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Sample records for shape selective alkylation

  1. The Scarlet Letter of Alkylation: A Mini Review of Selective Alkylating Agents

    OpenAIRE

    Oronsky, Bryan T; Reid, Tony; Knox, Susan J; Scicinski, Jan J

    2012-01-01

    If there were a stigma scale for chemotherapy, alkylating agents would be ranked at the top of the list. The chemical term alkylation is associated with nonselective toxicity, an association that dates back to the use of nitrogen mustards during World War I as chemical warfare agents. That this stigma persists and extends to compounds that, through selectivity, attempt to “tame” the indiscriminate destructive potential of alkylation is the subject of this review. Selective alkylation, as it i...

  2. The scarlet letter of alkylation: a mini review of selective alkylating agents.

    Science.gov (United States)

    Oronsky, Bryan T; Reid, Tony; Knox, Susan J; Scicinski, Jan J

    2012-08-01

    If there were a stigma scale for chemotherapy, alkylating agents would be ranked at the top of the list. The chemical term alkylation is associated with nonselective toxicity, an association that dates back to the use of nitrogen mustards during World War I as chemical warfare agents. That this stigma persists and extends to compounds that, through selectivity, attempt to "tame" the indiscriminate destructive potential of alkylation is the subject of this review. Selective alkylation, as it is referred to herein, constitutes an extremely nascent and dynamic field in oncology. The pharmacodynamic response to this selective strategy depends on a delicate kinetic balance between specificity and the rate and extent of binding. Three representative compounds are presented: RRx-001, 3-bromopyruvate, and TH-302. The main impetus for the development of these compounds has been the avoidance of the serious complications of traditional alkylating agents; therefore, it is the thesis of this review that they should not experience stigma by association.

  3. Bis(trialkylsilyl) peroxides as alkylating agents in the copper-catalyzed selective mono-N-alkylation of primary amides.

    Science.gov (United States)

    Sakamoto, Ryu; Sakurai, Shunya; Maruoka, Keiji

    2017-06-13

    The copper-catalyzed selective mono-N-alkylation of primary amides with bis(trialkylsilyl) peroxides as alkylating agents was reported. The results of a mechanistic study suggest that this reaction should proceed via a free radical process that includes the generation of alkyl radicals from bis(trialkylsilyl) peroxides.

  4. The Scarlet Letter of Alkylation: A Mini Review of Selective Alkylating Agents

    Science.gov (United States)

    Oronsky, Bryan T; Reid, Tony; Knox, Susan J; Scicinski, Jan J

    2012-01-01

    If there were a stigma scale for chemotherapy, alkylating agents would be ranked at the top of the list. The chemical term alkylation is associated with nonselective toxicity, an association that dates back to the use of nitrogen mustards during World War I as chemical warfare agents. That this stigma persists and extends to compounds that, through selectivity, attempt to “tame” the indiscriminate destructive potential of alkylation is the subject of this review. Selective alkylation, as it is referred to herein, constitutes an extremely nascent and dynamic field in oncology. The pharmacodynamic response to this selective strategy depends on a delicate kinetic balance between specificity and the rate and extent of binding. Three representative compounds are presented: RRx-001, 3-bromopyruvate, and TH-302. The main impetus for the development of these compounds has been the avoidance of the serious complications of traditional alkylating agents; therefore, it is the thesis of this review that they should not experience stigma by association. PMID:22937173

  5. Determination of Selected Perfluorinated Alkyl Acids in ...

    Science.gov (United States)

    The 1996 amendments to the Safe Drinking Water Act (SDWA) required EPA to establish a Contaminant Candidate List (CCL), that contains a list of drinking water contaminants that the Agency will consider for future regulation. EPA must make a regulatory determination on a minimum of five contaminants every five years. The first CCL was published in 1998, and updates were anticipated every five years thereafter. One of the key pieces of information that must be available in order to make a regulatory determination is nationwide occurrence data for the chemical contaminants under consideration. Historically, EPA has collected the necessary occurrence data under its Unregulated Contaminant Monitoring Regulations (UCMR). Under the UCMR, monitoring is conducted at selected drinking water utilities for specific contaminants of interest. The chemical analyses are usually performed by the utilities or by commercial laboratories. To meet the requirements of monitoring under the UCMR program, the analytical methods developed should be specific, sensitive, and practical enough for application in commercial laboratories. This task will focus on the development of analytical methods for chemicals identified on future CCLs or emerging contaminants not yet listed on the CCL. These methods will be used for the collection of occurrence data under future UCMRs. The objective of this research effort is to develop analytical methods to be used to measure the occurrence of

  6. Dependence of micelle size and shape on detergent alkyl chain length and head group.

    Directory of Open Access Journals (Sweden)

    Ryan C Oliver

    Full Text Available Micelle-forming detergents provide an amphipathic environment that can mimic lipid bilayers and are important tools for solubilizing membrane proteins for functional and structural investigations in vitro. However, the formation of a soluble protein-detergent complex (PDC currently relies on empirical screening of detergents, and a stable and functional PDC is often not obtained. To provide a foundation for systematic comparisons between the properties of the detergent micelle and the resulting PDC, a comprehensive set of detergents commonly used for membrane protein studies are systematically investigated. Using small-angle X-ray scattering (SAXS, micelle shapes and sizes are determined for phosphocholines with 10, 12, and 14 alkyl carbons, glucosides with 8, 9, and 10 alkyl carbons, maltosides with 8, 10, and 12 alkyl carbons, and lysophosphatidyl glycerols with 14 and 16 alkyl carbons. The SAXS profiles are well described by two-component ellipsoid models, with an electron rich outer shell corresponding to the detergent head groups and a less electron dense hydrophobic core composed of the alkyl chains. The minor axis of the elliptical micelle core from these models is constrained by the length of the alkyl chain, and increases by 1.2-1.5 Å per carbon addition to the alkyl chain. The major elliptical axis also increases with chain length; however, the ellipticity remains approximately constant for each detergent series. In addition, the aggregation number of these detergents increases by ∼16 monomers per micelle for each alkyl carbon added. The data provide a comprehensive view of the determinants of micelle shape and size and provide a baseline for correlating micelle properties with protein-detergent interactions.

  7. Alkylsilyl Peroxides as Alkylating Agents in the Copper-Catalyzed Selective Mono-N-Alkylation of Primary Amides and Arylamines.

    Science.gov (United States)

    Sakamoto, Ryu; Sakurai, Shunya; Maruoka, Keiji

    2017-07-06

    The copper-catalyzed selective mono-N-alkylation of primary amides or arylamines using alkylsilyl peroxides as alkylating agents is reported. The reaction proceeds under mild reaction conditions and exhibits a broad substrate scope with respect to the alkylsilyl peroxides, as well as to the primary amides and arylamines. Mechanistic studies suggest that the present reaction should proceed through a free-radical process that includes alkyl radicals generated from the alkylsilyl peroxides. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. C2-Selective Branched Alkylation of Benzimidazoles by Rhodium(I)-Catalyzed C-H Activation.

    Science.gov (United States)

    Tran, Gaël; Confair, Danielle; Hesp, Kevin D; Mascitti, Vincent; Ellman, Jonathan A

    2017-09-01

    Herein, we report a Rh(I)/bisphosphine/K 3 PO 4 catalytic system allowing for the first time the selective branched C-H alkylation of benzimidazoles with Michael acceptors. Branched alkylation with N,N-dimethyl acrylamide was successfully applied to the alkylation of a broad range of benzimidazoles incorporating a variety of N-substituents and with both electron-rich and -poor functionality displayed at different sites of the arene. Moreover, the introduction of a quaternary carbon was achieved by alkylation with ethyl methacrylate. The method was also shown to be applicable to the C2-selective branched alkylation of azabenzimidazoles.

  9. Selective Hydrodeoxygenation of Alkyl Lactates to Alkyl Propionates with Fe-based Bimetallic Supported Catalysts

    DEFF Research Database (Denmark)

    Khokarale, Santosh Govind; He, Jian; Schill, Leonhard

    2018-01-01

    Hydrodeoxygenation (HDO) of methyl lactate (ML) to methyl propionate (MP) was performed with various base-metal supported catalysts. A high yield of 77 % MP was obtained with bimetallic Fe-Ni/ZrO2 in methanol at 220 °C and 50 bar H2 . A synergistic effect of Ni increased the yield of MP...... of the material. Interestingly, it was observed that Fe-Ni/ZrO2 also effectively catalyzed methanol reforming to produce H2 in situ, followed by HDO of ML, yielding 60 % MP at 220 °C with 50 bar N2 instead of H2. Fe-Ni/ZrO2 also catalyzed HDO of other short-chain alkyl lactates to the corresponding alkyl...

  10. Selective alkylation of T–T mismatched DNA using vinyldiaminotriazine–acridine conjugate

    Science.gov (United States)

    Onizuka, Kazumitsu; Usami, Akira; Yamaoki, Yudai; Kobayashi, Tomohito; Hazemi, Madoka E; Chikuni, Tomoko; Sato, Norihiro; Sasaki, Kaname; Katahira, Masato

    2018-01-01

    Abstract The alkylation of the specific higher-order nucleic acid structures is of great significance in order to control its function and gene expression. In this report, we have described the T–T mismatch selective alkylation with a vinyldiaminotriazine (VDAT)–acridine conjugate. The alkylation selectively proceeded at the N3 position of thymidine on the T–T mismatch. Interestingly, the alkylated thymidine induced base flipping of the complementary base in the duplex. In a model experiment for the alkylation of the CTG repeats DNA which causes myotonic dystrophy type 1 (DM1), the observed reaction rate for one alkylation increased in proportion to the number of T–T mismatches. In addition, we showed that primer extension reactions with DNA polymerase and transcription with RNA polymerase were stopped by the alkylation. The alkylation of the repeat DNA will efficiently work for the inhibition of replication and transcription reactions. These functions of the VDAT–acridine conjugate would be useful as a new biochemical tool for the study of CTG repeats and may provide a new strategy for the molecular therapy of DM1. PMID:29309639

  11. Selective alkylation of T-T mismatched DNA using vinyldiaminotriazine-acridine conjugate.

    Science.gov (United States)

    Onizuka, Kazumitsu; Usami, Akira; Yamaoki, Yudai; Kobayashi, Tomohito; Hazemi, Madoka E; Chikuni, Tomoko; Sato, Norihiro; Sasaki, Kaname; Katahira, Masato; Nagatsugi, Fumi

    2018-02-16

    The alkylation of the specific higher-order nucleic acid structures is of great significance in order to control its function and gene expression. In this report, we have described the T-T mismatch selective alkylation with a vinyldiaminotriazine (VDAT)-acridine conjugate. The alkylation selectively proceeded at the N3 position of thymidine on the T-T mismatch. Interestingly, the alkylated thymidine induced base flipping of the complementary base in the duplex. In a model experiment for the alkylation of the CTG repeats DNA which causes myotonic dystrophy type 1 (DM1), the observed reaction rate for one alkylation increased in proportion to the number of T-T mismatches. In addition, we showed that primer extension reactions with DNA polymerase and transcription with RNA polymerase were stopped by the alkylation. The alkylation of the repeat DNA will efficiently work for the inhibition of replication and transcription reactions. These functions of the VDAT-acridine conjugate would be useful as a new biochemical tool for the study of CTG repeats and may provide a new strategy for the molecular therapy of DM1.

  12. Selectivity of alkyl radical formation from branched alkanes studied by electron spin resonance and electron spin echo spectroscopy

    International Nuclear Information System (INIS)

    Tsuneki, Ichikawa; Hiroshi, Yoshida

    1992-01-01

    Alkyl radicals generated from branched alkanes by γ radiation are being measuring by electron spin resonance and electron spin echo spectroscopy. This research is being conducted to determine the mechanism of selective alkyl radical formation in low-temperature solids

  13. Selective Hydrodeoxygenation of Alkyl Lactates to Alkyl Propionates with Fe-based Bimetallic Supported Catalysts.

    Science.gov (United States)

    Khokarale, Santosh Govind; He, Jian; Schill, Leonhard; Yang, Song; Riisager, Anders; Saravanamurugan, Shunmugavel

    2018-02-22

    Hydrodeoxygenation (HDO) of methyl lactate (ML) to methyl propionate (MP) was performed with various base-metal supported catalysts. A high yield of 77 % MP was obtained with bimetallic Fe-Ni/ZrO 2 in methanol at 220 °C and 50 bar H 2 . A synergistic effect of Ni increased the yield of MP significantly when using Fe-Ni/ZrO 2 instead of Fe/ZrO 2 alone. Moreover, the ZrO 2 support contributed to improve the yield as a phase transition of ZrO 2 from tetragonal to monoclinic occurred after metal doping giving rise to fine dispersion of the Fe and Ni on the ZrO 2 , resulting in a higher catalytic activity of the material. Interestingly, it was observed that Fe-Ni/ZrO 2 also effectively catalyzed methanol reforming to produce H 2 in situ, followed by HDO of ML, yielding 60 % MP at 220 °C with 50 bar N 2 instead of H 2 . Fe-Ni/ZrO 2 also catalyzed HDO of other short-chain alkyl lactates to the corresponding alkyl propionates in high yields around 70 %. No loss of activity of Fe-Ni/ZrO 2 occurred in five consecutive reaction runs demonstrating the high durability of the catalyst system. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Selective sp3 C-H alkylation via polarity-match-based cross-coupling.

    Science.gov (United States)

    Le, Chip; Liang, Yufan; Evans, Ryan W; Li, Ximing; MacMillan, David W C

    2017-07-06

    The functionalization of carbon-hydrogen (C-H) bonds is one of the most attractive strategies for molecular construction in organic chemistry. The hydrogen atom is considered to be an ideal coupling handle, owing to its relative abundance in organic molecules and its availability for functionalization at almost any stage in a synthetic sequence. Although many C-H functionalization reactions involve C(sp 3 )-C(sp 2 ) coupling, there is a growing demand for C-H alkylation reactions, wherein sp 3 C-H bonds are replaced with sp 3 C-alkyl groups. Here we describe a polarity-match-based selective sp 3 C-H alkylation via the combination of photoredox, nickel and hydrogen-atom transfer catalysis. This methodology simultaneously uses three catalytic cycles to achieve hydridic C-H bond abstraction (enabled by polarity matching), alkyl halide oxidative addition, and reductive elimination to enable alkyl-alkyl fragment coupling. The sp 3 C-H alkylation is highly selective for the α-C-H of amines, ethers and sulphides, which are commonly found in pharmaceutically relevant architectures. This cross-coupling protocol should enable broad synthetic applications in de novo synthesis and late-stage functionalization chemistry.

  15. Natural and bioremediated selective degradation of polycyclic aromatic alkyl isomers in oil-contaminated soils

    International Nuclear Information System (INIS)

    Sauer, T.C.; McCarthy, K.; Uhler, A.; Porta, A.

    1995-01-01

    In studies where 2- to 6-ring polycyclic aromatic hydrocarbons (PAHs) are determined as part of characterizing released oil constituents in environmental samples, the changes in composition of PAHs from weathering (e.g., evaporation, dissolution) and biodegradation are most often represented by PAH alkyl homologue distributions. Concentrations of PAH alkyl groups are the sum of individual PAH isomers of similar carbon number; such as for C2-naphthalenes, the C2 alkyl group consists of dimethyl and ethyl substitutions on the parent naphthalene. In weathering and degradation studies, the changes in relative concentration of the individual isomers within an alkyl group are rarely reported. In a field study of oiled soils, the authors looked at the selective losses, for a period of a year, of individual PAH alkyl isomers that occur both naturally by weathering processes and through the use of bioremediation technology. Results showed that decreases in alkyl group concentrations were not always represented by similar losses of each isomer in the alkyl group, but were often due to the preferential or selective loss of certain isomers in the group

  16. Selective sp3 C-H alkylation via polarity-match-based cross-coupling

    Science.gov (United States)

    Le, Chip; Liang, Yufan; Evans, Ryan W.; Li, Ximing; MacMillan, David W. C.

    2017-07-01

    The functionalization of carbon-hydrogen (C-H) bonds is one of the most attractive strategies for molecular construction in organic chemistry. The hydrogen atom is considered to be an ideal coupling handle, owing to its relative abundance in organic molecules and its availability for functionalization at almost any stage in a synthetic sequence. Although many C-H functionalization reactions involve C(sp3)-C(sp2) coupling, there is a growing demand for C-H alkylation reactions, wherein sp3 C-H bonds are replaced with sp3 C-alkyl groups. Here we describe a polarity-match-based selective sp3 C-H alkylation via the combination of photoredox, nickel and hydrogen-atom transfer catalysis. This methodology simultaneously uses three catalytic cycles to achieve hydridic C-H bond abstraction (enabled by polarity matching), alkyl halide oxidative addition, and reductive elimination to enable alkyl-alkyl fragment coupling. The sp3 C-H alkylation is highly selective for the α-C-H of amines, ethers and sulphides, which are commonly found in pharmaceutically relevant architectures. This cross-coupling protocol should enable broad synthetic applications in de novo synthesis and late-stage functionalization chemistry.

  17. Selective sp3 C–H alkylation via polarity-match-based cross-coupling

    Science.gov (United States)

    Le, Chip; Liang, Yufan; Evans, Ryan W.; Li, Ximing; MacMillan, David W. C.

    2017-01-01

    The functionalization of carbon–hydrogen (C–H) bonds is one of the most attractive strategies for molecular construction in organic chemistry. The hydrogen atom is considered to be an ideal coupling handle, owing to its relative abundance in organic molecules and its availability for functionalization at almost any stage in a synthetic sequence1. Although many C–H functionalization reactions involve C(sp3)–C(sp2) coupling, there is a growing demand for C–H alkylation reactions, wherein sp3 C–H bonds are replaced with sp3 C–alkyl groups. Here we describe a polarity-match-based selective sp3 C–H alkylation via the combination of photoredox, nickel and hydrogen-atom transfer catalysis. This methodology simultaneously uses three catalytic cycles to achieve hydridic C–H bond abstraction (enabled by polarity matching), alkyl halide oxidative addition, and reductive elimination to enable alkyl–alkyl fragment coupling. The sp3 C–H alkylation is highly selective for the α-C–H of amines, ethers and sulphides, which are commonly found in pharmaceutically relevant architectures. This cross-coupling protocol should enable broad synthetic applications in de novo synthesis and late-stage functionalization chemistry. PMID:28636596

  18. Effects of alkylating agents on dopamine D(3) receptors in rat brain: selective protection by dopamine.

    Science.gov (United States)

    Zhang, K; Weiss, N T; Tarazi, F I; Kula, N S; Baldessarini, R J

    1999-11-13

    Dopamine D(3) receptors are structurally highly homologous to other D(2)-like dopamine receptors, but differ from them pharmacologically. D(3) receptors are notably resistant to alkylation by 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), which readily alkylates D(2) receptors. We compared EEDQ with N-(p-isothiocyanatophenethyl)spiperone (NIPS), a selective D(2)-like receptor alkylating agent, for effects on D(3) and D(2) receptors in rat brain using autoradiographic analysis. Neither agent occluded D(3) receptors in vivo at doses that produced substantial blockade of D(2) receptors, even after catecholamine-depleting pretreatments. In vitro, however, D(3) receptors were readily alkylated by both NIPS (IC(50)=40 nM) and EEDQ (IC(50)=12 microM). These effects on D(3) sites were blocked by nM concentrations of dopamine, whereas microM concentrations were required to protect D(2) receptors from the alkylating agents. The findings are consistent with the view that alkylation of D(3) receptors in vivo is prevented by its high affinity for even minor concentrations of endogenous dopamine.

  19. A powerful selection assay for mixture libraries of DNA alkylating agents.

    Science.gov (United States)

    Ham, Young-Wan; Boger, Dale L

    2004-08-04

    A simple and powerful selection assay that permits the separation (rpHPLC), quantitation (ELSD), and identification (ESI-MS) of thermally released adenine adducts derived from duocarmycin analogues is detailed that can establish the most effective DNA alkylating agents in synthetic combinatorial mixtures.

  20. SHAPE selection (SHAPES) enrich for RNA structure signal in SHAPE sequencing-based probing data

    DEFF Research Database (Denmark)

    Poulsen, Line Dahl; Kielpinski, Lukasz Jan; Salama, Sofie R

    2015-01-01

    transcriptase. Here, we introduce a SHAPE Selection (SHAPES) reagent, N-propanone isatoic anhydride (NPIA), which retains the ability of SHAPE reagents to accurately probe RNA structure, but also allows covalent coupling between the SHAPES reagent and a biotin molecule. We demonstrate that SHAPES...

  1. Selective Alkylation of C-Rich Bulge Motifs in Nucleic Acids by Quinone Methide Derivatives.

    Science.gov (United States)

    Lönnberg, Tuomas; Hutchinson, Mark; Rokita, Steven

    2015-09-07

    A quinone methide precursor featuring a bis-cyclen anchoring moiety has been synthesized and its capacity to alkylate oligonucleotide targets quantified in the presence and absence of divalent metal ions (Zn(2+) , Ni(2+) and Cd(2+) ). The oligonucleotides were designed for testing the sequence and secondary structure specificity of the reaction. Gel electrophoretic analysis revealed predominant alkylation of C-rich bulges, regardless of the presence of divalent metal ions or even the bis-cyclen anchor. This C-selectivity appears to be an intrinsic property of the quinone methide electrophile as reflected by its reaction with an equimolar mixture of the 2'-deoxynucleosides. Only dA-N1 and dC-N3 alkylation products were detected initially and only the dC adduct persisted for detection under conditions of the gel electrophoretic analysis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Sequence-selective single-molecule alkylation with a pyrrole-imidazole polyamide visualized in a DNA nanoscaffold.

    Science.gov (United States)

    Yoshidome, Tomofumi; Endo, Masayuki; Kashiwazaki, Gengo; Hidaka, Kumi; Bando, Toshikazu; Sugiyama, Hiroshi

    2012-03-14

    We demonstrate a novel strategy for visualizing sequence-selective alkylation of target double-stranded DNA (dsDNA) using a synthetic pyrrole-imidazole (PI) polyamide in a designed DNA origami scaffold. Doubly functionalized PI polyamide was designed by introduction of an alkylating agent 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) and biotin for sequence-selective alkylation at the target sequence and subsequent streptavidin labeling, respectively. Selective alkylation of the target site in the substrate DNA was observed by analysis using sequencing gel electrophoresis. For the single-molecule observation of the alkylation by functionalized PI polyamide using atomic force microscopy (AFM), the target position in the dsDNA (∼200 base pairs) was alkylated and then visualized by labeling with streptavidin. Newly designed DNA origami scaffold named "five-well DNA frame" carrying five different dsDNA sequences in its cavities was used for the detailed analysis of the sequence-selectivity and alkylation. The 64-mer dsDNAs were introduced to five individual wells, in which target sequence AGTXCCA/TGGYACT (XY = AT, TA, GC, CG) was employed as fully matched (X = G) and one-base mismatched (X = A, T, C) sequences. The fully matched sequence was alkylated with 88% selectivity over other mismatched sequences. In addition, the PI polyamide failed to attach to the target sequence lacking the alkylation site after washing and streptavidin treatment. Therefore, the PI polyamide discriminated the one mismatched nucleotide at the single-molecule level, and alkylation anchored the PI polyamide to the target dsDNA.

  3. Sequence selectivity of azinomycin B in DNA alkylation and cross-linking: a QM/MM study.

    Science.gov (United States)

    Senthilnathan, Dhurairajan; Kalaiselvan, Anbarasan; Venuvanalingam, Ponnambalam

    2013-01-01

    Azinomycin B--a well-known antitumor drug--forms cross-links with DNA through alkylation of purine bases and blocks tumor cell growth. This reaction has been modeled using the ONIOM (B3LYP/6-31+g(d):UFF) method to understand the mechanism and sequence selectivity. ONIOM results have been checked for reliability by comparing them with full quantum mechanics calculations for selected paths. Calculations reveal that, among the purine bases, guanine is more reactive and is alkylated by aziridine ring through the C10 position, followed by alkylation of the epoxide ring through the C21 position of Azinomycin B. While the mono alkylation is controlled kinetically, bis-alkylation is controlled thermodynamically. Solvent effects were included using polarized-continuum-model calculations and no significant change from gas phase results was observed.

  4. Selective solvation extraction of gold from alkaline cyanide solution by alkyl phosphorus esters

    Energy Technology Data Exchange (ETDEWEB)

    Miller, J.D.; Wan, R.Y.; Mooiman, M.B.; Sibrell, P.L.

    1987-01-01

    Research efforts have shown that solvation extraction of gold from alkaline cyanide solution is possible by alkyl phosphorus esters. Both tributyl phosphate (TBP) and dibutyl butyl phosphonate (DBBP) appear to be effective extractants for gold and exhibit high loading capacities exceeding 30 gpl. Selective solvation extraction of gold from alkaline cyanide solution can be achieved with selectivity factors relative to other cyanoanions as high as 1000 under certain circumstances. Variables influencing the selectivity such as ionic strength, temperature, and extractant structure, are discussed in terms of the extraction chemistry, which seems to involve the solvation of a M dot, dot, dot Au(CN)2 ion pair.

  5. Transcriptional blockages in a cell-free system by sequence-selective DNA alkylating agents.

    Science.gov (United States)

    Ferguson, L R; Liu, A P; Denny, W A; Cullinane, C; Talarico, T; Phillips, D R

    2000-04-14

    There is considerable interest in DNA sequence-selective DNA-binding drugs as potential inhibitors of gene expression. Five compounds with distinctly different base pair specificities were compared in their effects on the formation and elongation of the transcription complex from the lac UV5 promoter in a cell-free system. All were tested at drug levels which killed 90% of cells in a clonogenic survival assay. Cisplatin, a selective alkylator at purine residues, inhibited transcription, decreasing the full-length transcript, and causing blockage at a number of GG or AG sequences, making it probable that intrastrand crosslinks are the blocking lesions. A cyclopropylindoline known to be an A-specific alkylator also inhibited transcription, with blocks at adenines. The aniline mustard chlorambucil, that targets primarily G but also A sequences, was also effective in blocking the formation of full-length transcripts. It produced transcription blocks either at, or one base prior to, AA or GG sequences, suggesting that intrastrand crosslinks could again be involved. The non-alkylating DNA minor groove binder Hoechst 33342 (a bisbenzimidazole) blocked formation of the full-length transcript, but without creating specific blockage sites. A bisbenzimidazole-linked aniline mustard analogue was a more effective transcription inhibitor than either chlorambucil or Hoechst 33342, with different blockage sites occurring immediately as compared with 2 h after incubation. The blockages were either immediately prior to AA or GG residues, or four to five base pairs prior to such sites, a pattern not predicted from in vitro DNA-binding studies. Minor groove DNA-binding ligands are of particular interest as inhibitors of gene expression, since they have the potential ability to bind selectively to long sequences of DNA. The results suggest that the bisbenzimidazole-linked mustard does cause alkylation and transcription blockage at novel DNA sites. in addition to sites characteristic of

  6. Selective N-alkylation of amines using nitriles under hydrogenation conditions: facile synthesis of secondary and tertiary amines.

    Science.gov (United States)

    Ikawa, Takashi; Fujita, Yuki; Mizusaki, Tomoteru; Betsuin, Sae; Takamatsu, Haruki; Maegawa, Tomohiro; Monguchi, Yasunari; Sajiki, Hironao

    2012-01-14

    Nitriles were found to be highly effective alkylating reagents for the selective N-alkylation of amines under catalytic hydrogenation conditions. For the aromatic primary amines, the corresponding secondary amines were selectively obtained under Pd/C-catalyzed hydrogenation conditions. Although the use of electron poor aromatic amines or bulky nitriles showed a lower reactivity toward the reductive alkylation, the addition of NH(4)OAc enhanced the reactivity to give secondary aromatic amines in good to excellent yields. Under the same reaction conditions, aromatic nitro compounds instead of the aromatic primary amines could be directly transformed into secondary amines via a domino reaction involving the one-pot hydrogenation of the nitro group and the reductive alkylation of the amines. While aliphatic amines were effectively converted to the corresponding tertiary amines under Pd/C-catalyzed conditions, Rh/C was a highly effective catalyst for the N-monoalkylation of aliphatic primary amines without over-alkylation to the tertiary amines. Furthermore, the combination of the Rh/C-catalyzed N-monoalkylation of the aliphatic primary amines and additional Pd/C-catalyzed alkylation of the resulting secondary aliphatic amines could selectively prepare aliphatic tertiary amines possessing three different alkyl groups. According to the mechanistic studies, it seems reasonable to conclude that nitriles were reduced to aldimines before the nucleophilic attack of the amine during the first step of the reaction.

  7. Catalyst-free dehydrative α-alkylation of ketones with alcohols: green and selective autocatalyzed synthesis of alcohols and ketones.

    Science.gov (United States)

    Xu, Qing; Chen, Jianhui; Tian, Haiwen; Yuan, Xueqin; Li, Shuangyan; Zhou, Chongkuan; Liu, Jianping

    2014-01-03

    Direct dehydrative α-alkylation reactions of ketones with alcohols are now realized under simple, practical, and green conditions without using external catalysts. These catalyst-free autocatalyzed alkylation methods can efficiently afford useful alkylated ketone or alcohol products in a one-pot manner and on a large scale by CC bond formation of the in situ generated intermediates with subsequent controllable and selective Meerwein-Pondorf-Verley-Oppenauer-type redox processes. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Site-directed alkylation of multiple opioid receptors. I. Binding selectivity

    International Nuclear Information System (INIS)

    James, I.F.; Goldstein, A.

    1984-01-01

    A method for measuring and expressing the binding selectivity of ligands for mu, delta, and kappa opioid binding sites is reported. Radioligands are used that are partially selective for these sites in combination with membrane preparations enriched in each site. Enrichment was obtained by treatment of membranes with the alkylating agent beta-chlornaltrexamine in the presence of appropriate protecting ligands. After enrichment for mu receptors, [ 3 H] dihydromorphine bound to a single type of site as judged by the slope of competition binding curves. After enrichment for delta or kappa receptors, binding sites for [ 3 H] [D-Ala2, D-Leu5]enkephalin and [3H]ethylketocyclazocine, respectively, were still not homogeneous. There were residual mu sites in delta-enriched membranes but no evidence for residual mu or delta sites in kappa-enriched membranes were found. This method was used to identify ligands that are highly selective for each of the three types of sites

  9. Selection on spur shape in Impatiens capensis.

    Science.gov (United States)

    Young, Helen J

    2008-06-01

    Rapid speciation within some plant families has been attributed to the evolution of floral spurs and to the effect of spur length on plant reproductive success. The flowers of Impatiens capensis (jewelweed) possess a long, curved spur in which nectar is produced and stored. Spur length and curvature varies among plants within one population. Here I document that spur shape is variable in natural populations, variation within plants is less than variation among plants, and spur shape is correlated with components of female and male reproductive success. The apparent natural selection is weakly directional in 1 of 2 years, with greatest seed production and pollen removal occurring in flowers with the greatest spur curvature. Bee pollinator visit length is longest at flowers with highly curved spurs, and they leave less nectar in these spurs than in flowers with straighter spurs. Spur angle evolution may be limited, at least in part, by opposing selection by nectar-robbers who prefer to visit flowers with greater spur curvature. Other factors that might contribute to the maintenance of spur angle variation are temporal variation in the strength of selection and potential genetic correlations of spur shape with other traits under selection.

  10. Mitsunobu mischief: Neighbor-directed histidine N(π)–alkylation provides access to peptides containing selectively functionalized imidazolium heterocycles

    Science.gov (United States)

    Qian, Wen-Jian

    2015-01-01

    There are few methodologies that yield peptides containing His residues with selective N(π), N(π)-bis-alkylated imidazole rings. We have found that, under certain conditions, on-resin Mitsunobu coupling of alcohols with peptides having a N(π)-alkylated His residue results in selective and high-yield alkylation of the imidazole N(π) nitrogen. The reaction requires the presence of a proximal phosphoric, carboxylic or sulfonic acid, and proceeds through an apparent intramolecular mechanism involving Mitsunobu intermediates. These transformations have particular application to phosphopeptides, where “charge masking” of one phosphoryl anionic charge by the cationic histidine imidazolium ion is now possible. This chemistry opens selective access to peptides containing differentially functionalized imidazolium heterocycles, which provide access to new classes of peptides and peptide mimetics. PMID:25739367

  11. 4-Alkylated homoibotenic acid (HIBO) analogues: versatile pharmacological agents with diverse selectivity profiles towards metabotropic and ionotropic glutamate receptor subtypes

    DEFF Research Database (Denmark)

    Madsen, Ulf; Pickering, Darryl S; Nielsen, Birgitte

    2005-01-01

    4-Alkylated analogues of homoibotenic acid (HIBO) have previously shown high potency and selectivity at ionotropic and metabotropic glutamic acid receptor (iGluR and mGluR) subtypes. Compounds with different selectivity profiles are valuable pharmacological tools for neuropharmacological studies...

  12. Active sites in the alkylation of toluene with methanol : a study by selective acid-base poisoning

    NARCIS (Netherlands)

    Borgna, A.; Sepulveda, J.; Magni, S.I.; Apesteguia, C.R.

    2004-01-01

    Selective acid–base poisoning of the alkylation of toluene with methanol was studied over alkali and alkaline-earth exchanged Y zeolites. Surface acid–base properties of the samples were determined by infrared spectroscopy using carbon dioxide and pyridine as probe molecules. Selective poisoning

  13. Dual platinum and pyrrolidine catalysis in the direct alkylation of allylic alcohols: selective synthesis of monoallylation products.

    Science.gov (United States)

    Shibuya, Ryozo; Lin, Lu; Nakahara, Yasuhito; Mashima, Kazushi; Ohshima, Takashi

    2014-04-22

    A dual platinum- and pyrrolidine-catalyzed direct allylic alkylation of allylic alcohols with various active methylene compounds to produce products with high monoallylation selectivity was developed. The use of pyrrolidine and acetic acid was essential, not only for preventing undesirable side reactions, but also for obtaining high monoallylation selectivity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Photogeneration and reactivity of naphthoquinone methides as purine selective DNA alkylating agents.

    Science.gov (United States)

    Verga, Daniela; Nadai, Matteo; Doria, Filippo; Percivalle, Claudia; Di Antonio, Marco; Palumbo, Manlio; Richter, Sara N; Freccero, Mauro

    2010-10-20

    A one-step protecting-group-free synthesis of both 6-hydroxy-naphthalene-2-carbaldehyde and the bifunctional binaphthalenyl derivative afforded 6-hydroxymethylnaphthalen-2-ol, 6-methylaminomethyl-naphthalen-2-ol, [(2-hydroxy-3-naphthyl)methyl]trimethyl ammonium iodide, and a small library of bifunctional binol analogues in good yields. Irradiation of naphthol quaternary ammonium salt and binol-derivatives (X = OH, NHR, NMe(3)(+), OCOCH(3), and L-proline) at 310 and 360 nm resulted in the photogeneration of the 2,6-naphthoquinone-6-methide (NQM) and binol quinone methide analogues (BQMs) by a water-mediated excited-state proton transfer (ESPT). The hydration, the mono- and bis-alkylation reactions of morpholine and 2-ethanethiol, as N and S prototype nucleophiles, by the transient NQM (λ(max) 310, 330 nm) and BQMs (λ(max) 360 nm) were investigated in water by product distribution analysis and laser flash photolysis (LFP). Both the photogeneration and the reactivity of NQM and BQMs exhibited striking differences. BQMs were at least 2 orders of magnitude more reactive than NQM, and they were generated much more efficiently from a greater variety of photoprecursors including the hydroxymethyl, quaternary ammonium salt and several binol-amino acids. On the contrary, the only efficient precursor of NQM was the quaternary ammonium salt. All water-soluble BQM precursors were further investigated for their ability to alkylate and cross-link plasmid DNA and oligonucleotides by gel electrophoresis: the BQMs were more efficient than the isomeric o-BQM (binol quinone methide analogue of 2,3-naphthoquinone-3-methide). Sequence analysis by gel electrophoresis, HPLC, and MS showed that the alkylation occurred at purines, with a preference for guanine. In particular, a BQM was able to alkylate N7 of guanines resulting in depurination at the oligonucleotide level, and ribose loss at the nucleotide level. The photoreactivity of BQM precursors translated into photocytotoxic and

  15. Efficient and selective N-alkylation of amines with alcohols catalysed by manganese pincer complexes

    Science.gov (United States)

    Elangovan, Saravanakumar; Neumann, Jacob; Sortais, Jean-Baptiste; Junge, Kathrin; Darcel, Christophe; Beller, Matthias

    2016-01-01

    Borrowing hydrogen (or hydrogen autotransfer) reactions represent straightforward and sustainable C–N bond-forming processes. In general, precious metal-based catalysts are employed for this effective transformation. In recent years, the use of earth abundant and cheap non-noble metal catalysts for this process attracted considerable attention in the scientific community. Here we show that the selective N-alkylation of amines with alcohols can be catalysed by defined PNP manganese pincer complexes. A variety of substituted anilines are monoalkylated with different (hetero)aromatic and aliphatic alcohols even in the presence of other sensitive reducible functional groups. As a special highlight, we report the chemoselective monomethylation of primary amines using methanol under mild conditions. PMID:27708259

  16. Investigation of J-shaped dose-responses induced by exposure to the alkylating agent N-methyl-N-nitrosourea.

    Science.gov (United States)

    Chapman, Katherine E; Hoffmann, George R; Doak, Shareen H; Jenkins, Gareth J S

    2017-07-01

    Hormesis is defined as a biphasic dose-response where biological effects of low doses of a stressor demonstrate the opposite effect to high-dose effects of the same stressor. Hormetic, or J-shaped, dose-response relationships are relatively rarely observed in toxicology, resulting in a limited understanding and even some skepticism of the concept. Low dose-response studies for genotoxicity endpoints have been performed at Swansea University for over a decade. However, no statistically significant decreases below control genotoxicity levels have been detected until recently. A hormetic-style dose-response following a 24h exposure to the alkylating agent N-methyl-N-nitrosourea (MNU) was observed in a previous study for HPRT mutagenesis in the human lymphoblastoid cell line AHH-1. A second recent study demonstrated a J-shaped dose-response for the induction of micronuclei by MNU in a 24h treatment in a similar test system. Following mechanistic investigations, it was hypothesized that p53 may be responsible for the observed hormetic phenomenon. As genotoxic carcinogens are a major causative factor of many cancers, consideration of hormesis in carcinogenesis could be important in safety assessment. The data examined here offer possible insights into hormesis, including its estimated prevalence, underlying mechanisms and lack of generalizability. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Effect of solid phase on the selectivity of alkyl radical formation by gamma-irradiation of branched alkanes

    International Nuclear Information System (INIS)

    Koizumi, Hitoshi; Hashino, Masatoshi; Ichikawa, Tsuneki; Yoshida, Hiroshi

    1992-01-01

    ESR and electron spin echo measurements of alkyl radicals generated by γ-irradiation of glassy and crystalline branched alkanes C 10 ∼ C 13 have been carried out to elucidate the effect of molecular structure and solid phase on the selectivity of alkyl radical formation. Alkyl radicals generated and stabilized at 77 K in the glassy alkanes are secondary penultimate radicals. Tertiary radicals and secondary radicals other than the penultimate one are not generated either by hydrogen abstraction or from ionized or excited molecules. In the crystalline alkanes, however, a small amount of secondary internal radicals are generated in addition to the predominant formation of the secondary penultimate radicals. It is concluded that the detachment of C-H hydrogen preferentially takes place at the location where the motion of carbon atoms assisting the detachment of the C-H hydrogen easily occurs. (author)

  18. Rh(III-Catalyzed, Highly Selectively Direct C–H Alkylation of Indoles with Diazo Compounds

    Directory of Open Access Journals (Sweden)

    Kang Wan

    2016-06-01

    Full Text Available Rh(III-catalyzed regioselective alkylation of indoles with diazo compounds as a highly efficient and atom-economic protocol for the synthesis of alkyl substituted indoles has been developed. The reaction could proceed under mild conditions and afford a series of desired products in good to excellent yields.

  19. Characterization and Design of Zeolite Catalysts Solid Acidity, Shape Selectivity and Loading Properties

    CERN Document Server

    Niwa, Miki; Okumura, Kazu

    2010-01-01

    Zeolites are microporous, aluminosilicate minerals commonly used as commercial adsorbents. Zeolite-based catalysts are used by industrial chemical companies in the interconversion of hydrocarbons and the alkylation of aromatic compounds. The current book deals with the characterization of specific properties of Zeolites and calculations for the design of catalysts. Measurements and utilization of solid acidity, shape selectivity, and loading properties, that are three prominent properties of a Zeolite catalyst, are treated in detail. These features concern chemical vapor deposition of silica, shape selectivity, loading properties, solid activity, Brønsted or Lewis character, ammonia temperature programmed desorption, control of the pore-opening size by chemical vapor deposition of silica and XAFS analysis of metals being highly dispersed inside and outside a framework.

  20. Quinone methides tethered to naphthalene diimides as selective G-quadruplex alkylating agents.

    Science.gov (United States)

    Di Antonio, Marco; Doria, Filippo; Richter, Sara N; Bertipaglia, Carolina; Mella, Mariella; Sissi, Claudia; Palumbo, Manlio; Freccero, Mauro

    2009-09-16

    We have developed novel G-quadruplex (G-4) ligand/alkylating hybrid structures, tethering the naphthalene diimide moiety to quaternary ammonium salts of Mannich bases, as quinone-methide precursors, activatable by mild thermal digestion (40 degrees C). The bis-substituted naphthalene diimides were efficiently synthesized, and their reactivity as activatable bis-alkylating agents was investigated in the presence of thiols and amines in aqueous buffered solutions. The electrophilic intermediate, quinone-methide, involved in the alkylation process was trapped, in the presence of ethyl vinyl ether, in a hetero Diels-Alder [4 + 2] cycloaddition reaction, yielding a substituted 2-ethoxychroman. The DNA recognition and alkylation properties of these new derivatives were investigated by gel electrophoresis, circular dichroism, and enzymatic assays. The alkylation process occurred preferentially on the G-4 structure in comparison to other DNA conformations. By dissecting reversible recognition and alkylation events, we found that the reversible process is a prerequisite to DNA alkylation, which in turn reinforces the G-quadruplex structural rearrangement.

  1. Ir/Sn dual-reagent catalysis towards highly selective alkylation of ...

    Indian Academy of Sciences (India)

    Wintec

    Organometallic; bimetallic; catalysis; alkylation; benzyl alcohol; iridium, tin. 1. Introduction ... cording to our proposal, the oxidative addition of tin(IV) halides across a ..... 33. 4. Conclusion. In summary, we have demonstrated here an Ir/Sn.

  2. Comb-shaped single ion conductors based on polyacrylate ethers and lithium alkyl sulfonate

    International Nuclear Information System (INIS)

    Sun Xiaoguang; Hou Jun; Kerr, John B.

    2005-01-01

    Comb-shaped single ion conductors have been synthesized by (1) sulfonation of small molecule chloroethyleneglycols, which, after ion exchange to the Li + salt were then converted to the acrylate by reaction with acryloyl chloride and copolymerized with polyethylene glycol monomethyl ether acrylate (Mn = 454, n = 8) (PAE 8 -co-E 3 SO 3 Li); (2) sulfonation of chloride end groups grafted on to prepolymers of polyacrylate ethers (PAE 8 -g-E n SO 3 Li, n = 2, 3). The highest conductivity at 25 deg. C of 2.0 x 10 -7 S cm -1 was obtained for the PAE 8 -co-E 3 SO 3 Li with a salt concentration of EO/Li = 40. The conductivity of PAE 8 -g-E 3 SO 3 Li is lower than that of PAE 8 -co-E 3 SO 3 Li at similar salt concentrations, which is related to the incomplete sulfonation of the grafted polymer that leads to a lower concentration of Li + . The addition of 50 wt.% of plasticizer, PC/EMC (1/1, v/v), to PAE 8 -g-E 2 SO 3 Li increases the ambient conductivity by three orders of magnitude, which is due to the increased ion mobility in a micro-liquid environment and an increase concentration of free ions as a result of the higher dielectric constant of the solvent. A symmetrical Li/Li cell with an electrolyte membrane consisting of 75 wt.% PC/EMC (1/1, v/v) was cycled at a current density of 100 μA cm -2 at 85 deg. C. The cycling profile showed no concentration polarization after a break-in period during the first few cycles, which was apparently due to reaction of the solvent at the lithium metal surface that reacted with lithium metal to form a stable SEI layer

  3. Selective Incorporation of Nitrile-Based Infrared Probes into Proteins via Cysteine Alkylation

    Science.gov (United States)

    Jo, Hyunil; Culik, Robert M.; Korendovych, Ivan V.; DeGrado, William F.; Gai, Feng

    2010-01-01

    The nitrile stretching vibration is increasingly used as a sensitive infrared probe of local protein environments. However, site-specific incorporation of a nitrile moiety into proteins is difficult. Here we show that various aromatic nitriles can be easily incorporated into peptides and proteins via either thiol alkylation or arylation reaction. PMID:21077670

  4. Selective Incorporation of Nitrile-Based Infrared Probes into Proteins via Cysteine Alkylation

    OpenAIRE

    Jo, Hyunil; Culik, Robert M.; Korendovych, Ivan V.; DeGrado, William F.; Gai, Feng

    2010-01-01

    The nitrile stretching vibration is increasingly used as a sensitive infrared probe of local protein environments. However, site-specific incorporation of a nitrile moiety into proteins is difficult. Here we show that various aromatic nitriles can be easily incorporated into peptides and proteins via either thiol alkylation or arylation reaction.

  5. Selective synthesis of linear alkylbenzene by alkylation of benzene with 1-dodecene over desilicated zeolites

    Czech Academy of Sciences Publication Activity Database

    Aslam, W.; Siddiqui, M. A. B.; Jermy, B. R.; Aitani, A.; Čejka, Jiří; Al-Khattaf, S.

    2014-01-01

    Roč. 227, MAY 2014 (2014), s. 187-197 ISSN 0920-5861 R&D Projects: GA ČR GBP106/12/G015 Institutional support: RVO:61388955 Keywords : zeolites * benzene alkylation * long-chain olefin Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.893, year: 2014

  6. Clean and Selective Catalytic C-H alkylation of Alkenes with Environmental friendly Alcohols

    KAUST Repository

    Poater, Albert; Vummaleti, Sai V. C.; Polo, Alfonso; Cavallo, Luigi

    2016-01-01

    Bearing the alkylation of alkene substrates using alcohol as solvent, catalysed by the cationic Ru-based catalyst [(C6H6)(PCy3)(CO)RuH]+, DFT calculations have been carried out to get mechanistic insights of such an environmental friendly reaction

  7. Does learning or instinct shape habitat selection?

    Directory of Open Access Journals (Sweden)

    Scott E Nielsen

    Full Text Available Habitat selection is an important behavioural process widely studied for its population-level effects. Models of habitat selection are, however, often fit without a mechanistic consideration. Here, we investigated whether patterns in habitat selection result from instinct or learning for a population of grizzly bears (Ursus arctos in Alberta, Canada. We found that habitat selection and relatedness were positively correlated in female bears during the fall season, with a trend in the spring, but not during any season for males. This suggests that habitat selection is a learned behaviour because males do not participate in parental care: a genetically predetermined behaviour (instinct would have resulted in habitat selection and relatedness correlations for both sexes. Geographic distance and home range overlap among animals did not alter correlations indicating that dispersal and spatial autocorrelation had little effect on the observed trends. These results suggest that habitat selection in grizzly bears are partly learned from their mothers, which could have implications for the translocation of wildlife to novel environments.

  8. Syn-Selective Synthesis of β-Branched α-Amino Acids by Alkylation of Glycine-Derived Imines with Secondary Sulfonates.

    Science.gov (United States)

    Lou, Sha; McKenna, Grace M; Tymonko, Steven A; Ramirez, Antonio; Benkovics, Tamas; Conlon, David A; González-Bobes, Francisco

    2015-10-16

    A syn-selective synthesis of β-branched α-amino acids has been developed based on the alkylation of glycine imine esters with secondary sulfonates. The potassium counterion for the enolate, the solvent, and the leaving group on the electrophile were key levers to maximize the diasteroselectivity of the alkylation. The optimized conditions enabled a straightforward preparation of a number of β-branched α-amino acids that can be challenging to obtain.

  9. Modeling shape selection of buckled dielectric elastomers

    Science.gov (United States)

    Langham, Jacob; Bense, Hadrien; Barkley, Dwight

    2018-02-01

    A dielectric elastomer whose edges are held fixed will buckle, given a sufficiently applied voltage, resulting in a nontrivial out-of-plane deformation. We study this situation numerically using a nonlinear elastic model which decouples two of the principal electrostatic stresses acting on an elastomer: normal pressure due to the mutual attraction of oppositely charged electrodes and tangential shear ("fringing") due to repulsion of like charges at the electrode edges. These enter via physically simplified boundary conditions that are applied in a fixed reference domain using a nondimensional approach. The method is valid for small to moderate strains and is straightforward to implement in a generic nonlinear elasticity code. We validate the model by directly comparing the simulated equilibrium shapes with the experiment. For circular electrodes which buckle axisymetrically, the shape of the deflection profile is captured. Annular electrodes of different widths produce azimuthal ripples with wavelengths that match our simulations. In this case, it is essential to compute multiple equilibria because the first model solution obtained by the nonlinear solver (Newton's method) is often not the energetically favored state. We address this using a numerical technique known as "deflation." Finally, we observe the large number of different solutions that may be obtained for the case of a long rectangular strip.

  10. Clean and Selective Catalytic C-H alkylation of Alkenes with Environmental friendly Alcohols

    KAUST Repository

    Poater, Albert

    2016-09-14

    Bearing the alkylation of alkene substrates using alcohol as solvent, catalysed by the cationic Ru-based catalyst [(C6H6)(PCy3)(CO)RuH]+, DFT calculations have been carried out to get mechanistic insights of such an environmental friendly reaction. Hard experimental conditions of Yi and coworkers [Science2011, 333, 1613] allow the formation of a C-C bond between indene and ethanol. The predicted mechanism suggests a cationic Ru-alkenyl species once two equivalents of indene interact releasing a molecule of indane subproduct. Then, oxidative addition of the Csingle bondO bond of alcohol to Ru-alkenyl species leads to Ru-alkenyl-alkyl species, followed by the reductive elimination process produces the desired alkylation product and a Ru-hydroxo complex. Finally, vinylic Csingle bondH activation and water elimination regenerates the Ru-alkenyl species. In this paper we present a full description of the complete reaction pathway along with possible alternative pathways, which are predicted to display higher upper barriers. Furthermore, the present study explains the possible reasons for the absence of undesired products such as indene dimer or hydroxylated indene in the experiments.

  11. Effect of ionic strength and cationic DNA affinity binders on the DNA sequence selective alkylation of guanine N7-positions by nitrogen mustards

    International Nuclear Information System (INIS)

    Hartley, J.A.; Forrow, S.M.; Souhami, R.L.

    1990-01-01

    Large variations in alkylation intensities exist among guanines in a DNA sequence following treatment with chemotherapeutic alkylating agents such as nitrogen mustards, and the substituent attached to the reactive group can impose a distinct sequence preference for reaction. In order to understand further the structural and electrostatic factors which determine the sequence selectivity of alkylation reactions, the effect of increase ionic strength, the intercalator ethidium bromide, AT-specific minor groove binders distamycin A and netropsin, and the polyamine spermine on guanine N7-alkylation by L-phenylalanine mustard (L-Pam), uracil mustard (UM), and quinacrine mustard (QM) was investigated with a modification of the guanine-specific chemical cleavage technique for DNA sequencing. The result differed with both the nitrogen mustard and the cationic agent used. The effect, which resulted in both enhancement and suppression of alkylation sites, was most striking in the case of netropsin and distamycin A, which differed from each other. DNA footprinting indicated that selective binding to AT sequences in the minor groove of DNA can have long-range effects on the alkylation pattern of DNA in the major groove

  12. Divergent Reactivity of Alkyl Aryl Sulfones with Bases: Selective Functionalization of ortho-Aryl and alpha-Alkyl Units Enabled by a Unique Carbanion Transmetalation

    Czech Academy of Sciences Publication Activity Database

    Řehová, Lucie; Císařová, I.; Jahn, Ullrich

    2014-01-01

    Roč. 2014, č. 7 (2014), s. 1461-1476 ISSN 1434-193X R&D Projects: GA ČR GAP207/11/1598 Institutional support: RVO:61388963 Keywords : sulfones * transmetalation * lithiation * deprotonation * alkylation * acidity Subject RIV: CC - Organic Chemistry Impact factor: 3.065, year: 2014

  13. Alkylation of phosphorothioated thrombin binding aptamers improves the selectivity of inhibition of tumor cell proliferation upon anticoagulation.

    Science.gov (United States)

    Yang, Xiantao; Zhu, Yuejie; Wang, Chao; Guan, Zhu; Zhang, Lihe; Yang, Zhenjun

    2017-07-01

    Recently, aptamers have been extensively researched for therapy and diagnostic applications. Thrombin-binding aptamer is a 15nt deoxyribonucleic acid screened by SELEX, it can specifically bind to thrombin and inhibit blood coagulation. Since it is also endowed with excellent antitumor activity, the intrinsic anticoagulation advantage converted to a main potential side effect for its further application in antiproliferative therapy. Site-specific alkylation was conducted through nucleophilic reaction of phosphorothioated TBAs using bromide reagents. Circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR) measurements were used to evaluate anticoagulation activity, and a CCK-8 assay was used to determine cell proliferation activity. The CD spectra of the modified TBAs were weakened, and their affinity for thrombin was dramatically reduced, as reflected by the K D values. On the other hand, their inhibition of A549 cells was retained. Incorporation of different alkyls apparently disrupted the binding of TBA to thrombin while maintaining the antitumor activity. A new modification strategy was established for the use of TBA as a more selective antitumor agent. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. A General Catalyst for Site-Selective C(sp(3))-H Bond Amination of Activated Secondary over Tertiary Alkyl C(sp(3))-H Bonds.

    Science.gov (United States)

    Scamp, Ryan J; Jirak, James G; Dolan, Nicholas S; Guzei, Ilia A; Schomaker, Jennifer M

    2016-06-17

    The discovery of transition metal complexes capable of promoting general, catalyst-controlled and selective carbon-hydrogen (C-H) bond amination of activated secondary C-H bonds over tertiary alkyl C(sp(3))-H bonds is challenging, as substrate control often dominates when reactive nitrene intermediates are involved. In this letter, we report the design of a new silver complex, [(Py5Me2)AgOTf]2, that displays general and good-to-excellent selectivity for nitrene insertion into propargylic, benzylic, and allylic C-H bonds over tertiary alkyl C(sp(3))-H bonds.

  15. Antimitotic antitumor agents: synthesis, structure-activity relationships, and biological characterization of N-aryl-N'-(2-chloroethyl)ureas as new selective alkylating agents.

    Science.gov (United States)

    Mounetou, E; Legault, J; Lacroix, J; C-Gaudreault, R

    2001-03-01

    A series of N-aryl-N'-(2-chloroethyl)ureas (CEUs) and derivatives were synthesized and evaluated for antiproliferative activity against a wide panel of tumor cell lines. Systematic structure--activity relationship (SAR) studies indicated that: (i) a branched alkyl chain or a halogen at the 4-position of the phenyl ring or a fluorenyl/indanyl group, (ii) an exocyclic urea function, and (iii) a N'-2-chloroethyl moiety were required to ensure significant cytotoxicity. Biological experiments, such as immunofluorescence microscopy, confirmed that these promising compounds alter the cytoskeleton by inducing microtubule depolymerization via selective alkylation of beta-tubulin. Subsequent evaluations demonstrated that potent CEUs were weak alkylators, were non-DNA-damaging agents, and did not interact with the thiol function of either glutathione or glutathione reductase. Therefore, CEUs are part of a new class of antimitotic agents. Finally, among the series of CEUs evaluated, compounds 12, 15, 16, and 27 were selected for further in vivo trials.

  16. Synthesis and evaluation of sequence-specific DNA alkylating agents: effect of alkylation subunits.

    Science.gov (United States)

    Shimizu, Tatsuhiko; Sasaki, Shunta; Minoshima, Masafumi; Shinohara, Ken-ichi; Bando, Toshikazu; Sugiyama, Hiroshi

    2006-01-01

    We have demonstrated that hairpin pyrrole (Py)- imidazole (Im) polyamide-CBI conjugates selectively alkylate predetermined sequences. In this study, we investigated the effect of alkylation subunits, for example conjugates 1-4 with three types of DNA alkylating units, and Py-Im polyamides with indole linker. Conjugate 3 and 4 selectively alkylated the predetermined sequences as described previously, while conjugates 1 and 2 alkylate at mismatched sites.

  17. Occurrence of selected perfluorinated alkyl acids in lunch meals served at school canteens in Italy and their relevance for children’s intake

    NARCIS (Netherlands)

    Dellatte, E.; Brambilla, G.; De Filippis, S.P.; Di Domenico, A.; Pulkrabova, J.; Eschauzier, C.; Klenow, S.; Heinemeyer, G.; de Voogt, P.

    2013-01-01

    Ready-to-eat servings may be more contaminated with perfluorinated alkyl acids (PFAAs) than the corresponding unprocessed foods due to the presence of PFAAs in and transfer from food contact materials (FCM) and cookware. Therefore, the presence of selected PFAAs in meals served weekly at lunch time

  18. On channel selection and shape co-existence

    International Nuclear Information System (INIS)

    Dracoulis, G.D.

    1993-08-01

    Ambivalence with respect to a favoured shape is emerging as a ubiquitous phenomenon in nuclei. Multiple minima in the nuclear potential well occur because of the delicate balance in nuclei between the long and short-range properties of the nuclear force and the contribution specific particle orbitals make in forcing the nucleus to a decision. Exploration of the dependence of the resulting shape co-existence on particle number and orbital is a prominent area of research. Experimental aspects of spectroscopy studies using heavy ion fusion, evaporation reactions and channel selection are discussed, with focus on shape co-existence in the light Os-Pt-Hg-Pb region. 42 refs., 8 figs

  19. Decarboxylative alkylation for site-selective bioconjugation of native proteins via oxidation potentials.

    Science.gov (United States)

    Bloom, Steven; Liu, Chun; Kölmel, Dominik K; Qiao, Jennifer X; Zhang, Yong; Poss, Michael A; Ewing, William R; MacMillan, David W C

    2018-02-01

    The advent of antibody-drug conjugates as pharmaceuticals has fuelled a need for reliable methods of site-selective protein modification that furnish homogeneous adducts. Although bioorthogonal methods that use engineered amino acids often provide an elegant solution to the question of selective functionalization, achieving homogeneity using native amino acids remains a challenge. Here, we explore visible-light-mediated single-electron transfer as a mechanism towards enabling site- and chemoselective bioconjugation. Specifically, we demonstrate the use of photoredox catalysis as a platform to selectivity wherein the discrepancy in oxidation potentials between internal versus C-terminal carboxylates can be exploited towards obtaining C-terminal functionalization exclusively. This oxidation potential-gated technology is amenable to endogenous peptides and has been successfully demonstrated on the protein insulin. As a fundamentally new approach to bioconjugation this methodology provides a blueprint toward the development of photoredox catalysis as a generic platform to target other redox-active side chains for native conjugation.

  20. Decarboxylative alkylation for site-selective bioconjugation of native proteins via oxidation potentials

    Science.gov (United States)

    Bloom, Steven; Liu, Chun; Kölmel, Dominik K.; Qiao, Jennifer X.; Zhang, Yong; Poss, Michael A.; Ewing, William R.; MacMillan, David W. C.

    2018-02-01

    The advent of antibody-drug conjugates as pharmaceuticals has fuelled a need for reliable methods of site-selective protein modification that furnish homogeneous adducts. Although bioorthogonal methods that use engineered amino acids often provide an elegant solution to the question of selective functionalization, achieving homogeneity using native amino acids remains a challenge. Here, we explore visible-light-mediated single-electron transfer as a mechanism towards enabling site- and chemoselective bioconjugation. Specifically, we demonstrate the use of photoredox catalysis as a platform to selectivity wherein the discrepancy in oxidation potentials between internal versus C-terminal carboxylates can be exploited towards obtaining C-terminal functionalization exclusively. This oxidation potential-gated technology is amenable to endogenous peptides and has been successfully demonstrated on the protein insulin. As a fundamentally new approach to bioconjugation this methodology provides a blueprint toward the development of photoredox catalysis as a generic platform to target other redox-active side chains for native conjugation.

  1. Non-covalent functionalization of carbon nanotubes: Controlling Chirality Selectivity via Alkyl Groups of Conjugated Co-Polymers

    Science.gov (United States)

    Weight, Braden; Gifford, Brendan; Kilina, Svetlana

    Carbon nanotubes (CNTs) play an important role in nanotechnology, including electronics, chemical sensors, and solar cells. Their electronic and optical properties depend on the size and geometry (chirality) of the nanotube. However, one main concern regarding nanotube application in optoelectronic devices is the difficulty of separating them based upon chirality after synthesis, as all known synthesis methods produce more than one chirality simultaneously. To get around this, one method is the functionalization of the CNTs via non-covalent bonding of co-polymers by wrapping them around the tube. We use force field simulations to explore the effects of various structural manipulations to the co-polymer 9,9-dialkylfluorenyl-2,7-diyl bipyridine (PFO-BPY) to find the preferential mechanisms of selective interactions between the PFO-BPY and CNTs of various chiralities. In particular, we focus on the effect of the branching in alkyl side-groups of PFO-BPY on their binding to the CNT surface. We have observed correlations between the side-group structures and their wrapping morphology on the CNT-Polymer interactions. Our calculations demonstrate that the branching in the position closest to the conjugated backboned results in the strongest interaction with all CNT. This research was supported by the National Science Foundation (CHE 1413614) and the Center for Computationally-Assisted Science and Technology at NDSU.

  2. Selection Shapes Transcriptional Logic and Regulatory Specialization in Genetic Networks.

    Science.gov (United States)

    Fogelmark, Karl; Peterson, Carsten; Troein, Carl

    2016-01-01

    Living organisms need to regulate their gene expression in response to environmental signals and internal cues. This is a computational task where genes act as logic gates that connect to form transcriptional networks, which are shaped at all scales by evolution. Large-scale mutations such as gene duplications and deletions add and remove network components, whereas smaller mutations alter the connections between them. Selection determines what mutations are accepted, but its importance for shaping the resulting networks has been debated. To investigate the effects of selection in the shaping of transcriptional networks, we derive transcriptional logic from a combinatorially powerful yet tractable model of the binding between DNA and transcription factors. By evolving the resulting networks based on their ability to function as either a simple decision system or a circadian clock, we obtain information on the regulation and logic rules encoded in functional transcriptional networks. Comparisons are made between networks evolved for different functions, as well as with structurally equivalent but non-functional (neutrally evolved) networks, and predictions are validated against the transcriptional network of E. coli. We find that the logic rules governing gene expression depend on the function performed by the network. Unlike the decision systems, the circadian clocks show strong cooperative binding and negative regulation, which achieves tight temporal control of gene expression. Furthermore, we find that transcription factors act preferentially as either activators or repressors, both when binding multiple sites for a single target gene and globally in the transcriptional networks. This separation into positive and negative regulators requires gene duplications, which highlights the interplay between mutation and selection in shaping the transcriptional networks.

  3. ENDOR with band-selective shaped inversion pulses

    Science.gov (United States)

    Tait, Claudia E.; Stoll, Stefan

    2017-04-01

    Electron Nuclear DOuble Resonance (ENDOR) is based on the measurement of nuclear transition frequencies through detection of changes in the polarization of electron transitions. In Davies ENDOR, the initial polarization is generated by a selective microwave inversion pulse. The rectangular inversion pulses typically used are characterized by a relatively low selectivity, with full inversion achieved only for a limited number of spin packets with small resonance offsets. With the introduction of pulse shaping to EPR, the rectangular inversion pulses can be replaced with shaped pulses with increased selectivity. Band-selective inversion pulses are characterized by almost rectangular inversion profiles, leading to full inversion for spin packets with resonance offsets within the pulse excitation bandwidth and leaving spin packets outside the excitation bandwidth largely unaffected. Here, we explore the consequences of using different band-selective amplitude-modulated pulses designed for NMR as the inversion pulse in ENDOR. We find an increased sensitivity for small hyperfine couplings compared to rectangular pulses of the same bandwidth. In echo-detected Davies-type ENDOR, finite Fourier series inversion pulses combine the advantages of increased absolute ENDOR sensitivity of short rectangular inversion pulses and increased sensitivity for small hyperfine couplings of long rectangular inversion pulses. The use of pulses with an almost rectangular frequency-domain profile also allows for increased control of the hyperfine contrast selectivity. At X-band, acquisition of echo transients as a function of radiofrequency and appropriate selection of integration windows during data processing allows efficient separation of contributions from weakly and strongly coupled nuclei in overlapping ENDOR spectra within a single experiment.

  4. Selection of genetically modified hematopoietic cells in vitro and in vivo using alkylating agent lysomustine.

    Science.gov (United States)

    Rozov, F N; Grinenko, T S; Levit, G L; Krasnov, V P; Belyavsky, A V

    2010-09-15

    Efficient gene transfer into hematopoietic stem cells is vital for the success of gene therapy of hematopoietic and immune system disorders. An in vivo selection system based on a mutant form of the O(6)-methylguanine-DNA-methyltransferase gene (MGMTm) is considered one of the more promising strategies for expansion of hematopoietic cells transduced with viral vectors. Here we demonstrate that MGMTm-expressing cells can be efficiently selected using lysomustine, a nitrosourea derivative of lysine. K562 and murine bone marrow cells expressing MGMTm are protected from the cytotoxic action of lysomustine in vitro. We also show in a murine model that MGMTm-transduced hematopoietic cells can be expanded in vivo on transplantation into sublethally irradiated recipients followed by lysomustine treatment. These results indicate that lysomustine can be used as a potent novel chemoselection drug applicable for gene therapy of hematopoietic and immune system disorders. 2010 Elsevier Inc. All rights reserved.

  5. [Alkylating agents].

    Science.gov (United States)

    Pourquier, Philippe

    2011-11-01

    With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

  6. Event Shape Sorting: selecting events with similar evolution

    Directory of Open Access Journals (Sweden)

    Tomášik Boris

    2017-01-01

    Full Text Available We present novel method for the organisation of events. The method is based on comparing event-by-event histograms of a chosen quantity Q that is measured for each particle in every event. The events are organised in such a way that those with similar shape of the Q-histograms end-up placed close to each other. We apply the method on histograms of azimuthal angle of the produced hadrons in ultrarelativsitic nuclear collisions. By selecting events with similar azimuthal shape of their hadron distribution one chooses events which are likely that they underwent similar evolution from the initial state to the freeze-out. Such events can more easily be compared to theoretical simulations where all conditions can be controlled. We illustrate the method on data simulated by the AMPT model.

  7. Profiling the nucleobase and structure selectivity of anticancer drugs and other DNA alkylating agents by RNA sequencing.

    Science.gov (United States)

    Gillingham, Dennis; Sauter, Basilius

    2018-05-06

    Drugs that covalently modify DNA are components of most chemotherapy regimens, often serving as first-line treatments. Classically the chemical reactivity of DNA alkylators has been determined in vitro with short oligonucleotides. Here we use next generation RNA sequencing to report on the chemoselectivity of alkylating agents. We develop the method with the well-known clinically used DNA modifiying drugs streptozotocin and temozolomide, and then apply the technique to profile RNA modification with uncharacterized alkylation reactions such as with powerful electrophiles like trimethylsilyldiazomethane. The multiplexed and massively parallel format of NGS offers analyses of chemical reactivity in nucleic acids to be accomplished in less time with greater statistical power. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Structure and thermal performance of poly(ethylene glycol) alkyl ether (Brij)/porous silica (MCM-41) composites as shape-stabilized phase change materials

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Lingjian; Shi, Haifeng, E-mail: haifeng.shi@gmail.com; Li, Weiwei; Han, Xu; Zhang, Xingxiang, E-mail: zhangpolyu@gmail.com

    2013-10-20

    Graphical abstract: The maximum 50 wt% Brij58 is loaded into the porous MCM-41 networks, and a new peak at 18.8° in XRD patterns confirmed the changes of crystallization behavior of Brij58 against the bulk one. - Highlights: • Poly(ethylene glycol) hexadecyl ether and poly(ethylene glycol) octadecyl ether have the good thermal storage ability. • New peak at 18.8° proved the coexisted confined crystallization and nucleation-induced crystallization. • Poly(ethylene glycol) alkyl ether/MCM-41 PCMs exhibits the good thermal stability. - Abstract: A series of shape-stabilized phase change materials (PCMs), composed of poly(ethylene glycol) hexadecyl ether (Brij58) or poly(ethylene glycol) octadecyl ether (Brij76) and porous silica (MCM-41), were prepared by the physical mixing method. The structure, thermal stability, energy storage ability and crystallization behavior of these composites are deeply investigated and characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), wide-angle X-ray diffraction (WAXD) and thermogravimetric analysis (TGA). Obvious phase transition behavior and energy storage capability are observed for these Brij/MCM-41 composites, and the heat storage efficiency increased with the weight of Brij component. New peak at 18.8° demonstrated that the pore size and the surface adsorption ability of MCM-41 affect the crystallization behavior of Brij molecule. The crystalline structure and energy storage ability of these Brij/MCM-41 composites are discussed based on the crystallization process.

  9. Mechanistic Insights of a Selective C-H Alkylation of Alkenes by a Ru-based Catalyst and Alcohols

    KAUST Repository

    Poater, Albert; Vummaleti, Sai V. C.; Polo, Alfonso; Cavallo, Luigi

    2016-01-01

    Density functional theory calculations have been used to investigate the reaction mechanism for [(C6H6)(PCy3)(CO) RuH](+) (1; Cy, cyclohexyl) mediated alkylation of indene substrate using ethanol as solvent. According to Yi et al. [ Science 2011

  10. Protein structure and ionic selectivity in calcium channels: selectivity filter size, not shape, matters.

    Science.gov (United States)

    Malasics, Attila; Gillespie, Dirk; Nonner, Wolfgang; Henderson, Douglas; Eisenberg, Bob; Boda, Dezso

    2009-12-01

    Calcium channels have highly charged selectivity filters (4 COO(-) groups) that attract cations in to balance this charge and minimize free energy, forcing the cations (Na(+) and Ca(2+)) to compete for space in the filter. A reduced model was developed to better understand the mechanism of ion selectivity in calcium channels. The charge/space competition (CSC) mechanism implies that Ca(2+) is more efficient in balancing the charge of the filter because it provides twice the charge as Na(+) while occupying the same space. The CSC mechanism further implies that the main determinant of Ca(2+) versus Na(+) selectivity is the density of charged particles in the selectivity filter, i.e., the volume of the filter (after fixing the number of charged groups in the filter). In this paper we test this hypothesis by changing filter length and/or radius (shape) of the cylindrical selectivity filter of our reduced model. We show that varying volume and shape together has substantially stronger effects than varying shape alone with volume fixed. Our simulations show the importance of depletion zones of ions in determining channel conductance calculated with the integrated Nernst-Planck equation. We show that confining the protein side chains with soft or hard walls does not influence selectivity.

  11. Laser-assisted shape selective fragmentation of nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Kazakevich, P.V. [Wave Research Center, General Physics Institute of the Russian Academy of Sciences, 38, Vavilov street, 117942 Moscow (Russian Federation); Simakin, A.V. [Wave Research Center, General Physics Institute of the Russian Academy of Sciences, 38, Vavilov street, 117942 Moscow (Russian Federation); Shafeev, G.A. [Wave Research Center, General Physics Institute of the Russian Academy of Sciences, 38, Vavilov street, 117942 Moscow (Russian Federation)]. E-mail: shafeev@kapella.gpi.ru; Viau, G. [ITODYS, UMR 7086, Universite Paris 7-Denis Diderot, case 7090, 2 place Jussieu, 75251 Paris Cedex 05 (France); Soumare, Y. [ITODYS, UMR 7086, Universite Paris 7-Denis Diderot, case 7090, 2 place Jussieu, 75251 Paris Cedex 05 (France); Bozon-Verduraz, F. [ITODYS, UMR 7086, Universite Paris 7-Denis Diderot, case 7090, 2 place Jussieu, 75251 Paris Cedex 05 (France)

    2007-07-31

    Experimental results are presented on laser-assisted fragmentation of gold-containing nanoparticles suspended in liquids (either ethanol or water). Two kinds of nanoparticles are considered: (i) elongated Au nanorods synthesized by laser ablation of a gold target immersed in liquid phase; (ii) gold-covered NiCo nanorods with high aspect ratio ({theta} {approx} 10) synthesized by wet chemistry processes. The shape selectivity induced by laser fragmentation of these nanorods is gained via tuning the wavelength of laser radiation into different parts of the spectrum of their plasmon resonance corresponding to different aspect ratios {theta}. Fragmentation is performed using three laser wavelengths, involving a Cu vapour laser (510 and 578 nm) and a Nd:YAG (1064 nm). Nanoparticles are characterized by UV-vis spectrometry, Transmission Electron Microscopy (TEM). The effect of laser pulse duration (nanosecond against picosecond range) is also studied in the case of fragmentation with an IR laser radiation.

  12. Shape-selective zeolite catalysis for bioplastics production

    Science.gov (United States)

    Dusselier, Michiel; Van Wouwe, Pieter; Dewaele, Annelies; Jacobs, Pierre A.; Sels, Bert F.

    2015-07-01

    Biodegradable and renewable polymers, such as polylactic acid, are benign alternatives for petrochemical-based plastics. Current production of polylactic acid via its key building block lactide, the cyclic dimer of lactic acid, is inefficient in terms of energy, time, and feedstock use. We present a direct zeolite-based catalytic process, which converts lactic acid into lactide. The shape-selective properties of zeolites are essential to attain record lactide yields, outperforming those of the current multistep process by avoiding both racemization and side-product formation. The highly productive process is strengthened by facile recovery and practical reactivation of the catalyst, which remains structurally fit during at least six consecutive reactions, and by the ease of solvent and side-product recycling.

  13. GREEN CHEMISTRY. Shape-selective zeolite catalysis for bioplastics production.

    Science.gov (United States)

    Dusselier, Michiel; Van Wouwe, Pieter; Dewaele, Annelies; Jacobs, Pierre A; Sels, Bert F

    2015-07-03

    Biodegradable and renewable polymers, such as polylactic acid, are benign alternatives for petrochemical-based plastics. Current production of polylactic acid via its key building block lactide, the cyclic dimer of lactic acid, is inefficient in terms of energy, time, and feedstock use. We present a direct zeolite-based catalytic process, which converts lactic acid into lactide. The shape-selective properties of zeolites are essential to attain record lactide yields, outperforming those of the current multistep process by avoiding both racemization and side-product formation. The highly productive process is strengthened by facile recovery and practical reactivation of the catalyst, which remains structurally fit during at least six consecutive reactions, and by the ease of solvent and side-product recycling. Copyright © 2015, American Association for the Advancement of Science.

  14. The Effect of Zeolite Structure on the Activity and Selectivity in p-Xylene Alkylation with Isopropyl Alcohol

    Czech Academy of Sciences Publication Activity Database

    Musilová, Zuzana; Kubů, Martin; Burton, A. W.; Zones, S. I.; Voláková, Martina; Čejka, Jiří

    2009-01-01

    Roč. 131, 3-4 (2009), s. 393-400 ISSN 1011-372X R&D Projects: GA AV ČR 1QS400400560; GA ČR GD203/08/H032 Institutional research plan: CEZ:AV0Z40400503 Keywords : SSZ-35 * SSZ-33 * p-xylene * alkylation Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.021, year: 2009

  15. Site selectivity in the addition of ketoximes to activated allenes and alkynes; N- versus O-alkylation

    OpenAIRE

    Heaney, Frances; Kelly, Bronwyn M.; Bourke, Sharon; Rooney, Oliver; Cunningham, Desmond; McArdle, Patrick

    1999-01-01

    Reaction of ketoximes with methyl propiolate afforded geometrical isomers of the methyl 3-(hydroxyimino)propanoates 4 and of the O-vinyl oximes 5 as well as the 2-isoxazoline 6. With dimethyl penta-2,3-diendioate 8c reaction progressed via an O-alkylation to give the O-oxime ethers 9, only in the case of cyclopentanone oxime was the spirocyclic dihydroazepinol 11 also obtained, its identity has been confirmed by an X-ray structure determination.

  16. From ketones to esters by a Cu-catalyzed highly selective C(CO)-C(alkyl) bond cleavage: aerobic oxidation and oxygenation with air.

    Science.gov (United States)

    Huang, Xiaoqiang; Li, Xinyao; Zou, Miancheng; Song, Song; Tang, Conghui; Yuan, Yizhi; Jiao, Ning

    2014-10-22

    The Cu-catalyzed aerobic oxidative esterification of simple ketones via C-C bond cleavage has been developed. Varieties of common ketones, even inactive aryl long-chain alkyl ketones, are selectively converted into esters. The reaction tolerates a wide range of alcohols, including primary and secondary alcohols, chiral alcohols with retention of the configuration, electron-deficient phenols, as well as various natural alcohols. The usage of inexpensive copper catalyst, broad substrate scope, and neutral and open air conditions make this protocol very practical. (18)O labeling experiments reveal that oxygenation occurs during this transformation. Preliminary mechanism studies indicate that two novel pathways are mainly involved in this process.

  17. Evidence of selection signatures that shape the Persian cat breed.

    Science.gov (United States)

    Bertolini, Francesca; Gandolfi, Barbara; Kim, Eui Soo; Haase, Bianca; Lyons, Leslie A; Rothschild, Max F

    2016-04-01

    The Persian cat is mainly characterized by an extremely brachycephalic face as part of the standard body conformation. Despite the popularity, world-wide distribution, and economic importance of the Persian cat as a fancy breed, little is known about the genetics of their hallmark morphology, brachycephaly. Over 800 cats from different breeds including Persian, non-Persian breeds (Abyssinian, Cornish Rex, Bengal, La Perm, Norwegian Forest, Maine Coon, Manx, Oriental, and Siamese), and Persian-derived breeds (British Shorthair, Scottish Fold, Selkirk Rex) were genotyped with the Illumina 63 K feline DNA array. The experimental strategy was composed of three main steps: (i) the Persian dataset was screened for runs of homozygosity to find and select highly homozygous regions; (ii) selected Persian homozygous regions were evaluated for the difference of homozygosity between Persians and those considered non-Persian breeds, and, (iii) the Persian homozygous regions most divergent from the non-Persian breeds were investigated by haplotype analysis in the Persian-derived breeds. Four regions with high homozygosity (H > 0.7) were detected, each with an average length of 1 Mb. Three regions can be considered unique to the Persian breed, with a less conservative haplotype pattern in the Persian-derived breeds. Moreover, two genes, CHL1 and CNTN6 known to determine face shape modification in humans, reside in one of the identified regions and therefore are positional candidates for the brachycephalic face in Persians. In total, the homozygous regions contained several neuronal genes that could be involved in the Persian cat behavior and can provide new insights into cat domestication.

  18. Alkylation of Isobutane/2-Butene Over Modified FAU-Type Zeolites.

    Science.gov (United States)

    Ro, Youngsoo; Gim, Min Yeoung; Lee, Jong Won; Lee, Eo Jin; Song, In Kyu

    2018-09-01

    A serious of mesoporous La-zeolite X catalysts (La-x-Zeol X (x = 0, 0.25, 0.5, 0.75, 1.0, and 2.0)) were prepared by a hydrothermal method with a variation of carbon template content (x, wt%). The prepared catalysts were applied to the isobutane/2-butene alkylation. Mesopore volume of the catalysts increased with increasing carbon template content, while acidity of the catalysts decreased with increasing carbon template content. In the catalytic reaction, productivity of C8 alkylate (C8 alkylate g/g-catalyst) and selectivity for C8 alkylate showed volcano-shaped trends with respect to carbon template content. Among the catalysts, La-0.5-Zeol X showed the highest productivity and selectivity for C8 alkylate. The maximum productivity and selectivity for C8 alkylate over La-0.5-Zeol X were due to the offset of two opposite trends between mesopore volume and acidity of La-x-Zeol X catalysts.

  19. Selected Alkylating Agents Can Overcome Drug Tolerance of G0-like Tumor Cells and Eradicate BRCA1-Deficient Mammary Tumors in Mice.

    Science.gov (United States)

    Pajic, Marina; Blatter, Sohvi; Guyader, Charlotte; Gonggrijp, Maaike; Kersbergen, Ariena; Küçükosmanoğlu, Aslι; Sol, Wendy; Drost, Rinske; Jonkers, Jos; Borst, Piet; Rottenberg, Sven

    2017-11-15

    Purpose: We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse. Experimental Design: We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for BRCA1/p53 -mutant breast cancer. Because of the large intragenic deletion of the Brca1 gene, no restoration of BRCA1 function is possible, and therefore, no BRCA1-dependent acquired resistance occurs. To characterize the cell-cycle stage from which Brca1 -/- ;p53 -/- mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell-cycle indicator (FUCCI) construct into the tumor cells. Results: Despite repeated sensitivity to the MTD of platinum drugs, the Brca1 -mutated mammary tumors are not eradicated, not even by a frequent dosing schedule. We show that relapse comes from single-nucleated cells delaying entry into the S-phase. Such slowly cycling cells, which are present within the drug-naïve tumors, are enriched in tumor remnants. Using the FUCCI construct, we identified nonfluorescent G 0 -like cells as the population most tolerant to platinum drugs. Intriguingly, these cells are more sensitive to the DNA-crosslinking agent nimustine, resulting in an increased number of multinucleated cells that lack clonogenicity. This is consistent with our in vivo finding that the nimustine MTD, among several alkylating agents, is the most effective in eradicating Brca1 -mutated mouse mammary tumors. Conclusions: Our data show that targeting G 0 -like cells is crucial for the eradication of BRCA1/p53-deficient tumor cells. This can be achieved with selected alkylating agents such as nimustine. Clin Cancer Res; 23(22); 7020-33. ©2017 AACR . ©2017 American Association for Cancer Research.

  20. Site-selective modification of peptides: From "customizable units" to novel α-aryl and α-alkyl glycine derivatives, and components of branched peptides.

    Science.gov (United States)

    Romero-Estudillo, Iván; Saavedra, Carlos; Boto, Alicia; Álvarez, Eleuterio

    2015-09-01

    The creation of peptide libraries by site-selective modification of a few peptide substrates would increase the efficiency of discovery processes, but still is a real synthetic challenge. The site-selective modification of small peptides at serine or threonine residues, by using a short scission-addition procedure, allows the preparation of peptides with unnatural α-aryl glycines. In a similar way, the scission of hydroxyproline residues is the key step in the production of optically pure α-alkyl glycines which are precursors or components of branched peptides. With these versatile processes, a single peptide can be transformed into a variety of peptide derivatives. The process takes place under mild conditions, and good global yields are obtained. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 650-662, 2015. © 2015 Wiley Periodicals, Inc.

  1. Mechanistic Insights of a Selective C-H Alkylation of Alkenes by a Ru-based Catalyst and Alcohols

    KAUST Repository

    Poater, Albert

    2016-09-11

    Density functional theory calculations have been used to investigate the reaction mechanism for [(C6H6)(PCy3)(CO) RuH](+) (1; Cy, cyclohexyl) mediated alkylation of indene substrate using ethanol as solvent. According to Yi et al. [ Science 2011, 333, 1613] the plausible reaction mechanism involves a cationic Rualkenyl species, which is initially formed from 1 with two equivalents of the olefin substrate via the vinylic C-H activation and an alkane elimination step. Once the active catalytic species is achieved the oxidative addition step is faced. The latter step together with the next C-C bond formation might display the upper barrier of the catalytic cycle. Having these experimental insights at hand, we investigated in detail the whole reaction pathway using several computational DFT approaches including alternative pathways, higher in energy.

  2. Bioaccumulation of per- and polyfluorinated alkyl substances (PFAS) in selected species from the Barents Sea food web.

    Science.gov (United States)

    Haukås, Marianne; Berger, Urs; Hop, Haakon; Gulliksen, Bjørn; Gabrielsen, Geir W

    2007-07-01

    The present study reports concentrations and biomagnification potential of per- and polyfluorinated alkyl substances (PFAS) in species from the Barents Sea food web. The examined species included sea ice amphipod (Gammarus wilkitzkii), polar cod (Boreogadus saida), black guillemot (Cepphus grylle) and glaucous gull (Larus hyperboreus). These were analyzed for PFAS, polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethanes (DDTs) and polybrominated diphenyl ethers (PBDEs). Perfluorooctane sulfonate (PFOS) was the predominant of the detected PFAS. Trophic levels and food web transfer of PFAS were determined using stable nitrogen isotopes (delta(15)N). No correlation was found between PFOS concentrations and trophic level within species. However, a non-linear relationship was established when the entire food web was analyzed. Biomagnification factors displayed values >1 for perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), PFOS and SigmaPFAS(7). Multivariate analyses showed that the degree of trophic transfer of PFAS is similar to that of PCB, DDT and PBDE, despite their accumulation through different pathways.

  3. Integrated shape and material selection for single and multi-performance criteria

    International Nuclear Information System (INIS)

    Singh, Jasveer; Mirjalili, Vahid; Pasini, Damiano

    2011-01-01

    Research highlights: → The method of shape transformers is extended to torsional stiffness and combined load design. → The method is generalized for multi-criteria selection of shape and material. → Performance charts are presented for single and multi-objective selection of cross-section shape and material. → A four quadrant performance chart is presented to visualize the relation between objective function space and design variable space. -- Abstract: A shape and material selection method, based on the concept of shape transformers, has been recently introduced to characterize the mass efficiency of lightweight beams under bending and shear. This paper extends this method to deal with the case of torsional stiffness design, and generalize it to single and multi-crieria selection of lightweight shafts subjected to a combination of bending, shear, and torsional load. The novel feature of the paper is the useful integration of shape and material to model and visualize multi-objective selection problems. The scheme is centered on concept selection in structural design, and hinges on measures that govern the shape properties of a cross-section regardless of its size. These measures, referred as shape transformers, can classify shapes in a way similar to material classification. The procedure is exemplified by considering torsional stiffness as a constraint. The performance charts are developed for single and multi-criteria to visualize in a glance the whole range of cross-sectional shapes for each material. Each design chart is explained with a brief example.

  4. Bioaccumulation of per- and polyfluorinated alkyl substances (PFAS) in selected species from the Barents Sea food web

    International Nuclear Information System (INIS)

    Haukas, Marianne; Berger, Urs; Hop, Haakon; Gulliksen, Bjorn; Gabrielsen, Geir W.

    2007-01-01

    The present study reports concentrations and biomagnification potential of per- and polyfluorinated alkyl substances (PFAS) in species from the Barents Sea food web. The examined species included sea ice amphipod (Gammarus wilkitzkii), polar cod (Boreogadus saida), black guillemot (Cepphus grylle) and glaucous gull (Larus hyperboreus). These were analyzed for PFAS, polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethanes (DDTs) and polybrominated diphenyl ethers (PBDEs). Perfluorooctane sulfonate (PFOS) was the predominant of the detected PFAS. Trophic levels and food web transfer of PFAS were determined using stable nitrogen isotopes (δ 15 N). No correlation was found between PFOS concentrations and trophic level within species. However, a non-linear relationship was established when the entire food web was analyzed. Biomagnification factors displayed values >1 for perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), PFOS and ΣPFAS(7). Multivariate analyses showed that the degree of trophic transfer of PFAS is similar to that of PCB, DDT and PBDE, despite their accumulation through different pathways. - The first comprehensive survey of fluoroorganic contamination in an European Arctic marine food web

  5. Shaping the future medical workforce: take care with selection tools.

    Science.gov (United States)

    Poole, Phillippa; Shulruf, Boaz

    2013-12-01

    Medical school selection is a first step in developing a general practice workforce. To determine the relationship between medical school selection scores and intention to pursue a career in general practice. A longitudinal cohort study of students selected in 2006 and 2007 for The University of Auckland medical programme, who completed an exit survey on career intentions. Students are ranked for selection into year 2 of a six-year programme by combining grade point average from prior university achievement (60%), interview (25%) and Undergraduate Medicine and Health Sciences Admission Test (UMAT) scores (15%). The main outcome measure was level of interest in general practice at exit. Logistic regression assessed whether any demographic variables or admission scores predicted a 'strong' interest in general practice. None of interview scores, grade point average, age, gender, or entry pathway predicted a 'strong' interest in general practice. Only UMAT scores differentiated between those with a 'strong' interest versus those with 'some' or 'no' interest, but in an inverse fashion. The best predictor of a 'strong' interest in general practice was a low UMAT score of between 45 and 55 on all three UMAT sections (OR 3.37, p=0.020). Yet, the academic scores at entry of students with these UMAT scores were not lower than those of their classmates. Setting inappropriately high cut-points for medical school selection may exclude applicants with a propensity for general practice. These findings support the use of a wider lens through which to view medical school selection tools.

  6. Toward hypoxia-selective DNA-alkylating agents built by grafting nitrogen mustards onto the bioreductively activated, hypoxia-selective DNA-oxidizing agent 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine).

    Science.gov (United States)

    Johnson, Kevin M; Parsons, Zachary D; Barnes, Charles L; Gates, Kent S

    2014-08-15

    Tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide) is a heterocyclic di-N-oxide that undergoes enzymatic deoxygenation selectively in the oxygen-poor (hypoxic) cells found in solid tumors to generate a mono-N-oxide metabolite. This work explored the idea that the electronic changes resulting from the metabolic deoxygenation of tirapazamine analogues might be exploited to activate a DNA-alkylating species selectively in hypoxic tissue. Toward this end, tirapazamine analogues bearing nitrogen mustard units were prepared. In the case of the tirapazamine analogue 18a bearing a nitrogen mustard unit at the 6-position, it was found that removal of the 4-oxide from the parent di-N-oxide to generate the mono-N-oxide analogue 17a did indeed cause a substantial increase in reactivity of the mustard unit, as measured by hydrolysis rates and DNA-alkylation yields. Hammett sigma values were measured to quantitatively assess the magnitude of the electronic changes induced by metabolic deoxygenation of the 3-amino-1,2,4-benzotriazine 1,4-dioxide heterocycle. The results provide evidence that the 1,2,4-benzotiazine 1,4-dioxide unit can serve as an oxygen-sensing prodrug platform for the selective unmasking of bioactive agents in hypoxic cells.

  7. DNA minor groove alkylating agents.

    Science.gov (United States)

    Denny, W A

    2001-04-01

    Recent work on a number of different classes of anticancer agents that alkylate DNA in the minor groove is reviewed. There has been much work with nitrogen mustards, where attachment of the mustard unit to carrier molecules can change the normal patterns of both regio- and sequence-selectivity, from reaction primarily at most guanine N7 sites in the major groove to a few adenine N3 sites at the 3'-end of poly(A/T) sequences in the minor groove. Carrier molecules discussed for mustards are intercalators, polypyrroles, polyimidazoles, bis(benzimidazoles), polybenzamides and anilinoquinolinium salts. In contrast, similar targeting of pyrrolizidine alkylators by a variety of carriers has little effect of their patterns of alkylation (at the 2-amino group of guanine). Recent work on the pyrrolobenzodiazepine and cyclopropaindolone classes of natural product minor groove binders is also reviewed.

  8. Enhancement of alkylation catalysts for improved supercritical fluid regeneration

    Science.gov (United States)

    Ginosar, Daniel M.; Petkovic, Lucia M.

    2010-12-28

    A method of modifying an alkylation catalyst to reduce the formation of condensed hydrocarbon species thereon. The method comprises providing an alkylation catalyst comprising a plurality of active sites. The plurality of active sites on the alkylation catalyst may include a plurality of weakly acidic active sites, intermediate acidity active sites, and strongly acidic active sites. A base is adsorbed to a portion of the plurality of active sites, such as the strongly acidic active sites, selectively poisoning the strongly acidic active sites. A method of modifying the alkylation catalyst by providing an alkylation catalyst comprising a pore size distribution that sterically constrains formation of the condensed hydrocarbon species on the alkylation catalyst or by synthesizing the alkylation catalyst to comprise a decreased number of strongly acidic active sites is also disclosed, as is a method of improving a regeneration efficiency of the alkylation catalyst.

  9. ShapeSelectForest: a new r package for modeling landsat time series

    Science.gov (United States)

    Mary Meyer; Xiyue Liao; Gretchen Moisen; Elizabeth Freeman

    2015-01-01

    We present a new R package called ShapeSelectForest recently posted to the Comprehensive R Archival Network. The package was developed to fit nonparametric shape-restricted regression splines to time series of Landsat imagery for the purpose of modeling, mapping, and monitoring annual forest disturbance dynamics over nearly three decades. For each pixel and spectral...

  10. Shape-Selection of Thermodynamically Stabilized Colloidal Pd and Pt Nanoparticles Controlled via Support Effects

    DEFF Research Database (Denmark)

    Ahmadi, M.; Behafarid, F.; Holse, Christian

    2015-01-01

    Colloidal chemistry, in combination with nanoparticle (NP)/support epitaxial interactions is used here to synthesize shape-selected and thermodynamically stable metallic NPs over a broad range of NP sizes. The morphology of three-dimensional palladium and platinum NPs supported on TiO2(110) was i......Colloidal chemistry, in combination with nanoparticle (NP)/support epitaxial interactions is used here to synthesize shape-selected and thermodynamically stable metallic NPs over a broad range of NP sizes. The morphology of three-dimensional palladium and platinum NPs supported on TiO2...... rows and was found to be responsible for the shape control. The ability of synthesizing thermally stable shape-selected metal NPs demonstrated here is expected to be of relevance for applications in the field of catalysis, since the activity and selectivity of NP catalysts has been shown to strongly...

  11. Shape-selective dependence of room temperature ferromagnetism induced by hierarchical ZnO nanostructures

    CSIR Research Space (South Africa)

    Motaung, DE

    2014-05-01

    Full Text Available . These materials were synthesized in a shape-selective manner using simple microwave assisted hydrothermal synthesis. Thermogravimetric analyses demonstrated the as-synthesized ZnO nanostructures to be stable and of high purity. Structural analyses showed...

  12. Shape-Selective Syntheses of Gold and Copper Nanostructures: Insights From Density-Functional Theory and Molecular Dynamics

    Science.gov (United States)

    Liu, Shih-Hsien

    Density-functional theory (DFT) and molecular dynamics (MD) were used to resolve the origins of shape-selective syntheses of {111}-faceted Au nanostructures mediated by polyvinylpyrrolidone (PVP) as well as {100}-faceted Cu nanostructures mediated by hex- adecylamine(HDA) seen in experiment. For the work in PVP on Au surfaces, the hexagonal reconstruction of Au(100) was considered. DFT results indicate that the Au(111) surface covered by the PVP segment, 2-pyrrolidone (2P), has a lower surface energy than the 2P- covered (5 x 1) Au(100)-hex surface, and that PVP may exhibit a binding affinity for Au(111) comparable to or greater than (5 x 1) Au(100)-hex. With MD, it is shown that the PVP-covered Au(111) surface has a lower surface energy than the PVP-covered (5 x 1) Au(100)-hex surface, and that the atactic PVP isosamer chains have a binding affinity for Au(111) comparable to (5 x 1) Au(100)-hex. Also, the (5 x 1) Au(100)-hex surface may have a higher flux of Au atoms than the Au(111) surface. Therefore, the Au(111) surface would be thermodynamically and kinetically favored in PVP-mediated syntheses, leading to {111}-faceted Au nanostructures. For the work in HDA on Cu surfaces, DFT results show that the HDA-covered Cu(100) surface has a slightly higher surface energy than the HDA- covered Cu(111) surface. However, HDA has a significant binding preference on Cu(100) over Cu(111). Therefore, the Cu(100) surface would be kinetically favored in HDA-mediated syn- theses, leading to {100}-faceted Cu nanostructures. Further, a metal-organic many-body (MOMB) force field for HDA-Cu interactions was developed based on the DFT work, and the force field was used to resolve the HDA binding patterns on Cu(100) at molecular level. With MD, it is found that decylamine (DA) may be used as an effective capping agent in the synthesis of {100}-faceted Cu nanostructures since DA as well as HDA are organized on Cu surfaces and have the same binding preference on Cu(100) over Cu(111

  13. The attention habit: how reward learning shapes attentional selection.

    Science.gov (United States)

    Anderson, Brian A

    2016-04-01

    There is growing consensus that reward plays an important role in the control of attention. Until recently, reward was thought to influence attention indirectly by modulating task-specific motivation and its effects on voluntary control over selection. Such an account was consistent with the goal-directed (endogenous) versus stimulus-driven (exogenous) framework that had long dominated the field of attention research. Now, a different perspective is emerging. Demonstrations that previously reward-associated stimuli can automatically capture attention even when physically inconspicuous and task-irrelevant challenge previously held assumptions about attentional control. The idea that attentional selection can be value driven, reflecting a distinct and previously unrecognized control mechanism, has gained traction. Since these early demonstrations, the influence of reward learning on attention has rapidly become an area of intense investigation, sparking many new insights. The result is an emerging picture of how the reward system of the brain automatically biases information processing. Here, I review the progress that has been made in this area, synthesizing a wealth of recent evidence to provide an integrated, up-to-date account of value-driven attention and some of its broader implications. © 2015 New York Academy of Sciences.

  14. Biometric evidence that sexual selection has shaped the hominin face.

    Directory of Open Access Journals (Sweden)

    Eleanor M Weston

    2007-08-01

    Full Text Available We consider sex differences in human facial morphology in the context of developmental change. We show that at puberty, the height of the upper face, between the lip and the brow, develops differently in males and females, and that these differences are not explicable in terms of sex differences in body size. We find the same dimorphism in the faces of human ancestors. We propose that the relative shortening in men and lengthening in women of the anterior upper face at puberty is the mechanistic consequence of extreme maxillary rotation during ontogeny. A link between this developmental model and sexual dimorphism is made for the first time, and provides a new set of morphological criteria to sex human crania. This finding has important implications for the role of sexual selection in the evolution of anthropoid faces and for theories of human facial attractiveness.

  15. Properties shaping and repair of selected types of cast iron

    Directory of Open Access Journals (Sweden)

    J. Szajnar

    2007-04-01

    Full Text Available The paper presents research results of twofold use of TIG - Tungsten Inert Gas also known as GTA - Gas Tungsten Arc. First is surfacing by welding on cold and hot-cold to repair chromium cast iron with chromium content about 15%. Second is remelting with electric arc of selected gray (with pearlitic matrix and ductile (with ferritic-pearlitic matrix cast iron. Repair of cast iron elements was realized in order to cut out a casting defects. Defects decrease a usability of castings for constructional application and increase a manufacturing costs. Application of surface heat treatment guarantees mechanical properties i.e. hardness and wear resistance improvement. The result of investigations show possibility of castings repair by put on defects a good quality padding welds, which have comparable properties with base material. Use of electric arc surface heat treatment resulted in increase of hardness and wear resistance, which was measured on the basis of ASTM G 65 - 00 standard.

  16. Chromatographic selectivity of poly(alkyl methacrylate-co-divinylbenzene) monolithic columns for polar aromatic compounds by pressure-driven capillary liquid chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Shu-Ling; Wang, Chih-Chieh; Fuh, Ming-Ren, E-mail: msfuh@scu.edu.tw

    2016-10-05

    In this study, divinylbenzene (DVB) was used as the cross-linker to prepare alkyl methacrylate (AlMA) monoliths for incorporating π-π interactions between the aromatic analytes and AlMA-DVB monolithic stationary phases in capillary LC analysis. Various AlMA/DVB ratios were investigated to prepare a series of 30% AlMA-DVB monolithic stationary phases in fused-silica capillaries (250-μm i.d.). The physical properties (such as porosity, permeability, and column efficiency) of the synthesized AlMA-DVB monolithic columns were investigated for characterization. Isocratic elution of phenol derivatives was first employed to evaluate the suitability of the prepared AlMA-DVB columns for small molecule separation. The run-to-run (0.16–1.20%, RSD; n = 3) and column-to-column (0.26–2.95%, RSD; n = 3) repeatabilities on retention times were also examined using the selected AlMA-DVB monolithic columns. The π-π interactions between the aromatic ring and the DVB-based stationary phase offered better recognition on polar analytes with aromatic moieties, which resulted in better separation resolution of aromatic analytes on the AlMA-DVB monolithic columns. In order to demonstrate the capability of potential environmental and/or food safety applications, eight phenylurea herbicides with single benzene ring and seven sulfonamide antibiotics with polyaromatic moieties were analyzed using the selected AlMA-DVB monolithic columns. - Highlights: • First investigation on chromatographic selectivity of AlMA-DVB monolithic columns. • Good run-to-run/column-to-column repeatability (<3%) on AlMA-DVB monolithic columns. • Efficient separation of phenylurea herbicides and sulfonamides on AlMA-DVB columns.

  17. Alkylation of N-substituted 2-phenylacetamides

    Directory of Open Access Journals (Sweden)

    SLOBODAN D. PETROVIC

    2004-10-01

    Full Text Available Various N-substituted phenylacetamides were alkylated using different alkylating agents under neutral and basic conditions. Reactions were performed at different reaction temperatures and in various solvents. Also, a number of various catalysts were used including phase-transfer catalysts. Reactions were followed using GC or GC-MS technique and the presence as well as the yields of the alkylation products were established. Generally, the best yield and high selectivity in the studied reactions were achieved under basic conditions where in the certain cases some products, mostly N-product, were obtained solely in quantitative yields.

  18. Development of novel alkylating drugs as anticancer agents.

    Science.gov (United States)

    Izbicka, Elzbieta; Tolcher, Anthony W

    2004-06-01

    Although conventional alkylating drugs have proven efficacy in the treatment of malignancies, the agents themselves are not selective. Therefore, non-specific alkylation of cellular nucleophilic targets may contribute to many of the observed toxic effects. Novel approaches to drug discovery have resulted in candidate agents that are focused on 'soft alkylation'--alkylators with greater target selectivity. This review highlights the discovery of small molecule drugs that bind to DNA with higher selectivity, act in a unique hypoxic tumor environment, or covalently bind specific protein targets overexpressed in cancer, such as topoisomerase II, glutathione transferase pi1, beta-tubulin and histone deacetylase.

  19. Intraspecific shape variation in horseshoe crabs: the importance of sexual and natural selection for local adaptation

    DEFF Research Database (Denmark)

    Faurby, Søren; Nielsen, Kasper Sauer Kollerup; Bussarawit, Somchai

    2011-01-01

    . Differences in shape variation between sexes were tested with F-tests, which showed lower intrapopulation morphometric variation in males than females. These results indicate a lower degree of local adaptation on body shape in C. rotundicauda and T. gigas than in L. polyphemus and a lower degree of local......A morphometric analysis of the body shape of three species of horseshoe crabs was undertaken in order to infer the importance of natural and sexual selection. It was expected that natural selection would be most intense, leading to highest regional differentiation, in the American species Limulus...... polyphemus, which has the largest climatic differences between different populations. Local adaptation driven by sexual selection was expected in males but not females because horseshoe crab mating behaviour leads to competition between males, but not between females. Three hundred fifty-nine horseshoe crabs...

  20. On the selection of shape and orientation of a greenhouse. Thermal modeling and experimental validation

    Energy Technology Data Exchange (ETDEWEB)

    Sethi, V.P. [Department of Mechanical Engineering, Punjab Agricultural University, Ludhiana 141 004, Punjab (India)

    2009-01-15

    In this study, five most commonly used single span shapes of greenhouses viz. even-span, uneven-span, vinery, modified arch and quonset type have been selected for comparison. The length, width and height (at the center) are kept same for all the selected shapes. A mathematical model for computing transmitted total solar radiation (beam, diffused and ground reflected) at each hour, for each month and at any latitude for the selected geometry greenhouses (through each wall, inclined surfaces and roofs) is developed for both east-west and north-south orientation. Computed transmitted solar radiation is then introduced in a transient thermal model developed to compute hourly inside air temperature for each shape and orientation. Experimental validation of both the models is carried out for the measured total solar radiation and inside air temperature for an east-west orientation, even-span greenhouse (for a typical day in summer) at Ludhiana (31 N and 77 E) Punjab, India. During the experimentation, capsicum crop is grown inside the greenhouse. The predicted and measured values are in close agreement. Results show that uneven-span shape greenhouse receives the maximum and quonset shape receives the minimum solar radiation during each month of the year at all latitudes. East-west orientation is the best suited for year round greenhouse applications at all latitudes as this orientation receives greater total radiation in winter and less in summer except near the equator. Results also show that inside air temperature rise depends upon the shape of the greenhouse and this variation from uneven-span shape to quonset shape is 4.6 C (maximum) and 3.5 C (daily average) at 31 N latitude. (author)

  1. Photoinduced alkylation reactions

    Energy Technology Data Exchange (ETDEWEB)

    Dondi, D.; Fagnoni, M.; Albini, A.

    2002-07-01

    Some {alpha}{beta}-unsaturated aldehydes have been alkylated generating alkyl radicals from alcohols and dioxolanes in mixed aqueous-organic solution though photoinduced hydrogen abstraction by disodium benzophenondisulfonate when exposed to solar light (6 to 14 hours for 10 g amounts). (Author) 8 refs.

  2. Interfce alkylation of ethyldiphenylphosphinylacetate

    International Nuclear Information System (INIS)

    Yarkevich, A.N.; Tsvetkov, E.N.

    1994-01-01

    The paper deals with the alkylation of the methyline group of ethyldiphenylphosphinylacetate (1) by different alkylating agents in the presence of Cs 2 CO 3 . In all cases the application of Cs 2 CO 3 results in a significant increase of reaction rate. 10 refs., 3 tabs

  3. DNA-directed alkylating ligands as potential antitumor agents: sequence specificity of alkylation by intercalating aniline mustards.

    Science.gov (United States)

    Prakash, A S; Denny, W A; Gourdie, T A; Valu, K K; Woodgate, P D; Wakelin, L P

    1990-10-23

    The sequence preferences for alkylation of a series of novel parasubstituted aniline mustards linked to the DNA-intercalating chromophore 9-aminoacridine by an alkyl chain of variable length were studied by using procedures analogous to Maxam-Gilbert reactions. The compounds alkylate DNA at both guanine and adenine sites. For mustards linked to the acridine by a short alkyl chain through a para O- or S-link group, 5'-GT sequences are the most preferred sites at which N7-guanine alkylation occurs. For analogues with longer chain lengths, the preference of 5'-GT sequences diminishes in favor of N7-adenine alkylation at the complementary 5'-AC sequence. Magnesium ions are shown to selectively inhibit alkylation at the N7 of adenine (in the major groove) by these compounds but not the alkylation at the N3 of adenine (in the minor groove) by the antitumor antibiotic CC-1065. Effects of chromophore variation were also studied by using aniline mustards linked to quinazoline and sterically hindered tert-butyl-9-aminoacridine chromophores. The results demonstrate that in this series of DNA-directed mustards the noncovalent interactions of the carrier chromophores with DNA significantly modify the sequence selectivity of alkylation by the mustard. Relationships between the DNA alkylation patterns of these compounds and their biological activities are discussed.

  4. Human Error Probabilites (HEPs) for generic tasks and Performance Shaping Factors (PSFs) selected for railway operations

    DEFF Research Database (Denmark)

    Thommesen, Jacob; Andersen, Henning Boje

    This report describes an HRA (Human Reliability Assessment) of six generic tasks and four Perfor-mance Shaping Factors (PSFs) targeted at railway operations commissioned by Banedanmark. The selection and characterization of generic tasks and PSFs are elaborated by DTU Management in close...

  5. Protein structure and ionic selectivity in calcium channels: Selectivity filter size, not shape, matters

    OpenAIRE

    Malasics, Attila; Gillespie, Dirk; Nonner, Wolfgang; Henderson, Douglas; Eisenberg, Bob; Boda, Dezső

    2009-01-01

    Calcium channels have highly charged selectivity filters (4 COO− groups) that attract cations in to balance this charge and minimize free energy, forcing the cations (Na+ and Ca2+) to compete for space in the filter. A reduced model was developed to better understand the mechanism of ion selectivity in calcium channels. The charge/space competition (CSC) mechanism implies that Ca2+ is more efficient in balancing the charge of the filter because it provides twice the charge as Na+ while occupy...

  6. N-O chemistry for antibiotics: discovery of N-alkyl-N-(pyridin-2-yl)hydroxylamine scaffolds as selective antibacterial agents using nitroso Diels-Alder and ene chemistry.

    Science.gov (United States)

    Wencewicz, Timothy A; Yang, Baiyuan; Rudloff, James R; Oliver, Allen G; Miller, Marvin J

    2011-10-13

    The discovery, syntheses, and structure-activity relationships (SAR) of a new family of heterocyclic antibacterial compounds based on N-alkyl-N-(pyridin-2-yl)hydroxylamine scaffolds are described. A structurally diverse library of ∼100 heterocyclic molecules generated from Lewis acid-mediated nucleophilic ring-opening reactions with nitroso Diels-Alder cycloadducts and nitroso ene reactions with substituted alkenes was evaluated in whole cell antibacterial assays. Compounds containing the N-alkyl-N-(pyridin-2-yl)hydroxylamine structure demonstrated selective and potent antibacterial activity against the Gram-positive bacterium Micrococcus luteus ATCC 10240 (MIC(90) = 2.0 μM or 0.41 μg/mL) and moderate activity against other Gram-positive strains including antibiotic resistant strains of Staphylococcus aureus (MRSA) and Enterococcus faecalis (VRE). A new synthetic route to the active core was developed using palladium-catalyzed Buchwald-Hartwig amination reactions of N-alkyl-O-(4-methoxybenzyl)hydroxylamines with 2-halo-pyridines that facilitated SAR studies and revealed the simplest active structural fragment. This work shows the value of using a combination of diversity-oriented synthesis (DOS) and parallel synthesis for identifying new antibacterial scaffolds.

  7. Application of Shape Similarity in Pose Selection and Virtual Screening in CSARdock2014 Exercise.

    Science.gov (United States)

    Kumar, Ashutosh; Zhang, Kam Y J

    2016-06-27

    To evaluate the applicability of shape similarity in docking-based pose selection and virtual screening, we participated in the CSARdock2014 benchmark exercise for identifying the correct docking pose of inhibitors targeting factor XA, spleen tyrosine kinase, and tRNA methyltransferase. This exercise provides a valuable opportunity for researchers to test their docking programs, methods, and protocols in a blind testing environment. In the CSARdock2014 benchmark exercise, we have implemented an approach that uses ligand 3D shape similarity to facilitate docking-based pose selection and virtual screening. We showed here that ligand 3D shape similarity between bound poses could be used to identify the native-like pose from an ensemble of docking-generated poses. Our method correctly identified the native pose as the top-ranking pose for 73% of test cases in a blind testing environment. Moreover, the pose selection results also revealed an excellent correlation between ligand 3D shape similarity scores and RMSD to X-ray crystal structure ligand. In the virtual screening exercise, the average RMSD for our pose prediction was found to be 1.02 Å, and it was one of the top performances achieved in CSARdock2014 benchmark exercise. Furthermore, the inclusion of shape similarity improved virtual screening performance of docking-based scoring and ranking. The coefficient of determination (r(2)) between experimental activities and docking scores for 276 spleen tyrosine kinase inhibitors was found to be 0.365 but reached 0.614 when the ligand 3D shape similarity was included.

  8. Natural selection maintains a single-locus leaf shape cline in Ivyleaf morning glory, Ipomoea hederacea.

    Science.gov (United States)

    Campitelli, Brandon E; Stinchcombe, John R

    2013-02-01

    Clines in phenotypic traits with an underlying genetic basis potentially implicate natural selection. However, neutral evolutionary processes such as random colonization, spatially restricted gene flow, and genetic drift could also result in similar spatial patterns, especially for single-locus traits because of their susceptibility to stochastic events. One way to distinguish between adaptive and neutral mechanisms is to compare the focal trait to neutral genetic loci to determine whether neutral loci demonstrate clinal variation (consistent with a neutral cline), or not. Ivyleaf morning glory, Ipomoea hederacea, exhibits a latitudinal cline for a Mendelian leaf shape polymorphism in eastern North America, such that lobed genotypes dominate northern populations and heart-shaped genotypes are restricted to southern populations. Here, we evaluate potential evolutionary mechanisms for this cline by first determining the allele frequencies at the leaf shape locus for 77 populations distributed throughout I. hederacea's range and then comparing the geographical pattern at this locus to neutral amplified fragment length polymorphism (AFLP) loci. We detected both significant clinal variation and high genetic differentiation at the leaf shape locus across all populations. In contrast, 99% of the putatively neutral loci do not display clinal variation, and I. hederacea populations show very little overall genetic differentiation, suggesting that there is a moderate level of gene flow. In addition, the leaf shape locus was identified as a major F(ST) outlier experiencing divergent selection, relative to all the AFLP loci. Together, these data strongly suggest that the cline in leaf shape is being maintained by spatially varying natural selection. © 2012 Blackwell Publishing Ltd.

  9. Antagonistic natural and sexual selection on wing shape in a scrambling damselfly.

    Science.gov (United States)

    Outomuro, David; Söderquist, Linus; Nilsson-Örtman, Viktor; Cortázar-Chinarro, María; Lundgren, Cecilia; Johansson, Frank

    2016-07-01

    Wings are a key trait underlying the evolutionary success of birds, bats, and insects. For over a century, researchers have studied the form and function of wings to understand the determinants of flight performance. However, to understand the evolution of flight, we must comprehend not only how morphology affects performance, but also how morphology and performance affect fitness. Natural and sexual selection can either reinforce or oppose each other, but their role in flight evolution remains poorly understood. Here, we show that wing shape is under antagonistic selection with regard to sexual and natural selection in a scrambling damselfly. In a field setting, natural selection (survival) favored individuals with long and slender forewings and short and broad hindwings. In contrast, sexual selection (mating success) favored individuals with short and broad forewings and narrow-based hindwings. Both types of selection favored individuals of intermediate size. These results suggest that individuals face a trade-off between flight energetics and maneuverability and demonstrate how natural and sexual selection can operate in similar directions for some wing traits, that is, wing size, but antagonistically for others, that is, wing shape. Furthermore, they highlight the need to study flight evolution within the context of species' mating systems and mating behaviors. © 2016 The Author(s).

  10. Isobutane alkylation over solid catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Kozorezov, Y.I.; Lisin, V.I.

    1979-05-01

    Commercial alumina modified with 6Vertical Bar3< by wt boron trifluoride was active in isobutane alkylation with ethylene in a flow reactor at 5:1 isobutane-ethylene and 5-20 min reaction time. The reaction rate was first-order in ethylene and increased with increasing temperature (20/sup 0/-80/sup 0/C) and ethylene pressure (0.2-3 atm). The calculated activation energy was 8.4 kj. Kinetic data and the activity of tert.-butyl chloride, but not ethyl chloride as alkylating agents in place of ethylene suggested a carbonium-ion chain mechanism involving both surface and gas-phase reactions. The ethylene-based yield of the alkylate decreased from 132 to 41Vertical Bar3< by wt after nine hours on stream, and its bromine number increased from 0.2 to 1 g Br/sub 2//100 ml. This inhibition was attributed to adsorption on the active acidic sites of the reaction products, particularly C/sub 10//sup +/ olefins. Catalyst stabilization could probably be achieved by selecting an appropriate solvent that would continuously desorb the inhibiting products from the catalyst surface.

  11. Complex responses to alkylating agents

    International Nuclear Information System (INIS)

    Samson, L.D.

    2003-01-01

    Using Affymetrix oligonucleotide GeneChip analysis, we previously found that, upon exposure to the simple alkylating agent methylmethane sulfonate, the transcript levels for about one third of the Saccharomyces cerevisiae genome (∼2,000 transcripts) are induced or repressed during the first hour or two after exposure. In order to determine whether the responsiveness of these genes has any relevance to the protection of cells against alkylating agents we have undertaken several follow-up studies. First, we explored the specificity of this global transcriptional response to MMS by measuring the global response of S. cerevisiae to a broad range of agents that are known to induce DNA damage. We found that each agent produced a very different mRNA transcript profile, even though the exposure doses produced similar levels of toxicity. We also found that the selection of genes that respond to MMS is highly dependent upon what cell cycle phase the cells are in at the time of exposure. Computational clustering analysis of the dataset derived from a large number of exposures identified several promoter motifs that are likely to control some of the regulons that comprise this large set of genes that are responsive to DNA damaging agents. However, it should be noted that these agents damage cellular components other than DNA, and that the responsiveness of each gene need not be in response to DNA damage per se. We have also begun to study the response of other organisms to alkylating agents, and these include E. coli, cultured mouse and human cells, and mice. Finally, we have developed a high throughput phenotypic screening method to interrogate the role of all non-essential S. cerevisiae genes (about 4,800) in protecting S. cerevisiae against the deleterious effects of alkylating agents; we have termed this analysis 'genomic phenotyping'. This study has uncovered a plethora of new pathways that play a role in the recovery of eukaryotic cells after exposure to toxic

  12. Alkylation damage by lipid electrophiles targets functional protein systems.

    Science.gov (United States)

    Codreanu, Simona G; Ullery, Jody C; Zhu, Jing; Tallman, Keri A; Beavers, William N; Porter, Ned A; Marnett, Lawrence J; Zhang, Bing; Liebler, Daniel C

    2014-03-01

    Protein alkylation by reactive electrophiles contributes to chemical toxicities and oxidative stress, but the functional impact of alkylation damage across proteomes is poorly understood. We used Click chemistry and shotgun proteomics to profile the accumulation of proteome damage in human cells treated with lipid electrophile probes. Protein target profiles revealed three damage susceptibility classes, as well as proteins that were highly resistant to alkylation. Damage occurred selectively across functional protein interaction networks, with the most highly alkylation-susceptible proteins mapping to networks involved in cytoskeletal regulation. Proteins with lower damage susceptibility mapped to networks involved in protein synthesis and turnover and were alkylated only at electrophile concentrations that caused significant toxicity. Hierarchical susceptibility of proteome systems to alkylation may allow cells to survive sublethal damage while protecting critical cell functions.

  13. Alkylation Damage by Lipid Electrophiles Targets Functional Protein Systems*

    Science.gov (United States)

    Codreanu, Simona G.; Ullery, Jody C.; Zhu, Jing; Tallman, Keri A.; Beavers, William N.; Porter, Ned A.; Marnett, Lawrence J.; Zhang, Bing; Liebler, Daniel C.

    2014-01-01

    Protein alkylation by reactive electrophiles contributes to chemical toxicities and oxidative stress, but the functional impact of alkylation damage across proteomes is poorly understood. We used Click chemistry and shotgun proteomics to profile the accumulation of proteome damage in human cells treated with lipid electrophile probes. Protein target profiles revealed three damage susceptibility classes, as well as proteins that were highly resistant to alkylation. Damage occurred selectively across functional protein interaction networks, with the most highly alkylation-susceptible proteins mapping to networks involved in cytoskeletal regulation. Proteins with lower damage susceptibility mapped to networks involved in protein synthesis and turnover and were alkylated only at electrophile concentrations that caused significant toxicity. Hierarchical susceptibility of proteome systems to alkylation may allow cells to survive sublethal damage while protecting critical cell functions. PMID:24429493

  14. Picture Yourself Healthy-How Users Select Mediated Images to Shape Health Intentions and Behaviors.

    Science.gov (United States)

    Wilson, Brianna; Knobloch-Westerwick, Silvia; Robinson, Melissa J

    2018-02-20

    Hypotheses on how selective viewing of mediated images may sustain eating habits and aid healthier eating were derived from the Selective Exposure Self- and Affect Management model. The model posits that individuals select to view media to manage their self-concepts-and that this exposure affects subsequent intentions and behaviors. Participants (N = 265) selectively viewed Instagram-like postings featuring healthy or unhealthy food imagery. Beforehand, participants reported habits and perceived expert recommendations regarding food intake. After viewing postings, participants chose gift cards representing healthy or unhealthy food purchases and indicated food intake intentions. Results show that existing eating behavior predicts selective exposure to healthy or unhealthy food imagery, which in turn shapes gift card choices and (both healthy and unhealthy) food intake intentions.

  15. Reaction of the (111) faces of single-crystal indium phosphide with alkylating agents: evidence for selective reaction of the p-rich face

    Energy Technology Data Exchange (ETDEWEB)

    Spool, A.M.; Daube, K.A.; Mallouk, T.E.; Belmont, J.A.; Wrighton, M.S.

    1986-05-28

    We wish to report that the P-rich, (111)B, face of single-crystal InP, but not the In-rich, (111)A, face of the same crystal, reacts with molecular reagents to yield surface-bound material derived from the apparent alkylation of a surface P atom. Exploitation of surface functional groups has been demonstrated to be very important in the attachment of molecular reagents and polymers to electrode surfaces. Electrodes derivatized with molecules have potential uses in analysis, fuel cells, electrosynthetic cells, and photoelectrochemical cells. We now wish to present evidence showing that an important photoelectrode material, InP, can be functionalized with molecules by reaction of the P-rich, (111)B, face with alkylating reagents.

  16. Angular and dose dependence of CR-39 neutron response for shape-selected tracks

    CERN Document Server

    Tam, N C; Lakosi, L

    1999-01-01

    A shape selection method corresponding to an energy discrimination was used to eliminate unwanted events disturbing evaluation of CR-39 detectors in detecting tracks induced by particles both of perpendicular and oblique incidence. The angular dependence of the response was examined, detecting fast neutrons from sup 2 sup 5 sup 2 Cf with shape selection technique at various angles and distances. Also, the CR-39 track detectors with the sup 2 sup 5 sup 2 Cf source were exposed to high gamma-intensity of a sup 6 sup 0 Co irradiation facility in the range 0.1 to 4.5 kGy, similar to the exposures inside spent fuel assemblies. Using the two functions the lower limit of burnup could be determined by the method.

  17. Direct, Regioselective N-Alkylation of 1,3-Azoles.

    Science.gov (United States)

    Chen, Shuai; Graceffa, Russell F; Boezio, Alessandro A

    2016-01-04

    Regioselective N-alkylation of 1,3-azoles is a valuable transformation. Organomagnesium reagents were discovered to be competent bases to affect regioselective alkylation of various 1,3-azoles. Counterintuitively, substitution selectively occurred at the more sterically hindered nitrogen atom. Numerous examples are provided, on varying 1,3-azole scaffolds, with yields ranging from 25 to 95%.

  18. Adaptive feature selection using v-shaped binary particle swarm optimization.

    Science.gov (United States)

    Teng, Xuyang; Dong, Hongbin; Zhou, Xiurong

    2017-01-01

    Feature selection is an important preprocessing method in machine learning and data mining. This process can be used not only to reduce the amount of data to be analyzed but also to build models with stronger interpretability based on fewer features. Traditional feature selection methods evaluate the dependency and redundancy of features separately, which leads to a lack of measurement of their combined effect. Moreover, a greedy search considers only the optimization of the current round and thus cannot be a global search. To evaluate the combined effect of different subsets in the entire feature space, an adaptive feature selection method based on V-shaped binary particle swarm optimization is proposed. In this method, the fitness function is constructed using the correlation information entropy. Feature subsets are regarded as individuals in a population, and the feature space is searched using V-shaped binary particle swarm optimization. The above procedure overcomes the hard constraint on the number of features, enables the combined evaluation of each subset as a whole, and improves the search ability of conventional binary particle swarm optimization. The proposed algorithm is an adaptive method with respect to the number of feature subsets. The experimental results show the advantages of optimizing the feature subsets using the V-shaped transfer function and confirm the effectiveness and efficiency of the feature subsets obtained under different classifiers.

  19. Tailoring the self-assembly of linear alkyl chains for the design of advanced materials with technological applications.

    Science.gov (United States)

    Hoppe, Cristina E; Williams, Roberto J J

    2018-03-01

    The self-assembly of n-alkyl chains at the bulk or at the interface of different types of materials and substrates has been extensively studied in the past. The packing of alkyl chains is driven by Van der Waals interactions and can generate crystalline or disordered domains, at the bulk of the material, or self-assembled monolayers at an interface. This natural property of alkyl chains has been employed in recent years to develop a new generation of materials for technological applications. These studies are dispersed in a variety of journals. The purpose of this article was to discuss some selected examples where these advanced properties arise from a process involving the self-assembly of alkyl chains. We included a description of electronic devices and new-generation catalysts with properties derived from a controlled two-dimensional (2D) or three-dimensional (3D) self-assembly of alkyl chains at an interface. Then, we showed that controlling the crystallization of alkyl chains at the bulk can be used to generate a variety of advanced materials such as superhydrophobic coatings, shape memory hydrogels, hot-melt adhesives, thermally reversible light scattering (TRLS) films for intelligent windows and form-stable phase change materials (FS-PCMs) for the storage of thermal energy. Finally, we discussed two examples where advanced properties derive from the formation of disordered domains by physical association of alkyl chains. This was the case of photoluminescent nanocomposites and materials used for reversible optical storage. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Isobutane/olefin-alkylation

    Energy Technology Data Exchange (ETDEWEB)

    Waitkamp, J.; Maixner, S.

    1983-11-01

    Isobutane/olefin-alkylation - technology and reaction mechanism of a refinery process for production of high octane gasoline components: The alkylation of i-butane with olefins, especially with butenes, is a process for the conversion of light byproducts of a catalytic cracker to high quality gasoline components. Alkylate is a complex mixture of i-paraffins containing 5 to ca. 12 carbon atoms. Due to their octane numbers the four trimethylpentane isomers are the most desirable product components. Indeed, under optimum process conditions these isomers are the main products. Presently, alkylation capacity in the western world amounts to more than 40x10/sup 6/ t/a. Most units are located in the USA. Two liquid-phase processes using sulfuric acid and hydrofluoric acid, respectively, are of commercial importance. At present, there is a definite trend towards HF-alkylation. The reaction mechanism which proceeds via carbocations, is extremely complex. It is composed of a great variety of individual steps. Modern mechanistic concepts are discussed.

  1. The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor (nAChR) ligands. Part 1: the influence of different hydrogen bond acceptor systems on alkyl and (hetero)aryl substituents.

    Science.gov (United States)

    Eibl, Christoph; Tomassoli, Isabelle; Munoz, Lenka; Stokes, Clare; Papke, Roger L; Gündisch, Daniela

    2013-12-01

    3,7-Diazabicyclo[3.3.1]nonane is a naturally occurring scaffold interacting with nicotinic acetylcholine receptors (nAChRs). When one nitrogen of the 3,7-diazabicyclo[3.3.1]nonane scaffold was implemented in a carboxamide motif displaying a hydrogen bond acceptor (HBA) functionality, compounds with higher affinities and subtype selectivity for α4β2(∗) were obtained. The nature of the HBA system (carboxamide, sulfonamide, urea) had a strong impact on nAChR interaction. High affinity ligands for α4β2(∗) possessed small alkyl chains, small un-substituted hetero-aryl groups or para-substituted phenyl ring systems along with a carboxamide group. Electrophysiological responses of selected 3,7-diazabicyclo[3.3.1]nonane derivatives to Xenopus oocytes expressing various nAChR subtypes showed diverse activation profiles. Compounds with strongest agonistic profiles were obtained with small alkyl groups whereas a shift to partial agonism/antagonism was observed for aryl substituents. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Star-shaped Polymers through Simple Wavelength-Selective Free-Radical Photopolymerization.

    Science.gov (United States)

    Eibel, Anna; Fast, David E; Sattelkow, Jürgen; Zalibera, Michal; Wang, Jieping; Huber, Alex; Müller, Georgina; Neshchadin, Dmytro; Dietliker, Kurt; Plank, Harald; Grützmacher, Hansjörg; Gescheidt, Georg

    2017-11-06

    Star-shaped polymers represent highly desired materials in nanotechnology and life sciences, including biomedical applications (e.g., diagnostic imaging, tissue engineering, and targeted drug delivery). Herein, we report a straightforward synthesis of wavelength-selective multifunctional photoinitiators (PIs) that contain a bisacylphosphane oxide (BAPO) group and an α-hydroxy ketone moiety within one molecule. By using three different wavelengths, these photoactive groups can be selectively addressed and activated, thereby allowing the synthesis of ABC-type miktoarm star polymers through a simple, highly selective, and robust free-radical polymerization method. The photochemistry of these new initiators and the feasibility of this concept were investigated in unprecedented detail by using various spectroscopic techniques. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Identify alkylation hazards

    International Nuclear Information System (INIS)

    Scott, B.

    1992-01-01

    This paper reports that extensive experience shows that alkylation plants regardless of acid catalyst choice, can be operated safely, and with minimum process risk to employees or neighbors. Both types of plants require a comprehensive and fully supported hazard management program that accounts for differing physical properties of the acids involved. Control and mitigation cost to refiners will vary considerably from plant to plant and location to location. In the author's experience, the order of magnitude costs will be about $1 to $2 million for a sulfuric acid (SA) alkylation plant, and about $10 to $15 million for a hydrofluoric acid (HF) plant. These costs include water supply systems and impoundment facilities for contaminated runoff water. The alkylation process, which chemically reacts isobutane and light olefins in the presence of a strong acid catalyst into a premium gasoline component is described

  4. Band-selective shaped pulse for high fidelity quantum control in diamond

    International Nuclear Information System (INIS)

    Chang, Yan-Chun; Xing, Jian; Liu, Gang-Qin; Jiang, Qian-Qing; Li, Wu-Xia; Zhang, Fei-Hao; Gu, Chang-Zhi; Pan, Xin-Yu; Long, Gui-Lu

    2014-01-01

    High fidelity quantum control of qubits is crucially important for realistic quantum computing, and it becomes more challenging when there are inevitable interactions between qubits. We introduce a band-selective shaped pulse, refocusing BURP (REBURP) pulse, to cope with the problems. The electron spin of nitrogen-vacancy centers in diamond is flipped with high fidelity by the REBURP pulse. In contrast with traditional rectangular pulses, the shaped pulse has almost equal excitation effect in a sharply edged region (in frequency domain). So the three sublevels of host 14 N nuclear spin can be flipped accurately simultaneously, while unwanted excitations of other sublevels (e.g., of a nearby 13 C nuclear spin) is well suppressed. Our scheme can be used for various applications such as quantum metrology, quantum sensing, and quantum information process.

  5. Band-selective shaped pulse for high fidelity quantum control in diamond

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yan-Chun; Xing, Jian; Liu, Gang-Qin; Jiang, Qian-Qing; Li, Wu-Xia [Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190 (China); Zhang, Fei-Hao [Tsinghua National Laboratory for Information Science and Technology, Beijing 100084 (China); State Key Laboratory of Low-Dimensional Physics and Department of Physics, Tsinghua University, Beijing 100084 (China); Gu, Chang-Zhi; Pan, Xin-Yu, E-mail: xypan@aphy.iphy.ac.cn [Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190 (China); Collaborative Innovation Center of Quantum Matter, Beijing 100871 (China); Long, Gui-Lu [Tsinghua National Laboratory for Information Science and Technology, Beijing 100084 (China); State Key Laboratory of Low-Dimensional Physics and Department of Physics, Tsinghua University, Beijing 100084 (China); Collaborative Innovation Center of Quantum Matter, Beijing 100871 (China)

    2014-06-30

    High fidelity quantum control of qubits is crucially important for realistic quantum computing, and it becomes more challenging when there are inevitable interactions between qubits. We introduce a band-selective shaped pulse, refocusing BURP (REBURP) pulse, to cope with the problems. The electron spin of nitrogen-vacancy centers in diamond is flipped with high fidelity by the REBURP pulse. In contrast with traditional rectangular pulses, the shaped pulse has almost equal excitation effect in a sharply edged region (in frequency domain). So the three sublevels of host {sup 14}N nuclear spin can be flipped accurately simultaneously, while unwanted excitations of other sublevels (e.g., of a nearby {sup 13}C nuclear spin) is well suppressed. Our scheme can be used for various applications such as quantum metrology, quantum sensing, and quantum information process.

