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Sample records for alkyne-azide click reaction

  1. A Highly Efficient Single-Chain Metal-Organic Nanoparticle Catalyst for Alkyne-Azide "Click" Reactions in Water and in Cells.

    PubMed

    Bai, Yugang; Feng, Xinxin; Xing, Hang; Xu, Yanhua; Kim, Boo Kyung; Baig, Noman; Zhou, Tianhui; Gewirth, Andrew A; Lu, Yi; Oldfield, Eric; Zimmerman, Steven C

    2016-09-01

    We show that copper-containing metal-organic nanoparticles (MONPs) are readily synthesized via Cu(II)-mediated intramolecular cross-linking of aspartate-containing polyolefins in water. In situ reduction with sodium ascorbate yields Cu(I)-containing MONPs that serve as highly efficient supramolecular catalysts for alkyne-azide "click chemistry" reactions, yielding the desired 1,4-adducts at low parts per million catalyst levels. The nanoparticles have low toxicity and low metal loadings, making them convenient, green catalysts for alkyne-azide "click" reactions in water. The Cu-MONPs enter cells and perform efficient, biocompatible click chemistry, thus acting as intracellular nanoscale molecular synthesizers. PMID:27529791

  2. Assessment of the Full Compatibility of Copper(I)-Catalyzed Alkyne-Azide Cycloaddition and Oxime Click Reactions for bis-Labelling of Oligonucleotides

    PubMed Central

    Estalayo-Adriàn, Sandra; Lartia, Rémy; Meyer, Albert; Vasseur, Jean-Jacques; Morvan, François; Defrancq, Eric

    2015-01-01

    The conjugation of oligonucleotides with reporters is of great interest for improving their intrinsic properties or endowing new ones. In this context, we report herein a new procedure for the bis-labelling of oligonucleotides through oxime ligation (Click-O) and copper(I)-catalyzed alkyne–azide cycloaddition (Click-H). 5′-Azido and 3′-aldehyde precursors were incorporated into oligonucleotides, and subsequent coupling reactions through Click-O and Click-H (or vice versa) were successfully achieved. In particular, we exhaustively investigated the full compatibility of each required step for both tethering strategies. The results demonstrate that click Huisgen and click oxime reactions are fully compatible. However, whilst both approaches can deliver the targeted doubly conjugated oligonucleotide, the route involving click oxime ligation prior to click Huisgen is significantly more successful. Thus the reactions investigated here can be considered to be key elements of the chemical toolbox for the synthesis of highly sophisticated bioconjugates. PMID:25969815

  3. Disorder-to-order transition of diblock copolymers induced by alkyne/azide click chemistry

    NASA Astrophysics Data System (ADS)

    Wei, Xinyu; Chen, Wei; Chen, Xiangji; Emrick, Todd; Russell, Thomas

    2010-03-01

    Alkyne/azide click chemistry is shown as a novel approach to induce the disorder-to-order transition (DOT) of diblock copolymers. A series of poly(ethylene oxide)-b-poly(n-butyl methacrylate-r-propargyl methacrylate) (PEO-b-P(nBMA-r-PgMA)) diblock copolymers were prepared and it is shown that the neat diblock copolymers are in the phase mixed state over the temperature range invetigated. Microphase separation was observed when the diblock copolymers were mixed with rhodamine B azide and annealed at elevated temperature. The azide molecule reacted with the terminal alkyne groups in P(nBMA-r-PgMA) block and attached to polymer backbone, resulting in a significant increase in the nonfavorable interaction between the two blocks. The DOT of these blends was observed both in the bulk and in thin films. The evolution of the morphology during the transition is determined by the mole ratio between alkyne and azide groups, annealing time and temperature, and interfacial energy.

  4. A highly active and magnetically recoverable tris(triazolyl)-Cu(I) catalyst for alkyne-azide cycloaddition reactions.

    PubMed

    Wang, Dong; Etienne, Laetitia; Echeverria, María; Moya, Sergio; Astruc, Didier

    2014-04-01

    Nanoparticle-supported tris(triazolyl)-CuBr, with a diameter of approximately 25 nm measured by TEM spectroscopy, has been easily prepared, and its catalytic activity was evaluated in the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. In initial experiments, 0.5 mol % loading successfully promoted the CuAAC reaction between benzyl azide and phenylacetylene, in water at room temperature (25 °C). During this process, the iron oxide nanoparticle-supported tris(triazolyl)-CuBr displayed good monodispersity, excellent recoverability, and outstanding reusability. Indeed, it was simply collected and separated from the reaction medium by using an external magnet, then used for another five catalytic cycles without significant loss of catalytic activity. Inductively coupled plasma (ICP) analysis for the first cycle revealed that the amount of copper leached from the catalyst into the reaction medium is negligible (1.5 ppm). The substrate scope has been examined, and it was found that the procedure can be successfully extended to various organic azides and alkynes and can also be applied to the one-pot synthesis of triazoles, through a cascade reaction involving benzyl bromides, alkynes, and sodium azide. In addition, the catalyst was shown to be an efficient CuAAC catalyst for the synthesis of allyl- and TEG-ended (TEG=triethylene glycol) 27-branch dendrimers. PMID:24574335

  5. Cyclization of Alkyne-Azide with Isonitrile/CO via Self-Relay Rhodium Catalysis.

    PubMed

    Zhang, Zhen; Xiao, Fan; Huang, Baoliang; Hu, Jincheng; Fu, Bin; Zhang, Zhenhua

    2016-03-01

    A self-relay rhodium(I)-catalyzed cyclization of alkyne-azides with two σ-donor/π-acceptor ligands (isonitriles and CO) to form sequentially multiple-fused heterocycle systems via tandem nitrene transformation and aza-Pauson-Khand cyclization has been developed. In this approach, an intriguing chemoselective insertion process of isonitriles superior to CO was observed. This reaction provides an alternative strategy to synthesize functionalized pyrrolo[2,3-b]indole scaffolds. PMID:26907671

  6. Strain-Promoted Alkyne-Azide Cycloadditions (SPAAC) Reveal New Features of Glycoconjugate Biosynthesis

    PubMed Central

    Mbua, Ngalle Eric; Guo, Jun; Wolfert, Margreet A.; Steet, Richard; Boons, Geert-Jan

    2011-01-01

    We have shown that 4-Dibenzocyclooctynol (DIBO), which can easily be obtained by a streamlined synthetic approach, reacts exceptionally fast in the absence of a CuI catalyst with azido-containing compounds to give stable triazoles. Chemical modifications of DIBO, such as oxidation of the alcohol to a ketone, increased the rate of strain promoted azide-alkyne cycloadditions (SPAAC). Installment of a ketone or oxime in the cyclooctyne ring resulted in fluorescent active compounds whereas this property was absent in the corresponding cycloaddition adducts, thereby providing the first example of a metal-free alkyne-azide fluoro-switch click reaction. The alcohol or ketone functions of the cyclooctynes offer a chemical handle to install a variety of different tags, thereby facilitating biological studies. It was found that DIBO modified with biotin combined with metabolic labeling with an azido-containing monosaccharide can determine relative quantities of sialic acid of living cells that have defects in glycosylation (Lec CHO cells). A combined use of metabolic labeling/SPAAC and lectin staining of cells that have defects in the Conserved Oligomeric Golgi (COG) complex revealed that such defects have a greater impact on O-glycan sialylation than galactosylation, whereas sialylation and galactosylation of N-glycans was similarly impacted. These results highlight that the fidelity of Golgi trafficking is a critical parameter for the types of oligosaccharides that are being biosynthesized by a cell. Furthermore, by modulating the quantity of biosynthesized sugar nucleotide, cells may have a means to selectively alter specific glycan structures of glycoproteins. PMID:21661087

  7. Rate determination of azide click reactions onto alkyne polymer brush scaffolds: a comparison of conventional and catalyst-free cycloadditions for tunable surface modification.

    PubMed

    Orski, Sara V; Sheppard, Gareth R; Arumugam, Selvanathan; Arnold, Rachelle M; Popik, Vladimir V; Locklin, Jason

    2012-10-16

    The postpolymerization functionalization of poly(N-hydroxysuccinimide 4-vinylbenzoate) brushes with reactive alkynes that differ in relative rates of activity of alkyne-azide cycloaddition reactions is described. The alkyne-derived polymer brushes undergo "click"-type cycloadditions with azido-containing compounds by two mechanisms: a strain-promoted alkyne-azide cycloaddition (SPAAC) with dibenzocyclooctyne (DIBO) and azadibenzocyclooctyne (ADIBO) or a copper-catalyzed alkyne-azide cycloaddition (CuAAC) to a propargyl group (PPG). Using a pseudo-first-order limited rate equation, rate constants for DIBO, ADIBO, and PPG-derivatized polymer brushes functionalized with an azide-functionalized dye were calculated as 7.7 × 10(-4), 4.4 × 10(-3), and 2.0 × 10(-2) s(-1), respectively. The SPAAC click reactions of the surface bound layers were determined to be slower than the equivalent reactions in solution, but the relative ratio of the reaction rates for the DIBO and ADIBO SPAAC reactions was consistent between solution and the polymer layer. The rate of functionalization was not influenced by the diffusion of azide into the polymer scaffold as long as the concentration of azide in solution was sufficiently high. The PPG functionalization by CuAAC had an extremely fast rate, which was comparable to other surface click reaction rates. Preliminary studies of dilute solution azide functionalization indicate that the diffusion-limited regime of brush functionalization impacts a 50 nm polymer brush layer and decreases the pseudo-first-order rate by a constant diffusion-limited factor of 0.233. PMID:23009188

  8. Chemoselective Immobilization of Proteins by Microcontact Printing and Bioorthogonal Click Reactions

    PubMed Central

    Tolstyka, Zachary P.; Richardson, Wade; Bat, Erhan; Stevens, Caitlin J.; Parra, Dayanara P.; Dozier, Jonathan K.; Distefano, Mark D.; Dunn, Bruce; Maynard, Heather D.

    2014-01-01

    Herein, a combination of microcontact printing of functionalized alkanethiols and site-specific modification of proteins is utilized to chemoselectively immobilize proteins onto gold surfaces either by oxime or copper catalyzed alkyne-azide click chemistry. Two molecules capable of click reactions, an aminooxy-functionalized alkanethiol and an azide-functionalized alkanethiol, were synthesized, and self-assembled monolayer (SAM) formation on gold was confirmed by IR spectroscopy. The alkanethiols were then individually patterned onto gold surfaces by microcontact printing. Site-specifically modified proteins, horse heart myoglobin (HHMb) containing an N-terminal α-oxoamide and a red-fluorescent protein (mCherry-CVIA) with a C-terminal alkyne, respectively were immobilized by incubation onto the stamped functionalized alkanethiol patterns. Pattern formation was confirmed by fluorescence microscopy. PMID:24166802

  9. Cu-Free 1,3-Dipolar Cycloaddition Click Reactions To Form Isoxazole Linkers in Chelating Ligands for fac-[MI(CO)3]+ Centers (M = Re, 99mTc)

    PubMed Central

    2015-01-01

    Isoxazole ring formation was examined as a potential Cu-free alternative click reaction to CuI-catalyzed alkyne/azide cycloaddition. The isoxazole reaction was explored at macroscopic and radiotracer concentrations with the fac-[MI(CO)3]+ (M = Re, 99mTc) core for use as a noncoordinating linker strategy between covalently linked molecules. Two click assembly methods (click, then chelate and chelate, then click) were examined to determine the feasibility of isoxazole ring formation with either alkyne-functionalized tridentate chelates or their respective fac-[MI(CO)3]+ complexes with a model nitrile oxide generator. Macroscale experiments, alkyne-functionalized chelates, or Re complexes indicate facile formation of the isoxazole ring. 99mTc experiments demonstrate efficient radiolabeling with click, then chelate; however, the chelate, then click approach led to faster product formation, but lower yields compared to the Re analogues. PMID:24483834

  10. Synthesis and post-synthetic modification of amine-, alkyne-, azide- and nitro-functionalized metal-organic frameworks based on DUT-5.

    PubMed

    Gotthardt, Meike A; Grosjean, Sylvain; Brunner, Tobias S; Kotzel, Johannes; Gänzler, Andreas M; Wolf, Silke; Bräse, Stefan; Kleist, Wolfgang

    2015-10-14

    Functionalized 4,4'-biphenyldicarboxylic acid molecules with additional amine, alkyne, azide or nitro groups were prepared and applied in the synthesis of novel metal-organic frameworks and mixed-linker metal-organic frameworks isoreticular to DUT-5. The properties of the frameworks could be tuned by varying the number of functional groups in the materials and the amine groups were employed in post-synthetic modification reactions without changing the framework structure or significantly decreasing the porosity of the materials. PMID:26336838

  11. Using click chemistry to modify block copolymers and their morphologies

    NASA Astrophysics Data System (ADS)

    Wollbold, Johannes

    Microphase separated block copolymers (BCPs) are emerging as promising templates and scaffolds for the fabrication of nanostructured materials. To achieve the desired nanostructures, it is necessary to establish convenient approaches to control the morphology of BCPs. It remains challenging to induce morphological transitions of BCPs via external fields. Click chemistry, especially alkyne/azide click chemistry, has been widely used to synthesize novel functionalized materials. Here, we demonstrate that alkyne/azide click chemistry can be used as an efficient approach to chemically modify BCPs and therefore induce morphological transitions. Alkyne-functionalized diblock copolymers (di-BCPs) poly(ethylene oxide)- block-poly(n-butyl methacrylate-random-propargyl methacrylate) (PEO-b-P(nBMA-r-PgMA)) have been successfully synthesized. When the di-BCP is blended with an azide additive Rhodamine B azide and annealed at elevated temperatures, click reaction occurs between the two components. With the Rhodamine B structure attached to the polymer backbone, the di-BCP shows dramatic change in the interactions between the two blocks and the volume fraction of each block. As a result, morphological transitions, such as disorder-to-order transitions (DOTs) and order-to-order transitions (OOTs), are observed. The reaction kinetics and morphology evolution during the click chemistry induced DOTs have been investigated by in-situ and ex-situ characterizations, and fast kinetics properties are observed. Microphase separated morphologies after the DOTs or OOTs are dictated by the composition of neat di-BCPs and the mole ratio between the alkyne and azide groups. The DOTs of PEO-b-P(nBMA-r-PgMA) di-BCPs induced by alkyne/azide click chemistry have also been achieved in thin film geometries, with comparable kinetics to bulk samples. The orientation of the microdomains is dependent on the grafting density of Rhodamine B structure as well as film thickness. At higher grafting densities

  12. Cooperative capture synthesis: yet another playground for copper-free click chemistry.

    PubMed

    Hou, Xisen; Ke, Chenfeng; Fraser Stoddart, J

    2016-07-21

    Click chemistry describes a family of modular, efficient, versatile and reliable reactions which have acquired a pivotal role as one of the most useful synthetic tools with a potentially broad range of applications. While copper(i)-catalysed alkyne-azide cycloaddition is the most widely adopted click reaction in the family, the fact that it is cytotoxic restricts its practice in certain situations, e.g., bioconjugation. Consequently, researchers have been exploring the development of copper-free click reactions, the most popular example so far being strain-promoted alkyne-azide cycloadditions. An early example of copper-free click reactions that is rarely mentioned in the literature is the cucurbit[6]uril (CB6) catalysed alkyne-azide cycloaddition (CB-AAC). Despite the unique ability of CB-AAC to generate mechanically interlocked molecules (MIMs) - in particular, rotaxanes - its slow reaction rate and narrow substrate acceptance limit its scope. In this Tutorial Review, we describe our efforts of late in developing the fundamental principles and practical applications of a new copper-free click reaction - namely, cooperative capture synthesis, whereby introducing a cyclodextrin (CD) as an accelerator in CB-AAC, hydrogen bonding networks are formed between the rims of CD and CB6 in a manner that is positively cooperative, giving rise to a high level of pre-organisation during efficient and quick rotaxane formation. For example, [4]rotaxanes can be prepared nearly quantitatively within a minute in water. Furthermore, we have demonstrated that CB-AAC can accommodate a wider substrate tolerance by introducing pillararenes as promoters. To date, we have put cooperative capture synthesis into practice by (i) preparing polyrotaxanes containing up to 200 rings in nearly quantitative yields, (ii) trapping conformational isomers of polymacrocycles as rings in rotaxanes, (iii) demonstrating solid-state fluorescence and Förster resonance energy transfer (FRET) processes by

  13. Covalent attachment of diphosphine ligands to glassy carbon electrodes via Cu-catalyzed alkyne-azide cycloaddition. Metallation with Ni(II).

    PubMed

    Das, Atanu K; Engelhard, Mark H; Lense, Sheri; Roberts, John A S; Bullock, R Morris

    2015-07-21

    Covalent tethering of P(Ph)2N(C6H4C≡CH)2 ligands (P(Ph)2N(C6H4C≡CH)2 = 1,5-di-(4-ethynylphenyl)-3,7-diphenyl-1,5-diaza-3,7-diphosphacyclooctane) to planar, azide-terminated glassy carbon electrode surfaces has been accomplished using a Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) coupling reaction, using a BH3←P protection-deprotection strategy. Deprotected, surface-confined ligands were metallated using [Ni(II)(MeCN)6](BF4)2. X-ray photoelectron spectroscopic measurements demonstrate that metallation introduced 1.3 equivalents Ni(II) per diphosphine onto the electrode surface. Exposure of the surface to a second diphosphine ligand, P(Ph)2N(Ph)2, resulted in the removal of Ni from the surface. Protection, coupling, deprotection, and metallation conditions were optimized using solution-phase model systems, with benzyl azide as a model for the azide-terminated carbon surface; these reactions generate a [Ni(II)(diphosphine)2](2+) complex. PMID:25811536

  14. Linking Metal Ions via Inorganic Click (iClick) Reactions

    SciTech Connect

    Veige, Adam

    2015-11-17

    This final report discusses the major objectives of the project, a discussion of the objectives achieved, a discussion of the objectives that failed, and finally, a discussion of future directions given the new knowledge obtained. This one-year seed project (with one year no-cost extension) contained three objectives: A) Expand the scope of iClick synthesis beyond AuI/AuI reactions. B) Elucidate a CuI-catalyzed iClick reaction. C) Synthesize and characterize tri- and tetra-metallic complexes as models for metallopolymers. Objectives A and C were achieved, whereas only parts of objective B were achieved.

  15. Preparing polymeric biomaterials using "click" chemistry techniques

    NASA Astrophysics Data System (ADS)

    Lin, Fei

    Significant efforts have been focused on preparing degradable polymeric biomaterials with controllable properties, which have the potential to stimulate specific cellular responses at the molecular level. Click reactions provide a universal tool box to achieve that goal through molecular level design and modification. This dissertation demonstrates multiple methodologies and techniques to develop advanced biomaterials through combining degradable polymers and click chemistry. In my initial work, a novel class of amino acid-based poly(ester urea)s (PEU) materials was designed and prepared for potential applications in bone defect treatment. PEUs were synthesized via interfacial polycondensation, and showed degradability in vivo and possessed mechanical strength superior to conventionally used polyesters. Further mechanical enhancement was achieved after covalent crosslinking with a short peptide crosslinker derived from osteogenic growth peptide (OGP). The in vitro and in an in vivo subcutaneous rat model demonstrated that the OGP-based crosslinkers promoted proliferative activity of cells and accelerated degradation properties of PEUs. As a continuous study, extra efforts were focused on the development of PEUs with functional pendant groups, including alkyne, azide, alkene, tyrosine phenol, and ketone groups. PEUs with Mw exceeding to 100K Da were obtained via interfacial polycondensation, and the concentration of pendent groups was varied using a copolymerization strategy. Electrospinning was used to fabricate PEU nanofiber matrices with mechanical strengths suitable for tissue engineering. A series of biomolecules were conjugated to nanofiber surface following electrospinning using click reactions in aqueous media. The ability to derivatize PEUs with biological motifs using high efficient chemical reactions will significantly expand their use in vitro and in vivo. Based on similar principles, a series of mono- and multifunctionalized polycaprolactone (PCL

  16. Application of catalyst-free click reactions in attaching affinity molecules to tips of atomic force microscopy for detection of protein biomarkers.

    PubMed

    Senapati, Subhadip; Manna, Saikat; Lindsay, Stuart; Zhang, Peiming

    2013-11-26

    Atomic force microscopy (AFM) has been extensively used in studies of biological interactions. Particularly, AFM based force spectroscopy and recognition imaging can sense biomolecules on a single molecule level, having great potential to become a tool for molecular diagnostics in clinics. These techniques, however, require affinity molecules to be attached to AFM tips in order to specifically detect their targets. The attachment chemistry currently used on silicon tips involves multiple steps of reactions and moisture sensitive chemicals, such as (3-aminopropyl)triethoxysilane (APTES) and N-hydroxysuccinimide (NHS) ester, making the process difficult to operate in aqueous solutions. In the present study, we have developed a user-friendly protocol to functionalize the AFM tips with affinity molecules. A key feature of it is that all reactions are carried out in aqueous solutions. In summary, we first synthesized a molecular anchor composed of cyclooctyne and silatrane for introduction of a chemically reactive function to AFM tips and a bifunctional polyethylene glycol linker that harnesses two orthogonal click reactions, copper free alkyne-azide cycloaddition and thiol-vinylsulfone Michael addition, for attaching affinity molecules to AFM tips. The attachment chemistry was then validated by attaching antithrombin DNA aptamers and cyclo-RGD peptides to silicon nitride (SiN) tips, respectively, and measuring forces of unbinding these affinity molecules from their protein cognates human α-thrombin and human α5β1-integrin immobilized on mica surfaces. In turn, we used the same attachment chemistry to functionalize silicon tips with the same affinity molecules for AFM based recognition imaging, showing that the disease-relevant biomarkers such as α-thrombin and α5β1-integrin can be detected with high sensitivity and specificity by the single molecule technique. These studies demonstrate the feasibility of our attachment chemistry for the use in functionalization

  17. Application of Catalyst-free Click Reactions in Attaching Affinity Molecules to Tips of Atomic Force Microscopy for Detection of Protein Biomarkers

    PubMed Central

    Senapati, Subhadip; Manna, Saikat; Lindsay, Stuart; Zhang, Peiming

    2013-01-01

    Atomic Force Microscopy (AFM) has been extensively used in studies of biological interactions. Particularly, AFM based force spectroscopy and recognition imaging can sense biomolecules on a single molecule level, having great potential to become a tool for molecular diagnostics in clinics. These techniques, however, require affinity molecules to be attached to AFM tips in order to specifically detect their targets. The attachment chemistry currently used on silicon tips involves multiple steps of reactions and moisture sensitive chemicals, such as (3-aminopropyl)triethoxysilane (APTES) and N-hydroxysuccinimide (NHS) ester, making the process difficult to operate in aqueous solutions. In the present study, we have developed a user-friendly protocol to functionalize the AFM tips with affinity molecules. A key feature of it is that all reactions are carried out in aqueous solutions. In summary, we first synthesized a molecular anchor composed of cyclooctyne and silatrane for introduction of a chemically reactive function to AFM tips and a bi-functional polyethylene glycol linker that harnesses two orthogonal click reactions, copper free alkyne-azide cycloaddition and thiol-vinylsulfone Michael addition, for attaching affinity molecules to AFM tips. The attachment chemistry was then validated by attaching anti-thrombin DNA aptamers and cyclo-RGD peptides to silicon nitride (SiN) tips respectively, and measuring forces of unbinding these affinity molecules from their protein cognates human α-thrombin and human α5β1-integrin immobilized on mica surfaces. In turn, we used the same attachment chemistry to functionalize silicon tips with the same affinity molecules for AFM based recognition imaging, showing that the disease-relevant biomarkers such as α-thrombin and α5β1-integrin can be detected with high sensitivity and specificity by the single molecule technique. These studies demonstrate the feasibility of our attachment chemistry for the use in functionalization

  18. Recyclable catalytic dendrimer nanoreactor for part-per-million Cu(I) catalysis of "click" chemistry in water.

    PubMed

    Deraedt, Christophe; Pinaud, Noël; Astruc, Didier

    2014-08-27

    Upon catalyst and substrate encapsulation, an amphiphilic dendrimer containing 27 triethylene glycol termini and 9 intradendritic triazole rings serves as a catalytic nanoreactor by considerably accelerating the Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) "click" reactions of various substrates in water using the catalyst Cu(hexabenzyltren)Br (tren = triaminoethylamine). Moreover this recyclable nanoreactor with intradendritic triazole rings strongly also activates the simple Sharpless-Fokin catalyst CuSO4 + sodium ascorbate in water under ambient conditions leading to exceptional TONs up to 510,000. This fully recyclable catalytic nanoreactor allows to considerably decrease the amount of this cheap copper catalyst down to industrially tolerable residues, and some biomedical and cosmetic applications are exemplified. PMID:25093967

  19. Cyclization of a cell-penetrating peptide via click-chemistry increases proteolytic resistance and improves drug delivery.

    PubMed

    Reichart, Florian; Horn, Mareike; Neundorf, Ines

    2016-06-01

    In this work we report synthesis and biological evaluation of a cell-penetrating peptide (CPP), that is partly cyclized via a triazole bridge. Recently, beneficious properties have been reported for cyclized peptides concerning their metabolic stability and intracellular uptake. A CPP based on human calcitonin was used in this study, and side chain cyclization was achieved via copper catalyzed alkyne-azide click reaction. Cell viability studies in several cell-lines revealed no cytotoxic effects. Furthermore, efficient uptake in breast cancer MCF-7 cells could be determined. Moreover, preliminary studies using this novel peptide as drug transporter for daunorubicin were performed. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID:27197760

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

    PubMed

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

    2013-01-01

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

  1. Nanoparticles under the light: click functionalization by photochemical thiol-yne reaction, towards double click functionalization.

    PubMed

    Demay-Drouhard, Paul; Nehlig, Emilie; Hardouin, Julie; Motte, Laurence; Guénin, Erwann

    2013-06-24

    A light click away: The first application of the thiol-yne reaction to nanoparticle functionalization is described (see figure). This metal-free click chemistry approach is compatible with the addition of various molecules at the surface and can be combined with CuAAC methodology to perform chemoselective double functionalization. PMID:23744751

  2. Comparative analysis of Cu (I)-catalyzed alkyne-azide cycloaddition (CuAAC) and strain-promoted alkyne-azide cycloaddition (SPAAC) in O-GlcNAc proteomics.

    PubMed

    Li, Shanshan; Zhu, He; Wang, Jiajia; Wang, Xiaomin; Li, Xu; Ma, Cheng; Wen, Liuqing; Yu, Bingchen; Wang, Yuehua; Li, Jing; Wang, Peng George

    2016-06-01

    O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an essential protein post-translational modification in a range of organisms. It is involved in various cellular processes such as nutrient sensing, protein degradation, gene expression, and is associated with many human diseases. Despite its importance, identifying O-GlcNAcylated proteins is a major challenge in proteomics. Here, using peracetylated N-azidoacetylglucosamine (Ac4 GlcNAz) as a bioorthogonal chemical handle, we described a gel-based mass spectrometry method for the identification of proteins with O-GlcNAc modification in A549 cells. In addition, we made a labeling efficiency comparison between two modes of azide-alkyne bioorthogonal reactions in click chemistry: copper-catalyzed azide-alkyne cycloaddition (CuAAC) with Biotin-Diazo-Alkyne and stain-promoted azide-alkyne cycloaddition (SPAAC) with Biotin-DIBO-Alkyne. After conjugation with click chemistry in vitro and enrichment via streptavidin resin, proteins with O-GlcNAc modification were separated by SDS-PAGE and identified with mass spectrometry. Proteomics data analysis revealed that 229 putative O-GlcNAc modified proteins were identified with Biotin-Diazo-Alkyne conjugated sample and 188 proteins with Biotin-DIBO-Alkyne conjugated sample, among which 114 proteins were overlapping. Interestingly, 74 proteins identified from Biotin-Diazo-Alkyne conjugates and 46 verified proteins from Biotin-DIBO-Alkyne conjugates could be found in the O-GlcNAc modified proteins database dbOGAP (http://cbsb.lombardi.georgetown.edu/hulab/OGAP.html). These results suggested that CuAAC with Biotin-Diazo-Alkyne represented a more powerful method in proteomics with higher protein identification and better accuracy compared to SPAAC. The proteomics credibility was also confirmed by the molecular function and cell component gene ontology (GO). Together, the method we reported here combining metabolic labeling, click chemistry, affinity-based enrichment, SDS

  3. F-18 Labeled RGD Probes Based on Bioorthogonal Strain-Promoted Click Reaction for PET Imaging

    PubMed Central

    2015-01-01

    A series of fluorine-substituted monomeric and dimeric cRGD peptide derivatives, such as cRGD-ADIBOT-F (ADIBOT = azadibenzocyclooctatriazole), di-cRGD-ADIBOT-F, cRGD-PEG5-ADIBOT-F, and di-cRGD-PEG5-ADIBOT-F, were prepared by strain-promoted alkyne azide cycloaddition (SPAAC) reaction of the corresponding aza-dibenzocyclooctyne (ADIBO) substituted peptides with a fluorinated azide 3. Among these cRGD derivatives, di-cRGD-PEG5-ADIBOT-F had the highest binding affinity in a competitive binding assay compared to other derivatives and even the original cRGDyk. On the basis of the in vitro study results, di-cRGD-PEG5-ADIBOT-18F was prepared from a SPAAC reaction with 18F-labeled azide and subsequent chemo-orthogonal scavenger-assisted separation without high performance liquid chromatography (HPLC) purification in 92% decay-corrected radiochemical yield (dcRCY) with high specific activity for further in vivo positron emission tomography (PET) imaging study. In vivo PET imaging study and biodistribution data showed that this radiotracer allowed successful visualization of tumors with good tumor-to-background contrast and significantly higher tumor uptake compared to other major organs. PMID:25893040

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

    NASA Astrophysics Data System (ADS)

    Purkait, Tapas Kumar

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

  5. Cu-free click cycloaddition reactions in chemical biology†

    PubMed Central

    Jewett, John C.

    2010-01-01

    Bioorthogonal chemical reactions are paving the way for new innovations in biology. These reactions possess extreme selectivity and biocompatibility, such that their participating reagents can form covalent bonds within richly functionalized biological systems—in some cases, living organisms. This tutorial review will summarize the history of this emerging field, as well as recent progress in the development and application of bioorthogonal copper-free click cycloaddition reactions. PMID:20349533

  6. Synthesis of Phenyl-Adducted Cyclodextrin through the Click Reaction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A new derivative of ß-cyclodextrin (CD) has been made incorporating the phenyl group through the use of click reaction. The resulting product exhibits a self-association phenomenon through the formation of inclusion compound between the phenyl group and CD. The product has been characterized by 1H...

  7. Origin of Orthogonality of Strain-Promoted Click Reactions

    PubMed Central

    Wagner, Johannes A; Mercadante, Davide; Nikić, Ivana; Lemke, Edward A; Gräter, Frauke

    2015-01-01

    Site-specific labeling of biomolecules is rapidly advancing due to the discovery of novel mutually orthogonal reactions. Quantum chemistry studies have also increased our understanding of their relative rates, although these have until now been based on highly simplified reactants. Here we examine a set of strain-promoted click-type cycloaddition reactions of n-propyl azide, 3-benzyl tetrazine and 3-benzyl-6-methyl tetrazine with cyclooctenes/ynes, in which we aim to address all relevant structural details of the reactants. Our calculations have included the obligatory handles used to attach the label and biomolecule as these can critically influence the stereochemistry and electron demand of the reaction. We systematically computed orbital gaps, activation and distortion energies using density functional theory and determined experimental rates for validation. Our results challenge the current paradigm of the inverse electron demand for this class of reactions. We found that the ubiquitous handles, when next to the triple bond of cyclooctynes, can switch the Diels–Alder type ligations to normal electron demand, a class we term as SPINEDAC reactions. Electron donating substituents on tetrazine can enhance normal demand but also increase distortion penalties. The presence and isomeric configuration of handles thus determine the reaction speed and regioselectivity. Our findings can be directly utilized in engineering genuine cycloaddition click chemistries for biological labeling. PMID:26178299

  8. Origin of Orthogonality of Strain-Promoted Click Reactions.

    PubMed

    Wagner, Johannes A; Mercadante, Davide; Nikić, Ivana; Lemke, Edward A; Gräter, Frauke

    2015-08-24

    Site-specific labeling of biomolecules is rapidly advancing due to the discovery of novel mutually orthogonal reactions. Quantum chemistry studies have also increased our understanding of their relative rates, although these have until now been based on highly simplified reactants. Here we examine a set of strain-promoted click-type cycloaddition reactions of n-propyl azide, 3-benzyl tetrazine and 3-benzyl-6-methyl tetrazine with cyclooctenes/ynes, in which we aim to address all relevant structural details of the reactants. Our calculations have included the obligatory handles used to attach the label and biomolecule as these can critically influence the stereochemistry and electron demand of the reaction. We systematically computed orbital gaps, activation and distortion energies using density functional theory and determined experimental rates for validation. Our results challenge the current paradigm of the inverse electron demand for this class of reactions. We found that the ubiquitous handles, when next to the triple bond of cyclooctynes, can switch the Diels-Alder type ligations to normal electron demand, a class we term as SPINEDAC reactions. Electron donating substituents on tetrazine can enhance normal demand but also increase distortion penalties. The presence and isomeric configuration of handles thus determine the reaction speed and regioselectivity. Our findings can be directly utilized in engineering genuine cycloaddition click chemistries for biological labeling. PMID:26178299

  9. Superstructures of fluorescent cyclodextrin via click-reaction.

    PubMed

    Maciollek, Arkadius; Ritter, Helmut; Beckert, Rainer

    2013-01-01

    Mono-(6-azido-6-deoxy)-β-cyclodextrin (CD) was covalently attached to an alkyne-modified 5-methyl-2-(pyridin-2-yl)thiazol-4-ol yielding a fluorophore containing CD in a click-type reaction. Intermolecular complexes were formed by poly(host-guest)-interactions. The supramolecular structures were characterized by (1)H NMR-ROESY spectroscopy, dynamic light scattering, UV-vis spectroscopy, fluorescence spectroscopy, and asymmetric flow field-flow fractionation. By adding potassium adamantane-1-carboxylate, the thiazol dye is displaced from the CD-cavity and the elongated noncovalent polymeric structures collapse. PMID:23766796

  10. Labeling proteins on live mammalian cells using click chemistry.

    PubMed

    Nikić, Ivana; Kang, Jun Hee; Girona, Gemma Estrada; Aramburu, Iker Valle; Lemke, Edward A

    2015-05-01

    We describe a protocol for the rapid labeling of cell-surface proteins in living mammalian cells using click chemistry. The labeling method is based on strain-promoted alkyne-azide cycloaddition (SPAAC) and strain-promoted inverse-electron-demand Diels-Alder cycloaddition (SPIEDAC) reactions, in which noncanonical amino acids (ncAAs) bearing ring-strained alkynes or alkenes react, respectively, with dyes containing azide or tetrazine groups. To introduce ncAAs site specifically into a protein of interest (POI), we use genetic code expansion technology. The protocol can be described as comprising two steps. In the first step, an Amber stop codon is introduced--by site-directed mutagenesis--at the desired site on the gene encoding the POI. This plasmid is then transfected into mammalian cells, along with another plasmid that encodes an aminoacyl-tRNA synthetase/tRNA (RS/tRNA) pair that is orthogonal to the host's translational machinery. In the presence of the ncAA, the orthogonal RS/tRNA pair specifically suppresses the Amber codon by incorporating the ncAA into the polypeptide chain of the POI. In the second step, the expressed POI is labeled with a suitably reactive dye derivative that is directly supplied to the growth medium. We provide a detailed protocol for using commercially available ncAAs and dyes for labeling the insulin receptor, and we discuss the optimal surface-labeling conditions and the limitations of labeling living mammalian cells. The protocol involves an initial cloning step that can take 4-7 d, followed by the described transfections and labeling reaction steps, which can take 3-4 d. PMID:25906116

  11. A sensitive fluorescent sensor for quantification of alpha-fetoprotein based on immunosorbent assay and click chemistry.

    PubMed

    Xie, Qunfang; Weng, Xiuhua; Lu, Lijun; Lin, Zhenyu; Xu, Xiongwei; Fu, Caili

    2016-03-15

    A novel fluoresencent immunosensor for determination of cancer biomarkers such as alpha-fetoprotein (AFP) was designed by utilizing both the high specificity of antigen-antibody sandwich structure and the high sensitivity of the click chemistry based fluorescence detection. Instead of an enzyme or fluorophore, the CuO nanoparticles are labeled on the detection antibody, which was not susceptible to the change of the external environments. The CuO nanoparticles which were modified on the sandwich structure can be dissolved to produce Cu(2+) ions with the help of HCl and then the Cu(2+) ions were reduced by sodium ascorbate to produce Cu(+) ions which triggered the Cu(+) catalyzed alkyne-azide cycloaddition (CuAAC) reaction between the weak fluorescent compound (3-azido-7-hydroxycoumarin) and propargyl alcohol to form a strong fluorescent compound. A good linear relationship was observed between the fluorescence increase factor of the system and the concentration of AFP in the range of 0.025-5.0 ng/mL with a detection limit of 12 pg/mL (S/N=3). The proposed fluorescent sensor had been applied to detect AFP in the human serum samples and gave satisfactory results. PMID:26386330

  12. A click strategy for the immobilization of MacMillan organocatalysts onto polymers and magnetic nanoparticles.

    PubMed

    Riente, Paola; Yadav, Jagjit; Pericàs, Miquel A

    2012-07-20

    A chemically modified, first generation MacMillan imidazolidin-4-one has been anchored onto 1% DVB Merrifield resin and Fe3O4 (5.3 ± 1.4 nm) magnetic nanoparticles through copper-catalyzed alkyne azide cycloaddition (CuAAC) reactions. The resulting immobilized catalysts have been successfully used in the asymmetric Friedel-Crafts alkylation of N-substituted pyrroles with α,β-unsaturated aldehydes. The PS-supported catalyst (B) showed higher catalytic activity and enantioselectivity, while the MNP-supported one (A) showed higher recyclability and could be used in a sequential process with intermediate magnetic decantation. PMID:22758605

  13. Current approaches for RNA labeling in vitro and in cells based on click reactions.

    PubMed

    Schulz, Daniela; Rentmeister, Andrea

    2014-11-01

    Over recent years, click reactions have become recognized as valuable and flexible tools to label biomacromolecules such as proteins, nucleic acids, and glycans. Some of the developed strategies can be performed not only in aqueous solution but also in the presence of cellular components, as well as on (or even in) living cells. These labeling strategies require the initial, specific modification of the target molecule with a small, reactive moiety. In the second step, a click reaction is used to covalently couple a reporter molecule to the biomolecule. Depending on the type of reporter, labeling by the click reaction can be used in many different applications, ranging from isolation to functional studies of biomacromolecules. In this minireview, we focus on labeling strategies for RNA that rely on the click reaction. We first highlight click reactions that have been used successfully to label modified RNA, and then describe different strategies to introduce the required reactive groups into target RNA. The benefits and potential limitations of the strategies are critically discussed with regard to possible future developments. PMID:25224574

  14. A photoreducible copper(II)-tren complex of practical value: generation of a highly reactive click catalyst.

    PubMed

    Harmand, Lydie; Lambert, Romain; Scarpantonio, Luca; McClenaghan, Nathan D; Lastécouères, Dominique; Vincent, Jean-Marc

    2013-11-25

    A detailed study on the photoreduction of the copper(II) precatalyst 1 to generate a highly reactive cuprous species for the copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction is presented. For the photoactive catalyst described herein, the activation is driven by a photoinduced electron transfer (PET) process harnessing a benzophenone-like ketoprofenate chromophore as a photosensitizer, which is equally the counterion. The solvent is shown to play a major role in the Cu(II) to Cu(I) reduction process as the final electron source, and the influence of the solvent nature on the photoreduction efficiency has been studied. Particular attention was paid to the use of water as a potential solvent, aqueous media being particularly appealing for CuAAC processes. The ability to solubilize the copper-tren complexes in water through the formation of inclusion complexes with β-CDs is demonstrated. Data is also provided on the fate of the copper(I)-tren catalytic species when reacting with O2, O2 being used to switch off the catalysis. These data show that partial oxidation of the secondary benzylamine groups of the ligand to benzylimines occurs. Preliminary results show that when prolonged irradiation times are employed a Cu(I) to Cu(0) over-reduction process takes place, leading to the formation of copper nanoparticles (NPs). Finally, the main objective of this work being the development of photoactivable catalysts of practical value for the CuAAC, the catalytic, photolatent, and recycling properties of 1 in water and organic solvents are reported. PMID:24127367

  15. Investigation of pyridine/propargyl bromide reaction and strong fluorescence enhancements of the resultant poly(propargyl pyridinium bromide).

    PubMed

    Zhou, Changming; Gao, Yong; Chen, Daoyong

    2012-09-20

    Poly(propargyl pyridinium bromide), a kind of conjugated polyelectrolyte with polyacetylene as the backbone and pyridinium as side groups, was synthesized simply via reaction between pyridine and propargyl bromide under mild conditions. The resultant polymer was characterized by (1)H NMR, elemental analysis, FT-IR, and GPC-MALLS. An alkyne group was confirmed as the end group of the polymer chains by the alkyne/azide click chemistry, which reveals that the polymerization is terminated by the reaction between propargyl bromide and carbon anions. It is known that monosubstituted polyacetylenes reported have very weak fluorescence intensities, which limit their applications. As a monosubstituted polyacetylene, the freshly prepared poly(propargyl pyridinium bromide) also has a very weak fluorescence. However, we confirmed that addition of some anions to the polymer solution in DMF or DMSO leads to the fluorescence enhancements up to 25 times. Besides, heating the polymer solution at a temperature between 70 and 130 °C for longer than 0.5 h greatly enhanced the fluorescence intensity. The interaction with the anions or the heating enhances the effective exciton confinement within the conjugated backbone and thus results in the fluorescence enhancements. After the fluorescence enhancements, poly(propargyl pyridinium bromide) has relatively strong fluorescence emissions, which will make it promising in fluorescence-based applications. PMID:22928912

  16. Ultrasound responsive block copolymer micelle of poly(ethylene glycol)-poly(propylene glycol) obtained through click reaction.

    PubMed

    Li, Fayong; Xie, Chuan; Cheng, Zhengang; Xia, Hesheng

    2016-05-01

    The well-defined amphiphilic poly(ethylene glycol)-block-poly(propylene glycol) copolymer containing 1, 2, 3-triazole moiety and multiple ester bonds (PEG-click-PPG) was prepared by click reaction strategy. The PEG-click-PPG copolymer can self-assemble into spherical micelles in aqueous solution. It is found that high intensity focused ultrasound (HIFU) can open the copolymer PEG-click-PPG micelles and trigger the release of the payload in the micelle. The multiple ester bonds introduced in the junction point of the copolymer chain through click reactions were cleaved under HIFU, and leads to the disruption of the copolymer micelle and fast release of loaded cargo. The click reaction provides a convenient way to construct ultrasound responsive copolymer micelles with weak bonds. PMID:26703197

  17. Light effect on Click reaction: Role of photonic quantum dot catalyst.

    PubMed

    Nandi, Debkumar; Taher, Abu; Islam, Rafique Ul; Choudhary, Meenakshi; Siwal, Samarjeet; Mallick, Kaushik

    2016-01-01

    Due to the light excitation, the valence band electron of the copper (I) sulfide quantum dot transfer to the conduction band and act as a scavenger of the terminal proton of the alkyne in the presence of organic azide with the formation of 1,4-disubstituted 1,2,3-triazoles, where the copper(I) species of Cu2S act as a catalyst for the reaction. The above cycloaddition reaction between alkyne and azide is commonly known as the Click reaction. In this study, experiments were carried out under the exposure of ultra-violate and daylight and also dark environment. According to the original recommendation for the Click reaction, the role of the base was also considered for this experiment. We found that the effect of conduction band electron is more efficient than the recommended conventional base mediated reaction procedure. PMID:27621031

  18. Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments

    NASA Astrophysics Data System (ADS)

    Deforest, Cole A.; Polizzotti, Brian D.; Anseth, Kristi S.

    2009-08-01

    Click chemistry provides extremely selective and orthogonal reactions that proceed with high efficiency and under a variety of mild conditions, the most common example being the copper(I)-catalysed reaction of azides with alkynes. While the versatility of click reactions has been broadly exploited, a major limitation is the intrinsic toxicity of the synthetic schemes and the inability to translate these approaches into biological applications. This manuscript introduces a robust synthetic strategy where macromolecular precursors react through a copper-free click chemistry, allowing for the direct encapsulation of cells within click hydrogels for the first time. Subsequently, an orthogonal thiol-ene photocoupling chemistry is introduced that enables patterning of biological functionalities within the gel in real time and with micrometre-scale resolution. This material system enables us to tailor independently the biophysical and biochemical properties of the cell culture microenvironments in situ. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gels with ideal structures that can be photopatterned, and all in the presence of cells.

  19. Tandem Catalysis of an Aldol-'Click' Reaction System within a Molecular Hydrogel.

    PubMed

    Araújo, Marco; Muñoz Capdevila, Iván; Díaz-Oltra, Santiago; Escuder, Beatriu

    2016-01-01

    A heterogeneous supramolecular catalytic system for multicomponent aldol-'click' reactions is reported. The copper(I) metallohydrogel functionalized with a phenyltriazole fragment was able to catalyze the multicomponent reaction between phenylacetylene, p-nitrobenzaldehyde, and an azide containing a ketone moiety, obtaining the corresponding aldol products in good yields. A possible mechanistic pathway responsible for this unexpected catalytic behavior has been proposed. PMID:27338313

  20. Discovery and enantiocontrol of axially chiral urazoles via organocatalytic tyrosine click reaction

    PubMed Central

    Zhang, Ji-Wei; Xu, Jin-Hui; Cheng, Dao-Juan; Shi, Chuan; Liu, Xin-Yuan; Tan, Bin

    2016-01-01

    Axially chiral compounds play an important role in areas such as asymmetric catalysis. The tyrosine click-like reaction is an efficient approach for synthesis of urazoles with potential applications in pharmaceutical and asymmetric catalysis. Here we discover a class of urazole with axial chirality by restricted rotation around an N–Ar bond. By using bifunctional organocatalyst, we successfully develop an organocatalytic asymmetric tyrosine click-like reaction in high yields with excellent enantioselectivity under mild reaction conditions. The excellent remote enantiocontrol of the strategy originates from the efficient discrimination of the two reactive sites in the triazoledione and transferring the stereochemical information of the catalyst into the axial chirality of urazoles at the remote position far from the reactive site. PMID:26864510

  1. Click Grafting of Alkyne-containing Vinyl Polymers onto Biosynthesized Extracellular Matrix Protein Containing Azide Functionality and Adhesion Control of Human Umbilical Vein Endothelial Cells

    PubMed Central

    Yamada, Tomoki

    2015-01-01

    In vivo incorporation of a phenylalanine (Phe) analogue, p-azidophenylalanine (p-N3Phe) into an artificial extracellular matrix protein (aECM-CS5-ELF) was accomplished using a bacterial expression host that harbors the mutant phenylalanyl-tRNA synthetase (PheRS) with an enlarged binding pocket, in which the Ala294Gly/Thr251Gly mutant PheRS (PheRS**) was expressed under the control of T7 promoters. In this study, biosynthesized aECM-CS5-ELF containing p-N3Phe (aECM-CS5-ELF-N3) was coupled with alkyne-containing vinyl polymers prepared via controlled radical polymerization of three vinyl monomers, (styrene, acrylamide, and N-isopropylacrylamide) using a trithiocarbonate as the RAFT agent. Grafting of the vinyl polymers onto the aECM was accomplished via a copper-catalyzed alkyne-azide click reaction. The lower critical transition temperature (LCST) was evaluated, as well as the solubility in aqueous and organic media, which are dependent on the incorporation ratio of p-N3Phe and species of graft chains, in which the LCST behavior was altered remarkably when poly(N-isopropylacrylamide) moieties were attached as side chains. Circular dichroism measurements indicate conformational change was not induced by the grafting. Specific adhesion of human umbilical vein endothelial cells (HUVECs) onto the aECM-CS5-ELF-N3-graft-poly(N-isopropylacrylamide) composite surface and subsequent temperature-sensitive detachment were also demonstrated. PMID:26294960

  2. A New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine--Tertiary Isocyanate Coupling for Polymer Ligation.

    PubMed

    Gody, Guillaume; Roberts, Derrick A; Maschmeyer, Thomas; Perrier, Sébastien

    2016-03-30

    Click reactions have provided access to an array of remarkably complex polymer architectures. However, the term "click" is often applied inaccurately to polymer ligation reactions that fail to respect the criteria that typify a true "click" reaction. With the purpose of providing a universal way to benchmark polymer-polymer coupling efficiency at equimolarity and thus evaluate the fulfilment of click criteria, we report a simple one-pot methodology involving the homodicoupling of α-end-functionalized polymers using a small-molecule bifunctional linker. A combination of SEC analysis and chromatogram deconvolution enables straightforward quantification of the coupling efficiency. We subsequently employ this methodology to evaluate an overlooked candidate for the click reaction family: the addition of primary amines to α-tertiary isocyanates (α-(t)NCO). Using our bifunctional linker coupling strategy, we show that the amine-(t)NCO reaction fulfills the criteria for a polymer-polymer click reaction, achieving rapid, chemoselective, and quantitative coupling at room temperature without generating any byproducts. We demonstrate that amine-(t)NCO coupling is faster and more efficient than the more common amine-tertiary active ester coupling under equivalent conditions. Additionally, we show that the α-(t)NCO end group is unprecedentedly stable in aqueous media. Thus, we propose that the amine-(t)NCO ligation is a powerful new click reaction for efficient macromolecular coupling. PMID:26927624

  3. Application of a Double Aza-Michael Reaction in a ‘Click, Click, Cy-Click’ Strategy: From Bench to Flow

    PubMed Central

    Zang, Qin; Javed, Salim; Ullah, Farman; Zhou, Aihua; Knudtson, Christopher A.; Bi, Danse; Basha, Fatima Z.; Organ, Michael G.; Hanson, Paul R.

    2011-01-01

    The development of a ‘click, click, cy-click’ process utilizing a double aza-Michael reaction to generate functionalized 1,2,5-thiadiazepane 1,1-dioxides is reported. Optimization in flow, followed by scale out of the inter-/intramolecular double aza-Michael addition has also been realized using a microwave-assisted, continuous flow organic synthesis platform (MACOS). In addition, a facile one-pot, sequential strategy employing in situ Huisgen cycloaddition post-double aza-Michael has been accomplished, and is applicable to library synthesis. PMID:21927510

  4. Multifunctional and Continuous Gradients of Biointerfaces Based on Dual Reverse Click Reactions.

    PubMed

    Guan, Zhen-Yu; Wu, Chih-Yu; Wu, Jyun-Ting; Tai, Ching-Heng; Yu, Jiashing; Chen, Hsien-Yeh

    2016-06-01

    Chemical or biological gradients that are composed of multifunctional and/or multidirectional guidance cues are of fundamental importance for prospective biomaterials and biointerfaces. As a proof of concept, a general modification approach for generating multifunctional and continuous gradients was realized via two controlled and reversed click reactions, namely, thermo-activated thiol-yne and copper-free alkyne and azide click reactions. The cell adhesion property of fibroblasts was guided in a gradient with an enhancement, showing that the PEG molecule and RGD peptide were countercurrently immobilized to form such reversed gradients (with negating of the cell adhesion property). Using the gradient modification protocol to also create countercurrent distributions of FGF-2 and BMP-2 gradients, the demonstration of not only multifunctional but also gradient biointerfacial properties was resolved in time latencies on one surface by showing the manipulation in gradients toward proliferation and osteogenic differentiation for adipose-derived stem cells. PMID:27182777

  5. Versatility of Alkyne-Modified Poly(Glycidyl Methacrylate) Layers for Click Reactions

    SciTech Connect

    Soto-Cantu, Dr. Erick; Lokitz, Bradley S; Hinestrosa Salazar, Juan Pablo; Deodhar, Chaitra; Messman, Jamie M; Ankner, John Francis; Kilbey, II, S Michael

    2011-01-01

    Functional soft interfaces are of interest for a variety of technologies. We describe three methods for preparing substrates with alkyne groups, which show versatility for 'click' chemistry reactions. Two of the methods have the same root: formation of thin, covalently attached, reactive interfacial layers of poly(glycidyl methacrylate) (PGMA) via spin coating onto silicon wafers followed by reactive modification with either propargylamine or 5-hexynoic acid. The amine or the carboxylic acid moieties react with the epoxy groups of PGMA, creating interfacial polymer layers decorated with alkyne groups. The third method consists of using copolymers comprising glycidyl methacrylate and propargyl methacrylate (pGP). The pGP copolymers are spin coated and covalently attached on silicon wafers. For each method, we investigate the factors that control film thickness and content of alkyne groups using ellipsometry, and study the nanophase structure of the films using neutron reflectometry. Azide-terminated polymers of methacrylic acid and 2-vinyl-4,4-dimethylazlactone synthesized via reversible addition-fragmentation chain transfer polymerization were attached to the alkyne-modified substrates using 'click' chemistry, and grafting densities in the range of 0.007-0.95 chains nm{sup -2} were attained. The maximum density of alkyne groups attained by functionalization of PGMA with propargylamine or 5-hexynoic acid was approximately 2 alkynes nm{sup -3}. The alkyne content obtained by the three decorating approaches was sufficiently high that it was not the limiting factor for the click reaction of azide-capped polymers.

  6. Plasmachemical Double Click Thiol-ene Reactions for Wet Electrical Barrier.

    PubMed

    Fraser, R C; Carletto, A; Wilson, M; Badyal, J P S

    2016-08-24

    Click thiol-ene chemistry is demonstrated for the reaction of thiol containing molecules with surface alkene bonds during electrical discharge activation. This plasmachemical reaction mechanism is shown to be 2-fold for allyl mercaptan (an alkene and thiol group containing precursor), comprising self-cross-linked nanolayer deposition in tandem with interfacial cross-linking to the surface alkene bonds of a polyisoprene base layer. A synergistic multilayer structure is attained which displays high wet electrical barrier performance during immersion in water. PMID:27505445

  7. CuAAC click reactions for the design of multifunctional luminescent ruthenium complexes.

    PubMed

    Zabarska, Natalia; Stumper, Anne; Rau, Sven

    2016-02-01

    CuAAC (Cu(i) catalyzed azide-alkyne cycloaddition) click chemistry has emerged as a versatile tool in the development of photoactive ruthenium complexes with multilateral potential applicability. In this contribution we discuss possible synthetic approaches towards CuAAC reactions with ruthenium(ii) polypyridine complexes and their differences with respect to possible applications. We focus on two main application possibilities of the click-coupled ruthenium assemblies. New results within the development of ruthenium based photosensitizers for the field of renewable energy supply, i.e. DSSCs (dye-sensitized solar cells) and artificial photocatalysis for the production of hydrogen, or for anticancer photodynamic therapeutic applications are reviewed. PMID:26758682

  8. Simultaneous electropolymerization and electro-click functionalization for highly versatile surface platforms.

    PubMed

    Rydzek, Gaulthier; Terentyeva, Tatyana G; Pakdel, Amir; Golberg, Dmitri; Hill, Jonathan P; Ariga, Katsuhiko

    2014-05-27

    Simple preparation methods of chemically versatile and highly functionalizable surfaces remain rare and present a challenging research objective. Here, we demonstrate a simultaneous electropolymerization and electro-click functionalization process (SEEC) for one-pot self-construction of aniline- and naphthalene-based functional polymer films where both polymerization and click functionalization are triggered by applying electrochemical stimuli. Cyclic voltammetry (CV) can be applied for the simultaneous oxidation of 4-azidoaniline and the reduction of Cu(II) ions, resulting in polymerization of the former, and the Cu(I)-catalyzed alkyne/azide cycloaddition ("click" chemistry). Properties of the films obtained can be tuned by varying their morphology, their chemically "clicked" content, or by postconstruction functionalization. To demonstrate this, the CV scan rates, component monomers, and "clicked" molecules were varied. Covalent postconstruction immobilization of horseradish peroxidase was also performed. Consequently, pseudocapacitance and enzyme activity were affected. SEEC provides surface scientists an easy access to a wide range of functionalization possibilities in several fields including sensors, fuel cells, photovoltaics, and biomaterials. PMID:24738664

  9. A New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine–Tertiary Isocyanate Coupling for Polymer Ligation

    PubMed Central

    2016-01-01

    Click reactions have provided access to an array of remarkably complex polymer architectures. However, the term “click” is often applied inaccurately to polymer ligation reactions that fail to respect the criteria that typify a true “click” reaction. With the purpose of providing a universal way to benchmark polymer–polymer coupling efficiency at equimolarity and thus evaluate the fulfilment of click criteria, we report a simple one-pot methodology involving the homodicoupling of α-end-functionalized polymers using a small-molecule bifunctional linker. A combination of SEC analysis and chromatogram deconvolution enables straightforward quantification of the coupling efficiency. We subsequently employ this methodology to evaluate an overlooked candidate for the click reaction family: the addition of primary amines to α-tertiary isocyanates (α-tNCO). Using our bifunctional linker coupling strategy, we show that the amine–tNCO reaction fulfills the criteria for a polymer–polymer click reaction, achieving rapid, chemoselective, and quantitative coupling at room temperature without generating any byproducts. We demonstrate that amine–tNCO coupling is faster and more efficient than the more common amine–tertiary active ester coupling under equivalent conditions. Additionally, we show that the α-tNCO end group is unprecedentedly stable in aqueous media. Thus, we propose that the amine–tNCO ligation is a powerful new click reaction for efficient macromolecular coupling. PMID:26927624

  10. Preparation of Metalloporphyrin-Bound Superparamagnetic Silica Particles via "Click" Reaction.

    PubMed

    Hollingsworth, Javoris V; Bhupathiraju, N V S Dinesh K; Sun, Jirun; Lochner, Eric; Vicente, M Graça H; Russo, Paul S

    2016-01-13

    A facile approach using click chemistry is demonstrated for immobilization of metalloporphyrins onto the surface of silica-coated iron oxide particles. Oleic-acid stabilized iron oxide nanocrystals were prepared by thermal decomposition of iron(III) acetylacetonate. Their crystallinity, morphology, and superparamagnetism were determined using X-ray diffraction, transmission electron microscopy, and a superconducting quantum interference device. Monodisperse core-shell particles were produced in the silica-coating of iron oxide via microemulsion synthesis. Surface modification of these particles was performed in two steps, which included the reaction of silica-coated iron oxide particles with 3-bromopropyltrichlorosilane, followed by azido-functionalization with sodium azide. Monoalkylated porphyrins were prepared using the Williamson ether synthesis of commercially available tetra(4-hydroxyphenyl) porphyrin with propargyl bromide in the presence of a base. (1)H NMR and matrix-assisted laser desorption ionization confirmed the identity of the compounds. The prepared monoalkyne porphyrins were zinc-metalated prior to their introduction to azide-functionalized, silica-coated iron oxide particles in the click reaction. X-ray photoelectron spectroscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy were used to characterize the surface chemistry after each step in the reaction. In addition, particle size was determined using dynamic light scattering and microscopy. The presented methodology is versatile and can be extended to other photoreactive systems, such as phthalocyanines and boron-dipyrromethane, which may lead to new materials for optical, photonic, and biological applications. PMID:26691852

  11. Click and Patterned Functionalization of Graphene by Diels-Alder Reaction.

    PubMed

    Li, Jing; Li, Meng; Zhou, Li-Li; Lang, Shuang-Yan; Lu, Hai-Yan; Wang, Dong; Chen, Chuan-Feng; Wan, Li-Jun

    2016-06-22

    Chemical functionalization is a promising approach to controllably manipulate the characteristics of graphene. Here, we designed cis-dienes, featuring two dihydronaphthalene backbones, to decorate a graphene surface via Diels-Alder (DA) click reaction. The installation of a diene moiety into a nonplanar molecular structure to form cis-conformation enables a rapid (∼5 min) DA reaction between graphene and diene groups. Patterned graphene of sub-micrometer resolution can be obtained by easily soaking poly(methyl methacrylate)-masked graphene in solution of hydroxyl-substituted cis-diene at room temperature. The functionalization degree can be further controlled by carrying out the reaction at higher temperature. The present result gives important insight into the effect of molecular conformation on the graphene functionalization process, and provides an effective and facile method for graphene functionalization. PMID:27264112

  12. Interfacial thiol-ene photo-click reactions for forming multilayer hydrogels

    PubMed Central

    Shih, Han; Fraser, Andrew K.; Lin, Chien-Chi

    2014-01-01

    Interfacial visible light-mediated thiol-ene photo-click reactions were developed for preparing step-growth hydrogels with multilayer structures. The effect of a non-cleavage type photoinitiator eosin-Y on visible light-mediated thiol-ene photopolymerization was first characterized using in situ photo-rheometry, gel fraction, and equilibrium swelling ratio. Next, spectrophotometric properties of eosin-Y in the presence of various relevant macromer species were evaluated using UV/Vis spectrometry. It was determined that eosin-Y was able to re-initiate thiol-ene photo-click reaction even after light exposure. Due to its small molecular weight, most eosin-Y molecules readily leached out from the hydrogels. The diffusion of residual eosin-Y from pre-formed hydrogels was exploited for fabricating multilayer step-growth hydrogels. Interfacial hydrogel coating was formed via the same visible light-mediated gelation mechanism without adding fresh initiator. The thickness of the thiol-ene gel coating could be easily controlled by adjusting visible light exposure time, eosin-Y concentration initially loaded in the core gel, or macromer concentration in the coating solution. The major benefits of this interfacial thiol-ene coating system include its simplicity and cytocompatibility. The formation of thiol-ene hydrogels and coatings neither requires nor generates any cytotoxic components. This new gelation chemistry may have great utilities in controlled release of multiple sensitive growth factors and encapsulation of multiple cell types for tissue regeneration. PMID:23384151

  13. Phospha-Michael Addition as a New Click Reaction for Protein Functionalization.

    PubMed

    Lee, Yan-Jiun; Kurra, Yadagiri; Liu, Wenshe R

    2016-03-15

    A new type of click reaction between an alkyl phosphine and acrylamide was developed and applied for site-specific protein labeling in vitro and in live cells. Acrylamide is a small electrophilic olefin that readily undergoes phospha-Michael addition with an alkyl phosphine. Our kinetic study indicated a second-order rate constant of 0.07 m(-1)  s(-1) for the reaction between tris(2-carboxyethyl)phosphine and acrylamide at pH 7.4. To demonstrate its application in protein functionalization, we used a dansyl-phosphine conjugate to successfully label proteins that were site-specifically installed with N(ɛ) -acryloyl-l-lysine and employed a biotin-phosphine conjugate to selectively probe human proteins that were metabolically labeled with N-acryloyl-galactosamine. PMID:26756316

  14. Resin-supported catalysts for CuAAC click reactions in aqueous or organic solvents.

    PubMed

    Presolski, Stanislav I; Mamidyala, Sreeman K; Manzenrieder, Florian; Finn, M G

    2012-10-01

    The copper-catalyzed azide-alkyne cycloaddition click reaction is a valuable process for the synthesis of libraries of drug candidates, derivatized polymers and materials, and a wide variety of other functional molecules. In some circumstances, the removal of the copper catalyst is both necessary and inconvenient. We describe here two immobilized forms of a Cu-binding ligand that has been shown to accelerate triazole formation under many different conditions, using different resin supports that are appropriate for aqueous or organic solvents. Copper leaching from these resins was modest, allowing them to be reused in many reaction/filtration cycles without recharging with metal ion. The utility of this catalyst form was demonstrated in the convenient synthesis of 20 N-acetylgalactosamine derivatives for biological testing. PMID:22946559

  15. Precision synthesis of functional materials via RAFT polymerization and click-type chemical reactions

    NASA Astrophysics Data System (ADS)

    Flores, Joel Diez

    2011-12-01

    The need to tailor polymeric architectures with specific physico-chemical properties via the simplest, cleanest, and most efficient synthetic route possible has become the ultimate goal in polymer synthesis. Recent progress in macromolecular science, such as the discoveries of controlled/"living" free radical polymerization (CRP) methods, has brought about synthetic capabilities to prepare (co)polymers with advanced topologies, predetermined molecular weights, narrow molecular weight distributions, and precisely located functional groups. In addition, the establishment of click chemistry has redefined the selected few highly efficient chemical reactions that become highly useful in post-polymerization modification strategies. Hence, the ability to make well-defined topologies afforded by controlled polymerization techniques and the facile incorporation of functionalities along the chain via click-type reactions have yielded complex architectures, allowing the investigation of physical phenomena which otherwise could not be studied with systems prepared via conventional methods. The overarching theme of the research work described in this dissertation is the fusion of the excellent attributes of reversible addition-fragmentation chain transfer (RAFT) polymerization method, which is one of the CRP techniques, and click-type chemical reactions in the precision of synthesis of advanced functional materials. Chapter IV is divided into three sections. In Section I, the direct RAFT homopolymerization of 2-(acryloyloxy)ethyl isocyanate (AOI) and subsequent post-polymerization modifications are described. The polymerization conditions were optimized in terms of the choice of RAFT chain transfer agent (CTA), polymerization temperature and the reaction medium. Direct RAFT polymerization of AOI requires a neutral CTA, and relatively low reaction temperature to yield AOI homopolymers with low polydispersities. Efficient side-chain functionalization of PAOI homopolymers was

  16. Applications of Click Chemistry Reactions to the Synthesis of Functional Materials

    NASA Astrophysics Data System (ADS)

    Accurso, Adrian A.

    This body of work focuses on the production of functional materials using the most reliable carbon-hetoratom bond-forming processes available, which are widely termed "click chemistry" reactions in the literature. This focus on function is enabled by a basis in synthetic chemistry, and where appropriate, brings in techniques from the related fields of materials science and biology to address current needs in those areas. Chapter 1 concerns the in situ production of azide and alkyne-based click chemistry adhesive polymers. Screening of a library of multivalent azides and alkynes was accomplished on a custom-built highthroughput instrument and followed up on a lap-shear testing apparatus. The conductivity of composites made of the adhesive was also explored according to standard methods. The second and third chapters explore the synthesis and function of a family of related [3.3.1]-bicyclononane dichlorides, which we have termed "WCL" electrophiles, and their potential applications for surface functionalization, the synthesis of polycations, and candidate membrane disruptive compounds. The rates of consumption of dichlorides and hydrolysis of model compounds were also explored using NMR, GC-MS, and HPLC-based methods.

  17. Synthesis and structure design of new bio-based elastomers via Thiol-ene-Click Reactions.

    PubMed

    Khan, Shafiullah; Wang, Zhao; Wang, Runguo; Zhang, Liqun

    2016-10-01

    The additions of 2-mercaptoethanol to (S)-(-)-limonene via click reaction is described as an adaptable and efficient way to obtain alcohol functionalized renewable monomer for the synthesis of new cross-linkable bio-based elastomers. Thiol first reacted with the limonene endocyclic double bond and then reacted with the exocyclics double bond to form the difunctional monomer. The structure of the monomer was determined by using FTIR, (1)H NMR and mass spectrometry. Thermal Gravimetric Analysis (TGA) and Differential Scanning Calorimetrys (DSC) characterization exposed that this monomer could be used to synthesize elastomers with excellent and adaptable thermal properties. The molecular weight of the synthesized elastomer could reach 186kDaa via melting polycondensation route and the structure-properties relationship was deliberated. Finally, these elastomers were mixed with dicumyl peroxide (DCP) to form cross-linked elastomers with certain mechanical property, and the gel contents of the elastomers were confirmed by using Soxhlet extraction method. PMID:27287154

  18. Synthesize of new fluorescent polymeric nanoparticle using modified cellulose nanowhisker through click reaction.

    PubMed

    Parsamanesh, Masoumeh; Dadkhah Tehrani, Abbas

    2016-01-20

    New biopolymeric nanoparticles consisting of cellulose nanowhisker (CNW) as support system and polyglycerol (PG) as surface modifying agent were prepared. PG was attached to the surface of CNW by click chemistry reaction. CdSe quantum dots then interact with the prepared system by noncovalent interaction. These new synthesized biopolymeric nanoparticles were characterized by spectroscopic measurement methods such as IR spectroscopy, UV-vis spectroscopy, NMR spectroscopy; scanning electron microscopy etc. due to the presence of hydrophilic polymerr at the surface of CNW, synthesized nanomaterials were water soluble, and have a large number of functional group for further modification. Also the presence of fluorescence quantum dots (QDS) caused fluorescence property of synthesized system. These new synthesized system has potential application to be used in different filed such as drug delivery, biomedical imaging etc. PMID:26572477

  19. Electroactive carbon nanoforms: a comparative study via sequential arylation and click chemistry reactions

    NASA Astrophysics Data System (ADS)

    Mateos-Gil, Jaime; Rodríguez-Pérez, Laura; Moreno Oliva, María; Katsukis, Georgios; Romero-Nieto, Carlos; Herranz, M. Ángeles; Guldi, Dirk M.; Martín, Nazario

    2014-12-01

    The reactivity of several carbon nanoforms (CNFs), single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs) and graphene, has been investigated through a combination of arylation and click chemistry CuI-mediated azide-alkyne cycloaddition (CuAAC) reactions. The approach is based on the incorporation of electroactive π-extended tetrathiafulvalene (exTTF) units into the triazole linkers to modulate the electronic properties of the obtained conjugates. The introduction of strain, by bending the planar graphene sheet into a 3D carbon framework, is responsible for the singular reactivity observed in carbon nanotubes. The formed nanoconjugates were fully characterized by analytical, spectroscopic, and microscopic techniques (TGA, FTIR, Raman, UV-Vis-NIR, cyclic voltammetry, TEM and XPS). In the case of SWCNT conjugates, where the functionalization degree is higher, a series of steady-state and time resolved spectroscopy experiments revealed a photoinduced electron transfer from the exTTF unit to the electron-accepting SWCNT.The reactivity of several carbon nanoforms (CNFs), single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs) and graphene, has been investigated through a combination of arylation and click chemistry CuI-mediated azide-alkyne cycloaddition (CuAAC) reactions. The approach is based on the incorporation of electroactive π-extended tetrathiafulvalene (exTTF) units into the triazole linkers to modulate the electronic properties of the obtained conjugates. The introduction of strain, by bending the planar graphene sheet into a 3D carbon framework, is responsible for the singular reactivity observed in carbon nanotubes. The formed nanoconjugates were fully characterized by analytical, spectroscopic, and microscopic techniques (TGA, FTIR, Raman, UV-Vis-NIR, cyclic voltammetry, TEM and XPS). In the case of SWCNT conjugates, where the functionalization degree is higher, a series of steady-state and time resolved

  20. Cu/Pd-Catalyzed, Three-Component Click Reaction of Azide, Alkyne, and Aryl Halide: One-Pot Strategy toward Trisubstituted Triazoles.

    PubMed

    Wei, Fang; Li, Haoyu; Song, Chuanling; Ma, Yudao; Zhou, Ling; Tung, Chen-Ho; Xu, Zhenghu

    2015-06-01

    A Cu/Pd-catalyzed, three-component click reaction of azide, alkyne, and aryl halide has been developed. By using this Cu/Pd transmetalation relay catalysis, a variety of 1,4,5-trisubstituted 1,2,3-triazoles were quickly assembled in one step in high yields with complete regioselectivity, just like assembling Lego bricks. Notably, different from the well-established CuAAC click reactions only working on terminal alkynes, this reaction offers an alternative solution for the problem of the click reaction of internal alkynes. PMID:26000564

  1. Biostability enhancement of oil core - polysaccharide multilayer shell via photoinitiator free thiol-ene 'click' reaction.

    PubMed

    Calcagno, Vincenzo; Vecchione, Raffaele; Sagliano, Angela; Carella, Antonio; Guarnieri, Daniela; Belli, Valentina; Raiola, Luca; Roviello, Antonio; Netti, Paolo A

    2016-06-01

    Layer-by-layer of polyelectrolytes has emerged as one of the easiest and most controlled techniques to deposit ultrathin polymer layers mainly driven by electrostatic interactions. However, this kind of interaction results to be weak and easily breakable in physiological environment. Here we report on the preparation of nanocapsules completely made of natural biomaterials: a lipophilic core (soybean oil and egg lecithin as surfactant) as nanometric template and a polysaccharide-based multilayer shell (glycol chitosan and heparin) covalently cross-linked. We first modified glycol chitosan with a thiol moiety and heparin with an alkene moiety, respectively, and then we built a polymer multilayer film with a covalent cross-linkage among layers, exploiting the light initiated thiol-ene reaction, known as click chemistry. We showed the possibility to perform the covalent cross-linkage without any photoinitiator or metal catalyst, thus avoiding cytotoxic effects and further purification steps. The so realized nanocapsules resulted to be stable and completely biocompatible and, therefore, of interest for the biotechnology fields, mainly for drug delivery. PMID:26962765

  2. