. These compounds have a normal adamantane structures and are isostructural with CuFeInSe3.

  15. Crystal structure of the quaternary compounds CuFe2AlSe4 and CuFe2GaSe4 from X-ray powder diffraction

    Indian Academy of Sciences (India)

    G E Delgado; A J Mora; P Grima-Gallardo; M Muñoz; S Durán; M Quintero; J M Briceño

    2015-08-01

    The crystal structure of the quaternary compounds CuFe2AlSe4 and CuFe2GaSe4, belonging to the system I–II2–III–VI4, were characterized using X-ray powder diffraction data. Both compounds crystallize in the tetragonal space group I42m (No. 121), = 2, with unit cell parameters = 5.609(1) Å, = 10.963(2) Å for CuFe2AlSe4 and = 5.6165(3) Å, = 11.075(1) Å for CuFe2GaSe4. These compounds are isostructural with CuFe2InSe4, and have a normal adamantane stannite structure.

  16. Passive immune neutralization strategies for prevention and control of influenza A infections.

    Science.gov (United States)

    Ye, Jianqiang; Shao, Hongxia; Perez, Daniel R

    2012-02-01

    Although vaccination significantly reduces influenza severity, seasonal human influenza epidemics still cause more than 250,000 deaths annually. Vaccine efficacy is limited in high-risk populations such as infants, the elderly and immunosuppressed individuals. In the event of an influenza pandemic (such as the 2009 H1N1 pandemic), a significant delay in vaccine availability represents a significant public health concern, particularly in high-risk groups. The increasing emergence of strains resistant to the two major anti-influenza drugs, adamantanes and neuraminidase inhibitors, and the continuous circulation of avian influenza viruses with pandemic potential in poultry, strongly calls for alternative prophylactic and treatment options. In this review, we focus on passive virus neutralization strategies for the prevention and control of influenza type A viruses.

  17. Synthesis of 2- (3-Hydroxy- 1-adamantyl) -2-glyoxylic Acid%2-(3-羟基-1-金刚烷基)-2-乙醛酸的合成

    Institute of Scientific and Technical Information of China (English)

    李靖柯; 周鸿睿; 彭俊; 冯悦; 胡湘南

    2012-01-01

    金刚烷经相继甲酸化、酰氯化后与丙二酸二乙酯乙氧基镁反应,得到1-金刚烷甲酰基丙二酸二乙酯,再经水解脱羧、高锰酸钾氧化得到沙克列汀中间体2-(3-羟基-1-金刚烷基)-2-乙醛酸,总收率约28%.%2-(3-Hydroxy-l-adamantyl)-2-glyoxyiic acid, the intermediate of saxagliptin, was synthesized from adamantane via successive reactions with formic acid, thiotiyl chloride and diethyl ethoxymagnesium malonate to give diethyl 1-adamantaneformyl malonate. which was subjected to hydrolysis and decarboxylation by mixed acid and then oxidation by potassium permanganate. The overall yield was about 28%.

  18. Development of Poly(ɛ-caprolactone Scaffold Loaded with Simvastatin and Beta-Cyclodextrin Modified Hydroxyapatite Inclusion Complex for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Jung Bok Lee

    2016-02-01

    Full Text Available In this study, we developed poly(ɛ-caprolactone (PCL 3D scaffolds using a solid free form fabrication (SFF technique. β-cyclodextrin (βCD was grafted to hydroxyapatite (HAp and this βCD grafted HAp was coated onto the PCL scaffold surface, followed by drug loading through an inclusion complex interaction between the βCD and adamantane (AD or between βCD and simvastatin (SIM. The scaffold structure was characterized by scanning electron microscopy (SEM. The release profile of simvastatin in the β-CD grafted HAp was also evaluated. Osteogenic differentiation of adipose-derived stromal cells (ADSCs was examined using an alkaline phosphatase activity (ALP assay. The results suggest that drug loaded PCL-HAp 3-D scaffolds enhances osteogenic differentiation of ADSCs.

  19. The influence of fat and monoacylglycerols on growth of spore-forming bacteria in processed cheese.

    Science.gov (United States)

    Hauerlandová, Iva; Lorencová, Eva; Buňka, František; Navrátil, Jan; Janečková, Kristýna; Buňková, Leona

    2014-07-16

    Highly undesirable microbial contaminants of processed cheese are endospore-forming bacteria of the genera Bacillus and Clostridium. Survival of Bacillus subtilis, B. cereus, Clostridium butyricum and C. sporogenes was examined in model processed cheese samples supplemented with monoacylglycerols. In processed cheese samples, monoacylglycerols of undecanoic, undecenoic, lauric and adamantane-1-carboxylic acid at concentration of 0.15% w/w prevented the growth and multiplication of both Bacillus species throughout the storage period. The two species of Clostridium were less affected by monoacylglycerols in processed cheese samples and only partial inhibition was observed. The effect of milk fat content on microbial survival in processed cheese was also evaluated. The growth of Bacillus sp. was affected by the fat level of processed cheese while population levels of Clostridium sp. did not differ in processed cheese samples with 30, 40 and 50% fat in dry matter.

  20. Simultaneous expression and transportation of insulin by supramolecular polysaccharide nanocluster

    Science.gov (United States)

    Zhang, Yu-Hui; Zhang, Ying-Ming; Zhao, Qi-Hui; Liu, Yu

    2016-01-01

    Drug/gene transportation systems with stimuli-responsive release behaviors are becoming research hotspots in biochemical and biomedical fields. In this work, a glucose-responsive supramolecular nanocluster was successfully constructed by the intermolecular complexation of phenylboronic acid modified β-cyclodextrin with adamantane modified polyethylenimine, which could be used as a biocompatible carrier for insulin and pCMV3-C-GFPSpark-Ins DNA which could express insulin co-delivery. Benefiting from the response capability of phenylboronic acid moiety toward glucose, the encapsulated insulin could be specifically released and the corresponding targeted DNA could efficiently express insulin in HepG2 cell, accompanied by the high-level insulin release in vitro. Our results demonstrate that the simultaneous insulin drug delivery and insulin gene transfection in a controlled mode may have great potential in the clinical diabetes treatments. PMID:26948978

  1. Host-Guest Strategy to Reversibly Control a Chloride Carrier Process with Cyclodextrins.

    Science.gov (United States)

    Gravel, Julien; Kempf, Julie; Schmitzer, Andreea

    2015-12-14

    Herein, we report a reversible modular chloride transport process based on host-guest competitive interactions between an imidazolium-based chloride carrier and beta-cyclodextrin. We report evidence for the formation of the supramolecular complex between 1,3-bis(2-(adamantan-1-yl)ethyl)imidazolium bis(trifluorometyl-sulfonyl)imide with two β-cyclodextrins. Through fluorescence assays in liposomes and black lipid membrane experiments, we demonstrate that the formation of the supramolecular complex results in the inhibition of the chloride transport. We show that the chloride transport process can be entirely restored in the presence of competitive adamantyl-functionalized guests. This is the first example of an entirely reversible modular chloride transport process in phospholipid bilayers involving a mobile carrier transporter and cyclodextrin supramolecular complex.

  2. A CCD area detector for X-ray diffraction under high pressure for rotating anode source

    Indian Academy of Sciences (India)

    Amar Sinha; Alka B Garg; V Vijayakumar; B K Godwal; S K Sikka

    2000-04-01

    Details of a two-dimensional X-ray area detector developed using a charge coupled device, a image intensifier and a fibre optic taper are given. The detector system is especially optimized for angle dispersive X-ray diffraction set up using rotating anode generator as X-ray source. The performance of this detector was tested by successfully carrying out powder X-ray diffraction measurements on various materials such as intermetallics AuIn2, AuGa2, high material Pd and low scatterer adamantane (C10H16) at ambient conditions. Its utility for quick detection of phase transitions at high pressures with diamond anvil cell is demonstrated by reproducing the known pressure induced structural transitions in RbI, KI and a new structural phase transition in AuGa2 above 10 GPa. Various softwares have also been developed to analyze data from this detector.

  3. 3-(1-Adamantyl-6-methyl-3-(3-methylbenzylisochroman-1-one

    Directory of Open Access Journals (Sweden)

    Eva Babjaková

    2009-06-01

    Full Text Available In the title compound, C28H32O2, the oxanone ring adopts distorted half-boat conformation with the following Cremer and Pople puckering parameters: Q = 0.619 (2 Å, θ = 0.75 (19 and ϕ = 172 (13°. The dihedral angle betwen two benzene rings is 21.32 (7°. The adamantane unit consists of three fused cyclohexane rings in classical chair conformations, with absolute values of C—C—C—C torsion angles in the range 57.5 (2–60.9 (2°. Weak interactions of the type C—H...O link molecules of each enantiomer into chains parallel to the b axis and lying about inversion centers. The crystal packing is also stabilized by intermolecular π-π stacking interactions [centroid–centroid distance of 3.8566 (11 Å].

  4. Cyclodextrin-Based [1]Rotaxanes on Gold Nanoparticles

    Directory of Open Access Journals (Sweden)

    Yanli Zhao

    2012-08-01

    Full Text Available Transformation of mechanically interlocked molecules (e.g., rotaxanes and catenanes into nanoscale materials or devices is an important step towards their real applications. In our current work, an azobenzene-modified β-cyclodextrin (β-CD derivative that can form a self-inclusion complex in aqueous solution was prepared. The self-included β-CD derivative was then functionalized onto a gold nanoparticle (AuNP surface via a ligand-exchange reaction in aqueous solution, leading to the formation of AuNP-[1]rotaxane hybrids. Corresponding non-self-included β-CD derivative functionalized AuNPs were also developed in a DMF/H2O mixture solution for control experiments. These hybrids were fully characterized by UV-vis and circular dichroism spectroscopies, together with transmission electron microscopy (TEM. The competitive binding behavior of the hybrids with an adamantane dimer was investigated.

  5. Crystal growth of CVD diamond and some of its peculiarities

    CERN Document Server

    Piekarczyk, W

    1999-01-01

    Experiments demonstrate that CVD diamond can form in gas environments that are carbon undersaturated with respect to diamond. This fact is, among others, the most serious violation of principles of chemical thermodynamics. In this $9 paper it is shown that none of the principles is broken when CVD diamond formation is considered not a physical process consisting in growth of crystals but a chemical process consisting in accretion of macro-molecules of polycyclic $9 saturated hydrocarbons belonging to the family of organic compounds the smallest representatives of which are adamantane, diamantane, triamantane and so forth. Since the polymantane macro-molecules are in every respect identical with $9 diamond single crystals with hydrogen-terminated surfaces, the accretion of polymantane macro- molecules is a process completely equivalent to the growth of diamond crystals. However, the accretion of macro-molecules must be $9 described in a way different from that used to describe the growth of crystals because so...

  6. Surface modification of cellulose fiber via supramolecular assembly of biodegradable polyesters by the aid of host-guest inclusion complexation.

    Science.gov (United States)

    Zhao, Qiang; Wang, Shufang; Cheng, Xinjian; Yam, Richard C M; Kong, Deling; Li, Robert K Y

    2010-05-10

    In this article, we report a novel surface modification method for cellulose fiber that is based on supramolecular assembly. Beta-cyclodextrin (beta-CD) was first covalently grafted onto the fiber surface. Then poly(epsilon-caprolactone) (PCL) oligomers having both ends capped with adamantane motifs (i.e., PCL-AD) were immobilized to the cellulose fiber surface through the host-guest inclusion complexation between beta-CD and AD motif. FTIR-ATR and XPS analyses confirmed the successful assembly of PCL-ADs, which was further supported by the increasing trend of weight gain with the concentration of CDs on the fiber surface. Contact angle and TGA measurements reflect the enhanced hydrophobicity and thermal stability of the cellulose fiber as a consequence of this modification. The morphologies of the cellulose fiber before and after the assembly process have also been compared by SEM.

  7. Sensitivity and resolution in frequency comb spectroscopy of buffer gas cooled polyatomic molecules

    Science.gov (United States)

    Changala, P. Bryan; Spaun, Ben; Patterson, David; Doyle, John M.; Ye, Jun

    2016-12-01

    We discuss the use of cavity-enhanced direct frequency comb spectroscopy in the mid-infrared region with buffer gas cooling of polyatomic molecules for high-precision rovibrational absorption spectroscopy. A frequency comb coupled to an optical enhancement cavity allows us to collect high-resolution, broad-bandwidth infrared spectra of translationally and rotationally cold (10-20 K) gas-phase molecules with high absorption sensitivity and fast acquisition times. The design and performance of the combined apparatus are discussed in detail. Recorded rovibrational spectra in the CH stretching region of several organic molecules, including vinyl bromide (CH_2CHBr), adamantane (C_{10}H_{16}), and diamantane (C_{14}H_{20}) demonstrate the resolution and sensitivity of this technique, as well as the intrinsic challenges faced in extending the frontier of high-resolution spectroscopy to large complex molecules.

  8. Small organic compounds enhance antigen loading of class II major histocompatibility complex proteins by targeting the polymorphic P1 pocket

    DEFF Research Database (Denmark)

    Höpner, Sabine; Dickhaut, Katharina; Hofstätter, Maria

    2006-01-01

    Major histocompatibility complex (MHC) molecules are a key element of the cellular immune response. Encoded by the MHC they are a family of highly polymorphic peptide receptors presenting peptide antigens for the surveillance by T cells. We have shown that certain organic compounds can amplify...... immune responses by catalyzing the peptide loading of human class II MHC molecules HLA-DR. Here we show now that they achieve this by interacting with a defined binding site of the HLA-DR peptide receptor. Screening of a compound library revealed a set of adamantane derivatives that strongly accelerated......, transient occupation of this pocket by the organic compound stabilizes the peptide-receptive conformation permitting rapid antigen loading. This interaction appeared restricted to the larger Gly(beta86) pocket and allowed striking enhancements of T cell responses for antigens presented by these "adamantyl...

  9. Simultaneous expression and transportation of insulin by supramolecular polysaccharide nanocluster

    Science.gov (United States)

    Zhang, Yu-Hui; Zhang, Ying-Ming; Zhao, Qi-Hui; Liu, Yu

    2016-03-01

    Drug/gene transportation systems with stimuli-responsive release behaviors are becoming research hotspots in biochemical and biomedical fields. In this work, a glucose-responsive supramolecular nanocluster was successfully constructed by the intermolecular complexation of phenylboronic acid modified β-cyclodextrin with adamantane modified polyethylenimine, which could be used as a biocompatible carrier for insulin and pCMV3-C-GFPSpark-Ins DNA which could express insulin co-delivery. Benefiting from the response capability of phenylboronic acid moiety toward glucose, the encapsulated insulin could be specifically released and the corresponding targeted DNA could efficiently express insulin in HepG2 cell, accompanied by the high-level insulin release in vitro. Our results demonstrate that the simultaneous insulin drug delivery and insulin gene transfection in a controlled mode may have great potential in the clinical diabetes treatments.

  10. Continuous probe of cold complex molecules with infrared frequency comb spectroscopy

    CERN Document Server

    Spaun, Ben; Patterson, David; Bjork, Bryce J; Heckl, Oliver H; Doyle, John M; Ye, Jun

    2016-01-01

    Cavity-enhanced frequency comb spectroscopy for molecule detection in the mid-infrared powerfully combines high resolution, high sensitivity, and broad spectral coverage. However, this technique, and essentially all spectroscopic methods, is limited in application to relatively small, simple molecules. Here we integrate comb spectroscopy with continuous, cold samples of molecules produced via buffer gas cooling, thus enabling the study of significantly more complex molecules. We report simultaneous gains in resolution, sensitivity, and bandwidth and demonstrate this combined capability with the first rotationally resolved direct absorption spectra in the CH stretch region of several complex molecules. These include nitromethane (CH$_3$NO$_2$), a model system that presents challenging questions to the understanding of large amplitude vibrational motion, as well as several large organic molecules with fundamental spectroscopic and astrochemical relevance, including naphthalene (C$_{10}$H$_8$), adamantane (C$_{1...

  11. INHIBITION OF SOLUBLE EPOXIDE HYDROLASE DOES NOT PROTECT AGAINST ENDOTOXIN-MEDIATED HEPATIC INFLAMMATION

    Science.gov (United States)

    Fife, Kimberly L.; Liu, YingMei; Schmelzer, Kara R.; Tsai, Hsing-Ju; Kim, In-Hae; Morisseau, Christophe; Hammock, Bruce D.; Kroetz, Deanna L.

    2009-01-01

    Epoxyeicosatrienoic acids (EETs) are derived from cytochrome P450 (CYP)-catalyzed epoxygenation of arachidonic acid and have emerged as important mediators of numerous biological effects. The major elimination pathway for EETs is through soluble epoxide hydrolase (sEH) catalyzed metabolism to dihydroxyeicosatrienoic acids (DHETs). Based on previous studies showing that EETs have anti-inflammatory effects, we hypothesized that chronic inhibition of sEH would attenuate a lipopolysaccharide (LPS)-induced inflammatory response in vivo. Continuous dosing of the sEH inhibitors 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a polyethylene glycol ester of AUDA (AUDA-PEG), and 1-adamantan-1-yl-3-(5-(2-(2-ethoxyethoxy)ethoxy)pentyl)urea (AEPU) resulted in robust exposure to the inhibitor and target engagement, as evidenced by significant increases in plasma EET/DHET ratios following six days of inhibitor treatment. However, sEH inhibitor treatment was not associated with an attenuation of LPS-induced inflammatory gene expression in the liver and AUDA did not protect from LPS-induced neutrophil infiltration. Furthermore, Ephx2 −/− mice that lack sEH expression and have significantly increased plasma EET/DHET ratios were not protected from LPS-induced inflammatory gene expression or neutrophil accumulation in the liver. LPS did have an effect on sEH expression and function, as evident from a significant downregulation of Ephx2 mRNA and a significant shift in plasma EET/DHET ratios four hours after LPS treatment. In conclusion, there was no evidence that increasing EET levels in vivo could modulate an LPS-induced inflammatory response in the liver. However, LPS did have significant effects on plasma eicosanoid levels and hepatic Ephx2 expression, suggesting that in vivo EET levels are modulated in response to an inflammatory signal. PMID:18815352

  12. Drug-loaded pseudo-block copolymer micelles with a multi-armed star polymer as the micellar exterior

    Science.gov (United States)

    Xie, Chen; Zhang, Peng; Zhang, Zhengkui; Yang, Chenchen; Zhang, Jialiang; Wu, Wei; Jiang, Xiqun

    2015-07-01

    Supramolecular constructed pseudo block copolymer micelles based on β-cyclodextrin terminated 4 and 7 armed star poly(N-vinylpyrrolidone) and adamantane terminated linear poly(ε-caprolactone) were prepared. The size, morphology, stability and protein adsorption were experimentally examined. The micelles with 7 armed PVP chains as the micellar exterior showed the lowest amount of protein adsorption and the best stability in media. When cabazitaxel, a new taxane, was loaded into the micelles, 14.4% drug loading content and 85% encapsulation efficacy were achieved. In vitro cytotoxicity studies demonstrated that the cabazitaxel-loaded micelles show significant cytotoxicity against drug-resistant A2780/T cell lines. Biodistribution studies showed that the micelles can almost double the content of cargo in tumor sites compared with the free cargo. In vivo antitumor activity examinations indicated that cabazitaxel-loaded micelles show superior antitumor activity over free paclitaxel and free cabazitaxel.Supramolecular constructed pseudo block copolymer micelles based on β-cyclodextrin terminated 4 and 7 armed star poly(N-vinylpyrrolidone) and adamantane terminated linear poly(ε-caprolactone) were prepared. The size, morphology, stability and protein adsorption were experimentally examined. The micelles with 7 armed PVP chains as the micellar exterior showed the lowest amount of protein adsorption and the best stability in media. When cabazitaxel, a new taxane, was loaded into the micelles, 14.4% drug loading content and 85% encapsulation efficacy were achieved. In vitro cytotoxicity studies demonstrated that the cabazitaxel-loaded micelles show significant cytotoxicity against drug-resistant A2780/T cell lines. Biodistribution studies showed that the micelles can almost double the content of cargo in tumor sites compared with the free cargo. In vivo antitumor activity examinations indicated that cabazitaxel-loaded micelles show superior antitumor activity over free

  13. The effect of hydrophobic absorbent for reducing charge recombination to improve dye-sensitized solar cell performance

    Science.gov (United States)

    Sae-Kung, C.; Hatha, E.; Sichanugrist, P.; Pungwiwut, N.; Laosooksathit, S.

    2007-09-01

    Normally, it has been widely acceptable that dye sensitized solar cell (DSSC) plays important roles compared to the conventional solar cells such as monocrystalline, polycrystalline, and even amorphous silicon in accordance with its low manufacturing and fabrication cost. However, the DSSC consists of many interfaces between anode and cathode such as semiconductor to dye and dye to electrolyte and electrolyte to platinum catalyst at the cathode. Therefore, the effect of charge recombination at dye-electrolyte interface is a major role to cell efficiency. One of major implementations to alleviate the recombination effect could be efficiently solved by adding hydrophobic co-adsorbent to dye solution. The co-absorbent molecule will be anchored to titanium dioxide semiconductor like dye and can be the barrier to protect the interface of the triiodide, dye and mesoporous titanium dioxide (TiO II). In our works, we investigate on various hydrophobic co-adsorbent such as 1-adamantane acetic acid, cholic acid and chenodeoxy cholic acid. The amounts of the co-absorbent were varied as well as the amount of dye N719. It was found that the cholic and chenodeoxy cholic acid increase photovoltage and photocurrent, especially when the concentration was increased. This may be due to shift of conduction band (CB) to negative direction by the co-absorbent but 1-adamantane-acetic acid could not resist charge recombination. In addition multilayer of titanium dioxide was also studied on the effect of conversion efficiency. The maximum 4 layers of TiO II provided the best cell performance of 8.3 efficiency with the presence of cholic acid.

  14. Diamondoid naphthenic acids cause in vivo genetic damage in gills and haemocytes of marine mussels.

    Science.gov (United States)

    Dissanayake, Awantha; Scarlett, Alan G; Jha, Awadhesh N

    2016-04-01

    Diamondoids are polycyclic saturated hydrocarbons that possess a cage-like carbon skeleton approaching that of diamond. These 'nano-diamonds' are used in a range of industries including nanotechnologies and biomedicine. Diamondoids were thought to be highly resistant to degradation, but their presumed degradation acid products have now been found in oil sands process-affected waters (OSPW) and numerous crude oils. Recently, a diamondoid-related structure, 3-noradamantane carboxylic acid, was reported to cause genetic damage in trout hepatocytes under in vitro conditions. This particular compound has never been reported in the environment but led us to hypothesise that other more environmentally relevant diamondoid acids could also be genotoxic. We carried out in vivo exposures (3 days, semi-static) of marine mussels to two environmentally relevant diamondoid acids, 1-adamantane carboxylic acid and 3,5-dimethyladamantane carboxylic acid plus 3-noradamantane carboxylic acid with genotoxic damage assessed using the Comet assay. An initial screening test confirmed that these acids displayed varying degrees of genotoxicity to haemocytes (increased DNA damage above that of controls) when exposed in vivo to a concentration of 30 μmol L(-1). In a further test focused on 1-adamantane carboxylic acid with varying concentrations (0.6, 6 and 30 μmol L(-1)), significant (P genetic damage was similar to that observed following exposure to a known genotoxin, benzo(a)pyrene (exposure concentration, 0.8 μmol L(-1)). These findings may have implications for a range of worldwide industries including oil extraction, nanotechnology and biomedicine.

  15. Structure-Activity Studies of N-Butyl-1-deoxynojirimycin (NB-DNJ) Analogs: Discovery of Potent and Selective Aminocyclopentitol Inhibitors of GBA1 and GBA2.

    Science.gov (United States)

    Georg, Gunda Ingrid; Gu, Xingxiang; Gupta, Vijayalaxmi; Yang, Yan; Zhu, Jinyi; Carlson, Erick; Kingsley, Carolyn; Tash, Joseph; Schonbrunn, Ernst; Hawkinson, Jon

    2017-10-03

    Analogs of N-butyl-1-deoxynojirimycin (NB-DNJ) were prepared and assayed for inhibition of ceramide-specific glucosyltransferase (CGT), non-lysosomal -glucosidase 2 (GBA2) and the lysosomal -glucosidase 1 (GBA1). Compounds 6a-6f that carry sterically demanding nitrogen substituents, and compound 14, devoid of the C3 and C5 hydroxyl groups present in DNJ/NB-DGJ (N-butyl-deoxygalactojirimycin showed no inhibitory activity for CGT or GBA2. Inversion of stereochemistry at C4 of N-(n-butyl)- and N-(n-nonyl)-DGJ (compounds 25) also led to a loss of activity in these assays. The aminocyclopentitols N-(n-butyl)- (36a), N-(n-nonyl)-4-amino-5-(hydroxymethyl)cyclopentane- (36b), and N-(1-(pentyloxy)methyl)adamantan-1-yl)-1,2,3-triol (36f), were selective inhibitors of GBA1 and GBA2 that did not inhibit CGT (>1mM) with the exception of 36f, which inhibited CGT with an IC50 of 1 mM. The N-butyl analog 36a was 1000-fold selective for inhibiting GBA1 over GBA2 (Ki values of 32 nM and 3.3 μM for GBA1 and GBA2, respectively). The N-nonyl analog 36b displayed a Ki of N-(1-(pentyloxy)methyl)adamantan-1-yl) derivative 36f had Ki values of ~16 nM and 14 nM for GBA1 and GBA2, respectively. The related N-bis-substituted aminocyclopentitols were significantly less potent inhibitors than their mono-substituted analogs. The aminocyclopentitol scaffold should hold promise for further inhibitor development. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Vladimir Prelog i organska kemija u proteklom stoljeću

    Directory of Open Access Journals (Sweden)

    Sunko, D.

    2007-03-01

    Full Text Available Organic chemistry in the past century has undergone several profound changes and Vlado Prelog, as the great organic chemist of our time, was actively involved in these changes. During the first half of the 20th century, synthesis of new organic compounds and the investigation of natural compounds were in the centre of interest of contemporary organic chemists. New methods enabled the preparation of new compounds such as numerous drugs and dyes, thus eliminating in some cases the tedious isolation from natural sources. The German chemical industry rapidly expanded and some small enterprises specialized in the preparation of tailored compounds for use in academic research. Until the first half of the last century, organic chemistry was based on empirical knowledge and meticulous and hard work in the laboratory, and it was practically separated from other branches of chemistry.In Prag, Prelog studied chemistry under the guidance of Emil Votoček, and his few years older mentor and friend Rudolf Lukeš. He practiced preparative organic chemistry in a small commercial outfit of G. J. Driza, who become his first doctoral student. He witnessed the structure of adamantane intuitively suggested by Lukeš, which by its highly symmetrical structure, fascinated Prelog and raised his interest in stereochemistry and the possible synthesis of adamantane. This remained a challenge for him in the years to come, to be solved in 1941 by his student and successor Rativoj Seiwerth at the very end of his stay as professor of organic chemistry at the University of Zagreb. Establishing collaboration with "Kaštel", the leading pharmaceutical factory in Zagreb, had secured him the financial support needed for his research in Zagreb. From the stereochemistry of adamantane to the formulation of the CIP classification of chirality and the awarding of the Nobel Prize jointly with John Cornforth in 1975, Prelog's life was devoted to the study of the structure and

  17. Functionalization of Mechanochemically Passivated Germanium Nanoparticles via "Click" Chemistry

    Science.gov (United States)

    Purkait, Tapas Kumar

    . Copper(I) catalyzed "click" chemistry also can be explored with azido-terminated Ge NPs which were synthesized by azidation of chloro-terminated Ge NPs. Water soluble PEGylated Ge NPs were synthesized by "click" reaction for biological application. PEGylated Ge NP clusters were prepared using alpha, o-bis alkyno or bis-azido polyethylene glycol (PEG) derivatives by copper catalyzed "click" reaction via inter-particle linking. These nanoparticles were further functionalized by azido beta-cyclodextrin (beta-CD) and azido adamantane via alkyne-azide "click" reactions. Nanoparticle clusters were made from the functionalized Ge NPs by "host-guest" chemistry of beta-CD functionalized Ge NPs either with adamantane functionalized Ge NPs or fullerene, C60.

  18. Mesostructured Metal Germanium Sulfide and Selenide Materials Based on the Tetrahedral [Ge 4S 10] 4- and [Ge 4Se 10] 4- Units: Surfactant Templated Three-Dimensional Disordered Frameworks Perforated with Worm Holes

    Science.gov (United States)

    Wachhold, Michael; Kasthuri Rangan, K.; Lei, Ming; Thorpe, M. F.; Billinge, Simon J. L.; Petkov, Valeri; Heising, Joy; Kanatzidis, Mercouri G.

    2000-06-01

    The polymerization of [Ge4S10]4- and [Ge4Se10]4- unit clusters with the divalent metal ions Zn2+, Cd2+, Hg2+, Ni2+, and Co2+ in the presence of various surfactant cations leads to novel mesostructured phases. The surfactants are the quaternary ammonium salts C12H25NMe3Br, C14H29NMe3Br, C16H33NMe3Br, and C18H37NMe3Br, which play the role of templates, helping to assemble a three-dimensional mesostructured metal-germanium chalcogenide framework. These materials are stoichiometric in nature and have the formula of (R-NMe3)2[MGe4Q10] (Q=S, Se). The local atomic structure was probed by X-ray diffuse scattering and pair distribution function analysis methods and indicates that the adamantane clusters stay intact while the linking metal atoms possess a tetrahedral coordination environment. A model can be derived, from the comparison of measured and simulated X-ray powder diffraction patterns, describing the structure as an amorphous three-dimensional framework consisting of adamantane [Ge4Q10]4- units that are bridged by tetrahedral coordinated M2+ cations. The network structures used in the simulations were derived from corresponding disordered structures developed for amorphous silicon. The frameworks in (R-NMe3)2[MGe4Q10] are perforated with worm hole-like tunnels, occupied by the surfactant cations, which show no long-range order. This motif is supported by transmission electron microscopy images of these materials. The pore sizes of these channels were estimated to lie in the range of 20-30 Å, depending on the appointed surfactant cation length. The framework wall thickness of ca. 10 Å is thereby independent from the surfactant molecules used. Up to 80% of the surfactant molecules can be removed by thermal degradation under vacuum without loss of mesostructural integrity. Physical, chemical, and spectroscopic properties of these materials are discussed.

  19. Multidrug resistant 2009 A/H1N1 influenza clinical isolate with a neuraminidase I223R mutation retains its virulence and transmissibility in ferrets.

    Directory of Open Access Journals (Sweden)

    Erhard van der Vries

    2011-09-01

    Full Text Available Only two classes of antiviral drugs, neuraminidase inhibitors and adamantanes, are approved for prophylaxis and therapy against influenza virus infections. A major concern is that influenza virus becomes resistant to these antiviral drugs and spreads in the human population. The 2009 pandemic A/H1N1 influenza virus is naturally resistant to adamantanes. Recently a novel neuraminidase I223R mutation was identified in an A/H1N1 virus showing cross-resistance to the neuraminidase inhibitors oseltamivir, zanamivir and peramivir. However, the ability of this virus to cause disease and spread in the human population is unknown. Therefore, this clinical isolate (NL/2631-R223 was compared with a well-characterized reference virus (NL/602. In vitro experiments showed that NL/2631-I223R replicated as well as NL/602 in MDCK cells. In a ferret pathogenesis model, body weight loss was similar in animals inoculated with NL/2631-R223 or NL/602. In addition, pulmonary lesions were similar at day 4 post inoculation. However, at day 7 post inoculation, NL/2631-R223 caused milder pulmonary lesions and degree of alveolitis than NL/602. This indicated that the mutant virus was less pathogenic. Both NL/2631-R223 and a recombinant virus with a single I223R change (recNL/602-I223R, transmitted among ferrets by aerosols, despite observed attenuation of recNL/602-I223R in vitro. In conclusion, the I223R mutated virus isolate has comparable replicative ability and transmissibility, but lower pathogenicity than the reference virus based on these in vivo studies. This implies that the 2009 pandemic influenza A/H1N1 virus subtype with an isoleucine to arginine change at position 223 in the neuraminidase has the potential to spread in the human population. It is important to be vigilant for this mutation in influenza surveillance and to continue efforts to increase the arsenal of antiviral drugs to combat influenza.

  20. Epidemiological and virological characteristics of influenza viruses circulating in Cambodia from 2009 to 2011.

    Directory of Open Access Journals (Sweden)

    Srey Viseth Horm

    Full Text Available BACKGROUND: The Cambodian National Influenza Center (NIC monitored and characterized circulating influenza strains from 2009 to 2011. METHODOLOGY/PRINCIPAL FINDINGS: Sentinel and study sites collected nasopharyngeal specimens for diagnostic detection, virus isolation, antigenic characterization, sequencing and antiviral susceptibility analysis from patients who fulfilled case definitions for influenza-like illness, acute lower respiratory infections and event-based surveillance. Each year in Cambodia, influenza viruses were detected mainly from June to November, during the rainy season. Antigenic analysis show that A/H1N1pdm09 isolates belonged to the A/California/7/2009-like group. Circulating A/H3N2 strains were A/Brisbane/10/2007-like in 2009 before drifting to A/Perth/16/2009-like in 2010 and 2011. The Cambodian influenza B isolates from 2009 to 2011 all belonged to the B/Victoria lineage represented by the vaccine strains B/Brisbane/60/2008 and B/Malaysia/2506/2004. Sequences of the M2 gene obtained from representative 2009-2011 A/H3N2 and A/H1N1pdm09 strains all contained the S31N mutation associated with adamantanes resistance except for one A/H1N1pdm09 strain isolated in 2011 that lacked this mutation. No reduction in the susceptibility to neuraminidase inhibitors was observed among the influenza viruses circulating from 2009 to 2011. Phylogenetic analysis revealed that A/H3N2 strains clustered each year to a distinct group while most A/H1N1pdm09 isolates belonged to the S203T clade. CONCLUSIONS/SIGNIFICANCE: In Cambodia, from 2009 to 2011, influenza activity occurred throughout the year with peak seasonality during the rainy season from June to November. Seasonal influenza epidemics were due to multiple genetically distinct viruses, even though all of the isolates were antigenically similar to the reference vaccine strains. The drug susceptibility profile of Cambodian influenza strains revealed that neuraminidase inhibitors would be the

  1. Nanoassemblies Based on Supramolecular Complexes of Nonionic Amphiphilic Cyclodextrin and Sorafenib as Effective Weapons to Kill Human HCC Cells.

    Science.gov (United States)

    Bondì, Maria Luisa; Scala, Angela; Sortino, Giuseppe; Amore, Erika; Botto, Chiara; Azzolina, Antonina; Balasus, Daniele; Cervello, Melchiorre; Mazzaglia, Antonino

    2015-12-14

    Sorafenib (Sor), an effective chemiotherapeutic drug utilized against hepatocellular carcinoma (HCC), robustly interacts with nonionic amphiphilic cyclodextrin (aCD, SC6OH), forming, in aqueous solution, supramolecular complexes that behave as building blocks of highly water-dispersible colloidal nanoassemblies. SC6OH/Sor complex has been characterized by complementary spectroscopic techniques, such as UV-vis, steady-state fluorescence and anisotropy, resonance light scattering and (1)H NMR. The spectroscopic evidences and experiments carried out in the presence of an adamantane derivative, which competes with drug for CD cavity, agree with the entrapment of Sor in aCD, pointing out the role of the aCD cavity in the interaction between drug and amphiphile. Nanoassemblies based on SC6OH/Sor display size of ∼200 nm, negative zeta-potential (ζ = -11 mV), and both maximum loading capacity (LC ∼ 17%) and entrapment efficiency (EE ∼ 100%). Kinetic release profiles show a slower release of Sor from nanoassemblies with respect to the free drug. SC6OH/Sor nanoassemblies have very low hemolytic activity and high efficiency in vitro in decreasing cell growth and viability of HCC cell lines, such as HepG2, Hep3B, and PLC/PRF/5, opening promising chances to their in vivo applications.

  2. Pharmacological Chaperones and Coenzyme Q10 Treatment Improves Mutant β-Glucocerebrosidase Activity and Mitochondrial Function in Neuronopathic Forms of Gaucher Disease.

    Science.gov (United States)

    de la Mata, Mario; Cotán, David; Oropesa-Ávila, Manuel; Garrido-Maraver, Juan; Cordero, Mario D; Villanueva Paz, Marina; Delgado Pavón, Ana; Alcocer-Gómez, Elizabet; de Lavera, Isabel; Ybot-González, Patricia; Paula Zaderenko, Ana; Ortiz Mellet, Carmen; García Fernández, José M; Sánchez-Alcázar, José A

    2015-06-05

    Gaucher disease (GD) is caused by mutations in the GBA1 gene, which encodes lysosomal β-glucocerebrosidase. Homozygosity for the L444P mutation in GBA1 is associated with high risk of neurological manifestations which are not improved by enzyme replacement therapy. Alternatively, pharmacological chaperones (PCs) capable of restoring the correct folding and trafficking of the mutant enzyme represent promising alternative therapies.Here, we report on how the L444P mutation affects mitochondrial function in primary fibroblast derived from GD patients. Mitochondrial dysfunction was associated with reduced mitochondrial membrane potential, increased reactive oxygen species (ROS), mitophagy activation and impaired autophagic flux.Both abnormalities, mitochondrial dysfunction and deficient β-glucocerebrosidase activity, were partially restored by supplementation with coenzyme Q10 (CoQ) or a L-idonojirimycin derivative, N-[N'-(4-adamantan-1-ylcarboxamidobutyl)thiocarbamoyl]-1,6-anhydro-L-idonojirimycin (NAdBT-AIJ), and more markedly by the combination of both treatments. These data suggest that targeting both mitochondria function by CoQ and protein misfolding by PCs can be promising therapies in neurological forms of GD.

  3. Hollow mesoporous silica nanoparticles facilitated drug delivery via cascade pH stimuli in tumor microenvironment for tumor therapy.

    Science.gov (United States)

    Liu, Junjie; Luo, Zhong; Zhang, Jixi; Luo, Tiantian; Zhou, Jun; Zhao, Xiaojing; Cai, Kaiyong

    2016-03-01

    To efficiently deliver anti-cancer drug to tumor site and reduce its toxic side effects on normal tissues, a polyethylene glycol (PEG) shielding and tumor microenvironment triggering cascade pH-responsive hollow mesoporous silica nanoparticles (HMSNs) drug delivery system was fabricated. 3-(3, 4-dihydroxyphenyl) propionic acid (DHPA) functionalized beta-cyclodextrin (β-CD) was grafted onto the surfaces of HMSNs via boronic acid-catechol ester bonds. Then, PEG conjugated adamantane (Ada) was anchored on HMSNs-β-CD nanocarrier via host-gust interaction. Various techniques proved the successful fabrication of the system. The in vitro tests confirmed that the system was biocompatible. After the system permeating into tumor via enhanced permeability and retention (EPR) effect, the benzoic-imine bonds between the PEG and Ada were cleaved under weak acid condition in tumor microenvironment (pH 6.8), while the dissociated PEG protective layer facilitating cellular uptake of HMSNs system. Subsequently, the boronic acid-catechol ester bonds linkers further hydrolyzed under even low endosomal pH (4.5-6.5) condition for intracellular drug delivery, leading to efficient cell apoptosis. The in vivo results demonstrated that drug loaded HMSNs significantly inhibited tumor growth while only with minimal toxic side effects. The strategy provides new insight into the development of new generation of drug delivery carriers triggering by tumor microenvironment.

  4. Theoretical Calculation of Jet Fuel Thermochemistry. 1; Tetrahydrodicylopentadiene (JP10) Thermochemistry Using the CBS-QB3 and G3(MP2)//B3LYP Methods

    Science.gov (United States)

    Zehe, Michael J.; Jaffe, Richard L.

    2010-01-01

    High-level ab initio calculations have been performed on the exo and endo isomers of gas-phase tetrahydrodicyclopentadiene (THDCPD), a principal component of the jet fuel JP10, using the Gaussian Gx and Gx(MPx) composite methods, as well as the CBS-QB3 method, and using a variety of isodesmic and homodesmotic reaction schemes. The impetus for this work is to help resolve large discrepancies existing between literature measurements of the formation enthalpy Delta (sub f)H deg (298) for exo-THDCPD. We find that use of the isodesmic bond separation reaction C10H16 + 14CH4 yields 12C2H6 yields results for the exo isomer (JP10) in between the two experimentally accepted values, for the composite methods G3(MP2), G3(MP2)//B3LYP, and CBS-QB3. Application of this same isodesmic bond separation scheme to gas-phase adamantane yields a value for Delta (sub f)H deg (298) within 5 kJ/mol of experiment. Isodesmic bond separation calculations for the endo isomer give a heat of formation in excellent agreement with the experimental measurement. Combining our calculated values for the gas-phase heat of formation with recent measurements of the heat of vaporization yields recommended values for Delta (sub f)H deg (298)liq of -126.4 and -114.7 kJ/mol for the exo and endo isomers, respectively.

  5. Near-Edge X-ray Absorption Fine Structure Spectroscopy of Diamondoid Thiol Monolayers on Gold

    Energy Technology Data Exchange (ETDEWEB)

    Willey, T M; Fabbri, J; Lee, J I; Schreiner, P; Fokin, A A; Tkachenko, B A; Fokina, N A; Dahl, J; Carlson, B; Vance, A L; Yang, W; Terminello, L J; van Buuren, T; Melosh, N

    2007-11-27

    Diamondoids, hydrocarbon molecules with cubic-diamond-cage structures, have unique properties with potential value for nanotechnology. The availability and ability to selectively functionalize this special class of nanodiamond materials opens new possibilities for surface-modification, for high-efficiency field emitters in molecular electronics, as seed crystals for diamond growth, or as robust mechanical coatings. The properties of self-assembled monolayers (SAMs) of diamondoids are thus of fundamental interest for a variety of emerging applications. This paper presents the effects of thiol substitution position and polymantane order on diamondoid SAMs on gold using near-edge X-ray absorption fine structure spectroscopy (NEXAFS) and X-ray photoelectron spectroscopy (XPS). A framework to determine both molecular tilt and twist through NEXAFS is presented and reveals highly ordered diamondoid SAMs, with the molecular orientation controlled by the thiol location. C 1s and S 2p binding energies are lower in adamantane thiol than alkane thiols on gold by 0.67 {+-} 0.05 eV and 0.16 {+-} 0.04 eV respectively. These binding energies vary with diamondoid monolayer structure and thiol substitution position, consistent with different amounts of steric strain and electronic interaction with the substrate. This work demonstrates control over the assembly, in particular the orientational and electronic structure, providing a flexible design of surface properties with this exciting new class of diamond clusters.

  6. Crystal structure of CuFeInSe{sub 3} from X-ray powder diffraction data

    Energy Technology Data Exchange (ETDEWEB)

    Mora, Asiloe J.; Delgado, Gerzon E. [Laboratorio de Cristalografia, Departamento de Quimica, Facultad de Ciencias, Universidad de Los Andes, Merida 5101 (Venezuela); Grima-Gallardo, Pedro [Centro de Estudios de Semiconductores, Departamento de Fisica, Facultad de Ciencias, Universidad de Los Andes, Merida 5101 (Venezuela)

    2007-02-15

    The crystal structure of the adamantane compound CuFeInSe{sub 3}, belonging to the system (CuInSe{sub 2}){sub 1-x}(FeSe){sub x} with x=0.5, was analyzed using X-ray powder diffraction data. Several model structures were derived from the structure of the selenium rich phase CuInSe{sub 2.3} by permuting the cations in the available Wyckoff positions. The refinement of the best model by the Rietveld method in the tetragonal space group P anti 42c (N 112), Z=1, with unit cell parameters a=5.7762(2) Aa, c=11.5982(7) Aa and V=386.97(3) Aa{sup 3} led to R{sub p}=8.0%, R{sub wp}=9.6%, R{sub exp}=6.2% and {chi}{sup 2}=1.7 for 134 independent reflections. The model that best fitted the diffraction data has the following atomic distribution: Cu in Wyckoff site 2f; Fe in Wyckoff site 2d; In in Wyckoff site 2b and 1/3Cu, 1/3Fe, 1/3In in Wyckoff site 2f; Se in Wyckoff site 8n. (copyright 2007 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  7. Structure-activity relationships of amide-phosphonate derivatives as inhibitors of the human soluble epoxide hydrolase.

    Science.gov (United States)

    Kim, In-Hae; Park, Yong-Kyu; Nishiwaki, Hisashi; Hammock, Bruce D; Nishi, Kosuke

    2015-11-15

    Structure-activity relationships of amide-phosphonate derivatives as inhibitors of the human soluble epoxide hydrolase (sEH) were investigated. First, a series of alkyl or aryl groups were substituted on the carbon alpha to the phosphonate function in amide compounds to see whether substituted phosphonates can act as a secondary pharmacophore. A tert-butyl group (16) on the alpha carbon was found to yield most potent inhibition on the target enzyme. A 4-50-fold drop in inhibition was induced by other substituents such as aryls, substituted aryls, cycloalkyls, and alkyls. Then, the modification of the O-substituents on the phosphonate function revealed that diethyl groups (16 and 23) were preferable for inhibition to other longer alkyls or substituted alkyls. In amide compounds with the optimized diethylphosphonate moiety and an alkyl substitution such as adamantane (16), tetrahydronaphthalene (31), or adamantanemethane (36), highly potent inhibitions were gained. In addition, the resulting potent amide-phosphonate compounds had reasonable water solubility, suggesting that substituted phosphonates in amide inhibitors are effective for both inhibition potency on the human sEH and water solubility as a secondary pharmacophore.

  8. Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats.

    Science.gov (United States)

    Iyer, Abishek; Kauter, Kathleen; Alam, Md Ashraful; Hwang, Sung Hee; Morisseau, Christophe; Hammock, Bruce D; Brown, Lindsay

    2012-01-01

    The signs of metabolic syndrome following chronic excessive macronutrient intake include body weight gain, excess visceral adipose deposition, hyperglycaemia, glucose and insulin intolerances, hypertension, dyslipidaemia, endothelial damage, cardiovascular hypertrophy, inflammation, ventricular contractile dysfunction, fibrosis, and fatty liver disease. Recent studies show increased activity of soluble epoxide hydrolase (sEH) during obesity and metabolic dysfunction. We have tested whether sEH inhibition has therapeutic potential in a rat model of diet-induced metabolic syndrome. In these high-carbohydrate, high-fat-fed rats, chronic oral treatment with trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (t-AUCB), a potent sEH inhibitor, alleviated the signs of metabolic syndrome in vivo including glucose, insulin, and lipid abnormalities, changes in pancreatic structure, increased systolic blood pressure, cardiovascular structural and functional abnormalities, and structural and functional changes in the liver. The present study describes the pharmacological responses to this selective sEH inhibitor in rats with the signs of diet-induced metabolic syndrome.

  9. Binding Cellulose and Chitosan via Intermolecular Inclusion Interaction: Synthesis and Characterisation of Gel

    Directory of Open Access Journals (Sweden)

    Jiufang Duan

    2015-01-01

    Full Text Available A novel cellulose-chitosan gel was successfully prepared in three steps: (1 ferrocene- (Fc- cellulose with degrees of substitution (DS of 0.5 wt% was synthesised by ferrocenecarboxylic acid and cellulose within dimethylacetamide/lithium chloride (DMAc/LiCl; (2 the β-cyclodextrin (β-CD groups were introduced onto the chitosan chains by reacting chitosan with epichlorohydrin in dimethyl sulphoxide and a DS of 0.35 wt%; (3 thus, the cellulose-chitosan gel was obtained via an intermolecular inclusion interaction of Fc-cellulose and β-CD-chitosan in DMA/LiCl, that is, by an intermolecular inclusion interaction, between the Fc groups of cellulose and the β-CD groups on the chitosan backbone at room temperature. The successful synthesis of Fc-cellulose and β-CD-chitosan was characterised by 13C-NMR spectroscopy. The gel based on β-CD-chitosan and Fc-cellulose was formed under mild conditions which can engender autonomous healing between cut surfaces after 24 hours: the gel cannot self-heal while the cut surfaces were coated with a solution of a competitive guest (adamantane acid. The cellulose-chitosan complex made by this method underwent self-healing. Therefore, this study provided a novel method of expanding the application of chitosan by binding it with another polymer.

  10. Polysaccharide Nanoparticles for Efficient siRNA Targeting in Cancer Cells by Supramolecular pKa Shift

    Science.gov (United States)

    Zhang, Ying-Ming; Yang, Yang; Zhang, Yu-Hui; Liu, Yu

    2016-01-01

    Biomacromolecular pKa shifting is considered as one of the most ubiquitous processes in biochemical events, e.g., the enzyme-catalyzed reaction and protein conformational stabilization. In this paper, we report on the construction of biocompatible polysaccharide nanoparticle with targeting ability and lower toxicity by supramolecular pKa shift strategy. This was realized through a ternary assembly constructed by the dual host‒guest interactions of an adamantane-bis(diamine) conjugate (ADA) with cucurbit[6]uril (CB[6]) and a polysaccharide. The potential application of such biocompatible nanostructure was further implemented by the selective transportation of small interfering RNA (siRNA) in a controlled manner. It is demonstrated that the strong encapsulation of the ADA’s diammonium tail by CB[6] not only reduced the cytotoxicity of the nano-scaled vehicle but also dramatically enhanced cation density through an obvious positive macrocycle-induced pKa shift, which eventually facilitated the subsequent siRNA binding. With a targeted polysaccharide shell containing a cyclodextrin‒hyaluronic acid conjugate, macrocycle-incorporated siRNA polyplexes were specifically delivered into malignant human prostate PC-3 cells. The supramolecular polysaccharide nanoparticles, the formation of which was enabled and promoted by the complexation-assisted pKa shift, may be used as a versatile tool for controlled capture and release of biofunctional substrates. PMID:27363811

  11. Spacer intercalated disassembly and photodynamic activity of zinc phthalocyanine inside nanochannels of mesoporous silica nanoparticles.

    Science.gov (United States)

    Ma, Xing; Sreejith, Sivaramapanicker; Zhao, Yanli

    2013-12-26

    Hydrophobic photosensitizer zinc(II) phthalocyanine (ZnPc) was loaded into adamantane (Ad) modified nanochannels of mesoporous silica nanoparticles (MSNPs). The Ad units on the surface of MSNPs were complexed with amino-substituted β-cyclodextrin to enhance the solubility of the hybrid in aqueous solution. The amino groups on β-cyclodextrin also provide functional sites for further conjugation with targeting ligands toward targeted cancer therapy. Since the intercalation of the Ad spacer isolates loaded ZnPc and prevents its aggregation inside MSNPs, ZnPc exhibits its monomeric characteristics to effectively generate cytotoxic singlet oxygen ((1)O2) upon light irradiation (675 nm) in aqueous conditions, leading to efficient photodynamic activity for successful cancer treatment in vitro. Current research presents a convenient approach to maintain the monomeric state of hydrophobic photosensitizer ZnPc by rationally utilizing multifunctional MSNPs as the carriers. The novel hybrid with targeting capability achieves active photodynamic property of monomeric ZnPc in aqueous solution under light irradiation, which may find its way for practical photodynamic therapy in the future.

  12. GBA2-encoded β-glucosidase activity is involved in the inflammatory response to Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Nicoletta Loberto

    Full Text Available Current anti-inflammatory strategies for the treatment of pulmonary disease in cystic fibrosis (CF are limited; thus, there is continued interest in identifying additional molecular targets for therapeutic intervention. Given the emerging role of sphingolipids (SLs in various respiratory disorders, including CF, drugs that selectively target the enzymes associated with SL metabolism are under development. Miglustat, a well-characterized iminosugar-based inhibitor of β-glucosidase 2 (GBA2, has shown promise in CF treatment because it reduces the inflammatory response to infection by P. aeruginosa and restores F508del-CFTR chloride channel activity. This study aimed to probe the molecular basis for the anti-inflammatory activity of miglustat by examining specifically the role of GBA2 following the infection of CF bronchial epithelial cells by P. aeruginosa. We also report the anti-inflammatory activity of another potent inhibitor of GBA2 activity, namely N-(5-adamantane-1-yl-methoxypentyl-deoxynojirimycin (Genz-529648. In CF bronchial cells, inhibition of GBA2 by miglustat or Genz-529648 significantly reduced the induction of IL-8 mRNA levels and protein release following infection by P. aeruginosa. Hence, the present data demonstrate that the anti-inflammatory effects of miglustat and Genz-529648 are likely exerted through inhibition of GBA2.

  13. Electrochemistry of the Self-Assembled Monolayers of Dyads Consisting of Tripod-Shaped Trithiol and Bithiophene on Gold

    Directory of Open Access Journals (Sweden)

    Toshikazu Kitagawa

    2014-09-01

    Full Text Available Self-assembled monolayers (SAMs of tripod-shaped trithiols, consisting of an adamantane core with three CH2SH legs and a bithiophene group, were prepared on a Au(111 surface. Adsorption in a tripod-like fashion was supported by polarization modulation-infrared reflection absorption spectroscopy (PM-IRRAS of the SAMs, which indicated the absence of free SH groups. Cyclic voltammetry showed an irreversible cathodic wave due to reductive desorption. The SAM also showed an anodic wave due to the single-electron oxidation of the bithiophene moiety without concomitant desorption of the molecules. Although oxidation was irreversible in the absence of a protecting group, it became reversible with the introduction of a terminal phenyl group. The charge of the oxidation was one-third that of the reductive desorption, confirming a three-point adsorption. The surface coverage was ca. 50% of that expected for the anti bithiophene conformation, which suggested that an increase in the surface area per molecule had been caused by the presence of an energetically high-lying syn conformer. In accordance with this, the line shape of the oxidation wave suggested an electrostatic repulsive interaction between neighboring molecules.

  14. Osmotic Stress Regulates the Strength and Kinetics of Sugar Binding to Maltoporin Channel

    Science.gov (United States)

    Gurnev, Philip A; Harries, Daniel; Parsegian, V Adrian; Bezrukov, Sergey M

    2011-01-01

    We study the effect of osmotic stress, exerted by salts, on carbohydrate binding to the sugar-specific bacterial channel maltoporin. When the channel is reconstituted into planar lipid bilayers, single events of its occlusion by sugar are seen as transient interruptions in the flow of small ions. We find that, for most salts, changes in the free energy of maltoporin-sugar binding vary linearly with solution osmotic pressure. Such a change in binding with solution osmolarity indicates that for each salt a constant number of salt-excluding water molecules is released upon sugar-maltoporin association at all salt concentrations. We find that larger numbers of water molecules are released upon binding of the cyclic carbohydrate β-cyclodextrin (CD) than upon binding of the corresponding linear homologue maltoheptaose (m7). Remarkably, the extent to which salts affect the binding constant depends sensitively on the type of salt; dehydration in solutions of different anions corresponds to the Hofmeister series. In sodium sulfate solutions, CD and m7 respectively release about 120 and 35 water molecules; in sodium chloride solutions, 35 and 15 waters. No water release is observed with sodium bromide. Finally, by adding adamantane, known to form an inclusion complex with CD, we can infer that CD not only dehydrates but also undergoes a conformational change upon binding to the channel. Our results demonstrate how osmotic stress can improve single-molecule detection of different solutes using protein-based nanopores. PMID:21339598

  15. Osmotic stress regulates the strength and kinetics of sugar binding to the maltoporin channel.

    Science.gov (United States)

    Gurnev, Philip A; Harries, Daniel; Parsegian, V Adrian; Bezrukov, Sergey M

    2010-11-17

    We study the effect of osmotic stress, exerted by salts, on carbohydrate binding to the sugar-specific bacterial channel maltoporin. When the channel is reconstituted into planar lipid bilayers, single events of its occlusion by sugar are seen as transient interruptions in the flow of small ions. We find that, for most salts, changes in the free energy of maltoporin-sugar binding vary linearly with solution osmotic pressure. Such a change in binding with solution osmolarity indicates that for each salt a constant number of salt-excluding water molecules is released upon sugar-maltoporin association at all salt concentrations. We find that larger numbers of water molecules are released upon binding of the cyclic carbohydrate β-cyclodextrin (CD) than upon binding of the corresponding linear homologue maltoheptaose (m7). Remarkably, the extent to which salts affect the binding constants and rates depends sensitively on the type of salt; dehydration in solutions of different anions corresponds to the Hofmeister series. In sodium sulfate solutions, CD and m7 respectively release about 120 and 35 salt-excluding water molecules; in sodium chloride solutions, 35 and 15 waters. No water release is observed with sodium bromide. Finally, by adding adamantane, known to form an inclusion complex with CD, we can infer that CD not only dehydrates but also undergoes a conformational change upon binding to the channel. As a practical outcome, our results also demonstrate how osmotic stress can improve single-molecule detection of different solutes using protein-based nanopores.

  16. Electronic structure, hydrogen bonding and spectroscopic profile of a new 1,2,4-triazole-5(4H)-thione derivative: A combined experimental and theoretical (DFT) analysis

    Science.gov (United States)

    Al-Tamimi, Abdul-Malek S.

    2016-09-01

    Density functional theory has been implemented to study the electronic structure, molecular properties and vibrational spectra of 3-(adamantan-1-yl)-4-(4-chlorophenyl)-1H-1,2,4-triazole-5(4H)-thione, a novel 1,2,4-triazole-5(4H)-thione derivative. Hydrogen bonded dimer of the title molecule has been studied using B3LYP, M06-2X and X3LYP functionals at 6-311++ G(d,p) level of theory. The intermolecular hydrogen bonding has been studied using NBO analysis of the dimer. Bader's AIM theory was also used to evaluate the strength as well as the hydrogen bonding characteristics. Experimental FT-IR and FT-Raman spectra of the title molecule were related with the spectral data obtained with DFT/B3LYP method. The 1H NMR chemical shifts of the title molecule were calculated by the GIAO method and compared with experimental results. Dipole moment, polarizability (α), first order static hyperpolarizability (β) along with molecular electrostatic potential surface have been calculated. Frequency-dependent first hyperpolarizabilities, β(-2ω;ω,ω) and β(-ω;ω,0) have also been evaluated to study the non-linear optical behavior of the title compound. UV-Vis spectrum of the title molecule was recorded and TD-DFT method has been used to calculate six lowest excited states and the corresponding excitation energies.

  17. Ligand-functionalized degradable polyplexes formed by cationic poly(aspartic acid)-grafted chitosan-cyclodextrin conjugates.

    Science.gov (United States)

    Song, Hai-Qing; Li, Rui-Quan; Duan, Shun; Yu, Bingran; Zhao, Hong; Chen, Da-Fu; Xu, Fu-Jian

    2015-03-19

    Polypeptide-based degradable polyplexes attracted considerable attention in drug delivery systems. Polysaccharides including cyclodextrin (CD), dextran, and chitosan (CS) were readily grafted with cationic poly(aspartic acid)s (PAsps). To further enhance the transfection performances of PAsp-based polyplexes, herein, different types of ligand (folic acid, FA)-functionalized degradable polyplexes were proposed based on the PAsp-grafted chitosan-cyclodextrin conjugate (CCPE), where multiple β-CDs were tied on a CS chain. The FA-functionalized CCPE (i.e., CCPE-FA) was obtained via a host-guest interaction between the CD units of CCPE and the adamantane (Ad) species of Ad-modified FA (Ad-FA). The resulting CCPE/pDNA, CCPE-FA/pDNA, and ternary CCPE-FA/CCPE/pDNA (prepared by layer-by-layer assembly) polyplexes were investigated in detail using different cell lines. The CCPE-based polyplexes displayed much higher transfection efficiencies than the CS-based polyplexes reported earlier by us. The ternary polyplexes of CCPE-FA/CCPE/pDNA produced excellent gene transfection abilities in the folate receptor (FR)-positive tumor cells. This work would provide a promising means to produce highly efficient polyplexes for future gene therapy applications.

  18. Pharmacological Inhibition of Soluble Epoxide Hydrolase Ameliorates Diet-Induced Metabolic Syndrome in Rats

    Directory of Open Access Journals (Sweden)

    Abishek Iyer

    2012-01-01

    Full Text Available The signs of metabolic syndrome following chronic excessive macronutrient intake include body weight gain, excess visceral adipose deposition, hyperglycaemia, glucose and insulin intolerances, hypertension, dyslipidaemia, endothelial damage, cardiovascular hypertrophy, inflammation, ventricular contractile dysfunction, fibrosis, and fatty liver disease. Recent studies show increased activity of soluble epoxide hydrolase (sEH during obesity and metabolic dysfunction. We have tested whether sEH inhibition has therapeutic potential in a rat model of diet-induced metabolic syndrome. In these high-carbohydrate, high-fat-fed rats, chronic oral treatment with trans-4-[4-(3-adamantan-1-ylureido-cyclohexyloxy]-benzoic acid (t-AUCB, a potent sEH inhibitor, alleviated the signs of metabolic syndrome in vivo including glucose, insulin, and lipid abnormalities, changes in pancreatic structure, increased systolic blood pressure, cardiovascular structural and functional abnormalities, and structural and functional changes in the liver. The present study describes the pharmacological responses to this selective sEH inhibitor in rats with the signs of diet-induced metabolic syndrome.

  19. Oseltamivir-resistant pandemic (H1N12009 in Yemen - case report

    Directory of Open Access Journals (Sweden)

    Al-Kohlani Abdulhakeem

    2010-05-01

    Full Text Available Abstract Background During the influenza season of 2007-08, oseltamivir-resistant influenza A (H1N1 viruses emerged in several countries in Europe, North America, and Asia. Despite substantial prevalence of oseltamivir-resistant viruses, few data are available on the clinical profile of subjects infected with these viruses. Objectives: to describe the first oseltamivir-resistant (H1N1 influenza virus pandemic 2009 from the Eastern Mediterranean Region including Yemen and to determine the evidence by clinical presentation of children infected with these oseltamivir - resistant viruses. Methodology History, physical examination and laboratory investigations including Complete Blood Count, chest x-ray, blood cultures, CSF examination, LFTs, RFTs, blood for sugar, H1N1 test and oseltamivir resistance test. Results Nasal swabs indicated positivity on both H1N1 test and the RNP gene (Human R Nase P gene that serves as internal positive control for Human RNA. Both clinical specimens presented the mutation S31N in the M2 gene associated with resistance to adamantanes and H274Y in NA gene associated with resistance to oseltamivir. This was the first diagnosed case of resistance to oseltamivir in Yemen and also it is the first reported case of oseltamivir resistance virus in the Eastern Mediterranean Region. Conclusion The pattern of resistance found in the oseltamivir resistant isolate collected from Yemen is the same as has been reported elsewhere in other WHO regions. Clinical description and outcomes are not different from what is described elsewhere.

  20. Oseltamivir-resistant pandemic influenza a (H1N1) 2009 viruses in Spain.

    Science.gov (United States)

    Ledesma, Juan; Vicente, Diego; Pozo, Francisco; Cilla, Gustavo; Castro, Sonia Pérez; Fernández, Jonathan Suárez; Ruiz, Mercedes Pérez; Navarro, José María; Galán, Juan Carlos; Fernández, Mirian; Reina, Jordi; Larrauri, Amparo; Cuevas, María Teresa; Casas, Inmaculada; Breña, Pilar Pérez

    2011-07-01

    Pandemic influenza A (H1N1) 2009 virus appeared in Spain on April 25, 2009 for the first time. This new virus was adamantane-resistant but it was sensitive to neuraminidase (NA) inhibitors oseltamivir and zanamivir. To detect oseltamivir-resistant pandemic influenza A (H1N1) 2009 viruses by the Spanish Influenza Surveillance System (SISS) and a possible spread of oseltamivir-resistant viruses in Spain since starting of the pandemic situation. A total of 1229 respiratory samples taken from 413 severe and 766 non-severe patients with confirmed viral detection of pandemic influenza A (H1N1) 2009 viruses from different Spanish regions were analyzed for the specific detection of the H275Y mutation in NA between April 2009 and May 2010. H275Y NA substitution was found in 8 patients infected with pandemic influenza A (H1N1) 2009 viruses collected in November and December 2009 and in January 2010. All oseltamivir-resistant viruses were detected in severe patients (8/413, 1.93%) who previously received treatment with oseltamivir. Six of these patients were immunocompromised. In Spain, the number of oseltamivir-resistant pandemic influenza A (H1N1) 2009 viruses is until now very low. No evidence for any spread of oseltamivir-resistant H1N1 viruses is achieved in our Country. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Polysaccharide Nanoparticles for Efficient siRNA Targeting in Cancer Cells by Supramolecular pKa Shift

    Science.gov (United States)

    Zhang, Ying-Ming; Yang, Yang; Zhang, Yu-Hui; Liu, Yu

    2016-07-01

    Biomacromolecular pKa shifting is considered as one of the most ubiquitous processes in biochemical events, e.g., the enzyme-catalyzed reaction and protein conformational stabilization. In this paper, we report on the construction of biocompatible polysaccharide nanoparticle with targeting ability and lower toxicity by supramolecular pKa shift strategy. This was realized through a ternary assembly constructed by the dual host‒guest interactions of an adamantane-bis(diamine) conjugate (ADA) with cucurbit[6]uril (CB[6]) and a polysaccharide. The potential application of such biocompatible nanostructure was further implemented by the selective transportation of small interfering RNA (siRNA) in a controlled manner. It is demonstrated that the strong encapsulation of the ADA’s diammonium tail by CB[6] not only reduced the cytotoxicity of the nano-scaled vehicle but also dramatically enhanced cation density through an obvious positive macrocycle-induced pKa shift, which eventually facilitated the subsequent siRNA binding. With a targeted polysaccharide shell containing a cyclodextrin‒hyaluronic acid conjugate, macrocycle-incorporated siRNA polyplexes were specifically delivered into malignant human prostate PC-3 cells. The supramolecular polysaccharide nanoparticles, the formation of which was enabled and promoted by the complexation-assisted pKa shift, may be used as a versatile tool for controlled capture and release of biofunctional substrates.

  2. Diamondoid Hydrocarbons as Maturity Indicators for Condensates from Southern Indus Basin, Pakistan

    Directory of Open Access Journals (Sweden)

    Shagufta Nasir

    2013-01-01

    Full Text Available Diamondoid hydrocarbons have been examined in condensates reservoired in the Southern Indus Basin using GC-MS. Bulk properties reveal that samples are waxy and low sulfur with the exception of Pakhro and Gopang which are nonwaxy. TIC show bimodal distribution of n-alkanes along with high abundance of C20+ n-alkanes indicating substantial contribution of terrigeneous OM in these samples. CPI close to one is consistent with mature nature of oils. The samples show two ranges of Pr/Ph ratios. Those within the range of 2.2–2.7 reflect marine depositional settings for OM while others with Pr/Ph >3 may have originated from terrestrial OM deposited under marine oxic conditions. The cross plot of Pr/n-C17 versus Ph/n-C18 indicate type III kerogen as main source of OM deposited under marine to marine oxic conditions. The values of diamondoid based maturity parameters, like methyladamantane index 54.1–75.8% and methyldiamantane index 34.9–56.3% indicate high level of thermal maturity corresponding to vitrinite reflectance 1.1–1.6%. No biodegradation is observed in any of these samples as shown by methyladamantanes/adamantane 3.99–5.52 and methyldiamantanes/diamantane 2.16–2.99 and supported by high values of API gravity (45.13°–60.02° and absence of UCM.

  3. Properties of Atoms in Molecules:  Caged Atoms and the Ehrenfest Force.

    Science.gov (United States)

    Bader, Richard F W; Fang, De-Cai

    2005-05-01

    This paper uses the properties of atom X enclosed within an adamantane cage, denoted by X@C10H16, as a vehicle to introduce the Ehrenfest force into the discussion of bonding, the properties being determined by the physics of an open system. This is the force acting on an atom in a molecule and determining the potential energy appearing in Slater's molecular virial theorem. The Ehrenfest force acting across the interatomic surface of a bonded pair atoms [Formula: see text] atoms linked by a bond path [Formula: see text] is attractive, each atom being drawn toward the other, and the associated surface virial that measures the contribution to the energy arising from the formation of the surface is stabilizing. It is the Ehrenfest force that determines the adhesive properties of surfaces. The endothermicity of formation for X = He or Ne is not a result of instabilities incurred in the interaction of X with the four methine carbons to which it is bonded, interactions that are stabilizing both in terms of the changes in the atomic energies and in the surface virials. The exothermicity for X = Be(2+), B(3+), and Al(3+) is a consequence of the transfer of electron density from the hydrogen atoms to the carbon and X atoms, the exothermicity increasing with charge transfer despite an increase in the contained volume of X.

  4. Two types of lanthanide selenidostannates(IV) first prepared under the same solvothermal conditions.

    Science.gov (United States)

    Zhou, Jian; Xiao, Hong; Xiao, Hong-Ping; Yang, Tao; Zou, Hua-Hong; Liu, Xing; Zhao, Rong-Qing; Tang, Qiuling

    2015-01-21

    Two types of lanthanide selenidostannates(iv) [Ln2(tepa)2(μ-OH)2Sn2Se6] {Ln = Y(), Pr (), Dy (), Er (), Tm (); tepa = tetraethylenepentamine} and [Ln2(tepa)2(μ2-OH)2Cl2]2[Sn4Se10]·4H2O {Ln = Y (), Dy (), Er (), Tm ()} have been synthesized under identical solvothermal conditions and characterized structurally. Type I (, , , and ) displays 1-D neutral chains [Ln2(tepa)2(μ-OH)2Sn2Se6]n, while type II (, , and ) contains discrete adamantane-like [Sn4Se10](4-) ions with binuclear lanthanide complex [Ln2(tepa)2(μ-OH)2Cl2](2+) ions as counterions. Although the solvothermal synthetic methods could result in the formation of various transition-metal chalcogenidometalates, such identical experimental conditions usually result in the only stable phases of lanthanide chalcogenidometalates. Hence, two different lanthanide selenidostannates(iv), obtained under same solvothermal conditions and starting materials, have been first observed in this work. The optical properties of all the compounds have been investigated by UV-vis spectra.

  5. Schedules of Controlled Substances: Temporary Placement of Six Synthetic Cannabinoids (5F-ADB, 5F-AMB, 5F-APINACA, ADB-FUBINACA, MDMB- CHMICA and MDMB-FUBINACA) Into Schedule I. Notice of Intent.

    Science.gov (United States)

    2016-12-21

    The Administrator of the Drug Enforcement Administration is issuing this notice of intent to temporarily schedule six synthetic cannabinoids: methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate [5F-ADB; 5F-MDMB-PINACA]; methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3-methylbutanoate [5F-AMB]; N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide [5F-APINACA, 5F-AKB48]; N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide [ADB-FUBINACA]; methyl 2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate [MDMB-CHMICA, MMB-CHMINACA] and methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate [MDMB-FUBINACA], into schedule I pursuant to the temporary scheduling provisions of the Controlled Substances Act (CSA). This action is based on a finding by the Administrator that the placement of these synthetic cannabinoids into schedule I of the Controlled Substances Act is necessary to avoid an imminent hazard to the public safety. Any final order will impose the administrative, civil, and criminal sanctions and regulatory controls applicable to schedule I substances under the Controlled Substances Act on the manufacture, distribution, possession, importation, exportation of, and research and conduct with, instructional activities of these synthetic cannabinoids.

  6. On the Importance of C-H/π and C-H⋅⋅⋅H-C Interactions in the Solid State Structure of 15-Lipoxygenase Inhibitors Based on Eugenol Derivatives.

    Science.gov (United States)

    Mirzaei, Masoud; Nikpour, Mohsen; Bauzá, Antonio; Frontera, Antonio

    2015-07-20

    In this manuscript the X-ray structures of two potent and known inhibitors of 15-lipoxygenase, that is, 4-allyl-2-methoxyphenyl-1-admantanecarboxylate (1) and allyl-2-methoxyphenyl-1-cyclohexanecarboxylate (2), are reported. Their solid-state architectures show that they have a strong ability to establish C-H/π and C-H⋅⋅⋅H-C interactions. For the former interaction, the adamantane or cyclohexane moieties are the C-H donors and the electron-rich methoxyphenyl ring is the π system. For the latter, the C-H bonds belong to the aliphatic rings of the inhibitors. Interestingly, the active site of lipoxygenase enzyme family is rich in isoleucine and leucine amino acids that participate in the binding of the unsaturated fatty acid substrate by means of multiple hydrophobic C-H⋅⋅⋅H-C interactions. By means of theoretical calculations, we analyze the ability of compounds 1 and 2 to establish C-H/π and C-H⋅⋅⋅H-C interactions in the solid state.

  7. Discovery of Potential M2 Channel Inhibitors Based on the Amantadine Scaffold via Virtual Screening and Pharmacophore Modeling

    Directory of Open Access Journals (Sweden)

    Ly Le

    2011-12-01

    Full Text Available The M2 channel protein on the influenza A virus membrane has become the main target of the anti-flu drugs amantadine and rimantadine. The structure of the M2 channel proteins of the H3N2 (PDB code 2RLF and 2009-H1N1 (Genbank accession number GQ385383 viruses may help researchers to solve the drug-resistant problem of these two adamantane-based drugs and develop more powerful new drugs against influenza A virus. In the present study, we searched for new M2 channel inhibitors through a combination of different computational methodologies, including virtual screening with docking and pharmacophore modeling. Virtual screening was performed to calculate the free energies of binding between receptor M2 channel proteins and 200 new designed ligands. After that, pharmacophore analysis was used to identify the important M2 protein-inhibitor interactions and common features of top binding compounds with M2 channel proteins. Finally, the two most potential compounds were determined as novel leads to inhibit M2 channel proteins in both H3N2 and 2009-H1N1 influenza A virus.

  8. Discovery of potential M2 channel inhibitors based on the amantadine scaffold via virtual screening and pharmacophore modeling.

    Science.gov (United States)

    Tran, Linh; Choi, Sy Bing; Al-Najjar, Belal O; Yusuf, Muhammad; Wahab, Habibah A; Le, Ly

    2011-12-08

    The M2 channel protein on the influenza A virus membrane has become the main target of the anti-flu drugs amantadine and rimantadine. The structure of the M2 channel proteins of the H3N2 (PDB code 2RLF) and 2009-H1N1 (Genbank accession number GQ385383) viruses may help researchers to solve the drug-resistant problem of these two adamantane-based drugs and develop more powerful new drugs against influenza A virus. In the present study, we searched for new M2 channel inhibitors through a combination of different computational methodologies, including virtual screening with docking and pharmacophore modeling. Virtual screening was performed to calculate the free energies of binding between receptor M2 channel proteins and 200 new designed ligands. After that, pharmacophore analysis was used to identify the important M2 protein-inhibitor interactions and common features of top binding compounds with M2 channel proteins. Finally, the two most potential compounds were determined as novel leads to inhibit M2 channel proteins in both H3N2 and 2009-H1N1 influenza A virus.

  9. Issues in pharmacotherapy of 2009 H1N1 influenza infection

    Directory of Open Access Journals (Sweden)

    Gupta Y

    2010-01-01

    Full Text Available The pandemic caused by the 2009 H1N1 influenza A virus has been a cause of great concern for healthcare professionals and the scientific community worldwide. Due to the widespread resistance of the virus to adamantanes, pharmacotherapy is currently limited to neuraminidase inhibitors, oseltamivir and zanamivir. The use of neuraminidase inhibitors in India is primarily associated with issues of patient and physician awareness, variability in disease management guidelines, safety and efficacy in the Indian population, need for active drug safety monitoring, and development of resistance due to possible misuse. In addition, other issues like availability of the drugs in retail and stockpiling by the public health authorities need careful introspection. The development of influenza vaccines in India and its adequate availability to the country′s populace also poses significant challenges in the management of the pandemic. In light of the limited therapeutic options available for the management of the disease, research on novel targets and pharmacological agents would also be beneficial in addressing the challenges of future outbreaks.

  10. Massively parallel and linear-scaling algorithm for second-order Møller-Plesset perturbation theory applied to the study of supramolecular wires

    Science.gov (United States)

    Kjærgaard, Thomas; Baudin, Pablo; Bykov, Dmytro; Eriksen, Janus Juul; Ettenhuber, Patrick; Kristensen, Kasper; Larkin, Jeff; Liakh, Dmitry; Pawłowski, Filip; Vose, Aaron; Wang, Yang Min; Jørgensen, Poul

    2017-03-01

    We present a scalable cross-platform hybrid MPI/OpenMP/OpenACC implementation of the Divide-Expand-Consolidate (DEC) formalism with portable performance on heterogeneous HPC architectures. The Divide-Expand-Consolidate formalism is designed to reduce the steep computational scaling of conventional many-body methods employed in electronic structure theory to linear scaling, while providing a simple mechanism for controlling the error introduced by this approximation. Our massively parallel implementation of this general scheme has three levels of parallelism, being a hybrid of the loosely coupled task-based parallelization approach and the conventional MPI +X programming model, where X is either OpenMP or OpenACC. We demonstrate strong and weak scalability of this implementation on heterogeneous HPC systems, namely on the GPU-based Cray XK7 Titan supercomputer at the Oak Ridge National Laboratory. Using the ;resolution of the identity second-order Møller-Plesset perturbation theory; (RI-MP2) as the physical model for simulating correlated electron motion, the linear-scaling DEC implementation is applied to 1-aza-adamantane-trione (AAT) supramolecular wires containing up to 40 monomers (2440 atoms, 6800 correlated electrons, 24 440 basis functions and 91 280 auxiliary functions). This represents the largest molecular system treated at the MP2 level of theory, demonstrating an efficient removal of the scaling wall pertinent to conventional quantum many-body methods.

  11. Observations of VOC emissions and photochemical products over US oil- and gas-producing regions using high-resolution H3O+ CIMS (PTR-ToF-MS

    Directory of Open Access Journals (Sweden)

    A. Koss

    2017-08-01

    Full Text Available VOCs related to oil and gas extraction operations in the United States were measured by H3O+ chemical ionization time-of-flight mass spectrometry (H3O+ ToF-CIMS/PTR-ToF-MS from aircraft during the Shale Oil and Natural Gas Nexus (SONGNEX campaign in March–April 2015. This work presents an overview of major VOC species measured in nine oil- and gas-producing regions, and a more detailed analysis of H3O+ ToF-CIMS measurements in the Permian Basin within Texas and New Mexico. Mass spectra are dominated by small photochemically produced oxygenates and compounds typically found in crude oil: aromatics, cyclic alkanes, and alkanes. Mixing ratios of aromatics were frequently as high as those measured downwind of large urban areas. In the Permian, the H3O+ ToF-CIMS measured a number of underexplored or previously unreported species, including aromatic and cycloalkane oxidation products, nitrogen heterocycles including pyrrole (C4H5N and pyrroline (C4H7N, H2S, and a diamondoid (adamantane or unusual monoterpene. We additionally assess the specificity of a number of ion masses resulting from H3O+ ion chemistry previously reported in the literature, including several new or alternate interpretations.

  12. Observations of VOC emissions and photochemical products over US oil- and gas-producing regions using high-resolution H3O+ CIMS (PTR-ToF-MS)

    Science.gov (United States)

    Koss, Abigail; Yuan, Bin; Warneke, Carsten; Gilman, Jessica B.; Lerner, Brian M.; Veres, Patrick R.; Peischl, Jeff; Eilerman, Scott; Wild, Rob; Brown, Steven S.; Thompson, Chelsea R.; Ryerson, Thomas; Hanisco, Thomas; Wolfe, Glenn M.; St. Clair, Jason M.; Thayer, Mitchell; Keutsch, Frank N.; Murphy, Shane; de Gouw, Joost

    2017-08-01

    VOCs related to oil and gas extraction operations in the United States were measured by H3O+ chemical ionization time-of-flight mass spectrometry (H3O+ ToF-CIMS/PTR-ToF-MS) from aircraft during the Shale Oil and Natural Gas Nexus (SONGNEX) campaign in March-April 2015. This work presents an overview of major VOC species measured in nine oil- and gas-producing regions, and a more detailed analysis of H3O+ ToF-CIMS measurements in the Permian Basin within Texas and New Mexico. Mass spectra are dominated by small photochemically produced oxygenates and compounds typically found in crude oil: aromatics, cyclic alkanes, and alkanes. Mixing ratios of aromatics were frequently as high as those measured downwind of large urban areas. In the Permian, the H3O+ ToF-CIMS measured a number of underexplored or previously unreported species, including aromatic and cycloalkane oxidation products, nitrogen heterocycles including pyrrole (C4H5N) and pyrroline (C4H7N), H2S, and a diamondoid (adamantane) or unusual monoterpene. We additionally assess the specificity of a number of ion masses resulting from H3O+ ion chemistry previously reported in the literature, including several new or alternate interpretations.

  13. In vitro antiproliferative study of novel adamantyl pyridin-4-ones.

    Science.gov (United States)

    Petrović Peroković, V; Car, Ž; Opačak-Bernardi, T; Martin-Kleiner, I; Kralj, M; Tomić, S

    2017-07-10

    The preparation of several N-aryl-substituted (phenyl, p-methylphenyl, p-methoxyphenyl, p-nitrophenyl, p-aminophenyl, p-hydroxyphenyl) 3-hydroxy-2-methylpyridin-4-ones as well as their adamantyl derivatives is described, and their in vitro antitumor properties were investigated. The compounds were synthesized in good yields using efficient synthetic routes and methods. Prepared derivatives were evaluated in an antiproliferative in vitro study on 4 cancer cell lines, namely HCT 116 (colon carcinoma), H 460 (lung carcinoma), MCF-7 (breast carcinoma) and K562 (chronic myelogenous leukemia). All tested compounds showed antiproliferative activity ranging from moderate to strong on all inspected cell lines with 4 adamantane containing derivatives being active and selective at low micromolar IC[Formula: see text] concentrations on HCT 116, H 460 and MCF-7. LDH cytotoxicity assay revealed that cytotoxic effects occur after 48 h of exposure. It was shown that there was no change in caspase activity in the treated cells, but there were changes in the cell cycle. All treated samples showed reduced number of cells in the S phase with increased G0/G1 (4b, 5a, 5b) and G2/M (4a) phase.

  14. Ligand-functionalized degradable polyplexes formed by cationic poly(aspartic acid)-grafted chitosan-cyclodextrin conjugates

    Science.gov (United States)

    Song, Hai-Qing; Li, Rui-Quan; Duan, Shun; Yu, Bingran; Zhao, Hong; Chen, Da-Fu; Xu, Fu-Jian

    2015-03-01

    Polypeptide-based degradable polyplexes attracted considerable attention in drug delivery systems. Polysaccharides including cyclodextrin (CD), dextran, and chitosan (CS) were readily grafted with cationic poly(aspartic acid)s (PAsps). To further enhance the transfection performances of PAsp-based polyplexes, herein, different types of ligand (folic acid, FA)-functionalized degradable polyplexes were proposed based on the PAsp-grafted chitosan-cyclodextrin conjugate (CCPE), where multiple β-CDs were tied on a CS chain. The FA-functionalized CCPE (i.e., CCPE-FA) was obtained via a host-guest interaction between the CD units of CCPE and the adamantane (Ad) species of Ad-modified FA (Ad-FA). The resulting CCPE/pDNA, CCPE-FA/pDNA, and ternary CCPE-FA/CCPE/pDNA (prepared by layer-by-layer assembly) polyplexes were investigated in detail using different cell lines. The CCPE-based polyplexes displayed much higher transfection efficiencies than the CS-based polyplexes reported earlier by us. The ternary polyplexes of CCPE-FA/CCPE/pDNA produced excellent gene transfection abilities in the folate receptor (FR)-positive tumor cells. This work would provide a promising means to produce highly efficient polyplexes for future gene therapy applications.Polypeptide-based degradable polyplexes attracted considerable attention in drug delivery systems. Polysaccharides including cyclodextrin (CD), dextran, and chitosan (CS) were readily grafted with cationic poly(aspartic acid)s (PAsps). To further enhance the transfection performances of PAsp-based polyplexes, herein, different types of ligand (folic acid, FA)-functionalized degradable polyplexes were proposed based on the PAsp-grafted chitosan-cyclodextrin conjugate (CCPE), where multiple β-CDs were tied on a CS chain. The FA-functionalized CCPE (i.e., CCPE-FA) was obtained via a host-guest interaction between the CD units of CCPE and the adamantane (Ad) species of Ad-modified FA (Ad-FA). The resulting CCPE/pDNA, CCPE

  15. Mixed-ligand hydroxocopper(II)/pyridazine clusters embedded into 3D framework lattices.

    Science.gov (United States)

    Degtyarenko, Anna S; Handke, Marcel; Krämer, Karl W; Liu, Shi-Xia; Decurtins, Silvio; Rusanov, Eduard B; Thompson, Laurence K; Krautscheid, Harald; Domasevitch, Konstantin V

    2014-06-14

    Rational combination of pyridazine, hydroxo and carboxylate bridging ligands led to the assembly of three types of mixed-ligand polynuclear Cu(II) clusters (A: [Cu2(μ-OH)(μ-pdz)(μ-COO)]; B: [Cu4(μ3-OH)2(μ-pdz)2]; C: [Cu5(μ-OH)2(μ-pdz)4(μ-COO)2(μ-H2O)2]) and their integration into 3D framework structures. Mixed-ligand complexes [Cu2(μ-OH){TMA}(L)(H2O)] (1), [Cu4(μ3-OH)2{ATC}2(L)2(H2O)2]·H2O (2) [Cu4(μ3-OH)2{TDC}3(L)2(H2O)2]·7H2O (3) (L = 1,3-bis(pyridazin-4-yl)adamantane; TMA(3-) = benzene-1,3,5-tricarboxylate, ATC(3-) = adamantane-1,3,5-tricarboxylate, TDC(2-) = 2,5-thiophenedicarboxylate) and [Cu5(μ-OH)2{X}4(L)2(H2O)2]·nH2O (X = benzene-1,3-dicarboxylate, BDC(2-), n = 5 (4) and 5-hydroxybenzene-1,3-dicarboxylate, HO-BDC(2-), n = 6 (5)) are prepared under hydrothermal conditions. Trigonal bridges TMA(3-) and ATC(3-) generate planar Cu(II)/carboxylate subtopologies further pillared into 3D frameworks (1: binodal 3,5-coordinated, doubly interpenetrated tcj-3,5-Ccc2; 2: binodal 3,8-coordinated tfz-d) by bitopic pyridazine ligands. Unprecedented triple bridges in 1 (cluster of type A) support short CuCu separations of 3.0746(6) Å. The framework in 3 is a primitive cubic net (pcu) with multiple bis-pyridazine and TDC(2-) links between the tetranuclear nodes of type . Compounds 4 and 5 adopt uninodal ten-coordinated framework topologies (bct) embedding unprecedented centrosymmetric open-chain pentanuclear clusters of type C with two kinds of multiple bridges, Cu(μ-OH)(μ-pdz)2Cu and Cu(μ-COO)(μ-H2O)Cu (CuCu distances are 3.175 and 3.324 Å, respectively). Magnetic coupling phenomena were detected for every type of cluster by susceptibility measurements of 1, 3 and 4. For binuclear clusters A in 1, the intracluster antiferromagnetic exchange interactions lead to a diamagnetic ground state (J = -17.5 cm(-1); g = 2.1). Strong antiferromagnetic coupling is relevant also for type B, which consequently results in a diamagnetic ground state (J1 = -110 cm(-1

  16. Soluble epoxide hydrolase activity determines the severity of ischemia-reperfusion injury in kidney.

    Directory of Open Access Journals (Sweden)

    Jung Pyo Lee

    Full Text Available Soluble epoxide hydrolase (sEH in endothelial cells determines the plasma concentrations of epoxyeicosatrienoic acids (EETs, which may act as vasoactive agents to control vascular tone. We hypothesized that the regulation of sEH activity may have a therapeutic value in preventing acute kidney injury by controlling the concentration of EETs. In this study, we therefore induced ischemia-reperfusion injury (IRI in C57BL/6 mice and controlled sEH activity by intraperitoneal administration of the sEH inhibitor 12-(3-adamantan-1-ylureido-dodecanoic acid (AUDA. The deterioration of kidney function induced by IRI was partially moderated and prevented by AUDA treatment. In addition, AUDA treatment significantly attenuated tubular necrosis induced by IRI. Ischemic injury induced the down-regulation of sEH, and AUDA administration had no effect on the expression pattern of sEH induced by IRI. In vivo sEH activity was assessed by measuring the substrate epoxyoctadecenoic acid (EpOME and its metabolite dihydroxyoctadec-12-enoic acid (DHOME. Ischemic injury had no effects on the plasma concentrations of EpOME and DHOME, but inhibition of sEH by AUDA significantly increased plasma EpOME and the EpOME/DHOME ratio. The protective effect of the sEH inhibitor was achieved by suppression of proinflammatory cytokines and up-regulation of regulatory cytokines. AUDA treatment prevented the intrarenal infiltration of inflammatory cells, but promoted endothelial cell migration and neovascularization. The results of this study suggest that treatment with sEH inhibitors can reduce acute kidney injury.

  17. Gênero Acosmium: composição química e potencial farmacológico Acosmium genus: chemical composition and pharmacological potential

    Directory of Open Access Journals (Sweden)

    Paulo T. Sousa Júnior

    2009-03-01

    Full Text Available O gênero Acosmium possui 17 espécies com distribuição geográfica que se estende do sudeste do México até o Nordeste da Argentina, sendo que a maioria das espécies está localizada no Brasil. A. dasycarpum, A. panamense, A. subelegans são as espécies mais utilizadas popularmente no tratamento de enfermidades. Uma busca na literatura, resguardando aspectos químicos e farmacológicos destas plantas, indicam atividade citotóxica, ação antitérmica, efeito hipoglicêmico, bem como tem sido usada no tratamento da doença de Alzheimer e desordens no sistema nervoso central. Investigação fitoquímica resultou principalmente no isolamento de terpenos, ácido cafêico, alcalóides do tipo diaza-adamantano e quinolizidínicos bem como pironas.The genus Acosmium is composed by c.a. 17 species, with geographic distribution from southeastern Mexico to Northwestern Argentina. Most of the species, however, are located in Brazil. A. dasycarpum, A. panamense, A. subelegans are used in folk medicine to treat several ailments. A search in the literature regarding the chemical and pharmacological aspects of these plants indicates cytotoxic activity, antithermal and hypoglycemic effects, as well as their use to treat Alzheimer's disease and CNS disorders. Phytochemical investigations resulted mainly in the isolation of terpenes, caffeic acid, diaza-adamantane and quinolizidines alkaloids as well as pyrones.

  18. High-Resolution NMR of Quadrupolar Nuclei in the Solid State

    Energy Technology Data Exchange (ETDEWEB)

    Gann, Sheryl Lee

    1995-11-30

    This dissertation describes recent developments in solid state nuclear magnetic resonance (NMR), for the most part involving the use of dynamic-angle spinning (DAS) NMR to study quadrupolar nuclei. Chapter 1 introduces some of the basic concepts and theory that will be referred to in later chapters, such as the density operator, product operators, rotations, coherence transfer pathways, phase cycling, and the various nuclear spin interactions, including the quadrupolar interaction. Chapter 2 describes the theory behind motional averaging experiments, including DAS, which is a technique where a sample is spun sequentially about two axis oriented at different angles with respect to the external magnetic field such that the chemical shift and quadrupolar anisotropy are averaged to zero. Work done on various rubidium-87 salts is presented as a demonstration of DAS. Chapter 3 explains how to remove sidebands from DAS and magic-angle spinning (MAS) experiments, which result from the time-dependence of the Hamiltonian under sample spinning conditions, using rotor-synchronized {pi}-pulses. Data from these experiments, known as DAH-180 and MAH-180, respectively, are presented for both rubidium and lead salts. In addition, the applicability of this technique to double rotation (DOR) experiments is discussed. Chapter 4 concerns the addition of cross-polarization to DAS (CPDAS). The theory behind spin locking and cross polarizing quadrupolar nuclei is explained and a method of avoiding the resulting problems by performing cross polarization at 0{sup o} (parallel) with respect to the magnetic field is presented. Experimental results are shown for a sodium-23 compound, sodium pyruvate, and for oxygen-17 labeled L-akmine. In Chapter 5, a method for broadening the Hartmann-Hahn matching condition under MAS, called variable effective field cross-polarization (VEFCI?), is presented, along with experimental work on adamantane and polycarbonate.

  19. Magnetic-particle-based, ultrasensitive chemiluminescence enzyme immunoassay for free prostate-specific antigen.

    Science.gov (United States)

    Liu, Ruping; Wang, Cheng; Jiang, Quan; Zhang, Wei; Yue, Zhao; Liu, Guohua

    2013-11-01

    We report a magnetic-particle (MMP)-based chemiluminescence enzyme immunoassay (CLEIA) for free prostate-specific antigen (f-PSA) in human serum. In this method, the f-PSA is sandwiched between the anti-PSA antibody coated MMPs and alkaline phosphatase (ALP)-labeled anti-f-PSA antibody. The signal produced by the emitted photons from the chemiluminescent substrate (4-methoxy-4-(3-phosphatephenyl)-spiro-(1,2-dioxetane-3,2'-adamantane)) is directly proportional to the amount of f-PSA in a sample. The present MMP-based assay can detect f-PSA in the range of 0.1-30 ng mL(-1) with the detection limit of 0.1 ng mL(-1). The linear detection range could match the concentration range within the "diagnostic gray zone" of serum f-PSA levels (4-10 ng mL(-1)). The detection limit was sufficient for measuring clinically relevant f-PSA levels (>4 ng mL(-1)). Furthermore, the method was highly selective; it was unaffected by cross-reaction with human glandular kallikrein-2, a kallikrein-like serine protease that is 80% similar to f-PSA. The proposed method was finally applied to determine f-PSA in 40 samples of human sera. Results obtained using the method showed high correlation with those obtained using a commercially available microplate CLEIA kit (correlation coefficient, 0.9821). This strategy shows great potential application in the fabrication of diagnostic kits for determining f-PSA in serum.

  20. Heterometallic Ti(IV)-Ru(II) and Ti(IV)-Re(I) sulfato complexes containing the Kläui tripodal ligand [(eta5-C5H5)Co{P(O)(OEt)2}3]-.

    Science.gov (United States)

    Yi, Xiao-Yi; Sung, Herman H Y; Zhang, Qian-Feng; Williams, Ian D; Leung, Wa-Hung

    2010-06-28

    Treatment of [(L(OEt))(2)Ti(2)(mu-O)(2)(mu-SO(4))] (L(OEt)(-) = [(eta(5)-C(5)H(5))Co{P(O)(OEt)(2)}(3)](-)) with [Ru(H)(Cl)(CO)(PPh(3))(3)] and Ag(OTf) (OTf(-) = triflate) in the presence of Na(2)CO(3) gave the Ti(IV)-Ru(II) complex [(L(OEt))(2)Ti(2)(mu-O)(3)(mu(3)-SO(4))Ru(CO)(PPh(3))(2)] (2) whereas that with [Re(CO)(5)(OTf)] afforded the Ti(IV)-Re(I) complex [H(L(OEt))(2)Ti(2)(mu-O)(3)(mu-SO(4))Re(CO)(3)(H(2)O)] (3). The crystal structures of complexes 2.HOTf and [3.2/3(Et(3)NHOTf).5/12(H(2)O)](3) have been determined. Complex 2 consists of an adamantane-like Ti(2)RuSO(6) core, in which the {Ru(II)(PPh(3))(2)(CO)} moiety is facially coordinated to a tridentate-O,O',O''(sulfate) [(L(OEt))(2)Ti(2)(mu-O)(3)(mu(3)-SO(4))](2-) metalloligand. The anion [(L(OEt))(2)Ti(2)(mu-O)(3)(mu-SO(4))Re(CO)(3)(H(2)O)](-) in 3 can be viewed as consisting of a fac-{Re(I)(CO)(3)} fragment coordinated with one aqua ligand and a bidentate-O,O'-[(L(OEt))(2)Ti(2)(mu-O)(3)(mu-SO(4))](2-) metalloligand.

  1. Early postnatal treatment with soluble epoxide hydrolase inhibitor or 15-deoxy-Δ(12,14)-prostagandin J2 prevents prenatal dexamethasone and postnatal high saturated fat diet induced programmed hypertension in adult rat offspring.

    Science.gov (United States)

    Lu, Pei-Chen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Lin, Yu-Ju; Chen, Chih-Cheng; Tiao, Mao-Meng; Tsai, Ching-Chou; Huang, Li-Tung; Tain, You-Lin

    2016-07-01

    Prenatal dexamethasone (DEX) exposure, postnatal high-fat (HF) intake, and arachidonic acid pathway are closely related to hypertension. We tested whether a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) therapy can rescue programmed hypertension in the DEX+HF two-hit model. Four groups of Sprague Dawley rats were studied: control, DEX+HF, AUDA, and 15dPGJ2. Dexamethasone (0.1mg/kg body weight) was intraperitoneally administered to pregnant rats from gestational day 16-22. Male offspring received high-fat diet (D12331, Research Diets) from weaning to 4 months of age. In AUDA group, mother rats received 25mg/L in drinking water during lactation. In the 15dPGJ2 group, male offspring received 15dPGJ2 1.5mg/kg BW by subcutaneous injection once daily for 1 week after birth. We found postnatal HF diet aggravated prenatal DEX-induced programmed hypertension, which was similarly prevented by early treatment with AUDA or 15dPGJ2. The beneficial effects of AUDA and 15d-PGJ2 therapy include inhibition of SEH, increases of renal angiotensin converting enzyme-2 (ACE2) and angiotensin II type 2 receptor (AT2R) protein levels, and restoration of nitric oxide bioavailability. Better understanding of the impact of arachidonic acid pathway in the two-hit model will help prevent programmed hypertension in children exposed to corticosteroids and postnatal HF intake.

  2. Targeting arachidonic acid pathway to prevent programmed hypertension in maternal fructose-fed male adult rat offspring.

    Science.gov (United States)

    Tain, You-Lin; Lee, Wei-Chia; Wu, Kay L H; Leu, Steve; Chan, Julie Y H

    2016-12-01

    Hypertension can be programmed in response to nutritional insults in early life. Maternal high-fructose (HF) intake induced programmed hypertension in adult male offspring, which is associated with renal programming and arachidonic acid metabolism pathway. We examined whether early treatment with a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-Deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) can prevent HF-induced programmed hypertension. Pregnant Sprague Dawley rats received regular chow or chow supplemented with fructose (60% diet by weight) during the whole period of pregnancy and lactation. Four groups of male offspring were studied: control, HF, HF+AUDA and HF+15dPGJ2. In HF+AUDA group, mother rats received AUDA 25 mg/L in drinking water during lactation. In the HF+15dPGJ2 group, male offspring received 15dPGJ2 1.5 mg/kg body weight by subcutaneous injection once daily for 1 week after birth. Rats were sacrificed at 12 weeks of age. Maternal HF-induced programmed hypertension is associated with increased renal protein level of SEH and oxidative stress, which early AUDA therapy prevents. Comparison of AUDA and 15dPGJ2 treatments demonstrated that AUDA was more effective in preventing HF-induced programmed hypertension. AUDA therapy increases angiotensin converting enzyme-2 (ACE2) protein levels and PGE2 levels in adult offspring kidney exposed to maternal HF. 15dPGJ2 therapy increases plasma asymmetric dimethylarginine (ADMA) levels and decreases L-arginine-to-ADMA ratio. Better understanding of the impact of arachidonic acid pathway, especially inhibition of SEH, on renal programming may aid in developing reprogramming strategy to prevent programmed hypertension in children exposed to antenatal HF intake.

  3. A novel pyrosequencing assay for the detection of neuraminidase inhibitor resistance-conferring mutations among clinical isolates of avian H7N9 influenza virus.

    Science.gov (United States)

    Qi, Yuhua; Fan, Huan; Qi, Xian; Zhu, Zheng; Guo, Xiling; Chen, Yin; Ge, Yiyue; Zhao, Kangchen; Wu, Tao; Li, Yan; Shan, Yunfeng; Zhou, Minghao; Shi, Zhiyang; Wang, Hua; Cui, Lunbiao

    2014-01-22

    A novel reassortant avian influenza A virus (H7N9) emerged in humans in Eastern China in late February 2013. All virus strains were resistant to adamantanes (amantadine and rimantadine), but susceptible to neuraminidase inhibitors (NAIs) (oseltamivir and zanamivir). One strain (A/shanghai/1/2013) contained the R294K substitution in the neuraminidase (NA) gene, indicating resistance to oseltamivir. Pyrosequencing has proven to be a useful tool in the surveillance of drug resistance in influenza A viruses. Here, we describe a reverse transcription (RT)-PCR assay coupled with pyrosequencing to identify the NA residues E120, H276, and R294 (N9 numbering) of H7N9 viruses. A total of 43 specimens (26 clinical samples and 17 isolates) were tested. Only one isolate containing the E120V heterogenic mutation was detected by pyrosequencing and confirmed by Sanger sequencing. However, this mutation was not detected in the original clinical specimen. Since virus isolation might lead to the selection of variants that might not fully represent the virus population in the clinical specimens, we suggest that using pyrosequencing to detect NAI resistance in H7N9 viruses directly from clinical specimens rather than from cultured isolates. No cross-reactions with other types of influenza virus and respiratory tract viruses were found, and this assay has a sensitivity of 100 copies of synthetic RNA for all three codons. The high sensitivity and specificity of the assay should be sufficient for the detection of positive clinical specimens. In this study, we provide a rapid and reliable method for the characterization of NAI resistance in H7N9 viruses.

  4. Peramivir injection in the treatment of acute influenza: a review of the literature

    Directory of Open Access Journals (Sweden)

    Wester A

    2016-08-01

    Full Text Available Ashley Wester,1 Avinash K Shetty2 1Department of Pharmacy, 2Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: Influenza virus infection is a major cause of morbidity and mortality in children and adults globally. Seasonal epidemics are common due to the rapid virus evolution, whereas the frequent emergence of antigenic variants can result in pandemics and sporadic/endemic avian influenza virus infections. Although annual vaccination is the mainstay for influenza prevention and control, the use of antiviral agents must be considered for treatment and prophylaxis against influenza. Currently available antiviral drugs include neuraminidase inhibitors (NAIs, adamantanes, and a novel polymerase inhibitor (favipiravir. Peramivir is a recently US Food and Drug Administration-approved NAI for the treatment of acute uncomplicated influenza in adults. The chemical structure of peramivir allows it to bind to the influenza neuraminidase with much higher affinity than oseltamivir. Peramivir is effective against a variety of influenza A and B subtypes and has a lower half-maximal inhibitory concentration compared to other NAIs in in vitro studies. Peramivir can be administered intravenously, a route that is favorable for hospitalized, critically ill patients with influenza. The long half-life of peramivir allows for once-daily dosing. The drug is eliminated primarily by the kidneys, warranting dose adjustments in patients with renal dysfunction. Studies have assessed the clinical efficacy of peramivir for treatment of pandemic influenza A (H1N1. Although anecdotal evidence supports the use of peramivir in pediatric patients, pregnant women, and hospitalized patients with severe influenza receiving continuous renal replacement therapy and extracorporeal membrane oxygenation, well-designed, controlled clinical trials should be conducted in order to assess its clinical efficacy in these patient populations. Keywords

  5. Peramivir injection in the treatment of acute influenza: a review of the literature.

    Science.gov (United States)

    Wester, Ashley; Shetty, Avinash K

    2016-01-01

    Influenza virus infection is a major cause of morbidity and mortality in children and adults globally. Seasonal epidemics are common due to the rapid virus evolution, whereas the frequent emergence of antigenic variants can result in pandemics and sporadic/endemic avian influenza virus infections. Although annual vaccination is the mainstay for influenza prevention and control, the use of antiviral agents must be considered for treatment and prophylaxis against influenza. Currently available antiviral drugs include neuraminidase inhibitors (NAIs), adamantanes, and a novel polymerase inhibitor (favipiravir). Peramivir is a recently US Food and Drug Administration-approved NAI for the treatment of acute uncomplicated influenza in adults. The chemical structure of peramivir allows it to bind to the influenza neuraminidase with much higher affinity than oseltamivir. Peramivir is effective against a variety of influenza A and B subtypes and has a lower half-maximal inhibitory concentration compared to other NAIs in in vitro studies. Peramivir can be administered intravenously, a route that is favorable for hospitalized, critically ill patients with influenza. The long half-life of peramivir allows for once-daily dosing. The drug is eliminated primarily by the kidneys, warranting dose adjustments in patients with renal dysfunction. Studies have assessed the clinical efficacy of peramivir for treatment of pandemic influenza A (H1N1). Although anecdotal evidence supports the use of peramivir in pediatric patients, pregnant women, and hospitalized patients with severe influenza receiving continuous renal replacement therapy and extracorporeal membrane oxygenation, well-designed, controlled clinical trials should be conducted in order to assess its clinical efficacy in these patient populations.

  6. Virological surveillance of influenza and other respiratory viruses during six consecutive seasons from 2006 to 2012 in Catalonia, Spain.

    Science.gov (United States)

    Antón, A; Marcos, M A; Torner, N; Isanta, R; Camps, M; Martínez, A; Domínguez, A; Jané, M; Jiménez de Anta, M T; Pumarola, T

    2016-06-01

    Most attention is given to seasonal influenza and respiratory syncytial virus outbreaks, but the cumulative burden caused by other respiratory viruses (RV) is not widely considered. The aim of the present study is to describe the circulation of RV in the general population during six consecutive seasons from 2006 to 2012 in Catalonia, Spain. Cell culture, immunofluorescence and PCR-based assays were used for the RV laboratory-confirmation and influenza subtyping. Phylogenetic and molecular characterizations of viral haemagglutinin, partial neuraminidase and matrix 2 proteins were performed from a representative sampling of influenza viruses. A total of 6315 nasopharyngeal samples were collected, of which 64% were laboratory-confirmed, mainly as influenza A viruses and rhinoviruses. Results show the significant burden of viral aetiological agents in acute respiratory infection, particularly in the youngest cases. The study of influenza strains reveals their continuous evolution through either progressive mutations or by segment reassortments. Moreover, the predominant influenza B lineage was different from that included in the recommended vaccine in half of the studied seasons, supporting the formulation and use of a quadrivalent influenza vaccine. Regarding neuraminidase inhibitors resistance, with the exception of the 2007/08 H275Y seasonal A(H1N1) strains, no other circulating influenza strains carrying known resistance genetic markers were found. Moreover, all circulating A(H1N1)pdm09 and A(H3N2) strains finally became genetically resistant to adamantanes. A wide knowledge of the seasonality patterns of the RV in the general population is well-appreciated, but it is a challenge due to the unpredictable circulation of RV, highlighting the value of local and global RV surveillance.

  7. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

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    Helena Grgić

    Full Text Available The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1pdm09. One H1N2 isolate had hemagglutinin (HA, polymerase A (PA and non-structural (NS genes closely related to A(H1N1pdm09, and neuraminidase (NA, matrix (M, polymerase B1 (PB1, polymerase B2 (PB2, and nucleoprotein (NP genes originating from a triple-reassortant H3N2 virus (tr H3N2. The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

  8. Microfabricated inserts for magic angle coil spinning (MACS wireless NMR spectroscopy.

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    Vlad Badilita

    Full Text Available This article describes the development and testing of the first automatically microfabricated probes to be used in conjunction with the magic angle coil spinning (MACS NMR technique. NMR spectroscopy is a versatile technique for a large range of applications, but its intrinsically low sensitivity poses significant difficulties in analyzing mass- and volume-limited samples. The combination of microfabrication technology and MACS addresses several well-known NMR issues in a concerted manner for the first time: (i reproducible wafer-scale fabrication of the first-in-kind on-chip LC microresonator for inductive coupling of the NMR signal and reliable exploitation of MACS capabilities; (ii improving the sensitivity and the spectral resolution by simultaneous spinning the detection microcoil together with the sample at the "magic angle" of 54.74° with respect to the direction of the magnetic field (magic angle spinning - MAS, accompanied by the wireless signal transmission between the microcoil and the primary circuit of the NMR spectrometer; (iii given the high spinning rates (tens of kHz involved in the MAS methodology, the microfabricated inserts exhibit a clear kinematic advantage over their previously demonstrated counterparts due to the inherent capability to produce small radius cylindrical geometries, thus tremendously reducing the mechanical stress and tearing forces on the sample. In order to demonstrate the versatility of the microfabrication technology, we have designed MACS probes for various Larmor frequencies (194, 500 and 700 MHz testing several samples such as water, Drosophila pupae, adamantane solid and LiCl at different magic angle spinning speeds.

  9. Construction of polar and hydrophobic pores and channels by assembly of peptide molecules

    Science.gov (United States)

    Karle, Isabella; Ranganathan, Darshan

    2003-02-01

    Selected peptides and hybrid peptides (combinations of peptide sequences with organic moieties in a single molecule) self-assemble to form pores, channels and tubules. The assemblies occur in a variety of motifs. Various physiological functions, such as ion transport through cell membranes, and physical functions, such as solubilizing difficult-to-dissolve molecules, are facilitated by the tubes that are formed by molecular assemblies. Examples from nature are the ionophores zervamicin and antiamoebin that transport K + ions through cell membranes. In the area of the constriction of the hour-glass shaped channel in the ionophores, the channel becomes quite convoluted and contains the double-gating mechanism that controls the ion passage. The formation of fairly straight tubules has been accomplished by designing cyclic peptides that have a relatively flat backbone, with extended side-chains, and with amide groups and carbonyl groups that are perpendicular to the plane of the backbone. Further, the amide groups and carbonyl groups have to be spaced so that they are in register from one peptide to another, stacked over or under it, in order to form intermolecular NH⋯OC hydrogen bonds. Tubules of this type can be made if the amino acid residues alternate between α- and β-residues or between D- and L-residues. In order to obviate the register problem with all α-amino acid residues of the same hand, peptide segments have been interspersed with a number of different organic moieties, such as 1,3-adamantane dicarbonyl, norbornene dicarbonyl, 2,6-pyridyl dicarbonyl, cystine and -(CH 2) n chains. Macrocycles that stacked vertically and formed tubules through hydrogen bonding, are hollow, open-ended, and continue to infinity. The inside diameter of the hollow tubules has varied to more than 10 Å. The hydrophobic tubules are able to accommodate highly lipophilic substances. Successes and failures to make tubules and crystal structures of a number of the tubules

  10. Immobilized Multifunctional Polymersomes on Solid Surfaces: Infrared Light-Induced Selective Photochemical Reactions, pH Responsive Behavior, and Probing Mechanical Properties under Liquid Phase.

    Science.gov (United States)

    Iyisan, Banu; Janke, Andreas; Reichenbach, Philipp; Eng, Lukas M; Appelhans, Dietmar; Voit, Brigitte

    2016-06-22

    Fixing polymersomes onto surfaces is in high demand not only for the characterization with advanced microscopy techniques but also for designing specific compartments in microsystem devices in the scope of nanobiotechnology. For this purpose, this study reports the immobilization of multifunctional, responsive, and photo-cross-linked polymersomes on solid substrates by utilizing strong adamantane-β-cyclodextrin host-guest interactions. To reduce nonspecific binding and retain better spherical shape, the level of attractive forces acting on the immobilized polymersomes was tuned through poly(ethylene glycol) passivation as well as decreased β-cyclodextrin content on the corresponding substrates. One significant feature of this system is the pH responsivity of the polymersomes which has been demonstrated by swelling of the immobilized vesicles at acidic condition through in situ AFM measurements. Also, light responsivity has been provided by introducing nitroveratryloxycarbonyl (NVOC) protected amine molecules as photocleavable groups to the polymersome surface before immobilization. The subsequent low-energy femtosecond pulsed laser irradiation resulted in the cleavage of NVOC groups on immobilized polymersomes which in turn led to free amino groups as an additional functionality. The freed amines were further conjugated with a fluorescent dye having an activated ester that illustrates the concept of bio/chemo recognition for a potential binding of biological compounds. In addition to the responsive nature, the mechanical stability of the analyzed polymersomes was supported by computing Young's modulus and bending modulus of the membrane through force curves obtained by atomic force microscopy measurements. Overall, polymersomes with a robust and pH-swellable membrane combined with effective light responsive behavior are promising tools to design smart and stable compartments on surfaces for the development of microsystem devices such as chemo/biosensors.

  11. Novel cycloheximide derivatives targeting the moonlighting protein Mip exhibit specific antimicrobial activity against Legionella pneumophila

    Directory of Open Access Journals (Sweden)

    Janine eRasch

    2015-03-01

    Full Text Available Mip (macrophage infectivity potentiator and Mip-like proteins are virulence factors in a wide range of pathogens including Legionella pneumophila. These proteins belong to the FK506 binding protein (FKBP family of peptidyl-prolyl-cis/trans-isomerases (PPIases. In L. pneumophila the PPIase activity of Mip is required for invasion of macrophages, transmigration through an in vitro lung-epithelial barrier, and full virulence in the guinea pig infection model. Additionally, Mip is a moonlighting protein that binds to collagen IV in the extracellular matrix. Here, we describe the development, and synthesis of cycloheximide derivatives with adamantyl moieties as novel FKBP ligands, and analyze their effect on the viability of L. pneumophila and other bacteria. All compounds efficiently inhibited PPIase activity of the prototypic human FKBP12 as well as Mip with IC50-values as low as 180 nM and 1.7 µM, respectively. Five of these derivatives inhibited the growth of L. pneumophila at concentrations of 30 to 40 µM, but exhibited no effect on other tested bacterial species indicating a specific spectrum of antibacterial activity. The derivatives carrying a 3,5‐dimethyladamantan‐1‐[yl]acetamide substitution (MT_30.32, and a 3‐ethyladamantan‐1‐[yl]acetamide substitution (MT_30.51 had the strongest effects in PPIase- and liquid growth assays. MT_30.32 and MT_30.51 were also inhibitory in macrophage infection studies without being cytotoxic. Accordingly, by applying a combinatorial approach we were able to generate novel, hybrid inhibitors consisting of cycloheximide and adamantane, two known FKBP inhibitors that interact with different parts of the PPIase domain, respectively. Interestingly, despite the proven Mip-inhibitory activity, the viability of a Mip-deficient strain was affected to the same degree as its wild type. Hence, we also propose that cycloheximide derivatives with adamantyl moieties are potent PPIase inhibitors with multiple

  12. Multifunctional halloysite nanotubes for targeted delivery and controlled release of doxorubicin in-vitro and in-vivo studies

    Science.gov (United States)

    Hu, Yuwei; Chen, Jian; Li, Xiufang; Sun, Yanhua; Huang, Shen; Li, Yuqing; Liu, Hui; Xu, Jiangfeng; Zhong, Shian

    2017-09-01

    The current state of cancer therapy encourages researchers to develop novel efficient nanocarriers. Halloysite nanotubes (HNTs) are good nanocarrier candidates due to their unique nanoscale (40-80 nm in diamter and 200-500 nm in length) and hollow lumen, as well as good biocompatibility and low cost. In our study, we prepared a type of folate-mediated targeting and redox-triggered anticancer drug delivery system, so that Doxorubicin (DOX) can be specifically transported to tumor sites due to the over-expressed folate-receptors on the surface of cancer cells. Furthermore, it can then be released by the reductive agent glutathione (GSH) in cancer cells where the content of GSH is nearly 103-fold higher than in the extracellular matrix. A series of methods have demonstrated that per-thiol-β-cyclodextrin (β-CD-(SH)7) was successfully combined with HNTs via a redox-responsive disulfide bond, and folic acid-polyethylene glycol-adamantane (FA-PEG-Ad) was immobilized on the HNTs through the strong complexation between β-CD/Ad. In vitro studies indicated that the release rate of DOX raised sharply in dithiothreitol (DTT) reducing environment and the amount of released DOX reached 70% in 10 mM DTT within the first 10 h, while only 40% of DOX was released in phosphate buffer solution (PBS) even after 79 h. Furthermore, the targeted HNTs could be specifically endocytosed by over-expressed folate-receptor cancer cells and significantly accelerate the apoptosis of cancer cells compared to non-targeted HNTs. In vivo studies further verified that the targeted HNTs had the best therapeutic efficacy and no obvious side effects for tumor-bearing nude mice, while free DOX showed damaging effects on normal tissues. In summary, this novel nanocarrier system shows excellent potential for targeted delivery and controlled release of anticancer drugs and provides a potential platform for tumor therapy.

  13. Quantitative determination of VEGF165 in cell culture medium by aptamer sandwich based chemiluminescence assay.

    Science.gov (United States)

    Shan, Siwen; He, Ziyi; Mao, Sifeng; Jie, Mingsha; Yi, Linglu; Lin, Jin-Ming

    2017-08-15

    In this work, we have developed a sensitive and selective chemiluminescence (CL) assay for vascular endothelial growth factor (VEGF165) quantitative detection based on two specific VEGF165 binding aptamers (Apt). VEGF is a predominant biomarker in cancer angiogenesis, and sensitive detection method of VEGF are highly demanded for both academic study and clinical diagnosis of multiple cancers. In our experiment, VEGF165 was captured in a sandwich structure assembled by two binding aptamers, one capture aptamer was immobilized on streptavidin-coated magnetic beads (MBs) and another VEGF-binding aptamer was labeled by biotin for further phosphatase conjunction. After Apt-VEGF-Apt sandwich was formed on MBs surface, alkaline phosphatase (ALP) was modified to the second aptamer to catalyze CL reaction. By applying 4-methoxy-4-(3-phosphatephenyl)-spiro-(1,2-dioxetane-3,2-adamantane) (AMPPD) as CL substrate, strong signal intensity was achieved. VEGF165 content as low as 1ng/mL was detected in standard spiked samples by our assay, and linear range of working curve was confirmed from 1 to 20ng/mL. Then our method was successfully applied for cell culture medium analysis and on-chip hypoxic HepG2-HUVEC co-culture model study with excellent accuracy equal to ELISA Kit. Our developed assay demonstrated an outstanding performance in VEGF165 quantification and may be further extended to clinical testing of important biomarkers as well as probing microchip cell culture model. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Self-construction of supramolecular polyrotaxane films by an electrotriggered morphogen-driven process.

    Science.gov (United States)

    Rydzek, Gaulthier; Garnier, Tony; Schaaf, Pierre; Voegel, Jean-Claude; Senger, Bernard; Frisch, Benoît; Haikel, Youssef; Petit, Corinne; Schlatter, Guy; Jierry, Loïc; Boulmedais, Fouzia

    2013-08-27

    The design of films using a one-pot process has recently attracted increasing interest in the field of polymer thin film formation. Herein we describe the preparation of one-pot supramolecular polyrotaxane (PRX) films using the morphogen-driven self-construction process. This one-pot buildup strategy where the film growth is triggered by the electrochemical formation and diffusion of a catalyst in close vicinity of the substrate has recently been introduced by our group. A one-pot mixture was used that contained (i) poly(acrylic acid) (PAA) functionalized by azide groups grafted on the polymer chain through oligo(ethylene glycol) (EG) arms, leading to PAA-EG13-N3, (ii) cyclodextrins (α and β CD), as macrocycles that can be threaded along EG arms, (iii) alkyne-functionalized stoppers (ferrocene or adamantane), to cap the PRX assembly by click chemistry, and (iv) copper sulfate. The one-pot mixture solution was brought into contact with a gold electrode. Cu(I), the morphogen, was generated electrochemically from Cu(II) at the electrode/one-pot solution interface. This electrotriggered click reaction leads to the capping of polypseudorotaxane yielding to PRXs. The PRXs can self-assemble through lateral supramolecular interactions to form aggregates and ensure the cohesion of the film. The film buildup was investigated using different types of CD and alkyne functionalized stoppers. Supramolecular PRX aggregates were characterized by X-ray diffraction measurements. The film topographies were imaged by atomic force microscopy. The influence of the concentration in CD and the presence of a competitor were studied as well. The stability of the resulting film was tested in contact with 8 M urea and during the electrochemical oxidation of ferrocene.

  15. Experimental quantification of decoherence via the Loschmidt echo in a many spin system with scaled dipolar Hamiltonians.

    Science.gov (United States)

    Buljubasich, Lisandro; Sánchez, Claudia M; Dente, Axel D; Levstein, Patricia R; Chattah, Ana K; Pastawski, Horacio M

    2015-10-28

    We performed Loschmidt echo nuclear magnetic resonance experiments to study decoherence under a scaled dipolar Hamiltonian by means of a symmetrical time-reversal pulse sequence denominated Proportionally Refocused Loschmidt (PRL) echo. The many-spin system represented by the protons in polycrystalline adamantane evolves through two steps of evolution characterized by the secular part of the dipolar Hamiltonian, scaled down with a factor |k| and opposite signs. The scaling factor can be varied continuously from 0 to 1/2, giving access to a range of complexity in the dynamics. The experimental results for the Loschmidt echoes showed a spreading of the decay rates that correlate directly to the scaling factors |k|, giving evidence that the decoherence is partially governed by the coherent dynamics. The average Hamiltonian theory was applied to give an insight into the spin dynamics during the pulse sequence. The calculations were performed for every single radio frequency block in contrast to the most widely used form. The first order of the average Hamiltonian numerically computed for an 8-spin system showed decay rates that progressively decrease as the secular dipolar Hamiltonian becomes weaker. Notably, the first order Hamiltonian term neglected by conventional calculations yielded an explanation for the ordering of the experimental decoherence rates. However, there is a strong overall decoherence observed in the experiments which is not reflected by the theoretical results. The fact that the non-inverted terms do not account for this effect is a challenging topic. A number of experiments to further explore the relation of the complete Hamiltonian with this dominant decoherence rate are proposed.

  16. Size variation of infrared vibrational spectra from molecules to hydrogenated diamond nanocrystals: a density functional theory study

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    Mudar A. Abdulsattar

    2013-04-01

    Full Text Available Infrared spectra of hydrogenated diamond nanocrystals of one nanometer length are calculated by ab initio methods. Positions of atoms are optimized via density functional theory at the level of the generalized gradient approximation of Perdew, Burke and Ernzerhof (PBE using 3-21G basis states. The frequencies in the vibrational spectrum are analyzed against reduced masses, force constants and intensities of vibration. The spectrum can be divided into two regions depending on the properties of the vibrations or the gap separating them. In the first region, results show good matching to several experimentally obtained lines. The 500 cm−1 broad-peak acoustical branch region is characterized by pure C–C vibrations. The optical branch is centered at 1185 cm−1. Calculations show that several C–C vibrations are mixed with some C–H vibrations in the first region. In the second region the matching also extends to C–H vibration frequencies that include different modes such as symmetric, asymmetric, wagging, scissor, rocking and twisting modes. In order to complete the picture of the size dependence of the vibrational spectra, we analyzed the spectra of ethane and adamantane. The present analysis shows that acoustical and optical branches in diamond nanocrystals approach each other and collapse at 963 cm−1 in ethane. Variation of the highest reduced-mass-mode C–C vibrations from 1332 cm−1 of bulk diamond to 963 cm−1 for ethane (red shift is shown. The analysis also shows the variation of the radial breathing mode from 0 cm−1 of bulk diamond to 963 cm−1 for ethane (blue shift. These variations compare well with experiment. Experimentally, the above-mentioned modes appear shifted from their exact positions due to overlap with neighboring modes.

  17. Acute toxicity of aromatic and non-aromatic fractions of naphthenic acids extracted from oil sands process-affected water to larval zebrafish.

    Science.gov (United States)

    Scarlett, A G; Reinardy, H C; Henry, T B; West, C E; Frank, R A; Hewitt, L M; Rowland, S J

    2013-09-01

    The toxicity of oil sands process-affected water (OSPW) has regularly been attributed to naphthenic acids, which exist in complex mixtures. If on remediation treatment (e.g., ozonation) or on entering the environment, the mixtures of these acids all behave in the same way, then they can be studied as a whole. If, however, some acids are resistant to change, whilst others are not, or are less resistant, it is important to establish which sub-classes of acids are the most toxic. In the present study we therefore assayed the acute toxicity to larval fish, of a whole acidified OSPW extract and an esterifiable naphthenic acids fraction, de-esterified with alkali: both fractions were toxic (LC50 ∼5-8mgL(-1)). We then fractionated the acids by argentation solid phase extraction of the esters and examined the acute toxicity of two fractions: a de-esterified alicyclic acids fraction, which contained, for example, adamantane and diamantane carboxylic acids, and an aromatic acids fraction. The alicyclic acids were toxic (LC50 13mgL(-1)) but the higher molecular weight aromatic acids fraction was somewhat more toxic, at least on a weight per volume basis (LC50 8mgL(-1); P<0.05) (for comparison, the monoaromatic dehydroabietic acid had a LC50 of ∼1mgL(-1)). These results show how toxic naphthenic acids of OSPW are to these larval fish and that on a weight per volume basis, the aromatic acids are at least as toxic as the 'classical' alicyclic acids. The environmental fates and other toxic effects, if any, of the fractions remain to be established. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Diamondoid diacids ('O4' species) in oil sands process-affected water.

    Science.gov (United States)

    Lengger, Sabine K; Scarlett, Alan G; West, Charles E; Rowland, Steven J

    2013-12-15

    As a by-product of oil sands extraction, large volumes of oil sands process water (OSPW) are generated, which are contaminated with a large range of water-soluble organic compounds. The acids are thought to be derived from hydrocarbons via natural biodegradation pathways such as α- and β-oxidation of alkyl substituents, which could produce mono- and diacids, for example. However, while several monoacids ('O2' species) have been identified, the presence of diacids (i.e. 'O4' species) has only been deduced from results obtained via Fourier transform infrared (FTIR) spectroscopy, Fourier transform ion cyclotron resonance high-resolution mass spectrometry (FTICR-HRMS) and nuclear magnetic resonance ((1)H-NMR) spectroscopy and the structures have never been confirmed. An extract of an OSPW from a Canadian tailings pond was analysed and the retention times and the electron ionization mass spectra of some analytes were compared with those of bis-methyl esters of authentic diacids by gas chromatography × gas chromatography/time-of-flight mass spectrometry (GCxGC/TOFMS) in nominal and accurate mass configurations. Two diamondoid diacids (3-carboxymethyladamantane-1-carboxylic acid and adamantane-1,3-dicarboxylic acid) were firmly identified as their bis-methyl esters by retention time and mass spectral matching and several other structural isomers were more tentatively assigned. Diacids have substantially increased polarity over the hydrocarbon and monoacid species from which they probably derive: as late members of biodegradation processes they may be useful indicators of weathering and ageing, not only of OSPW, but potentially of crude oil residues more generally. Structures of O4 species in OSPW have been identified. This confirms pathways of microbial biodegradation, which were only postulated previously, and may be a further indication that remediation of OSPW toxicity can occur by natural microbial action. The presence and abundance of these diacids might

  19. Improper hydrogen bonded cyclohexane C-Hax···Yax contacts: theoretical predictions and experimental evidence from 1H NMR spectroscopy of suitable axial cyclohexane models.

    Science.gov (United States)

    Kolocouris, Antonios; Zervos, Nikolaos; De Proft, Frank; Koch, Andreas

    2011-06-03

    C-H(ax)···Y(ax) contacts are a textbook prototype of steric hindrance in organic chemistry. The nature of these contacts is investigated in this work. MP2/6-31+G(d,p) calculations predicted the presence of improper hydrogen bonded C-H(ax)···Y(ax) contacts of different strength in substituted cyclohexane rings. To support the theoretical predictions with experimental evidence, several synthetic 2-substituted adamantane analogues (1-24) with suitable improper H-bonded C-H(ax)···Y(ax) contacts of different strength were used as models of a substituted cyclohexane ring. The (1)H NMR signal separation, Δδ(γ-CH(2)), within the cyclohexane ring γ-CH(2)s is raised when the MP2/6-31+G(d,p) calculated parameters, reflecting the strength of the H-bonded C-H(ax)···Y(ax) contact, are increased. In molecules with enhanced improper H-bonded contacts C-H(ax)···Y(ax), like those having sterically crowded contacts (Y(ax) = t-Bu) or contacts including considerable electrostatic attractions (Y(ax) = O-C or O═C) the calculated DFT steric energies of the γ-axial hydrogens are considerably reduced reflecting their electron cloud compression. The results suggest that the proton H(ax) electron cloud compression, caused by the C-H(ax)···Y(ax) contacts, and the resulting increase in Δδ(γ-CH(2)) value can be effected not just from van der Waals spheres compression, but more generally from electrostatic attraction forces and van der Waals repulsion, both of which are improper H-bonding components.

  20. Schedules of Controlled Substances: Temporary Placement of Six Synthetic Cannabinoids (5F-ADB, 5F-AMB, 5F-APINACA, ADB-FUBINACA, MDMB-CHMICA and MDMB-FUBINACA) into Schedule I. Temporary Scheduling Order.

    Science.gov (United States)

    2017-04-10

    The Administrator of the Drug Enforcement Administration is issuing this temporary scheduling order to schedule six synthetic cannabinoids: methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate [5F-ADB; 5F-MDMB-PINACA]; methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3-methylbutanoate [5F-AMB]; N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide [5F-APINACA, 5F-AKB48]; N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide [ADB-FUBINACA]; methyl 2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate [MDMB-CHMICA, MMB-CHMINACA] and methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate [MDMB-FUBINACA], and their optical, positional, and geometric isomers, salts, and salts of isomers into schedule I pursuant to the temporary scheduling provisions of the Controlled Substances Act. This action is based on a finding by the Administrator that the placement of these synthetic cannabinoids into schedule I of the Controlled Substances Act is necessary to avoid an imminent hazard to the public safety. As a result of this order, the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances will be imposed on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis, or possess), or propose to handle, 5F-ADB, 5F-AMB, 5F-APINACA, ADB-FUBINACA, MDMB-CHMICA or MDMB-FUBINACA.

  1. Genetic programming based quantitative structure-retention relationships for the prediction of Kovats retention indices.

    Science.gov (United States)

    Goel, Purva; Bapat, Sanket; Vyas, Renu; Tambe, Amruta; Tambe, Sanjeev S

    2015-11-13

    The development of quantitative structure-retention relationships (QSRR) aims at constructing an appropriate linear/nonlinear model for the prediction of the retention behavior (such as Kovats retention index) of a solute on a chromatographic column. Commonly, multi-linear regression and artificial neural networks are used in the QSRR development in the gas chromatography (GC). In this study, an artificial intelligence based data-driven modeling formalism, namely genetic programming (GP), has been introduced for the development of quantitative structure based models predicting Kovats retention indices (KRI). The novelty of the GP formalism is that given an example dataset, it searches and optimizes both the form (structure) and the parameters of an appropriate linear/nonlinear data-fitting model. Thus, it is not necessary to pre-specify the form of the data-fitting model in the GP-based modeling. These models are also less complex, simple to understand, and easy to deploy. The effectiveness of GP in constructing QSRRs has been demonstrated by developing models predicting KRIs of light hydrocarbons (case study-I) and adamantane derivatives (case study-II). In each case study, two-, three- and four-descriptor models have been developed using the KRI data available in the literature. The results of these studies clearly indicate that the GP-based models possess an excellent KRI prediction accuracy and generalization capability. Specifically, the best performing four-descriptor models in both the case studies have yielded high (>0.9) values of the coefficient of determination (R(2)) and low values of root mean squared error (RMSE) and mean absolute percent error (MAPE) for training, test and validation set data. The characteristic feature of this study is that it introduces a practical and an effective GP-based method for developing QSRRs in gas chromatography that can be gainfully utilized for developing other types of data-driven models in chromatography science.

  2. Proteasomal degradation of sphingosine kinase 1 and inhibition of dihydroceramide desaturase by the sphingosine kinase inhibitors, SKi or ABC294640, induces growth arrest in androgen-independent LNCaP-AI prostate cancer cells.

    Science.gov (United States)

    McNaughton, Melissa; Pitman, Melissa; Pitson, Stuart M; Pyne, Nigel J; Pyne, Susan

    2016-03-29

    Sphingosine kinases (two isoforms termed SK1 and SK2) catalyse the formation of the bioactive lipid sphingosine 1-phosphate. We demonstrate here that the SK2 inhibitor, ABC294640 (3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide) or the SK1/SK2 inhibitor, SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole)) induce the proteasomal degradation of SK1a (Mr = 42 kDa) and inhibit DNA synthesis in androgen-independent LNCaP-AI prostate cancer cells. These effects are recapitulated by the dihydroceramide desaturase (Des1) inhibitor, fenretinide. Moreover, SKi or ABC294640 reduce Des1 activity in Jurkat cells and ABC294640 induces the proteasomal degradation of Des1 (Mr = 38 kDa) in LNCaP-AI prostate cancer cells. Furthermore, SKi or ABC294640 or fenretinide increase the expression of the senescence markers, p53 and p21 in LNCaP-AI prostate cancer cells. The siRNA knockdown of SK1 or SK2 failed to increase p53 and p21 expression, but the former did reduce DNA synthesis in LNCaP-AI prostate cancer cells. Moreover, N-acetylcysteine (reactive oxygen species scavenger) blocked the SK inhibitor-induced increase in p21 and p53 expression but had no effect on the proteasomal degradation of SK1a. In addition, siRNA knockdown of Des1 increased p53 expression while a combination of Des1/SK1 siRNA increased the expression of p21. Therefore, Des1 and SK1 participate in regulating LNCaP-AI prostate cancer cell growth and this involves p53/p21-dependent and -independent pathways. Therefore, we propose targeting androgen-independent prostate cancer cells with compounds that affect Des1/SK1 to modulate both de novo and sphingolipid rheostat pathways in order to induce growth arrest.

  3. Continuous probing of cold complex molecules with infrared frequency comb spectroscopy

    Science.gov (United States)

    Spaun, Ben; Changala, P. Bryan; Patterson, David; Bjork, Bryce J.; Heckl, Oliver H.; Doyle, John M.; Ye, Jun

    2016-05-01

    For more than half a century, high-resolution infrared spectroscopy has played a crucial role in probing molecular structure and dynamics. Such studies have so far been largely restricted to relatively small and simple systems, because at room temperature even molecules of modest size already occupy many millions of rotational/vibrational states, yielding highly congested spectra that are difficult to assign. Targeting more complex molecules requires methods that can record broadband infrared spectra (that is, spanning multiple vibrational bands) with both high resolution and high sensitivity. However, infrared spectroscopic techniques have hitherto been limited either by narrow bandwidth and long acquisition time, or by low sensitivity and resolution. Cavity-enhanced direct frequency comb spectroscopy (CE-DFCS) combines the inherent broad bandwidth and high resolution of an optical frequency comb with the high detection sensitivity provided by a high-finesse enhancement cavity, but it still suffers from spectral congestion. Here we show that this problem can be overcome by using buffer gas cooling to produce continuous, cold samples of molecules that are then subjected to CE-DFCS. This integration allows us to acquire a rotationally resolved direct absorption spectrum in the C-H stretching region of nitromethane, a model system that challenges our understanding of large-amplitude vibrational motion. We have also used this technique on several large organic molecules that are of fundamental spectroscopic and astrochemical relevance, including naphthalene, adamantane and hexamethylenetetramine. These findings establish the value of our approach for studying much larger and more complex molecules than have been probed so far, enabling complex molecules and their kinetics to be studied with orders-of-magnitude improvements in efficiency, spectral resolution and specificity.

  4. Concise NMR approach for molecular dynamics characterizations in organic solids.

    Science.gov (United States)

    Aliev, Abil E; Courtier-Murias, Denis

    2013-08-22

    Molecular dynamics characterisations in solids can be carried out selectively using dipolar-dephasing experiments. Here we show that the introduction of a sum of Lorentzian and Gaussian functions greatly improve fittings of the "intensity versus time" data for protonated carbons in dipolar-dephasing experiments. The Lorentzian term accounts for remote intra- and intermolecular (1)H-(13)C dipole-dipole interactions, which vary from one molecule to another or for different carbons within the same molecule. Thus, by separating contributions from weak remote interactions, more accurate Gaussian decay constants, T(dd), can be extracted for directly bonded (1)H-(13)C dipole-dipole interactions. Reorientations of the (1)H-(13)C bonds lead to the increase of T(dd), and by measuring dipolar-dephasing constants, insight can be gained into dynamics in solids. We have demonstrated advantages of the method using comparative dynamics studies in the α and γ polymorphs of glycine, cyclic amino acids L-proline, DL-proline and trans-4-hydroxy-L-proline, the Ala residue in different dipeptides, as well as adamantane and hexamethylenetetramine. It was possible to distinguish subtle differences in dynamics of different carbon sites within a molecule in polymorphs and in L- and DL-forms. The presence of overall molecular motions is shown to lead to particularly large differences in dipolar-dephasing experiments. The differences in dynamics can be attributed to differences in noncovalent interactions. In the case of hexamethylenetetramine, for example, the presence of C-H···N interactions leads to nearly rigid molecules. Overall, the method allows one to gain insight into the role of noncovalent interactions in solids and their influence on the molecular dynamics.

  5. Experimental quantification of decoherence via the Loschmidt echo in a many spin system with scaled dipolar Hamiltonians

    Energy Technology Data Exchange (ETDEWEB)

    Buljubasich, Lisandro; Dente, Axel D.; Levstein, Patricia R.; Chattah, Ana K.; Pastawski, Horacio M. [Instituto de Física Enrique Gaviola (IFEG-CONICET), Córdoba 5000 (Argentina); Facultad de Matemática, Astronomía y Física, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba 5000 (Argentina); Sánchez, Claudia M. [Facultad de Matemática, Astronomía y Física, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba 5000 (Argentina)

    2015-10-28

    We performed Loschmidt echo nuclear magnetic resonance experiments to study decoherence under a scaled dipolar Hamiltonian by means of a symmetrical time-reversal pulse sequence denominated Proportionally Refocused Loschmidt (PRL) echo. The many-spin system represented by the protons in polycrystalline adamantane evolves through two steps of evolution characterized by the secular part of the dipolar Hamiltonian, scaled down with a factor |k| and opposite signs. The scaling factor can be varied continuously from 0 to 1/2, giving access to a range of complexity in the dynamics. The experimental results for the Loschmidt echoes showed a spreading of the decay rates that correlate directly to the scaling factors |k|, giving evidence that the decoherence is partially governed by the coherent dynamics. The average Hamiltonian theory was applied to give an insight into the spin dynamics during the pulse sequence. The calculations were performed for every single radio frequency block in contrast to the most widely used form. The first order of the average Hamiltonian numerically computed for an 8-spin system showed decay rates that progressively decrease as the secular dipolar Hamiltonian becomes weaker. Notably, the first order Hamiltonian term neglected by conventional calculations yielded an explanation for the ordering of the experimental decoherence rates. However, there is a strong overall decoherence observed in the experiments which is not reflected by the theoretical results. The fact that the non-inverted terms do not account for this effect is a challenging topic. A number of experiments to further explore the relation of the complete Hamiltonian with this dominant decoherence rate are proposed.

  6. The bird flu: a new emerging pandemic threat and its pharmacological intervention.

    Science.gov (United States)

    Mittal, Niti; Medhi, Bikash

    2007-07-01

    Bird flu is an infection caused by avian influenza viruses, which are of different types A, B and C. Type A avian influenza viruses are the most frequently associated with avian influenza epidemics and pandemics. There are 16 hemagglutinin (H1 to H16) and 9 neuraminidase types (N1 to N9) identified till date. A peculiar characteristic of influenza A viruses is their propensity for genetic change by two main processes: antigenic drift (small, gradual changes) and antigenic shift (abrupt, major change producing a novel influenza A virus subtype).There are various modes of transmission of human influenza including inhalation, direct or indirect (fomite) contact etc., can have manifestations ranging from mild to severe or fatal disease, depend on the viral subtype causing the disease. Avian influenza A (H5N1) results in high death rate amongst infants and young children.The first outbreak of human infection by avian influenza viruses (H5N1) was observed in 1997 in Hong Kong. Since then a large number of outbreaks have been reported in different parts of the world. In fact, the spread of avian influenza H5N1 in various species including humans has lead to a current pandemic threat.Human avian influenza infections in persons at high risk of exposure can be prevented by adopting a series of protective measures, anti-viral vaccination and health monitoring. Drugs currently available for the treatment or prophylaxis of influenza infections include the adamantanes (amantadine and rimantadine) and the newer class of neuraminidase inhibitors (zanamivir, oseltamivir and peramivir). However, vaccines are considered the first line of defense for reducing the excess morbidity and mortality that invariably accompany pandemics and a number of clinical trials are under way to test them.

  7. Dinuclear Pt(II)-bisphosphonate complexes: a scaffold for multinuclear or different oxidation state platinum drugs.

    Science.gov (United States)

    Piccinonna, Sara; Margiotta, Nicola; Pacifico, Concetta; Lopalco, Antonio; Denora, Nunzio; Fedi, Serena; Corsini, Maddalena; Natile, Giovanni

    2012-08-28

    Geminal bisphosphonates (BPs), used in the clinic for the treatment of hypercalcaemia and skeletal metastases, have been also exploited for promoting the specific accumulation of platinum antitumor drugs in bone tissue. In this work, the platinum dinuclear complex [{Pt(en)}(2)(μ-AHBP-H(2))](+) (1) (the carbon atom bridging the two phosphorous atoms carrying a 2-ammonioethyl and a hydroxyl group, AHBP-H(2)) has been used as scaffold for the synthesis of a Pt(II) trinuclear complex, [{Pt(en)}(3)(μ-AHBP)](+) (2), and a Pt(IV) adamantane-shaped dinuclear complex featuring an oxo-bridge, [{Pt(IV)(en)Cl}(2)(μ-O)(μ-AHBP-H(2))](+) (3) (X-ray structure). Compound 2 undergoes a reversible, pH dependent, rearrangement with a neat switch point around pH = 5.4. Compound 3 undergoes a one-step electrochemical reduction at E(pc) = -0.84 V affording compound 1. Such a potential is far lower than that of glutathione (-0.24 V), nevertheless compound 3 can undergo chemical reduction to 1 by GSH, most probably through a different (inner-sphere) mechanism. In vitro cytotoxicity of the new compounds, tested against murine glioma (C6) and human cervix (HeLa) and hepatoma (HepG2) cell lines, has shown that, while the Pt(IV) dimer 3 is inactive up to a concentration of 50 μM, the two Pt(II) polynuclear compounds 1 and 2 have a cytotoxicity comparable to that of cisplatin with the trinuclear complex 2 generally more active than the dinuclear complex 1.

  8. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

    Science.gov (United States)

    Grgić, Helena; Costa, Marcio; Friendship, Robert M; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

    2015-01-01

    The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

  9. H5N1 surveillance in migratory birds in Java, Indonesia.

    Science.gov (United States)

    Stoops, Arthur C; Barbara, Katie A; Indrawan, Mochamad; Ibrahim, Ima N; Petrus, Wicaksana B; Wijaya, Susan; Farzeli, Arik; Antonjaya, Ungke; Sin, Lim W; Hidayatullah, N; Kristanto, Ige; Tampubolon, A M; Purnama, S; Supriatna, Adam; Burgess, Timothy H; Williams, Maya; Putnam, Shannon D; Tobias, Steve; Blair, Patrick J

    2009-12-01

    We sought to elucidate the role of migratory birds in transmission of H5N1 in an enzoonotic area. Resident, captive, and migratory birds were sampled at five sites in Java, Indonesia. Mist nets were used to trap birds. Birds were identified to species. RNA was extracted from swabs and reverse transcriptase polymerase chain reaction (RT-PCR) conducted for the HA and M genes of H5N1. Antibodies were detected by enzyme-linked immunosorbent assay and hemagglutination inhibition test. Between October 2006 and September 2007, a total of 4,067 captive, resident, and migratory birds comprising 98 species in 23 genera were sampled. The most commonly collected birds were the common sandpiper (6% of total), striated heron (3%), and the domestic chicken (14%). The overall prevalence of H5N1 antibodies was 5.3%. A significantly higher percentage of captive birds (16.1%) showed antibody evidence of H5N1 exposure when compared to migratory or resident birds. The greatest number of seropositive birds in each category were Muschovy duck (captive), striated heron (resident), and the Pacific golden plover (migratory). Seven apparently well captive birds yielded molecular evidence of H5N1 infection. Following amplification, the HA, NA, and M genes were analyzed. Phylogenetic analysis of the HA gene showed that the isolates were 97% similar to EU124153.1 A/chicken/West Java/Garut May 2006, an isolate obtained in a similar region of West Java. While no known markers of neuraminidase inhibitor resistance were found within the NA gene, M segment analysis revealed the V27A mutation known to confer resistance to adamantanes. Our results demonstrate moderate serologic evidence of H5N1 infection in captive birds, sampled in five sites in Java, Indonesia, but only occasional infection in resident and migratory birds. These data imply that in an enzoonotic region of Indonesia the role of migratory birds in transmission of H5N1 is limited.

  10. On the fly estimation of host-guest binding free energies using the movable type method: participation in the SAMPL5 blind challenge

    Science.gov (United States)

    Bansal, Nupur; Zheng, Zheng; Cerutti, David S.; Merz, Kenneth M.

    2017-01-01

    We review our performance in the SAMPL5 challenge for predicting host-guest binding affinities using the movable type (MT) method. The challenge included three hosts, acyclic Cucurbit[2]uril and two octa-acids with and without methylation at the entrance to their binding cavities. Each host was associated with 6-10 guest molecules. The MT method extrapolates local energy landscapes around particular molecular states and estimates the free energy by Monte Carlo integration over these landscapes. Two blind submissions pairing MT with variants of the KECSA potential function yielded mean unsigned errors of 1.26 and 1.53 kcal/mol for the non-methylated octa-acid, 2.83 and 3.06 kcal/mol for the methylated octa-acid, and 2.77 and 3.36 kcal/mol for Cucurbit[2]uril host. While our results are in reasonable agreement with experiment, we focused on particular cases in which our estimates gave incorrect results, particularly with regard to association between the octa-acids and an adamantane derivative. Working on the hypothesis that differential solvation effects play a role in effecting computed binding affinities for the parent octa-acid and the methylated octa-acid and that the ligands bind inside the pockets (rather than on the surface) we devised a new solvent accessible surface area term to better quantify solvation energy contributions in MT based studies. To further explore this issue a, molecular dynamics potential of mean force (PMF) study indicates that, as found by our docking calculations, the stable binding mode for this ligand is inside (rather than surface bound) the octa-acid cavity whether the entrance is methylated or not. The PMF studies also obtained the correct order for the methylation-induced change in binding affinities and associated the difference, to a large extent to differential solvation effects. Overall, the SAMPL5 challenge yielded in improvements our solvation modeling and also demonstrated the need for thorough validation of input data

  11. Supported Oxide Catalysts from Chelating Precursors

    Science.gov (United States)

    Prieto-Centurion, Dario

    Supported Fe catalysts and, in particular, Fe and substituted MFI zeolites have attracted industrial and academic attention due to their ability to promote selective catalytic reduction of NOx and selective partial oxidation of hydrocarbons. It is generally accepted that some form of highly dispersed, binuclear or atomically-isolated metal species are involved in the selective processes catalyzed these materials. Several studies have sought to reproduce the structures and reactivity of these substituted zeolites on dierent supports. Given that specialized reagents or preparation conditions that are required in some of these preparation methods, and that multiple surface structures are often formed, this dissertation aimed to develop a route to highly dispersed supported transition metals using commonly available reactants and synthesis routes. Described here is a straightforward and effective procedure to control dispersion and surface speciation of Fe on SiO2 and CeO2 through incipient wetness impregnation (IWI) of the support with aqueous, anionic complexes of Fe3+ and ethylenediaminetetraacetic acid (EDTA) followed by oxidative heat-treatment. On SiO2, this method preferentially creates isolated surface structures up to loading of 0.9 Fe nm-2 if using alkali counter-cations. This isolated species display classic 'single-site' behavior|constant turn over frequency (TOF) with increasing Fe surface density|in the oxidation of adamantane with H 2O2, indicating active sites are equally accessible and equally active within this range of surface density. Additionally, TOF increases linearly with electronegativity of the alkali counter-cation, suggesting electronic promotion. Conversely, IWI of unprotected Fe3+ produces agglomerates less active in this reaction. On CeO2, the sterics and negative charge imparted on Fe 3+ by EDTA4- inhibits incorporation of Fe into surface vacancies. Instead, formation of two-dimensional oligomeric structures which can undergo Fe3+-Fe2

  12. Triazolyl-based copper-molybdate hybrids: from composition space diagram to magnetism and catalytic performance.

    Science.gov (United States)

    Senchyk, Ganna A; Lysenko, Andrey B; Babaryk, Artem A; Rusanov, Eduard B; Krautscheid, Harald; Neves, Patrícia; Valente, Anabela A; Gonçalves, Isabel S; Krämer, Karl W; Liu, Shi-Xia; Decurtins, Silvio; Domasevitch, Konstantin V

    2014-10-06

    The multicomponent mixed-metal Cu(II)/Mo(VI) oxides/1,3-bis(1,2,4-triazol-4-yl)adamantane (tr2ad) system was thoroughly studied employing a compositional diagram approach. The concept allowed us to prepare three layered copper-molybdate hybrid solids [Cu(II)2(tr2ad)4](Mo8O26) (1), [Cu4(II)(μ4-O)(tr2ad)2(MoO4)3]·7.5H2O (2), and [Cu(I)2(tr2ad)2](Mo2O7)·H2O (3), and to elucidate the relationship between initial reagent concentration/stoichiometry and the stability of the resultant structural motifs. Compounds 1 and 2 were found to dominate throughout a wide crystallization range of the concentration triangle, whereas compound 3 was formed by redox processes in the narrow crystallization area having a high excess of Cu(OAc)2·H2O. Independent experiments carried out with Cu(OAc)2 and (NH4)6Mo7O24 in the absence of tr2ad, under the same conditions, revealed the formation of low-valent and bimetallic oxides, including Cu2O, MoO2, Cu(Mo3O10)·H2O, and Cu3(MoO4)2(OH)2. Compounds 1 and 2 show high thermal and chemical stability as examined as catalysts in the epoxidation of cis-cyclooctene and the oxidation of benzyl alcohol (BzOH) with different types of oxidants. The oxidation reaction of BzOH using tert-butyl hydroperoxide (TBHP) as the oxidant, in the presence of 1 or 2, led to benzaldehyde and benzoic acid (PhCO2H), with the latter being formed in up to 90% yield at 24 h. The results suggest that 1 and 2 may be favorable heterogeneous catalysts for the synthesis of PhCO2H. Whereas compound 1 only reveals a weak ferromagnetic coupling between neighboring Cu(II) centers (J = 0.41 cm(-1)), compound 2 shows distinct intracluster antiferromagnetic exchange interactions (J = -29.9 cm(-1), J' = -25.7 cm(-1)), which consequently results in a diamagnetic ground state.

  13. Tricyclic pyrazoles. Part 8. Synthesis, biological evaluation and modelling of tricyclic pyrazole carboxamides as potential CB2 receptor ligands with antagonist/inverse agonist properties.

    Science.gov (United States)

    Deiana, Valeria; Gómez-Cañas, María; Pazos, M Ruth; Fernández-Ruiz, Javier; Asproni, Battistina; Cichero, Elena; Fossa, Paola; Muñoz, Eduardo; Deligia, Francesco; Murineddu, Gabriele; García-Arencibia, Moisés; Pinna, Gerard A

    2016-04-13

    Previous studies have investigated the relevance and structure-activity relationships (SARs) of pyrazole derivatives in relation with cannabinoid receptors, and the series of tricyclic 1,4-dihydroindeno[1,2-c]pyrazoles emerged as potent CB2 receptor ligands. In the present study, novel 1,4-dihydroindeno[1,2-c]pyrazole and 1H-benzo[g]indazole carboxamides containing a cyclopropyl or a cyclohexyl substituent were designed and synthesized to evaluate the influence of these structural modifications towards CB1 and CB2 receptor affinities. Among these derivatives, compound 15 (6-cyclopropyl-1-(2,4-dichlorophenyl)-N-(adamantan-1-yl)-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide) showed the highest CB2 receptor affinity (Ki = 4 nM) and remarkable selectivity (KiCB1/KiCB2 = 2232), whereas a similar affinity, within the nM range, was seen for the fenchyl derivative (compound 10: Ki = 6 nM), for the bornyl analogue (compound 14: Ki = 38 nM) and, to a lesser extent, for the aminopiperidine derivative (compound 6: Ki = 69 nM). Compounds 10 and 14 were also highly selective for the CB2 receptor (KiCB1/KiCB2 > 1000), whereas compound 6 was relatively selective (KiCB1/KiCB2 = 27). The four compounds were also subjected to GTPγS binding analysis showing antagonist/inverse agonist properties (IC50 for compound 14 = 27 nM, for 15 = 51 nM, for 10 = 80 nM and for 6 = 294 nM), and this activity was confirmed for the three more active compounds in a CB2 receptor-specific in vitro bioassay consisting in the quantification of prostaglandin E2 release by LPS-stimulated BV2 cells, in the presence and absence of WIN55,212-2 and/or the investigated compounds. Modelling studies were also conducted with the four compounds, which conformed with the structural requirements stated for the binding of antagonist compounds to the human CB2 receptor.

  14. Meloxicam fails to augment the reno-protective effects of soluble epoxide hydrolase inhibition in streptozotocin-induced diabetic rats via increased 20-HETE levels.

    Science.gov (United States)

    Katary, Mohamed M; Pye, Chelsey; Elmarakby, Ahmed A

    2016-09-03

    The pro-inflammatory cyclooxygenase (COX)-derived prostaglandins and the anti-inflammatory cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) play an important role in the regulation of renal injury. The current study examined whether COX inhibition augments the reno-protective effects of increased EETs levels via inhibiting EETs degradation by soluble epoxide hydrolase (sEH) in diabetic rats. Streptozotocin (50mg/kg, i.v) was used to induce diabetes in male Sprague Dawley rats. Rats were then divided into 5 groups (n=6-8); control non diabetic, diabetic, diabetic treated with the sEH inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), diabetic treated with the COX inhibitor meloxicam and diabetic treated with meloxicam plus t-AUCB for 2 months. Glomerular albumin permeability and urinary albumin and nephrin excretion levels were significantly elevated in diabetic rats together with decreased glomerular α3 integrin and nephrin expression levels. Inhibition of sEH reduced glomerular albumin permeability, albumin and nephrin excretion levels and restored the decrease in glomerular α3 integrin and nephrin expression in diabetic rats. Meloxicam failed to reduce renal injury or even to synergize the reno-protective effects of sEH inhibition in diabetic rats. Furthermore, inhibition of sEH reduced the elevation in renal collagen deposition and urinary MCP-1 excretion levels together with a reduction in the number of renal TUNEL positive cells in diabetic vs. control rats (PMeloxicam did not reduce renal inflammation or apoptosis in diabetic rats or even exacerbate the anti-inflammatory and anti-apoptotic effects of sEH inhibition. Renal 20-hydroxyeicosatetranoic acid (20-HETE) levels were elevated in diabetic rats and meloxicam further exacerbated this elevation. In conclusion, our study suggests that inhibition of COX failed to provide renal protection or to augment the reno-protective effects of sEH inhibition in

  15. Electrochemical properties and lithium ion solvation behavior of sulfone-ester mixed electrolytes for high-voltage rechargeable lithium cells

    Science.gov (United States)

    Watanabe, Yuu; Kinoshita, Shin-ichi; Wada, Satoshi; Hoshino, Keiji; Morimoto, Hideyuki; Tobishima, Shin-ichi

    2008-05-01

    Sulfone-ester mixed solvent electrolytes were examined for 5 V-class high-voltage rechargeable lithium cells. As the base-electrolyte, sulfolane (SL)-ethyl acetate (EA) (1:1 mixing volume ratio) containing 1 M LiBF4 solute was investigated. Electrolyte conductivity, electrochemical stability, Li+ ion solvation behavior and cycleability of lithium electrode were evaluated. 13C NMR measurement results suggest that Li+ ions are solvated with both SL and EA. Charge-discharge cycling efficiency of lithium anode in SL-EA electrolytes was poor, being due to its poor tolerance for reduction. To improve lithium charge-discharge cycling efficiency in SL-EA electrolytes, following three trials were carried out: (i) improvement of the cathodic stability of electrolyte solutions by change in polarization through modification of solvent structure; isopropyl methyl sulfone and methyl isobutyrate were investigated as alternative SL and EA, respectively, (ii) suppression of the reaction between lithium and electrolyte solutions by addition of low reactivity surfactants of cycloalkanes (decalin and adamantane) or triethylene glycol derivatives (triglyme, 1,8-bis(tert-butyldimethylsilyloxy)-3,6-dioxaoctane and triethylene glycol di(methanesulfonate)) into SL-EA electrolytes, and (iii) change in surface film by addition of surface film formation agent of vinylene carbonate (VC) into SL-EA electrolytes. These trials made lithium cycling behavior better. Lithium cycling efficiency tended to increase with a decrease in overpotential. VC addition was most effective for improvement of lithium cycling efficiency among these additives. Stable surface film is formed on lithium anode by adding VC and the resistance between anode/electrolyte interfaces showed a constant value with an increase in cycle number. When the electrolyte solutions without VC, the interfacial resistance increased with an increase in cycle number. VC addition to SL-EA was effective not only for Li/LiCoO2 cell with charge

  16. Culturing oil sands microbes as mixed species communities enhances ex situ model naphthenic acid degradation.

    Science.gov (United States)

    Demeter, Marc A; Lemire, Joseph A; Yue, Gordon; Ceri, Howard; Turner, Raymond J

    2015-01-01

    Oil sands surface mining for bitumen results in the formation of oil sands process water (OSPW), containing acutely toxic naphthenic acids (NAs). Potential exists for OSPW toxicity to be mitigated by aerobic degradation of the NAs by microorganisms indigenous to the oil sands tailings ponds, the success of which is dependent on the methods used to exploit the metabolisms of the environmental microbial community. Having hypothesized that the xenobiotic tolerant biofilm mode-of-life may represent a feasible way to harness environmental microbes for ex situ treatment of OSPW NAs, we aerobically grew OSPW microbes as single and mixed species biofilm and planktonic cultures under various conditions for the purpose of assaying their ability to tolerate and degrade NAs. The NAs evaluated were a diverse mixture of eight commercially available model compounds. Confocal microscopy confirmed the ability of mixed and single species OSPW cultures to grow as biofilms in the presence of the NAs evaluated. qPCR enumeration demonstrated that the addition of supplemental nutrients at concentrations of 1 g L(-1) resulted in a more numerous population than 0.001 g L(-1) supplementation by approximately 1 order of magnitude. GC-FID analysis revealed that mixed species cultures (regardless of the mode of growth) are the most effective at degrading the NAs tested. All constituent NAs evaluated were degraded below detectable limits with the exception of 1-adamantane carboxylic acid (ACA); subsequent experimentation with ACA as the sole NA also failed to exhibit degradation of this compound. Single species cultures degraded select few NA compounds. The degradation trends highlighted many structure-persistence relationships among the eight NAs tested, demonstrating the effect of side chain configuration and alkyl branching on compound recalcitrance. Of all the isolates, the Rhodococcus spp. degraded the greatest number of NA compounds, although still less than the mixed species cultures

  17. Mono- and dinuclear iron complexes of bis(1-methylimidazol-2-yl)ketone (bik): structure, magnetic properties, and catalytic oxidation studies.

    Science.gov (United States)

    Bruijnincx, Pieter C A; Buurmans, Inge L C; Huang, Yuxing; Juhász, Gergely; Viciano-Chumillas, Marta; Quesada, Manuel; Reedijk, Jan; Lutz, Martin; Spek, Anthony L; Münck, Eckard; Bominaar, Emile L; Klein Gebbink, Robertus J M

    2011-10-03

    The newly synthesized dinuclear complex [Fe(III)(2)(μ-OH)(2)(bik)(4)](NO(3))(4) (1) (bik, bis(1-methylimidazol-2-yl)ketone) shows rather short Fe···Fe (3.0723(6) Å) and Fe-O distances (1.941(2)/1.949(2) Å) compared to other unsupported Fe(III)(2)(μ-OH)(2) complexes. The bridging hydroxide groups of 1 are strongly hydrogen-bonded to a nitrate anion. The (57)Fe isomer shift (δ = 0.45 mm s(-1)) and quadrupole splitting (ΔE(Q) = 0.26 mm s(-1)) obtained from Mössbauer spectroscopy are consistent with the presence of two identical high-spin iron(III) sites. Variable-temperature magnetic susceptibility studies revealed antiferromagnetic exchange (J = 35.9 cm(-1) and H = JS(1)·S(2)) of the metal ions. The optimized DFT geometry of the cation of 1 in the gas phase agrees well with the crystal structure, but both the Fe···Fe and Fe-OH distances are overestimated (3.281 and 2.034 Å, respectively). The agreement in these parameters improves dramatically (3.074 and 1.966 Å) when the hydrogen-bonded nitrate groups are included, reducing the value calculated for J by 35%. Spontaneous reduction of 1 was observed in methanol, yielding a blue [Fe(II)(bik)(3)](2+) species. Variable-temperature magnetic susceptibility measurements of [Fe(II)(bik)(3)](OTf)(2) (2) revealed spin-crossover behavior. Thermal hysteresis was observed with 2, due to a loss of cocrystallized solvent molecules, as monitored by thermogravimetric analysis. The hysteresis disappears once the solvent is fully depleted by thermal cycling. [Fe(II)(bik)(3)](OTf)(2) (2) catalyzes the oxidation of alkanes with t-BuOOH. High selectivity for tertiary C-H bond oxidation was observed with adamantane (3°/2° value of 29.6); low alcohol/ketone ratios in cyclohexane and ethylbenzene oxidation, a strong dependence of total turnover number on the presence of O(2), and a low retention of configuration in cis-1,2-dimethylcyclohexane oxidation were observed. Stereoselective oxidation of olefins with dihydrogen

  18. Isolation and estimation of the 'aromatic' naphthenic acid content of an oil sands process-affected water extract.

    Science.gov (United States)

    Jones, David; West, Charles E; Scarlett, Alan G; Frank, Richard A; Rowland, Steven J

    2012-07-20

    The naphthenic acids of oil sands process-affected water (OSPW) are said to be important toxicants. The major acids are stated to have alicyclic structures and recently, numerous of these have been identified, but some evidence suggests 'aromatic' acids are also present. The proportions of such acids have not been reported because they exist in so-called supercomplex mixtures with the alicyclic species. Their contribution to the toxicity of OSPW, if any, is therefore unknown. Here we report the use of multidimensional comprehensive gas chromatography-mass spectrometry (GC×GC-MS) with polar first dimension and non-polar second dimension GC columns and argentation solid phase extraction, to separate methyl esters of the acids of an OSPW supercomplex, into distinct fractions. A major fraction (ca 70%) was shown to contain acids (methyl esters) previously identified as alicyclic species. Authentic adamantane acid methyl esters were shown to chromatograph in this fraction. This fraction was isolated by argentation solid phase extraction (SPE) by elution with hexane. GC-MS and GC×GC-MS confirmed this to be the major fraction in the original supercomplex containing alicyclic acids (methyl esters). A second fraction shown to contain monoaromatic acids (methyl esters) by GC×GC-MS was unexpectedly abundant (ca 30% relative to the acyclic acids). The naphtheno-aromatic dehydroabietic acid was confirmed by co-injection with an authentic compound and several acids previously tentatively identified as naphtheno-monoaromatics were present. This fraction was isolated by argentation SPE by elution with more polar 5% diethyl ether in hexane. GC-MS and GC×GC-MS confirmed that the fraction represented a significant proportion of the original supercomplex. A further fraction, eluting from the argentation SPE column with more 5% diethyl ether in hexane in the same retention volume as authentic methyl naphthoate, contained, in addition to some of the second fraction, a third, much

  19. D2d(23)-C84 versus Sc2C2@D2d(23)-C84: Impact of Endohedral Sc2C2 Doping on Chemical Reactivity in the Photolysis of Diazirine.

    Science.gov (United States)

    Yamada, Michio; Tanabe, Yukiko; Dang, Jing-Shuang; Sato, Satoru; Mizorogi, Naomi; Hachiya, Makoto; Suzuki, Mitsuaki; Abe, Tsuneyuki; Kurihara, Hiroki; Maeda, Yutaka; Zhao, Xiang; Lian, Yongfu; Nagase, Shigeru; Akasaka, Takeshi

    2016-12-21

    We compared the chemical reactivity of D2d(23)-C84 and that of Sc2C2@D2d(23)-C84, both having the same carbon cage geometry, in the photolysis of 2-adamantane-2,3'-[3H]-diazirine, to clarify metal-atom doping effects on the chemical reactivity of the carbon cage. Experimental and computational studies have revealed that the chemical reactivity of the D2d(23)-C84 carbon cage is altered drastically by endohedral Sc2C2 doping. The reaction of empty D2d(23)-C84 with the diazirine under photoirradiation yields two adamantylidene (Ad) adducts. NMR spectroscopic studies revealed that the major Ad monoadduct (C84(Ad)-A) has a fulleroid structure and that the minor Ad monoadduct (C84(Ad)-B) has a methanofullerene structure. The latter was also characterized using X-ray crystallography. C84(Ad)-A is stable under photoirradiation, but it interconverted to C84(Ad)-B by heating at 80 °C. In contrast, the reaction of endohedral Sc2C2@D2d(23)-C84 with diazirine under photoirradiation affords four Ad monoadducts (Sc2C2@C84(Ad)-A, Sc2C2@C84(Ad)-B, Sc2C2@C84(Ad)-C, and Sc2C2@C84(Ad)-D). The structure of Sc2C2@C84(Ad)-C was characterized using X-ray crystallography. Thermal interconversion of Sc2C2@C84(Ad)-A and Sc2C2@C84(Ad)-B to Sc2C2@C84(Ad)-C was also observed. The reaction mechanisms of the Ad addition and thermal interconversion were elucidated from theoretical calculations. Calculation results suggest that C84(Ad)-B and Sc2C2@C84(Ad)-C are thermodynamically favorable products. Their different chemical reactivities derive from Sc2C2 doping, which raises the HOMO and LUMO levels of the D2d(23)-C84 carbon cage.

  20. Supramolecular Nanoparticles for Molecular Diagnostics and Therapeutics

    Science.gov (United States)

    Chen, Kuan-Ju

    Over the past decades, significant efforts have been devoted to explore the use of various nanoparticle-based systems in the field of nanomedicine, including molecular imaging and therapy. Supramolecular synthetic approaches have attracted lots of attention due to their flexibility, convenience, and modularity for producing nanoparticles. In this dissertation, the developmental story of our size-controllable supramolecular nanoparticles (SNPs) will be discussed, as well as their use in specific biomedical applications. To achieve the self-assembly of SNPs, the well-characterized molecular recognition system (i.e., cyclodextrin/adamantane recognition) was employed. The resulting SNPs, which were assembled from three molecular building blocks, possess incredible stability in various physiological conditions, reversible size-controllability and dynamic disassembly that were exploited for various in vitro and in vivo applications. An advantage of using the supramolecular approach is that it enables the convenient incorporation of functional ligands onto SNP surface that confers functionality ( e.g., targeting, cell penetration) to SNPs. We utilized SNPs for molecular imaging such as magnetic resonance imaging (MRI) and positron emission tomography (PET) by introducing reporter systems (i.e., radio-isotopes, MR contrast agents, and fluorophores) into SNPs. On the other hand, the incorporation of various payloads, including drugs, genes and proteins, into SNPs showed improved delivery performance and enhanced therapeutic efficacy for these therapeutic agents. Leveraging the powers of (i) a combinatorial synthetic approach based on supramolecular assembly and (ii) a digital microreactor, a rapid developmental pathway was developed that is capable of screening SNP candidates for the ideal structural and functional properties that deliver optimal performance. Moreover, SNP-based theranostic delivery systems that combine reporter systems and therapeutic payloads into a

  1. Biomimetic oxidation studies. 5. Mechanistic aspects of alkane functionalization with Fe, Fe sub 2 O, and Fe sub 4 O sub 2 complexes in the presence of hydrogen peroxide

    Energy Technology Data Exchange (ETDEWEB)

    Fish, R.H.; Konings, M.S.; Oberhausen, K.J.; Fong, R.H.; Yu, W.M. (Univ. of California, Berkeley (United States)); Christou, G.; Vincent, J.B.; Coggin, D.K. (Indiana Univ., Bloomington (United States)); Buchanan, R.M. (Univ. of Louisville, KY (United States))

    1991-07-24

    The biomimetic oxidation reactions of a variety of hydrocarbons with iron complexes, Fe{sub 2}O(OAc){sub 2}(bpy){sub 2}Cl{sub 2} (1), Fe{sub 4}O{sub 2}(OAc){sub 7}(bpy){sub 2}(ClO{sub 4}) (2) Fe{sub 2}O(OAc)(tmima){sub 2}(ClO{sub 4}){sub 3} (3) (tmima = tris((methylimadazol-2-yl)methyl)amine), and Fe(ClO{sub 4}){sub 3}{times}6H{sub 2}O (4), using H{sub 2}O{sub 2}/O{sub 2} as the oxidant were studied. Functionalization of cyclohexane gave cyclohexanol (CyOH) and cylcohexanone (CyONE). The presence of an oxidizing intermediate was suggested by iodometric titration in the functionalization of cyclohexane with complexes 1-4 and H{sub 2}O{sub 2}. This intermediate was isolated from the reaction mixture and identified by {sup 13}C NMR as cyclohexyl hydroperoxide (CyOOH) as compared to an independently prepared sample. The decomposition of CyOOH by 1-4 and H{sub 2}O{sub 2} gave CyOH/CyONE ratios of 0.7, 0.9, 0.7, and 2.8, respectively, in the ranges observed in the actual cyclohexane oxidation reactions. These hydrocarbon oxidation reactions were also inhibited by 2,4,6-tri-tert-butylphenol. Reactions run under a sweep of argon gave mmol of product/mmol of Fe complex 0-31% of the normal values. These results are consistent with a free-radical chain mechanism in which an initially formed cyclohexyl radical is trapped by oxygen gas to give a cyclohexyl peroxyl radical, which abstracts a hydrogen atom to give CyOOH and carry the chain. The tertiary hydrogen of adamantane was selectively abstracted with complexes 1-4 to obtain normalized C{sup 3}/C{sup 2} values of 3.5, 3.3, 3.4 and 5.6, respectively. Functionalization of methane, ethane, and propane was also observed. 22 refs., 1 fig., 2 tabs.

  2. Controlling adsorbate interactions for advanced chemical patterning

    Science.gov (United States)

    Saavedra Garcia, Hector M.

    -situ esterification results in the creation of subtle chemical and structural defects that promote molecular exchange reactions to go to completion. The complementary hydrolysis reaction can be employed to quench the reacted monolayer, significantly hindering further displacement. The generality of reversible lability was tested by applying the in-situ esterification reaction to the structurally distinct carboxyl-functionalized molecule 3-mercapto-1-adamantane-carboxylic acid. In addition to the studies of manipulating the interactions in self-assembled monolayers, materials with tunable optical and electronic properties were fabricated using atomic clusters as building blocks. It was shown that materials assembled from the same cluster motif, in this case As3-7 , can result in materials with band gaps that vary predictably between 1.09 to 2.08 eV. The size and highest occupied molecular orbital of the alkali metal counter-cation used in the assembly was shown to affect the band gap of the cluster-assembled solids. Furthermore, the dimensionality of the cluster-cluster interactions played a crucial role in determining the resulting properties. These results demonstrate how complex surface assemblies, or novel solid materials, can be fabricated by manipulating the interactions between the individual components within the assemblies, paving the way for the fabrication of next-generation devices and materials.

  3. Preparation and Immunomodulatory Properties of Modified Peptidoglycan Fragments

    Directory of Open Access Journals (Sweden)

    Tomić, S.

    2013-01-01

    Full Text Available Immunostimulators, known also as adjuvants, are added to vaccines to accelerate, extend or amplify the specific immune reaction to a specific antigen. One well known class of immuno- modulating compounds is based on muramylpeptides which are fragments of peptidoglycans, natural polymers that build up the cell wall of bacteria. Muramyldipeptide, N-acetyl- muramyl-L-alanyl-D-isoglutamine (MDP, Fig. 1 is the smallest structural unit of the peptidoglycan monomer (PGM, Fig. 2 which shows immunostimulating activity. PGM isolated from Brevibacterium divaricatum, acts in itself as an effective adjuvant, and several derivatives were prepared to study the possible influence of different substituents on the immunomodulatory activity. Thus, lipophilic derivativestert-butyloxycarbonyl-L-tyrosyl-PGM and (adamant- 1-ylacetyl-PGM (Fig. 3 were prepared and their activities studied. They were also shown to be good substrates for N-acetylmuramyl-L-alanine amidase from human serum (Scheme 1 which specifically hydrolyzes the lactylamide bond. MDP which is an integral part of PGM and proven to be an effective adjuvant was further synthetically modified and obtained derivatives tested as possible immunomodulators. Romutide (MDP-Lys(L18, approved by Food and Drug Administration (FDA, and mifamurtide (L-MTP-PE, approved by European Medicines Agency (EMA, highlight among many other MDP derivatives (Fig. 4. Since N-acetylglucosamine in the structure of MDP is not essential for the immunostimulating effect, desmuramyldipeptides (Fig. 5 with different acyl groups at N-terminus of L-Ala-D-isoGln dipeptide were prepared. In ada mantyl desmuramyldipeptides such as adamantylamide dipeptide (Fig 6, adamantyl tripeptides (Fig. 7 and desmuramylpeptides with (adamant-1-ylcarboxyamido group (Fig. 8, lipophilic adamantane moiety is bound to the dipeptide part. Binding of some specific sugars to immune active substances may help their targeted delivery. An example is mannose which

  4. Dynamics of biomolecules, ligand binding & biological functions

    Science.gov (United States)

    Yi, Myunggi

    validation of Gouy-Chapman (GC) theory to charged lipid membranes, a test of GC theory by MD simulations has been elusive. Here we demonstrate that the ion distributions at different salt concentrations in anionic lipid bilayer systems agree well with GC predictions using MD simulations. Na+ ions are adsorbed to the bilayer through favorable interactions with carbonyls and hydroxyls, reducing the surface charge density by 72.5%. The interactions of amantadine, an antiinfluenza A drug, with DMPC bilayers are investigated by an MD simulation and by solid-state NMR. The MD simulation results and NMR data demonstrate that amantadine is located within the interfacial region with upward orientation and interacts with the lipid headgroup and glycerol backbone, while the adamantane group of amantadine interacts with the glycerol backbone and much of fatty acyl chain, as it wraps underneath of the drug. The lipid headgroup orientation is influenced by the drug as well. The recent prevalence of amantadine-resistant mutants makes a development of new drug urgent. The mechanism of inhibition of M2 proton channel in influenza virus A by amantadine is investigated. In the absence of high resolution structure, we model the apo and drug bound forms based on NMR structures. MD simulations demonstrate that channel pore is blocked by a primary gate formed by Trp41 helped by His37 and a secondary gate formed by Val27. The blockage by the secondary gate is extended by the drug bound just below the gate, resulting in a broken water wire throughout the simulation, suggesting a novel role of Val27 in the inhibition by amantadine. Recent X-ray structure validates the simulation results.

  5. Controllable drug uptake and nongenomic response through estrogen-anchored cyclodextrin drug complex

    Directory of Open Access Journals (Sweden)

    Yin JJ

    2015-07-01

    Full Text Available Juan-Juan Yin,1,2 Stepan P Shumyak,2 Christopher Burgess,2 Zhi-Wei Zhou,2 Zhi-Xu He,3 Xue-Ji Zhang,4 Shu-Ting Pan,2,5 Tian-Xin Yang,6 Wei Duan,7 Jia-Xuan Qiu,5 Shu-Feng Zhou21Xiaolan People’s Hospital, Southern Medical University, Zhongshan, Guangdong, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, 4Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, 5Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 6Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, USA; 7School of Medicine, Deakin University, Waurn Ponds, VIC, AustraliaAbstract: Breast cancer is a leading killer of women worldwide. Cyclodextrin-based estrogen receptor-targeting drug-delivery systems represent a promising direction in cancer therapy but have rarely been investigated. To seek new targeting therapies for membrane estrogen receptor-positive breast cancer, an estrogen-anchored cyclodextrin encapsulating a doxorubicin derivative Ada-DOX (CDE1-Ada-DOX has been synthesized and evaluated in human breast cancer MCF-7 cells. First, we synthesized estrone-conjugated cyclodextrin (CDE1, which formed the complex CDE1-Ada-DOX via molecular recognition with the derivative adamantane-doxorubicin (Ada-DOX (Kd=1,617 M-1. The structure of the targeting vector CDE1 was fully characterized using 1H- and 13C-nuclear magnetic resonance, mass spectrometry, and electron microscopy. CDE1-Ada-DOX showed two-phase drug-release kinetics with much slower release than Ada-DOX. The

  6. Selective homogeneous and heterogeneous catalytic conversion of methanol/dimethyl ether to triptane.

    Science.gov (United States)

    Hazari, Nilay; Iglesia, Enrique; Labinger, Jay A; Simonetti, Dante A

    2012-04-17

    reaction, the methylative homologation of alkanes, offers the possibility of upgrading low-value refinery byproducts such as isobutane and isopentane to more valuable gasoline components. With the addition of adamantane, a hydride transfer catalyst that promotes activation of alkanes, both systems effectively catalyze the reaction of methanol/DME with lighter alkanes to produce heavier ones. This transformation has the further advantage of providing stoichiometric balance, whereas the stoichiometry for conversion of methanol/DME to alkanes is deficient in hydrogen and requires rejection of excess carbon in the form of carbon-rich arenes, which lowers the overall yield of desired products. Alternatively, other molecules can serve as sacrificial sources of hydrogen atoms: H(2) on heterogeneous catalysts modified by cations that activate it, and H(3)PO(2) or H(3)PO(3) on homogeneous catalysts. We have interpreted most of the features of these potentially useful reactions at a highly detailed level of mechanistic understanding, and we show that this interpretation applies equally to these two widely disparate types of catalysts. Such approaches can play a key role in developing and optimizing the catalysts that are needed to solve our energy problems.

  7. Vladimir Prelog i Zavod za organsku kemiju

    Directory of Open Access Journals (Sweden)

    Jakopčić, K.

    2007-03-01

    -operation from the small but prosperous pharmaceutical company "Kaštel" in Zagreb. On behalf of the agreement, Prelog and his department obtained funds to fit up the laboratory and to start very prosperous research in the synthesis and studies of pharmaceutically interesting compounds. With his assistants, students and other collaborators, Prelog started research of cinchona bark alkaloids, preferentially oriented to the synthesis of quinine. For example, Prelog's method of double intramolecular alkylation to synthetize the quinuclidine moiety of quinine was patented by "Kaštel". With R. Seiwerth he developed the first useful synthesis of adamantane. Prelog's group started research in the field of sulphonamides and commercial success of "Streptazole" stimulated the development of the research laboratories within "Kaštel". The collaboration in the research continued in fields of other chemotherapeutics, analeptics, spasmolitics, barbiturates etc. Within the period 1935-1941, Prelog published 48 scientific papers and 8 patents. In less than seven years, his results enormously influenced the entire organic chemistry in Zagreb till nowadays. Under the confused and uncertain circumstances caused by the beginning of World War II, Prelog left Zagreb in 1941 and continued his extraordinary scientific career at the ETH in Zürich.During the war (1942-1945 the tuition and the Department were run by Dr. Rativoj Seiwerth, former collaborator and first assistant to V. Prelog. In almost unbelievable conditions, the young assistant, then assistant professor (since January 1943, R. Seiwerth fully succeeded in continuing most activities founded by Professor Prelog. After the war (1945, R. Seiwerth was forced to resign. Nevertheless, soon after R. Seiwerth continued his research work, firstly in the Institute for Industrial Research in Zagreb (1946-1952, and later in the Research Institute of "Pliva" in Zagreb. He retired in 1980.In post-war conditions (1945/46, the activity of the Technical

  8. PREFACE: IUMRS-ICA 2008 Symposium, Sessions 'X. Applications of Synchrotron Radiation and Neutron Beam to Soft Matter Science' and 'Y. Frontier of Polymeric Nano-Soft-Materials - Precision Polymer Synthesis, Self-assembling and Their Functionalization'

    Science.gov (United States)

    Takahara, Atsushi; Kawahara, Seiichi

    2009-09-01

    aimed to provide recent advances in polymer synthesis, self-assembling processes and morphologies, and functionalization of nano-soft-materials in order to initiate mutual and collaborative research interest that is essential to develop revolutionarily new nano-soft-materials in the decades ahead. Four Keynote lectures, 15 invited talks and 30 posters presented important new discoveries in polymeric nano-soft-materials, precision polymer synthesis, self-assembling and their functionalization. As for the precision polymer synthesis, the latest results were provided for studies on synthesis of polyrotaxane with movable graft chains, organic-inorganic hybridization of polymers, supra-molecular coordination assembly of conjugated polymers, precision polymerization of adamantane-containing monomers, production of high density polymer brush and synthesis of rod coil type polymer. The state-of-the-art results were introduced for the formation of nano-helical-structure of block copolymer containing asymmetric carbon atoms, self-assembling of block copolymers under the electric field, self-assembling of liquid crystalline elastomers, preparation of nano cylinder template films and mesoscopic simulation of phase transition of polymers and so forth. Moreover, recent advantages of three-dimensional electron microtomography and scanning force microscopy were proposed for analyses of nano-structures and properties of polymeric multi-component systems. Syntheses, properties and functions of slide-ring-gel, organic-inorganic hybrid hydrogels, hydrogel nano-particles, liquid-crystalline gels, the self-oscillating gels, and double network gels attracted participants' attention. Modifications of naturally occurring polymeric materials with supercritical carbon dioxide were introduced as a novel technology. Some of the attractive topics are presented in this issue. We are grateful to all the speakers and participants for valuable contributions and active discussions. Organizing committee

  9. Design, synthesis, and characterization of new phosphazene related materials, and study the structure property correlations

    Science.gov (United States)

    Tian, Zhicheng

    various gelation rates depending on the polymer structures and the concentrations. The rheological measurements of the supramolecular hydrogels indicate a fast gelation process and flowable character under a large stain. Chapter 4 outlines the preparation of a number of amphiphilic diblock copolymers based on poly[bis(trifluoroethoxy)phosphazene] (TFE) as the hydrophobic block and poly(dimethylaminoethylmethacrylate) (PDMAEMA) as the hydrophilic block. The TFE block was synthesized first by the controlled living cationic polymerization of a phosphoranimine, followed by replacement of all the chlorine atoms using sodium trifluoroethoxide. To allow for the growth of the PDMAEMA block, 3-azidopropyl-2-bromo-2-methylpropanoate, an atom transfer radical polymerization (ATRP) initiator, was grafted onto the endcap of the TFE block via the 'click' reaction followed by the ATRP of 2-(dimethylamino)ethyl methacrylate (DMAEMA). Chapter 5 is a report on the design and assembly of polyphosphazene materials based on the non-covalent "host--guest" interactions either at the terminus of the polymeric main-chains or the pendant side-chains. The supramolecular interaction at the main chain terminus was used to produce amphiphilic palm-tree like pseudo-block copolymers via host-guest interactions between an adamantane end-functionalized polyphosphazene and a 4-armed beta-cyclodextrin (beta-CD) initiated poly[poly(ethylene glycol) methyl ether methacylate] branched-star type polymer. The formation of micelles of the obtained amphiphiles was analyzed by fluorescence technique, dynamic light scattering, transmission electron microscopy, and atomic force microscopy. Chapter 6 is an investigation of the influence of bulky fluoroalkoxy side groups on the properties of polyphosphazenes. A new series of mixed-substituent high polymeric poly(fluoroalkoxyphosphazenes) containing trifluoroethoxy and branched fluoroalkoxy side groups was synthesized and characterized by NMR and GPC methods. These