  6. An event-related brain potential study of visual selective attention to conjunctions of color and shape.

    Science.gov (United States)

    Smid, H G; Jakob, A; Heinze, H J

    1999-03-01

    What cognitive processes underlie event-related brain potential (ERP) effects related to visual multidimensional selective attention and how are these processes organized? We recorded ERPs when participants attended to one conjunction of color, global shape and local shape and ignored other conjunctions of these attributes in three discriminability conditions. Attending to color and shape produced three ERP effects: frontal selection positivity (FSP), central negativity (N2b), and posterior selection negativity (SN). The results suggested that the processes underlying SN and N2b perform independent within-dimension selections, whereas the process underlying the FSP performs hierarchical between-dimension selections. At posterior electrodes, manipulation of discriminability changed the ERPs to the relevant but not to the irrelevant stimuli, suggesting that the SN does not concern the selection process itself but rather a cognitive process initiated after selection is finished. Other findings suggested that selection of multiple visual attributes occurs in parallel.

  7. Population structure and strong divergent selection shape phenotypic diversification in maize landraces.

    Science.gov (United States)

    Pressoir, G; Berthaud, J

    2004-02-01

    To conserve the long-term selection potential of maize, it is necessary to investigate past and present evolutionary processes that have shaped quantitative trait variation. Understanding the dynamics of quantitative trait evolution is crucial to future crop breeding. We characterized population differentiation of maize landraces from the State of Oaxaca, Mexico for quantitative traits and molecular markers. Qst values were much higher than Fst values obtained for molecular markers. While low values of Fst (0.011 within-village and 0.003 among-villages) suggest that considerable gene flow occurred among the studied populations, high levels of population differentiation for quantitative traits were observed (ie an among-village Qst value of 0.535 for kernel weight). Our results suggest that although quantitative traits appear to be under strong divergent selection, a considerable amount of gene flow occurs among populations. Furthermore, we characterized nonproportional changes in the G matrix structure both within and among villages that are consequences of farmer selection. As a consequence of these differences in the G matrix structure, the response to multivariate selection will be different from one population to another. Large changes in the G matrix structure could indicate that farmers select for genes of major and pleiotropic effect. Farmers' decision and selection strategies have a great impact on phenotypic diversification in maize landraces.

  8. Bifunctional Molybdenum Polyoxometalates for the Combined Hydrodeoxygenation and Alkylation of Lignin-Derived Model Phenolics.

    Science.gov (United States)

    Anderson, Eric; Crisci, Anthony; Murugappan, Karthick; Román-Leshkov, Yuriy

    2017-05-22

    Reductive catalytic fractionation of biomass has recently emerged as a powerful lignin extraction and depolymerization method to produce monomeric aromatic oxygenates in high yields. Here, bifunctional molybdenum-based polyoxometalates supported on titania (POM/TiO 2 ) are shown to promote tandem hydrodeoxygenation (HDO) and alkylation reactions, converting lignin-derived oxygenated aromatics into alkylated benzenes and alkylated phenols in high yields. In particular, anisole and 4-propylguaiacol were used as model compounds for this gas-phase study using a packed-bed flow reactor. For anisole, 30 % selectivity for alkylated aromatic compounds (54 % C-alkylation of the methoxy groups by methyl balance) with an overall 72 % selectivity for HDO at 82 % anisole conversion was observed over H 3 PMo 12 O 40 /TiO 2 at 7 h on stream. Under similar conditions, 4-propylguaiacol was mainly converted into 4-propylphenol and alkylated 4-propylphenols with a selectivity to alkylated 4-propylphenols of 42 % (77 % C-alkylation) with a total HDO selectivity to 4-propylbenzene and alkylated 4-propylbenzenes of 4 % at 92 % conversion (7 h on stream). Higher catalyst loadings pushed the 4-propylguaiacol conversion to 100 % and resulted in a higher selectivity to propylbenzene of 41 %, alkylated aromatics of 21 % and alkylated phenols of 17 % (51 % C-alkylation). The reactivity studies coupled with catalyst characterization revealed that Lewis acid sites act synergistically with neighboring Brønsted acid sites to simultaneously promote alkylation and hydrodeoxygenation activity. A reaction mechanism is proposed involving activation of the ether bond on a Lewis acid site, followed by methyl transfer and C-alkylation. Mo-based POMs represent a versatile catalytic platform to simultaneously upgrade lignin-derived oxygenated aromatics into alkylated arenes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Investigating selective transport and abrasion on an alluvial fan using quantitative grain size and shape analysis

    Science.gov (United States)

    Litwin, K. L.; Jerolmack, D. J.

    2011-12-01

    Selective sorting and abrasion are the two major fluvial processes that are attributed to the downstream fining of sediments in rivers and alluvial fans. Selective transport is the process by which smaller grains are preferentially transported downstream while larger grains are deposited closer to the source. Abrasion is defined by the production of fine sediments and sand that occurs by saltation of gravel, where particle-to-particle collisions supply the energy required to break apart grains. We hypothesize that abrasion results in the gradual fining of large grains and the production of fine sands and silts, while sorting accounts for the differences in transport of these two grain-size fractions produced from abrasion, thereby creating the abrupt gravel-sand transition observed in many channel systems. In this research, we explore both selective transport and abrasion processes on the Dog Canyon alluvial fan near Alamogordo, New Mexico. We complete an extensive grain size analysis down the main channel of the fan employing an image-based technique that utilizes an autocorrelation process. We also characterize changes in grain shape using standard shape parameters, as well as Fourier analysis, which allows the study of contributions of grain roughness on a variety of length scales. Sorting appears to dominate the upper portion of the fan; the grain-size distribution narrows moving downstream until reaching a point of equal mobility, at which point sorting ceases. Abrasion exerts a subtle but persistent effect on grains during transport down the fan. Shape analysis reveals that particles become more rounded by the removal of small-scale textural features, a process that is expected to only modestly influence grain size of gravel, but should produce significant quantities of sand. This study provides a better understanding of the importance of grain abrasion and sorting on the downstream fining of channel grains in an alluvial fan, as well as an improved knowledge

  10. Rejecting escape events in large volume Ge detectors by a pulse shape selection procedure

    International Nuclear Information System (INIS)

    Del Zoppo, A.; Agodi, C.; Alba, R.; Bellia, G.; Coniglione, R.; Loukachine, K.; Maiolino, C.; Migneco, E.; Piattelli, P.; Santonocito, D.; Sapienza, P.

    1993-01-01

    The dependence of the response to γ-rays of a large volume Ge detector on the interval width of a selected initial rise pulse slope is investigated. The number of escape events associated with a small pulse slope is found to be greater than the corresponding number of full energy events. An escape event rejection procedure based on the observed correlation between energy deposition and pulse shape is discussed. Such a procedure seems particularly suited for the design of highly granular large volume Ge detector arrays. (orig.)

  11. Inhibition shapes selectivity to vocalizations in the inferior colliculus of awake mice

    Directory of Open Access Journals (Sweden)

    Zachary eMayko

    2012-10-01

    Full Text Available The inferior colliculus (IC is a major center for integration of auditory information as itreceives ascending projections from a variety of brainstem nuclei as well as descending projectionsfrom the thalamus and auditory cortex. The ascending projections are both excitatory andinhibitory and their convergence at the IC results in a microcircuitry that is important forshaping responses to simple, binaural, and modulated sounds in the IC. Here, we examined therole inhibition plays in shaping selectivity to vocalizations in the IC of awake, normal-hearingadult mice (CBA/CaJ strain. Neurons in the IC of mice show selectivity in their responses tovocalizations, and we hypothesized that this selectivity is created by inhibitory microcircuitryin the IC. We compared single unit responses in the IC to pure tones and a variety of ultrasonicmouse vocalizations before and after iontophoretic application of GABAA receptor (GABAARand glycine receptor (GlyR antagonists. The most pronounced effects of blocking GABAAR andGlyR on IC neurons were to increase spike rates and broaden excitatory frequency tuning curvesin response to pure tone stimuli, and to decrease selectivity to vocalizations. Thus, inhibitionplays an important role in creating selectivity to vocalizations in the inferior colliculus.

  12. A Review of Selective Laser Melted NiTi Shape Memory Alloy

    Science.gov (United States)

    Khoo, Zhong Xun; Shen, Yu Fang

    2018-01-01

    NiTi shape memory alloys (SMAs) have the best combination of properties among the different SMAs. However, the limitations of conventional manufacturing processes and the poor manufacturability of NiTi have critically limited its full potential applicability. Thus, additive manufacturing, commonly known as 3D printing, has the potential to be a solution in fabricating complex NiTi smart structures. Recently, a number of studies on Selective Laser Melting (SLM) of NiTi were conducted to explore the various aspects of SLM-produced NiTi. Compared to producing conventional metals through the SLM process, the fabrication of NiTi SMA is much more challenging. Not only do the produced parts require a high density that leads to good mechanical properties, strict composition control is needed as well for the SLM NiTi to possess suitable phase transformation characteristics. Additionally, obtaining a good shape memory effect from the SLM NiTi samples is another challenging task that requires further understanding. This paper presents the results of the effects of energy density and SLM process parameters on the properties of SLM NiTi. Its shape memory properties and potential applications were then reviewed and discussed. PMID:29596320

  13. Feedbacks between community assembly and habitat selection shape variation in local colonization

    Science.gov (United States)

    Kraus, J.M.; Vonesh, J.R.

    2010-01-01

    1. Non-consumptive effects of predators are increasingly recognized as important drivers of community assembly and structure. Specifically, habitat selection responses to top predators during colonization and oviposition can lead to large differences in aquatic community structure, composition and diversity. 2. These differences among communities due to predators may develop as communities assemble, potentially altering the relative quality of predator vs. predator-free habitats through time. If so, community assembly would be expected to modify the subsequent behavioural responses of colonists to habitats containing top predators. Here, we test this hypothesis by manipulating community assembly and the presence of fish in experimental ponds and measuring their independent and combined effects on patterns of colonization by insects and amphibians. 3. Assembly modified habitat selection of dytscid beetles and hylid frogs by decreasing or even reversing avoidance of pools containing blue-spotted sunfish (Enneacanthus gloriosus). However, not all habitat selection responses to fish depended on assembly history. Hydrophilid beetles and mosquitoes avoided fish while chironomids were attracted to fish pools, regardless of assembly history. 4. Our results show that community assembly causes taxa-dependent feedbacks that can modify avoidance of habitats containing a top predator. Thus, non-consumptive effects of a top predator on community structure change as communities assemble and effects of competitors and other predators combine with the direct effects of top predators to shape colonization. 5. This work reinforces the importance of habitat selection for community assembly in aquatic systems, while illustrating the range of factors that may influence colonization rates and resulting community structure. Directly manipulating communities both during colonization and post-colonization is critical for elucidating how sequential processes interact to shape communities.

  14. Source characterisation and distribution of selected PCBs, PAHs and alkyl PAHs in sediments from the Klip and Jukskei Rivers, South Africa.

    Science.gov (United States)

    Rimayi, Cornelius; Chimuka, Luke; Odusanya, David; de Boer, Jacob; Weiss, Jana M

    2017-07-01

    A study of the distribution of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) utilising 16 priority PAHs, benzo(e)pyrene, perylene, 19 alkylated PAHs and 31 ortho substituted PCBs in South Africa is presented. It was aimed to (a) deduce characteristic contamination patterns for both PCBs and PAHs and (b) provide the first comprehensive dataset for establishment of source characterisation of PCBs and PAHs. This is in line with new South African legislation on mandatory monitoring of PCB and PAH emissions. Bar charts, principal component analysis (PCA) and biplots were utilised to identify signature contamination patterns and distribution of PCBs and PAHs within the Jukskei and Klip Rivers. Sediments from the Jukskei and Klip River catchments both showed distinct contamination signatures for hexa to nonachlorinated PCBs, characteristic of contamination by Aroclor 1254 and 1260 technical mixtures. PCB signature patterns in order of abundance were 138 > 180 > 206 > 153 > 187 > 149 and 138 > 153 > 180 > 149 > 187 > 110 > 170 for the Jukskei and Klip River sediments, respectively. The upstream Alberton point had the highest Σ31 PCB and Σ (parent+alkyl) PAH concentrations in the Klip River of 61 and 6000 μg kg -1 dry weight (dw), respectively. In the Jukskei River, the upstream Marlboro point had the highest Σ31 PCB concentration of 19 μg kg -1 dw and the N14 site recorded the highest Σ (parent+alkyl) PAH concentration of 2750 μg kg -1 dw. PAH concentrations in both the Jukskei and Klip Rivers were significantly higher than the PCB concentrations. Fluoranthene, phenanthrene and pyrene were found in the highest concentrations in both the Jukskei and Klip River sediments. Both the Jukskei and Klip River sediments showed trends of a mixed pyrogenic-petrogenic PAH source contamination.

  15. Adsorbate shape selectivity: Separation of the HF/134a azeotrope over carbogenic molecular sieve

    Energy Technology Data Exchange (ETDEWEB)

    Hong, A.; Mariwala, R.K.; Kane, M.S.; Foley, H.C. [Univ. of Delaware, Nework, DE (United States)

    1995-03-01

    Experimental evidence is provided for adsorptive shape selectivity in the separation of the azeotrope between HF and 1,1,1,2-tetrafluoroethane (134a) over pyrolyzed poly(furfuryl alcohol)-derived carbogenic molecular sieve (PPFA-CMS). The separation can be accomplished over coconut charcoal or Carbosieve G on the basis of the differences in the extent of equilibrium adsorption of HF and 134a. On these adsorbents 134a is more strongly bound than HF, thus it elutes much more slowly from the bed. The heat of adsorption for 134a in the vicinity of 200 C on Carbosieve G is {approximately}8.8 kcal/mol. In contrast, when the same azeotropic mixture is separated over PPFA-CMS prepared at 500 C, 134a is not adsorbed. As a result 134a elutes from the bed first, followed by HF. The reversal is brought about by the narrower pore size and pore size distribution of the PPFA-CMS versus that for Carbosieve G. Thus the separation over PPFA-CMS is an example of adsorbate shape selectivity and represents a limiting case of kinetic separation.

  16. An event-related brain potential study of visual selective attention to conjunctions of color and shape

    NARCIS (Netherlands)

    Smid, HGOM; Jakob, A; Heinze, HJ

    What cognitive processes underlie event-related brain potential (ERP) effects related to visual multidimensional selective attention and how are these processes organized? We recorded ERPs when participants attended to one conjunction of color, global shape and local shape and ignored other

  17. A New Spectral Shape-Based Record Selection Approach Using Np and Genetic Algorithms

    Directory of Open Access Journals (Sweden)

    Edén Bojórquez

    2013-01-01

    Full Text Available With the aim to improve code-based real records selection criteria, an approach inspired in a parameter proxy of spectral shape, named Np, is analyzed. The procedure is based on several objectives aimed to minimize the record-to-record variability of the ground motions selected for seismic structural assessment. In order to select the best ground motion set of records to be used as an input for nonlinear dynamic analysis, an optimization approach is applied using genetic algorithms focuse on finding the set of records more compatible with a target spectrum and target Np values. The results of the new Np-based approach suggest that the real accelerograms obtained with this procedure, reduce the scatter of the response spectra as compared with the traditional approach; furthermore, the mean spectrum of the set of records is very similar to the target seismic design spectrum in the range of interest periods, and at the same time, similar Np values are obtained for the selected records and the target spectrum.

  18. Feature diagnosticity and task context shape activity in human scene-selective cortex.

    Science.gov (United States)

    Lowe, Matthew X; Gallivan, Jason P; Ferber, Susanne; Cant, Jonathan S

    2016-01-15

    Scenes are constructed from multiple visual features, yet previous research investigating scene processing has often focused on the contributions of single features in isolation. In the real world, features rarely exist independently of one another and likely converge to inform scene identity in unique ways. Here, we utilize fMRI and pattern classification techniques to examine the interactions between task context (i.e., attend to diagnostic global scene features; texture or layout) and high-level scene attributes (content and spatial boundary) to test the novel hypothesis that scene-selective cortex represents multiple visual features, the importance of which varies according to their diagnostic relevance across scene categories and task demands. Our results show for the first time that scene representations are driven by interactions between multiple visual features and high-level scene attributes. Specifically, univariate analysis of scene-selective cortex revealed that task context and feature diagnosticity shape activity differentially across scene categories. Examination using multivariate decoding methods revealed results consistent with univariate findings, but also evidence for an interaction between high-level scene attributes and diagnostic visual features within scene categories. Critically, these findings suggest visual feature representations are not distributed uniformly across scene categories but are shaped by task context and feature diagnosticity. Thus, we propose that scene-selective cortex constructs a flexible representation of the environment by integrating multiple diagnostically relevant visual features, the nature of which varies according to the particular scene being perceived and the goals of the observer. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Directional selection has shaped the oral jaws of Lake Malawi cichlid fishes.

    Science.gov (United States)

    Albertson, R Craig; Streelman, J Todd; Kocher, Thomas D

    2003-04-29

    East African cichlid fishes represent one of the most striking examples of rapid and convergent evolutionary radiation among vertebrates. Models of ecological speciation would suggest that functional divergence in feeding morphology has contributed to the origin and maintenance of cichlid species diversity. However, definitive evidence for the action of natural selection has been missing. Here we use quantitative genetics to identify regions of the cichlid genome responsible for functionally important shape differences in the oral jaw apparatus. The consistent direction of effects for individual quantitative trait loci suggest that cichlid jaws and teeth evolved in response to strong, divergent selection. Moreover, several chromosomal regions contain a disproportionate number of quantitative trait loci, indicating a prominent role for pleiotropy or genetic linkage in the divergence of this character complex. Of particular interest are genomic intervals with concerted effects on both the length and height of the lower jaw. Coordinated changes in this area of the oral jaw apparatus are predicted to have direct consequences for the speed and strength of jaw movement. Taken together, our results imply that the rapid and replicative nature of cichlid trophic evolution is the result of directional selection on chromosomal packages that encode functionally linked aspects of the craniofacial skeleton.

  20. Formation of titanium oxide coatings on NiTi shape memory alloys by selective oxidation

    International Nuclear Information System (INIS)

    Pohl, M.; Glogowski, T.; Kuehn, S.; Hessing, C.; Unterumsberger, F.

    2008-01-01

    Materials used for medical devices that are in contact with human tissue must have good corrosion resistance and biocompatibility. NiTi shape memory alloys (SMAs) are often used in medical applications due to their special functional and mechanical properties (shape memory effect, pseudo elasticity). Because of the high Ni content in nearly stoichiometric NiTi SMAs, the possibility of Ni being released needs to be considered as Ni may cause problems in the human body. SMAs exhibit a high intrinsic corrosion resistance because of the thermodynamic stability of Ni (thermodynamic reason) and the low degree of disorder in a thin protective TiO 2 -layer (kinetic reason). While therefore there is no need to be concerned too much about a normal corrosive attack in the human body, it has to be kept in mind that in medical applications, these materials represent one part of a tribological system where wear processes need to be considered. The formation of a uniform TiO 2 -layer can be beneficial in this respect. The selective oxidation of Ti to TiO 2 on the surface is a promising method to decrease the Ni release significantly. This can be achieved by controlling the partial pressure of oxygen during a controlled oxidation process. The atmosphere must be adjusted so that TiO 2 is stable while NiO cannot yet form. The result of a selective oxidation is a TiO 2 -layer that has an excellent degree of purity and represents a safe barrier against Ni emission

  1. Manganese-catalyzed Dehydrogenative Alkylation or α-Olefination of Alkyl-N-Heteroaromatics by Alcohols.

    Science.gov (United States)

    Kempe, Rhett; Zhang, Guoying; Irrgang, Torsten; Dietel, Thomas; Kallmeier, Fabian

    2018-05-02

    Catalysis involving earth-abundant transition metals is an option to help save our rare noble metal resources and is especially interesting if novel reactivity or selectivity patterns are observed. We report here on a novel reaction: the dehydrogenative alkylation or α-olefination of alkyl-N-heteroaromatics by alcohols. Manganese complexes developed in our laboratory catalyze the reaction efficiently. Fe and Co complexes stabilized by such ligands are essentially inactive. Hydrogen is liberated during the reaction and bromo or iodo functional groups and olefins can be tolerated. A variety of alkyl-N-heteroaromatics can be functionalized, and benzyl and aliphatic alcohols undergo the reaction. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Exogenous selection rather than cytonuclear incompatibilities shapes asymmetrical fitness of reciprocal Arabidopsis hybrids.

    Science.gov (United States)

    Muir, Graham; Ruiz-Duarte, Paola; Hohmann, Nora; Mable, Barbara K; Novikova, Polina; Schmickl, Roswitha; Guggisberg, Alessia; Koch, Marcus A

    2015-04-01

    Reciprocal crosses between species often display an asymmetry in the fitness of F1 hybrids. This pattern, referred to as isolation asymmetry or Darwin's corollary to Haldane's rule, is a general feature of reproductive isolation in plants, yet factors determining its magnitude and direction remain unclear. We evaluated reciprocal species crosses between two naturally hybridizing diploid species of Arabidopsis to assess the degree of isolation asymmetry at different postmating life stages. We found that pollen from Arabidopsis arenosa will usually fertilize ovules from Arabidopsis lyrata; the reverse receptivity being less complete. Maternal A. lyrata parents set more F1 hybrid seed, but germinate at lower frequency, reversing the asymmetry. As predicted by theory, A. lyrata (the maternal parent with lower seed viability in crosses) exhibited accelerated chloroplast evolution, indicating that cytonuclear incompatibilities may play a role in reproductive isolation. However, this direction of asymmetrical reproductive isolation is not replicated in natural suture zones, where delayed hybrid breakdown of fertility at later developmental stages, or later-acting selection against A. arenosa maternal hybrids (unrelated to hybrid fertility, e.g., substrate adaptation) may be responsible for an excess of A. lyrata maternal hybrids. Exogenous selection rather than cytonuclear incompatibilities thus shapes the asymmetrical postmating isolation in nature.

  3. Facile preparation of an alternating copolymer-based high molecular shape-selective organic phase for reversed-phase liquid chromatography.

    Science.gov (United States)

    Mallik, Abul K; Noguchi, Hiroki; Rahman, Mohammed Mizanur; Takafuji, Makoto; Ihara, Hirotaka

    2018-06-22

    The synthesis of a new alternating copolymer-grafted silica phase is described for the separation of shape-constrained isomers of polycyclic aromatic hydrocarbons (PAHs) and tocopherols in reversed-phase high-performance liquid chromatography (RP-HPLC). Telomerization of the monomers (octadecyl acrylate and N-methylmaleimide) was carried out with a silane coupling agent; 3-mercaptopropyltrimethoxysilane (MPS), and the telomer (T) was grafted onto porous silica surface to prepare the alternating copolymer-grafted silica phase (Sil-alt-T). The new hybrid material was characterized by elemental analyses, diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, and solid-state 13 C and 29 Si cross-polarization magic-angle spinning (CP/MAS) NMR spectroscopy. The results of 13 C CP/MAS NMR demonstrated that the alkyl chains of the grafted polymers in Sil-alt-T remained disordered, amorphous, and mobile represented by gauche conformational form. Separation abilities and molecular-shape selectivities of the prepared organic phase were evaluated by the separation of PAHs isomers and Standard Reference Material 869b, Column Selectivity Test Mixture for Liquid Chromatography, respectively and compared with commercially available octadecylsilylated silica (ODS) and C 30 columns as well as previously reported alternating copolymer-based column. The effectiveness of this phase is also demonstrated by the separation of tocopherol isomers. Oriented functional groups along the polymer main chains and cavity formations are investigated to be the driving force for better separation with multiple-interactions with the solutes. One of the advantages of the Sil-alt-T phase to that of the previously reported phase is the synthesis of the telomer first and then immobilized onto silica surface. In this case, the telomer was characterized easily with simple spectroscopic techniques and the molecular mass and polydispersity index of the telomer were determined by size exclusion

  4. Iminium Salts by Meerwein Alkylation of Ehrlich’s Aldehyde

    Directory of Open Access Journals (Sweden)

    Gerhard Laus

    2013-03-01

    Full Text Available 4-(Dimethylaminobenzaldehyde is alkylated at the N atom by dialkyl sulfates, MeI, or Me3O BF4. In contrast, ethylation by Et3O BF4 occurs selectively at the O atom yielding a quinoid iminium ion. 4-(Diethylaminobenzaldehyde is alkylated only at O by either Et or Me oxonium reagent. The iminium salts are prone to hydrolysis giving the corresponding hydrotetrafluoroborates. Five crystal structures were determined.

  5. Synthesis of E-Alkyl Alkenes from Terminal Alkynes via Ni-Catalyzed Cross-Coupling of Alkyl Halides with B-Alkenyl-9-borabicyclo[3.3.1]nonanes.

    Science.gov (United States)

    Di Franco, Thomas; Epenoy, Alexandre; Hu, Xile

    2015-10-02

    The first Ni-catalyzed Suzuki-Miyaura coupling of alkyl halides with alkenyl-(9-BBN) reagents is reported. Both primary and secondary alkyl halides including alkyl chlorides can be coupled. The coupling method can be combined with hydroboration of terminal alkynes, allowing the expedited synthesis of functionalized alkyl alkenes from readily available alkynes with complete (E)-selectivity in one pot. The method was applied to the total synthesis of (±)-Recifeiolide, a natural macrolide.

  6. Heterofacial alkylation of alkylenediamines by higher alkyl halides

    International Nuclear Information System (INIS)

    Semenov, V.A.; Kryshko, G.M.; Sokal'skaya, L.I.; Zhukova, N.G.

    1985-01-01

    A study of the physiochemical properties of alkylenediamines substituted by lower alkyls, showed that they possess increased complex-forming ability with respect to salts of different metals as titanium, niobium, zirconium, molybdenum, and zinc. To create a simpler method of synthesis of higher tetraaklyalkylalklyenediamines, based on the use of the accessible domestic raw material, the authors investigated the reaction of alkylenediamines with various alkyl halides. It was established that the best reagents can be obtained using alkyl bromides. It is concluded that the procedure of alkylation of alkylenediamines by higher alkyl halides in the presence of water developed permits the production of terraalkylalkylenediamines in one step with good yield and with purity acceptable for use as extraction reagents

  7. Exploring Solvent Shape and Function Using - and Isomer-Selective Vibrational Spectroscopy

    Science.gov (United States)

    Johnson, Mark

    2010-06-01

    We illustrate the new types of information than can be obtained through isomer-selective ``hole-burning'' spectroscopy carried out in the vibrational manifolds of Ar-tagged cluster ions. Three examples of increasing complexity will be presented where the changes in a solute ion are correlated with different morphologies of a surrounding solvent cage. In the first, we discuss the weak coupling limit where different hydration morphologies lead to small distortions of a covalent ion. We then introduce the more interesting case of the hydrated electron, where different shapes of the water network lead to dramatic changes in the extent of delocalization in the diffuse excess electron cloud. We then turn to the most complex case involving hydration of the nitrosonium ion, where different arrangements of the same number of water molecules span the range in behavior from simple solvation to actively causing a chemical reaction. The latter results are particularly interesting as they provide a microscopic, molecular-level picture of the ``solvent coordinate'' commonly used to describe solvent mediated processes.

  8. Shape selectivity in organic synthesis; Selectividad de forma en sintesis organica

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Luenga, M.A.; Yates, M. [Instituto de Quimica-Fisica Rocasolano CSIC, Madrid (Spain)

    1995-12-31

    Heterogeneous catalysis is the most convenient method for many organic syntheses due mainly to the ease of experimental handling and the savings in costs, since finely divided catalysts suspended in the reaction medium (liquid in a high percentage of cases, due to the need for working at low temperatures to avoid undesired side reactions) can be easily recovered at the end of the reaction. Zeotypes are amongst the most important solid catalysts to be used in organic synthesis (1-5), due to their porous nature with controllable properties such as acidity,and molecular sized cavities where reactions take place in quasi-enzymatic conditions, since molecules of greater size than the pore opening are not able to enter react. This steric hindrance gives rise to the property defined as shape selectivity (2). Between the 1960`s and 1980`s catalysis with zeotypes was dedicated to petrochemical processes (refining and hydrotreating), due to the petroleum crises during that period. More recently their uses have been broadened to incorporate all types of organic syntheses, with appreciable advantages over more conventional catalysts in a number of processes. (Author)

  9. Morpho morphometrics: Shared ancestry and selection drive the evolution of wing size and shape in Morpho butterflies.

    Science.gov (United States)

    Chazot, Nicolas; Panara, Stephen; Zilbermann, Nicolas; Blandin, Patrick; Le Poul, Yann; Cornette, Raphaël; Elias, Marianne; Debat, Vincent

    2016-01-01

    Butterfly wings harbor highly diverse phenotypes and are involved in many functions. Wing size and shape result from interactions between adaptive processes, phylogenetic history, and developmental constraints, which are complex to disentangle. Here, we focus on the genus Morpho (Nymphalidae: Satyrinae, 30 species), which presents a high diversity of sizes, shapes, and color patterns. First, we generate a comprehensive molecular phylogeny of these 30 species. Next, using 911 collection specimens, we quantify the variation of wing size and shape across species, to assess the importance of shared ancestry, microhabitat use, and sexual selection in the evolution of the wings. While accounting for phylogenetic and allometric effects, we detect a significant difference in wing shape but not size among microhabitats. Fore and hindwings covary at the individual and species levels, and the covariation differs among microhabitats. However, the microhabitat structure in covariation disappears when phylogenetic relationships are taken into account. Our results demonstrate that microhabitat has driven wing shape evolution, although it has not strongly affected forewing and hindwing integration. We also found that sexual dimorphism of forewing shape and color pattern are coupled, suggesting a common selective force. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  10. Genomic architecture of habitat-related divergence and signature of directional selection in the body shapes of Gnathopogon fishes.

    Science.gov (United States)

    Kakioka, Ryo; Kokita, Tomoyuki; Kumada, Hiroki; Watanabe, Katsutoshi; Okuda, Noboru

    2015-08-01

    Evolution of ecomorphologically relevant traits such as body shapes is important to colonize and persist in a novel environment. Habitat-related adaptive divergence of these traits is therefore common among animals. We studied the genomic architecture of habitat-related divergence in the body shape of Gnathopogon fishes, a novel example of lake-stream ecomorphological divergence, and tested for the action of directional selection on body shape differentiation. Compared to stream-dwelling Gnathopogon elongatus, the sister species Gnathopogon caerulescens, exclusively inhabiting a large ancient lake, had an elongated body, increased proportion of the caudal region and small head, which would be advantageous in the limnetic environment. Using an F2 interspecific cross between the two Gnathopogon species (195 individuals), quantitative trait locus (QTL) analysis with geometric morphometric quantification of body shape and restriction-site associated DNA sequencing-derived markers (1622 loci) identified 26 significant QTLs associated with the interspecific differences of body shape-related traits. These QTLs had small to moderate effects, supporting polygenic inheritance of the body shape-related traits. Each QTL was mostly located on different genomic regions, while colocalized QTLs were detected for some ecomorphologically relevant traits that are proxy of body and caudal peduncle depths, suggesting different degree of modularity among traits. The directions of the body shape QTLs were mostly consistent with the interspecific difference, and QTL sign test suggested a genetic signature of directional selection in the body shape divergence. Thus, we successfully elucidated the genomic architecture underlying the adaptive changes of the quantitative and complex morphological trait in a novel system. © 2015 John Wiley & Sons Ltd.

  11. Hydride Transfer versus Deprotonation Kinetics in the Isobutane–Propene Alkylation Reaction: A Computational Study

    OpenAIRE

    Liu, Chong; van Santen, Rutger A.; Poursaeidesfahani, Ali; Vlugt, Thijs J. H.; Pidko, Evgeny A.; Hensen, Emiel J. M.

    2017-01-01

    The alkylation of isobutane with light alkenes plays an essential role in modern petrochemical processes for the production of high-octane gasoline. In this study we have employed periodic DFT calculations combined with microkinetic simulations to investigate the complex reaction mechanism of isobutane–propene alkylation catalyzed by zeolitic solid acids. Particular emphasis was given to addressing the selectivity of the alkylate formation versus alkene formation, which requires a high rate o...

  12. Patch-based generative shape model and MDL model selection for statistical analysis of archipelagos

    DEFF Research Database (Denmark)

    Ganz, Melanie; Nielsen, Mads; Brandt, Sami

    2010-01-01

    We propose a statistical generative shape model for archipelago-like structures. These kind of structures occur, for instance, in medical images, where our intention is to model the appearance and shapes of calcifications in x-ray radio graphs. The generative model is constructed by (1) learning ...

  13. An algorithm for selecting the most accurate protocol for contact angle measurement by drop shape analysis.

    Science.gov (United States)

    Xu, Z N

    2014-12-01

    In this study, an error analysis is performed to study real water drop images and the corresponding numerically generated water drop profiles for three widely used static contact angle algorithms: the circle- and ellipse-fitting algorithms and the axisymmetric drop shape analysis-profile (ADSA-P) algorithm. The results demonstrate the accuracy of the numerically generated drop profiles based on the Laplace equation. A significant number of water drop profiles with different volumes, contact angles, and noise levels are generated, and the influences of the three factors on the accuracies of the three algorithms are systematically investigated. The results reveal that the above-mentioned three algorithms are complementary. In fact, the circle- and ellipse-fitting algorithms show low errors and are highly resistant to noise for water drops with small/medium volumes and contact angles, while for water drop with large volumes and contact angles just the ADSA-P algorithm can meet accuracy requirement. However, this algorithm introduces significant errors in the case of small volumes and contact angles because of its high sensitivity to noise. The critical water drop volumes of the circle- and ellipse-fitting algorithms corresponding to a certain contact angle error are obtained through a significant amount of computation. To improve the precision of the static contact angle measurement, a more accurate algorithm based on a combination of the three algorithms is proposed. Following a systematic investigation, the algorithm selection rule is described in detail, while maintaining the advantages of the three algorithms and overcoming their deficiencies. In general, static contact angles over the entire hydrophobicity range can be accurately evaluated using the proposed algorithm. The ease of erroneous judgment in static contact angle measurements is avoided. The proposed algorithm is validated by a static contact angle evaluation of real and numerically generated water drop

  14. Selective axonal growth of embryonic hippocampal neurons according to topographic features of various sizes and shapes

    Directory of Open Access Journals (Sweden)

    Christine E Schmidt

    2010-12-01

    Full Text Available David Y Fozdar1*, Jae Y Lee2*, Christine E Schmidt2–6, Shaochen Chen1,3–5,7,1Departments of Mechanical Engineering, 2Chemical Engineering, 3Biomedical Engineering; 4Center for Nano Molecular Science and Technology; 5Texas Materials Institute; 6Institute of Neuroscience; 7Microelectronics Research Center, The University of Texas at Austin, Austin, TX, USA *Contributed equally to this workPurpose: Understanding how surface features influence the establishment and outgrowth of the axon of developing neurons at the single cell level may aid in designing implantable scaffolds for the regeneration of damaged nerves. Past studies have shown that micropatterned ridge-groove structures not only instigate axon polarization, alignment, and extension, but are also preferred over smooth surfaces and even neurotrophic ligands.Methods: Here, we performed axonal-outgrowth competition assays using a proprietary four-quadrant topography grid to determine the capacity of various micropatterned topographies to act as stimuli sequestering axon extension. Each topography in the grid consisted of an array of microscale (approximately 2 µm or submicroscale (approximately 300 nm holes or lines with variable dimensions. Individual rat embryonic hippocampal cells were positioned either between two juxtaposing topographies or at the borders of individual topographies juxtaposing unpatterned smooth surface, cultured for 24 hours, and analyzed with respect to axonal selection using conventional imaging techniques.Results: Topography was found to influence axon formation and extension relative to smooth surface, and the distance of neurons relative to topography was found to impact whether the topography could serve as an effective cue. Neurons were also found to prefer submicroscale over microscale features and holes over lines for a given feature size.Conclusion: The results suggest that implementing physical cues of various shapes and sizes on nerve guidance conduits

  15. Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety.

    Science.gov (United States)

    Cohen, Joshua L; Glover, Matthew E; Pugh, Phyllis C; Fant, Andrew D; Simmons, Rebecca K; Akil, Huda; Kerman, Ilan A; Clinton, Sarah M

    2015-01-01

    The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high versus low behavioral response to novelty and found that high-reactive (bred high-responder, bHR) rats displayed greater risk-taking, impulsivity and aggression relative to low-reactive (bred low-responder, bLR) rats, which showed high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable, but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior to the brain development and emotional behavior of bLR offspring. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine the effects on the following: (1) developmental gene expression in the hippocampus and amygdala and (2) adult anxiety/depression-like behavior. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus), reduced adult anxiety and enhanced social interaction. Our findings illustrate how an early-life manipulation such as cross-fostering changes the brain's developmental trajectory and ultimately impacts adult behavior. Moreover, while earlier studies highlighted hippocampal differences contributing to the bHR/bLR phenotypes, our results point to a role of the amygdala as well. Future work will pursue genetic and cellular mechanisms within the amygdala that contribute to bHR/bLR behavior either at baseline or following environmental manipulations. © 2015 S. Karger AG, Basel.

  16. DNA modification by alkylating compounds

    Energy Technology Data Exchange (ETDEWEB)

    Kruglyakova, E.E.

    1985-09-01

    Results are given for research on the physico-chemical properties of alkylating compounds - nitroso alkyl ureas (NAU) which possess a broad spectrum of biological activity, such as mutagenic, carcinogenic, and anti-tumor action that is due to the alkylation and carbamoylation of DNA as well as other cellular components. Identified chemical products of NAU interaction with DNA and its components are cited. Structural conversions of a DNA macromolecule resulting from its chemical modification are examined. NAU are used to discuss possible biological consequences of DNA modification. 148 references.

  17. Formation of enamines by alkylation of imines

    NARCIS (Netherlands)

    Heiszwolf, G.J.; Kloosterziel, H.

    1966-01-01

    cf. CA 64, 12473c. With ice-cooling, 1 equiv. alkylating agent was added to one equiv. of the imine in 1M soln. in a solvent in the presence of NaH to give both N- and C-alkylated products. The following summarizes the date (imine, solvent, alkylating agent, % unreacted imine, % N-alkylated product,

  18. Regioselective 1-N-Alkylation and Rearrangement of Adenosine Derivatives.

    Science.gov (United States)

    Oslovsky, Vladimir E; Drenichev, Mikhail S; Mikhailov, Sergey N

    2015-01-01

    Several methods for the preparation of some N(6)-substituted adenosines based on selective 1-N-alkylation with subsequent Dimroth rearrangement were developed. The proposed methods seem to be effective for the preparation of natural N(6)-isopentenyl- and N(6)-benzyladenosines, which are known to possess pronounced biological activities. Direct 1-N-alkylation of 2',3',5'-tri-O-acetyladenosine and 3',5'-di-O-acetyl-2'-deoxyadenosine with alkyl halides in N,N-dimethylformamide (DMF) in the presence of BaCO3 and KI gave 1-N-substituted derivatives with quantitative yields, whereas 1-N-alkylation of adenosine was accompanied by significant O-alkylation. Moreover, the reaction of trimethylsilyl derivatives of N(6)-acetyl-2',3',5'-tri-O-acetyladenosine and N(6)-acetyl-3',5'-di-O-acetyl-2'-deoxyadenosine with alkyl halides leads to the formation of the stable 1-N-substituted adenosines. Dimroth rearrangement of 1-N-substituted adenosines in aqueous ammonia yields pure N(6)-substituted adenosines.

  19. α-Selective Ni-Catalyzed Hydroalumination of Aryl- and Alkyl-Substituted Terminal Alkynes. Practical Syntheses of Internal Vinyl Aluminums, Halides or Boronates

    Science.gov (United States)

    Gao, Fang; Hoveyda, Amir H.

    2010-01-01

    Methods for Ni-catalyzed hydroalumination of terminal alkynes, leading to the formation of α-vinylaluminum isomers efficiently (>98% conv in 2–12 h) and with high selectivity (95% to >98% α), are described. Catalytic α-selective hydroalumination reactions proceed in the presence of a reagent (diisobutylaluminum hydride; dibal–H) and 3.0 mol % metal complex (Ni(dppp)Cl2) that are commercially available and inexpensive. Under the same conditions, but with Ni(PPh3)2Cl2, hydroalumination becomes highly β-selective, and, unlike uncatalyzed transformations with dibal–H, generates little or no alkynylaluminum byproducts. All hydrometallation reactions are reliable, operationally simple and practical, and afford an assortment of vinylaluminums that are otherwise not easily accessible. The derived α-vinyl halides and boronates can be synthesized through direct treatment with the appropriate electrophiles [e.g., Br2 and methoxy(pinacolato)boron, respectively]. Ni-catalyzed hydroaluminations can be performed with as little as 0.1 mol % catalyst and on gram scale with equally high efficiency and selectivity. PMID:20698643

  20. Target objects defined by a conjunction of colour and shape can be selected independently and in parallel.

    Science.gov (United States)

    Jenkins, Michael; Grubert, Anna; Eimer, Martin

    2017-11-01

    It is generally assumed that during search for targets defined by a feature conjunction, attention is allocated sequentially to individual objects. We tested this hypothesis by tracking the time course of attentional processing biases with the N2pc component in tasks where observers searched for two targets defined by a colour/shape conjunction. In Experiment 1, two displays presented in rapid succession (100 ms or 10 ms SOA) each contained a target and a colour-matching or shape-matching distractor on opposite sides. Target objects in both displays elicited N2pc components of similar size that overlapped in time when the SOA was 10 ms, suggesting that attention was allocated in parallel to both targets. Analogous results were found in Experiment 2, where targets and partially matching distractors were both accompanied by an object without target-matching features. Colour-matching and shape-matching distractors also elicited N2pc components, and the target N2pc was initially identical to the sum of the two distractor N2pcs, suggesting that the initial phase of attentional object selection was guided independently by feature templates for target colour and shape. Beyond 230 ms after display onset, the target N2pc became superadditive, indicating that attentional selection processes now started to be sensitive to the presence of feature conjunctions. Results show that independent attentional selection processes can be activated in parallel by two target objects in situations where these objects are defined by a feature conjunction.

  1. Cyclodextrin Films with Fast Solvent Transport and Shape-Selective Permeability

    KAUST Repository

    Villalobos, Luis Francisco; Huang, Tiefan; Peinemann, Klaus-Viktor

    2017-01-01

    paths of defined aperture in the separation layer that can effectively discriminate between molecules. The transport of molecules through these membranes is highly shape-sensitive. In addition, the presence of hydrophobic (cavity) and hydrophilic (ester

  2. Poly(alkyl acrylate) nonparticles

    International Nuclear Information System (INIS)

    Kreuter, J.

    1985-01-01

    This study deals with the preparation of poly(alkyl acrylic) and poly(alkyl cyanocrylic) nanoparticles. Nonoparticles are solid colloidal particles, consisting of macromolecular materials in which drugs or biologically active materials are dissolved, entrapped, and encapsulated, and/or to which the active substance is adsorbed or attached. Poly(alkyl acrylic) nanoparticles are much more slowly biodegradable than poly(alkyl cyanoacrylate) nanoparticles, and are thus more suitable for drug delivery purposes. Poly(methyl methacrylate) is the material of choice for the use of nanoparticles as an adjuvant for vaccines and are produced by emulsifier-free polymerization in aqueous media. The polymerization, which can be initiated with gamma rays or with potassium peroxodisulfate, is described

  3. Synthesis of Alkanethiolate-Capped Metal Nanoparticles Using Alkyl Thiosulfate Ligand Precursors: A Method to Generate Promising Reagents for Selective Catalysis

    Directory of Open Access Journals (Sweden)

    Khin Aye San

    2018-05-01

    Full Text Available Evaluation of metal nanoparticle catalysts functionalized with well-defined thiolate ligands can be potentially important because such systems can provide a spatial control in the reactivity and selectivity of catalysts. A synthetic method utilizing Bunte salts (sodium S-alkylthiosulfates allows the formation of metal nanoparticles (Au, Ag, Pd, Pt, and Ir capped with alkanethiolate ligands. The catalysis studies on Pd nanoparticles show a strong correlation between the surface ligand structure/composition and the catalytic activity and selectivity for the hydrogenation/isomerization of alkenes, dienes, trienes, and allylic alcohols. The high selectivity of Pd nanoparticles is driven by the controlled electronic properties of the Pd surface limiting the formation of Pd–alkene adducts (or intermediates necessary for (additional hydrogenation. The synthesis of water soluble Pd nanoparticles using ω-carboxylate-S-alkanethiosulfate salts is successfully achieved and these Pd nanoparticles are examined for the hydrogenation of various unsaturated compounds in both homogeneous and heterogeneous environments. Alkanethiolate-capped Pt nanoparticles are also successfully synthesized and further investigated for the hydrogenation of various alkynes to understand their geometric and electronic surface properties. The high catalytic activity of activated terminal alkynes, but the significantly low activity of internal alkynes and unactivated terminal alkynes, are observed for Pt nanoparticles.

  4. Evaluation of fluorine-18-labeled alkylating agents as potential synthons for the labeling of oligonucleotides

    NARCIS (Netherlands)

    de Vries, EFJ; Vroegh, J; Elsinga, PH; Vaalburg, W

    Six fluorine-18-labeled alkylating agents were selected as potentially suitable synthons for the labeling of antisense oligonucleotides. The selected synthons were evaluated in a model reaction with the monomer adenosine 5'-O-thiomonophosphate. Of these synthons,

  5. DNA minor groove targeted alkylating agents based on bisbenzimidazole carriers: synthesis, cytotoxicity and sequence-specificity of DNA alkylation.

    Science.gov (United States)

    Smaill, J B; Fan, J Y; Denny, W A

    1998-12-01

    respect to the bisbenzimidazole carrier. The 'targeted' bisbenzimidazole bis(hydroxymethyl)pyrrole- and imidazole analogues showed very similar patterns of alkylation to the corresponding 'untargeted' compounds, with little evidence of additional selectivity imposed by this AT-preferring carrier.

  6. Selection on the Major Color Gene Melanocortin-1-Receptor Shaped the Evolution of the Melanocortin System Genes

    Directory of Open Access Journals (Sweden)

    Linda Dib

    2017-12-01

    Full Text Available Modular genetic systems and networks have complex evolutionary histories shaped by selection acting on single genes as well as on their integrated function within the network. However, uncovering molecular coevolution requires the detection of coevolving sites in sequences. Detailed knowledge of the functions of each gene in the system is also necessary to identify the selective agents driving coevolution. Using recently developed computational tools, we investigated the effect of positive selection on the coevolution of ten major genes in the melanocortin system, responsible for multiple physiological functions and human diseases. Substitutions driven by positive selection at the melanocortin-1-receptor (MC1R induced more coevolutionary changes on the system than positive selection on other genes in the system. Contrarily, selection on the highly pleiotropic POMC gene, which orchestrates the activation of the different melanocortin receptors, had the lowest coevolutionary influence. MC1R and possibly its main function, melanin pigmentation, seems to have influenced the evolution of the melanocortin system more than functions regulated by MC2-5Rs such as energy homeostasis, glucocorticoid-dependent stress and anti-inflammatory responses. Although replication in other regulatory systems is needed, this suggests that single functional aspects of a genetic network or system can be of higher importance than others in shaping coevolution among the genes that integrate it.

  7. Synthesis of alkylated deoxyno irimycin and 1,5-dideoxy-1,5-iminoxylitol analogues:

    DEFF Research Database (Denmark)

    Szczepina, M.G.; Johnston, B.D; Yuan, Y.

    2004-01-01

    The syntheses of N-alkylated deoxynojirimycin and 1,5-dideoxy-1,5-iminoxylitol derivatives having either a D- or an L-erythritol-3-sulfate functionalized N-substituent are reported. The alkylating agent used was a cyclic sulfate derivative, whereby selective attack of the nitrogen atom at the least...

  8. Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

    Directory of Open Access Journals (Sweden)

    Michele Mari

    2014-08-01

    Full Text Available The reaction of 3-substituted indoles with dehydroalanine (Dha derivatives under Lewis acid-mediated conditions has been investigated. The formation of 2-substituted tryptophans is proposed to occur through a selective alkylative dearomatization–cyclization followed by C3- to C2-alkyl migration and rearomatization.

  9. Cyclodextrin Films with Fast Solvent Transport and Shape-Selective Permeability

    KAUST Repository

    Villalobos, Luis Francisco

    2017-04-24

    This study describes the molecular-level design of a new type of filtration membrane made of crosslinked cyclodextrins-inexpensive macrocycles of glucose, shaped like hollow truncated cones. The channel-like cavities of cyclodextrins spawn numerous paths of defined aperture in the separation layer that can effectively discriminate between molecules. The transport of molecules through these membranes is highly shape-sensitive. In addition, the presence of hydrophobic (cavity) and hydrophilic (ester-crosslinked outer part) domains in these films results in high permeances for both polar and nonpolar solvents.

  10. Shape selection in Landsat time series: A tool for monitoring forest dynamics

    Science.gov (United States)

    Gretchen G. Moisen; Mary C. Meyer; Todd A. Schroeder; Xiyue Liao; Karen G. Schleeweis; Elizabeth A. Freeman; Chris Toney

    2016-01-01

    We present a new methodology for fitting nonparametric shape-restricted regression splines to time series of Landsat imagery for the purpose of modeling, mapping, and monitoring annual forest disturbance dynamics over nearly three decades. For each pixel and spectral band or index of choice in temporal Landsat data, our method delivers a smoothed rendition of...

  11. Systems and methods for selective detection and imaging in coherent Raman microscopy by spectral excitation shaping

    Science.gov (United States)

    Xie, Xiaoliang Sunney; Freudiger, Christian; Min, Wei

    2016-03-15

    A microscopy imaging system is disclosed that includes a light source system, a spectral shaper, a modulator system, an optics system, an optical detector and a processor. The light source system is for providing a first train of pulses and a second train of pulses. The spectral shaper is for spectrally modifying an optical property of at least some frequency components of the broadband range of frequency components such that the broadband range of frequency components is shaped producing a shaped first train of pulses to specifically probe a spectral feature of interest from a sample, and to reduce information from features that are not of interest from the sample. The modulator system is for modulating a property of at least one of the shaped first train of pulses and the second train of pulses at a modulation frequency. The optical detector is for detecting an integrated intensity of substantially all optical frequency components of a train of pulses of interest transmitted or reflected through the common focal volume. The processor is for detecting a modulation at the modulation frequency of the integrated intensity of substantially all of the optical frequency components of the train of pulses of interest due to the non-linear interaction of the shaped first train of pulses with the second train of pulses as modulated in the common focal volume, and for providing an output signal for a pixel of an image for the microscopy imaging system.

  12. Investigating category- and shape-selective neural processing in ventral and dorsal visual stream under interocular suppression.

    Science.gov (United States)

    Ludwig, Karin; Kathmann, Norbert; Sterzer, Philipp; Hesselmann, Guido

    2015-01-01

    Recent behavioral and neuroimaging studies using continuous flash suppression (CFS) have suggested that action-related processing in the dorsal visual stream might be independent of perceptual awareness, in line with the "vision-for-perception" versus "vision-for-action" distinction of the influential dual-stream theory. It remains controversial if evidence suggesting exclusive dorsal stream processing of tool stimuli under CFS can be explained by their elongated shape alone or by action-relevant category representations in dorsal visual cortex. To approach this question, we investigated category- and shape-selective functional magnetic resonance imaging-blood-oxygen level-dependent responses in both visual streams using images of faces and tools. Multivariate pattern analysis showed enhanced decoding of elongated relative to non-elongated tools, both in the ventral and dorsal visual stream. The second aim of our study was to investigate whether the depth of interocular suppression might differentially affect processing in dorsal and ventral areas. However, parametric modulation of suppression depth by varying the CFS mask contrast did not yield any evidence for differential modulation of category-selective activity. Together, our data provide evidence for shape-selective processing under CFS in both dorsal and ventral stream areas and, therefore, do not support the notion that dorsal "vision-for-action" processing is exclusively preserved under interocular suppression. © 2014 Wiley Periodicals, Inc.

  13. The role of protozoa-driven selection in shaping human genetic variability.

    Science.gov (United States)

    Pozzoli, Uberto; Fumagalli, Matteo; Cagliani, Rachele; Comi, Giacomo P; Bresolin, Nereo; Clerici, Mario; Sironi, Manuela

    2010-03-01

    Protozoa exert a strong selective pressure in humans. The selection signatures left by these pathogens can be exploited to identify genetic modulators of infection susceptibility. We show that protozoa diversity in different geographic locations is a good measure of protozoa-driven selective pressure; protozoa diversity captured selection signatures at known malaria resistance loci and identified several selected single nucleotide polymorphisms in immune and hemolytic anemia genes. A genome-wide search enabled us to identify 5180 variants mapping to 1145 genes that are subjected to protozoa-driven selective pressure. We provide a genome-wide estimate of protozoa-driven selective pressure and identify candidate susceptibility genes for protozoa-borne diseases. Copyright 2010 Elsevier Ltd. All rights reserved.

  14. The role of parasite-driven selection in shaping landscape genomic structure in red grouse (Lagopus lagopus scotica).

    Science.gov (United States)

    Wenzel, Marius A; Douglas, Alex; James, Marianne C; Redpath, Steve M; Piertney, Stuart B

    2016-01-01

    Landscape genomics promises to provide novel insights into how neutral and adaptive processes shape genome-wide variation within and among populations. However, there has been little emphasis on examining whether individual-based phenotype-genotype relationships derived from approaches such as genome-wide association (GWAS) manifest themselves as a population-level signature of selection in a landscape context. The two may prove irreconcilable as individual-level patterns become diluted by high levels of gene flow and complex phenotypic or environmental heterogeneity. We illustrate this issue with a case study that examines the role of the highly prevalent gastrointestinal nematode Trichostrongylus tenuis in shaping genomic signatures of selection in red grouse (Lagopus lagopus scotica). Individual-level GWAS involving 384 SNPs has previously identified five SNPs that explain variation in T. tenuis burden. Here, we examine whether these same SNPs display population-level relationships between T. tenuis burden and genetic structure across a small-scale landscape of 21 sites with heterogeneous parasite pressure. Moreover, we identify adaptive SNPs showing signatures of directional selection using F(ST) outlier analysis and relate population- and individual-level patterns of multilocus neutral and adaptive genetic structure to T. tenuis burden. The five candidate SNPs for parasite-driven selection were neither associated with T. tenuis burden on a population level, nor under directional selection. Similarly, there was no evidence of parasite-driven selection in SNPs identified as candidates for directional selection. We discuss these results in the context of red grouse ecology and highlight the broader consequences for the utility of landscape genomics approaches for identifying signatures of selection. © 2015 John Wiley & Sons Ltd.

  15. Dynamic stereoscopic selective visual attention (dssva): integrating motion and shape with depth in video segmentation

    OpenAIRE

    López Bonal, María Teresa; Fernández Caballero, Antonio; Saiz Valverde, Sergio

    2008-01-01

    Depth inclusion as an important parameter for dynamic selective visual attention is presented in this article. The model introduced in this paper is based on two previously developed models, dynamic selective visual attention and visual stereoscopy, giving rise to the so-called dynamic stereoscopic selective visual attention method. The three models are based on the accumulative computation problem-solving method. This paper shows how software reusability enables enhancing results in vision r...

  16. Alkyl and aryl phosphorodiiodidites. Pt. 2

    International Nuclear Information System (INIS)

    Feshchenko, N.G.; Kostina, V.G.

    1976-01-01

    Alkyl phosphorodiiodidites are formed in the reactions of alkyl phosphorodichloridites with lithium iodide. They are stable at -60 to -50 0 . When warmed to 20 0 , they disproportionate with conversion into trialkyl phosphites and phosphorus triiodide. The latter also react together and give alkyl iodides, diphosphorus tetraiodide, and a polymer of unestablished structure. Diaryl and dialkyl phosphoriodidites are stable only in solution at low temperatures. They disproportionate in a similar way to aryl and alkyl phosphorodiiodidites. Alkyl phosphorodiiodidites react with iodine with the formation of alkyl iodides and phosphoryl iodide

  17. Twenty years of artificial directional selection have shaped the genome of the Italian Large White pig breed.

    Science.gov (United States)

    Schiavo, G; Galimberti, G; Calò, D G; Samorè, A B; Bertolini, F; Russo, V; Gallo, M; Buttazzoni, L; Fontanesi, L

    2016-04-01

    In this study, we investigated at the genome-wide level if 20 years of artificial directional selection based on boar genetic evaluation obtained with a classical BLUP animal model shaped the genome of the Italian Large White pig breed. The most influential boars of this breed (n = 192), born from 1992 (the beginning of the selection program of this breed) to 2012, with an estimated breeding value reliability of >0.85, were genotyped with the Illumina Porcine SNP60 BeadChip. After grouping the boars in eight classes according to their year of birth, filtered single nucleotide polymorphisms (SNPs) were used to evaluate the effects of time on genotype frequency changes using multinomial logistic regression models. Of these markers, 493 had a PBonferroni  selection program. The obtained results indicated that the genome of the Italian Large White pigs was shaped by a directional selection program derived by the application of methodologies assuming the infinitesimal model that captured a continuous trend of allele frequency changes in the boar population. © 2015 Stichting International Foundation for Animal Genetics.

  18. The Effect of Divergent Selection on 4-wk BW on the Shape of Growth Curve in Japanese Quail

    Directory of Open Access Journals (Sweden)

    H Beyki

    2011-12-01

    Full Text Available The current study was conducted to investigate the effect of short-term divergent selection on the shape growth curve in different lines of Japanese quail. The Quail lines utilized in this study were two divergently selected for high (HW and low (LW 4-wk body weight during 7 generation and also a control line (C. The Richard function parameters were used to describe growth curves of different lines. The weight at hatch was approximately similar among lines (8.08 g, 7.55 g and 8.76 g for HW, LW and C line respectively. The results of current study indicated that the selected lines (HW & LW were immediately diverged from the C line after hatch. Sexes within each line had no difference in average growth rate, age and body weight at inflection point and adult body weight. However significant differences were found in the growth curve parameters among lines. The results of current study indicated that short term divergent selection for 4-wk BW in Japanese quail can change the growth pattern and the carcass compartments of the selected birds. Therefore to avoid undesirable side effects due to selection in Japanese quails it is recommended to consider the growth pattern changes of the selected birds in the breeding programs

  19. Shape-selective Valorization of Biomass-derived Glycolaldehyde using Tin-containing Zeolites

    DEFF Research Database (Denmark)

    Tolborg, Søren; Meier, Sebastian; Shunmugavel, Saravanamurugan

    2016-01-01

    sugars while hindering consecutive aldol reactions leading to hexose sugars. High yields of tetrose sugars (74 %) with minor amounts of vinyl glycolic acid (VGA), an α-hydroxyacid, are obtained using Sn-MFI with selectivities towards C4 products reaching 97 %. Tin catalysts having large pores or no pore...... structure (Sn-Beta, Sn-MCM-41, Sn-SBA-15, tin chloride) led to lower selectivities for C4 sugars due to formation of hexose sugars. In the case of Sn-Beta, VGA is the main product (30 %), illustrating differences in selectivity of the Sn sites in the different frameworks. Under optimized conditions, GA can...

  20. Ionic liquid containing hydroxamate and N-alkyl sulfamate ions

    Science.gov (United States)

    Friesen, Cody A.; Wolfe, Derek; Johnson, Paul Bryan

    2016-03-15

    Embodiments of the invention are related to ionic liquids and more specifically to ionic liquids used in electrochemical metal-air cells in which the ionic liquid includes a cation and an anion selected from hydroxamate and/or N-alkyl sulfamate anions.

  1. Manganese Catalyzed Regioselective C–H Alkylation: Experiment and Computation

    KAUST Repository

    Wang, Chengming

    2018-05-08

    A new efficient manganese-catalyzed selective C2-alkylation of indoles via carbenoid insertion has been achieved. The newly developed C-H functionalization protocol provides access to diverse products and shows good functional group tolerance. Mechanistic and computational studies support the formation of a Mn(CO)3 acetate complex as the catalytically active species.

  2. Manganese Catalyzed Regioselective C–H Alkylation: Experiment and Computation

    KAUST Repository

    Wang, Chengming; Maity, Bholanath; Cavallo, Luigi; Rueping, Magnus

    2018-01-01

    A new efficient manganese-catalyzed selective C2-alkylation of indoles via carbenoid insertion has been achieved. The newly developed C-H functionalization protocol provides access to diverse products and shows good functional group tolerance. Mechanistic and computational studies support the formation of a Mn(CO)3 acetate complex as the catalytically active species.

  3. Photochemical synthesis of shape-selective palladium nanocubes in aqueous solution

    International Nuclear Information System (INIS)

    Kundu, Subrata; Wang Ke; Lau, Sean; Liang Hong

    2010-01-01

    We have developed a seedless, citrateless one-step synthetic process for the formation of shape controlled monodisperse Pd nanoparticles (NPs) in 4 h of UV-photoirradiation. The synthesis was done in cetyl trimethylammonium bromide (CTAB) surfactant media in the presence of ascorbic acid as a reducing agent. The size and shape of the particles can be tuned easily by varying the molar ratio of the CTAB with the Pd salt and by controlling the UV-photoirradiation time. The preferential binding of CTAB to the (100) facets of Pd leads to the formation of Pd nanorods and nanocubes. The approach developed here would reduce the use of seed particles and tri-sodium citrate for the fast synthesis of faceted Pd NPs. The synthesized particles were found to be stable for at least 3 months under ambient conditions at room temperature. This newly developed process might find potential applications in the formation of other materials like Au, Ag, and CdS NPs and applicable in surface enhanced Raman scattering, and different catalysis reactions.Graphical AbstractWe have developed a seedless, citrateless one-step synthetic process for the formation of shape controlled monodisperse Pd nanoparticles (NPs) in 4 h of UV-photoirradiation. The synthesis was done in cetyl trimethylammonium bromide (CTAB) surfactant media in the presence of ascorbic acid as a reducing agent. The size and shape of the particles can be tuned easily by varying the molar ratio of the CTAB with the Pd salt and by controlling the UV-photoirradiation time. The preferential binding of CTAB to the (100) facets of Pd leads to the formation of Pd nanorods and nanocubes. The approach developed here would reduce the use of seed particles and tri-sodium citrate for the fast synthesis of faceted Pd NPs. The synthesized particles were found to be stable for at least 3 months under ambient conditions at room temperature. This newly developed process might find potential applications in the formation of other materials like

  4. Photochemical synthesis of shape-selective palladium nanocubes in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Kundu, Subrata, E-mail: skundu@tamu.edu; Wang Ke; Lau, Sean; Liang Hong, E-mail: hliang@tamu.ed [Texas A and M University, Materials Science and Mechanical Engineering (United States)

    2010-10-15

    We have developed a seedless, citrateless one-step synthetic process for the formation of shape controlled monodisperse Pd nanoparticles (NPs) in 4 h of UV-photoirradiation. The synthesis was done in cetyl trimethylammonium bromide (CTAB) surfactant media in the presence of ascorbic acid as a reducing agent. The size and shape of the particles can be tuned easily by varying the molar ratio of the CTAB with the Pd salt and by controlling the UV-photoirradiation time. The preferential binding of CTAB to the (100) facets of Pd leads to the formation of Pd nanorods and nanocubes. The approach developed here would reduce the use of seed particles and tri-sodium citrate for the fast synthesis of faceted Pd NPs. The synthesized particles were found to be stable for at least 3 months under ambient conditions at room temperature. This newly developed process might find potential applications in the formation of other materials like Au, Ag, and CdS NPs and applicable in surface enhanced Raman scattering, and different catalysis reactions.Graphical AbstractWe have developed a seedless, citrateless one-step synthetic process for the formation of shape controlled monodisperse Pd nanoparticles (NPs) in 4 h of UV-photoirradiation. The synthesis was done in cetyl trimethylammonium bromide (CTAB) surfactant media in the presence of ascorbic acid as a reducing agent. The size and shape of the particles can be tuned easily by varying the molar ratio of the CTAB with the Pd salt and by controlling the UV-photoirradiation time. The preferential binding of CTAB to the (100) facets of Pd leads to the formation of Pd nanorods and nanocubes. The approach developed here would reduce the use of seed particles and tri-sodium citrate for the fast synthesis of faceted Pd NPs. The synthesized particles were found to be stable for at least 3 months under ambient conditions at room temperature. This newly developed process might find potential applications in the formation of other materials like

  5. General Allylic C–H Alkylation with Tertiary Nucleophiles

    Science.gov (United States)

    2015-01-01

    A general method for intermolecular allylic C–H alkylation of terminal olefins with tertiary nucleophiles has been accomplished employing palladium(II)/bis(sulfoxide) catalysis. Allylic C–H alkylation furnishes products in good yields (avg. 64%) with excellent regio- and stereoselectivity (>20:1 linear:branched, >20:1 E:Z). For the first time, the olefin scope encompasses unactivated aliphatic olefins as well as activated aromatic/heteroaromatic olefins and 1,4-dienes. The ease of appending allyl moieties onto complex scaffolds is leveraged to enable this mild and selective allylic C–H alkylation to rapidly diversify phenolic natural products. The tertiary nucleophile scope is broad and includes latent functionality for further elaboration (e.g., aliphatic alcohols, α,β-unsaturated esters). The opportunities to effect synthetic streamlining with such general C–H reactivity are illustrated in an allylic C–H alkylation/Diels–Alder reaction cascade: a reactive diene is generated via intermolecular allylic C–H alkylation and approximated to a dienophile contained within the tertiary nucleophile to furnish a common tricyclic core found in the class I galbulimima alkaloids. PMID:24641574

  6. General allylic C-H alkylation with tertiary nucleophiles.

    Science.gov (United States)

    Howell, Jennifer M; Liu, Wei; Young, Andrew J; White, M Christina

    2014-04-16

    A general method for intermolecular allylic C-H alkylation of terminal olefins with tertiary nucleophiles has been accomplished employing palladium(II)/bis(sulfoxide) catalysis. Allylic C-H alkylation furnishes products in good yields (avg. 64%) with excellent regio- and stereoselectivity (>20:1 linear:branched, >20:1 E:Z). For the first time, the olefin scope encompasses unactivated aliphatic olefins as well as activated aromatic/heteroaromatic olefins and 1,4-dienes. The ease of appending allyl moieties onto complex scaffolds is leveraged to enable this mild and selective allylic C-H alkylation to rapidly diversify phenolic natural products. The tertiary nucleophile scope is broad and includes latent functionality for further elaboration (e.g., aliphatic alcohols, α,β-unsaturated esters). The opportunities to effect synthetic streamlining with such general C-H reactivity are illustrated in an allylic C-H alkylation/Diels-Alder reaction cascade: a reactive diene is generated via intermolecular allylic C-H alkylation and approximated to a dienophile contained within the tertiary nucleophile to furnish a common tricyclic core found in the class I galbulimima alkaloids.

  7. Alkylating agents for Waldenstrom's macroglobulinaemia.

    Science.gov (United States)

    Yang, Kun; Tan, Jianlong; Wu, Taixiang

    2009-01-21

    Waldenstrom's macroglobulinaemia (WM) is an uncommon B-cell lymphoproliferative disorder characterized by bone marrow infiltration and production of monoclonal immunoglobulin. Uncertainty remains if alkylating agents, such as chlorambucil, melphalan or cyclophosphamide, are an effective form of management. To assess the effects and safety of the alkylating agents on Waldenstrom's macroglobulinaemia (WM). We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2008), MEDLINE (1966 to 2008), EMBASE (1980 to 2008), the Chinese Biomedical Base (1982 to 2008) and reference lists of articles.We also handsearched relevant conference proceedings from 1990 to 2008. Randomised controlled trials (RCTs) comparing alkylating agents given concomitantly with radiotherapy, splenectomy, plasmapheresis, stem-cell transplantation in patients with a confirmed diagnosis of WM. Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials. One trial involving 92 participants with pretreated/relapsed WM compared the effect of fludarabine versus the combination of cyclophosphamide (the alkylating agent), doxorubicin and prednisone (CAP). Compared to CAP, the Hazard ratio (HR) for deaths of treatment with fludarabine was estimated to be 1.04, with a standard error of 0.30 (95% CI 0.58 to 1.48) and it indicated that the mean difference of median survival time was -4.00 months, and 16.00 months for response duration. The relative risks (RR) of response rate was 2.80 (95% CI 1.10 to 7.12). There were no statistically difference in overall survival rate and median survival months, while on the basis of response rate and response duration, fludarabine seemed to be superior to CAP for pretreated/relapsed patients with macroglobulinaemia. Although alkylating agents have been used for decades they have never actually been tested in a proper randomised trial. This

  8. Shape-selective synthesis of non-micellar cobalt oxide (CoO) nanomaterials by microwave irradiations

    International Nuclear Information System (INIS)

    Kundu, Subrata; Jayachandran, M.

    2013-01-01

    Shape-selective formation of CoO nanoparticles has been developed using a simple one-step in situ non-micellar microwave (MW) heating method. CoO NPs were synthesized by mixing aqueous CoCl 2 ·6H 2 O solution with poly (vinyl) alcohol (PVA) in the presence of sodium hydroxide (NaOH). The reaction mixture was irradiated using MW for a total time of 2 min. This process exclusively generated different shapes like nanosphere, nanosheet, and nanodendrite structures just by tuning the Co(II) ion to PVA molar ratios and controlling other reaction parameters. The proposed synthesis method is efficient, straightforward, reproducible, and robust. Other than in catalysis, these cobalt oxide nanomaterials can be used for making pigments, battery materials, for developing solid state sensors, and also as an anisotropy source for magnetic recording.Graphical Abstract

  9. Alkyl-halogenide promoted ionic liquid catalysis of isobutane/butene-alkylation

    Energy Technology Data Exchange (ETDEWEB)

    Schilder, L.; Korth, W.; Jess, A. [Bayreuth Univ. (Germany). Dept. of Chemical Engineering

    2011-07-01

    The effect of two different types of promoters on the performance of Lewis-acidic chloroaluminate ionic liquid catalysts was studied for liquid liquid biphasic isobutane/2-butene alkylation. In particular, the activity and selectivity of such catalytic systems was investigated. Experimental results obtained from a batch reactor show, that tert-butyl halides increase the reaction rate significantly and shift the C8-selectivity towards the desired high-octane trimethylpentanes (TMPs). But, secondary reactions like oligomerization and cracking are not affected by the use of these promoters. (orig.)

  10. Thioimidazolium Ionic Liquids as Tunable Alkylating Agents.

    Science.gov (United States)

    Guterman, Ryan; Miao, Han; Antonietti, Markus

    2018-01-19

    Alkylating ionic liquids based on the thioimidazolium structure combine the conventional properties of ionic liquids, including low melting point and nonvolatility, with the alkylating function. Alkyl transfer occurs exclusively from the S-alkyl position, thus allowing for easy derivatization of the structure without compromising specificity. We apply this feature to tune the electrophilicty of the cation to profoundly affect the reactivity of these alkylating ionic liquids, with a caffeine-derived compound possessing the highest reactivity. Anion choice was found to affect reaction rates, with iodide anions assisting in the alkylation reaction through a "shuttling" process. The ability to tune the properties of the alkylating agent using the toolbox of ionic liquid chemistry highlights the modular nature of these compounds as a platform for alkylating agent design and integration in to future systems.

  11. Alkylation of imidazole under ultrasound irradiation over alkaline carbons

    International Nuclear Information System (INIS)

    Costarrosa, L.; Calvino-Casilda, V.; Ferrera-Escudero, S.; Duran-Valle, C.J.; Martin-Aranda, R.M.

    2006-01-01

    N-Alkyl-imidazole has been synthesized by sonochemical irradiation of imidazole and 1-bromobutane using alkaline-promoted carbons (exchanged with the binary combinations of Na, K and Cs). The catalysts were characterized by X-ray photoelectron spectroscopy, thermal analysis and N 2 adsorption isotherms. Under the experimental conditions, N-alkyl-imidazoles can be prepared with a high activity and selectivity. It is observed that imidazole conversion increases in parallel with increasing the basicity of the catalyst. The influence of the alkaline promoter, the reaction temperature, and the amount of catalyst on the catalytic activity has been studied. For comparison, the alkylation of imidazole has also been performed in a batch reactor system under thermal activation

  12. Photochemical synthesis of shape-selective palladium nanocubes in aqueous solution

    Science.gov (United States)

    Kundu, Subrata; Wang, Ke; Lau, Sean; Liang, Hong

    2010-10-01

    We have developed a seedless, citrateless one-step synthetic process for the formation of shape controlled monodisperse Pd nanoparticles (NPs) in 4 h of UV-photoirradiation. The synthesis was done in cetyl trimethylammonium bromide (CTAB) surfactant media in the presence of ascorbic acid as a reducing agent. The size and shape of the particles can be tuned easily by varying the molar ratio of the CTAB with the Pd salt and by controlling the UV-photoirradiation time. The preferential binding of CTAB to the (100) facets of Pd leads to the formation of Pd nanorods and nanocubes. The approach developed here would reduce the use of seed particles and tri-sodium citrate for the fast synthesis of faceted Pd NPs. The synthesized particles were found to be stable for at least 3 months under ambient conditions at room temperature. This newly developed process might find potential applications in the formation of other materials like Au, Ag, and CdS NPs and applicable in surface enhanced Raman scattering, and different catalysis reactions.

  13. Chichibabin-type direct alkylation of pyridyl alcohols with alkyl lithium reagents.

    Science.gov (United States)

    Jeffrey, Jenna L; Sarpong, Richmond

    2012-11-02

    Direct C(6) alkylation of pyridyl alcohols can be achieved following an initial deprotonation of the hydroxy group. This transformation, which is believed to occur by a Chichibabin-type alkylation, avoids lateral deprotonation prior to pyridine ring alkylation and gives increased regioselectivity for C(6) over C(4) alkylation.

  14. Ruthenium-complex catalyzed N-(cyclo)alkylation of aromatic amines with diols. Selective synthesis of N-(n-hydroixyalkyl)anilines of type PhNH(CH2)nOH and of some bioactive arylpiperazines,

    NARCIS (Netherlands)

    Koten, G. van; Abbenhuis, R.A.T.M.; Boersma, J.

    1998-01-01

    A new class of well-defined neutral mono-, and dicationic ruthenium(II) complexes containing a neutral terdentate donor system [C5H3N(CH2E)(2)-2,6] (E = PPh2 (PNP) or NMe2 (NN'N)) has been found effective as catalyst precursor in N-(cyclo)alkylation reactions of aromatic amines with diols

  15. Synthesis and Study of Shape-Memory Polymers Selectively Induced by Near-Infrared Lights via In Situ Copolymerization

    Directory of Open Access Journals (Sweden)

    Tianyu Fang

    2017-05-01

    Full Text Available Shape-memory polymers (SMPs selectively induced by near-infrared lights of 980 or 808 nm were synthesized via free radical copolymerization. Methyl methacrylate (MMA monomer, ethylene glycol dimethylacrylate (EGDMA as a cross-linker, and organic complexes of Yb(TTA2AAPhen or Nd(TTA2AAPhen containing a reactive ligand of acrylic acid (AA were copolymerized in situ. The dispersion of the organic complexes in the copolymer matrix was highly improved, while the transparency of the copolymers was negligibly influenced in comparison with the pristine cross-linked PMMA. In addition, the thermal resistance of the copolymers was enhanced with the complex loading, while their glass transition temperature, cross-linking level, and mechanical properties were to some extent reduced. Yb(TTA2AAPhen and Nd(TTA2AAPhen provided the prepared copolymers with selective photothermal effects and shape-memory functions for 980 and 808 nm NIR lights, respectively. Finally, smart optical devices which exhibited localized transparency or diffraction evolution procedures were demonstrated based on the prepared copolymers, owing to the combination of good transparency and selective light wavelength responsivity.

  16. Natural Selection and Recombination Rate Variation Shape Nucleotide Polymorphism Across the Genomes of Three Related Populus Species.

    Science.gov (United States)

    Wang, Jing; Street, Nathaniel R; Scofield, Douglas G; Ingvarsson, Pär K

    2016-03-01

    A central aim of evolutionary genomics is to identify the relative roles that various evolutionary forces have played in generating and shaping genetic variation within and among species. Here we use whole-genome resequencing data to characterize and compare genome-wide patterns of nucleotide polymorphism, site frequency spectrum, and population-scaled recombination rates in three species of Populus: Populus tremula, P. tremuloides, and P. trichocarpa. We find that P. tremuloides has the highest level of genome-wide variation, skewed allele frequencies, and population-scaled recombination rates, whereas P. trichocarpa harbors the lowest. Our findings highlight multiple lines of evidence suggesting that natural selection, due to both purifying and positive selection, has widely shaped patterns of nucleotide polymorphism at linked neutral sites in all three species. Differences in effective population sizes and rates of recombination largely explain the disparate magnitudes and signatures of linked selection that we observe among species. The present work provides the first phylogenetic comparative study on a genome-wide scale in forest trees. This information will also improve our ability to understand how various evolutionary forces have interacted to influence genome evolution among related species. Copyright © 2016 by the Genetics Society of America.

  17. Disentangling the roles of natural selection and genetic drift in shaping variation at MHC immunity genes.

    Science.gov (United States)

    Sutton, Jolene T; Nakagawa, Shinichi; Robertson, Bruce C; Jamieson, Ian G

    2011-11-01

    The major histocompatibility complex (MHC) forms an integral component of the vertebrate immune response and, due to strong selection pressures, is one of the most polymorphic regions of the entire genome. Despite over 15 years of research, empirical studies offer highly contradictory explanations of the relative roles of different evolutionary forces, selection and genetic drift, acting on MHC genes during population bottlenecks. Here, we take a meta-analytical approach to quantify the results of studies into the effects of bottlenecks on MHC polymorphism. We show that the consequences of selection acting on MHC loci prior to a bottleneck event, combined with drift during the bottleneck, will result in overall loss of MHC polymorphism that is ∼15% greater than loss of neutral genetic diversity. These results are counter to general expectations that selection should maintain MHC polymorphism, but do agree with the results of recent simulation models and at least two empirical studies. Notably, our results suggest that negative frequency-dependent selection could be more important than overdominance for maintaining high MHC polymorphism in pre-bottlenecked populations. © 2011 Blackwell Publishing Ltd.

  18. Optimization of the alkyl side chain length of fluorine-18-labeled 7α-alkyl-fluoroestradiol

    International Nuclear Information System (INIS)

    Okamoto, Mayumi; Shibayama, Hiromitsu; Naka, Kyosuke; Kitagawa, Yuya; Ishiwata, Kiichi; Shimizu, Isao; Toyohara, Jun

    2016-01-01

    Introduction: Several lines of evidence suggest that 7α-substituted estradiol derivatives bind to the estrogen receptor (ER). In line with this hypothesis, we designed and synthesized 18 F-labeled 7α-fluoroalkylestradiol (Cn-7α-[ 18 F]FES) derivatives as molecular probes for visualizing ERs. Previously, we successfully synthesized 7α-(3-[ 18 F]fluoropropyl)estradiol (C3-7α-[ 18 F]FES) and showed promising results for quantification of ER density in vivo, although extensive metabolism was observed in rodents. Therefore, optimization of the alkyl side chain length is needed to obtain suitable radioligands based on Cn-7α-substituted estradiol pharmacophores. Methods: We synthesized fluoromethyl (23; C1-7α-[ 18 F]FES) to fluorohexyl (26; C6-7α-[ 18 F]FES) derivatives, except fluoropropyl (C3-7α-[ 18 F]FES) and fluoropentyl derivatives (C5-7α-[ 18 F]FES), which have been previously synthesized. In vitro binding to the α-subtype (ERα) isoform of ERs and in vivo biodistribution studies in mature female mice were carried out. Results: The in vitro IC 50 value of Cn-7α-FES tended to gradually decrease depending on the alkyl side chain length. C1-7α-[ 18 F]FES (23) showed the highest uptake in ER-rich tissues such as the uterus. Uterus uptake also gradually decreased depending on the alkyl side chain length. As a result, in vivo uterus uptake reflected the in vitro ERα affinity of each compound. Bone uptake, which indicates de-fluorination, was marked in 7α-(2-[ 18 F]fluoroethyl)estradiol (C2-7α-[ 18 F]FES) (24) and 7α-(4-[ 18 F]fluorobutyl)estradiol (C4-7α-[ 18 F]FES) (25) derivatives. However, C1-7α-[ 18 F]FES (23) and C6-7α-[ 18 F]FES (26) showed limited uptake in bone. As a result, in vivo bone uptake (de-fluorination) showed a bell-shaped pattern, depending on the alkyl side chain length. C1-7α-[ 18 F]FES (23) showed the same levels of uptake in uterus and bone compared with those of 16α-[ 18 F]fluoro-17β-estradiol. Conclusions: The optimal alkyl

  19. 40 CFR 721.9892 - Alkylated urea.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkylated urea. 721.9892 Section 721... Alkylated urea. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as an alkylated urea (PMN P-93-1649) is subject to reporting under this...

  20. SHAPE SELECTIVE NANO-CATALYSTS: TOWARD DIRECT METHANOL FUEL CELLS APPLICATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Murph, S.

    2010-06-16

    A series of bimetallic core-shell-alloy type Au-Pt nanomaterials with various morphologies, aspect ratios and compositions, were produced in a heterogenous epitaxial fashion. Gold nanoparticles with well-controlled particle size and shape, e.g. spheres, rods and cubes, were used as 'seeds' for platinum growth in the presence of a mild reducing agent, ascorbic acid and a cationic surfactant cethyltrimethyl ammonium bromide (CTAB). The reactions take place in air and water, and are quick, economical and amenable for scaling up. The synthesized nanocatalysts were characterized by electron microscopy techniques and energy dispersive X-ray analysis. Nafion membranes were embedded with the Au-Pt nanomaterials and analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM) for their potential in direct methanol fuel cells applications.

  1. Similar Efficacies of Selection Shape Mitochondrial and Nuclear Genes in Both Drosophila melanogaster and Homo sapiens.

    Science.gov (United States)

    Cooper, Brandon S; Burrus, Chad R; Ji, Chao; Hahn, Matthew W; Montooth, Kristi L

    2015-08-21

    Deleterious mutations contribute to polymorphism even when selection effectively prevents their fixation. The efficacy of selection in removing deleterious mitochondrial mutations from populations depends on the effective population size (Ne) of the mitochondrial DNA and the degree to which a lack of recombination magnifies the effects of linked selection. Using complete mitochondrial genomes from Drosophila melanogaster and nuclear data available from the same samples, we reexamine the hypothesis that nonrecombining animal mitochondrial DNA harbor an excess of deleterious polymorphisms relative to the nuclear genome. We find no evidence of recombination in the mitochondrial genome, and the much-reduced level of mitochondrial synonymous polymorphism relative to nuclear genes is consistent with a reduction in Ne. Nevertheless, we find that the neutrality index, a measure of the excess of nonsynonymous polymorphism relative to the neutral expectation, is only weakly significantly different between mitochondrial and nuclear loci. This difference is likely the result of the larger proportion of beneficial mutations in X-linked relative to autosomal loci, and we find little to no difference between mitochondrial and autosomal neutrality indices. Reanalysis of published data from Homo sapiens reveals a similar lack of a difference between the two genomes, although previous studies have suggested a strong difference in both species. Thus, despite a smaller Ne, mitochondrial loci of both flies and humans appear to experience similar efficacies of purifying selection as do loci in the recombining nuclear genome. Copyright © 2015 Cooper et al.

  2. Selection of a LGp0-shaped fundamental mode in a laser cavity: Phase versus amplitude masks

    CSIR Research Space (South Africa)

    Hasnaoui, A

    2012-01-01

    Full Text Available Laser beams of a single high-order transverse mode have been of interest to the laser community for several years now. In order to achieve such a mode as the fundamental mode of the cavity, mode selecting elements in the form of a phase or amplitude...

  3. In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release.

    Science.gov (United States)

    Oh, Seung Soo; Plakos, Kory; Xiao, Yi; Eisenstein, Michael; Soh, H Tom

    2013-11-26

    Many biological systems employ allosteric regulatory mechanisms, which offer a powerful means of directly linking a specific binding event to a wide spectrum of molecular functionalities. There is considerable interest in generating synthetic allosteric regulators that can perform useful molecular functions for applications in diagnostics, imaging and targeted therapies, but generating such molecules through either rational design or directed evolution has proven exceptionally challenging. To address this need, we present an in vitro selection strategy for generating conformation-switching DNA nanostructures that selectively release a small-molecule payload in response to binding of a specific trigger molecule. As an exemplar, we have generated a DNA nanostructure that hybridizes with a separate 'cargo strand' containing an abasic site. This abasic site stably sequesters a fluorescent cargo molecule in an inactive state until the DNA nanostructure encounters an ATP trigger molecule. This ATP trigger causes the nanostructure to release the cargo strand, thereby liberating the fluorescent payload and generating a detectable fluorescent readout. Our DNA nanostructure is highly sensitive, with an EC50 of 30 μM, and highly specific, releasing its payload in response to ATP but not to other chemically similar nucleotide triphosphates. We believe that this selection approach could be generalized to generate synthetic nanostructures capable of selective and controlled release of other small-molecule cargos in response to a variety of triggers, for both research and clinical applications.

  4. Population Level Purifying Selection and Gene Expression Shape Subgenome Evolution in Maize.

    Science.gov (United States)

    Pophaly, Saurabh D; Tellier, Aurélien

    2015-12-01

    The maize ancestor experienced a recent whole-genome duplication (WGD) followed by gene erosion which generated two subgenomes, the dominant subgenome (maize1) experiencing fewer deletions than maize2. We take advantage of available extensive polymorphism and gene expression data in maize to study purifying selection and gene expression divergence between WGD retained paralog pairs. We first report a strong correlation in nucleotide diversity between duplicate pairs, except for upstream regions. We then show that maize1 genes are under stronger purifying selection than maize2. WGD retained genes have higher gene dosage and biased Gene Ontologies consistent with previous studies. The relative gene expression of paralogs across tissues demonstrates that 98% of duplicate pairs have either subfunctionalized in a tissuewise manner or have diverged consistently in their expression thereby preventing functional complementation. Tissuewise subfunctionalization seems to be a hallmark of transcription factors, whereas consistent repression occurs for macromolecular complexes. We show that dominant gene expression is a strong determinant of the strength of purifying selection, explaining the inferred stronger negative selection on maize1 genes. We propose a novel expression-based classification of duplicates which is more robust to explain observed polymorphism patterns than the subgenome location. Finally, upstream regions of repressed genes exhibit an enrichment in transposable elements which indicates a possible mechanism for expression divergence. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Synergistic effect of shape-selective silver nanostructures decorating reduced graphene oxide nanoplatelets for enhanced cytotoxicity against breast cancer

    Science.gov (United States)

    Derakhshi, Maryam; Ashkarran, Ali Akbar; Bahari, Ali; Bonakdar, Shahin

    2018-07-01

    Graphene-based nanomaterials contain unique physicochemical properties and have been widely investigated due to a variety of applications particularly in cancer therapy. Furthermore, Ag has been known for its extensive historical background for biomedical applications. Therefore, conjugation of shape-selective Ag nanostructures with graphene may provide new horizons for pharmaceutical applications such as cancer treatments. Here we report on the synthesis of Ag nanoparticles (NPs)/reduced graphene oxide (AgNPs/RGO) conjugate nanomaterials containing various shapes of AgNPs by a novel and simple synthesis route using the deformation of dimethylformamide (DMF) as the reducing and coupling agent. The cytotoxicity and anticancer properties of AgNPs, AgNPs/RGO conjugate nanomaterials, RGO and graphene oxide (GO) were probed against MDA-MB-231 cancer and MCF-10A normal human breast cells in vitro. The AgNPs/RGO nanocomposites exhibited a strong anticancer effect by penetration and apoptosis in cancer cells as well as the lowest influence on the viability of normal cells. It was found that cancer cell viability not only depends on the geometry of Ag nanostructures but also on the interaction between AgNPs and RGO nanoplatelets. It is suggested that AgNPs/RGO conjugate nanomaterials with various shapes of AgNPs is a promising therapeutic platform for cancer therapy.

  6. Natural selection interacts with recombination to shape the evolution of hybrid genomes.

    Science.gov (United States)

    Schumer, Molly; Xu, Chenling; Powell, Daniel L; Durvasula, Arun; Skov, Laurits; Holland, Chris; Blazier, John C; Sankararaman, Sriram; Andolfatto, Peter; Rosenthal, Gil G; Przeworski, Molly

    2018-05-11

    To investigate the consequences of hybridization between species, we studied three replicate hybrid populations that formed naturally between two swordtail fish species, estimating their fine-scale genetic map and inferring ancestry along the genomes of 690 individuals. In all three populations, ancestry from the "minor" parental species is more common in regions of high recombination and where there is linkage to fewer putative targets of selection. The same patterns are apparent in a reanalysis of human and archaic admixture. These results support models in which ancestry from the minor parental species is more likely to persist when rapidly uncoupled from alleles that are deleterious in hybrids. Our analyses further indicate that selection on swordtail hybrids stems predominantly from deleterious combinations of epistatically interacting alleles. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  7. Selective Bottlenecks Shape Evolutionary Pathways Taken during Mammalian Adaptation of a 1918-like Avian Influenza Virus.

    Science.gov (United States)

    Moncla, Louise H; Zhong, Gongxun; Nelson, Chase W; Dinis, Jorge M; Mutschler, James; Hughes, Austin L; Watanabe, Tokiko; Kawaoka, Yoshihiro; Friedrich, Thomas C

    2016-02-10

    Avian influenza virus reassortants resembling the 1918 human pandemic virus can become transmissible among mammals by acquiring mutations in hemagglutinin (HA) and polymerase. Using the ferret model, we trace the evolutionary pathway by which an avian-like virus evolves the capacity for mammalian replication and airborne transmission. During initial infection, within-host HA diversity increased drastically. Then, airborne transmission fixed two polymerase mutations that do not confer a detectable replication advantage. In later transmissions, selection fixed advantageous HA1 variants. Transmission initially involved a "loose" bottleneck, which became strongly selective after additional HA mutations emerged. The stringency and evolutionary forces governing between-host bottlenecks may therefore change throughout host adaptation. Mutations occurred in multiple combinations in transmitted viruses, suggesting that mammalian transmissibility can evolve through multiple genetic pathways despite phenotypic constraints. Our data provide a glimpse into avian influenza virus adaptation in mammals, with broad implications for surveillance on potentially zoonotic viruses. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Directional selection has shaped the oral jaws of Lake Malawi cichlid fishes

    OpenAIRE

    Albertson, R. Craig; Streelman, J. Todd; Kocher, Thomas D.

    2003-01-01

    East African cichlid fishes represent one of the most striking examples of rapid and convergent evolutionary radiation among vertebrates. Models of ecological speciation would suggest that functional divergence in feeding morphology has contributed to the origin and maintenance of cichlid species diversity. However, definitive evidence for the action of natural selection has been missing. Here we use quantitative genetics to identify regions of the cichlid genome responsible for functionally ...

  9. Artificial selection on introduced Asian haplotypes shaped the genetic architecture in European commercial pigs.

    Science.gov (United States)

    Bosse, Mirte; Lopes, Marcos S; Madsen, Ole; Megens, Hendrik-Jan; Crooijmans, Richard P M A; Frantz, Laurent A F; Harlizius, Barbara; Bastiaansen, John W M; Groenen, Martien A M

    2015-12-22

    Early pig farmers in Europe imported Asian pigs to cross with their local breeds in order to improve traits of commercial interest. Current genomics techniques enabled genome-wide identification of these Asian introgressed haplotypes in modern European pig breeds. We propose that the Asian variants are still present because they affect phenotypes that were important for ancient traditional, as well as recent, commercial pig breeding. Genome-wide introgression levels were only weakly correlated with gene content and recombination frequency. However, regions with an excess or absence of Asian haplotypes (AS) contained genes that were previously identified as phenotypically important such as FASN, ME1, and KIT. Therefore, the Asian alleles are thought to have an effect on phenotypes that were historically under selection. We aimed to estimate the effect of AS in introgressed regions in Large White pigs on the traits of backfat (BF) and litter size. The majority of regions we tested that retained Asian deoxyribonucleic acid (DNA) showed significantly increased BF from the Asian alleles. Our results suggest that the introgression in Large White pigs has been strongly determined by the selective pressure acting upon the introgressed AS. We therefore conclude that human-driven hybridization and selection contributed to the genomic architecture of these commercial pigs. © 2015 The Author(s).

  10. The genomic landscape shaped by selection on transposable elements across 18 mouse strains.

    Science.gov (United States)

    Nellåker, Christoffer; Keane, Thomas M; Yalcin, Binnaz; Wong, Kim; Agam, Avigail; Belgard, T Grant; Flint, Jonathan; Adams, David J; Frankel, Wayne N; Ponting, Chris P

    2012-06-15

    Transposable element (TE)-derived sequence dominates the landscape of mammalian genomes and can modulate gene function by dysregulating transcription and translation. Our current knowledge of TEs in laboratory mouse strains is limited primarily to those present in the C57BL/6J reference genome, with most mouse TEs being drawn from three distinct classes, namely short interspersed nuclear elements (SINEs), long interspersed nuclear elements (LINEs) and the endogenous retrovirus (ERV) superfamily. Despite their high prevalence, the different genomic and gene properties controlling whether TEs are preferentially purged from, or are retained by, genetic drift or positive selection in mammalian genomes remain poorly defined. Using whole genome sequencing data from 13 classical laboratory and 4 wild-derived mouse inbred strains, we developed a comprehensive catalogue of 103,798 polymorphic TE variants. We employ this extensive data set to characterize TE variants across the Mus lineage, and to infer neutral and selective processes that have acted over 2 million years. Our results indicate that the majority of TE variants are introduced though the male germline and that only a minority of TE variants exert detectable changes in gene expression. However, among genes with differential expression across the strains there are twice as many TE variants identified as being putative causal variants as expected. Most TE variants that cause gene expression changes appear to be purged rapidly by purifying selection. Our findings demonstrate that past TE insertions have often been highly deleterious, and help to prioritize TE variants according to their likely contribution to gene expression or phenotype variation.

  11. Alkylation sensitivity screens reveal a conserved cross-species functionome

    Science.gov (United States)

    Svilar, David; Dyavaiah, Madhu; Brown, Ashley R.; Tang, Jiang-bo; Li, Jianfeng; McDonald, Peter R.; Shun, Tong Ying; Braganza, Andrea; Wang, Xiao-hong; Maniar, Salony; St Croix, Claudette M.; Lazo, John S.; Pollack, Ian F.; Begley, Thomas J.; Sobol, Robert W.

    2013-01-01

    To identify genes that contribute to chemotherapy resistance in glioblastoma, we conducted a synthetic lethal screen in a chemotherapy-resistant glioblastoma derived cell line with the clinical alkylator temozolomide (TMZ) and an siRNA library tailored towards “druggable” targets. Select DNA repair genes in the screen were validated independently, confirming the DNA glycosylases UNG and MYH as well as MPG to be involved in the response to high dose TMZ. The involvement of UNG and MYH is likely the result of a TMZ-induced burst of reactive oxygen species. We then compared the human TMZ sensitizing genes identified in our screen with those previously identified from alkylator screens conducted in E. coli and S. cerevisiae. The conserved biological processes across all three species composes an Alkylation Functionome that includes many novel proteins not previously thought to impact alkylator resistance. This high-throughput screen, validation and cross-species analysis was then followed by a mechanistic analysis of two essential nodes: base excision repair (BER) DNA glycosylases (UNG, human and mag1, S. cerevisiae) and protein modification systems, including UBE3B and ICMT in human cells or pby1, lip22, stp22 and aim22 in S. cerevisiae. The conserved processes of BER and protein modification were dual targeted and yielded additive sensitization to alkylators in S. cerevisiae. In contrast, dual targeting of BER and protein modification genes in human cells did not increase sensitivity, suggesting an epistatic relationship. Importantly, these studies provide potential new targets to overcome alkylating agent resistance. PMID:23038810

  12. Social Groups Prioritize Selective Attention to Faces: How Social Identity Shapes Distractor Interference.

    Directory of Open Access Journals (Sweden)

    Gewnhi Park

    Full Text Available Human faces automatically attract visual attention and this process appears to be guided by social group memberships. In two experiments, we examined how social groups guide selective attention toward in-group and out-group faces. Black and White participants detected a target letter among letter strings superimposed on faces (Experiment 1. White participants were less accurate on trials with racial out-group (Black compared to in-group (White distractor faces. Likewise, Black participants were less accurate on trials with racial out-group (White compared to in-group (Black distractor faces. However, this pattern of out-group bias was only evident under high perceptual load-when the task was visually difficult. To examine the malleability of this pattern of racial bias, a separate sample of participants were assigned to mixed-race minimal groups (Experiment 2. Participants assigned to groups were less accurate on trials with their minimal in-group members compared to minimal out-group distractor faces, regardless of race. Again, this pattern of out-group bias was only evident under high perceptual load. Taken together, these results suggest that social identity guides selective attention toward motivationally relevant social groups-shifting from out-group bias in the domain of race to in-group bias in the domain of minimal groups-when perceptual resources are scarce.

  13. Does selection against transcriptional interference shape retroelement-free regions in mammalian genomes?

    DEFF Research Database (Denmark)

    Mourier, Tobias; Willerslev, Eske

    2008-01-01

    in generating and maintaining retroelement-free regions in the human genome. METHODOLOGY/PRINCIPAL FINDINGS: Based on the known transcriptional properties of retroelements, we expect long interspersed elements (LINEs) to be able to display a high degree of transcriptional interference. In contrast, we expect......BACKGROUND: Eukaryotic genomes are scattered with retroelements that proliferate through retrotransposition. Although retroelements make up around 40 percent of the human genome, large regions are found to be completely devoid of retroelements. This has been hypothesised to be a result of genomic...... activity of LINEs has been identified previously. CONCLUSIONS/SIGNIFICANCE: Our observations are consistent with the notion that selection against transcriptional interference has contributed to the maintenance and/or generation of retroelement-free regions in the human genome....

  14. GPR Detection of Buried Symmetrically Shaped Mine-like Objects using Selective Independent Component Analysis

    DEFF Research Database (Denmark)

    Karlsen, Brian; Sørensen, Helge Bjarup Dissing; Larsen, Jan

    2003-01-01

    from small-scale anti-personal (AP) mines to large-scale anti-tank (AT) mines were designed. Large-scale SF-GPR measurements on this series of mine-like objects buried in soil were performed. The SF-GPR data was acquired using a wideband monostatic bow-tie antenna operating in the frequency range 750......This paper addresses the detection of mine-like objects in stepped-frequency ground penetrating radar (SF-GPR) data as a function of object size, object content, and burial depth. The detection approach is based on a Selective Independent Component Analysis (SICA). SICA provides an automatic...... ranking of components, which enables the suppression of clutter, hence extraction of components carrying mine information. The goal of the investigation is to evaluate various time and frequency domain ICA approaches based on SICA. Performance comparison is based on a series of mine-like objects ranging...

  15. Natural selection shaped the rise and fall of passenger pigeon genomic diversity.

    Science.gov (United States)

    Murray, Gemma G R; Soares, André E R; Novak, Ben J; Schaefer, Nathan K; Cahill, James A; Baker, Allan J; Demboski, John R; Doll, Andrew; Da Fonseca, Rute R; Fulton, Tara L; Gilbert, M Thomas P; Heintzman, Peter D; Letts, Brandon; McIntosh, George; O'Connell, Brendan L; Peck, Mark; Pipes, Marie-Lorraine; Rice, Edward S; Santos, Kathryn M; Sohrweide, A Gregory; Vohr, Samuel H; Corbett-Detig, Russell B; Green, Richard E; Shapiro, Beth

    2017-11-17

    The extinct passenger pigeon was once the most abundant bird in North America, and possibly the world. Although theory predicts that large populations will be more genetically diverse, passenger pigeon genetic diversity was surprisingly low. To investigate this disconnect, we analyzed 41 mitochondrial and 4 nuclear genomes from passenger pigeons and 2 genomes from band-tailed pigeons, which are passenger pigeons' closest living relatives. Passenger pigeons' large population size appears to have allowed for faster adaptive evolution and removal of harmful mutations, driving a huge loss in their neutral genetic diversity. These results demonstrate the effect that selection can have on a vertebrate genome and contradict results that suggested that population instability contributed to this species's surprisingly rapid extinction. Copyright © 2017, American Association for the Advancement of Science.

  16. Does selection against transcriptional interference shape retroelement-free regions in mammalian genomes?

    Directory of Open Access Journals (Sweden)

    Tobias Mourier

    Full Text Available BACKGROUND: Eukaryotic genomes are scattered with retroelements that proliferate through retrotransposition. Although retroelements make up around 40 percent of the human genome, large regions are found to be completely devoid of retroelements. This has been hypothesised to be a result of genomic regions being intolerant to insertions of retroelements. The inadvertent transcriptional activity of retroelements may affect neighbouring genes, which in turn could be detrimental to an organism. We speculate that such retroelement transcription, or transcriptional interference, is a contributing factor in generating and maintaining retroelement-free regions in the human genome. METHODOLOGY/PRINCIPAL FINDINGS: Based on the known transcriptional properties of retroelements, we expect long interspersed elements (LINEs to be able to display a high degree of transcriptional interference. In contrast, we expect short interspersed elements (SINEs to display very low levels of transcriptional interference. We find that genomic regions devoid of long interspersed elements (LINEs are enriched for protein-coding genes, but that this is not the case for regions devoid of short interspersed elements (SINEs. This is expected if genes are subject to selection against transcriptional interference. We do not find microRNAs to be associated with genomic regions devoid of either SINEs or LINEs. We further observe an increased relative activity of genes overlapping LINE-free regions during early embryogenesis, where activity of LINEs has been identified previously. CONCLUSIONS/SIGNIFICANCE: Our observations are consistent with the notion that selection against transcriptional interference has contributed to the maintenance and/or generation of retroelement-free regions in the human genome.

  17. Investigation into the optimum beam shape and fluence for selective ablation of dental calculus at lambda = 400 nm.

    Science.gov (United States)

    Schoenly, Joshua E; Seka, Wolf; Rechmann, Peter

    2010-01-01

    A frequency-doubled Ti:sapphire laser is shown to selectively ablate dental calculus. The optimal transverse shape of the laser beam, including its variability under water-cooling, is determined for selective ablation of dental calculus. Intensity profiles under various water-cooling conditions were optically observed. The 400-nm laser was coupled into a multimode optical fiber using an f = 2.5-cm lens and light-shaping diffuser. Water-cooling was supplied coaxially around the fiber. Five human tooth samples (four with calculus and one pristine) were irradiated perpendicular to the tooth surface while the tooth was moved back and forth at 0.3 mm/second, varying between 20 and 180 iterations. The teeth were imaged before and after irradiation using light microscopy with a flashing blue light-emitting diode (LED). An environmental scanning electron microscope imaged each tooth after irradiation. High-order super-Gaussian intensity profiles are observed at the output of a fiber coiled around a 4-in. diameter drum. Super-Gaussian beams have a more-homogenous fluence distribution than Gaussian beams and have a higher energy efficiency for selective ablation. Coaxial water-cooling does not noticeably distort the intensity distribution within 1 mm from the optical fiber. In contrast, lasers focused to a Gaussian cross section (Calculus is preferentially ablated at high fluences (> or =2 J/cm(2)); below this fluence, stalling occurs because of photo-bleaching of the calculus. Healthy dental hard tissue is not removed at fluences calculus with a frequency-doubled Ti:sapphire laser. Fluences over 2 J/cm(2) are required to remove calculus efficiently since photo-bleaching stalls calculus removal below that value.

  18. Classification of Alzheimer's disease patients with hippocampal shape wrapper-based feature selection and support vector machine

    Science.gov (United States)

    Young, Jonathan; Ridgway, Gerard; Leung, Kelvin; Ourselin, Sebastien

    2012-02-01

    It is well known that hippocampal atrophy is a marker of the onset of Alzheimer's disease (AD) and as a result hippocampal volumetry has been used in a number of studies to provide early diagnosis of AD and predict conversion of mild cognitive impairment patients to AD. However, rates of atrophy are not uniform across the hippocampus making shape analysis a potentially more accurate biomarker. This study studies the hippocampi from 226 healthy controls, 148 AD patients and 330 MCI patients obtained from T1 weighted structural MRI images from the ADNI database. The hippocampi are anatomically segmented using the MAPS multi-atlas segmentation method, and the resulting binary images are then processed with SPHARM software to decompose their shapes as a weighted sum of spherical harmonic basis functions. The resulting parameterizations are then used as feature vectors in Support Vector Machine (SVM) classification. A wrapper based feature selection method was used as this considers the utility of features in discriminating classes in combination, fully exploiting the multivariate nature of the data and optimizing the selected set of features for the type of classifier that is used. The leave-one-out cross validated accuracy obtained on training data is 88.6% for classifying AD vs controls and 74% for classifying MCI-converters vs MCI-stable with very compact feature sets, showing that this is a highly promising method. There is currently a considerable fall in accuracy on unseen data indicating that the feature selection is sensitive to the data used, however feature ensemble methods may overcome this.

  19. Non-Random Inversion Landscapes in Prokaryotic Genomes Are Shaped by Heterogeneous Selection Pressures.

    Science.gov (United States)

    Repar, Jelena; Warnecke, Tobias

    2017-08-01

    Inversions are a major contributor to structural genome evolution in prokaryotes. Here, using a novel alignment-based method, we systematically compare 1,651 bacterial and 98 archaeal genomes to show that inversion landscapes are frequently biased toward (symmetric) inversions around the origin-terminus axis. However, symmetric inversion bias is not a universal feature of prokaryotic genome evolution but varies considerably across clades. At the extremes, inversion landscapes in Bacillus-Clostridium and Actinobacteria are dominated by symmetric inversions, while there is little or no systematic bias favoring symmetric rearrangements in archaea with a single origin of replication. Within clades, we find strong but clade-specific relationships between symmetric inversion bias and different features of adaptive genome architecture, including the distance of essential genes to the origin of replication and the preferential localization of genes on the leading strand. We suggest that heterogeneous selection pressures have converged to produce similar patterns of structural genome evolution across prokaryotes. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  20. Selected properties of laser cladding coatings shaped using Flow drill technology

    Directory of Open Access Journals (Sweden)

    Bartkowski Dariusz

    2017-01-01

    Full Text Available The paper presents the investigations of selected chemical and mechanical properties as well as macro- and microstructure of materials formed using thermal drilling process (Flow drill. The aim of this study was to determine the microstructure of the coatings produced using laser cladding with powder technology. The coatings were produced on the low-carbon steel using 1 kW disc laser. After modification of surface, the thermal drilling process was applied. To produce all coatings, the pure copper powder was used. In this study the laser power equal of 500, 700 and 900 W were used. The microstructure, chemical composition (EDS and microhardness were investigation. It was found that the surface modification of low carbon steel and next conducted thermal drilling process caused change the surface properties on the hole flange. It was found that surface modification of steel using laser cladding with cooper powder and next Flow drill process contributes to the change in microhardness and chemical composition on hole flange.

  1. Quantitative structure-activity relationships for chronic toxicity of alkyl-chrysenes and alkyl-benz[a]anthracenes to Japanese medaka embryos (Oryzias latipes).

    Science.gov (United States)

    Lin, Hongkang; Morandi, Garrett D; Brown, R Stephen; Snieckus, Victor; Rantanen, Toni; Jørgensen, Kåre B; Hodson, Peter V

    2015-02-01

    Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and logKow values provided a rough estimation of structure-activity relationships for alkyl-PAHs, but Kow alone did not provide a complete explanation of the chronic toxicity of alkyl PAHs. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Boron-Catalyzed N-Alkylation of Amines using Carboxylic Acids.

    Science.gov (United States)

    Fu, Ming-Chen; Shang, Rui; Cheng, Wan-Min; Fu, Yao

    2015-07-27

    A boron-based catalyst was found to catalyze the straightforward alkylation of amines with readily available carboxylic acids in the presence of silane as the reducing agent. Various types of primary and secondary amines can be smoothly alkylated with good selectivity and good functional-group compatibility. This metal-free amine alkylation was successfully applied to the synthesis of three commercial medicinal compounds, Butenafine, Cinacalcet. and Piribedil, in a one-pot manner without using any metal catalysts. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Cytotoxicity of alkylating agents towards sensitive and resistant strains of Escherichia coli in relation to extent and mode of alkylation of cellular macromolecules and repair of alkylation lesions in deoxyribonucleic acids.

    Science.gov (United States)

    Lawley, P D; Brookes, P

    1968-09-01

    1. A quantitative study was made of the relationship between survival of colony-forming ability in Escherichia coli strains B/r and B(s-1) and the extents of alkylation of cellular DNA, RNA and protein after treatment with mono- or di-functional sulphur mustards, methyl methanesulphonate or iodoacetamide. 2. The mustards and methyl methanesulphonate react with nucleic acids in the cells, in the same way as found previously from chemical studies in vitro, and with proteins. Iodoacetamide reacts only with protein, principally with the thiol groups of cysteine residues. 3. The extents of alkylation of cellular constituents required to prevent cell division vary widely according to the strain of bacteria and the nature of the alkylating agent. 4. The extents of alkylation of the sensitive and resistant strains at a given dose of alkylating agent do not differ significantly. 5. Removal of alkyl groups from DNA of cells of the resistant strains B/r and 15T(-) after alkylation with difunctional sulphur mustard was demonstrated; the product di(guanin-7-ylethyl) sulphide, characteristic of di- as opposed to mono-functional alkylation, was selectively removed; the time-scale of this effect suggests an enzymic rather than a chemical mechanism. 6. The sensitive strain B(s-1) removed alkyl groups from DNA in this way only at very low extents of alkylation. When sensitized to mustard action by treatment with iodoacetamide, acriflavine or caffeine, the extent of alkylation of cellular DNA corresponding to a mean lethal dose was decreased to approximately 3 molecules of di(guanin-7-ylethyl) sulphide in the genome of this strain. 7. Relatively large numbers of monofunctional alkylations per genome can be withstood by this sensitive strain. Iodoacetamide had the weakest cytotoxic action of the agents investigated; methyl methanesulphonate was significantly weaker in effect than the monofunctional sulphur mustard, which was in turn weaker than the difunctional sulphur mustard. 8

  4. The effects of patch shape and connectivity on nest site selection and reproductive success of the Indigo Bunting.

    Energy Technology Data Exchange (ETDEWEB)

    Weldon, Aimee Jean

    2004-07-01

    Description – Ph.D Dissertation. North Carolina State University. Raleigh, North Carolina. 135 pp. Abatract - Habitat fragmentation and its associated effects have been blamed for the recent population declines of many Neotropical migratory bird species. Increased predation and parasitism resulting from edge-related effects have been implicated for poor nesting success in many studies, mostly of forest interior species. However, little attention has been devoted to disturbance-dependent birds. In this study, I examine how patch shape and connectivity in fragmented landscapes affects the reproductive success of disturbance-dependent bird species, specifically the Indigo Bunting (Passerina cyanea). I conducted my study in a landscape-scale experimental system of similar-area habitat patches that differed in connectivity and in shape. Shapes differed between edgy and rectangular forms, where edgy patches contained 50% more edge than rectangular patches. I tested whether edgy patches function as ecological traps for species with strong edge preferences, by leading them to select dangerous habitats. Indigo Buntings preferentially selected edgy patches over rectangular patches, but experienced significantly lower reproductive success in edgy patches early in the season. Although predation pressure intensified in rectangular patches late in the season, seasonal fecundity was still significantly lower in edgy patches, providing the first empirical evidence that edges can function as ecological traps for Indigo Buntings. A second objective of my study was to evaluate the efficacy of conservation corridors for disturbance-dependent bird species. Conservation corridors have become a popular strategy to preserve biodiversity and promote gene flow in fragmented landscapes, but corridors may also have negative consequences. I tested the hypothesis that corridors can increase nest predation risk in connected patches relative to unconnected patches. Nest predation rates

  5. Spatially varying selection shapes life history clines among populations of Drosophila melanogaster from sub-Saharan Africa.

    Science.gov (United States)

    Fabian, D K; Lack, J B; Mathur, V; Schlötterer, C; Schmidt, P S; Pool, J E; Flatt, T

    2015-04-01

    Clines in life history traits, presumably driven by spatially varying selection, are widespread. Major latitudinal clines have been observed, for example, in Drosophila melanogaster, an ancestrally tropical insect from Africa that has colonized temperate habitats on multiple continents. Yet, how geographic factors other than latitude, such as altitude or longitude, affect life history in this species remains poorly understood. Moreover, most previous work has been performed on derived European, American and Australian populations, but whether life history also varies predictably with geography in the ancestral Afro-tropical range has not been investigated systematically. Here, we have examined life history variation among populations of D. melanogaster from sub-Saharan Africa. Viability and reproductive diapause did not vary with geography, but body size increased with altitude, latitude and longitude. Early fecundity covaried positively with altitude and latitude, whereas lifespan showed the opposite trend. Examination of genetic variance-covariance matrices revealed geographic differentiation also in trade-off structure, and QST -FST analysis showed that life history differentiation among populations is likely shaped by selection. Together, our results suggest that geographic and/or climatic factors drive adaptive phenotypic differentiation among ancestral African populations and confirm the widely held notion that latitude and altitude represent parallel gradients. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  6. Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma.

    Science.gov (United States)

    Head, R J; Fay, M F; Cosgrove, L; Y C Fung, K; Rundle-Thiele, D; Martin, J H

    2017-12-02

    Glioblastoma is a lethal form of brain tumour usually treated by surgical resection followed by radiotherapy and an alkylating chemotherapeutic agent. Key to the success of this multimodal approach is maintaining apoptotic sensitivity of tumour cells to the alkylating agent. This initial treatment likely establishes conditions contributing to development of drug resistance as alkylating agents form the O 6 -methylguanine adduct. This activates the mismatch repair (MMR) process inducing apoptosis and mutagenesis. This review describes key juxtaposed drivers in the balance between alkylation induced mutagenesis and apoptosis. Mutations in MMR genes are the probable drivers for alkylation based drug resistance. Critical to this interaction are the dose-response and temporal interactions between adduct formation and MMR mutations. The precision in dose interval, dose-responses and temporal relationships dictate a role for alkylating agents in either promoting experimental tumour formation or inducing tumour cell death with chemotherapy. Importantly, this resultant loss of chemotherapeutic selective pressure provides opportunity to explore novel therapeutics and appropriate combinations to minimise alkylation based drug resistance and tumour relapse.

  7. Iminium ion chemistry of mitosene DNA alkylating agents. Enriched 13C NMR and isolation studies.

    Science.gov (United States)

    Ouyang, A; Skibo, E B

    2000-05-16

    Described herein is a study of the reductive alkylation chemistry of mitosene antitumor agents. We employed a 13C-enriched electrophilic center to probe the fate of the iminium ion resulting from reductive activation. The 13C-labeled center permitted the identification of complex products resulting from alkylation reactions. In the case of DNA reductive alkylation, the type and number of alkylation sites were readily assessed by 13C NMR. Although there has been much excellent work done in the area of mitosene chemistry and biochemistry, the present study provides a number of new findings: (1) The major fate of the iminium ion is head-to-tail polymerization, even in dilute solutions. (2) Dithionite reductive activation results in the formation of mitosene sulfite esters as well as the previously observed sulfonate adducts. (3) The mitosene iminium ion alkylates the adenosine 6-amino group as well as the guanosine 2-amino group. The identification of the latter adduct was greatly facilitated by the 13C-label at the electrophilic center. (4) The mitosene iminium ion alkylates DNA at both nitrogen and oxygen centers without any apparent base selectivity. The complexity of mitosene reductive alkylation of DNA will require continued adduct isolation studies.

  8. Mechanical and shape memory properties of porous Ni50.1Ti49.9 alloys manufactured by selective laser melting.

    Science.gov (United States)

    Taheri Andani, Mohsen; Saedi, Soheil; Turabi, Ali Sadi; Karamooz, M R; Haberland, Christoph; Karaca, Haluk Ersin; Elahinia, Mohammad

    2017-04-01

    Near equiatomic NiTi shape memory alloys were fabricated in dense and designed porous forms by Selective Laser Melting (SLM) and their mechanical and shape memory properties were systematically characterized. Particularly, the effects of pore morphology on their mechanical responses were investigated. Dense and porous NiTi alloys exhibited good shape memory effect with a recoverable strain of about 5% and functional stability after eight cycles of compression. The stiffness and residual plastic strain of porous NiTi were found to depend highly on the pore shape and the level of porosity. Since porous NiTi structures have lower elastic modulus and density than dense NiTi with still good shape memory properties, they are promising materials for lightweight structures, energy absorbers, and biomedical implants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Shape-selective synthesis of Sn(MoO4)2 nanomaterials for catalysis and supercapacitor applications.

    Science.gov (United States)

    Sakthikumar, K; Ede, Sivasankara Rao; Mishra, Soumyaranjan; Kundu, Subrata

    2016-06-07

    Size and shape-selective Sn(MoO4)2 nanomaterials have been synthesized for the first time using a simple hydrothermal route by the reaction of Sn(ii) chloride salt with sodium molybdate in CTAB micellar media under stirring at 60 °C temperature for about three hours. Needle-like and flake-like Sn(MoO4)2 nanomaterials were synthesized by optimizing the CTAB to metal salt molar ratio and by controlling other reaction parameters. The eventual diameter and length of the nanoneedles are ∼100 ± 10 nm and ∼850 ± 100 nm respectively. The average diameter of the flakes is ∼250 ± 50 nm. The synthesized Sn(MoO4)2 nanomaterials can be used in two potential applications, namely, catalytic reduction of nitroarenes and as an anodic material in electrochemical supercapacitors. From the catalysis study, it was observed that the Sn(MoO4)2 nanomaterials could act as a potential catalyst for the successful photochemical reduction of nitroarenes into their respective aminoarenes within a short reaction time. From the supercapacitor study, it was observed that the Sn(MoO4)2 nanomaterials of different shapes show different specific capacitance (Cs) values and the highest Cs value was observed for Sn(MoO4)2 nanomaterials having a flake-like morphology. The highest Cs value observed was 109 F g(-1) at a scan rate of 5 mV s(-1) for the flake-like Sn(MoO4)2 nanomaterials. The capacitor shows an excellent long cycle life along with 70% retention of the Cs value, even after 4000 consecutive cycles at a current density of 8 mA cm(-2). Other than the applications in catalysis and supercapacitors, the synthesized nanomaterials can find further applications in photoluminescence, sensor and other energy-related devices.

  10. New potential of the reductive alkylation of amines

    International Nuclear Information System (INIS)

    Gusak, K N; Ignatovich, Zh V; Koroleva, E V

    2015-01-01

    Available data on the reductive alkylation of amines with carbonyl compounds — a key method for the preparation of secondary and tertiary amines — are described systematically. The review provides information on the relevant reducing agents and catalysts and on the use of chiral catalysts in stereo- and enantiocontrolled reactions of amine synthesis. The effect of the reactant and catalyst structures on the reaction rates and chemo- and stereo(enantio)selectivity is considered. The bibliography includes 156 references

  11. Alkylation of isobutane by butenes on zirconium sulfate catalysts

    International Nuclear Information System (INIS)

    Lavrenov, A.V.; Perelevskij, E.V.; Finevich, V.P.; Zajkovskij, V.I.; Paukshtis, E.A.; Duplyakiv, V.K.; Bal'zhinimaev, B.S.

    2003-01-01

    Preparation of applied zirconium sulfate catalysts obtained by the method of impregnation is investigated. Results of comparative study of structural, acid-base and catalytic properties of sulfated zirconium dioxide applied on silica gel and aluminium oxide are represented. Intervals of values of synthesis basic parameters and characteristics of catalysts properties providing achievement of high activity and selectivity in isobutane alkylation by butenes in liquid phase are determined [ru

  12. A new phenylethyl alkyl amide from the Ambrostoma quadriimpressum Motschulsky

    Directory of Open Access Journals (Sweden)

    Guolei Zhao

    2011-09-01

    Full Text Available A new phenylethyl alkyl amide, (10R-10-hydroxy-N-phenethyloctadecanamide (1, was isolated from the beetle Ambrostoma quadriimpressum Motschulsky. The structure of the amide was determined by NMR and MS. The absolute configuration of compound 1 was confirmed by an asymmetric total synthesis, which was started from L-glutamic acid. The construction of the aliphatic chain was accomplished by the selective protection of the hydroxy groups and two-time implementation of the Wittig olefination reaction.

  13. Shape Engineering Driven by Selective Growth of SnO2 on Doped Ga2O3 Nanowires.

    Science.gov (United States)

    Alonso-Orts, Manuel; Sánchez, Ana M; Hindmarsh, Steven A; López, Iñaki; Nogales, Emilio; Piqueras, Javier; Méndez, Bianchi

    2017-01-11

    Tailoring the shape of complex nanostructures requires control of the growth process. In this work, we report on the selective growth of nanostructured tin oxide on gallium oxide nanowires leading to the formation of SnO 2 /Ga 2 O 3 complex nanostructures. Ga 2 O 3 nanowires decorated with either crossing SnO 2 nanowires or SnO 2 particles have been obtained in a single step treatment by thermal evaporation. The reason for this dual behavior is related to the growth direction of trunk Ga 2 O 3 nanowires. Ga 2 O 3 nanowires grown along the [001] direction favor the formation of crossing SnO 2 nanowires. Alternatively, SnO 2 forms rhombohedral particles on [110] Ga 2 O 3 nanowires leading to skewer-like structures. These complex oxide structures were grown by a catalyst-free vapor-solid process. When pure Ga and tin oxide were used as source materials and compacted powders of Ga 2 O 3 acted as substrates, [110] Ga 2 O 3 nanowires grow preferentially. High-resolution transmission electron microscopy analysis reveals epitaxial relationship lattice matching between the Ga 2 O 3 axis and SnO 2 particles, forming skewer-like structures. The addition of chromium oxide to the source materials modifies the growth direction of the trunk Ga 2 O 3 nanowires, growing along the [001], with crossing SnO 2 wires. The SnO 2 /Ga 2 O 3 junctions does not meet the lattice matching condition, forming a grain boundary. The electronic and optical properties have been studied by XPS and CL with high spatial resolution, enabling us to get both local chemical and electronic information on the surface in both type of structures. The results will allow tuning optical and electronic properties of oxide complex nanostructures locally as a function of the orientation. In particular, we report a dependence of the visible CL emission of SnO 2 on its particular shape. Orange emission dominates in SnO 2 /Ga 2 O 3 crossing wires while green-blue emission is observed in SnO 2 particles attached to Ga 2

  14. Quantitative structure–activity relationships for chronic toxicity of alkyl-chrysenes and alkyl-benz[a]anthracenes to Japanese medaka embryos (Oryzias latipes)

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Hongkang [Department of Biology, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Morandi, Garrett D. [School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Brown, R. Stephen [School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Department of Chemistry, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Snieckus, Victor; Rantanen, Toni [Department of Chemistry, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Jørgensen, Kåre B. [Department of Mathematics and Natural Sciences, University of Stavanger, 4036 Stavanger (Norway); Hodson, Peter V., E-mail: peter.hodson@queensu.ca [Department of Biology, Queen' s University, Kingston, Ontario K7L3N6 (Canada); School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada)

    2015-02-15

    Highlights: • Medaka embryos were exposed to alkyl chrysenes and benzo[a]anthracenes (BAA). • Concentrations were kept constant by partition controlled delivery. • Chrysene was not toxic within solubility limits, in contrast to BAA. • Alkylation increased the toxicity of chrysene and BAA. • Toxicity was related to hydrophobicity and to specific modes of action. - Abstract: Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and log K{sub ow} values provided a rough estimation of structure–activity relationships for alkyl-PAHs, but K{sub ow} alone did not provide

  15. Characterization of reaction conditions providing rapid and specific cysteine alkylation for peptide-based mass spectrometry.

    Science.gov (United States)

    Paulech, Jana; Solis, Nestor; Cordwell, Stuart J

    2013-01-01

    Alkylation converts Cys thiols to thioethers and prevents unwanted side reactions, thus facilitating mass spectrometric identification of Cys-containing peptides. Alkylation occurs preferentially at Cys due to its high nucleophilicity, however reactions at other such sites are possible. N-ethylmaleimide (NEM) shows rapid reaction kinetics with Cys and careful definition of reaction conditions results in little reactivity at other sites. Analysis of a protein standard alkylated under differing reaction conditions (pH, NEM concentrations and reaction times) was performed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) and selected reaction monitoring (SRM) of NEM-modified and unmodified peptide pairs. Mis-alkylation sites at primary and secondary amines were identified and limited to one equivalent of NEM. No evidence for hydroxyl or thioether alkylation was observed. Improved specificity was achieved by restricting the pH below neutral, NEM concentration below 10mM and/or reaction time to below 5min. Maximal removal of Cys activity was observed in tissue homogenates at 40mM NEM within 1min, dependent upon efficient protein denaturation. SRM assays identified peptide-specific levels of mis-alkylation, indicating that NEM-modified to unmodified ratios did not exceed 10%, with the exception of Cys alkylation that proceeded to 100%, and some Lys residues that resulted in tryptic missed cleavages. High reactivity was observed for His residues considering their relatively low abundance. These data indicate that rapid and specific Cys alkylation is possible with NEM under relatively mild conditions, with more abrasive conditions leading to increased non-specific alkylation without appreciable benefit for MS-based proteomics. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) for direct, versatile and accurate RNA structure analysis.

    Science.gov (United States)

    Smola, Matthew J; Rice, Greggory M; Busan, Steven; Siegfried, Nathan A; Weeks, Kevin M

    2015-11-01

    Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemistries exploit small electrophilic reagents that react with 2'-hydroxyl groups to interrogate RNA structure at single-nucleotide resolution. Mutational profiling (MaP) identifies modified residues by using reverse transcriptase to misread a SHAPE-modified nucleotide and then counting the resulting mutations by massively parallel sequencing. The SHAPE-MaP approach measures the structure of large and transcriptome-wide systems as accurately as can be done for simple model RNAs. This protocol describes the experimental steps, implemented over 3 d, that are required to perform SHAPE probing and to construct multiplexed SHAPE-MaP libraries suitable for deep sequencing. Automated processing of MaP sequencing data is accomplished using two software packages. ShapeMapper converts raw sequencing files into mutational profiles, creates SHAPE reactivity plots and provides useful troubleshooting information. SuperFold uses these data to model RNA secondary structures, identify regions with well-defined structures and visualize probable and alternative helices, often in under 1 d. SHAPE-MaP can be used to make nucleotide-resolution biophysical measurements of individual RNA motifs, rare components of complex RNA ensembles and entire transcriptomes.

  17. S-alkylation of soft scorpionates.

    Science.gov (United States)

    Rajasekharan-Nair, Rajeev; Moore, Dean; Chalmers, Kirsten; Wallace, Dawn; Diamond, Louise M; Darby, Lisa; Armstrong, David R; Reglinski, John; Spicer, Mark D

    2013-02-11

    The alkylation reactions of soft scorpionates are reported. The hydrotris(S-alkyl-methimazolyl)borate dications (alkyl = methyl, allyl, benzyl), which were prepared by the reaction of Tm(Me) anion and primary alkyl halides, have been isolated and structurally characterised. The reaction is, however, not universally successful. DFT analysis of these alkylation reactions (C=S versus B-H alkylation) indicates that the observed outcome is driven by kinetic factors. Extending the study to incorporate alternative imine thiones (mercaptobenzothiazole, bz; thiazoline, tz) led to the structural characterisation of di[aquo-μ-aquohydrotris(mercaptobenzothiazolyl)boratosodium], which contains sodium atoms in the κ(3)-S,S,S coordination mode. Alkylation of Na[Tbz] and Na[tzTtz] leads to decomposition resulting in the formation of the simple S-alkylated heterocycles. The analysis of the species involved in these reactions shows an inherent weakness in the B-N bond in soft scorpionates, which has implications for their use in more advanced chemistry. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Process for production of an alkyl methacrylate

    NARCIS (Netherlands)

    Eastham, Graham Ronald; Johnson, David William; Fraaije, Marco; Winter, Remko

    2015-01-01

    A process for the production of an alkyl methacrylate, particularly methyl methacrylate, is provided, in which a Baeyer-Villiger Monooxygenase enzyme is used to convert an alkylisopropenylketone substrate to the relevant alkyl methacrylate by abnormal asymmetric oxygen insertion. The invention

  19. Isobutane alkylation. Recent developments and future perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Hommeltoft, Sven Ivar [Haldor Topsoe A/S, Nymoellevej 55, DK-2800 Lyngby (Denmark)

    2001-11-30

    In the isobutane alkylation, alkylated gasoline is obtained which is a valuable blending component for the gasoline pool. Thereby the C{sub 3}-C{sub 4} cut from the FCC units can be extensively used. Established technologies and recent developments will be reviewed and future perspectives will be given.

  20. Multiple selective events at the PRDM16 functional pathway shaped adaptation of western European populations to different climate conditions.

    Science.gov (United States)

    Quagliarello, Andrea; De Fanti, Sara; Giuliani, Cristina; Abondio, Paolo; Serventi, Patrizia; Sarno, Stefania; Sazzini, Marco; Luiselli, Donata

    2017-12-30

    Several studies highlighted the role of climate in shaping many human evolutionary processes. This occurred even in relatively recent times, having affected various human phenotypic traits, among which metabolic processes that orchestrate absorption and accumulation of substances to maintain energy homeostasis, that is critical for the survival of individuals in high energy-expenditure environments. To date, most researches have focalized on detection of climatic influence on SNPs' frequency in populations exposed to extreme environmental conditions or by comparing variation patterns between populations from different continents. In this study, we instead explored the genetic background of distinct western European human groups at loci involved in nutritional and thermoregulation processes, to test whether patterns of differential local adaptation to environmental conditions could be appreciated also at a lower geographical scale. Taking advantage from the 1000 Genomes Project data, genetic information for 21 genes involved in nutritional and thermoregulation processes was analysed for three western European populations. The applied Anthropological Genetics methods pointed to appreciable differentiation between the examined groups especially for the PRDM16 gene. Moreover, several neutrality tests suggested that balancing selection has acted on different regions of the gene in people from Great Britain, as well as that more recent positive selection could have also targeted some PRDM16 SNPs in Finn and Italian populations. These series of adaptive footprints are plausibly related to climate variability in both ancient and relatively recent times. Since this locus is involved in thermoregulation mechanisms and adipogenesis, local adaptations mediated by a pathway related to the brown adipose tissue activity could have evolved in response to changing cold temperature exposures of such populations.

  1. Silver ion mediated shape control of platinum nanoparticles: Removal of silver by selective etching leads to increased catalytic activity

    Energy Technology Data Exchange (ETDEWEB)

    Grass, Michael E.; Yue, Yao; Habas, Susan E.; Rioux, Robert M.; Teall, Chelsea I.; Somorjai, G.A.

    2008-01-09

    A procedure has been developed for the selective etching of Ag from Pt nanoparticles of well-defined shape, resulting in the formation of elementally-pure Pt cubes, cuboctahedra, or octahedra, with a largest vertex-to-vertex distance of {approx}9.5 nm from Ag-modified Pt nanoparticles. A nitric acid etching process was applied Pt nanoparticles supported on mesoporous silica, as well as nanoparticles dispersed in aqueous solution. The characterization of the silica-supported particles by XRD, TEM, and N{sub 2} adsorption measurements demonstrated that the structure of the nanoparticles and the mesoporous support remained conserved during etching in concentrated nitric acid. Both elemental analysis and ethylene hydrogenation indicated etching of Ag is only effective when [HNO{sub 3}] {ge} 7 M; below this concentration, the removal of Ag is only {approx}10%. Ethylene hydrogenation activity increased by four orders of magnitude after the etching of Pt octahedra that contained the highest fraction of silver. High-resolution transmission electron microscopy of the unsupported particles after etching demonstrated that etching does not alter the surface structure of the Pt nanoparticles. High [HNO{sub 3}] led to the decomposition of the capping agent, polyvinylpyrollidone (PVP); infrared spectroscopy confirmed that many decomposition products were present on the surface during etching, including carbon monoxide.

  2. Direct observation of enhanced magnetism in individual size- and shape-selected 3 d transition metal nanoparticles

    Science.gov (United States)

    Kleibert, Armin; Balan, Ana; Yanes, Rocio; Derlet, Peter M.; Vaz, C. A. F.; Timm, Martin; Fraile Rodríguez, Arantxa; Béché, Armand; Verbeeck, Jo; Dhaka, R. S.; Radovic, Milan; Nowak, Ulrich; Nolting, Frithjof

    2017-05-01

    Magnetic nanoparticles are critical building blocks for future technologies ranging from nanomedicine to spintronics. Many related applications require nanoparticles with tailored magnetic properties. However, despite significant efforts undertaken towards this goal, a broad and poorly understood dispersion of magnetic properties is reported, even within monodisperse samples of the canonical ferromagnetic 3 d transition metals. We address this issue by investigating the magnetism of a large number of size- and shape-selected, individual nanoparticles of Fe, Co, and Ni using a unique set of complementary characterization techniques. At room temperature, only superparamagnetic behavior is observed in our experiments for all Ni nanoparticles within the investigated sizes, which range from 8 to 20 nm. However, Fe and Co nanoparticles can exist in two distinct magnetic states at any size in this range: (i) a superparamagnetic state, as expected from the bulk and surface anisotropies known for the respective materials and as observed for Ni, and (ii) a state with unexpected stable magnetization at room temperature. This striking state is assigned to significant modifications of the magnetic properties arising from metastable lattice defects in the core of the nanoparticles, as concluded by calculations and atomic structural characterization. Also related with the structural defects, we find that the magnetic state of Fe and Co nanoparticles can be tuned by thermal treatment enabling one to tailor their magnetic properties for applications. This paper demonstrates the importance of complementary single particle investigations for a better understanding of nanoparticle magnetism and for full exploration of their potential for applications.

  3. Amino acid nitrosation products as alkylating agents.

    Science.gov (United States)

    García-Santos, M del P; Calle, E; Casado, J

    2001-08-08

    Nitrosation reactions of alpha-, beta-, and gamma-amino acids whose reaction products can act as alkylating agents of DNA were investigated. To approach in vivo conditions for the two-step mechanism (nitrosation and alkylation), nitrosation reactions were carried out in aqueous acid conditions (mimicking the conditions of the stomach lumen) while the alkylating potential of the nitrosation products was investigated at neutral pH, as in the stomach lining cells into which such products can diffuse. These conclusions were drawn: (i) The alkylating species resulting from the nitrosation of amino acids with an -NH(2) group are the corresponding lactones; (ii) the sequence of alkylating power is: alpha-lactones > beta-lactones > gamma-lactones, coming respectively from the nitrosation of alpha-, beta-, and gamma-amino acids; and (iii) the results obtained may be useful in predicting the mutagenic effectiveness of the nitrosation products of amino acids.

  4. Study on the Alkylation Reactions of N(7)-Unsubstituted 1,3-Diazaoxindoles.

    Science.gov (United States)

    Kókai, Eszter; Halász, Judit; Dancsó, András; Nagy, József; Simig, Gyula; Volk, Balázs

    2017-05-19

    The chemistry of the 5,7-dihydro-6 H -pyrrolo[2,3- d ]pyrimidin-6-one (1,3-diazaoxindole) compound family, possessing a drug-like scaffold, is unexplored. In this study, the alkylation reactions of N (7)-unsubstituted 5-isopropyl-1,3-diazaoxindoles bearing various substituents at the C (2) position have been investigated. The starting compounds were synthesized from the C (5)-unsubstituted parent compounds by condensation with acetone and subsequent catalytic reduction of the 5-isopropylidene moiety. Alkylation of the thus obtained 5-isopropyl derivatives with methyl iodide or benzyl bromide in the presence of a large excess of sodium hydroxide led to 5,7-disubstituted derivatives. Use of butyllithium as the base rendered alkylation in the C (5) position possible with reasonable selectivity, without affecting the N (7) atom. During the study on the alkylation reactions, some interesting by-products were also isolated and characterized.

  5. Toxicity assessment and selective leaching characteristics of Cu-Al-Ni shape memory alloys in biomaterials applications.

    Science.gov (United States)

    Chang, Shih-Hang; Chen, Bor-Yann; Lin, Jin-Xiang

    2016-04-06

    Cu-Al-Ni shape memory alloys (SMAs) possess two-way shape memory effects, superelasticity, and damping capacity. Nonetheless, Cu-Al-Ni SMAs remain promising candidates for use in biomedical applications, as they are more economical and machinable than other SMAs. Ensuring the biocompatibility of Cu-Al-Ni SMAs is crucial to their development for biomedical applications. Therefore, this study aimed to assess the toxicity of Cu-Al-Ni SMAs using a Probit dose-response model and augmented simplex design. In this study, the effects of Cu2+, Al3+ and Ni2+ metal ions on bacteria (Escherichia coli DH5α) using Probit dose-response analysis and augmented simplex design to assess the actual toxicity of the Cu-Al-Ni SMAs. Extraction and repetition of Escherichia coli DH5α solutions with high Cu2+ ion concentrations and 30-hour incubation demonstrated that Escherichia coli DH5α was able to alter its growth mechanisms in response to toxins. Metal ions leached from Cu-Al-Ni SMAs appeared in a multitude of compositions with varying degrees of toxicity, and those appearing close to a saddle region identified in the contour plot of the augmented simplex model were identified as candidates for elevated toxicity levels. When the Cu-13.5Al-4Ni SMA plate was immersed in Ringer's solution, the selective leaching rate of Ni2+ ions far exceeded that of Cu2+ and Al3+. The number of Cu2+, Al3+ and Ni2+ ions leached from Cu-Al-Ni SMAs increased with immersion time; however, at higher ratios, toxicity interactions among the metal ions had the effect of gradually reducing overall toxicity levels with regard to Escherichia coli DH5α. The quantities of Cu2+, Al3+ and Ni2+ ions leached from the Cu-13.5Al-4Ni SMA plate increased with immersion time, the toxicity interactions associated with these compositions reduced the actual toxicity to Escherichia coli DH5α.

  6. Alkylation of isobutane by ethylene: A thermodynamic study

    Energy Technology Data Exchange (ETDEWEB)

    Goupil, J.M.; Poirier, J.L.; Cornet, D. (Univ. of Caen (France). Lab. Catalyse et Spectrochimie)

    1994-03-01

    Alkylation of isobutane by ethylene produces mainly hexanes, but a variety of other compounds, alkanes or alkenes, may be formed by secondary reactions such as successive alkylations, isomerization, and ethylene polymerization. The equilibrium distribution of products is evaluated in the temperature range 280--680 K and at various initial compositions and pressures. Isomer groups are treated using Alberty's formulation. Calculations show that alkenes are thermodynamically unstable under usual reaction conditions. The equilibrium amounts of alkanes are such that C[sub 6] [much gt] C[sub 8] [much gt] C[sub 10] and heavy alkanes also appear unstable. The selective formation of particular isomers (dimethylbutanes, trimethylpentanes) is also integrated in the equilibrium equations. The calculated compositions (C[sub 6]:C[sub 8]:C[sub 10]) are compared with experimental data.

  7. Asymmetric Alkylation and Aldol Reactions of D-Mannitol-Derived Chiral Oxazolidin-2-one Derivatives

    International Nuclear Information System (INIS)

    Maeng, Yun Hee; Jun, Jong Gab

    2004-01-01

    In the preceding article, we have introduced a new chiral oxazolidin-2-one auxiliary (1) derived from a cheap Dmannitol, and demonstrated the chiral selectivity in alkylation, aldol reaction and β-lactam synthesis.1 The present work began with a search for useful chiral directing groups with which to control the chiral selectivity. Because the rigidity of cyclic structures contributes significantly to control of chirality,2 the 1,2:5,6-di-O-cyclohexylidene-Dmannitol (2) was used for the synthesis of oxazolidin-2-one chiral auxiliary (3) comparing the selectivity with the auxiliary (1) in alkylation and aldol reactions.

  8. Product shape selectivity of MFI-type, MEL-type, and BEA-type zeolites in the catalytic hydroconversion of heptane

    NARCIS (Netherlands)

    Poursaeidesfahani, A.; de Lange, M.F.; Khodadadian, F.; Dubbeldam, D.; Rigutto, Marcello; Nair, Nitish; Vlugt, T.J.H.

    2017-01-01

    The influence of product shape selectivity on the bifunctional conversion of n-C7 by zeolite catalysts is investigated. Three different zeolite catalysts with different pore sizes (MFI-type, MEL-type, and BEA-type zeolites) have been investigated experimentally. For all three

  9. Introduction of a Simple Experiment for the Undergraduate Organic Chemistry Laboratory Demonstrating the Lewis Acid and Shape-Selective Properties of Zeolite Na-Y

    Science.gov (United States)

    Maloney, Vincent; Szczepanski, Zach

    2017-01-01

    A simple, inexpensive, discovery-based experiment for undergraduate organic laboratories has been developed that demonstrates the Lewis acid and shape-selective properties of zeolites. Calcined zeolite Na-Y promotes the electrophilic aromatic bromination of toluene with a significantly higher para/ortho ratio than observed under conventional…

  10. Isobutane/2-butene alkylation over potential heterogeneous catalysts in a slurry reactor

    Energy Technology Data Exchange (ETDEWEB)

    Roervik, T.

    1996-12-31

    The trend towards more effective use of fossil fuels and reduced environmental pollution represents a major task of improvement within the refinery processes. The highly isomerized and high octane paraffins produced from isobutane and light olefins by alkylation fulfill all the requirements for reformulated gasoline. This doctoral thesis discusses new catalyst systems because of their potential in alkylation. A slurry reactor apparatus for solid-acid catalysed isobutane/butene alkylation was developed and used to investigate the performance of various heterogeneous catalysts. The selected materials were mainly zeolite types with faujasite structures. The samples were characterized by various methods before alkylation. In general, the order of decreasing catalyst activity after 3 h of reaction at 80{sup o}C was found to be: H-EMT >> H-FAU, dealuminated H-FAU >> NS.500, TA-Y, CeY-98 > Nafion-H. The order of decreasing alkylate selectivity of the catalysts was: H-EMT >> dealuminated H-FAU > H-FAU >> Nafion-H > CeY-98 > TA-Y > H-SAPO-37, NS.500. H-EMT was the most promising system for further development, also because of the very low formation of the undesirable isooctenes and a high selectivity towards isooctanes among the alkylates. A high density of accessible strong acid sites was found to be essential for a high alkylation activity and selectivity. Open structure, like hexagonal faujasite, was advantageous. The distribution of trimethylpentanes formed in zeolites was ascribed to pore restrictions as a major factor. The effect of operating conditions on catalyst performance was investigated statistically, and a high dilution of butene in the slurry reactor was found to be very important. 153 refs., 40 figs., 12 tabs.

  11. Oxidative 1,2-carboamination of alkenes with alkyl nitriles and amines toward γ-amino alkyl nitriles

    Science.gov (United States)

    Liu, Yan-Yun; Yang, Xu-Heng; Song, Ren-Jie; Luo, Shenglian; Li, Jin-Heng

    2017-04-01

    Difunctionalization of alkenes has become a powerful tool for quickly increasing molecular complexity in synthesis. Despite significant progress in the area of alkene difunctionalization involving the incorporation of a nitrogen atom across the C-C double bonds, approaches for the direct 1,2-carboamination of alkenes to produce linear N-containing molecules are scarce and remain a formidable challenge. Here we describe a radical-mediated oxidative intermolecular 1,2-alkylamination of alkenes with alkyl nitriles and amines involving C(sp3)-H oxidative functionalization catalysed by a combination of Ag2CO3 with iron Lewis acids. This three-component alkene 1,2-alkylamination method is initiated by the C(sp3)-H oxidative radical functionalization, which enables one-step formation of two new chemical bonds, a C-C bond and a C-N bond, to selectively produce γ-amino alkyl nitriles.

  12. Alkylation of organic aromatic compounds

    Science.gov (United States)

    Smith, Jr., Lawrence A.

    1989-01-01

    Aromatic compounds are alkylated in a catalytic distillation, wherein the catalyst structure also serves as a distillation component by contacting the aromatic compound with a C.sub.2 to C.sub.10 olefin in the catalyst bed under 0.25 to 50 atmospheres of pressure and at temperatures in the range of 80.degree. C. to 500.degree. C., using as the catalyst a mole sieve characterized as acidic or an acidic cation exchange resin. For example, ethyl benzene is produced by feeding ethylene below the catalyst bed while benzene is conveniently added through the reflux in molar excess to that required to react with ethylene, thereby reacting substantially all of the ethylene and recovering benzene as the principal overhead and ethyl benzene in the bottoms.

  13. Alkylation of organic aromatic compounds

    Science.gov (United States)

    Smith, L.A. Jr.

    1989-07-18

    Aromatic compounds are alkylated in a catalytic distillation, wherein the catalyst structure also serves as a distillation component by contacting the aromatic compound with a C[sub 2] to C[sub 10] olefin in the catalyst bed under 0.25 to 50 atmospheres of pressure and at temperatures in the range of 80 C to 500 C, using as the catalyst a mole sieve characterized as acidic or an acidic cation exchange resin. For example, ethyl benzene is produced by feeding ethylene below the catalyst bed while benzene is conveniently added through the reflux in molar excess to that required to react with ethylene, thereby reacting substantially all of the ethylene and recovering benzene as the principal overhead and ethyl benzene in the bottoms. 1 fig.

  14. Lithium-Catalyzed Thiol Alkylation with Tertiary and Secondary Alcohols: Synthesis of 3-Sulfanyl-Oxetanes as Bioisosteres.

    Science.gov (United States)

    Croft, Rosemary A; Mousseau, James J; Choi, Chulho; Bull, James A

    2018-01-19

    3-Sulfanyl-oxetanes are presented as promising novel bioisosteric replacements for thioesters or benzyl sulfides. From oxetan-3-ols, a mild and inexpensive Li catalyst enables chemoselective C-OH activation and thiol alkylation. Oxetane sulfides are formed from various thiols providing novel motifs in new chemical space and specifically as bioisosteres for thioesters due to their similar shape and electronic properties. Under the same conditions, various π-activated secondary and tertiary alcohols are also successful. Derivatization of the oxetane sulfide linker provides further novel oxetane classes and building blocks. Comparisons of key physicochemical properties of the oxetane compounds to selected carbonyl and methylene analogues indicate that these motifs are suitable for incorporation into drug discovery efforts. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. The alkylation of imine anions formation of enamines

    NARCIS (Netherlands)

    Heiszwolf, G.J.; Kloosterziel, H.

    1970-01-01

    The ambident anions derived from imines were alkylated using a variety of solvents and alkylating agents. Under reactive conditions enamines (N-alkylation) are formed as the main products instead of the usually obsd. homologous imines (C-alkylation). The influence of the type of imine, solvent, and

  16. Alkylation of enolate anions formation of enol ethers

    NARCIS (Netherlands)

    Heiszwolf, G.J.; Kloosterziel, H.

    1970-01-01

    The alkylation of ambident enolate anions-obtained from aliphatic ketones (and one particular type of aldehyde)-was studied using various solvents, bases, alkylating agents and substrates. Alkylation with a reactive alkylating agent (dialkyl sulfates, triethyloxonium fluoroborate) in an aprotic

  17. Experimental and QSAR study on the surface activities of alkyl imidazoline surfactants

    Science.gov (United States)

    Kong, Xiangjun; Qian, Chengduo; Fan, Weiyu; Liang, Zupei

    2018-03-01

    15 alkyl imidazoline surfactants with different structures were synthesized and their critical micelle concentration (CMC) and surface tension under the CMC (σcmc) in aqueous solution were measured at 298 K. 54 kinds of molecular structure descriptors were selected as independent variables and the quantitative structure-activity relationship (QSAR) between surface activities of alkyl imidazoline and molecular structure were built through the genetic function approximation (GFA) method. Experimental results showed that the maximum surface excess of alkyl imidazoline molecules at the gas-liquid interface increased and the area occupied by each surfactant molecule and the free energies of micellization ΔGm decreased with increasing carbon number (NC) of the hydrophobic chain or decreasing hydrophilicity of counterions, which resulted in a CMC and σcmc decrease, while the log CMC and NC had a linear relationship and a negative correlation. The GFA-QSAR model, which was generated by a training set composed of 13 kinds of alkyl imidazoline though GFA method regression analysis, was highly correlated with predicted values and experimental values of the CMC. The correlation coefficient R was 0.9991, which means high prediction accuracy. The prediction error of 2 kinds of alkyl imidazoline CMCs in the Validation Set that quantitatively analyzed the influence of the alkyl imidazoline molecular structure on the CMC was less than 4%.

  18. An in-situ FTIR study of the side-chain alkylation of toluene with methanol

    International Nuclear Information System (INIS)

    King, S.T.; Garces, J.

    1985-01-01

    The side-chain alkylation of toluene with methanol to styrene and ethylbenzene can be an economically attractive industrial process if it has high enough conversion and selectivity. This process has been investigated by many others using zeolites or metal oxides as the catalyst. It has been generally accepted that high basicity in certain size pores in the catalyst is required for such side-chain alkylation. However, the actual reaction mechanism is still not understood. In this paper the results of an in-situ FT-IR study of the side-chain alkylation in Li, Na, K, Rb and Cs exchanged X zeolites is discussed. It was found that the KX, RbX and CsX zeolites, which are capable of side-chain alkylation, also form surface formate and a surface precursor of formate from methanol decomposition. While the surface formate itself is not the alkylation agent, the observed formate precursor may be the intermediate for side-chain alkylation

  19. Hybrid ligand-alkylating agents targeting telomeric G-quadruplex structures.

    Science.gov (United States)

    Doria, Filippo; Nadai, Matteo; Folini, Marco; Di Antonio, Marco; Germani, Luca; Percivalle, Claudia; Sissi, Claudia; Zaffaroni, Nadia; Alcaro, Stefano; Artese, Anna; Richter, Sara N; Freccero, Mauro

    2012-04-14

    The synthesis, physico-chemical properties and biological effects of a new class of naphthalene diimides (NDIs) capable of reversibly binding telomeric DNA and alkylate it through an electrophilic quinone methide moiety (QM), are reported. FRET and circular dichroism assays showed a marked stabilization and selectivity towards telomeric G4 DNA folded in a hybrid topology. NDI-QMs' alkylating properties revealed a good reactivity on single nucleosides and selectivity towards telomeric G4. A selected NDI was able to significantly impair the growth of melanoma cells by causing telomere dysfunction and down-regulation of telomerase expression. These findings points to our hybrid ligand-alkylating NDIs as possible tools for the development of novel targeted anticancer therapies. This journal is © The Royal Society of Chemistry 2012

  20. N-Alkylation Using Sodium Triacetoxyborohydride with Carboxylic Acids as Alkyl Sources.

    Science.gov (United States)

    Tamura, Satoru; Sato, Keigo; Kawano, Tomikazu

    2018-01-01

    A versatile N-alkylation was performed using sodium triacetoxyborohydride and carboxylic acid as an alkyl source. The combination of these reagents furnished products different from those given previously by a similar reaction. Moreover, the mild conditions of our method allowed some functional groups to remain through the reaction, whereas they would react and be converted into other moieties in the similar reductive N-alkylation reported previously. Herein, we provide a new procedure for the preparation of various compounds containing nitrogen atoms.

  1. Synthesis of alkyl phenols by means of radiofrequency plasmas

    International Nuclear Information System (INIS)

    Ropero, M.; Armas, F.; Iacocca, D.; Patino, P.

    1992-01-01

    New and promising possibilities in chemical synthesis have been opened through the interactions of oxygen plasmas with liquid alkyl benzene compounds. The alkyl phenols are the main products of the reaction mixtures (> 80%) oxygen, excited by radio-frequency (R.F.) is allowed to reach the surface of the liquid organic compound. The R.F. power supply is a Branson/IPC-PM 118. The substrate we have chosen are: methyl, ethyl, propyl, n-butyl, t-butyl, dimethyl and trimethyl benzenes. Under the same O 2 pressure and a power of 60 W, m-xylene and mesethylene behaved similarly. For all these substrates, values for the temperature of the liquid surface seem to indicate that oxidation tends to an optimum when P O 2 /vapor pressure (substrate) is higher than 20. In our experiments oxygen pressure in the reactor was about 0.2 Torr. Oxidation is basically attributed to O 3 P and the addition to alkyl benzenes selectively takes place on the aromatic rings, at low reactor pressure. The oxygen atom impinges on the liquid surface and epoxy intermediates could be formed. These intermediates then progress to the corresponding phenols. (author)

  2. Morphological selection in an extreme flow environment: body shape and waterfall-climbing success in the Hawaiian stream fish Sicyopterus stimpsoni.

    Science.gov (United States)

    Blob, Richard W; Bridges, William C; Ptacek, Margaret B; Maie, Takashi; Cediel, Roberto A; Bertolas, Morgan M; Julius, Matthew L; Schoenfuss, Heiko L

    2008-12-01

    Flow characteristics are a prominent factor determining body shapes in aquatic organisms, and correlations between body shape and ambient flow regimes have been established for many fish species. In this study, we investigated the potential for a brief period of extreme flow to exert selection on the body shape of juvenile climbing Hawaiian gobiid fishes. Because of an amphidromous life history, juvenile gobies that complete an oceanic larval phase return to freshwater habitats, where they become adults. Returning juveniles often must scale waterfalls (typically with the use of a ventral sucker) in order to reach the habitats they will use as adults, thereby exposing these animals to brief periods of extreme velocities of flow. Hydrodynamic theory predicts that bodies with larger suckers and with lower heights that reduce drag would have improved climbing success and, thus, be well suited to meet the demands of the flows in waterfalls. To test the potential for the flow environment of waterfalls to impose selection that could contribute to differences in body shape between islands, we subjected juvenile Sicyopterus stimpsoni to climbing trials up artificial waterfalls (∼100 body lengths) and measured differences in body shape between successful and unsuccessful climbers. Waterfalls appear to represent a significant selective barrier to these fishes, as nearly 30% failed our climbing test. However, the effects of selection on morphology were not straightforward, as significant differences in shape between successful and unsuccessful climbers did not always match hydrodynamic predictions. In both selection experiments and in adult fish collected from habitats with different prevailing conditions of flow (the islands of Hawai'i versus Kaua'i), lower head heights were associated with exposure to high-flow regimes, as predicted by hydrodynamic theory. Thus, a premium appears to be placed on the reduction of drag via head morphology throughout the ontogeny of this

  3. Nickel-Catalyzed C–O Bond-Cleaving Alkylation of Esters: Direct Replacement of the Ester Moiety by Functionalized Alkyl Chains

    KAUST Repository

    Liu, Xiangqian; Jia, Jiaqi; Rueping, Magnus

    2017-01-01

    Two efficient protocols for the nickel-catalyzed aryl–alkyl cross-coupling reactions using esters as coupling components have been established. The methods enable the selective oxidative addition of nickel to acyl C–O and aryl C–O bonds and allow the aryl–alkyl cross-coupling via decarbonylative bond cleavage or through cleavage of a C–O bond with high efficiency and good functional group compatibility. The protocols allow the streamlined, unconventional utilization of widespread ester groups and their precursors, carboxylic acids and phenols, in synthetic organic chemistry.

  4. Nickel-Catalyzed C–O Bond-Cleaving Alkylation of Esters: Direct Replacement of the Ester Moiety by Functionalized Alkyl Chains

    KAUST Repository

    Liu, Xiangqian

    2017-06-07

    Two efficient protocols for the nickel-catalyzed aryl–alkyl cross-coupling reactions using esters as coupling components have been established. The methods enable the selective oxidative addition of nickel to acyl C–O and aryl C–O bonds and allow the aryl–alkyl cross-coupling via decarbonylative bond cleavage or through cleavage of a C–O bond with high efficiency and good functional group compatibility. The protocols allow the streamlined, unconventional utilization of widespread ester groups and their precursors, carboxylic acids and phenols, in synthetic organic chemistry.

  5. Alkylation of Zwitterionic Thiooxalic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Manfred Michalik

    2001-05-01

    Full Text Available The new S-alkyl thiooxal-1-hydrazono-2-amidrazonium halides 2-4 were synthesized by reaction of the corresponding zwitterionic thiooxalic acid derivatives 1 with alkyl halides in methanol. The structures of compounds 4b and 4d were proven by X-ray structural analysis. Both compounds form an interesting intermolecular network of hydrogen bonds in the solid state.

  6. Mechanochemical N-alkylation of imides

    Directory of Open Access Journals (Sweden)

    Anamarija Briš

    2017-08-01

    Full Text Available The mechanochemical N-alkylation of imide derivatives was studied. Reactions under solvent-free conditions in a ball mill gave good yields and could be put in place of the classical solution conditions. The method is general and can be applied to various imides and alkyl halides. Phthalimides prepared under ball milling conditions were used in a mechanochemical Gabriel synthesis of amines by their reaction with 1,2-diaminoethane.

  7. N-Alkylation by Hydrogen Autotransfer Reactions.

    Science.gov (United States)

    Ma, Xiantao; Su, Chenliang; Xu, Qing

    2016-06-01

    Owing to the importance of amine/amide derivatives in all fields of chemistry, and also the green and environmentally benign features of using alcohols as alkylating reagents, the relatively high atom economic dehydrative N-alkylation reactions of amines/amides with alcohols through hydrogen autotransfer processes have received much attention and have developed rapidly in recent decades. Various efficient homogeneous and heterogeneous transition metal catalysts, nano materials, electrochemical methods, biomimetic methods, asymmetric N-alkylation reactions, aerobic oxidative methods, and even certain transition metal-free, catalyst-free, or autocatalyzed methods, have also been developed in recent years. With a brief introduction to the background and developments in this area of research, this chapter focuses mainly on recent progress and technical and conceptual advances contributing to the development of this research in the last decade. In addition to mainstream research on homogeneous and heterogeneous transition metal-catalyzed reactions, possible mechanistic routes for hydrogen transfer and alcohol activation, which are key processes in N-alkylation reactions but seldom discussed in the past, the recent reports on computational mechanistic studies of the N-alkylation reactions, and the newly emerged N-alkylation methods based on novel alcohol activation protocols such as air-promoted reactions and transition metal-free methods, are also reviewed in this chapter. Problems and bottlenecks that remained to be solved in the field, and promising new research that deserves greater future attention and effort, are also reviewed and discussed.

  8. Alkylation of reticular polymers of ethynyl piperidol by alkyl halogen and investigation of the swelling of the products in water

    International Nuclear Information System (INIS)

    Khakimkhodjaev, S.N.; Khalikov, D.Kh.

    1999-01-01

    In the paper the results of investigation on alkylation of reticular polymer of ethyl piperidol by methyl Iodide and ethyl Iodide are adduced. It have been shown that in the first case the reaction of an alkylation proceeds up to 100% of a degree of completion. In the second case of an alkylation the highest degree of alkylation reaches only 60% which is connected with formation of secondary structures. In both cases the process of an alkylation results in deriving highly swelled system

  9. Shape-selective catalysts for Fischer-Tropsch chemistry. Final report: January 1, 2001 - December 31, 2008

    International Nuclear Information System (INIS)

    Cronauer, D.C.

    2011-01-01

    Argonne National Laboratory carried out a research program to create, prepare, and evaluate catalysts to promote Fischer-Tropsch (FT) chemistry-specifically, the reaction of hydrogen with carbon monoxide to form long-chain hydrocarbons. In addition to needing high activity, it was desirable that the catalysts have high selectivity and stability with respect to both mechanical strength and aging properties. It was desired that selectivity be directed toward producing diesel fraction components and avoiding excess yields of both light hydrocarbons and heavy waxes. The original goal was to produce shape-selective catalysts that had the potential to limit the formation of long-chain products and yet retain the active metal sites in a protected 'cage.' This cage would also restrict their loss by attrition during use in slurry-bed reactors. The first stage of this program was to prepare and evaluate iron-containing particulate catalysts. Such catalysts were prepared with silica-containing fractal cages. The activity and strength was essentially the same as that of catalysts without the cages. Since there was no improvement, the program plan was modified as discussed below. A second experimental stage was undertaken to prepare and evaluate active FT catalysts formed by atomic-layer deposition [ALD] of active components on supported membranes and particulate supports. The concept was that of depositing active metals (i.e. ruthenium, iron or cobalt) upon membranes with well defined flow channels of small diameter and length such that the catalytic activity and product molecular weight distribution could be controlled. In order to rapidly evaluate the catalytic membranes, the ALD coating processes were performed in an 'exploratory mode' in which ALD procedures from the literature appropriate for coating flat surfaces were applied to the high surface area membranes. Consequently, the Fe and Ru loadings in the membranes were likely to be smaller than those expected for

  10. Shape-selective catalysts for Fischer-Tropsch chemistry. Final report : January 1, 2001 - December 31, 2008.

    Energy Technology Data Exchange (ETDEWEB)

    Cronauer, D. C. (Chemical Sciences and Engineering Division)

    2011-04-11

    Argonne National Laboratory carried out a research program to create, prepare, and evaluate catalysts to promote Fischer-Tropsch (FT) chemistry-specifically, the reaction of hydrogen with carbon monoxide to form long-chain hydrocarbons. In addition to needing high activity, it was desirable that the catalysts have high selectivity and stability with respect to both mechanical strength and aging properties. It was desired that selectivity be directed toward producing diesel fraction components and avoiding excess yields of both light hydrocarbons and heavy waxes. The original goal was to produce shape-selective catalysts that had the potential to limit the formation of long-chain products and yet retain the active metal sites in a protected 'cage.' This cage would also restrict their loss by attrition during use in slurry-bed reactors. The first stage of this program was to prepare and evaluate iron-containing particulate catalysts. Such catalysts were prepared with silica-containing fractal cages. The activity and strength was essentially the same as that of catalysts without the cages. Since there was no improvement, the program plan was modified as discussed below. A second experimental stage was undertaken to prepare and evaluate active FT catalysts formed by atomic-layer deposition [ALD] of active components on supported membranes and particulate supports. The concept was that of depositing active metals (i.e. ruthenium, iron or cobalt) upon membranes with well defined flow channels of small diameter and length such that the catalytic activity and product molecular weight distribution could be controlled. In order to rapidly evaluate the catalytic membranes, the ALD coating processes were performed in an 'exploratory mode' in which ALD procedures from the literature appropriate for coating flat surfaces were applied to the high surface area membranes. Consequently, the Fe and Ru loadings in the membranes were likely to be smaller than those

  11. Sequence-specific DNA alkylation by tandem Py-Im polyamide conjugates.

    Science.gov (United States)

    Taylor, Rhys Dylan; Kawamoto, Yusuke; Hashiya, Kaori; Bando, Toshikazu; Sugiyama, Hiroshi

    2014-09-01

    Tandem N-methylpyrrole-N-methylimidazole (Py-Im) polyamides with good sequence-specific DNA-alkylating activities have been designed and synthesized. Three alkylating tandem Py-Im polyamides with different linkers, which each contained the same moiety for the recognition of a 10 bp DNA sequence, were evaluated for their reactivity and selectivity by DNA alkylation, using high-resolution denaturing gel electrophoresis. All three conjugates displayed high reactivities for the target sequence. In particular, polyamide 1, which contained a β-alanine linker, displayed the most-selective sequence-specific alkylation towards the target 10 bp DNA sequence. The tandem Py-Im polyamide conjugates displayed greater sequence-specific DNA alkylation than conventional hairpin Py-Im polyamide conjugates (4 and 5). For further research, the design of tandem Py-Im polyamide conjugates could play an important role in targeting specific gene sequences. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Molecular design of sequence specific DNA alkylating agents.

    Science.gov (United States)

    Minoshima, Masafumi; Bando, Toshikazu; Shinohara, Ken-ichi; Sugiyama, Hiroshi

    2009-01-01

    Sequence-specific DNA alkylating agents have great interest for novel approach to cancer chemotherapy. We designed the conjugates between pyrrole (Py)-imidazole (Im) polyamides and DNA alkylating chlorambucil moiety possessing at different positions. The sequence-specific DNA alkylation by conjugates was investigated by using high-resolution denaturing polyacrylamide gel electrophoresis (PAGE). The results showed that polyamide chlorambucil conjugates alkylate DNA at flanking adenines in recognition sequences of Py-Im polyamides, however, the reactivities and alkylation sites were influenced by the positions of conjugation. In addition, we synthesized conjugate between Py-Im polyamide and another alkylating agent, 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI). DNA alkylation reactivies by both alkylating polyamides were almost comparable. In contrast, cytotoxicities against cell lines differed greatly. These comparative studies would promote development of appropriate sequence-specific DNA alkylating polyamides against specific cancer cells.

  13. Alkylation of isobutane with light olefins: Yields of alkylates for different olefins

    Energy Technology Data Exchange (ETDEWEB)

    Albright, L.F. [Purdue Univ., West Lafayette, IN (United States); Kranz, K.E.; Masters, K.R. [STRATCO, Inc., Leawood, KS (United States)

    1993-12-01

    For alkylation of isobutane with C{sub 3}-C{sub 5} olefins using sulfuric acid as the catalyst, the yields of alkylates with different olefins are compared as the operating conditions are changed. The results of recent pilot plant experiments with propylene, C{sub 4} olefins, and C{sub 5} olefins permit such comparisons. The yields expressed as weight of alkylate produced per 100 wt of olefin consumed varied from about 201:100 to 220:100. Weight ratios of the isobutane consumed per olefin consumed vary from about 101:100 to 120:100. differences of yield values are explained by the changes in the overall chemistry. The procedure employed to calculate yields with good accuracy is based on the analysis of the alkylate and the amount of conjunct polymers produced. Based on literature data, yields are also reported for alkylations using HF as the catalyst.

  14. A detachable ester bond enables perfect Z-alkylations of olefins for the synthesis of tri- and tetrasubstituted alkenes.

    Science.gov (United States)

    Nishikata, Takashi; Nakamura, Kimiaki; Inoue, Yuki; Ishikawa, Shingo

    2015-06-25

    2-Vinyl-substituted phenol and an alpha-bromoester undergo a tandem esterification-alkylation reaction in the presence of a Cu-amine catalyst system to produce benzene-fused lactone. Z-Alkylated styrene is obtained after hydrolysis of the lactone with perfect selectivity. The simple protocol developed in this work opens a new avenue in the multi-substitution chemistry of alkenes.

  15. Effect of alkyl glycerophosphate on the activation of peroxisome proliferator-activated receptor gamma and glucose uptake in C2C12 cells

    Energy Technology Data Exchange (ETDEWEB)

    Tsukahara, Tamotsu, E-mail: ttamotsu@shinshu-u.ac.jp [Department of Integrative Physiology and Bio-System Control, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Haniu, Hisao [Department of Orthopedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Matsuda, Yoshikazu [Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, Ina-machi, Saitama 362-0806 (Japan)

    2013-04-12

    Highlights: •Alkyl-LPA specifically interacts with PPARγ. •Alkyl-LPA treatments induces lipid accumulation in C2C12 cells. •Alkyl-LPA enhanced glucose uptake in C2C12 cells. •Alkyl-LPA-treated C2C12 cells express increased amounts of GLUT4 mRNA. •Alkyl-LPA is a novel therapeutic agent that can be used for the treatment of obesity and diabetes. -- Abstract: Studies on the effects of lipids on skeletal muscle cells rarely examine the effects of lysophospholipids. Through our recent studies, we identified select forms of phospholipids, such as alkyl-LPA, as ligands for the intracellular receptor peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ is a nuclear hormone receptor implicated in many human diseases, including diabetes and obesity. We previously showed that alkyl-LPA is a specific agonist of PPARγ. However, the mechanism by which the alkyl-LPA–PPARγ axis affects skeletal muscle cells is poorly defined. Our objective in the present study was to determine whether alkyl-LPA and PPARγ activation promotes glucose uptake in skeletal muscle cells. Our findings indicate that PPARγ1 mRNA is more abundant than PPARγ2 mRNA in C2C12 cells. We showed that alkyl-LPA (3 μM) significantly activated PPARγ and increased intracellular glucose levels in skeletal muscle cells. We also showed that incubation of C2C12 cells with alkyl-LPA led to lipid accumulation in the cells. These findings suggest that alkyl-LPA activates PPARγ and stimulates glucose uptake in the absence of insulin in C2C12 cells. This may contribute to the plasma glucose-lowering effect in the treatment of insulin resistance.

  16. Effect of alkyl glycerophosphate on the activation of peroxisome proliferator-activated receptor gamma and glucose uptake in C2C12 cells

    International Nuclear Information System (INIS)

    Tsukahara, Tamotsu; Haniu, Hisao; Matsuda, Yoshikazu

    2013-01-01

    Highlights: •Alkyl-LPA specifically interacts with PPARγ. •Alkyl-LPA treatments induces lipid accumulation in C2C12 cells. •Alkyl-LPA enhanced glucose uptake in C2C12 cells. •Alkyl-LPA-treated C2C12 cells express increased amounts of GLUT4 mRNA. •Alkyl-LPA is a novel therapeutic agent that can be used for the treatment of obesity and diabetes. -- Abstract: Studies on the effects of lipids on skeletal muscle cells rarely examine the effects of lysophospholipids. Through our recent studies, we identified select forms of phospholipids, such as alkyl-LPA, as ligands for the intracellular receptor peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ is a nuclear hormone receptor implicated in many human diseases, including diabetes and obesity. We previously showed that alkyl-LPA is a specific agonist of PPARγ. However, the mechanism by which the alkyl-LPA–PPARγ axis affects skeletal muscle cells is poorly defined. Our objective in the present study was to determine whether alkyl-LPA and PPARγ activation promotes glucose uptake in skeletal muscle cells. Our findings indicate that PPARγ1 mRNA is more abundant than PPARγ2 mRNA in C2C12 cells. We showed that alkyl-LPA (3 μM) significantly activated PPARγ and increased intracellular glucose levels in skeletal muscle cells. We also showed that incubation of C2C12 cells with alkyl-LPA led to lipid accumulation in the cells. These findings suggest that alkyl-LPA activates PPARγ and stimulates glucose uptake in the absence of insulin in C2C12 cells. This may contribute to the plasma glucose-lowering effect in the treatment of insulin resistance

  17. Alkyl phosphonic acids and sulfonic acids in the Murchison meteorite

    Science.gov (United States)

    Cooper, George W.; Onwo, Wilfred M.; Cronin, John R.

    1992-01-01

    Homologous series of alkyl phosphonic acids and alkyl sulfonic acids, along with inorganic orthophosphate and sulfate, are identified in water extracts of the Murchison meteorite after conversion to their t-butyl dimethylsilyl derivatives. The methyl, ethyl, propyl, and butyl compounds are observed in both series. Five of the eight possible alkyl phosphonic acids and seven of the eight possible alkyl sulfonic acids through C4 are identified. Abundances decrease with increasing carbon number as observed of other homologous series indigenous to Murchison. Concentrations range downward from approximately 380 nmol/gram in the alkyl sulfonic acid series, and from 9 nmol/gram in the alkyl phosphonic acid series.

  18. The light activated alkylation of glycine

    International Nuclear Information System (INIS)

    Knowles, H.S.

    2001-04-01

    The work contained in this thesis focuses on the light-initiated alkylation of the α-centre of glycine compounds. The elaboration of the glycines in this manner represents a versatile, clean and cost effective alternative to ionic routes to higher α-amino acids. Preliminary investigations demonstrated that a range of nitrogen protecting groups were compatible with the radical alkylation. A variety of solvents could also be used although solvents with easily removable hydrogen atoms were found to interfere with the alkylation. Furthermore, a number of photo-initiators were investigated and the use of di-tert-butyl peroxide was found to afford the desired phenylalanine products in up to 27% yield (54% based on recovered starting material) when toluene was used as the alkylating agent. A range of different precursor concentrations was investigated and it was found that the optimum concentration of the glycine precursor was 0.13 mol dm -3 ; the phenylalanine yields were reduced when the concentration was less than this value. Owing to the poor UV absorption by di-tert-butyl peroxide, benzophenone (an effective photosensitiser) was added to the reaction mixture and this was shown to increase the alkylation yields. The ratio of reagents which produced the highest yield of phenylalanine products was found to be 1 : 5 : 5 : 10 for glycine : di-tert-butyl peroxide : benzophenone : toluene. This produced the phenylalanine product in up to 37% yield (57% based on recovered starting material). A number of substituents. (e.g. F, Cl etc.) could be attached to the aromatic ring of the toluene alkylating agent, affording substituted phenylalanines in 5 - 36% under these conditions. The formation of chiral phenylalanine products was probed by reacting glycine precursors bearing chiral auxiliaries. However, low diastereoselectivities were observed; the d.r. ranged from 1 : 1.1 to 1 : 1.5 only when chiral ester and amide protecting groups were used. In the final chapter, the α-alkylation

  19. hf alkylation in the 1980's: the role of isobutane/olefin ratio

    Energy Technology Data Exchange (ETDEWEB)

    Hutson, T. Jr.

    1978-08-01

    Research devoted to maximizing no-lead octane numbers in motor fuel is reported. Results of the studies are the basis for the following conclusions: 1. Isobutane alkylate made from either propylene, butene-2, or C/sub 3/--C/sub 4/ mixed olefins is a low sensitivity, high motor octane product. Typically, C/sub 3/--C/sub 4/ mixed olefin alkylate has a clear motor octane number of about 92.2 and a clear Research octane number of about 93.5. 2. In separate studies with propylene, butene-2 and C/sub 3/--C/sub 4/ mixed olefins, increasing the isobutane-to-olefin ratio suppressed the formation of high molecular weight residue, indicating a substantial reduction in the role of olefin polymerization to large ions. The overall result of increasing ratio was an improvement in selectivity to high-octane components in the alkylate. 3. When alkylating isobutane with propylene, increasing the ratio resulted in a decrease in the concentration of C/sub 7/-fraction (primary product) and an increase in the C/sub 8/-fraction (from chain initiation and subsequent hydrogen transfer). At the same time, the production of chain-termination-product propane also increased. 4. When alkylating isobutane with C/sub 3/--C/sub 4/ mixed olefins, increasing the ratio showed the same trend obtained in separate alkylation tests with propylene and butene-2. As the ratio increased, the concentration of C/sub 7/-fraction (primary propylene--isobutane product) decreased and the concentration of C/sub 8/-fraction increased markedly. Thus, increasing isobutane-to-olefin ratio exerted a strong effect on alkylate quality in the area of about 5 to 1 to 20 to 1; this effect diminished at ratios 20:1.

  20. A pulse shape discriminator with high precision of neutron and gamma ray selection at high counting rate

    International Nuclear Information System (INIS)

    Bialkowski, J.; Moszynski, M.; Wolski, D.

    1989-01-01

    A pulse shape discriminator based on the zero-crossing principle is described. Due to dc negative feedback loops stabilizing the shaping amplifier and the zero-crossing discriminator, the working of the circuit is not affected by the high counting rate and the temperature variations. The pileup rejection circuit built into the discriminator improves the quality of the n-γ separation at high counting rates. A full γ-ray rejection is obtained for a recoil energy of electrons down to 25 keV. At high counting rates the remaining γ-ray contribution is evidently due to the pileup effect which is equal to about 2% at 4x10 5 counts/s. (orig.)

  1. Aryl sulfonate based anticancer alkylating agents.

    Science.gov (United States)

    Sheikh, Hamdullah Khadim; Arshad, Tanzila; Kanwal, Ghazala

    2018-05-01

    This research work revolves around synthesis of antineoplastic alkylating sulfonate esters with dual alkylating sites for crosslinking of the DNA strands. These molecules were evaluated as potential antineoplastic cross linking alkylating agents by reaction with the nucleoside of Guanine DNA nucleobase at both ends of the synthesized molecule. Synthesis of the alkylating molecules and the crosslinking with the guanosine nucleoside was monitored by MALDITOF mass spectroscopy. The synthesized molecule's crosslinking or adduct forming rate with the nucleoside was compared with that of 1,4 butane disulfonate (busulfan), in form of time taken for the appearance of [M+H] + . It was found that aryl sulfonate leaving group was causing higher rate of nucleophilic attack by the Lewis basic site of the nucleobase. Furthermore, the rate was also found to be a function of electron withdrawing or donating nature of the substituent on the aryl ring. Compound with strong electron withdrawing substituent on the para position of the ring reacted fastest. Hence, new alkylating agents were synthesized with optimized or desired reactivity.

  2. Tripodal (N-alkylated) CMP(O) and malonamide ligands: synthesis, extraction of metal ions, and potentiometric studies

    Energy Technology Data Exchange (ETDEWEB)

    Janczewski, D.; Reinhoudt, D.N.; Verboom, W. [Twente Univ., Lab. of Supramolecular Chemistry and Technology, Mesa Research Institute for Nanotechnology, Enschede (Netherlands); Malinowska, E.; Pietrzak, M. [Warsaw Univ. of Technology, Dept. of Analytical Chemistry, Faculty of Chemistry (Poland); Hill, C.; Allignol, C. [CEA Valrho, 30 - Marcoule (France)

    2007-01-15

    Tripodal ligands build on the C-pivot (9b-e, 13b-d, and 17a-d) and tri-alkyl-benzene platforms (10a,b, 11, 12, 14a,b, and 18a,b) bearing (N-alkylated) carbamoyl-methyl-phosphine oxide (CMPO), carbamoyl-methyl-phosphonate (CMP), and malonamide moieties were synthesized. Extraction studies with Am{sup 3+} and Eu{sup 3+} show that in general there is a positive influence of the N-alkyl substituents in C-pivot CMP(O) ligands on the D(distribution) coefficients. The tri-alkyl-benzene CMPO ligands 10a,b, 11, and 12 have considerably larger D coefficients than the corresponding C-pivot analogues 9a-e, although hardly having any selectivity, while N-alkylation gives rise to smaller D coefficients. Although less effective the extraction behavior of the C-pivot CMP analogues 13b-d shows more or less the same trend as the corresponding CMPO ligands 9b-e upon substitution of the carboxamide N-atom with different alkyl chains. The different malonamide ligands 17a-d and 18a,b are bad extractants, while N-alkylation makes them even worse. Potentiometric studies of CMP(O) and malonamide ligands in polymeric membranes on Pb{sup 2+}, Cu{sup 2+}, Ca{sup 2+}, Mg{sup 2+}, Na{sup +}, and K{sup +} salts revealed that N-alkyl substituents increase the stability constants of ion-ionophore complexes compared to unsubstituted ligands. In polymeric membrane electrodes the ligands induce a selectivity pattern that differs significantly from the so-called Hofmeister series, giving the highest selectivity coefficients for UO{sub 2}{sup 2+} among all examined cations (Pb{sup 2+}, Cu{sup 2+}, Ca{sup 2+}, Mg{sup 2+}, Na{sup +}, K{sup +}). (authors)

  3. Tripodal (N-alkylated) CMP(O) and malonamide ligands: synthesis, extraction of metal ions, and potentiometric studies

    International Nuclear Information System (INIS)

    Janczewski, D.; Reinhoudt, D.N.; Verboom, W.; Malinowska, E.; Pietrzak, M.; Hill, C.; Allignol, C.

    2007-01-01

    Tripodal ligands build on the C-pivot (9b-e, 13b-d, and 17a-d) and tri-alkyl-benzene platforms (10a,b, 11, 12, 14a,b, and 18a,b) bearing (N-alkylated) carbamoyl-methyl-phosphine oxide (CMPO), carbamoyl-methyl-phosphonate (CMP), and malonamide moieties were synthesized. Extraction studies with Am 3+ and Eu 3+ show that in general there is a positive influence of the N-alkyl substituents in C-pivot CMP(O) ligands on the D(distribution) coefficients. The tri-alkyl-benzene CMPO ligands 10a,b, 11, and 12 have considerably larger D coefficients than the corresponding C-pivot analogues 9a-e, although hardly having any selectivity, while N-alkylation gives rise to smaller D coefficients. Although less effective the extraction behavior of the C-pivot CMP analogues 13b-d shows more or less the same trend as the corresponding CMPO ligands 9b-e upon substitution of the carboxamide N-atom with different alkyl chains. The different malonamide ligands 17a-d and 18a,b are bad extractants, while N-alkylation makes them even worse. Potentiometric studies of CMP(O) and malonamide ligands in polymeric membranes on Pb 2+ , Cu 2+ , Ca 2+ , Mg 2+ , Na + , and K + salts revealed that N-alkyl substituents increase the stability constants of ion-ionophore complexes compared to unsubstituted ligands. In polymeric membrane electrodes the ligands induce a selectivity pattern that differs significantly from the so-called Hofmeister series, giving the highest selectivity coefficients for UO 2 2+ among all examined cations (Pb 2+ , Cu 2+ , Ca 2+ , Mg 2+ , Na + , K + ). (authors)

  4. Selection shaped the evolution of mouse androgen-binding protein (ABP) function and promoted the duplication of Abp genes.

    Science.gov (United States)

    Karn, Robert C; Laukaitis, Christina M

    2014-08-01

    In the present article, we summarize two aspects of our work on mouse ABP (androgen-binding protein): (i) the sexual selection function producing incipient reinforcement on the European house mouse hybrid zone, and (ii) the mechanism behind the dramatic expansion of the Abp gene region in the mouse genome. Selection unifies these two components, although the ways in which selection has acted differ. At the functional level, strong positive selection has acted on key sites on the surface of one face of the ABP dimer, possibly to influence binding to a receptor. A different kind of selection has apparently driven the recent and rapid expansion of the gene region, probably by increasing the amount of Abp transcript, in one or both of two ways. We have shown previously that groups of Abp genes behave as LCRs (low-copy repeats), duplicating as relatively large blocks of genes by NAHR (non-allelic homologous recombination). The second type of selection involves the close link between the accumulation of L1 elements and the expansion of the Abp gene family by NAHR. It is probably predicated on an initial selection for increased transcription of existing Abp genes and/or an increase in Abp gene number providing more transcriptional sites. Either or both could increase initial transcript production, a quantitative change similar to increasing the volume of a radio transmission. In closing, we also provide a note on Abp gene nomenclature.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-07-07

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

  6. Organic and inorganic ion exchangers as catalysts for the heterogeneous alkylation of aromatics

    Energy Technology Data Exchange (ETDEWEB)

    Klein, J; Widdecke, H [Technische Univ. Braunschweig (Germany, F.R.). Inst. fuer Chemische Technologie

    1979-06-01

    Ion exchangers have advantages over low molecular for use in industrial alkylation reactions. The reactivity and selectivity behaviour of the polymeric catalysts was found to be markedly influenced by the structure of the polymeric matrix as well as the type and number of the functional groups. In this connection many similarities between inorganic ion exchangers (zeolites) and organic ion exchange resins were detected.

  7. Influence of diluent alkyl substitution on the extraction of Am(III) and Eu(III) by a 6,6'-bis(1,2,4-triazin-3-yl)-2,2'-bipyridine ligand dissolved in alkylated cyclohexanone diluents

    International Nuclear Information System (INIS)

    Distler, P.; Spendlikova, I.; John, J.; Czech Technical Univ., Prague; Harwood, L.M.; Hudson, M.J.; Lewis, F.W.

    2012-01-01

    Several alkylated cyclohexanones were investigated as potential diluents for the selective extraction of Am(III) from Eu(III) from nitric acid solutions by the CyMe 4 -BTBP ligand. No significant extraction of either of the metal ions was observed for these diluents themselves. In the extractions from 1 M HNO 3 , 3-methylcyclohexanone and 4-methylcyclohexanone gave comparable results to cyclohexanone whereas in the extractions from 4 M HNO 3 , 2-methylcyclohexanone, 3-methylcyclohexanone and 4-methylcyclohexanone all gave superior results. For the monomethylated diluents, D Am and SF Am/Eu decreased in the order of alkyl substitution 2 > 4 ∝ 3. However, alkyl substitution of cyclohexanone significantly slows down the extraction kinetics compared to cyclohexanone, and the position of alkyl substitution was found to play an important role in the solvents properties. 3-Methylcyclohexanone was identified as the most promising of the diluents. (orig.)

  8. Outlook for the U.S. alkylation industry

    International Nuclear Information System (INIS)

    Felten, J.R.; Bradshaw, T.; McCarthy, K.

    1994-01-01

    Alkylation has long been recognized in the refining industry as one of the best options to convert refinery olefins into valuable, clean, high octane blending components. In fact, refinery alkylation is a preferred source of blending stocks for reformulated gasoline. However, the hydrofluoric acid (HF) alkylation process and, to a lesser extent, the sulfuric acid (SA) process have come under increasing pressure in the US due to safety and environmental concerns. This paper examines the current outlook for the US alkylation industry including: key trends and driving forces in the industry, the impact of environmental issues on both HF and SA alkylation, US alkylation supply/demand forecast including the outlook for oxygenates, how US refines will respond to the increased demand and restricted supply for alkylates, and the outlook for new solid acid alkylation (SAC) technology

  9. Rhodium(III)- and iridium(III)-catalyzed C7 alkylation of indolines with diazo compounds.

    Science.gov (United States)

    Ai, Wen; Yang, Xueyan; Wu, Yunxiang; Wang, Xuan; Li, Yuanchao; Yang, Yaxi; Zhou, Bing

    2014-12-22

    A Rh(III)-catalyzed procedure for the C7-selective C-H alkylation of various indolines with α-diazo compounds at room temperature is reported. The advantages of this process are: 1) simple, mild, and pH-neutral reaction conditions, 2) broad substrate scope, 3) complete regioselectivity, 4) no need for an external oxidant, and 5) N2 as the sole byproduct. Furthermore, alkylation and bis-alkylation of carbazoles at the C1 and C8 positions have also been developed. More significantly, for the first time, a successful Ir(III)-catalyzed intermolecular insertion of arene C-H bonds into α-diazo compounds is reported. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Bifunctional rhodium intercalator conjugates as mismatch-directing DNA alkylating agents.

    Science.gov (United States)

    Schatzschneider, Ulrich; Barton, Jacqueline K

    2004-07-21

    A conjugate of a DNA mismatch-specific rhodium intercalator, containing the bulky chrysenediimine ligand, and an aniline mustard has been prepared, and targeting of mismatches in DNA by this conjugate has been examined. The preferential alkylation of mismatched over fully matched DNA is found by a mobility shift assay at concentrations where untethered organic mustards show little reaction. The binding site of the Rh intercalator was determined by DNA photocleavage, and the position of covalent modification was established on the basis of the enhanced depurination associated with N-alkylation. The site-selective alkylation at mismatched DNA renders these conjugates useful tools for the covalent tagging of DNA base pair mismatches and new chemotherapeutic design.

  11. Isobutane/butene alkylation on solid catalysts. Where do we stand?

    Energy Technology Data Exchange (ETDEWEB)

    Weitkamp, J.; Traa, Y. [Institute of Chemical Technology I, University of Stuttgart, D-70550 Stuttgart (Germany)

    1999-02-24

    Liquid-phase processes with concentrated sulfuric acid or hydrogen fluoride as catalysts are currently being used in petroleum refining for the manufacture of alkylation gasoline from isobutane and butenes. While the product, i.e., alkylate, is a most valuable gasoline component, the existing processes for its manufacture are less satisfactory. Replacement of the liquid catalysts by a solid acid is an important target of modern research. In the past two decades, a large number of solid acids have been scrutinized, and at least four developments were driven till the pilot plant stage. In this paper, an attempt is made to rationalize, on a mechanistic basis, the selectivity loss almost always encountered with solid acids after relatively short times-on-stream. Suggestions are made concerning a more target-oriented research on isobutane/alkene alkylation in the future

  12. Orientational diffusion of n-alkyl cyanides

    International Nuclear Information System (INIS)

    Zhu Xiang; Farrer, Richard A; Zhong Qin; Fourkas, John T

    2005-01-01

    Ultrafast optical Kerr effect spectroscopy has been used to study the temperature-dependent orientational dynamics of a series of nitriles with n-alkyl chains ranging from one to 11 carbons in length. In all cases the orientational diffusion is found to be described by a single-exponential decay. Analysis of the orientational correlation times using the Debye-Stokes-Einstein equation suggests that the molecules adopt extended configurations and reorient as rigid rods. The liquids with shorter alkyl chains undergo an apparent ordering transition as they are cooled

  13. Mechanisms of resistance to alkylating agents

    OpenAIRE

    Damia, G.; D‘Incalci, M.

    1998-01-01

    Alkylating agents are the most widely used anticancer drugs whose main target is the DNA, although how exactly the DNA lesions cause cell death is still not clear. The emergence of resistance to this class of drugs as well as to other antitumor agents is one of the major causes of failure of cancer treatment. This paper reviews some of the best characterized mechanisms of resistance to alkylating agents. Pre- and post-target mechanisms are recognized, the former able to limit the formation of...

  14. Graft copolymerization of a series of alkyl acrylates and alkyl methacrylates onto polyethylene

    International Nuclear Information System (INIS)

    Zurakowska-Orszagh, J.; Soerjosoeharto, K.; Busz, W.; Oldziejewski, J.

    1977-01-01

    Graft copolymerization of a series of alkyl acrylates and alkyl methacrylates into polyethylene of Polish production was investigated, using benzoyl peroxide as the initiator as well as preirradiation technique, namely ionizing radiation from a 60 Co γ-source. The effect of α-carbon methyl substituent of methacrylates as well as the influence of the length of alkyl chains in the ester groups of both series of monomers into the grafting process was observed. The ungrafted and some of the grafted polyethylene film obtained was studied by infrared spectrophotometry. (author)

  15. Can you hear me now? Musical training shapes functional brain networks for selective auditory attention and hearing speech in noise

    Directory of Open Access Journals (Sweden)

    Dana L Strait

    2011-06-01

    Full Text Available Even in the quietest of rooms, our senses are perpetually inundated by a barrage of sounds, requiring the auditory system to adapt to a variety of listening conditions in order to extract signals of interest (e.g., one speaker’s voice amidst others. Brain networks that promote selective attention are thought to sharpen the neural encoding of a target signal, suppressing competing sounds and enhancing perceptual performance. Here, we ask: does musical training benefit cortical mechanisms that underlie selective attention to speech? To answer this question, we assessed the impact of selective auditory attention on cortical auditory-evoked response variability in musicians and nonmusicians. Outcomes indicate strengthened brain networks for selective auditory attention in musicians in that musicians but not nonmusicians demonstrate decreased prefrontal response variability with auditory attention. Results are interpreted in the context of previous work from our laboratory documenting perceptual and subcortical advantages in musicians for the hearing and neural encoding of speech in background noise. Musicians’ neural proficiency for selectively engaging and sustaining auditory attention to language indicates a potential benefit of music for auditory training. Given the importance of auditory attention for the development of language-related skills, musical training may aid in the prevention, habilitation and remediation of children with a wide range of attention-based language and learning impairments.

  16. IONIC LIQUID-CATALYZED ALKYLATION OF ISOBUTANE WITH 2-BUTENE

    Science.gov (United States)

    A detailed study of the alkylation of isobutane with 2-butene in ionic liquid media has been conducted using 1-alkyl-3-methylimidazolium halides?aluminum chloride encompassing various alkyl groups (butyl-, hexyl-, and octyl-) and halides (Cl, Br, and I) on its cations and anions,...

  17. 40 CFR 721.555 - Alkyl amino nitriles (generic).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl amino nitriles (generic). 721... Substances § 721.555 Alkyl amino nitriles (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl amino nitriles (PMNs P-96...

  18. 40 CFR 721.1878 - Alkali metal alkyl borohydride (generic).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkali metal alkyl borohydride... Specific Chemical Substances § 721.1878 Alkali metal alkyl borohydride (generic). (a) Chemical substance... alkali metal alkyl borohydride (PMN P-00-1089) is subject to reporting under this section for the...

  19. CC-1065 and the duocarmycins: unraveling the keys to a new class of naturally derived DNA alkylating agents.

    Science.gov (United States)

    Boger, D L; Johnson, D S

    1995-01-01

    Key studies defining the DNA alkylation properties and selectivity of a new class of exceptionally potent, naturally occurring antitumor antibiotics including CC-1065, duocarmycin A, and duocarmycin SA are reviewed. Recent studies conducted with synthetic agents containing deep-seated structural changes and the unnatural enantiomers of the natural products and related analogs have defined the structural basis for the sequence-selective alkylation of duplex DNA and fundamental relationships between chemical structure, functional reactivity, and biological properties. The agents undergo a reversible, stereoelectronically controlled adenine-N3 addition to the least substituted carbon of the activated cyclopropane within selected AT-rich sites. The preferential AT-rich non-covalent binding selectivity of the agents within the narrower, deeper AT-rich minor groove and the steric accessibility to the alkylation site that accompanies deep AT-rich minor groove penetration control the sequence-selective DNA alkylation reaction and stabilize the resulting adduct. For the agents that possess sufficient reactivity to alkylate DNA, a direct relationship between chemical or functional stability and biological potency has been defined. Images Fig. 1 Fig. 2 PMID:7731958

  20. Experimental evidence of stress-field-induced selection of variants in Ni-Mn-Ga ferromagnetic shape-memory alloys

    International Nuclear Information System (INIS)

    Wang, Y. D.; Brown, D. W.; Choo, H.; Liaw, P. K.; Benson, M. L.; Cong, D. Y.; Zuo, L.

    2007-01-01

    The in situ time-of-flight neutron-diffraction measurements captured well the martensitic transformation behavior of the Ni-Mn-Ga ferromagnetic shape-memory alloys under uniaxial stress fields. We found that a small uniaxial stress applied during phase transformation dramatically disturbed the distribution of variants in the product phase. The observed changes in the distributions of variants may be explained by considering the role of the minimum distortion energy of the Bain transformation in the effective partition among the variants belonging to the same orientation of parent phase. It was also found that transformation kinetics under various stress fields follows the scale law. The present investigations provide the fundamental approach for scaling the evolution of microstructures in martensitic transitions, which is of general interest to the condensed matter community

  1. The use of polynuclear aromatic hydrocarbon (PAH) alkyl homologues in determining petroleum source identification and weathering

    International Nuclear Information System (INIS)

    Brown, J.S.; Boehm, P.D.; Sauer, T.C.; Wong, W.M.C.

    1993-01-01

    Techniques utilizing double ratio plots of selected polynuclear aromatic hydrocarbon (PAH) alkyl homologues were used to identify and distinguish crude oils and refined petroleum products from each other and to distinguish petroleum sources in complex pollutant regimes. Petroleum samples were fractionated by high performance liquid chromatography (HPLC) into saturated and aromatic (PAH) hydrocarbon fractions. The saturated hydrocarbon fractions were then analyzed by gas chromatography/flame ionization detection (GC/FID) to obtain a resolved/unresolved alkane fingerprint of each oil. The aromatic fractions of the oils were analyzed by gas chromatography/mass spectrometry (GC/MS) for PAH and selected alkyl homologues. Comparisons of the saturated hydrocarbon fingerprints indicated that some oils were indistinguishable based on the alkane fingerprint alone. Another double ratio plot of the alkyl chrysenes and alkyl dibenzothiophenes was effective in establishing the weathering of oil in environmental samples which were processed using the same analytical techniques, since the dibenzothiophenes are degraded more rapidly than the chrysenes. The application of selected ratios in oil spill source identification in complex environmental samples from Suisin Bay California and Boston Harbor are discussed. The use of ratios to measure the extent of weathering in oil spill samples from Prince William Sound and the Gulf of Alaska is examined

  2. Quantitative estimation of the extent of alkylation of DNA following treatment of mammalian cells with non-radioactive alkylating agents

    Energy Technology Data Exchange (ETDEWEB)

    Snyder, R.D. (Univ. of Tennessee, Oak Ridge); Regan, J.D.

    1981-01-01

    Alkaline sucrose sedimentation has been used to quantitate phosphotriester formation following treatment of human cells with the monofunctional alkylating agents methyl and ethyl methanesulfonate. These persistent alkaline-labile lesions are not repaired during short-term culture conditions and thus serve as a useful and precise index of the total alkylation of the DNA.Estimates of alkylation by this procedure compare favorably with direct estimates by use of labeled alkylating agents.

  3. Williamson alkylation approach to the synthesis of poly(alkyl vinyl ether) copolymers

    International Nuclear Information System (INIS)

    Markova, D.; Christova, D.; Velichkova, R.

    2008-01-01

    A method for synthesis of poly(alkyl vinyl ether-co-vinyl alcohol) copolymers was developed based on the Williamson's alkylation of poly(vinyl acetate) (PVAc) with alkyl iodides. The influence of the alkylating agent and the reaction conditions on the efficiency of the modification reaction was investigated. The copolymers obtained were characterized by means of 1 H NMR and GPC. It was proved that by applying the proposed method copolymers of different composition and properties containing methyl vinyl ether, ethyl vinyl ether as well as n-butyl vinyl ether units could be prepared. Poly(methyl vinyl ether-co-vinyl alcohol)s of high degree of methylation exhibit sharp temperature response at 38-39 deg C in aqueous solution typical of the so-called smart polymers. (authors)

  4. Stereoselective Alkylation of Thiacalix[4]arenes

    Czech Academy of Sciences Publication Activity Database

    Himl, M.; Pojarová, M.; Stibor, I.; Sýkora, Jan; Lhoták, P.

    2005-01-01

    Roč. 46, č. 3 (2005), s. 461-464 ISSN 0040-4039 R&D Projects: GA ČR(CZ) GA104/00/1722 Institutional research plan: CEZ:AV0Z40720504 Keywords : calixarene * alkylation * conformations Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.477, year: 2005

  5. Polypyrrole Doped with Alkyl Benzene Sulphonates

    DEFF Research Database (Denmark)

    Bay, Lasse; Mogensen, Naja; Skaarup, Steen

    2002-01-01

    The properties of polypyrrole (PPy) are to a large extent determined by the condition of synthesis and especially by the counterion incorporated as dopant during synthesis. In this work, PPy doped with different alkyl benzenesulfonates are compared. The polymer films are prepared by constant curr...

  6. Biodesulfurization of dibenzothiophene and its alkylated derivatives ...

    African Journals Online (AJOL)

    RIPI-S81 is a new dibenzothiophene (DBT)-desulfurizing bacterium, which was isolated by Research Institute of Petroleum Industry in Iran. Resting cells and growing cells of RIPI-S81 was able to convert alkylated dibenzothiophenes (Cx DBTs) to hydroxybiphenyls such that they were almost stoichiometrically accumulated ...

  7. Poly(ethyleneoxide) functionalization through alkylation

    Science.gov (United States)

    Sivanandan, Kulandaivelu; Eitouni, Hany Basam; Li, Yan; Pratt, Russell Clayton

    2015-04-21

    A new and efficient method of functionalizing high molecular weight polymers through alkylation using a metal amide base is described. This novel procedure can also be used to synthesize polymer-based macro-initiators containing radical initiating groups at the chain-ends for synthesis of block copolymers.

  8. Spurious cooperativity in alkylated succinic acids

    Science.gov (United States)

    Ben-Naim, A.

    1998-03-01

    The proton-proton correlation, as measured by the ratio between the second and the first dissociation constants of dibasic acid, is sometimes very large and far beyond what could be explained by electrostatic theories. We propose a novel interpretation of this phenomenon based on the idea of spurious cooperativity. The general theoretical framework underlying the onset of spurious cooperativity is developed first. The basic result is that whenever a binding (or dissociating) two-site (or more) system splits into a mixture of noninterconverting isomers the binding isotherm (or the titration curve) behaves as if it is more negatively cooperative compared with the genuine cooperativities of the individual isomer. The theory is applied to a specific system of α-α' dialkyl succinic acid. It is known that the Meso form of these alkylated derivatives show a normal correlation of the same order of magnitude as in succinic acid. On the other hand, the Racemic form of these alkylated derivatives shows anomalous strong negative correlations when the alkyl groups become large (e.g., isopropyl and tert butyl). It is shown that the theory of spurious cooperativity can explain the different behavior of the Racemic and the Meso forms, as well as the onset of anomalous strong negative correlations when the alkyl groups become large.

  9. Recent developments in isobutane/olefin alkylation

    Energy Technology Data Exchange (ETDEWEB)

    Lercher, J.A.; Feller, A. [Inst. fuer Technische Chemie, Technische Univ. Muenchen (Germany)

    2002-07-01

    The isobutane/alkene alkylation is reviewed with respect to recent process developments based on liquid and solid acid catalysts. A brief overview about the established processes is given followed by the description of new processes based on solid acids under development. (orig.)

  10. Catalytic Asymmetric Alkylation of Aryl Heteroaryl Ketones

    NARCIS (Netherlands)

    Ortiz, Pablo; Harutyunyan, Syuzanna; del Hoyo, Ana

    Tertiary diarylmethanols are highly bioactive structural motifs. A new strategy to access chiral tertiary diarylmethanols through copper-catalyzed direct alkylation of (di)(hetero)aryl ketones by using Grignard reagents was developed. The low reactivity and the similarity of the enantiotopic faces

  11. Iridium-catalyzed direct synthesis of tryptamine derivatives from indoles: exploiting n-protected β-amino alcohols as alkylating agents.

    Science.gov (United States)

    Bartolucci, Silvia; Mari, Michele; Bedini, Annalida; Piersanti, Giovanni; Spadoni, Gilberto

    2015-03-20

    The selective C3-alkylation of indoles with N-protected ethanolamines involving the "borrowing hydrogen" strategy is described. This method provides convenient and sustainable access to several tryptamine derivatives.

  12. Mechanisms of action of quinone-containing alkylating agents: DNA alkylation by aziridinylquinones.

    Science.gov (United States)

    Hargreaves, R H; Hartley, J A; Butler, J

    2000-11-01

    Aziridinyl quinones can be activated by cellular reductases eg. DT-diaphorase and cytochrome P450 reductase to form highly reactive DNA alkylating agents. The mechanisms by which this activation and alkylation take place are many and varied. Using clinically relevant and experimental agents this review will describe many of these mechanisms. The agents discussed are Mitomycin C, EO9 and analogues, diaziridinylbenzoquinones and the pyrrolo[1, 2-alpha]benzimidazolequinones.

  13. Sulfonium Salts as Alkylating Agents for Palladium-Catalyzed Direct Ortho Alkylation of Anilides and Aromatic Ureas.

    Science.gov (United States)

    Simkó, Dániel Cs; Elekes, Péter; Pázmándi, Vivien; Novák, Zoltán

    2018-02-02

    A novel method for the ortho alkylation of acetanilide and aromatic urea derivatives via C-H activation was developed. Alkyl dibenzothiophenium salts are considered to be new reagents for the palladium-catalyzed C-H activation reaction, which enables the transfer of methyl and other alkyl groups from the sulfonium salt to the aniline derivatives under mild catalytic conditions.

  14. Assessing the morphology of selective laser melted NiTi-scaffolds for a three-dimensional quantification of the one-way shape memory effect

    Science.gov (United States)

    Bormann, Therese; de Wild, Michael; Beckmann, Felix; Müller, Bert

    2013-04-01

    NiTi is promising for the use as bone scaffold, because the pseudoelasticity or the one- and two-way shape memory effect in the physiological window can mechanically stimulate the adherent cells. Such stimuli can enhance osseointegration and might reduce stress shielding associated with load bearing implants. The present study is based on the additive manufacturing technique of selective laser melting (SLM) to fabricate three-dimensional NiTi scaffolds. We demonstrate that the morphology of the scaffolds can be quantified using synchrotron radiation-based micro computed tomography (SRμCT) and sophisticated registration software. Comparing the CAD file with the SLM scaffolds, quality factors are derived. With respect to the CAD file, the overlap corresponds to (92.5 +/- 0.6) %. (7.4 +/- 0.42) % of material was missing and (48.9 +/- 2.3) % of excess material found. This means that the actual scaffold is less porous than expected, a fact that has to be considered for the scaffold design. In order to quantify the shape memory effect during the shape recovery process, we acquired radiographs rotating an initially deformed scaffold in angular steps of 0.2 degree during controlled heating. The continuously acquired radiographs were combined to tomography data, showing that the quality factors evolved with temperature as the scaffold height, measured by conventional thermo-mechanical analysis. Furthermore, the data comprise the presence of compressive and tensile local strains in the three-dimensional scaffolds to be compared with the physiological situation.

  15. Facile alkylation of 4-nitrobenzotriazole and its platelet aggregation inhibitory activity.

    Science.gov (United States)

    Singh, Dhandeep; Silakari, Om

    2017-10-15

    We explored the facile alkylation of 4-nitrobenzotriazole under basic conditions and the synthesized derivatives were tested for their potential ADP induced platelet aggregation inhibition activity in comparison with standard drug ticagrelor (selective P2Y12 inhibitor). The nitro group at 4-position is highly activating toward alkylation reactions (under strong basic conditions) and resulted in formation of degradation product like 3-nitrobenzene-1,2-diamine which make isolation of alkyl products very difficult. We optimized the reaction under mild basic condition (potassium carbonate and DMF) which is devoid of any degradation product. This is perhaps the first report of 4-nitrobenzotriazole derivatives possessing platelet aggregation inhibitory activity. Generally activity increases with increase in length of alkyl chain and 1-alkyl positional isomers were found to be more potent than 2-alkyl isomers. The benzoyl derivative was found to be the most potent [compound 22; (4-Nitro-1H-benzotriazol-1-yl)(phenyl)methanone; IC 50 =0.65±0.10mM] which may be attributed to electronegative oxygen atom and aromatic ring. Benzyl derivatives [compound 20; 1-Benzyl-4-nitro-1H-benzotriazole; IC 50 =0.81±0.08mM, compound 21; 2-Benzyl-4-nitro-2H-benzotriazole; IC 50 =0.82±0.19mM] and sulfonyl derivative [compound 23; 1-[(4-Methylphenyl)sulfonyl]-4-nitro-1H-benzotriazole; IC 50 =0.82±0.19mM] are also found to be highly active. Furthermore, all compounds possess P2Y12 binding affinity as confirmed by VASP/P2Y12 phosphorylation assay. Copyright © 2017. Published by Elsevier Ltd.

  16. Nonlinear selection and a blend of convergent, divergent and parallel evolution shapes natural variation in glucosinolates

    DEFF Research Database (Denmark)

    Kliebenstein, Daniel James; Cacho, N. Ivalú

    2016-01-01

    and traits that is highly similar both within and between species. Further, early field trials with single gene recreations of natural variation are showing that selection is highly fluctuating both from site to site and from year to year within a location. This review goes into the specific ecological......The molecular mechanisms underlying organismal fitness in complex environments is just beginning to be illuminated. One of the pre-eminent model systems that span the molecular to field fitness chasm is the natural variation in glucosinolate defence metabolites within the Capparales. In this system......, evolutionary and molecular observations for each of the major loci controlling natural variation in glucosinolates....

  17. Embryotoxicity induced by alkylating agents. Some methodological aspects of DNA alkylation studies in murine embryos using ethylmethanesulfonate.

    Science.gov (United States)

    Platzek, T; Bochert, G; Rahm, U; Neubert, D

    1987-05-01

    Synthesis and spectroscopic analysis of some alkylated DNA purine bases are described. HPLC separation methods are developed for the determination of DNA alkylation rates in mammalian embryonic tissues. Following treatment of pregnant mice with the ethylating agent ethylmethanesulfonate (EMS), an appreciable amount of alkylation (ethylation and methylation) was found in the nuclear DNA of the embryos during organogenesis. The results are discussed in context of our thesis that a certain amount of DNA alkylation in the embryos is correlated to the teratogenic potential of alkylating agents.

  18. Hydride Transfer versus Deprotonation Kinetics in the Isobutane–Propene Alkylation Reaction: A Computational Study

    Science.gov (United States)

    2017-01-01

    The alkylation of isobutane with light alkenes plays an essential role in modern petrochemical processes for the production of high-octane gasoline. In this study we have employed periodic DFT calculations combined with microkinetic simulations to investigate the complex reaction mechanism of isobutane–propene alkylation catalyzed by zeolitic solid acids. Particular emphasis was given to addressing the selectivity of the alkylate formation versus alkene formation, which requires a high rate of hydride transfer in comparison to the competitive oligomerization and deprotonation reactions resulting in catalyst deactivation. Our calculations reveal that hydride transfer from isobutane to a carbenium ion occurs via a concerted C–C bond formation between a tert-butyl fragment and an additional olefin, or via deprotonation of the tert-butyl fragment to generate isobutene. A combination of high isobutane concentration and low propene concentration at the reaction center favor the selective alkylation. The key reaction step that has to be suppressed to increase the catalyst lifetime is the deprotonation of carbenium intermediates that are part of the hydride transfer reaction cycle. PMID:29226012

  19. Hydride Transfer versus Deprotonation Kinetics in the Isobutane-Propene Alkylation Reaction: A Computational Study.

    Science.gov (United States)

    Liu, Chong; van Santen, Rutger A; Poursaeidesfahani, Ali; Vlugt, Thijs J H; Pidko, Evgeny A; Hensen, Emiel J M

    2017-12-01

    The alkylation of isobutane with light alkenes plays an essential role in modern petrochemical processes for the production of high-octane gasoline. In this study we have employed periodic DFT calculations combined with microkinetic simulations to investigate the complex reaction mechanism of isobutane-propene alkylation catalyzed by zeolitic solid acids. Particular emphasis was given to addressing the selectivity of the alkylate formation versus alkene formation, which requires a high rate of hydride transfer in comparison to the competitive oligomerization and deprotonation reactions resulting in catalyst deactivation. Our calculations reveal that hydride transfer from isobutane to a carbenium ion occurs via a concerted C-C bond formation between a tert -butyl fragment and an additional olefin, or via deprotonation of the tert -butyl fragment to generate isobutene. A combination of high isobutane concentration and low propene concentration at the reaction center favor the selective alkylation. The key reaction step that has to be suppressed to increase the catalyst lifetime is the deprotonation of carbenium intermediates that are part of the hydride transfer reaction cycle.

  20. Sequence-specific DNA alkylation targeting for Kras codon 13 mutation by pyrrole-imidazole polyamide seco-CBI conjugates.

    Science.gov (United States)

    Taylor, Rhys Dylan; Asamitsu, Sefan; Takenaka, Tomohiro; Yamamoto, Makoto; Hashiya, Kaori; Kawamoto, Yusuke; Bando, Toshikazu; Nagase, Hiroki; Sugiyama, Hiroshi

    2014-01-27

    Hairpin N-methylpyrrole-N-methylimidazole polyamide seco-CBI conjugates 2-6 were designed for synthesis by Fmoc solid-phase synthesis, and their DNA-alkylating activities against the Kras codon 13 mutation were compared by high-resolution denaturing gel electrophoresis with 225 base pair (bp) DNA fragments. Conjugate 5 had high reactivity towards the Kras codon 13 mutation site, with alkylation occurring at the A of the sequence 5'-ACGTCACCA-3' (site 2), including minor 1 bp-mismatch alkylation against wild type 5'-ACGCCACCA-3' (site 3). Conjugate 6, which differs from conjugate 5 by exchanging one Py unit with a β unit, showed high selectivity but only weakly alkylated the A of 5'-ACGTCACCA-3' (site 2). The hairpin polyamide seco-CBI conjugate 5 thus alkylates according to Dervan's pairing rule with the pairing recognition which β/β pair targets T-A and A-T pairs. SPR and a computer-minimized model suggest that 5 binds to the target sequence with high affinity in a hairpin conformation, allowing for efficient DNA alkylation. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Electronic Control on Linear versus Branched Alkylation of 2-/3-Aroylbenzofurans with Acrylates: Combined DFT and Synthetic Studies.

    Science.gov (United States)

    Srinivas, Kolluru; Dangat, Yuvraj; Kommagalla, Yadagiri; Vanka, Kumar; Ramana, Chepuri V

    2017-06-01

    Investigations on the factors that govern unusual branched alkylation of 2-aroylbenzofurans with acrylates by Ru-catalyzed carbonyl-directed C-H activation has been carried out by calculating the kinetics associated with the two key steps-the coordination of the acrylate with the intermediate ruthenacycle and the subsequent migratory insertion reaction-studied with the help of DFT calculations. Eight possible orientations for each mode of alkylation have been considered for the calculations. From these calculations, it has been understood that there is a synergistic operation of the steric and electronic effects favoring the branched alkylation. Further DFT investigations on the alkylation of the isomeric 3-aroylbenzofurans indicated a preference for the linear alkylation and this has been verified experimentally. Overall, the observed/calculated complementary selectivity in the alkylation of 2-/3-aroylbenzofurans with acrylates reveals that the substrate-dependent charge distribution of the Ru-C bond in the intermediate ruthenacycle is an important determining factor and thus the current work opens up a new domain of substrate design for controlling regioselectivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Mechanistic Insights into Solvent and Ligand Dependency in Cu(I)-Catalyzed Allylic Alkylation with gem-Diborylalkanes.

    Science.gov (United States)

    Zhang, Qi; Wang, Bing; Liu, Jia-Qin; Fu, Yao; Wu, Yu-Cheng

    2018-01-19

    The recent Cu-catalyzed allylic substitution reaction between gem-diboryalkane and allyl electrophiles shows intriguing solvent and ligand-controlled regioselectivity. The α-alkylation product was obtained in DMF solvent, while γ-alkylation product was obtained in dioxane solvent and the dioxane and NHC ligand situation. In the present study, density functional theory calculations have been used to investigate the reaction mechanism and origin of the regioselectivity. For both dioxane and DMF, γ-alkylation undergoes successive oxidative addition (CH 2 Bpin trans to leaving group) and direct Cγ-C reductive elimination. The α-alkylation is found to undergo oxidative addition (CH 2 Bpin trans to leaving group), isomerization, and Cα-C reductive elimination rather than the previously proposed oxidative addition (-CH 2 Bpin cis to the leaving group) and Cα-C reductive elimination. The γ-alkylation and α-alkylation is, respectively, favorable for dioxane and DMF solvent, which is consistent with the γ- and α-selectivity in experiment. The solvent interferes the isomerization step, thereby affects the relative facility of the α- and γ-alkylation. Further investigation shows that η 1 -intermediate formation promoted by solvent is the rate-determining step of the isomerization. The stronger electron-donating ability of DMF than dioxane facilitates the η 1 -intermediate formation and finally results in the easier isomerization in DMF. For dioxane and NHC situation, in the presence of neutral NHC ligand, the -PO 4 Et 2 group tightly coordinates with the Cu center after the oxidative addition, preventing the isomerization process. The regioselectivity is determined by the relative facility of the oxidative addition step. Therefore, the favorable oxidative addition (in which -CH 2 Bpin trans to the leaving group) results in the facility of γ-alkylation.

  3. Structure-function relationship of substituted bromomethylcoumarins in nucleoside specificity of RNA alkylation.

    Science.gov (United States)

    Kellner, Stefanie; Kollar, Laura Bettina; Ochel, Antonia; Ghate, Manjunath; Helm, Mark

    2013-01-01

    Selective alkylation of RNA nucleotides is an important field of RNA biochemistry, e.g. in applications of fluorescent labeling or in structural probing experiments, yet detailed structure-function studies of labeling agents are rare. Here, bromomethylcoumarins as reactive compounds for fluorescent labeling of RNA are developed as an attractive scaffold on which electronic properties can be modulated by varying the substituents. Six different 4-bromomethyl-coumarins of various substitution patterns were tested for nucleotide specificity of RNA alkylation using tRNA from Escherichia coli as substrate. Using semi-quantitative LC-MS/MS analysis, reactions at mildly acidic and slightly alkaline pH were compared. For all tested compounds, coumarin conjugates with 4-thiouridine, pseudouridine, guanosine, and uridine were identified, with the latter largely dominating. This data set shows that selectivity of ribonucleotide alkylation depends on the substitution pattern of the reactive dye, and even more strongly on the modulation of the reaction conditions. The latter should be therefore carefully optimized when striving to achieve selectivity. Interestingly, the highest selectivity for labeling of a modified nucleoside, namely of 4-thiouridine, was achieved with a compound whose selectivity was somewhat less dependent on reaction conditions than the other compounds. In summary, bromomethylcoumarin derivatives are a highly interesting class of compounds, since their selectivity for 4-thiouridine can be efficiently tuned by variation of substitution pattern and reaction conditions.

  4. Rotational diffusion of nonpolar and ionic solutes in 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imides: is solute rotation always influenced by the length of the alkyl chain on the imidazolium cation?

    Science.gov (United States)

    Gangamallaiah, V; Dutt, G B

    2012-10-25

    In an attempt to find out whether the length of the alkyl chain on the imidazolium cation has a bearing on solute rotation, temperature-dependent fluorescence anisotropies of three structurally similar solutes have been measured in a series of 1-alkyl-3-methylimidazolium (alkyl = methyl, ethyl, propyl, butyl, and hexyl) bis(trifluoromethylsulfonyl)imides. Solute-solvent coupling constants obtained from the experimentally measured reorientation times with the aid of Stokes-Einstein-Debye hydrodynamic theory indicate that there is no influence of the length of the alkyl chain on the rotation of nonpolar, anionic, and cationic solutes 9-phenylanthracene (9-PA), fluorescein (FL), and rhodamine 110 (R110), respectively. It has also been noticed that the rotational diffusion of 9-PA is closer to the predictions of slip hydrodynamics, whereas the rotation of negatively charged FL and positively charged R110 is almost identical and follows stick hydrodynamics in these ionic liquids. Despite having similar shape and size, ionic solutes rotate slower by a factor of 3-4 compared to the nonpolar solute. Interplay of specific and electrostatic interactions between FL and the imidazolium cation of the ionic liquids, and between R110 and the bis(trifluoromethylsulfonyl)imide anion, appear to be responsible for the observed behavior. These results are an indication that the length of the alkyl chain on the imidazolium cation does not alter their physical properties in a manner that has an effect on solute rotation.

  5. A highly selective and sensitive "turn-on" fluorescence chemodosimeter for the detection of mustard gas.

    Science.gov (United States)

    Raghavender Goud, D; Purohit, Ajay Kumar; Tak, Vijay; Dubey, Devendra Kumar; Kumar, Pravin; Pardasani, Deepak

    2014-10-21

    A new chemodosimetric protocol based on a tandem S-alkylation followed by desulfurisation reaction of rhodamine-thioamide with mustard gas is reported. The chemodosimeter is highly selective for potential DNA alkylating agents like sulfur mustard, over other simple alkyl halides with the limit of detection of 4.75 μM.

  6. A Selective Bottleneck Shapes the Evolutionary Mutant Spectra of Enterovirus A71 during Viral Dissemination in Humans.

    Science.gov (United States)

    Huang, Sheng-Wen; Huang, Yi-Hui; Tsai, Huey-Pin; Kuo, Pin-Hwa; Wang, Shih-Min; Liu, Ching-Chuan; Wang, Jen-Ren

    2017-12-01

    RNA viruses accumulate mutations to rapidly adapt to environmental changes. Enterovirus A71 (EV-A71) causes various clinical manifestations with occasional severe neurological complications. However, the mechanism by which EV-A71 evolves within the human body is unclear. Utilizing deep sequencing and haplotype analyses of viruses from various tissues of an autopsy patient, we sought to define the evolutionary pathway by which enterovirus A71 evolves fitness for invading the central nervous system in humans. Broad mutant spectra with divergent mutations were observed at the initial infection sites in the respiratory and digestive systems. After viral invasion, we identified a haplotype switch and dominant haplotype, with glycine at VP1 residue 31 (VP1-31G) in viral particles disseminated into the integumentary and central nervous systems. In vitro viral growth and fitness analyses indicated that VP1-31G conferred growth and a fitness advantage in human neuronal cells, whereas VP1-31D conferred enhanced replication in human colorectal cells. A higher proportion of VP1-31G was also found among fatal cases, suggesting that it may facilitate central nervous system infection in humans. Our data provide the first glimpse of EV-A71 quasispecies from oral tissues to the central nervous system within humans, showing broad implications for the surveillance and pathogenesis of this reemerging viral pathogen. IMPORTANCE EV-A71 continues to be a worldwide burden to public health. Although EV-A71 is the major etiological agent of hand, foot, and mouth disease, it can also cause neurological pulmonary edema, encephalitis, and even death, especially in children. Understanding selection processes enabling dissemination and accurately estimating EV-A71 diversity during invasion in humans are critical for applications in viral pathogenesis and vaccine studies. Here, we define a selection bottleneck appearing in respiratory and digestive tissues. Glycine substitution at VP1 residue 31

  7. Introgression and selection shaped the evolutionary history of sympatric sister-species of coral reef fishes (genus: Haemulon)

    KAUST Repository

    Bernal, Moisé s A.; Gaither, Michelle R.; Simison, W. Brian; Rocha, Luiz A.

    2016-01-01

    Closely related marine species with large overlapping ranges provide opportunities to study mechanisms of speciation, particularly when there is evidence of gene flow between such lineages. Here, we focus on a case of hybridization between the sympatric sister-species Haemulon maculicauda and H. flaviguttatum, using Sanger sequencing of mitochondrial and nuclear loci, as well as 2422 single nucleotide polymorphisms (SNPs) obtained via restriction site-associated DNA sequencing (RADSeq). Mitochondrial markers revealed a shared haplotype for COI and low divergence for CytB and CR between the sister-species. On the other hand, complete lineage sorting was observed at the nuclear loci and most of the SNPs. Under neutral expectations, the smaller effective population size of mtDNA should lead to fixation of mutations faster than nDNA. Thus, these results suggest that hybridization in the recent past (0.174-0.263Ma) led to introgression of the mtDNA, with little effect on the nuclear genome. Analyses of the SNP data revealed 28 loci potentially under divergent selection between the two species. The combination of mtDNA introgression and limited nuclear DNA introgression provides a mechanism for the evolution of independent lineages despite recurrent hybridization events. This study adds to the growing body of research that exemplifies how genetic divergence can be maintained in the presence of gene flow between closely related species.

  8. Introgression and selection shaped the evolutionary history of sympatric sister-species of coral reef fishes (genus: Haemulon)

    KAUST Repository

    Bernal, Moisés A.

    2016-11-22

    Closely related marine species with large overlapping ranges provide opportunities to study mechanisms of speciation, particularly when there is evidence of gene flow between such lineages. Here, we focus on a case of hybridization between the sympatric sister-species Haemulon maculicauda and H. flaviguttatum, using Sanger sequencing of mitochondrial and nuclear loci, as well as 2422 single nucleotide polymorphisms (SNPs) obtained via restriction site-associated DNA sequencing (RADSeq). Mitochondrial markers revealed a shared haplotype for COI and low divergence for CytB and CR between the sister-species. On the other hand, complete lineage sorting was observed at the nuclear loci and most of the SNPs. Under neutral expectations, the smaller effective population size of mtDNA should lead to fixation of mutations faster than nDNA. Thus, these results suggest that hybridization in the recent past (0.174-0.263Ma) led to introgression of the mtDNA, with little effect on the nuclear genome. Analyses of the SNP data revealed 28 loci potentially under divergent selection between the two species. The combination of mtDNA introgression and limited nuclear DNA introgression provides a mechanism for the evolution of independent lineages despite recurrent hybridization events. This study adds to the growing body of research that exemplifies how genetic divergence can be maintained in the presence of gene flow between closely related species.

  9. Convection shapes the trade-off between antibiotic efficacy and the selection for resistance in spatial gradients

    Science.gov (United States)

    Gralka, Matti; Fusco, Diana; Martis, Stephen; Hallatschek, Oskar

    2017-08-01

    Since penicillin was discovered about 90 years ago, we have become used to using drugs to eradicate unwanted pathogenic cells. However, using drugs to kill bacteria, viruses or cancer cells has the serious side effect of selecting for mutant types that survive the drug attack. A crucial question therefore is how one could eradicate as many cells as possible for a given acceptable risk of drug resistance evolution. We address this general question in a model of drug resistance evolution in spatial drug gradients, which recent experiments and theories have suggested as key drivers of drug resistance. Importantly, our model takes into account the influence of convection, resulting for instance from blood flow. Using stochastic simulations, we study the fates of individual resistance mutations and quantify the trade-off between the killing of wild-type cells and the rise of resistance mutations: shallow gradients and convection into the antibiotic region promote wild-type death, at the cost of increasing the establishment probability of resistance mutations. We can explain these observed trends by modeling the adaptation process as a branching random walk. Our analysis reveals that the trade-off between death and adaptation depends on the relative length scales of the spatial drug gradient and random dispersal, and the strength of convection. Our results show that convection can have a momentous effect on the rate of establishment of new mutations, and may heavily impact the efficiency of antibiotic treatment.

  10. Radioiodination of proteins by reductive alkylation

    International Nuclear Information System (INIS)

    Panuska, J.R.; Parker, C.W.

    1987-01-01

    The use of the aliphatic aldehyde, para-hydroxyphenylacetaldehyde as the reactive moiety in the radioiodination of proteins by reductive alkylation is described. The para-hydroxyphenyl group is radiolabeled with 125 I, reacted through its aliphatic aldehyde group with primary amino groups on proteins to form a reversible Schiff base linkage which can then be stabilized with the mild reducing agent NaCNBH 3 . The introduction of the methylene group between the benzene ring and the aldehyde group increases its reactivity with protein amino groups permitting efficient labeling at low aldehyde concentrations. Using this method, radioiodinated proteins with high specific activity can be produced. The reductive alkylation procedure is advantageous in that the labeling conditions are mild, the reaction is specific for lysyl residues, and the modification of the epsilon-ammonium group of lysine results in ionizable secondary amino groups avoiding major changes in protein charge

  11. Palladium Catalyzed Allylic C-H Alkylation

    DEFF Research Database (Denmark)

    Engelin, Casper Junker; Fristrup, Peter

    2011-01-01

    are highlighted with emphasis on those leading to C-C bond formation, but where it was deemed necessary for the general understanding of the process closely related C-H oxidations and aminations are also included. It is found that C-H cleavage is most likely achieved by ligand participation which could involve......-H alkylation reaction which is the topic of the current review. Particular emphasis is put on current mechanistic proposals for the three reaction types comprising the overall transformation: C-H activation, nucleophillic addition, and re-oxidation of the active catalyst. Recent advances in C-H bond activation...... an acetate ion coordinated to Pd. Several of the reported systems rely on benzoquinone for re-oxidation of the active catalyst. The scope for nucleophilic addition in allylic C-H alkylation is currently limited, due to demands on pKa of the nucleophile. This limitation could be due to the pH dependence...

  12. Influence of Odd and Even Alkyl Chains on Supramolecular Nanoarchitecture via Self-Assembly of Tetraphenylethylene-Based AIEgens

    Directory of Open Access Journals (Sweden)

    Mina Salimimarand

    2017-10-01

    Full Text Available The Tetraphenylethylene (TPE based dumbbell shaped molecules TPE-Pi, TPE-Su, TPE-Az, and TPE-Se were synthesised bearing odd-even alkyl chains containing 7, 8, 9 and 10 carbons respectively. These molecules reveal typical Aggregation Induced Emission (AIE behaviour. The influence of the odd or even alkyl chain length was shown by studying the morphology of self-assembled nanostructures formed in a range of tetrahydrofuran (THF/water solvent systems. For example, with a water fraction of 80%, TPE derivatives with odd alkyl chains (TPE-Pi and TPE-Az self-assembled into nanosphere structures, while TPE-Su with 8 alkyl chains formed microbelts and TPE-Se with 10 alkyl chains aggregated into flower-like superstructures. These TPE derivatives also revealed interesting mechanochromic properties upon grinding, fuming and heating, which reveal the importance of molecular stacking in the crystal structure to the luminescent properties of the aggregates .The mechanochromic properties of TPE-Pi, TPE-Su, and TPE-Az were also demonstrated by the process of grounding, fuming, and heating.

  13. Photoinduced, copper-catalyzed alkylation of amides with unactivated secondary alkyl halides at room temperature.

    Science.gov (United States)

    Do, Hien-Quang; Bachman, Shoshana; Bissember, Alex C; Peters, Jonas C; Fu, Gregory C

    2014-02-05

    The development of a mild and general method for the alkylation of amides with relatively unreactive alkyl halides (i.e., poor substrates for SN2 reactions) is an ongoing challenge in organic synthesis. We describe herein a versatile transition-metal-catalyzed approach: in particular, a photoinduced, copper-catalyzed monoalkylation of primary amides. A broad array of alkyl and aryl amides (as well as a lactam and a 2-oxazolidinone) couple with unactivated secondary (and hindered primary) alkyl bromides and iodides using a single set of comparatively simple and mild conditions: inexpensive CuI as the catalyst, no separate added ligand, and C-N bond formation at room temperature. The method is compatible with a variety of functional groups, such as an olefin, a carbamate, a thiophene, and a pyridine, and it has been applied to the synthesis of an opioid receptor antagonist. A range of mechanistic observations, including reactivity and stereochemical studies, are consistent with a coupling pathway that includes photoexcitation of a copper-amidate complex, followed by electron transfer to form an alkyl radical.

  14. A genome-wide metabolic QTL analysis in Europeans implicates two loci shaped by recent positive selection.

    Directory of Open Access Journals (Sweden)

    George Nicholson

    2011-09-01

    Full Text Available We have performed a metabolite quantitative trait locus (mQTL study of the (1H nuclear magnetic resonance spectroscopy ((1H NMR metabolome in humans, building on recent targeted knowledge of genetic drivers of metabolic regulation. Urine and plasma samples were collected from two cohorts of individuals of European descent, with one cohort comprised of female twins donating samples longitudinally. Sample metabolite concentrations were quantified by (1H NMR and tested for association with genome-wide single-nucleotide polymorphisms (SNPs. Four metabolites' concentrations exhibited significant, replicable association with SNP variation (8.6×10(-11selection in European populations. Genes NAT8 and PYROXD2, both with relatively uncharacterized functional roles, are good candidates for mediating the corresponding mQTL associations. The study's longitudinal twin design allowed detailed variance-components analysis of the sources of population variation in metabolite levels. The mQTLs explained 40%-64% of biological population variation in the corresponding metabolites' concentrations. These effect sizes are stronger than those reported in a recent, targeted mQTL study of metabolites in serum using the targeted-metabolomics Biocrates platform. By re-analysing our plasma samples using the Biocrates platform, we replicated the mQTL findings of the previous study and discovered a previously uncharacterized yet substantial familial component of variation in metabolite levels in addition to the heritability contribution from

  15. Nickel-Catalyzed Alkoxy-Alkyl Interconversion with Alkylborane Reagents through C−O Bond Activation of Aryl and Enol Ethers

    KAUST Repository

    Guo, Lin

    2016-11-07

    A nickel-catalyzed alkylation of polycyclic aromatic methyl ethers as well as methyl enol ethers with B-alkyl 9-BBN and trialkylborane reagents that involves the cleavage of stable C(sp2)−OMe bonds is described. The transformation has a wide substrate scope and good chemoselectivity profile while proceeding under mild reaction conditions; it provides a versatile way to form C(sp2)−C(sp3) bonds that does not suffer from β-hydride elimination. Furthermore, a selective and sequential alkylation process by cleavage of inert C−O bonds is presented to demonstrate the advantage of this method.

  16. Distribution of methyl and ethyl adducts following alkylation with monofunctional alkylating agents.

    Science.gov (United States)

    Beranek, D T

    1990-07-01

    Alkylating agents, because of their ability to react directly with DNA either in vitro or in vivo, or following metabolic activation as in the case of the dialkylnitrosamines, have been used extensively in studying the mechanisms of mutagenicity and carcinogenicity. Their occurrence is widespread in the environment and human exposure from natural and pollutant sources is universal. Since most of these chemicals show varying degrees of both carcinogenicity and mutagenicity, and exhibit compound-specific binding patterns, they provide an excellent model for studying molecular dosimetry. Molecular dosimetry defines dose as the number of adducts bound per macromolecule and relates the binding of these adducts to the human mutagenic or carcinogenic response. This review complies DNA alkylation data for both methylating and ethylating agents in a variety of systems and discusses the role these alkylation products plays in molecular mutagenesis.

  17. Isolation of the antibiotic pseudopyronine B and SAR evaluation of C3/C6 alkyl analogs.

    Science.gov (United States)

    Bouthillette, Leah M; Darcey, Catherine A; Handy, Tess E; Seaton, Sarah C; Wolfe, Amanda L

    2017-06-15

    Natural products are an abundant source of structurally diverse compounds with antibacterial activity that can be used to develop new and potent antibiotics. One such class of natural products is the pseudopyronines. Here we present the isolation of pseudopyronine B (2) from a Pseudomonas species found in garden soil in Western North Carolina, and SAR evaluation of C3 and C6 alkyl analogs of the natural product for antibacterial activity against Gram-positive and Gram-negative bacteria. We found a direct relationship between antibacterial activity and C3/C6 alkyl chain length. For inhibition of Gram-positive bacteria, alkyl chain lengths between 6 and 7 carbons were found to be the most active (IC 50 =0.04-3.8µg/mL) whereas short alkyl chain analogs showed modest activity against Gram-negative bacteria (IC 50 =223-304µg/mL). This demonstrates the potential for this class of natural products to be optimized for selective activity against either Gram-positive or Gram-negative bacteria. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Visible light- and radiation-induced alkylation of pyridine ring with alkanoic acid

    International Nuclear Information System (INIS)

    Sugimori, Akira; Yamada, Tetsuo

    1986-01-01

    Quinoline and 4-methylquinoline are efficiently alkylated with alkanoic acid in the presence of iron(III) sulfate upon visible light-irradiation. Iron(III) sulfate not only accelerates the photoreaction but also increases the yield of alkylation. Gamma-irradiation also brings about the alkylation. In the photo- and radiation-induced alkylation with alkanoic acid, alkyl radicals play important roles. (author)

  19. Copper-catalyzed radical carbooxygenation: alkylation and alkoxylation of styrenes.

    Science.gov (United States)

    Liao, Zhixiong; Yi, Hong; Li, Zheng; Fan, Chao; Zhang, Xu; Liu, Jie; Deng, Zixin; Lei, Aiwen

    2015-01-01

    A simple copper-catalyzed direct radical carbooxygenation of styrenes is developed utilizing alkyl bromides as radical resources. This catalytic radical difunctionalization accomplishes both alkylation and alkoxylation of styrenes in one pot. A broad range of styrenes and alcohols are well tolerated in this transformation. The EPR experiment shows that alkyl halides could oxidize Cu(I) to Cu(II) in this transformation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. A new strategy for aromatic ring alkylation in cylindrocyclophane biosynthesis.

    Science.gov (United States)

    Nakamura, Hitomi; Schultz, Erica E; Balskus, Emily P

    2017-08-01

    Alkylation of aromatic rings with alkyl halides is an important transformation in organic synthesis, yet an enzymatic equivalent is unknown. Here, we report that cylindrocyclophane biosynthesis in Cylindrospermum licheniforme ATCC 29412 involves chlorination of an unactivated carbon center by a novel halogenase, followed by a previously uncharacterized enzymatic dimerization reaction featuring sequential, stereospecific alkylations of resorcinol aromatic rings. Discovery of the enzymatic machinery underlying this unique biosynthetic carbon-carbon bond formation has implications for biocatalysis and metabolic engineering.

  1. Toward Efficient Palladium-Catalyzed Allylic C-H Alkylation

    DEFF Research Database (Denmark)

    Jensen, Thomas; Fristrup, Peter

    2009-01-01

    Recent breakthroughs have proved that direct palladium (II)-catalyzed allylic C-H alkylation can be achieved. This new procedure shows that the inherent requirement for a leaving group in the Tsuji-Trost palladium-catalyzed allylic alkylation can be lifted. These initial reports hold great promise...... for the development of allylic C-H alkylation into a widely applicable methodology, thus providing a means to enhance synthetic efficiency in these reactions....

  2. Possible targets for the aneugenic activity of alkylating agents

    Energy Technology Data Exchange (ETDEWEB)

    Pellerano, P. [IST-National Institute for Research on Cancer, Genova (Italy); Abbondandolo, A. [Univ. of Genova (Italy); Bonatti, S.; Simili, M. [CNR Institute of Mutagenesis and Differentiation, Pisa (Italy)

    1993-12-31

    Alkylating agents have been of invaluable help in mutation research for half a century. In all tested organisms, they have proved able to induce a large variety of genetic effects, including aneuploidy. Credible molecular models exist to explain the ability of alkylating agents to induce gene mutation and to act as initiators in carcinogenesis as a consequence of DNA alkylation at specific sites. On the contrary, neither the mechanism of aneuploidy induction nor the relevant cellular targets are known.

  3. The effect of the cation alkyl chain length on density and diffusion in dialkylpyrrolidinium bis(mandelato)borate ionic liquids.

    Science.gov (United States)

    Filippov, Andrei; Taher, Mamoun; Shah, Faiz Ullah; Glavatskih, Sergei; Antzutkin, Oleg N

    2014-12-28

    The physicochemical properties of ionic liquids are strongly affected by the selective combination of the cations and anions comprising the ionic liquid. In particular, the length of the alkyl chains of ions has a clear influence on the ionic liquid's performance. In this paper, we study the self-diffusion of ions in a series of halogen-free boron-based ionic liquids (hf-BILs) containing bis(mandelato)borate anions and dialkylpyrrolidinium cations with long alkyl chains CnH2n+1 with n from 4 to 14 within a temperature range of 293-373 K. It was found that the hf-BILs with n = 4-7 have very similar diffusion coefficients, while hf-BILs with n = 10-14 exhibit two liquid sub-phases in almost the entire temperature range studied (293-353 K). Both liquid sub-phases differ in their diffusion coefficients, while values of the slower diffusion coefficients are close to those of hf-BILs with shorter alkyl chains. To explain the particular dependence of diffusion on the alkyl chain length, we examined the densities of the hf-BILs studied here. It was shown that the dependence of the density on the number of CH2 groups in long alkyl chains of cations can be accurately described using a "mosaic type" model, where regions of long alkyl chains of cations (named 'aliphatic' regions) and the residual chemical moieties in both cations and anions (named 'ionic' regions) give additive contributions. Changes in density due to an increase in temperature and the number of CH2 groups in the long alkyl chains of cations are determined predominantly by changes in the free volume of the 'ionic' regions, while 'aliphatic' regions are already highly compressed by van der Waals forces, which results in only infinitesimal changes in their free volumes with temperature.

  4. Recent developments in nanostructured inorganic materials for sorption of cesium and strontium: Synthesis and shaping, sorption capacity, mechanisms, and selectivity-A review.

    Science.gov (United States)

    Alby, Delhia; Charnay, Clarence; Heran, Marc; Prelot, Bénédicte; Zajac, Jerzy

    2018-02-15

    Liquid wastes containing non-ferrous heavy metal ions and some radionuclides, 137 Cs and 90 Sr in particular, represent one of the most dangerous sources of environmental contamination. The remediation of wastewater containing such pollutants continue to be among the biggest challenges of Sustainable Development and Environmental Safety. Sorption-based technologies have proven their efficiency also in reducing the radionuclide content in aqueous streams to low-level residual activity, with the concomitant decrease in the amount of ultimate solid waste generated. Although sorption of cesium and strontium by resins, clays, and zeolites has been investigated intensively and even used in real applications, there is still considerable scope for improvement in terms of retention capacity and selectivity. Recent progress in design and preparation of nanostructured inorganic materials has attracted growing interest based on the potential for improving the retention performance when coupling such functionalities as ion exchange capacity, structural flexibility that may result in steric retention effects, as well as the propensity to interact specifically with the target metal cations. Titanate, vanadate, and tungsten based materials, manganese oxides, hexacyanoferrates, metal sulfides, ammonium molybdophosphates, or hydroxyapatite, characterized by various structures and morphologies, are reviewed with the emphasis being put on synthesis and shaping of such materials, their structure in relationship with the capacity and selectivity of trapping cesium and strontium from either single or multi-component aqueous solutions, as well as the possible retention mechanism. The potential candidates for remediation uses are selected with regard to their sorption capacity and distribution coefficient towards target cations, and also the pH window for an optimum cation capture. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Determination of reaction rate constants for alkylation of 4-(p-nitrobenzyl) pyridine by different alkylating agents.

    Science.gov (United States)

    Walles, S A

    1980-02-01

    The rate constants have been determined for the reaction between some different alkylating agents and 4-(p-nitrobenzyl) pyridine (NBP) in methanol. These constants have been compared with those for alkylation of aniline in water. All the constants were lower in methanol than in water but in different degrees. The rate constants of the different alkylating agents have been calculated at a nucleophilic strength n=2. The genetic risk defined as the degree of alkylation of a nucleophile (n=2) is equivalent to the rate constant kn=2 and the target dose. The dependence of the genetic risk on the rate constant (kn=2) is discussed.

  6. Thermogravimetric studies on alkyl methacrylate polymers and poly(alkyl methacrylate)-grafted polypropylene fibers

    International Nuclear Information System (INIS)

    Hayakawa, Kiyoshi; Taoda, Hiroshi; Kawase, Kaoru; Tazawa, Masato; Yamakita, Hiromi

    1986-01-01

    Thermal behavior of several kinds of poly (alkyl methacrylate) and polypropylene-g-poly (alkyl methacrylate) fibers prepared by γ-irradiation was investigated by thermogravimetric measurements with the intermittent analysis of the gaseous products. The degradation of poly (methyl methacrylate) proceeded according to the deploymerization mechanism reproducing the pristine monomer exclusively. The thermogram in inert atmosphere showed the features of a two-step depolymerization, while in air it showed no such a stepwise decrease with the elevating temperature. The dissolution-precipitation treatment of polymer seemed to affect the decomposition behavior. On other alkyl methacrylate polymers, the thermal decomposition generally proceeded also according to the depolymerization mechanism. But, for instance, at least two kinds of products besides its own monomer were formed from poly (isobutyl methacrylate), and their relative fractions differed with the temperature. Polypropylene-g-poly (alkyl methacrylate) fibers showed lowering of initiation temperature of decomposition with the increase in extent of the grafting, and their initiation temperatures of decomposition in air were lower than those in inert atmosphere. (author)

  7. Hydration of urea and alkylated urea derivatives

    Science.gov (United States)

    Kaatze, Udo

    2018-01-01

    Compressibility data and broadband dielectric spectra of aqueous solutions of urea and some of its alkylated derivatives have been evaluated to yield their numbers Nh of hydration water molecules per molecule of solute. Nh values in a broad range of solute concentrations are discussed and are compared to hydration numbers of other relevant molecules and organic ions. Consistent with previous results, it is found that urea differs from other solutes in its unusually small hydration number, corresponding to just one third of the estimated number of nearest neighbor molecules. This remarkable hydration behavior is explained by the large density φH of hydrogen bonding abilities offered by the urea molecule. In terms of currently discussed models of reorientational motions and allied dynamics in water and related associating liquids, the large density φH causes a relaxation time close to that of undisturbed water with most parts of water encircling the solute. Therefore only a small part of disturbed ("hydration") water is left around each urea molecule. Adding alkyl groups to the basic molecule leads to Nh values which, within the series of n-alkylurea derivatives, progressively increase with the number of methyl groups per solute. With n-butylurea, Nh from dielectric spectra, in conformity with many other organic solutes, slightly exceeds the number of nearest neighbors. Compared to such Nh values, hydration numbers from compressibility data are substantially smaller, disclosing incorrect assumptions in the formula commonly used to interpret the experimental compressibilities. Similar to other series of organic solutes, effects of isomerization have been found with alkylated urea derivatives, indicating that factors other than the predominating density φH of hydrogen bond abilities contribute also to the hydration properties.

  8. Selective alkylation by photogenerated aryl and vinyl cation

    NARCIS (Netherlands)

    Slegt, Micha

    2006-01-01

    Seven para-substituted phenyl cations and the parent phenyl cation were prepared from iodonium salt precursors. Product studies revealed remarkable chemoselectivity and regioselectivity that could be related to the spin multiplicity of the cations. Also an universal method to fingerprint singlet and

  9. Sorbate-nitrite interactions: acetonitrile oxide as an alkylating agent.

    Science.gov (United States)

    Pérez-Prior, M Teresa; Gómez-Bombarelli, Rafael; González-Pérez, Marina; Manso, José A; García-Santos, M Pilar; Calle, Emilio; Casado, Julio

    2009-07-01

    Because chemical species with DNA-damaging and mutagenic activity are formed in sorbate-nitrite mixtures and because sorbic acid sometimes coexists with nitrite occurring naturally or incorporated as a food additive, the study of sorbate-nitrite interactions is important. Here, the alkylating potential of the products resulting from such interactions was investigated. Drawn were the following conclusions: (i) Acetonitrile oxide (ACNO) is the compound responsible for the alkylating capacity of sorbate-nitrite mixtures; (ii) ACNO alkylates 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases, forming an adduct (AD; epsilon = 1.4 x 10(4) M(-1) cm(-1); lambda = 519 nm); (iii) the NBP alkylation reaction complies with the rate equation, r = d[AD]/dt = k(alk)(ACNO)[ACNO][NBP]-k(hyd)(AD)[AD], k(alk)(ACNO) being the NBP alkylation rate constant for ACNO and k(hyd)(AD) the rate constant for the adduct hydrolysis reaction; (iv) the small fraction of ACNO forming the adduct with NBP, as well as the small magnitude of the quotient (k(alk) (ACNO)/k(hyd)(ACNO)) as compared with those reported for other alkylating agents, such as some lactones and N-alkyl-N-nitrosoureas, reveals the ACNO effective alkylating capacity to be less significant; (v) the low value of the NBP-ACNO adduct life (defined as the total amount of adduct present along the progression of the NBP alkylation per unit of alkylating agent concentration) points to the high instability of this adduct; and (vi) the obtained results are in accordance with the low carcinogenicity of ACNO.

  10. The role of natural selection in shaping genetic variation in a promising Chagas disease drug target: Trypanosoma cruzi trans-sialidase.

    Science.gov (United States)

    Gallant, Joseph P; Lima-Cordón, Raquel Asunción; Justi, Silvia A; Monroy, Maria Carlota; Viola, Toni; Stevens, Lori

    2018-04-21

    Rational drug design creates innovative therapeutics based on knowledge of the biological target to provide more effective and responsible therapeutics. Chagas disease, endemic throughout Latin America, is caused by Trypanosoma cruzi, a protozoan parasite. Current therapeutics are problematic with widespread calls for new approaches. Researchers are using rational drug design for Chagas disease and one target receiving considerable attention is the T. cruzi trans-sialidase protein (TcTS). In T. cruzi, trans-sialidase catalyzes the transfer of sialic acid from a mammalian host to coat the parasite surface membrane and avoid immuno-detection. However, the role of TcTS in pathology variance among and within genetic variants of the parasite is not well understood despite numerous studies. Previous studies reported the crystalline structure of TcTS and the TS protein structure in other trypanosomes where the enzyme is often inactive. However, no study has examined the role of natural selection in genetic variation in TcTS. To understand the role of natural selection in TcTS DNA sequence and protein variation, we examined a 471 bp portion of the TcTS gene from 48 T. cruzi samples isolated from insect vectors. Because there may be multiple parasite genotypes infecting one insect and there are multiple copies of TcTS per parasite genome, all 48 sequences had multiple polymorphic bases. To resolve these polymorphisms, we examined cloned sequences from two insect vectors. The data are analyzed to understand the role of natural selection in shaping genetic variation in TcTS and interpreted in light of the possible role of TcTS as a drug target. The analysis highlights negative or purifying selection on three amino acids previously shown to be important in TcTS transfer activity. One amino acid in particular, Tyr342, is a strong candidate for a drug target because it is under negative selection and amino acid substitutions inactivate TcTS transfer activity. Chagas disease

  11. Alkylation of hydrothiophosphoryl compounds in conditions of interphase catalysis

    International Nuclear Information System (INIS)

    Aladzheva, I.M.; Odinets, I.L.; Petrovskij, P.V.; Mastryukova, T.A.; Kabachkin, M.I.

    1993-01-01

    A method of interphase catalysis permitted to develop a common method for synthesis of compounds with thiophosphoryl group. The effect of nature of hydrothiophosphoryl compound, alkylating agent, two-phase system and reaction conditions on alkylation product yields was investigated in detail

  12. Oxidative Umpolung α‐Alkylation of Ketones

    DEFF Research Database (Denmark)

    Shneider, O. Svetlana; Pisarevsky, Evgeni; Fristrup, Peter

    2015-01-01

    We disclose a hypervalent iodine mediated α-alkylative umpolung reaction of carbonyl compounds with dialkylzinc as the alkyl source. The reaction is applicable to all common classes of ketones including 1,3-dicarbonyl compounds and regular ketones via their lithium enolates. The α...

  13. Physicochemical properties of phosphatidylcholine (PC) monolayers with different alkyl chains, at the air/water interface

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Hee Jung; Choi, Young Wook [Hanyang Univ., Seoul (Korea, Republic of); Kim, Nam Jeong; Sohn, Dae Won [Sahmyook Univ., Seoul (Korea, Republic of)

    2003-03-01

    Physicochemical properties of a series of PC monolayers with different alkyl chains (C24, C20, C16, and C8), at the air/water interface were investigated. The surface pressure is influenced mainly by the hydrophobicity of the PCs, which is confirmed by the curve shape and the on-set value of {pi}-A isotherms at the air/water interface by increasing the number of alkyl chain. The on-set values of surface pressure were 125 A{sup 2}/molecule for DOPC(C8), 87 A{sup 2}/molecule for DPPC(C16), 75 A{sup 2}/molecule for DAPC(C20), and 55 A{sup 2}/molecule for DLPC(C24), respectively. The orientations of alkyl chains at the air/water interface are closely connected with the rigidity of the monolayers, and it was confirmed by the tendency of monolayer thickness in ellipsometry data. The temperature dependence of a series of PCs shows that the surface pressure decreases by increasing temperature, because the longer the alkyl chain length, the larger the hydrophobic interaction in surface pressure. The temperature effects and the conformational changes of unsaturated and saturated PCs were confirmed by the computer simulation study of the cis-trans transition with POPC and DPPC(C16). The cis-trans conformational energy difference of POPC is 62.06 kcal/mol and that of DPPC(C16) is 6.75 kcal/mol. Due to the high conformational energy barrier of POPC, phase transition of POPC is limited in comparison with DPPC(C16)

  14. Physicochemical properties of phosphatidylcholine (PC) monolayers with different alkyl chains, at the air/water interface

    International Nuclear Information System (INIS)

    Yun, Hee Jung; Choi, Young Wook; Kim, Nam Jeong; Sohn, Dae Won

    2003-01-01

    Physicochemical properties of a series of PC monolayers with different alkyl chains (C24, C20, C16, and C8), at the air/water interface were investigated. The surface pressure is influenced mainly by the hydrophobicity of the PCs, which is confirmed by the curve shape and the on-set value of π-A isotherms at the air/water interface by increasing the number of alkyl chain. The on-set values of surface pressure were 125 A 2 /molecule for DOPC(C8), 87 A 2 /molecule for DPPC(C16), 75 A 2 /molecule for DAPC(C20), and 55 A 2 /molecule for DLPC(C24), respectively. The orientations of alkyl chains at the air/water interface are closely connected with the rigidity of the monolayers, and it was confirmed by the tendency of monolayer thickness in ellipsometry data. The temperature dependence of a series of PCs shows that the surface pressure decreases by increasing temperature, because the longer the alkyl chain length, the larger the hydrophobic interaction in surface pressure. The temperature effects and the conformational changes of unsaturated and saturated PCs were confirmed by the computer simulation study of the cis-trans transition with POPC and DPPC(C16). The cis-trans conformational energy difference of POPC is 62.06 kcal/mol and that of DPPC(C16) is 6.75 kcal/mol. Due to the high conformational energy barrier of POPC, phase transition of POPC is limited in comparison with DPPC(C16)

  15. Preparation of trialkylindium by alkylation of metallic indium

    International Nuclear Information System (INIS)

    Eremeev, I.V.; Danov, S.M.; Sakhipov, V.R.

    1995-01-01

    The investigation results on production of trialkyl indium by alkylation of metallic indium are presented. In contradistinction to the known techniques for the production of trialkyls on indium by alkylation it is suggested to separate the synthesis into two steps. At the first step indium is alkylated by alkylhalide to alkyl indium halide, and at the second alkylation is carried out using. Grignard reagent. The techniques for preparation of trimethyl- and triethylindium, developed on the bases of this scheme, are noted for good reproducibility, allow to preclude, agglomeration of indium during the synthesis, as well as to reduce the consumption coefficients, and amounts, of the introduced starting reagents, i.e. magnesium and alkylhalide. Refs. 16

  16. Nanostructured poly(benzimidazole membranes by N-alkylation

    Directory of Open Access Journals (Sweden)

    J. Weber

    2014-01-01

    Full Text Available Modification of poly(benzimidazole (PBI by N-alkylation leads to polymers capable of undergoing microphase separation. Polymers with different amounts of C18 alkyl chains have been prepared. The polymers were analyzed by spectroscopy, thermal analysis, electron microscopy and X-ray scattering. The impact of the amount of alkyl chains on the observed microphase separation was analyzed. Membranes prepared from the polymers do show microphase separation, as evidenced by scattering experiments. While no clear morphology could be derived for the domains in the native state, evidence for the formation of lamellar morphologies upon doping with phosphoric acid is provided. Finally, the proton conductivity of alkyl-modified PBI is compared with that of pure PBI, showing that the introduction of alkyl side chains does not result in significant conductivity changes.

  17. Nanopolaritonics with a continuum of molecules: simulations of molecular-induced selectivity in plasmonics transport through a continuous Y-shape.

    Science.gov (United States)

    Neuhauser, Daniel

    2011-11-28

    Using the recent NF (near-field) formulation for electrodynamics on the nanoscale, we simulate transport in a Y-shape gold nanostructure in the presence of 2-level molecules. NF is shown to be easily integrated with the Liouville equation, producing a simple and efficient nanopolaritons (plasmons-excitons) solver, with a large time step. Two cases are considered: coating of the gold structure with molecular layers thinner than the structure, and filling space with aligned molecules. In both cases significant effects on the radiation transport are obtained even for low molecular densities. At low densities the effects are primarily an overall reduction of the plasmonics peak, but at higher densities there is a significant selectivity control by the molecules. A redshift is predicted, especially for the space-filling case. The combined nanopolariton shows qualitative hybridization, and the spectral peaks separate with increasing coupling, i.e., with increasing molecular densities. The results open the way to "control of light by light," i.e., controlling plasmonic light transport by inducing a change in the direction of the guiding molecular dipoles through radiation or other means.

  18. UV absorption spectra, kinetics and mechanism for alkyl and alkyl peroxy radicals originating from t-butyl alcohol

    DEFF Research Database (Denmark)

    Langer, S.; Ljungström, E.; Sehested, J.

    1994-01-01

    Alkyl and alkyl peroxy radicals from 1-butyl alcohol (TBA), HOC (CH3)2CH2. and HOC(CH3)2CH2O2. have been studied in the ps phase at 298 K. Two techniques were used: pulse radiolysis UV absorption to measure the spectra and kinetics, and long path-length Fourier transform infrared spectroscopy (FTIR...

  19. Alkylation of terminal alkynes with transient σ-alkylpalladium(II) complexes: a carboalkynylation route to alkyl-substituted alkynes.

    Science.gov (United States)

    Zhou, Ming-Bo; Huang, Xiao-Cheng; Liu, Yan-Yun; Song, Ren-Jie; Li, Jin-Heng

    2014-02-10

    A mild and general alkylation of terminal alkynes with transient σ-alkylpalladium(II) complexes for assembling alkyl-substituted alkynes is described. This method represents a new way to the use of transient σ-alkylpalladium(II) complexes in organic synthesis through 1,2-carboalkynylation of alkenes. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Cu(I)-Catalyzed Enantioselective Friedel-Crafts Alkylation of Indoles with 2-Aryl-N-sulfonylaziridines as Alkylating Agents.

    Science.gov (United States)

    Ge, Chen; Liu, Ren-Rong; Gao, Jian-Rong; Jia, Yi-Xia

    2016-07-01

    A highly enantioselective Friedel-Crafts alkylation of indoles with N-sulfonylaziridines as alkylating agents has been developed by utilizing the complex of Cu(CH3CN)4BF4/(S)-Segphos as a catalyst. A range of optically active tryptamine derivatives are obtained in good to excellent yields and enantioselectivities (up to >99% ee) via a kinetic resolution process.

  1. Photo-triggered fluorescent theranostic prodrugs as DNA alkylating agents for mechlorethamine release and spatiotemporal monitoring.

    Science.gov (United States)

    Cao, Yanting; Pan, Rong; Xuan, Weimin; Wei, Yongyi; Liu, Kejian; Zhou, Jiahong; Wang, Wei

    2015-06-28

    We describe a new theranostic strategy for selective delivery and spatiotemporal monitoring of mechlorethamine, a DNA alkylating agent. A photo-responsive prodrug is designed and composed of a photolabile o-nitrophenylethyl group, a DNA alkylating mechlorethamine drug and a coumarin fluorophore. Masking of the "N" in mechlorethamine in a positively charged state in the prodrug renders it inactive, non-toxic, selective and non-fluorescent. Indeed, the stable prodrug shows negligible cytotoxicity towards normal cells with and without UV activation and is completely non-fluorescent. However, upon photo-irradiation, the active mechlorethamine is released and induces efficient DNA cross-links, accompanied by a strong fluorescence enhancement (152 fold). Furthermore, DNA cross-linking activity from the release can be transformed into anticancer activity observed in in vitro studies of tumor cells. Importantly, the drug release progress and the movement can be conveniently monitored by fluorescence spectroscopy. The mechanistic study proves that the DNA cross-linking activity is mainly due to the release of DNA alkylating mechlorethamine. Altogether, the studies show the power of the theranostic strategy for efficient therapy in cancer treatment.

  2. Diphenylphosphino Styrene-Containing Homopolymers: Influence of Alkylation and Mobile Anions on Physical Properties.

    Science.gov (United States)

    Jangu, Chainika; Schultz, Alison R; Wall, Candace E; Esker, Alan R; Long, Timothy E

    2016-07-01

    Conventional free radical polymerization and post-alkylation of 4-diphenylphosphino styrene (DPPS) generate a new class of high-molecular-weight phosphonium-containing homopolymers with tunable thermal, viscoelastic, and wetting properties. Post-alkylation and subsequent anion exchange provide an effective method for tuning Tg values and thermal stability as a function of alkyl chain length and counteranion selection (X(-) , BF4 (-) , TfO(-) , and Tf2 N(-) ). Rheological characterization facilitates the generation of time-temperature-superposition (TTS) pseudomaster curves and subsequent analysis of frequency sweeps at various temperatures reveals two relaxation modes corresponding to long-range segmental motion and the onset of viscous flow. Contact angle measurements reveal the influence of counteranion selection on wetting properties, revealing increased contact angles for homopolymers containing nucleophilic counteranions. These investigations provide fundamental insight into phosphonium-containing polymers, aiming to guide future research and applications involving electro-active polymeric devices. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. The Cysteine S-Alkylation Reaction as a Synthetic Method to Covalently Modify Peptide Sequences.

    Science.gov (United States)

    Calce, Enrica; De Luca, Stefania

    2017-01-05

    Synthetic methodologies to chemically modify peptide molecules have long been investigated for their impact in the field of chemical biology. They allow the introduction of biochemical probes useful for studying protein functions, for manipulating peptides with therapeutic potential, and for structure-activity relationship investigations. The commonly used approach was the derivatization of an amino acid side chain. In this regard, the cysteine, for its unique reactivity, has been widely employed as the substrate for such modifications. Herein, we report on methodologies developed to modify the cysteine thiol group through the S-alkylation reaction. Some procedures perform the alkylation of cysteine derivatives, in order to prepare building blocks to be used during the peptide synthesis, whilst some others selectively modify peptide sequences containing a cysteine residue with a free thiol group, both in solution and in the solid phase. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Alkylation of mixed olefins with isobutane in a stratco chemical reactor

    Energy Technology Data Exchange (ETDEWEB)

    Vichailak, M. [ABB Lummus Global Inc., Houston, TX (United States); Hopper, J.R.; Yaws, C.L. [Lamar Univ., Beaumont, TX (United States); Pike, R.W. [Louisiana State Univ., Baton Rouge, LA (United States)

    1996-12-31

    The 17 reaction model for the sulfuric acid alkylation of isobutane with propylene as proposed by Langley and Pike has been used to simulate the effluent refrigeration reactor. The simulation conditions selected to minimize the formation of light and heavy by-product were determined to be: Temperature: 9 - 10 {degrees}C,- Isobutane/Olefin Ratio: 8 - 10; % Volume of Acid: 50 %. The reactor effluent composition from the simulation program has been used to compare with several sets of published data with reasonable agreement. This model has been extrapolated to simulate the alkylation of isobutane with butylenes and amylenes. The model will be optimized with commercial data. 9 refs., 6 figs., 1 tab.

  5. Catalytic Gas-Phase Production of Lactide from Renewable Alkyl Lactates.

    Science.gov (United States)

    De Clercq, Rik; Dusselier, Michiel; Makshina, Ekaterina; Sels, Bert F

    2018-03-12

    A new route to lactide, which is a key building block of the bioplastic polylactic acid, is proposed involving a continuous catalytic gas-phase transesterification of renewable alkyl lactates in a scalable fixed-bed setup. Supported TiO 2 /SiO 2 catalysts are highly selective to lactide, with only minimal lactide racemization. The solvent-free process allows for easy product separation and recycling of unconverted alkyl lactates and recyclable lactyl intermediates. The catalytic activity of TiO 2 /SiO 2 catalysts was strongly correlated to their optical properties by DR UV/Vis spectroscopy. Catalysts with high band-gap energy of the supported TiO 2 phase, indicative of a high surface spreading of isolated Ti centers, show the highest turnover frequency per Ti site. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Extractive alkylation of 6-mercaptopurine and determination in plasma by gas chromatography-mass spectrometry.

    Science.gov (United States)

    Floberg, S; Hartvig, P; Lindström, B; Lönner-Holm, G; Odlind, B

    1981-09-11

    An analytical procedure was developed for the determination of 6-mercaptopurine in plasma. Owing to the polar character and low plasma concentration of the compound, extraction and derivatization was carried out directly from the plasma sample by extractive alkylation. Determination was made using gas chromatography-mass spectrometry with multiple-ion detection. Conditions with respect to the rate of formation and the stability of the derivative formed in the extractive alkylation step were evaluated. The selectively of the method to azathioprine and to metabolites was thoroughly investigated. No 6-mercaptopurine was formed from azathioprine added to water or plasma and run through the method. The method enables the detection of 2 ng of 6 mercaptopurine in a 1.0-ml plasma sample. Quantitative determinations were done down to 10 ng/ml 6 mercaptopurine in plasma.

  7. Literature Survey and Further Studies on the 3-Alkylation of N-Unprotected 3-Monosubstituted Oxindoles. Practical Synthesis of N-Unprotected 3,3-Disubstituted Oxindoles and Subsequent Transformations on the Aromatic Ring.

    Science.gov (United States)

    Kókai, Eszter; Simig, Gyula; Volk, Balázs

    2016-12-26

    The paper provides a comprehensive review of the base-catalysed C3-alkylation of N-unprotected-3-monosubstituted oxindoles. Based on a few, non-systematic studies described in the literature using butyllithium as the deprotonating agent, an optimized method has now been elaborated, via the corresponding lithium salt, for the selective C3-alkylation of this family of compounds. The optimal excess of butyllithium and alkylating agent, and the role of the halogen atom in the latter (alkyl bromides vs. iodides) were also studied. The alkylation protocol has also been extended to some derivatives substituted at the aromatic ring. Finally, various substituents were introduced into the aromatic ring of the N-unprotected 3,3-dialkyloxindoles obtained by this optimized method.

  8. Literature Survey and Further Studies on the 3-Alkylation of N-Unprotected 3-Monosubstituted Oxindoles. Practical Synthesis of N-Unprotected 3,3-Disubstituted Oxindoles and Subsequent Transformations on the Aromatic Ring

    Directory of Open Access Journals (Sweden)

    Eszter Kókai

    2016-12-01

    Full Text Available The paper provides a comprehensive review of the base-catalysed C3-alkylation of N-unprotected-3-monosubstituted oxindoles. Based on a few, non-systematic studies described in the literature using butyllithium as the deprotonating agent, an optimized method has now been elaborated, via the corresponding lithium salt, for the selective C3-alkylation of this family of compounds. The optimal excess of butyllithium and alkylating agent, and the role of the halogen atom in the latter (alkyl bromides vs. iodides were also studied. The alkylation protocol has also been extended to some derivatives substituted at the aromatic ring. Finally, various substituents were introduced into the aromatic ring of the N-unprotected 3,3-dialkyloxindoles obtained by this optimized method.

  9. Cytotoxicity of Poly(Alkyl Cyanoacrylate Nanoparticles

    Directory of Open Access Journals (Sweden)

    Einar Sulheim

    2017-11-01

    Full Text Available Although nanotoxicology has become a large research field, assessment of cytotoxicity is often reduced to analysis of one cell line only. Cytotoxicity of nanoparticles is complex and should, preferentially, be evaluated in several cell lines with different methods and on multiple nanoparticle batches. Here we report the toxicity of poly(alkyl cyanoacrylate nanoparticles in 12 different cell lines after synthesizing and analyzing 19 different nanoparticle batches and report that large variations were obtained when using different cell lines or various toxicity assays. Surprisingly, we found that nanoparticles with intermediate degradation rates were less toxic than particles that were degraded faster or more slowly in a cell-free system. The toxicity did not vary significantly with either the three different combinations of polyethylene glycol surfactants or with particle size (range 100–200 nm. No acute pro- or anti-inflammatory activity on cells in whole blood was observed.

  10. Evaluation of fluorine-18-labeled alkylating agents as potential synthons for the labeling of oligonucleotides

    Energy Technology Data Exchange (ETDEWEB)

    Vries, E.F.J. de E-mail: e.f.j.de.vries@pet.azg.nl; Vroegh, Joke; Elsinga, P.H.; Vaalburg, Willem

    2003-04-01

    Six fluorine-18-labeled alkylating agents were selected as potentially suitable synthons for the labeling of antisense oligonucleotides. The selected synthons were evaluated in a model reaction with the monomer adenosine 5'-O-thiomonophosphate. Of these synthons, {alpha}-bromo-{alpha}'-[{sup 18}F]fluoro-m-xylene and N-(4-[{sup 18}F]fluorobenzyl)-2-bromoacetamide were found to be the most promising. Labeling with the former synthon was less complicated and time consuming and gave higher uncorrected overall yields. The latter synthon required smaller amounts of the costly precursor to achieve acceptable labeling yields.

  11. An adaptive response to alkylating agents in Aspergillus nidulans.

    Science.gov (United States)

    Hooley, P; Shawcross, S G; Strike, P

    1988-11-01

    A simple method is described for demonstrating adaptation to alkylation damage in Aspergillus nidulans. One wild type, two MNNG-sensitive, and one MNNG-resistant strain all showed improvement in colony growth when challenged with MNNG following appropriate inducing pretreatments. Other alkylating agents (MMS, EMS) could also adapt mycelium to later MNNG challenge, while 4NQO and UV could not. The inducible effect was not transmissible through conidia. A standard reversion assay based upon methG proved impractical for studying mutation frequencies during alkylation treatments owing to variations in MNNG resistance amongst revertants.

  12. A yeast mutant specifically sensitive to bifunctional alkylation

    International Nuclear Information System (INIS)

    Ruhland, A.; Kircher, M.; Wilborn, F.; Brendel, M.

    1981-01-01

    A mutation that specifically confers sensitivity to bi- and tri-functional alkylating agents is presented. No or little cross-sensitivity to radiation or monofunctional agents could be detected. Sensitivity does not seem to be due to preferential alkylation of mutant DNA as parent and mutant strain exhibit the same amount of DNA alkylation and the same pattern of DNA lesions including interstrand crosslinks. The mutation is due to a defect in a nuclear gene which has been designated SNM1 (sensitive to nitrogen mustard); it may control an important step in the repair of DNA interstrand crosslinks (orig.(AJ)

  13. Quantitative chemoproteomics for site-specific analysis of protein alkylation by 4-hydroxy-2-nonenal in cells.

    Science.gov (United States)

    Yang, Jing; Tallman, Keri A; Porter, Ned A; Liebler, Daniel C

    2015-03-03

    Protein alkylation by 4-hydroxy-2-nonenal (HNE), an endogenous lipid derived electrophile, contributes to stress signaling and cellular toxicity. Although previous work has identified protein targets for HNE alkylation, the sequence specificity of alkylation and dynamics in a cellular context remain largely unexplored. We developed a new quantitative chemoproteomic platform, which uses isotopically tagged, photocleavable azido-biotin reagents to selectively capture and quantify the cellular targets labeled by the alkynyl analogue of HNE (aHNE). Our analyses site-specifically identified and quantified 398 aHNE protein alkylation events (386 cysteine sites and 12 histidine sites) in intact cells. This data set expands by at least an order of magnitude the number of such modification sites previously reported. Although adducts formed by Michael addition are thought to be largely irreversible, we found that most aHNE modifications are lost rapidly in situ. Moreover, aHNE adduct turnover occurs only in intact cells and loss rates are site-selective. This quantitative chemoproteomics platform provides a versatile general approach to map bioorthogonal-chemically engineered post-translational modifications and their cellular dynamics in a site-specific and unbiased manner.

  14. Selective 2′-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) for direct, versatile, and accurate RNA structure analysis

    Science.gov (United States)

    Smola, Matthew J.; Rice, Greggory M.; Busan, Steven; Siegfried, Nathan A.; Weeks, Kevin M.

    2016-01-01

    SHAPE chemistries exploit small electrophilic reagents that react with the 2′-hydroxyl group to interrogate RNA structure at single-nucleotide resolution. Mutational profiling (MaP) identifies modified residues based on the ability of reverse transcriptase to misread a SHAPE-modified nucleotide and then counting the resulting mutations by massively parallel sequencing. The SHAPE-MaP approach measures the structure of large and transcriptome-wide systems as accurately as for simple model RNAs. This protocol describes the experimental steps, implemented over three days, required to perform SHAPE probing and construct multiplexed SHAPE-MaP libraries suitable for deep sequencing. These steps include RNA folding and SHAPE structure probing, mutational profiling by reverse transcription, library construction, and sequencing. Automated processing of MaP sequencing data is accomplished using two software packages. ShapeMapper converts raw sequencing files into mutational profiles, creates SHAPE reactivity plots, and provides useful troubleshooting information, often within an hour. SuperFold uses these data to model RNA secondary structures, identify regions with well-defined structures, and visualize probable and alternative helices, often in under a day. We illustrate these algorithms with the E. coli thiamine pyrophosphate riboswitch, E. coli 16S rRNA, and HIV-1 genomic RNAs. SHAPE-MaP can be used to make nucleotide-resolution biophysical measurements of individual RNA motifs, rare components of complex RNA ensembles, and entire transcriptomes. The straightforward MaP strategy greatly expands the number, length, and complexity of analyzable RNA structures. PMID:26426499

  15. Influence of diluent alkyl substitution on the extraction of Am(III) and Eu(III) by a 6,6'-bis(1,2,4-triazin-3-yl)-2,2'-bipyridine ligand dissolved in alkylated cyclohexanone diluents

    Energy Technology Data Exchange (ETDEWEB)

    Distler, P.; Spendlikova, I. [Czech Technical Univ., Prague (Czech Republic). Dept. of Nuclear Chemistry; John, J. [Czech Technical Univ., Prague (Czech Republic). Dept. of Nuclear Chemistry; Czech Technical Univ., Prague (Czech Republic). Centre for Radiochemistry and Radiation Chemistry; Harwood, L.M.; Hudson, M.J.; Lewis, F.W. [Reading Univ., Berkshire (United Kingdom). Dept. of Chemistry

    2012-07-01

    Several alkylated cyclohexanones were investigated as potential diluents for the selective extraction of Am(III) from Eu(III) from nitric acid solutions by the CyMe{sub 4}-BTBP ligand. No significant extraction of either of the metal ions was observed for these diluents themselves. In the extractions from 1 M HNO{sub 3}, 3-methylcyclohexanone and 4-methylcyclohexanone gave comparable results to cyclohexanone whereas in the extractions from 4 M HNO{sub 3}, 2-methylcyclohexanone, 3-methylcyclohexanone and 4-methylcyclohexanone all gave superior results. For the monomethylated diluents, D{sub Am} and SF{sub Am/Eu} decreased in the order of alkyl substitution 2 > 4 {proportional_to} 3. However, alkyl substitution of cyclohexanone significantly slows down the extraction kinetics compared to cyclohexanone, and the position of alkyl substitution was found to play an important role in the solvents properties. 3-Methylcyclohexanone was identified as the most promising of the diluents. (orig.)

  16. Inducible Alkylation of DNA by a Quinone Methide-Peptide Nucleic Acid Conjugate†

    Science.gov (United States)

    Liu, Yang; Rokita, Steven E.

    2012-01-01

    The reversibility of alkylation by a quinone methide intermediate (QM) avoids the irreversible consumption that plagues most reagents based on covalent chemistry and allows for site specific reaction that is controlled by the thermodynamics rather than kinetics of target association. This characteristic was originally examined with an oligonucleotide QM conjugate but broad application depends on alternative derivatives that are compatible with a cellular environment. Now, a peptide nucleic acid (PNA) derivative has been constructed and shown to exhibit an equivalent ability to delivery the reactive QM in a controlled manner. This new conjugate demonstrates high selectivity for a complementary sequence of DNA even when challenged with an alternative sequence containing a single T/T mismatch. Alkylation of non-complementary sequences is only possible when a template strand is present to co-localize the conjugate and its target. For efficient alkylation in this example, a single-stranded region of the target is required adjacent to the QM conjugate. Most importantly, the intrastrand self adducts formed between the PNA and its attached QM remained active and reversible over more than eight days in aqueous solution prior to reaction with a chosen target added subsequently. PMID:22243337

  17. Detection of Alkylating Agents using Electrical and Mechanical Means

    Science.gov (United States)

    Gerchikov, Yulia; Borzin, Elena; Gannot, Yair; Shemesh, Ariel; Meltzman, Shai; Hertzog-Ronen, Carmit; Tal, Shay; Stolyarova, Sara; Nemirovsky, Yael; Tessler, Nir; Eichen, Yoav

    2011-08-01

    Alkylating agents are reactive molecules having at least one polar bond between a carbon atom and a good leaving group. These often simple molecules are frequently used in organic synthesis, as sterilizing agents in agriculture and even as anticancer agents in medicine. Unfortunately, for over a century, some of the highly reactive alkylating agents are also being used as blister chemical warfare agents. Being relatively simple to make, the risk is that these will be applied by terrorists as poor people warfare agents. The detection and identification of such alkylating agents is not a simple task because of their high reactivity and simple structure of the reactive site. Here we report on new approaches to the detection and identification of such alkylating agents using electrical (organic field effect transistors) and mechanical (microcantilevers) means.

  18. Detection of Alkylating Agents using Electrical and Mechanical Means

    International Nuclear Information System (INIS)

    Gerchikov, Yulia; Borzin, Elena; Gannot, Yair; Shemesh, Ariel; Meltzman, Shai; Hertzog-Ronen, Carmit; Eichen, Yoav; Tal, Shay; Stolyarova, Sara; Nemirovsky, Yael; Tessler, Nir

    2011-01-01

    Alkylating agents are reactive molecules having at least one polar bond between a carbon atom and a good leaving group. These often simple molecules are frequently used in organic synthesis, as sterilizing agents in agriculture and even as anticancer agents in medicine. Unfortunately, for over a century, some of the highly reactive alkylating agents are also being used as blister chemical warfare agents. Being relatively simple to make, the risk is that these will be applied by terrorists as poor people warfare agents. The detection and identification of such alkylating agents is not a simple task because of their high reactivity and simple structure of the reactive site. Here we report on new approaches to the detection and identification of such alkylating agents using electrical (organic field effect transistors) and mechanical (microcantilevers) means.

  19. Regulation of DNA Alkylation Damage Repair: Lessons and Therapeutic Opportunities.

    Science.gov (United States)

    Soll, Jennifer M; Sobol, Robert W; Mosammaparast, Nima

    2017-03-01

    Alkylation chemotherapy is one of the most widely used systemic therapies for cancer. While somewhat effective, clinical responses and toxicities of these agents are highly variable. A major contributing factor for this variability is the numerous distinct lesions that are created upon alkylation damage. These adducts activate multiple repair pathways. There is mounting evidence that the individual pathways function cooperatively, suggesting that coordinated regulation of alkylation repair is critical to prevent toxicity. Furthermore, some alkylating agents produce adducts that overlap with newly discovered methylation marks, making it difficult to distinguish between bona fide damaged bases and so-called 'epigenetic' adducts. Here, we discuss new efforts aimed at deciphering the mechanisms that regulate these repair pathways, emphasizing their implications for cancer chemotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. 21 CFR 176.120 - Alkyl ketene dimers.

    Science.gov (United States)

    2010-04-01

    ..., processing, preparing, treating, packaging, transporting, or holding food, subject to the provisions of this... paperboard. (c) The alkyl ketene dimers may be used in the form of an aqueous emulsion which may contain...

  1. Detection of Alkylating Agents using Electrical and Mechanical Means

    Energy Technology Data Exchange (ETDEWEB)

    Gerchikov, Yulia; Borzin, Elena; Gannot, Yair; Shemesh, Ariel; Meltzman, Shai; Hertzog-Ronen, Carmit; Eichen, Yoav [Schulich Department of Chemistry, Technion-Israel Institute of Technology, Technion City, 32000, Haifa (Israel) (Israel); Tal, Shay [Present address: Systems Biology Department, Harvard Medical School, Boston, MA 02115 (United States); Stolyarova, Sara; Nemirovsky, Yael; Tessler, Nir, E-mail: chryoav@tx.technion.ac.il [Department of Electrical Engineering, Technion-Israel Institute of Technology, Technion City, 32000, Haifa (Israel)

    2011-08-17

    Alkylating agents are reactive molecules having at least one polar bond between a carbon atom and a good leaving group. These often simple molecules are frequently used in organic synthesis, as sterilizing agents in agriculture and even as anticancer agents in medicine. Unfortunately, for over a century, some of the highly reactive alkylating agents are also being used as blister chemical warfare agents. Being relatively simple to make, the risk is that these will be applied by terrorists as poor people warfare agents. The detection and identification of such alkylating agents is not a simple task because of their high reactivity and simple structure of the reactive site. Here we report on new approaches to the detection and identification of such alkylating agents using electrical (organic field effect transistors) and mechanical (microcantilevers) means.

  2. Regeneration of a deactivated USY alkylation catalyst using supercritical isobutane

    Energy Technology Data Exchange (ETDEWEB)

    Daniel M. Ginosar; David N. Ghompson; Kyle C. Burch

    2005-01-01

    Off-line, in-situ alkylation activity recovery from a completely deactivated solid acid catalyst was examined in a continuous-flow reaction system employing supercritical isobutane. A USY zeolite catalyst was initially deactivated during the liquid phase alkylation of butene with isobutane in a single-pass reactor and then varying amounts of alkylation activity were recovered by passing supercritical isobutane over the catalyst bed at different reactivation conditions. Temperature, pressure and regeneration time were found to play important roles in the supercritical isobutane regeneration process when applied to a completely deactivated USY zeolite alkylation catalyst. Manipulation of the variables that influence solvent strength, diffusivity, surface desorption, hydride transfer rates, and coke aging, strongly influence regeneration effectiveness.

  3. Solid acid zeolite catalysts for benzene/ ethylene alkylation reactions

    OpenAIRE

    2011-01-01

    Alkylation of benzene with ethylene to ethylbenzene is widely used in the petrochemical industry. Ethylbenzene is an important raw material in the petrochemical industry. It is used as feedstock for the production of styrene, an important material for plastic and rubber production.The conventional catalyst for this alkylation process is AlCl₃, which accounted for 24% of the worldwide ethylbenzene production in 2009.As utilization of this catalyst involves problems with separation, handling, s...

  4. Enantioselective γ-Alkylation of α,β-Unsaturated Malonates and Ketoesters by a Sequential Ir-Catalyzed Asymmetric Allylic Alkylation/Cope Rearrangement

    OpenAIRE

    Liu, Wen-Bo; Okamoto, Noriko; Alexy, Eric J.; Hong, Allen Y.; Tran, Kristy; Stoltz, Brian M.

    2016-01-01

    A catalytic, enantioselective ? -alkylation of ?,?-unsaturated malonates and ketoesters is reported. This strategy entails a highly regio- and enantioselective iridium-catalyzed ?-alkylation of an extended enolate, and a subsequent translocation of chirality to the ?-position via a Cope rearrangement.

  5. Mechanisms of chemoresistance to alkylating agents in malignant glioma.

    Science.gov (United States)

    Sarkaria, Jann N; Kitange, Gaspar J; James, C David; Plummer, Ruth; Calvert, Hilary; Weller, Michael; Wick, Wolfgang

    2008-05-15

    Intrinsic or acquired chemoresistance to alkylating agents is a major cause of treatment failure in patients with malignant brain tumors. Alkylating agents, the mainstay of treatment for brain tumors, damage the DNA and induce apoptosis, but the cytotoxic activity of these agents is dependent on DNA repair pathways. For example, O6-methylguanine DNA adducts can cause double-strand breaks, but this is dependent on a functional mismatch repair pathway. Thus, tumor cell lines deficient in mismatch repair are resistant to alkylating agents. Perhaps the most important mechanism of resistance to alkylating agents is the DNA repair enzyme O6-methylguanine methyltransferase, which can eliminate the cytotoxic O6-methylguanine DNA adduct before it causes harm. Another mechanism of resistance to alkylating agents is the base excision repair (BER) pathway. Consequently, efforts are ongoing to develop effective inhibitors of BER. Poly(ADP-ribose)polymerase plays a pivotal role in BER and is an important therapeutic target. Developing effective strategies to overcome chemoresistance requires the identification of reliable preclinical models that recapitulate human disease and which can be used to facilitate drug development. This article describes the diverse mechanisms of chemoresistance operating in malignant glioma and efforts to develop reliable preclinical models and novel pharmacologic approaches to overcome resistance to alkylating agents.

  6. Alcohols as alkylating agents in heteroarene C-H functionalization

    Science.gov (United States)

    Jin, Jian; MacMillan, David W. C.

    2015-09-01

    Redox processes and radical intermediates are found in many biochemical processes, including deoxyribonucleotide synthesis and oxidative DNA damage. One of the core principles underlying DNA biosynthesis is the radical-mediated elimination of H2O to deoxygenate ribonucleotides, an example of `spin-centre shift', during which an alcohol C-O bond is cleaved, resulting in a carbon-centred radical intermediate. Although spin-centre shift is a well-understood biochemical process, it is underused by the synthetic organic chemistry community. We wondered whether it would be possible to take advantage of this naturally occurring process to accomplish mild, non-traditional alkylation reactions using alcohols as radical precursors. Because conventional radical-based alkylation methods require the use of stoichiometric oxidants, increased temperatures or peroxides, a mild protocol using simple and abundant alkylating agents would have considerable use in the synthesis of diversely functionalized pharmacophores. Here we describe the development of a dual catalytic alkylation of heteroarenes, using alcohols as mild alkylating reagents. This method represents the first, to our knowledge, broadly applicable use of unactivated alcohols as latent alkylating reagents, achieved via the successful merger of photoredox and hydrogen atom transfer catalysis. The value of this multi-catalytic protocol has been demonstrated through the late-stage functionalization of the medicinal agents, fasudil and milrinone.

  7. Salvage of failed protein targets by reductive alkylation.

    Science.gov (United States)

    Tan, Kemin; Kim, Youngchang; Hatzos-Skintges, Catherine; Chang, Changsoo; Cuff, Marianne; Chhor, Gekleng; Osipiuk, Jerzy; Michalska, Karolina; Nocek, Boguslaw; An, Hao; Babnigg, Gyorgy; Bigelow, Lance; Joachimiak, Grazyna; Li, Hui; Mack, Jamey; Makowska-Grzyska, Magdalena; Maltseva, Natalia; Mulligan, Rory; Tesar, Christine; Zhou, Min; Joachimiak, Andrzej

    2014-01-01

    The growth of diffraction-quality single crystals is of primary importance in protein X-ray crystallography. Chemical modification of proteins can alter their surface properties and crystallization behavior. The Midwest Center for Structural Genomics (MCSG) has previously reported how reductive methylation of lysine residues in proteins can improve crystallization of unique proteins that initially failed to produce diffraction-quality crystals. Recently, this approach has been expanded to include ethylation and isopropylation in the MCSG protein crystallization pipeline. Applying standard methods, 180 unique proteins were alkylated and screened using standard crystallization procedures. Crystal structures of 12 new proteins were determined, including the first ethylated and the first isopropylated protein structures. In a few cases, the structures of native and methylated or ethylated states were obtained and the impact of reductive alkylation of lysine residues was assessed. Reductive methylation tends to be more efficient and produces the most alkylated protein structures. Structures of methylated proteins typically have higher resolution limits. A number of well-ordered alkylated lysine residues have been identified, which make both intermolecular and intramolecular contacts. The previous report is updated and complemented with the following new data; a description of a detailed alkylation protocol with results, structural features, and roles of alkylated lysine residues in protein crystals. These contribute to improved crystallization properties of some proteins.

  8. Salvage of Failed Protein Targets by Reductive Alkylation

    Science.gov (United States)

    Tan, Kemin; Kim, Youngchang; Hatzos-Skintges, Catherine; Chang, Changsoo; Cuff, Marianne; Chhor, Gekleng; Osipiuk, Jerzy; Michalska, Karolina; Nocek, Boguslaw; An, Hao; Babnigg, Gyorgy; Bigelow, Lance; Joachimiak, Grazyna; Li, Hui; Mack, Jamey; Makowska-Grzyska, Magdalena; Maltseva, Natalia; Mulligan, Rory; Tesar, Christine; Zhou, Min; Joachimiak, Andrzej

    2014-01-01

    The growth of diffraction-quality single crystals is of primary importance in protein X-ray crystallography. Chemical modification of proteins can alter their surface properties and crystallization behavior. The Midwest Center for Structural Genomics (MCSG) has previously reported how reductive methylation of lysine residues in proteins can improve crystallization of unique proteins that initially failed to produce diffraction-quality crystals. Recently, this approach has been expanded to include ethylation and isopropylation in the MCSG protein crystallization pipeline. Applying standard methods, 180 unique proteins were alkylated and screened using standard crystallization procedures. Crystal structures of 12 new proteins were determined, including the first ethylated and the first isopropylated protein structures. In a few cases, the structures of native and methylated or ethylated states were obtained and the impact of reductive alkylation of lysine residues was assessed. Reductive methylation tends to be more efficient and produces the most alkylated protein structures. Structures of methylated proteins typically have higher resolution limits. A number of well-ordered alkylated lysine residues have been identified, which make both intermolecular and intramolecular contacts. The previous report is updated and complemented with the following new data; a description of a detailed alkylation protocol with results, structural features, and roles of alkylated lysine residues in protein crystals. These contribute to improved crystallization properties of some proteins. PMID:24590719

  9. Alcohols as alkylating agents in heteroarene C–H functionalization

    Science.gov (United States)

    Jin, Jian; MacMillan, David W. C.

    2015-01-01

    Redox processes and radical intermediates are found in many biochemical processes, including deoxyribonucleotide synthesis and oxidative DNA damage1. One of the core principles that underlies DNA biosynthesis is the radical-mediated elimnation of H2O to deoxygenate ribonucleotides, an example of ‘spin-center shift’ (SCS)2, during which an alcohol C–O bond is cleaved, resulting in a carbon-centered radical intermediate. While SCS is a well-understood biochemical process, it is underutilized by the synthetic organic chemistry community. We wondered whether it would be possible to take advantage of this naturally occurring process to accomplish mild, non-traditional alkylations using alcohols as radical precursors. Considering traditional radical-based alkylation methods require the use of stoichiometric oxidants, elevated temperatures, or peroxides3–7, the development of a mild protocol using simple and abundant alkylating agents would have significant utility in the synthesis of diversely functionalized pharmacophores. In this manuscript, we describe the successful execution of this idea via the development of a dual catalytic alkylation of heteroarenes using alcohols as mild alkylating reagents. This method represents the first broadly applicable use of unactivated alcohols as latent alkylating reagents, achieved via the successful merger of photoredox and hydrogen atom transfer (HAT) catalysis. The utility of this multi-catalytic protocol has been demonstrated through the late-stage functionalization of the medicinal agents, fasudil and milrinone. PMID:26308895

  10. Final Technical Report [Development of Catalytic Alkylation and Fluoroalkylation Methods

    Energy Technology Data Exchange (ETDEWEB)

    Vicic, David A.

    2014-05-01

    In the early stages of this DOE-funded research project, we sought to prepare and study a well-defined nickel-alkyl complex containing tridentate nitrogen donor ligands. We found that reaction of (TMEDA)NiMe2 (1) with terpyridine ligand cleanly led to the formation of (terpyridyl)NiMe (2), which we also determined to be an active alkylation catalyst. The thermal stability of 2 was unlike that seen for any of the active pybox ligands, and enabled a number of key studies on alkyl transfer reactions to be performed, providing new insights into the mechanism of nickel-mediated alkyl-alkyl cross-coupling reactions. In addition to the mechanistic studies, we showed that the terpyridyl nickel compounds can catalytically cross-couple alkyl iodides in yields up to 98% and bromides in yields up to 46 %. The yields for the bromides can be increased up to 67 % when the new palladium catalyst [(tpy’)Pd-Ph]I is used. The best route to the targeted [(tpy)NiBr] (1) was found to involve the comproportionation reaction of [(dme)NiBr{sub 2}] and [Ni(COD){sub 2}] in the presence of two equivalents of terpyridine. This reaction was driven to high yields of product formation (72 % isolated) by the precipitation of 1 from THF solvent.

  11. Alcohols as alkylating agents in heteroarene C-H functionalization.

    Science.gov (United States)

    Jin, Jian; MacMillan, David W C

    2015-09-03

    Redox processes and radical intermediates are found in many biochemical processes, including deoxyribonucleotide synthesis and oxidative DNA damage. One of the core principles underlying DNA biosynthesis is the radical-mediated elimination of H2O to deoxygenate ribonucleotides, an example of 'spin-centre shift', during which an alcohol C-O bond is cleaved, resulting in a carbon-centred radical intermediate. Although spin-centre shift is a well-understood biochemical process, it is underused by the synthetic organic chemistry community. We wondered whether it would be possible to take advantage of this naturally occurring process to accomplish mild, non-traditional alkylation reactions using alcohols as radical precursors. Because conventional radical-based alkylation methods require the use of stoichiometric oxidants, increased temperatures or peroxides, a mild protocol using simple and abundant alkylating agents would have considerable use in the synthesis of diversely functionalized pharmacophores. Here we describe the development of a dual catalytic alkylation of heteroarenes, using alcohols as mild alkylating reagents. This method represents the first, to our knowledge, broadly applicable use of unactivated alcohols as latent alkylating reagents, achieved via the successful merger of photoredox and hydrogen atom transfer catalysis. The value of this multi-catalytic protocol has been demonstrated through the late-stage functionalization of the medicinal agents, fasudil and milrinone.

  12. Thermal aromatic Claisen rearrangement and Strecker reaction of alkyl(allyl-aryl ethers under green reaction conditions: Efficient and clean preparation of ortho-allyl phenols (naphthols and alkyl(allyloxyarene-based γ-amino nitriles

    Directory of Open Access Journals (Sweden)

    Kheila N. Silgado-Gómez

    2017-11-01

    Full Text Available Chemical transformations of 13 diverse allyl(alkyl-aryl ethers, easily prepared using Williamson reaction of different hydroxyarenes and allyl bromide and alkyl (n-butyl, n-octyl bromides, were studied. Thermal aromatic Claisen rearrangement of allyl-aryl ethers to obtain ortho-allyl phenols (naphthols employing propylene carbonate as a nontoxic and biodegradable solvent was described for the first time. The use of this green solvent allowed to enhance notably product yields and reduce significantly the reaction time comparing with the use of 1,2-dichlorobenzene, toxic solvent, which is traditionally employed in this type of Claisen rearrangement. Three-component Strecker reaction of selected alkyl(allyl-aryl ethers with formyl function on aryl fragment and, piperidine and potassium cyanide in the presence of sulfuric acid supported on silica gel (SSA, SiO2-O-SO3H under mild reaction conditions was used in the preparation of new γ-amino nitriles, analogues of alkaloid girgensohnine [2-(4-hydroxyphenyl-2-(piperidin-1-ylacetonitrile], a perspective biological model in the search for new insecticidal agrochemicals against Aedes aegypti. The use of SSA, an inexpensive and reusable solid catalyst, allowed to obtain new series of 2-[4-alkyl(allyloxyphenyl]-2-(piperidin-1-ylacetonitriles in short time at room temperature with good yields.

  13. UV absorption spectra and kinetics for alkyl and alkyl peroxy radicals originating from di-tert-butyl ether

    DEFF Research Database (Denmark)

    Nielsen, O.J.; Sehested, J.; Langer, S.

    1995-01-01

    Alkyl, (CH3)(3)COC(CH3)(2)CH2, and alkyl peroxy, (CH3)(3)COC(CH3)(2)CH2O2, radicals from di-tert-butyl ether (DTBE), have been studied in the gas phase at 296 K. A pulse radiolysis UV absorption technique was used to measure the spectra and kinetics. Absorption cross sections were quantified over...

  14. Propargyl organometallic compounds. II. Alkylation of sodium derivatives of 1-alkyl-1-aryl-2-alkynes in liquid ammonia

    International Nuclear Information System (INIS)

    Libman, N.M.; Sevryukov, Yu.P.

    1987-01-01

    In most cases the alkylation of the sodium derivatives of 1-phenyl-1-alkyl-2-alkynes by methyl, ethyl, isopropyl, and tert-butyl bromides in liquid ammonia takes place preferentially at the sp 2 -hybridized carbon atom, and this leads to the formation of the corresponding acetylenes, The regioselectivity of the reaction is explained by the greater softness of the trigonal atom of the ambient propargyl anion and its smaller screening by the solvate shell compared with the diagonal atom

  15. Beyond Alkylating Agents for Gliomas: Quo Vadimus?

    Science.gov (United States)

    Puduvalli, Vinay K; Chaudhary, Rekha; McClugage, Samuel G; Markert, James

    2017-01-01

    Recent advances in therapies have yielded notable success in terms of improved survival in several cancers. However, such treatments have failed to improve outcome in patients with gliomas for whom surgery followed by radiation therapy and chemotherapy with alkylating agents remain the standard of care. Genetic and epigenetic studies have helped identify several alterations specific to gliomas. Attempts to target these altered pathways have been unsuccessful due to various factors, including tumor heterogeneity, adaptive resistance of tumor cells, and limitations of access across the blood-brain barrier. Novel therapies that circumvent such limitations have been the focus of intense study and include approaches such as immunotherapy, targeting of signaling hubs and metabolic pathways, and use of biologic agents. Immunotherapeutic approaches including tumor-targeted vaccines, immune checkpoint blockade, antibody-drug conjugates, and chimeric antigen receptor-expressing cell therapies are in various stages of clinical trials. Similarly, identification of key metabolic pathways or converging hubs of signaling pathways that are tumor specific have yielded novel targets for therapy of gliomas. In addition, the failure of conventional therapies against gliomas has led to a growing interest among patients in the use of alternative therapies, which in turn has necessitated developing evidence-based approaches to the application of such therapies in clinical studies. The development of these novel approaches bears potential for providing breakthroughs in treatment of more meaningful and improved outcomes for patients with gliomas.

  16. Bell-shaped size selection in a bottom trawl: A case study for Nephrops directed fishery with reduced catches of cod

    DEFF Research Database (Denmark)

    Lövgren, Johan; Herrmann, Bent; Feekings, Jordan P.

    2016-01-01

    and size selectivity have motivated the development of selective systems in trawl fisheries that utilize more than one selective device simultaneously. An example can be found in the Swedish demersal trawl fishery targeting Norway lobster (Nephrops norvegicus), which simultaneously aims at avoiding catches...

  17. The influence of intraannular templates on the liquid crystallinity of shape-persistent macrocycles

    Directory of Open Access Journals (Sweden)

    Joscha Vollmeyer

    2014-04-01

    Full Text Available A series of shape-persistent phenylene–ethynylene–naphthylene–butadiynylene macrocycles with different extraannular alkyl groups and intraannular bridges is synthesized by oxidative Glaser-coupling of the appropriate precursors. The intraannular bridges serve in this case as templates that reduce the oligomerization even when the reaction is not performed under pseudo high-dilution conditions. The extraannular as well as the intraannular substituents have a strong influence on the thermal behavior of the compounds. With branched alkyl chains at the periphery, the macrocycles exhibit liquid crystalline (lc phases when the interior is empty or when the length of the alkyl bridge is just right to cross the ring. With a longer alkyl or an oligoethylene oxide bridge no lc phase is observed, most probably because the mesogene is no longer planar.

  18. Depolymerization of coal by oxidation and alkylation; Sanka bunkai to alkyl ka ni yoru sekitan kaijugo

    Energy Technology Data Exchange (ETDEWEB)

    Tomita, H.; Isoda, T.; Kusakabe, K.; Morooka, S. [Kyushu University, Fukuoka (Japan). Faculty of Engineering; Hayashi, J. [Hokkaido University, Sapporo (Japan). Center for Advanced Research of Energy Technology

    1996-10-28

    Change in depolymerization degree and coal structure was studied for depolymerization treatment of coal in various alcohol containing aqueous hydrogen peroxide. In experiment, the mixture of Yallourn coal, alcohol and aqueous hydrogen peroxide was agitated in nitrogen atmosphere of normal pressure at 70{degree}C for 12 hours. As the experimental result, the methanol solubility of only 5% of raw coal increased up to 35.2% by hydrogen peroxide treatment, while the yield of insoluble matters also decreased from 94% to 62%. Most of the gas produced during treatment was composed of inorganic gases such as CO and CO2, and its carbon loss was extremely decreased by adding alcohol. From the analytical result of carbon loss in hydrogen peroxide treatment, it was clarified that alkylation advances with introduction of alkyl group derived from alcohol into coal by hydrogen peroxide treatment under a coexistence of alcohol, and depolymerization reaction of coal itself is thus promoted by alcohol. 4 refs., 7 figs., 1 tab.

  19. Metal alkyls programmed to generate metal alkylidenes by α-H abstraction: prognosis from NMR chemical shift† †Electronic supplementary information (ESI) available: Experimental and computational details, NMR spectra, results of NMR calculations and NCS analysis, graphical representation of shielding tensors, molecular orbital diagrams of selected compounds, optimized structures for all calculated species. See DOI: 10.1039/c7sc05039a

    Science.gov (United States)

    Gordon, Christopher P.; Yamamoto, Keishi; Searles, Keith; Shirase, Satoru

    2018-01-01

    Metal alkylidenes, which are key organometallic intermediates in reactions such as olefination or alkene and alkane metathesis, are typically generated from metal dialkyl compounds [M](CH2R)2 that show distinctively deshielded chemical shifts for their α-carbons. Experimental solid-state NMR measurements combined with DFT/ZORA calculations and a chemical shift tensor analysis reveal that this remarkable deshielding originates from an empty metal d-orbital oriented in the M–Cα–Cα′ plane, interacting with the Cα p-orbital lying in the same plane. This π-type interaction inscribes some alkylidene character into Cα that favors alkylidene generation via α-H abstraction. The extent of the deshielding and the anisotropy of the alkyl chemical shift tensors distinguishes [M](CH2R)2 compounds that form alkylidenes from those that do not, relating the reactivity to molecular orbitals of the respective molecules. The α-carbon chemical shifts and tensor orientations thus predict the reactivity of metal alkyl compounds towards alkylidene generation. PMID:29675237

  20. Regioselectivity of tributyltin ether mediated alkylations. A 119Sn and 13C NMR study

    International Nuclear Information System (INIS)

    Cruzado, C.; Bernabe, M.; Martin-Lomas, M.

    1989-01-01

    The 119 Sn and 13 C NMR spectra of the stannylated species resulting from the treatment of conformationally rigid polyhydroxylated compounds with bis(tributyltin) oxide have been determined and the effect of N-methylimidazole, added as catalyst in tributyltin ether mediated regioselective alkylations, has been investigated. The observed signal intensity changes, upfield shifts, signal broadenings, and the results of variable temperature experiments have been interpreted as indicative of the selective formation of pentacoordinated tin species, involving conveniently disposed adjacent hydroxyl groups, on addition of the catalyst. On these bases, a mechanistic hypothesis for the observed regioselectivity of N-methylimidazole-catalyzed tributyltin ether mediated benzylations is proposed. 13 references, 5 tables

  1. Induction of specific Escherichia coli genes by sublethal treatments with alkylating agents.

    OpenAIRE

    Volkert, M R; Nguyen, D C

    1984-01-01

    Fusions of the lac operon to genes induced by treatment with sublethal levels of alkylating agents have been selected from random insertions of the Mu-dl(ApRlac) phage by screening for induction of beta-galactosidase activity in the presence of methyl methanesulfonate. Genetic analysis reveals that these fusions resulted from insertion of Mu-dl(ApRlac) into two regions of the chromosome. One region (aidA) is near his and, based on phenotypic effects, appears to represent insertion into the al...

  2. Geometric Topology and Shape Theory

    CERN Document Server

    Segal, Jack

    1987-01-01

    The aim of this international conference the third of its type was to survey recent developments in Geometric Topology and Shape Theory with an emphasis on their interaction. The volume contains original research papers and carefully selected survey of currently active areas. The main topics and themes represented by the papers of this volume include decomposition theory, cell-like mappings and CE-equivalent compacta, covering dimension versus cohomological dimension, ANR's and LCn-compacta, homology manifolds, embeddings of continua into manifolds, complement theorems in shape theory, approximate fibrations and shape fibrations, fibered shape, exact homologies and strong shape theory.

  3. Interactive shape metamorphosis

    Science.gov (United States)

    Chen, David T.; State, Andrei; Banks, David

    1994-01-01

    A technique for controlled metamorphosis between surfaces in 3-space is described. Well-understood techniques to produce shape metamorphosis between models in a 2D parametric space is applied. The user selects morphable features interactively, and the morphing process executes in real time on a high-performance graphics multicomputer.

  4. SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

    Science.gov (United States)

    Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

    2013-01-01

    Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for an organism's favorable response to alkylating agents. Furthermore, an individual's response to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity. PMID:22237395

  5. When alcohol is the answer: Trapping, identifying and quantifying simple alkylating species in aqueous environments.

    Science.gov (United States)

    Penketh, Philip G; Shyam, Krishnamurthy; Baumann, Raymond P; Zhu, Rui; Ishiguro, Kimiko; Sartorelli, Alan C; Ratner, Elena S

    2016-09-01

    Alkylating agents are a significant class of environmental carcinogens as well as commonly used anticancer therapeutics. Traditional alkylating activity assays have utilized the colorimetric reagent 4-(4-nitrobenzyl)pyridine (4NBP). However, 4NBP based assays have a relatively low sensitivity towards harder, more oxophilic alkylating species and are not well suited for the identification of the trapped alkyl moiety due to adduct instability. Herein we describe a method using water as the trapping agent which permits the trapping of simple alkylating electrophiles with a comparatively wide range of softness/hardness and permits the identification of donated simple alkyl moieties. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Mutants of Aspergillus nidulans with increased resistance to the alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine.

    Science.gov (United States)

    Hooley, P; Shawcross, S G; Strike, P

    1988-05-01

    The isolation and characterisation of mutants of Aspergillus nidulans showing resistance to MNNG is described. Such isolates were stable through prolonged subculture in the absence of the selective agent, and resistance segregated as an allele of a single gene in meiotic and mitotic analysis. MNNG-resistant strains showed an increase in resistance to EMS and UV irradiation but no cross-resistance to MMS was detected. Possible mechanisms of resistance to alkylating agents are discussed.

  7. Extended exposure to alkylator chemotherapy: delayed appearance of myelodysplasia.

    Science.gov (United States)

    Chamberlain, Marc C; Raizer, Jeffrey

    2009-06-01

    A case series of gliomas treated with alkylator-based chemotherapy who subsequently developed myelodysplastic syndrome (tMDS) or acute myelocytic leukemia (AML). Alkylator-based chemotherapy is recognized to be leukemogenic; however, it is infrequently described as a delayed consequence of anti-glioma treatment. Seven patients (4 men; 3 women) ages 34-69 years (median 44), with gliomas (3 Grade 2; 4 Grade 3) were treated with surgery, all but one with involved-field radiotherapy and all with alkylator-based chemotherapy (temozolomide; 6 patients, nitrosoureas; 5 patients, both agents; 5 patients). Exposure to alkylator-based chemotherapy ranged from 8 to 30 months (median 24). The diagnosis of tMDS was determined by bone marrow biopsy in 7 patients. Seven patients showed chromosomal abnormalities consistent with chemotherapy induced MDS. Three patients were diagnosed with AML as well (in two determined by bone marrow and one at autopsy). Interval from last chemotherapy exposure to diagnosis of tMDS/AML ranged from 3 to 31 months (median 24 months). Two patients were treated with bone marrow transplantation and 5 received supportive care only. Five patients have died, 2 as a consequence of recurrent brain tumor, 1 as a complication of transplantation, and 2 due to AML. Although rare, induction of tMDS/AML following extended use of alkylator-based chemotherapy may become more relevant with the evolving practice to treat gliomas for protracted periods. Future work to determine at risk patients would be important.

  8. Effect of Amphiphilic Alkyl Chain Length Upon Purified LATEX Stability

    International Nuclear Information System (INIS)

    Amira Amir Hassan; Amir Hashim Mohd Yatim

    2015-01-01

    Rubber particles in purified latex (PL) are stabilized by a film of protein and fatty acid soap (surfactant). Saturated straight-chain fatty acid soaps can assist an enhancement of latex stability. However, whether the alkyl chain length plays an important role in increasing the stability is still an issue. The aim of this study is to investigate the effect of alkyl chain length of anionic surfactant on the stability of purified latex. The fatty acid soap of decanoate (9), laurate (11), sodium dodecyl sulphate (SDS) (12) and palmitate (15) were used. The numbers in parentheses indicating the number of carbon present in alkyl chain of the soap. The results showed that the impact of alkyl chain length on the stability of latex is in the order of laurate > decanoate > SDS > palmitate > purified latex accordingly. The alkyl chain length does giving a significant effect on latex stability after longer stirring time. The particle size of latex with the presence of surfactant is greater compare to a single particle itself due to extension of particles diameter. Thus suitable interaction of the nonpolar tail of surfactant with the hydrophobic regions of latex surface played a major role in maintaining a stable latex system. (author)

  9. Solubility of gases in 1-alkyl-3methylimidazolium alkyl sulfate ionic liquids: Experimental determination and modeling

    International Nuclear Information System (INIS)

    Bermejo, María Dolores; Fieback, Tobias M.; Martín, Ángel

    2013-01-01

    Highlights: ► The solubility of CO 2 , CH 4 and C 2 H 6 in [emim][EtSO 4 ] is measured with a magnetic suspension balance. ► New data and literature results have been modeled with a Group Contribution equation of state. ► A specific group definition is required to model data of ionic liquids with a [MeSO 4 ] anion. ► Deviations between model and experiments are lower than 10% in most cases. ► Deviations of 34% are observed in the case of the solubility of ethane in the ionic liquid. -- Abstract: The solubility of different gases (carbon dioxide, methane, ethane, carbon monoxide and hydrogen) in ionic liquids with an alkyl sulfate anion has been modeled with the Group Contribution equation of state developed by Skjold-Jørgensen. New gas solubility measurements have been carried out with a high pressure magnetic suspension balance in order to cover pressure and temperature ranges not considered in previous studies and to obtain more experimental information for the correlation of parameters of the equation of state. New solubility measurements include the solubility of carbon dioxide in 1-ethyl 3-methyl imidazolium ethyl sulfate [emim][EtSO 4 ] at temperatures of 298 K and 348 K and pressures ranging from 0.3 MPa to 6.5 MPa, the solubility of methane in [emim][EtSO 4 ] at a temperature of 293 K and pressures ranging from 0.2 MPa to 10.2 MPa, and the solubility of ethane in [emim][EtSO 4 ] at temperatures of 323 K and 350 K and pressures ranging from 0.2 MPa to 4 MPa. Results show that the Group Contribution equation of state can be used to describe the solubility of gases in alkyl sulfate ionic liquids as well as infinite dilution coefficients of alkanes in the ionic liquids, with average deviations between experiments and calculations ranging from 1% to 10% in the case of mixtures with CO 2 , CO, CH 4 and H 2 with the alkyl sulfate ionic liquids to up to 34% in the case of the solubility of ethane in [emim][EtSO 4

  10. From old alkylating agents to new minor groove binders.

    Science.gov (United States)

    Puyo, Stéphane; Montaudon, Danièle; Pourquier, Philippe

    2014-01-01

    Alkylating agents represent the oldest class of anticancer agents with the approval of mechloretamine by the FDA in 1949. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in the treatment of specific malignancies, sometimes representing the unique option for the treatment of refractory tumors. Here, we are reviewing the major classes of alkylating agents, with a particular focus on the latest generations of compounds that specifically target the minor groove of the DNA. These naturally occurring derivatives have a unique mechanism of action that explains the recent regain of interest in developing new classes of alkylating agents that could be used in combination with other anticancer drugs to enhance tumor response in the clinic. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Alkylation and arylation of alkenes by transition metal complexes

    International Nuclear Information System (INIS)

    Volkova, L.G.; Levitin, I.Ya.; Vol'pin, M.E.

    1975-01-01

    In this paper are reviewed methods of alkylation and irylation of unsaturated compounds with complexes of transition metals (Rh, Pd). Analysis of alkylation and arylation of olefines with organic derivatives of transition metals, obtained as a result of exchange reactions between organic compounds of transition metals and salts of metals of the 8th group of the periodic system, allows a conclusion as to the wide possibilities of these reactions in the synthesis of various derivatives of unsaturated compounds. In all the reactions under consideration, intermediate formation of sigma-complexes is assumed. Also considered are alkylation and arylation of olefines with organic derivatives of halogens in the presence of compounds of metals of the 8th group of the periodic system, as well as arylation of olefines with aromatic compounds in the presence of salts of transition metals

  12. Alkyl Radicals as Hydrogen Bond Acceptors: Computational Evidence

    DEFF Research Database (Denmark)

    Hammerum, Steen

    2009-01-01

    Spectroscopic, energetic and structural information obtained by DFT and G3-type computational studies demonstrates that charged proton donors can form moderately strong hydrogen bonds to simple alkyl radicals. The presence of these bonds stabilizes the adducts and modifies their structure......, and gives rise to pronounced shifts of IR stretching frequencies and to increased absorption intensities. The hydrogen bond acceptor properties of alkyl radicals equal those of many conventional acceptors, e.g., the bond length changes and IR red-shifts suggest that tert-butyl radicals are slightly better...... acceptors than formaldehyde molecules, while propyl radicals are as good as H2O. The hydrogen bond strength appears to depend on the proton affinity of the proton donor and on the ionization energy of the acceptor alkyl radical, not on the donor-acceptor proton affinity difference, reflecting...

  13. Highly Effective Gene Transfection In Vivo by Alkylated Polyethylenimine

    Directory of Open Access Journals (Sweden)

    Jennifer A. Fortune

    2011-01-01

    Full Text Available We mechanistically explored the effect of increased hydrophobicity of the polycation on the efficacy and specificity of gene delivery in mice. N-Alkylated linear PEIs with varying alkyl chain lengths and extent of substitution were synthesized and characterized by biophysical methods. Their in vivo transfection efficiency, specificity, and biodistribution were investigated. N-Ethylation improves the in vivo efficacy of gene expression in the mouse lung 26-fold relative to the parent polycation and more than quadruples the ratio of expression in the lung to that in all other organs. N-Propyl-PEI was the best performer in the liver and heart (581- and 3.5-fold enhancements, resp. while N-octyl-PEI improved expression in the kidneys over the parent polymer 221-fold. As these enhancements in gene expression occur without changing the plasmid biodistribution, alkylation does not alter the cellular uptake but rather enhances transfection subsequent to cellular uptake.

  14. Radiation-chemical alkylation of olefines with adamantane

    International Nuclear Information System (INIS)

    Podkhalyuzin, A.T.; Vikulin, V.V.; Morozov, V.A.; Nazarova, M.P.; Vereshchinskii, I.V.

    1977-01-01

    Radiation-chemical alkylation of C 2 to C 4 olefines with adamantane was studied in gas phase at temperatures 270 to 430 0 C. The main reaction product is monoalkyladamantane. The reaction proceeds by a free radical chain mechanism. The effective activation energy is of the order of 8 to 10 kcal/mole. Thermal alkylation was carried out for comparison and the contribution of the thermal component to the radiation-thermal process was estimated. Liquid phase alkylation of hexafluoropropylene with adamantane was studied in the presence of solvents. Under various conditions mono- and di-substituted adamantanes are produced containing fluorine in end groups. These compounds were converted to corresponding fluoroalkenyladamantanes by dehydrofluorination. The kinetic parameters were calculated and physical-chemical data concerning some of the resulting products were determined. (author)

  15. Hydrogen-Bond Directed Regioselective Pd-Catalyzed Asymmetric Allylic Alkylation: The Construction of Chiral α-Amino Acids with Vicinal Tertiary and Quaternary Stereocenters.

    Science.gov (United States)

    Wei, Xuan; Liu, Delong; An, Qianjin; Zhang, Wanbin

    2015-12-04

    A Pd-catalyzed asymmetric allylic alkylation of azlactones with 4-arylvinyl-1,3-dioxolan-2-ones was developed, providing "branched" chiral α-amino acids with vicinal tertiary and quaternary stereocenters, in high yields and with excellent selectivities. Mechanistic studies revealed that the formation of a hydrogen bond between the Pd-allylic complex and azlactone isomer is responsible for the excellent regioselectivities. This asymmetric alkylation can be carried out on a gram scale without a loss of catalytic efficiency, and the resulting product can be further transformed to a chiral azetidine in two simple steps.

  16. Halogen effect on structure and 13C NMR chemical shift of 3,6-disubstituted-N-alkyl carbazoles

    DEFF Research Database (Denmark)

    Radula-Janik, Klaudia; Kupka, Teobald; Ejsmont, Krzysztof

    2013-01-01

    Structures of selected 3,6-dihalogeno-N-alkyl carbazole derivatives were calculated at the B3LYP/6-311++G(3df,2pd) level of theory and their 13C NMR isotropic nuclear shieldings were predicted using density functional theory (DFT). The model compounds contained 9H-, N-methyl and N-ethyl derivatives...

  17. Universality of fragment shapes.

    Science.gov (United States)

    Domokos, Gábor; Kun, Ferenc; Sipos, András Árpád; Szabó, Tímea

    2015-03-16

    The shape of fragments generated by the breakup of solids is central to a wide variety of problems ranging from the geomorphic evolution of boulders to the accumulation of space debris orbiting Earth. Although the statistics of the mass of fragments has been found to show a universal scaling behavior, the comprehensive characterization of fragment shapes still remained a fundamental challenge. We performed a thorough experimental study of the problem fragmenting various types of materials by slowly proceeding weathering and by rapid breakup due to explosion and hammering. We demonstrate that the shape of fragments obeys an astonishing universality having the same generic evolution with the fragment size irrespective of materials details and loading conditions. There exists a cutoff size below which fragments have an isotropic shape, however, as the size increases an exponential convergence is obtained to a unique elongated form. We show that a discrete stochastic model of fragmentation reproduces both the size and shape of fragments tuning only a single parameter which strengthens the general validity of the scaling laws. The dependence of the probability of the crack plan orientation on the linear extension of fragments proved to be essential for the shape selection mechanism.

  18. Solid-Phase S-Alkylation Promoted by Molecular Sieves.

    Science.gov (United States)

    Calce, Enrica; Leone, Marilisa; Mercurio, Flavia Anna; Monfregola, Luca; De Luca, Stefania

    2015-11-20

    A solid-phase S-alkylation procedure to introduce chemical modification on the cysteine sulfhydryl group of a peptidyl resin is reported. The reaction is promoted by activated molecular sieves and consists of a solid-solid process, since both the catalyst and the substrate are in a solid state. The procedure was revealed to be efficient and versatile, particularly when used in combination with the solution S-alkylation approach, allowing for the introduction of different molecular diversities on the same peptide molecule.

  19. The effect of alkylating agents on model supported metal clusters

    Energy Technology Data Exchange (ETDEWEB)

    Erdem-Senatalar, A.; Blackmond, D.G.; Wender, I. (Pittsburgh Univ., PA (USA). Dept. of Chemical and Petroleum Engineering); Oukaci, R. (CERHYD, Algiers (Algeria))

    1988-01-01

    Interactions between model supported metal clusters and alkylating agents were studied in an effort to understand a novel chemical trapping technique developed for identifying species adsorbed on catalyst surfaces. It was found that these interactions are more complex than had previously been suggested. Studies were completed using deuterium-labeled dimethyl sulfate (DMS), (CH{sub 3}){sub 2}SO{sub 4}, as a trapping agent to interact with the supported metal cluster ethylidyne tricobalt enneacarbonyl. Results showed that oxygenated products formed during the trapping reaction contained {minus}OCD{sub 3} groups from the DMS, indicating that the interaction was not a simple alkylation. 18 refs., 1 fig., 3 tabs.

  20. Direct α-alkylation of ketones with alcohols in water.

    Science.gov (United States)

    Xu, Guoqiang; Li, Qiong; Feng, Jiange; Liu, Qiang; Zhang, Zuojun; Wang, Xicheng; Zhang, Xiaoyun; Mu, Xindong

    2014-01-01

    The direct α-alkylation of ketones with alcohols has emerged as a new green protocol to construct C-C bonds with H2 O as the sole byproduct. In this work, a very simple and convenient Pd/C catalytic system for the direct α-alkylation of ketones with primary alcohols in pure water is developed. Based on this catalytic system, aqueous mixtures of dilute acetone, 1-butanol, and ethanol (mimicking ABE fermentation products) can be directly transformed into C5 -C11 or longer-chain ketones and alcohols, which are precursors to fuels. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Regeneration of zeolite catalysts of isobutane alkylation with butenes

    Energy Technology Data Exchange (ETDEWEB)

    Manza, I.A.; Tsupryk, I.N.; Bartyshevskii, V.A.; Gaponenko, O.I.; Petrilyak, K.I.

    1986-12-10

    The industrial adoption of alkylation of isoalkanes with alkenes is held back by the rapid and irreversible deactivation of the zeolite catalysts appropriate to the process. This paper is aimed specifically at the restoration of the catalytic activity and increase in the service life of zeolite alkylation catalysts. The catalyst chosen for the investigation was HLaCaNaX zeolite both unmodified and modified with various multivalence cations. The thermochemical and oxidative regeneration process as well as the equipment utilized are described. Both the advantages and the drawbacks of the method are given; explanations for the possibly irreversible losses of the catalytic properties in the regenerated zeolites are also put forward.

  2. Across-environment genetic correlations and the frequency of selective environments shape the evolutionary dynamics of growth rate in Impatiens capensis.

    Science.gov (United States)

    Stinchcombe, John R; Izem, Rima; Heschel, M Shane; McGoey, Brechann V; Schmitt, Johanna

    2010-10-01

    Trade-offs can exist within and across environments, and constrain evolutionary trajectories. To examine the effects of competition and resource availability on trade-offs, we grew individuals of recombinant inbred lines of Impatiens capensis in a factorial combination of five densities with two light environments (full light and neutral shade) and used a Bayesian logistic growth analysis to estimate intrinsic growth rates. To estimate across-environment constraints, we developed a variance decomposition approach to principal components analysis, which accounted for sample size, model-fitting, and within-RIL variation prior to eigenanalysis. We detected negative across-environment genetic covariances in intrinsic growth rates, although only under full-light. To evaluate the potential importance of these covariances, we surveyed natural populations of I. capensis to measure the frequency of different density environments across space and time. We combined our empirical estimates of across-environment genetic variance-covariance matrices and frequency of selective environments with hypothetical (yet realistic) selection gradients to project evolutionary responses in multiple density environments. Selection in common environments can lead to correlated responses to selection in rare environments that oppose and counteract direct selection in those rare environments. Our results highlight the importance of considering both the frequency of selective environments and the across-environment genetic covariances in traits simultaneously. © 2010 The Author(s). Journal compilation © 2010 The Society for the Study of Evolution.

  3. A Theoretical Study of the Mechanism of the Alkylation of Guanine by N- Nitroso Compounds.

    Science.gov (United States)

    1992-01-01

    these chemical agents alkylate DNA, but, as yet, the precise mechanism is unknown. What is known is that the result is a DNA-mutagen adduct with an alkyl ... nitrosoureas , Singer et. al. found that about 25% of the alkylation caused by MNU was on the DNA phospate backbone while, for ENU, phosphate...sites. 1.3 Mutagenicity of N-Nitroso Compounds In early experimental work with agents which alkylate DNA, comparisons of ultraviolet absorption

  4. Immobilization of lipases on alkyl silane modified magnetic nanoparticles: effect of alkyl chain length on enzyme activity.

    Directory of Open Access Journals (Sweden)

    Jiqian Wang

    Full Text Available BACKGROUND: Biocatalytic processes often require a full recycling of biocatalysts to optimize economic benefits and minimize waste disposal. Immobilization of biocatalysts onto particulate carriers has been widely explored as an option to meet these requirements. However, surface properties often affect the amount of biocatalysts immobilized, their bioactivity and stability, hampering their wide applications. The aim of this work is to explore how immobilization of lipases onto magnetite nanoparticles affects their biocatalytic performance under carefully controlled surface modification. METHODOLOGY/PRINCIPAL FINDINGS: Magnetite nanoparticles, prepared through a co-precipitation method, were coated with alkyl silanes of different alkyl chain lengths to modulate their surface hydrophobicity. Candida rugosa lipase was then directly immobilized onto the modified nanoparticles through hydrophobic interaction. Enzyme activity was assessed by catalytic hydrolysis of p-nitrophenyl acetate. The activity of immobilized lipases was found to increase with increasing chain length of the alkyl silane. Furthermore, the catalytic activities of lipases immobilized on trimethoxyl octadecyl silane (C18 modified Fe(3O(4 were a factor of 2 or more than the values reported from other surface immobilized systems. After 7 recycles, the activities of the lipases immobilized on C18 modified nanoparticles retained 65%, indicating significant enhancement of stability as well through hydrophobic interaction. Lipase immobilized magnetic nanoparticles facilitated easy separation and recycling with high activity retaining. CONCLUSIONS/SIGNIFICANCE: The activity of immobilized lipases increased with increasing alkyl chain length of the alkyl trimethoxy silanes used in the surface modification of magnetite nanoparticles. Lipase stability was also improved through hydrophobic interaction. Alkyl silane modified magnetite nanoparticles are thus highly attractive carriers for

  5. Immobilization of lipases on alkyl silane modified magnetic nanoparticles: effect of alkyl chain length on enzyme activity.

    Science.gov (United States)

    Wang, Jiqian; Meng, Gang; Tao, Kai; Feng, Min; Zhao, Xiubo; Li, Zhen; Xu, Hai; Xia, Daohong; Lu, Jian R

    2012-01-01

    Biocatalytic processes often require a full recycling of biocatalysts to optimize economic benefits and minimize waste disposal. Immobilization of biocatalysts onto particulate carriers has been widely explored as an option to meet these requirements. However, surface properties often affect the amount of biocatalysts immobilized, their bioactivity and stability, hampering their wide applications. The aim of this work is to explore how immobilization of lipases onto magnetite nanoparticles affects their biocatalytic performance under carefully controlled surface modification. Magnetite nanoparticles, prepared through a co-precipitation method, were coated with alkyl silanes of different alkyl chain lengths to modulate their surface hydrophobicity. Candida rugosa lipase was then directly immobilized onto the modified nanoparticles through hydrophobic interaction. Enzyme activity was assessed by catalytic hydrolysis of p-nitrophenyl acetate. The activity of immobilized lipases was found to increase with increasing chain length of the alkyl silane. Furthermore, the catalytic activities of lipases immobilized on trimethoxyl octadecyl silane (C18) modified Fe(3)O(4) were a factor of 2 or more than the values reported from other surface immobilized systems. After 7 recycles, the activities of the lipases immobilized on C18 modified nanoparticles retained 65%, indicating significant enhancement of stability as well through hydrophobic interaction. Lipase immobilized magnetic nanoparticles facilitated easy separation and recycling with high activity retaining. The activity of immobilized lipases increased with increasing alkyl chain length of the alkyl trimethoxy silanes used in the surface modification of magnetite nanoparticles. Lipase stability was also improved through hydrophobic interaction. Alkyl silane modified magnetite nanoparticles are thus highly attractive carriers for enzyme immobilization enabling efficient enzyme recovery and recycling.

  6. 40 CFR 721.10143 - Amines, bis (C11-14-branched and linear alkyl).

    Science.gov (United States)

    2010-07-01

    ... linear alkyl). 721.10143 Section 721.10143 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10143 Amines, bis (C11-14-branched and linear alkyl). (a) Chemical..., bis (C11-14-branched and linear alkyl) (PMN P-06-733; CAS No. 900169-60-0) is subject to reporting...

  7. 40 CFR 721.520 - Alanine, N-(2-carboxyethyl)-N-alkyl-, salt.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alanine, N-(2-carboxyethyl)-N-alkyl... Specific Chemical Substances § 721.520 Alanine, N-(2-carboxyethyl)-N-alkyl-, salt. (a) Chemical substance... alanine, N-(2-carboxyethyl)-N- alkyl-, salt (P-89-336) is subject to reporting under this section for the...

  8. 40 CFR 721.5985 - Fatty alkyl phosphate, alkali metal salt (generic).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Fatty alkyl phosphate, alkali metal... Specific Chemical Substances § 721.5985 Fatty alkyl phosphate, alkali metal salt (generic). (a) Chemical... as a fatty alkyl phosphate, alkali metal salt (PMN P-99-0385) is subject to reporting under this...

  9. 40 CFR 721.2565 - Alkylated sulfonated diphenyl oxide, alkali and amine salts.

    Science.gov (United States)

    2010-07-01

    ..., alkali and amine salts. 721.2565 Section 721.2565 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.2565 Alkylated sulfonated diphenyl oxide, alkali and... substances identified as alkylated sulfonated diphenyl oxide, alkali salt (PMN P-93-352) and alkylated...

  10. A Short Review on the Synthetic Strategies of Duocarmycin Analogs that are Powerful DNA Alkylating Agents.

    Science.gov (United States)

    Patil, Pravin C; Satam, Vijay; Lee, Moses

    2015-01-01

    The duocarmycins and CC-1065 are members of a class of DNA minor groove, AT-sequence selective, and adenine-N3 alkylating agents, isolated from Streptomyces sp. that exhibit extremely potent cytotoxicity against the growth of cancer cells grown in culture. Initial synthesis and structural modification of the cyclopropa[c] pyrrolo[3,2-e]indole (CPI) DNA-alkylating motif as well as the indole non-covalent binding region in the 1980s have led to several compounds that entered clinical trials as potential anticancer drugs. However, due to significant systemic toxicity none of the analogs have passed clinical evaluation. As a result, the intensity in the design, synthesis, and development of novel analogs of the duocarmycins has continued. Accordingly, in this review, which covers a period from the 1990s through the present time, the design and synthesis of duocarmycin SA are described along with the synthesis of novel and highly cytotoxic analogs that lack the chiral center. Examples of achiral analogs of duocarmycin SA described in this review include seco-DUMSA (39 and 40), seco-amino-CBI-TMI (13, Centanamycin), and seco-hydroxy-CBI-TMI (14). In addition, another novel class of biologically active duocarmycin SA analogs that contained the seco-iso-cyclopropylfurano[2,3-e]indoline (seco-iso-CFI) and seco-cyclopropyltetrahydrofurano[2,3-f]quinoline (seco-CFQ) DNA alkylating submit was also designed and synthesized. The synthesis of seco-iso-CFI-TMI (10, Tafuramycin A) and seco-CFQ-TMI (11, Tafuramycin B) is included in this review.

  11. Inhibition of RecBCD enzyme by antineoplastic DNA alkylating agents.

    Science.gov (United States)

    Dziegielewska, Barbara; Beerman, Terry A; Bianco, Piero R

    2006-09-01

    To understand how bulky adducts might perturb DNA helicase function, three distinct DNA-binding agents were used to determine the effects of DNA alkylation on a DNA helicase. Adozelesin, ecteinascidin 743 (Et743) and hedamycin each possess unique structures and sequence selectivity. They bind to double-stranded DNA and alkylate one strand of the duplex in cis, adding adducts that alter the structure of DNA significantly. The results show that Et743 was the most potent inhibitor of DNA unwinding, followed by adozelesin and hedamycin. Et743 significantly inhibited unwinding, enhanced degradation of DNA, and completely eliminated the ability of the translocating RecBCD enzyme to recognize and respond to the recombination hotspot chi. Unwinding of adozelesin-modified DNA was accompanied by the appearance of unwinding intermediates, consistent with enzyme entrapment or stalling. Further, adozelesin also induced "apparent" chi fragment formation. The combination of enzyme sequestering and pseudo-chi modification of RecBCD, results in biphasic time-courses of DNA unwinding. Hedamycin also reduced RecBCD activity, albeit at increased concentrations of drug relative to either adozelesin or Et743. Remarkably, the hedamycin modification resulted in constitutive activation of the bottom-strand nuclease activity of the enzyme, while leaving the ability of the translocating enzyme to recognize and respond to chi largely intact. Finally, the results show that DNA alkylation does not significantly perturb the allosteric interaction that activates the enzyme for ATP hydrolysis, as the efficiency of ATP utilization for DNA unwinding is affected only marginally. These results taken together present a unique response of RecBCD enzyme to bulky DNA adducts. We correlate these effects with the recently determined crystal structure of the RecBCD holoenzyme bound to DNA.

  12. Concerted bis-alkylating reactivity of clerocidin towards unpaired cytosine residues in DNA

    Science.gov (United States)

    Richter, Sara N.; Menegazzo, Ileana; Fabris, Daniele; Palumbo, Manlio

    2004-01-01

    Clerocidin (CL) is a topoisomerase II poison, which cleaves DNA irreversibly at guanines (G) and reversibly at cytosines (C). Furthermore, the drug can induce enzyme-independent strand breaks at the G and C level. It has been previously shown that G-damage is induced by alkylation of the guanine N7, followed by spontaneous depurination and nucleic acid cleavage, whereas scission at C is obtained only after treatment with hot alkali, and no information is available to explain the nature of this damage. We present here a systematic study on the reactivity of CL towards C both in the DNA environment and in solution. Selected synthetic derivatives were employed to evaluate the role of each chemical group of the drug. The structure of CL–dC adduct was then characterized by tandem mass spectrometry and NMR: the adduct is a stable condensed ring system resulting from a concerted electrophilic attack of the adjacent carbonyl and epoxide groups of CL towards the exposed NH2 and N3, respectively. This reaction mechanism, shown here for the first time, is characterized by faster kinetic rates than alkylation at G, due to the fact that the rate-determining step, alkylation at the epoxide, is an intramolecular process, provided a Schiff base linking CL and C can rapidly form, whereas the corresponding reaction of G N7 is intermolecular. These results provide helpful hints to explain the reversible/irreversible nature of topoisomerase II mediated DNA damage produced by CL at C/G steps. PMID:15494453

  13. Preparation of shaped bodies

    International Nuclear Information System (INIS)

    Sutcliffe, P.W.; Isaacs, J.W.; Lyon, C.E.

    1979-01-01

    A method for the preparation of a shaped body includes pressing a powder to give a 'green' shaped body, the powder having been made by comminuting a material prepared by means of a gelation process, the material prior to comminuting being of a selected physical configuration (e.g. spherical). Thus, a material prepared by means of a gelation process can be transported and handled in an environmentally desirable, substantially dust-free form (e.g. spherical particles) and then comminuted to produce a powder for pressing into e.g. a shaped nuclear fuel body (e.g. pellets of (70%U/30%Pu)O 2 ), which can be sintered. (author)

  14. Frequency and spectrum of chlorophyll-deficient mutations in rice after treatment with radiation and alkylating agents

    International Nuclear Information System (INIS)

    Bhan, A.K.; Kaul, M.L.H.

    1976-01-01

    Three varieties of rice were treated with gamma rays and two alkylating agents EMS and DES, separately and in combinations, with a view to finding out the frequency and spectrum of chlorophyll mutations in relation to the genotype and the nature of the mutagen. Chlorophyll mutation frequency was enhanced with increasing dose but dropped at very high doses (doses that induced over 90% seeding lethality in M 1 ). The fall was attributed to either the increased mutated sector and diplontic selection after exposure to very high doses or relatively high resistance of some of the seeds. Among chlorophyll mutants in M 2 induced by radiations as well as alkylating agents, the albina type formed the majority class. EMS induced a significantly higher proportion of albinas than did gamma rays

  15. Synthesis and Performance of a Biomimetic Indicator for Alkylating Agents.

    Science.gov (United States)

    Provencher, Philip A; Love, Jennifer A

    2015-10-02

    4-(4-Nitrobenzyl)pyridine (NBP) is a colorimetric indicator compound for many types of carcinogenic alkylating agents. Because of the similar reactivity of NBP and guanine in DNA, NBP serves as a DNA model. NBP assays are used in the toxicological screening of pharmaceutical compounds, detection of chemical warfare agents, environmental hygiene technology, preliminary toxicology tests, mutagenicity of medicinal compounds, and other chemical analyses. Nevertheless, the use of NBP as a DNA model suffers from the compound's low water solubility, its lack of reactive oxygen sites, and dissimilar steric encumbrance compared to DNA. We report herein the design and synthesis of NBP derivatives that address some of these issues. These derivatives have been tested in solution and found to be superior in the colorimetric assay of the alkylating anticancer drug cyclophosphamide. The derivatives have also been integrated into a polymeric silica material which changes color upon the exposure to dangerous alkylating agents, such as iodomethane vapor, without the need for an exogenous base. This material modernizes the NBP assay from a time-consuming laboratory analysis to a real-time solid state sensor, which requires neither solvent nor additional reagents and can detect both gas- and solution-phase alkylating agents.

  16. Synthesis and Antiangiogenic Activity of N-Alkylated Levamisole Derivatives

    DEFF Research Database (Denmark)

    Hansen, Anders N.; Bendiksen, Christine D.; Sylvest, Lene

    2012-01-01

    profile, was recently shown to be an inhibitor of angiogenesis in vitro and exhibited tumor growth inhibition in mice. Here we describe the synthesis and in vitro evaluation of a series of N-alkylated analogues of levamisole with the aim of characterizing structure-activity relationships with regard...

  17. Leukemia after therapy with alkylating agents for childhood cancer

    International Nuclear Information System (INIS)

    Tucker, M.A.; Meadows, A.T.; Boice, J.D. Jr.

    1987-01-01

    The risk of leukemia was evaluated in 9,170 2-or-more-year survivors of childhood cancer in the 13 institutions of the Late Effects Study Group. Secondary leukemia occurred in 22 nonreferred individuals compared to 1.52 expected, based on general population rates [relative risk (RR) = 14; 95% confidence interval (CI), 9-22]. The influence of therapy for the first cancer on subsequent leukemia risk was determined by a case-control study conducted on 25 cases and 90 matched controls. Treatment with alkylating agents was associated with a significantly elevated risk of leukemia (RR = 4.8; 95% CI, 1.2-18.9). A strong dose-response relationship was also observed between leukemia risk and total dose of alkylating agents, estimated by an alkylator score. The RR of leukemia reached 23 in the highest dose category. Radiation therapy, however, did not increase risk. Although doxorubicin was also identified as a possible risk factor, the excess risk of leukemia following treatment for childhood cancer appears almost entirely due to alkylating agents

  18. Alkyl chitosan film-high strength, functional biomaterials.

    Science.gov (United States)

    Lu, Li; Xing, Cao; Xin, Shen; Shitao, Yu; Feng, Su; Shiwei, Liu; Fusheng, Liu; Congxia, Xie

    2017-11-01

    Biofilm with strong tensile strength is a topic item in the area of tissue engineering, medicine engineering, and so forth. Here we introduced an alkyl chitosan film with strong tensile strength and its possibility for an absorbable anticoagulation material in vivo was tested in the series of blood test, such as dynamic coagulation time, plasma recalcification time and hemolysis. Alkyl chitosan film was a better biomaterial than traditional chitosan film in the anticoagulation, tissue compatibility and cell compatibility. The unique trait of alkyl chitosan film may be for its greater contact angle and hydrophobicity ability to reduce the adsorption capacity for the blood component and the activity of fibrinolytic enzymes, enhance the antibacterial capacity than chitosan film. Moreover, none of chitosan film or butyl chitosan film exhibited quick inflammation or other disadvantage and degraded quickly by implanted test. Therefore, Alkyl chitosan film is of prospective properties as an implantable, absorbable agent for tissue heals, and this material need further research. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3034-3041, 2017. © 2017 Wiley Periodicals, Inc.

  19. A Green Alternative to Aluminum Chloride Alkylation of Xylene

    Science.gov (United States)

    Sereda, Grigoriy A.; Rajpara, Vikul B.

    2007-01-01

    An acutely less toxic 2-bromobutane is used to develop a simple graphite-promoted procedure of alkylation of p-xylene. It is further demonstrated that aluminum chloride is not required, the need for aqueous workup is eliminated, waste solutions are not produced and the multiple use of the catalyst is allowed.

  20. An efficient, heterogeneous and reusable catalyst for -alkylation of ...

    Indian Academy of Sciences (India)

    Fe(HSO4)3(FHS) was used as an efficient catalyst for the heterogeneous addition of a series of benzylic and allylic alcohols to various -dicarbonyl compounds, which afforded moderate to excellent yields of -alkylated products in 1,2-dichloroethane. In comparison with the previous methods, the present research ...

  1. Alkoxy(alkyl)silylalkyl derivatives of nitrogen-containing heterocycles

    International Nuclear Information System (INIS)

    Trofimova, Ol'ga M; Voronkov, Mikhail G; Chernov, Nikolai F

    1999-01-01

    The published data on the synthesis, properties and transformations of alkoxy(alkyl)silylalkyl derivatives of nitrogen-containing heterocycles of the general formula Het(CH 2 ) n SiX 3 are surveyed and systematised. Data on the biological activities and applications of these compounds are presented. The bibliography includes 255 references.

  2. 40 CFR 721.10087 - Substituted alkyl phosphine oxide (generic).

    Science.gov (United States)

    2010-07-01

    ... are: (i) Industrial, commercial, and consumer activities. Requirements as specified in § 721.80(s... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted alkyl phosphine oxide (generic). 721.10087 Section 721.10087 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

  3. Alkylation of isobutane with light olefins catalyzed by zeolite beta

    NARCIS (Netherlands)

    Nivarthy, G.S.; Feller, A.P.; Seshan, Kulathuiyer; Lercher, J.A.

    2000-01-01

    Alkylation of isobutane with ethene and propene was studied over an H-BEA catalyst in a well-stirred reactor. Under similar conditions of space velocity and paraffin-to-olefin feed ratio, lower initial olefin conversions were observed with ethene or propene than those reported earlier for butene.

  4. Isobutane/olefin alkylation - present state and recent developments

    Energy Technology Data Exchange (ETDEWEB)

    Feller, A.; Lercher, J.A. [Inst. fuer Technische Chemie, Technische Univ. Muenchen (Germany)

    2002-12-01

    Isobutane/alkene alkylation is reviewed with respect to recent process developments based on liquid and solid acid catalysts. The reaction mechanism and its consequences for both liquid and solid acid based processes is briefly discussed. Established liquid acid catalyzed processes are introduced followed by the description of new processes based on solid acids, which are currently under development. (orig.)

  5. Copper-Catalyzed Synthesis of Mixed Alkyl Aryl Phosphonates

    NARCIS (Netherlands)

    Fañanás-Mastral, Martín; Feringa, Ben L

    2014-01-01

    Copper-catalysis allows the direct oxygenarylation of dialkyl phosphonates with diaryliodonium salts. This novel methodology proceeds with a wide range of phosphonates and phosphoramidates under mild conditions and gives straightforward access to valuable mixed alkyl aryl phosphonates in very good

  6. A new route alpha-alkyl-alpha-fluoromethylenebisphosphonates

    Czech Academy of Sciences Publication Activity Database

    Beier, Petr; Opekar, Stanislav; Zibinsky, M.; Bychinskaya, I.; Prakash, G. K. S.

    2011-01-01

    Roč. 9, č. 11 (2011), s. 4035-4038 ISSN 1477-0520 R&D Projects: GA ČR GP203/08/P310 Institutional research plan: CEZ:AV0Z40550506 Keywords : fluorine * phosphonate * alkylation Subject RIV: CC - Organic Chemistry Impact factor: 3.696, year: 2011

  7. On the Boiling Points of the Alkyl Halides.

    Science.gov (United States)

    Correia, John

    1988-01-01

    Discusses the variety of explanations in organic chemistry textbooks of a physical property of organic compounds. Focuses on those concepts explaining attractive forces between molecules. Concludes that induction interactions play a major role in alkyl halides and other polar organic molecules and should be given wider exposure in chemistry texts.…

  8. Students' Understanding of Alkyl Halide Reactions in Undergraduate Organic Chemistry

    Science.gov (United States)

    Cruz-Ramirez de Arellano, Daniel

    2013-01-01

    Organic chemistry is an essential subject for many undergraduate students completing degrees in science, engineering, and pre-professional programs. However, students often struggle with the concepts and skills required to successfully solve organic chemistry exercises. Since alkyl halides are traditionally the first functional group that is…

  9. Alkyltransferase-like proteins: brokers dealing with alkylated DNA bases.

    Science.gov (United States)

    Schärer, Orlando D

    2012-07-13

    A new pathway for the repair of DNA alkylation damage is described in this issue of Molecular Cell (Latypov et al., 2012). Alkyltransferase-like enzymes mark O(6)-alkylguanine lesions and, depending on adduct size, channel them into global genome or transcription-coupled nucleotide excision repair pathways. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Predicting Alkylate Yield and its Hydrocarbon Composition for Sulfuric Acid Catalyzed Isobutane Alkylation with Olefins Using the Method of Mathematical Modeling

    OpenAIRE

    Nurmakanova, А. Е.; Ivashkina, Elena Nikolaevna; Ivanchina, Emilia Dmitrievna; Dolganov, I. A.; Boychenko, S. S.

    2015-01-01

    The article provides the results of applied mathematical model of isobutane alkylation with olefins catalyzed by sulfuric acid to predict yield and hydrocarbon composition of alkylate caused by the changes in the feedstock composition and process parameters. It is shown that the alkylate produced from feedstock with less mass fraction of isobutane has lower octane value. Wherein the difference in composition of the feedstock contributes to antiknock index by the amount of 1.0-2.0 points.

  11. Design of novel antitumor DNA alkylating agents: the benzacronycine series.

    Science.gov (United States)

    David-Cordonnier, Marie-Hélène; Laine, William; Gaslonde, Thomas; Michel, Sylvie; Tillequin, Francois; Koch, Michel; Léonce, Stéphane; Pierré, Alain; Bailly, Christian

    2004-03-01

    Acronycine, a natural alkaloid originally extracted from the bark of the Australian ash scrub Acronychia baueri, has shown a significant antitumor activity in animal models. Acronycine has been tested against human cancers in the early 1980s, but the clinical trials showed modest therapeutic effects and its development was rapidly discontinued. In order to optimize the antineoplastic effect, different benzoacronycine derivatives were synthesized. Among those, the di-acetate compound S23906-1 was recently identified as a promising anticancer drug candidate and a novel alkylating agent specifically reacting with the exocylic 2-NH2 group of guanines in DNA. The study of DNA bonding capacity of acronycine derivatives leads to the identification of the structural requirements for DNA alkylation. In nearly all cases, the potent alkylating agents, such as S23906-1, were found to be much more cytotoxic than the unreactive analogs such as acronycine itself or diol derivatives. Alkylation of DNA by the monoacetate derivative S28687-1, which is a highly reactive hydrolysis metabolite of S23906-1, occurs with a marked preference for the N2 position of guanine. Other bionucleophiles can react with S23906-1. The benzacronycine derivatives, which efficiently alkylate DNA, also covalently bind to the tripeptide glutathione (GSH) but not to the oxidized product glutathione disulfide. Here we review the reactivity of S23906-1 and some derivatives toward DNA and GSH. The structure-activity relationships in the benzacronycine series validate the reaction mechanism implicating DNA as the main molecular target. S23906-1 stands as the most promising lead of a medicinal chemistry program aimed at discovering novel antitumor drugs based on the acronycine skeleton.

  12. Process and analytical studies of enhanced low severity co-processing using selective coal pretreatment

    Energy Technology Data Exchange (ETDEWEB)

    Baldwin, R.M.; Miller, R.L.

    1991-12-01

    The findings in the first phase were as follows: 1. Both reductive (non-selective) alkylation and selective oxygen alkylation brought about an increase in liquefaction reactivity for both coals. 2. Selective oxygen alkylation is more effective in enhancing the reactivity of low rank coals. In the second phase of studies, the major findings were as follows: 1. Liquefaction reactivity increases with increasing level of alkylation for both hydroliquefaction and co-processing reaction conditions. 2. the increase in reactivity found for O-alkylated Wyodak subbituminous coal is caused by chemical changes at phenolic and carboxylic functional sites. 3. O-methylation of Wyodak subbituminous coal reduced the apparent activation energy for liquefaction of this coal.

  13. Study of hydrogen mobility by hydrogen-deuterium exchange. II. Theoretical kinetic study in alkyl and amino-alkyl pyrimidines

    International Nuclear Information System (INIS)

    Pompon, Alain

    1975-01-01

    Alkyl groups bound to the pyrimidine ring can be deuterium substituted on the carbon adjacent to the ring, in acidic D 2 O; kinetic equations corresponding to various exchange mechanism hypothesis are established. It is shown that theoretical and experimental results can be compared in order to precise the mechanism and to measure the characteristic parameters of the exchange reaction [fr

  14. 4-Alkyl radical extrusion in the cytochrome P-450-catalyzed oxidation of 4-alkyl-1,4-dihydropyridines

    International Nuclear Information System (INIS)

    Lee, J.S.; Jacobsen, N.E.; Ortiz de Montellano, P.R.

    1988-01-01

    Rat liver microsomal cytochrome P-450 oxidizes the 4-methyl, 4-ethyl (DDEP), and 4-isopropyl derivatives of 3,5-bis(carbethoxy)-2,6-dimethyl-1,4,-dihydropyridine to mixtures of the corresponding 4-alkyl and 4-dealkyl pyridines. A fraction of the total microsomal enzyme is destroyed in the process. The 4-dealkyl to 4-alkyl pyridine metabolite ratio, the extent of cytochrome P-450 destruction, and the rate of spin-trapped radical accumulation are correlated in a linear inverse manner with the homolytic or heterolytic bond energies of the 4-alkyl groups of the 4-alkyl-1,4-dihydropyridines. No isotope effects are observed on the pyridine matabolite ratio, the destruction of cytochrome P-450, or the formation of ethyl radicals when [4- 2 H]DDEP is used instead of DDEP. N-Methyl- and N-ethyl-DDEP undergo N-dealkylation rather than aromatization but N-phenyl-DDEP is oxidized to a mixture of the 4-ethyl and 4-deethyl N-phenylpyridinium metabolites. In contrast to the absence of an isotope effect in the oxidation of DDEP, the 4-deethyl to 4-ethyl N-phenylpyridinium metabolite ratio increases 6-fold when N-phenyl[4- 2 H]DDEP is used. The results support the hypothesis that cytochrome P-450 catalyzes the oxidation of dihydropyridines to radical cations and show that the radical cations decay to nonradical products by multiple, substituent-dependent, mechanisms

  15. Determination of alkylation of bacterial DNA as a rapid test for toxicological evaluation of alkylating xenobiotic agents

    Energy Technology Data Exchange (ETDEWEB)

    Botzenhart, K.; Waldner-Sander, S.; Schweinsberg, F.

    1986-05-01

    Alkylated purine bases from hydrolized DNA can be separated by HPLC and quantified with a fluorescence detector. We applied this method to bacterial DNA. 7-methylguanine was detected after treatment of Serratia marcescens with iodoacetamide, dimethyl sulfate and with polluted air.

  16. Considering photodynamic therapy as a therapeutic modality in selected cases of dome-shaped macula complicated by foveal serous retinal detachment.

    Science.gov (United States)

    Arapi, Ilir; Neri, Piergiorgio; Mariotti, Cesare; Gesuita, Rosaria; Pirani, Vittorio; Freddo, Francesco; Lutaj, Pajtim; Giovannini, Alfonso

    2015-02-01

    To study the role of photodynamic therapy (PDT) as a therapeutic modality in myopic patients with dome-shaped macula (DSM) associated with foveal serous retinal detachment (SRD). Retrospective interventional case series. The medical records of 10 consecutive myopic patients (10 eyes) with DSM associated with subfoveal SRD and treated with PDT were reviewed. Visual gain and loss were considered as increasing or decreasing of two or more lines of best corrected visual acuity (BCVA), respectively, and eyes with fluid resolution were deemed responsive to PDT. All eyes underwent several PDT treatments, with a median of three and a median follow-up time of 15.5 months. At final follow-up, six eyes (60%) showed complete resolution of the foveal SRD. The baseline hypocyanescent macular area observed during late indocyanine green angiography (ICGA) frames was significantly lower in the group of patients who responded to PDT and had an increase of at least two Snellen lines in BCVA (P = .01). Data suggest that myopic eyes associated with DSM and foveal SRD may be responsive to PDT, showing total resolution of fluid accumulation and positive BCVA changes if baseline ICGA findings show evidence of a limited hypocyanescent macular area. Copyright 2015, SLACK Incorporated.

  17. 2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53-compromised cells.

    Science.gov (United States)

    Bauer, Matthias R; Joerger, Andreas C; Fersht, Alan R

    2016-09-06

    The tumor suppressor p53 has the most frequently mutated gene in human cancers. Many of p53's oncogenic mutants are just destabilized and rapidly aggregate, and are targets for stabilization by drugs. We found certain 2-sulfonylpyrimidines, including one named PK11007, to be mild thiol alkylators with anticancer activity in several cell lines, especially those with mutationally compromised p53. PK11007 acted by two routes: p53 dependent and p53 independent. PK11007 stabilized p53 in vitro via selective alkylation of two surface-exposed cysteines without compromising its DNA binding activity. Unstable p53 was reactivated by PK11007 in some cancer cell lines, leading to up-regulation of p53 target genes such as p21 and PUMA. More generally, there was cell death that was independent of p53 but dependent on glutathione depletion and associated with highly elevated levels of reactive oxygen species and induction of endoplasmic reticulum (ER) stress, as also found for the anticancer agent PRIMA-1(MET)(APR-246). PK11007 may be a lead for anticancer drugs that target cells with nonfunctional p53 or impaired reactive oxygen species (ROS) detoxification in a wide variety of mutant p53 cells.

  18. Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus.

    Science.gov (United States)

    O'Hanlon, Karen A; Margison, Geoffrey P; Hatch, Amy; Fitzpatrick, David A; Owens, Rebecca A; Doyle, Sean; Jones, Gary W

    2012-09-01

    An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O(6)-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O(6)-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system.

  19. Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents

    International Nuclear Information System (INIS)

    Kaina, B.; Lohrer, H.; Karin, M.; Herrlich, P.

    1990-01-01

    Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x-ray-sensitive derivative were transfected with a bovine papillomavirus (BPV)-linked construct carrying the human metallothionein IIA (hMT-IIA) gene. Transfectants survived 40-fold higher levels of cadmium chloride, harbored at least 30 copies of hMT-IIA, and contained 25- to 166-fold more MT than the parent cells. Even under conditions of reduced glutathione synthesis, the transfectants were not more resistant to the lethal effects of ionizing radiation and bleomycin than the parent cells. Thus free radicals generated by these agents cannot be scavenged efficiently by MT in vivo. The hMT-IIA transfectants, however, but not control transfectants harboring a BPV-MT promoter-neo construct, tolerated significantly higher doses of the alkylating agents N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. Resistance and MT overexpression occurred irrespective of selection and cultivation in cadmium and zinc. There was no increase in resistance to methyl methanesulfonate and N-hydroxyethyl-N-chloroethylnitrosourea. MT did not affect the degree of overall DNA methylation after N-methyl-N-nitrosourea treatment nor the level of O6-methylguanine-DNA methyltransferase. The results suggest that MT participates as a cofactor or regulatory element in repair or tolerance of toxic alkylation lesions

  20. Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents

    Energy Technology Data Exchange (ETDEWEB)

    Kaina, B.; Lohrer, H.; Karin, M.; Herrlich, P. (Kernforschungszentrum Karlsruhe, Karlsruhe (Germany, F.R.))

    1990-04-01

    Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x-ray-sensitive derivative were transfected with a bovine papillomavirus (BPV)-linked construct carrying the human metallothionein IIA (hMT-IIA) gene. Transfectants survived 40-fold higher levels of cadmium chloride, harbored at least 30 copies of hMT-IIA, and contained 25- to 166-fold more MT than the parent cells. Even under conditions of reduced glutathione synthesis, the transfectants were not more resistant to the lethal effects of ionizing radiation and bleomycin than the parent cells. Thus free radicals generated by these agents cannot be scavenged efficiently by MT in vivo. The hMT-IIA transfectants, however, but not control transfectants harboring a BPV-MT promoter-neo construct, tolerated significantly higher doses of the alkylating agents N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. Resistance and MT overexpression occurred irrespective of selection and cultivation in cadmium and zinc. There was no increase in resistance to methyl methanesulfonate and N-hydroxyethyl-N-chloroethylnitrosourea. MT did not affect the degree of overall DNA methylation after N-methyl-N-nitrosourea treatment nor the level of O6-methylguanine-DNA methyltransferase. The results suggest that MT participates as a cofactor or regulatory element in repair or tolerance of toxic alkylation lesions.

  1. Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus

    Science.gov (United States)

    O’Hanlon, Karen A.; Margison, Geoffrey P.; Hatch, Amy; Fitzpatrick, David A.; Owens, Rebecca A.; Doyle, Sean; Jones, Gary W.

    2012-01-01

    An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O6-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O6-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system. PMID:22669901

  2. Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents.

    Science.gov (United States)

    Kaina, B; Lohrer, H; Karin, M; Herrlich, P

    1990-01-01

    Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x-ray-sensitive derivative were transfected with a bovine papillomavirus (BPV)-linked construct carrying the human metallothionein IIA (hMT-IIA) gene. Transfectants survived 40-fold higher levels of cadmium chloride, harbored at least 30 copies of hMT-IIA, and contained 25- to 166-fold more MT than the parent cells. Even under conditions of reduced glutathione synthesis, the transfectants were not more resistant to the lethal effects of ionizing radiation and bleomycin than the parent cells. Thus free radicals generated by these agents cannot be scavenged efficiently by MT in vivo. The hMT-IIA transfectants, however, but not control transfectants harboring a BPV-MT promoter-neo construct, tolerated significantly higher doses of the alkylating agents N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. Resistance and MT overexpression occurred irrespective of selection and cultivation in cadmium and zinc. There was no increase in resistance to methyl methanesulfonate and N-hydroxyethyl-N-chloroethylnitrosourea. MT did not affect the degree of overall DNA methylation after N-methyl-N-nitrosourea treatment nor the level of O6-methylguanine-DNA methyltransferase. The results suggest that MT participates as a cofactor or regulatory element in repair or tolerance of toxic alkylation lesions. Images PMID:2320583

  3. Alkyl ammonium cation stabilized biocidal polyiodides with adaptable high density and low pressure.

    Science.gov (United States)

    He, Chunlin; Parrish, Damon A; Shreeve, Jean'ne M

    2014-05-26

    The effective application of biocidal species requires building the active moiety into a molecular back bone that can be delivered and decomposed on demand under conditions of low pressure and prolonged high-temperature detonation. The goal is to destroy storage facilities and their contents while utilizing the biocidal products arising from the released energy to destroy any remaining harmful airborne agents. Decomposition of carefully selected iodine-rich compounds can produce large amounts of the very active biocides, hydroiodic acid (HI) and iodine (I2). Polyiodide anions, namely, I3(-), I5(-), which are excellent sources of such biocides, can be stabilized through interactions with large, symmetric cations, such as alkyl ammonium salts. We have designed and synthesized suitable compounds of adaptable high density up to 3.33 g cm(-3) that are low-pressure polyiodides with various alkyl ammonium cations, deliverable iodine contents of which range between 58.0-90.9%. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Studies of alkyl porphyrin distributions in organic-rich sediments using LC-MS

    International Nuclear Information System (INIS)

    Eckardt, C.B.; Carter, J.F.; Keely, B.J.; Maxwell, J.R.; Kilpatrick, G.

    1992-01-01

    In recent years, structure elucidation of a wide variety of sedimentary tetrapyrroles has provided clear molecular evidence for the presence of primary photosynthetic communities in palaeo water columns. The reported structures indicate an origin from algal chlorophylls c for certain components, while an origin from photosynthetic bacteria is apparent from the carbon skeletons of other components. In particular, the structures of ≤C 34 porphyrin carboxylic acids in the Eocene Messel shale indicate an origin from Chloroblum bacteria. Since such bacteria are strict anaerobes, the presence of these species is evidence for anoxic conditions extending into the photic zone of Messel lake. By analogy, the presence in the more widely-occurring alkyl porphyrin distributions of components >C 33 would also suggest a Chlorobium chlorophyll origin. Hence, in this paper, the authors studied by LC-MS, the distributions of alkyl porphyrins in selected sediments and searched for the presence of such components, in order to determine photic zone anoxia in the respective palaeo environments

  5. Radiation recall and radiosensitisation with alkylating agents

    Energy Technology Data Exchange (ETDEWEB)

    Kellie, S.J.; Plowman, P.N.; Malpas, J.S.

    1987-05-16

    This brief note records the results of experiments with Adriamycin, 1,2:5,6 dianhydrodulcit and hydroxyurea combined with an endogenous substance inhibiting myeloid proliferation selectively against target cells taken from normal rat, mouse or human haemopoietic lines, spontaneous human leukaemias and the HL-60 established promyelocytic cell line.

  6. Influence of process variables on the continuous alkylation of isobutane with 2-butene on superacid sulfated zirconia catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Corma, A.; Martinez, A.; Martinez, C. [Instituto de Tecnologia Quimica, Valencia (Spain)

    1994-09-01

    Two sulfated zirconia catalysts have been prepared by impregnation of zirconium hydroxide with H{sub 2}SO{sub 4} 0.3 N and 1 N. Both samples showed superacid sites as shown by a desorption temperature peak in the NH{sub 3} TPD at ca. 813 K. The activity and selectivity of these catalysts have been studied for the alkylation of isobutane with trans-2 butene in a computer-controlled continuous fixed bed reactor coupled with a sampling system which allows to make differential analysis of the products from very short reaction times. In this way, the influence of the main process variables, i.e, time on stream, reaction temperature, olefin WHSV, and isoparaffin/olefin ratio, on the 2-butene conversation and product distribution has been investigated. Cracking of larger carbocations and alkylation of isobutane with 2-butene to give trimethylpentanes were the predominant reactions occurring on the superacid catalyst in the initial stages of the reaction. The alkylation/cracking ratio increased when decreasing reaction temperature. A fast catalyst decay with time on stream was also observed, and this was accompanied by an increase in the oligomerization of butene. 23 refs., 5 figs., 4 tabs.

  7. Column selectivity in reversed-phase liquid chromatography I. A general quantitative relationship.

    Science.gov (United States)

    Wilson, N S; Nelson, M D; Dolan, J W; Snyder, L R; Wolcott, R G; Carr, P W

    2002-07-05

    Retention factors k have been measured for 67 neutral, acidic and basic solutes of highly diverse molecular structure (size, shape, polarity, hydrogen bonding, pKa, etc.) on 10 different C18 columns (other conditions constant). These data have been combined with k values from a previous study (86 solutes, five different C8 and C18 columns) to develop a six-term equation for the correlation of retention as a function of solute and column. Values of k can be correlated with an accuracy of +/- 1-2% (1 standard deviation). This suggests that all significant contributions to column selectivity have been identified (and can be measured) for individual alkyl-silica columns which do not have an embedded polar group. That is, columns of the latter kind can be quantitatively characterized in terms of selectivity for use in the separation of any sample.

  8. The ada operon of Mycobacterium tuberculosis encodes two DNA methyltransferases for inducible repair of DNA alkylation damage.

    Science.gov (United States)

    Yang, Mingyi; Aamodt, Randi M; Dalhus, Bjørn; Balasingham, Seetha; Helle, Ina; Andersen, Pernille; Tønjum, Tone; Alseth, Ingrun; Rognes, Torbjørn; Bjørås, Magnar

    2011-06-10

    The ada operon of Mycobacterium tuberculosis, which encodes a composite protein of AdaA and AlkA and a separate AdaB/Ogt protein, was characterized. M. tuberculosis treated with N-methyl-N'-nitro-N-nitrosoguanidine induced transcription of the adaA-alkA and adaB genes, suggesting that M. tuberculosis mount an inducible response to methylating agents. Survival assays of the methyltransferase defective Escherichia coli mutant KT233 (ada ogt), showed that expression of the adaB gene rescued the alkylation sensitivity. Further, adaB but not adaA-alkA complemented the hypermutator phenotype of KT233. Purified AdaA-AlkA and AdaB possessed methyltransferase activity. These data suggested that AdaB counteract the cytotoxic and mutagenic effect of O(6)-methylguanine, while AdaA-AlkA most likely transfers methyl groups from innocuous methylphosphotriesters. AdaA-AlkA did not possess alkylbase DNA glycosylase activity nor rescue the alkylation sensitivity of the E. coli mutant BK2118 (tag alkA). We propose that AdaA-AlkA is a positive regulator of the adaptive response in M. tuberculosis. It thus appears that the ada operon of M. tuberculosis suppresses the mutagenic effect of alkylation but not the cytotoxic effect of lesions such as 3-methylpurines. Collectively, these data indicate that M. tuberculosis hypermutator strains with defective adaptive response genes might sustain robustness to cytotoxic alkylation DNA damage and confer a selective advantage contributing to host adaptation. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Time course evaluation of N-nitrosodialkylamines-induced DNA alkylation and oxidation in liver of mosquito fish

    International Nuclear Information System (INIS)

    Chao, M.-R.; Chang, Y.-Z.; Wong, R.-H.; Hu, C.-W.

    2009-01-01

    Here we simultaneously measured N7-alkylguanines and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in liver of small fish, respectively, to assess the time course of the formation and removal of alkylation and oxidative damage to DNA caused by N-nitrosodialkylamines. Mosquito fish (Gambusia affinis) were killed at various times during (4 days) and post-exposure (16 days) to N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) alone or their combination with concentrations of 10 and 50 mg/l. The modified guanine adducts were sensitively and selectively quantitated by isotope-dilution LC-MS/MS methods. During exposure, N7-methylguanine (N7-MeG) and N7-ethylguanine (N7-EtG) in liver DNA increased with the duration and dose of N-nitrosodialkylamine exposure, while 8-oxodG was dose-dependently induced within 1 day. It was found that NDMA formed substantially more N7-alkylated guanines and 8-oxodG than NDEA on the basis of adducts formed per micromolar concentration, suggesting that NDMA can be more easily bioactivated than NDEA to form reactive alkylating agents with the concomitant formation of oxygen radicals. After cessation of exposure, N7-alkylguanines remained elevated for 1 day and then gradually decreased over time but still higher than the background levels, even at day 16 (half-lives of 7-8 days). However, 8-oxodG was excised quickly from liver DNA and returned to the background level within 4 days post-exposure (half-lives less than 2 days). Taken together, this study firstly demonstrated that in addition to alkylation, N-nitrosodialkylamines can concurrently cause oxidative damage to DNA in vivo

  10. Time course evaluation of N-nitrosodialkylamines-induced DNA alkylation and oxidation in liver of mosquito fish

    Energy Technology Data Exchange (ETDEWEB)

    Chao, M -R [Department of Occupational Safety and Health, Chung Shan Medical University, Taichung 402, Taiwan (China); Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung 402, Taiwan (China); Chang, Y -Z [Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung 402, Taiwan (China); Wong, R -H [Department of Public Health, Chung Shan Medical University, Taichung 402, Taiwan (China); Hu, C.-W. [Department of Public Health, Chung Shan Medical University, Taichung 402, Taiwan (China)], E-mail: windyhu@csmu.edu.tw

    2009-01-15

    Here we simultaneously measured N7-alkylguanines and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in liver of small fish, respectively, to assess the time course of the formation and removal of alkylation and oxidative damage to DNA caused by N-nitrosodialkylamines. Mosquito fish (Gambusia affinis) were killed at various times during (4 days) and post-exposure (16 days) to N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) alone or their combination with concentrations of 10 and 50 mg/l. The modified guanine adducts were sensitively and selectively quantitated by isotope-dilution LC-MS/MS methods. During exposure, N7-methylguanine (N7-MeG) and N7-ethylguanine (N7-EtG) in liver DNA increased with the duration and dose of N-nitrosodialkylamine exposure, while 8-oxodG was dose-dependently induced within 1 day. It was found that NDMA formed substantially more N7-alkylated guanines and 8-oxodG than NDEA on the basis of adducts formed per micromolar concentration, suggesting that NDMA can be more easily bioactivated than NDEA to form reactive alkylating agents with the concomitant formation of oxygen radicals. After cessation of exposure, N7-alkylguanines remained elevated for 1 day and then gradually decreased over time but still higher than the background levels, even at day 16 (half-lives of 7-8 days). However, 8-oxodG was excised quickly from liver DNA and returned to the background level within 4 days post-exposure (half-lives less than 2 days). Taken together, this study firstly demonstrated that in addition to alkylation, N-nitrosodialkylamines can concurrently cause oxidative damage to DNA in vivo.

  11. Time course evaluation of N-nitrosodialkylamines-induced DNA alkylation and oxidation in liver of mosquito fish

    Energy Technology Data Exchange (ETDEWEB)

    Chao, M.-R. [Department of Occupational Safety and Health, Chung Shan Medical University, Taichung 402, Taiwan (China); Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung 402, Taiwan (China); Chang, Y.-Z. [Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung 402, Taiwan (China); Wong, R.-H. [Department of Public Health, Chung Shan Medical University, Taichung 402, Taiwan (China); Hu, C.-W. [Department of Public Health, Chung Shan Medical University, Taichung 402, Taiwan (China)], E-mail: windyhu@csmu.edu.tw

    2009-01-15

    Here we simultaneously measured N7-alkylguanines and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in liver of small fish, respectively, to assess the time course of the formation and removal of alkylation and oxidative damage to DNA caused by N-nitrosodialkylamines. Mosquito fish (Gambusia affinis) were killed at various times during (4 days) and post-exposure (16 days) to N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) alone or their combination with concentrations of 10 and 50 mg/l. The modified guanine adducts were sensitively and selectively quantitated by isotope-dilution LC-MS/MS methods. During exposure, N7-methylguanine (N7-MeG) and N7-ethylguanine (N7-EtG) in liver DNA increased with the duration and dose of N-nitrosodialkylamine exposure, while 8-oxodG was dose-dependently induced within 1 day. It was found that NDMA formed substantially more N7-alkylated guanines and 8-oxodG than NDEA on the basis of adducts formed per micromolar concentration, suggesting that NDMA can be more easily bioactivated than NDEA to form reactive alkylating agents with the concomitant formation of oxygen radicals. After cessation of exposure, N7-alkylguanines remained elevated for 1 day and then gradually decreased over time but still higher than the background levels, even at day 16 (half-lives of 7-8 days). However, 8-oxodG was excised quickly from liver DNA and returned to the background level within 4 days post-exposure (half-lives less than 2 days). Taken together, this study firstly demonstrated that in addition to alkylation, N-nitrosodialkylamines can concurrently cause oxidative damage to DNA in vivo.

  12. Production of high-octane, unleaded motor fuel by alkylation of isobutane with isoamylenes obtained by dehydrogenation of isopentane

    Energy Technology Data Exchange (ETDEWEB)

    Hutson, T. Jr.; Hann, P.D.

    1981-01-31

    A process combination, with inter-cooperation, for producing high-octane alkylates comprising (a) dehydrogenating isopentane to isopentenes (amylenes), (b) introducing the mixture of said amylenes and unconverted isopentane into an HF alkylation unit for reaction with fresh or recycled isobutane, (c) separating the alkylation products into high octane alkylates, isopentane (for recycling to the dehydrogenation reactor) and isobutane (for recycling to the alkylation reactor).

  13. Alkylating agent (MNU)-induced mutation in space environment

    Science.gov (United States)

    Ohnishi, T.; Takahashi, A.; Ohnishi, K.; Takahashi, S.; Masukawa, M.; Sekikawa, K.; Amano, T.; Nakano, T.; Nagaoka, S.

    2001-01-01

    In recent years, some contradictory data about the effects of microgravity on radiation-induced biological responses in space experiments have been reported. We prepared a damaged template DNA produced with an alkylating agent (N-methyl-N-nitroso urea; MNU) to measure incorrect base-incorporation during DNA replication in microgravity. We examined whether mutation frequency is affected by microgravity during DNA replication for a DNA template damaged by an alkylating agent. Using an in vitro enzymatic reaction system, DNA synthesis by Taq polymerase or polymerase III was done during a US space shuttle mission (Discovery, STS-91). After the flight, DNA replication and mutation frequencies were measured. We found that there was almost no effect of microgravity on DNA replication and mutation frequency. It is suggested that microgravity might not affect at the stage of substrate incorporation in induced-mutation frequency.

  14. Conformational Restriction of Peptides Using Dithiol Bis-Alkylation.

    Science.gov (United States)

    Peraro, L; Siegert, T R; Kritzer, J A

    2016-01-01

    Macrocyclic peptides are highly promising as inhibitors of protein-protein interactions. While many bond-forming reactions can be used to make cyclic peptides, most have limitations that make this chemical space challenging to access. Recently, a variety of cysteine alkylation reactions have been used in rational design and library approaches for cyclic peptide discovery and development. We and others have found that this chemistry is versatile and robust enough to produce a large variety of conformationally constrained cyclic peptides. In this chapter, we describe applications, methods, mechanistic insights, and troubleshooting for dithiol bis-alkylation reactions for the production of cyclic peptides. This method for efficient solution-phase macrocyclization is highly useful for the rapid production and screening of loop-based inhibitors of protein-protein interactions. © 2016 Elsevier Inc. All rights reserved.

  15. Method for reactivating solid catalysts used in alkylation reactions

    Science.gov (United States)

    Ginosar, Daniel M.; Thompson, David N.; Coates, Kyle; Zalewski, David J.; Fox, Robert V.

    2003-06-17

    A method for reactivating a solid alkylation catalyst is provided which can be performed within a reactor that contains the alkylation catalyst or outside the reactor. Effective catalyst reactivation is achieved whether the catalyst is completely deactivated or partially deactivated. A fluid reactivating agent is employed to dissolve catalyst fouling agents and also to react with such agents and carry away the reaction products. The deactivated catalyst is contacted with the fluid reactivating agent under pressure and temperature conditions such that the fluid reactivating agent is dense enough to effectively dissolve the fouling agents and any reaction products of the fouling agents and the reactivating agent. Useful pressures and temperatures for reactivation include near-critical, critical, and supercritical pressures and temperatures for the reactivating agent. The fluid reactivating agent can include, for example, a branched paraffin containing at least one tertiary carbon atom, or a compound that can be isomerized to a molecule containing at least one tertiary carbon atom.

  16. Rapid NIR determination of alkyl esters in virgin olive oil

    International Nuclear Information System (INIS)

    Cayuela, J.A.

    2017-01-01

    The regulation of The European Union for olive oil and olive pomace established the limit of 35 mg·kg-1 for fatty acids ethyl ester contents in extra virgin olive oils, from grinding seasons after 2016. In this work, predictive models have been established for measuring fatty acid ethyl and methyl esters and to measure the total fatty acid alkyl esters based on near infrared spectroscopy (NIRS), and used successfully for this purpose. The correlation coefficients from the external validation exercises carried out with these predictive models ranged from 0.84 to 0.91. Different classification tests using the same models for the thresholds 35 mg·kg-1 for fatty acid ethyl esters and 75 mg·kg-1 for fatty acid alkyl esters provided success percentages from 75.0% to 95.2%. [es

  17. Synthesis and Antioxidant Activity of Alkyl Nitroderivatives of Hydroxytyrosol

    Directory of Open Access Journals (Sweden)

    Elena Gallardo

    2016-05-01

    Full Text Available A series of alkyl nitrohydroxytyrosyl ether derivatives has been synthesized from free hydroxytyrosol (HT, the natural olive oil phenol, in order to increase the assortment of compounds with potential neuroprotective activity in Parkinson’s disease. In this work, the antioxidant activity of these novel compounds has been evaluated using Ferric Reducing Antioxidant Power (FRAP, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt (ABTS, and Oxygen Radical Scavenging Capacity (ORAC assays compared to that of nitrohydroxytyrosol (NO2HT and free HT. New compounds showed variable antioxidant activity depending on the alkyl side chain length; compounds with short chains (2–4 carbon atoms maintained or even improved the antioxidant activity compared to NO2HT and/or HT, whereas those with longer side chains (6–8 carbon atoms showed lower activity than NO2HT but higher than HT.

  18. New unit for sulfuric acid alkylation of isobutane by olefins

    Energy Technology Data Exchange (ETDEWEB)

    Khadzhiev, S.N.; Baiburskii, V.L.; Deineko, P.S.; Gruzdev, A.S.; Tagavov, I.T.

    1987-01-01

    The authors describe and illustrate a sulfuric acid alkylation unit with a horizontal contact. As a result of the use of this design solution, the isobutane/olefin ratio is 10/1 in comparison with 4/1 to 5/1 in the other types of units, namely vertical reactors and cascade tank reactors. The unit was designed to process the butane-butylene cut (BBC) and part of the propane-propylene cut (PPC) from the G-43-107 cat cracker. The unit design includes provisions for controlled caustic washing of the feed and dehydration in an electric field. The authors present the basic data obtained in the three months of unit operation after startup, in comparison with the operating indexes of a sulfuric acid alkylation unit.

  19. Antioxidant activity of alkyl gallates and glycosyl alkyl gallates in fish oil in water emulsions: relevance of their surface active properties and of the type of emulsifier.

    Science.gov (United States)

    González, María J; Medina, Isabel; Maldonado, Olivia S; Lucas, Ricardo; Morales, Juan C

    2015-09-15

    The antioxidant activity of gallic acid and a series of alkyl gallates (C4-C18) and glycosylated alkyl gallates (C4-C18) on fish oil-in-water emulsions was studied. Three types of emulsifiers, lecithin, Tween-20 and sodium dodecyl sulphate (SDS) were tested. A nonlinear behavior of the antioxidant activity of alkyl gallates when increasing alkyl chain length was observed for emulsions prepared with lecithin. Medium-size alkyl gallates (C6-C12) were the best antioxidants. In contrast, for emulsions prepared with Tween-20, the antioxidants seem to follow the polar paradox. Glucosyl alkyl gallates were shown previously to be better surfactants than alkyl gallates. Nevertheless, they exhibited a worse antioxidant capacity than their corresponding alkyl gallates, in emulsions prepared with lecithin or Tween-20, indicating the greater relevance of having three OH groups at the polar head in comparison with having improved surfactant properties but just a di-ortho phenolic structure in the antioxidant. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. The formation of quasi-alicyclic rings in alkyl-aromatic compounds

    Science.gov (United States)

    Straka, Pavel; Buryan, Petr; Bičáková, Olga

    2018-02-01

    The alkyl side chains of n-alkyl phenols, n-alkyl benzenes and n-alkyl naphthalenes are cyclised, as demonstrated by GC measurements, FTIR spectroscopy and molecular mechanics calculations. Cyclisation occurs due to the intramolecular interaction between an aromatic ring (-δ) and a hydrogen of the terminal methyl group (+δ) of an alkyl chain. In fact, conventional molecules are not aliphatic-aromatic, but quasi-alicyclic-aromatic. With the aromatic molecules formed with a quasi-alicyclic ring, the effect of van der Waals attractive forces increases not only intramolecularly but also intermolecularly. This effect is strong in molecules with propyl and higher alkyl substituents. The increase of intermolecular van der Waals attractive forces results in bi-linearity in the GC retention time of the compounds in question, observed in the dependence of the logarithm of the relative retention time on the number of carbons in a molecule in both polar and nonpolar stationary phases with both capillary and packed columns. The role of van der Waals forces has been demonstrated using the potential energies of covalent and noncovalent interactions for 2-n-alkyl phenols, n-alkyl benzenes and 1-n-alkyl- and 2-n-alkyl naphthalenes.

  1. A Convenient Approach to Synthesizing Peptide C-Terminal N-Alkyl Amides

    Science.gov (United States)

    Fang, Wei-Jie; Yakovleva, Tatyana; Aldrich, Jane V.

    2014-01-01

    Peptide C-terminal N-alkyl amides have gained more attention over the past decade due to their biological properties, including improved pharmacokinetic and pharmacodynamic profiles. However, the synthesis of this type of peptide on solid phase by current available methods can be challenging. Here we report a convenient method to synthesize peptide C-terminal N-alkyl amides using the well-known Fukuyama N-alkylation reaction on a standard resin commonly used for the synthesis of peptide C-terminal primary amides, the PAL-PEG-PS (Peptide Amide Linker-polyethylene glycol-polystyrene) resin. The alkylation and oNBS deprotection were conducted under basic conditions and were therefore compatible with this acid labile resin. The alkylation reaction was very efficient on this resin with a number of different alkyl iodides or bromides, and the synthesis of model enkephalin N-alkyl amide analogs using this method gave consistently high yields and purities, demonstrating the applicability of this methodology. The synthesis of N-alkyl amides was more difficult on a Rink amide resin, especially the coupling of the first amino acid to the N-alkyl amine, resulting in lower yields for loading the first amino acid onto the resin. This method can be widely applied in the synthesis of peptide N-alkyl amides. PMID:22252422

  2. Influence of crystallite size and shape of zeolite ZSM-22 on its activity and selectivity in the catalytic cracking of n-octane

    Energy Technology Data Exchange (ETDEWEB)

    Bager, F.; Ernst, S. [Kaiserslautern Univ. (Germany). Dept. of Chemistry, Chemical Technology

    2013-11-01

    Light olefins belong to the major building blocks for the petrochemical industry, particularly for the production of polymers. It has become necessary to increase the production of light olefins specifically in the case for propene with so called 'on-purpose propene' technologies. One possible route is to increase the amount of propene that can be obtained from Fluid Catalytic Cracking (FCC) by optimizing the catalyst through introducing new additives, which offer a high selectivity to propene. Zeolite ZSM-22 samples with different crystallite sizes and morphologies have been synthesized via hydrothermal syntheses and characterized by powder X-Ray diffraction, nitrogen physisorption, atomic absorption spectroscopy, scanning electron microscopy and solid-state NMR spectroscopy. The zeolites in the Broensted-acid form have been tested as catalysts in the catalytic cracking of n-octane as a model hydrocarbon. Clear influences of the crystallite size on the deactivation behavior have been observed. Larger crystals of zeolite ZSM-22 produce an increased amount of coke deposits resulting in a faster deactivation of the catalyst. The experimental results suggest that there is probably some influence of pore diffusion on the catalytic activity of the ZSM-22 sample with the large crystallite size. However a noticeable influence on the general product distribution could not be observed. (orig.)

  3. Diagnosis of the σ-, π- and (σ+π-Aromaticity by the Shape of the NICSzz-Scan Curves and Symmetry-Based Selection Rules

    Directory of Open Access Journals (Sweden)

    Constantinos A. Tsipis

    2010-03-01

    Full Text Available The NICSzz-scan curves of aromatic organic, inorganic and “all-metal” molecules in conjunction with symmetry-based selection rules provide efficient diagnostic tools of the σ-, π- and/or double (σ + π-aromaticity. The NICSzz-scan curves of σ-aromatic molecules are symmetric around the z-axis, having half-band widths approximately less than 3 Å with the induced diatropic ring current arising from Tx,y-allowed transitions involving exclusively σ-type molecular orbitals. Broad NICSzz-scan curves (half-band width approximately higher than 3 Å characterize double (σ + π-aromaticity, the chief contribution to the induced diatropic ring current arising from Tx,y-allowed transitions involving both σ- and π-type molecular orbitals. NICSzz-scan curves exhibiting two maxima at a certain distance above and below the molecular plane are typical for (σ + π-aromatics where the π-diatropic ring current overwhelms the σ-type one. In the absence of any contribution from the σ-diatropic ring current, the NICSzz(0 value is close to zero and the molecule exhibits pure π-aromaticity.

  4. Lysosomes shape Ins(1,4,5)P3-evoked Ca2+ signals by selectively sequestering Ca2+ released from the endoplasmic reticulum

    Science.gov (United States)

    López-Sanjurjo, Cristina I.; Tovey, Stephen C.; Prole, David L.; Taylor, Colin W.

    2013-01-01

    Summary Most intracellular Ca2+ signals result from opening of Ca2+ channels in the plasma membrane or endoplasmic reticulum (ER), and they are reversed by active transport across these membranes or by shuttling Ca2+ into mitochondria. Ca2+ channels in lysosomes contribute to endo-lysosomal trafficking and Ca2+ signalling, but the role of lysosomal Ca2+ uptake in Ca2+ signalling is unexplored. Inhibition of lysosomal Ca2+ uptake by dissipating the H+ gradient (using bafilomycin A1), perforating lysosomal membranes (using glycyl-L-phenylalanine 2-naphthylamide) or lysosome fusion (using vacuolin) increased the Ca2+ signals evoked by receptors that stimulate inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] formation. Bafilomycin A1 amplified the Ca2+ signals evoked by photolysis of caged Ins(1,4,5)P3 or by inhibition of ER Ca2+ pumps, and it slowed recovery from them. Ca2+ signals evoked by store-operated Ca2+ entry were unaffected by bafilomycin A1. Video-imaging with total internal reflection fluorescence microscopy revealed that lysosomes were motile and remained intimately associated with the ER. Close association of lysosomes with the ER allows them selectively to accumulate Ca2+ released by Ins(1,4,5)P3 receptors. PMID:23097044

  5. DNA Damage Induced by Alkylating Agents and Repair Pathways

    OpenAIRE

    Natsuko Kondo; Akihisa Takahashi; Koji Ono; Takeo Ohnishi

    2010-01-01

    The cytotoxic effects of alkylating agents are strongly attenuated by cellular DNA repair processes, necessitating a clear understanding of the repair mechanisms. Simple methylating agents form adducts at N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O 6-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O 6-methylguanine-DNA methyltransferase, and O 6MeG:T mispairs are recognized...

  6. Optimizing the use of alkylators in neuro-oncology

    OpenAIRE

    Perry, J R; Wick, W; Weller, M

    2011-01-01

    For more than three decades, alkylating agents have been the most widely used class of chemotherapeutic agents for the treatment of glial brain tumors. Today, concomitant and adjuvant temozolomide is the standard of care for newly diagnosed glioblastoma. Temozolomide alone or in combination with radiotherapy is being explored in ongoing trials in newly diagnosed patients with low-grade and anaplastic glioma. Rechallenge with alternative dosing schedules of temozolomide is a valid treatment op...

  7. 3-alkyl fentanyl analogues: Structure-activity-relationship study

    OpenAIRE

    Vučković, Sonja; Savić-Vujović, Katarina; Srebro, Dragana; Ivanović, Milovan; Došen-Mićović, Ljiljana; Stojanović, Radan; Prostran, Milica

    2012-01-01

    Introduction. Fentanyl belongs to 4-anilidopiperidine class of synthetic opioid analgesics. It is characterized by high potency, rapid onset and short duration of action. A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful analgesic drugs. Objective. In this study, newly synthesized 3-alkyl fentanyl analogues were examined for analgesic activity and compared with fentanyl. Methods. ...

  8. Ruthenium-Catalyzed Alkylation of Oxindole with Alcohols

    DEFF Research Database (Denmark)

    Jensen, Thomas; Madsen, Robert

    2009-01-01

    An atom-economical and solvent-free catalytic procedure for the mono-3-alkylation of oxindole with alcohols is described. The reaction is mediated by the in situ generated catalyst from RuCl3 center dot xH(2)O and PPh3 in the presence of sodium hydroxide, The reactions proceed in good to excellent...... yields with a wide range of aromatic, heteroaromatic, and aliphatic alcohols....

  9. Chemotherapy-induced pulmonary hypertension: role of alkylating agents.

    Science.gov (United States)

    Ranchoux, Benoît; Günther, Sven; Quarck, Rozenn; Chaumais, Marie-Camille; Dorfmüller, Peter; Antigny, Fabrice; Dumas, Sébastien J; Raymond, Nicolas; Lau, Edmund; Savale, Laurent; Jaïs, Xavier; Sitbon, Olivier; Simonneau, Gérald; Stenmark, Kurt; Cohen-Kaminsky, Sylvia; Humbert, Marc; Montani, David; Perros, Frédéric

    2015-02-01

    Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by progressive obstruction of small pulmonary veins and a dismal prognosis. Limited case series have reported a possible association between different chemotherapeutic agents and PVOD. We evaluated the relationship between chemotherapeutic agents and PVOD. Cases of chemotherapy-induced PVOD from the French PH network and literature were reviewed. Consequences of chemotherapy exposure on the pulmonary vasculature and hemodynamics were investigated in three different animal models (mouse, rat, and rabbit). Thirty-seven cases of chemotherapy-associated PVOD were identified in the French PH network and systematic literature analysis. Exposure to alkylating agents was observed in 83.8% of cases, mostly represented by cyclophosphamide (43.2%). In three different animal models, cyclophosphamide was able to induce PH on the basis of hemodynamic, morphological, and biological parameters. In these models, histopathological assessment confirmed significant pulmonary venous involvement highly suggestive of PVOD. Together, clinical data and animal models demonstrated a plausible cause-effect relationship between alkylating agents and PVOD. Clinicians should be aware of this uncommon, but severe, pulmonary vascular complication of alkylating agents. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. Effects of alkylating carcinogens on human tumor cells in culture

    International Nuclear Information System (INIS)

    Goth-Goldstein, R.; Hughes, M.

    1987-01-01

    In Escherichia coli 3-methyladenine and 3-methylguanine have been identified as lethal lesions, since two types of alkylating agent-sensitive mutants were deficient in repair of either of these lesions. Similar alkylation-sensitive human cell lines exist. These are the tumor cell lines of the complex Mer - phenotype. All Mer - cells examined were hypersensitive to killing by MNNG and other alkylating agents, and failed to repair O 6 -methylguanine. The widely studied HeLa S3 cell line has the Mer + phenotype, but a Mer - variant (HeLa MR) has arisen. This offers the possibility to study Mer - and Mer + cells of otherwise similar genetic background. We are using these two variants to analyze the Mer - phenotype further. When HeLa S3 and HeLa MR were treated with a highly dose of MNNG, and the surviving population exposed to a second dose of MNNG 2-3 weeks later, HeLa S3 (Mer + ) cells were equally or even slightly more sensitive to a second exposure of MNNG, whereas the surviving HeLa MR (Mer - ) population was much more resistant to MNNG. 1 fig., 1 tab

  11. DNA Damage Induced by Alkylating Agents and Repair Pathways

    Science.gov (United States)

    Kondo, Natsuko; Takahashi, Akihisa; Ono, Koji; Ohnishi, Takeo

    2010-01-01

    The cytotoxic effects of alkylating agents are strongly attenuated by cellular DNA repair processes, necessitating a clear understanding of the repair mechanisms. Simple methylating agents form adducts at N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O6-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O6-methylguanine-DNA methyltransferase, and O6MeG:T mispairs are recognized by the mismatch repair system (MMR). MMR cannot repair the O6MeG/T mispairs, which eventually lead to double-strand breaks. Bifunctional alkylating agents form interstrand cross-links (ICLs) which are more complex and highly cytotoxic. ICLs are repaired by complex of NER factors (e.g., endnuclease xeroderma pigmentosum complementation group F-excision repair cross-complementing rodent repair deficiency complementation group 1), Fanconi anemia repair, and homologous recombination. A detailed understanding of how cells cope with DNA damage caused by alkylating agents is therefore potentially useful in clinical medicine. PMID:21113301

  12. Decreased stability of DNA in cells treated with alkylating agents

    Energy Technology Data Exchange (ETDEWEB)

    Frankfurt, O.S. (Cedars Medical Center, Miami, FL (United States))

    1990-12-01

    A modified highly sensitive procedure for the evaluation of DNA damage in individual cells treated with alkylating agents is reported. The new methodology is based on the amplification of single-strandedness in alkylated DNA by heating in the presence of Mg{sup 2+}. Human ovarian carcinoma cells A2780 were treated with nitrogen mustard (HN2), fixed in methanol, and stained with monoclonal antibody (MOAB) F7-26 generated against HN2-treated DNA. Binding of MOAB was measured by flow cytometry with indirect immunofluorescence. Intensive binding of MOAB to control and drug-treated cells was observed after heating in Tris buffer supplemented with MgCl{sub 2}. Thus, the presence of phosphates and MgCl{sub 2} during heating was necessary for the detection of HN2-induced changes in DNA stability. Fluorescence of HN2-treated cells decreased to background levels after treatment with single-strand-specific S{sub 1} nuclease. MOAB F7-26 interacted with single-stranded regions in DNA and did not bind to dsDNA or other cellular antigens. It is suggested that alkylation of guanines decreased the stability of the DNA molecule and increased the access of MOAB F7-26 to deoxycytidines on the opposite DNA strand.

  13. Separation of products of alkylation of isobutane by olefins

    Energy Technology Data Exchange (ETDEWEB)

    Ward, J.

    1979-03-15

    The alkylation (A1) of isobutane (I) by propylene, butylene and amylenes is carried out at 24-52 degrees, pressure sufficient to maintain the liquid phase, and a molar ratio of I to olefins (O1) 10:1-15:1. The bulk ratio of catalysts to hydrocarbons in the reaction zone was 0.5:1-10:1; when using HF-K-T as the catalysts, it should contain less than 5 percent water and greater than or equal to 65 percent titrated HF. The hydrocarbon products (UP) from the alkylation zone are added after separating the catalyst in a fractionation tower; distillation is carried out at 38-49 degrees and 1.03-1.3 NPa. The head fraction containing I and less than 50 molar percent C3H8 and also fraction I at the point below the input side of the UP which contains less than 8 molar percent C3H8 and fraction n-C4H10 at the point below the point of discharge of fraction I is drained from the tower. The alkylate is discharged at the bottom of the tower. According to the patent the tower operates at low pressure. This improves relative volatility of individual components and reduces heat consumption. The best results are obtained when a head fraction or the concentration C3H8 approximately 25 molar percent is discharged.

  14. Oxidation and N-alkylation of galactomannan extracted from Caesalpinia ferrea var. ferrea seeds

    International Nuclear Information System (INIS)

    Souza, Clayton F. de; Lucyszyn, Neoli; Ferraz, Fernando A.; Sierakowski, Maria Rita

    2009-01-01

    The objective of this work was the synthesis and characterization of carboxyl (polyelectrolyte, GMPFOXT) and amino alkylate (amphiphilic, GMPFOXD) derivatives of the galactomannan extracted from the seeds of native specie Pau-ferro (Caesalpinia ferrea - GMPF). The derivatives were obtained by selective modification of GMPF at C-6 in the presence of TEMPO reagent (N-oxil-2,2,6,6-tetramethyl-piperidine) and dodecylamine showed high yields (∼ 77 and 94% for GMPFOXT and GMPFOXD, respectively). The characteristics of the derivatives were confirmed by spectroscopic techniques of FTIR and 13 C-NMR. By gel permeation chromatography (GPC), was observed a decrease of molar mass values and increase in polydispersity after derivatization, indicating change in the aggregation state in solution, caused by modification on the superficial structure. The development of these products can expand the use of them in different areas such as cosmetics and pharmaceutics, among others. (author)

  15. One-electron reduction of 2- and 6-methyl-1,4-naphthoquinone bioreductive alkylating agents

    International Nuclear Information System (INIS)

    Wilson, I.; Wardman, P.; Lin, T.S.; Sartorelli, A.C.

    1986-01-01

    The semiquinones, Q.-, of derivatives of 2- and 6-methyl-1,4-naphthoquinones, some incorporating leaving groups with substituents such as CH 2 Br or CH 2 OCONHCH 3 , have been produced by radiolytic reduction of Q by (CH 3 )2COH radicals. The absorption spectra and decay kinetics of Q.- were all closely similar to that produced from 2-methyl-1,4-naphthoquinone, with no evidence for unimolecular elimination of a leaving group in the semiquinone form, but immediate loss of leaving group upon two-electron reduction of Q to the hydroquinone. The redox equilibria between Q/Q.- and O2/O2.- were characterized, and reduction potentials of the couples Q/Q.- in water at pH 7.6 were calculated. The implications of these observations for the use of these compounds as bioreductive alkylating agents or as radiosensitizers with potential selective activity toward hypoxic cells are discussed

  16. Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes.

    Science.gov (United States)

    Tran, Thai Q; Ishak Gabra, Mari B; Lowman, Xazmin H; Yang, Ying; Reid, Michael A; Pan, Min; O'Connor, Timothy R; Kong, Mei

    2017-11-01

    Driven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH) enzymes activity and induces DNA alkylation damage. As a result, glutamine deprivation or glutaminase inhibitor treatment triggers DNA damage accumulation independent of cell death. In addition, low glutamine-induced DNA damage is abolished in ALKBH deficient cells. Importantly, we show that glutaminase inhibitors, 6-Diazo-5-oxo-L-norleucine (DON) or CB-839, hypersensitize cancer cells to alkylating agents both in vitro and in vivo. Together, the crosstalk between glutamine metabolism and the DNA repair pathway identified in this study highlights a potential role of metabolic stress in genomic instability and therapeutic response in cancer.

  17. Linear shaped charge

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, David; Stofleth, Jerome H.; Saul, Venner W.

    2017-07-11

    Linear shaped charges are described herein. In a general embodiment, the linear shaped charge has an explosive with an elongated arrowhead-shaped profile. The linear shaped charge also has and an elongated v-shaped liner that is inset into a recess of the explosive. Another linear shaped charge includes an explosive that is shaped as a star-shaped prism. Liners are inset into crevices of the explosive, where the explosive acts as a tamper.

  18. Efficient synthesis of N-alkyl-2,7-dihalocarbazoles by simultaneous carbazole ring closure and N-alkylation

    Czech Academy of Sciences Publication Activity Database

    Výprachtický, Drahomír; Kmínek, Ivan; Pokorná, Veronika; Cimrová, Věra

    2012-01-01

    Roč. 68, č. 25 (2012), s. 5075-5080 ISSN 0040-4020 R&D Projects: GA MŠk(CZ) 1M06031; GA ČR GAP106/12/0827 Institutional research plan: CEZ:AV0Z40500505 Institutional support: RVO:61389013 Keywords : carbazole ring closure * carbazole alkylation * heterocycles Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 2.803, year: 2012

  19. Protein Recognition in Drug-Induced DNA Alkylation: When the Moonlight Protein GAPDH Meets S23906-1/DNA Minor Groove Adducts.

    Science.gov (United States)

    Savreux-Lenglet, Gaëlle; Depauw, Sabine; David-Cordonnier, Marie-Hélène

    2015-11-05

    DNA alkylating drugs have been used in clinics for more than seventy years. The diversity of their mechanism of action (major/minor groove; mono-/bis-alkylation; intra-/inter-strand crosslinks; DNA stabilization/destabilization, etc.) has undoubtedly major consequences on the cellular response to treatment. The aim of this review is to highlight the variety of established protein recognition of DNA adducts to then particularly focus on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) function in DNA adduct interaction with illustration using original experiments performed with S23906-1/DNA adduct. The introduction of this review is a state of the art of protein/DNA adducts recognition, depending on the major or minor groove orientation of the DNA bonding as well as on the molecular consequences in terms of double-stranded DNA maintenance. It reviews the implication of proteins from both DNA repair, transcription, replication and chromatin maintenance in selective DNA adduct recognition. The main section of the manuscript is focusing on the implication of the moonlighting protein GAPDH in DNA adduct recognition with the model of the peculiar DNA minor groove alkylating and destabilizing drug S23906-1. The mechanism of action of S23906-1 alkylating drug and the large variety of GAPDH cellular functions are presented prior to focus on GAPDH direct binding to S23906-1 adducts.

  20. Balancing repair and tolerance of DNA damage caused by alkylating agents.

    Science.gov (United States)

    Fu, Dragony; Calvo, Jennifer A; Samson, Leona D

    2012-01-12

    Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity.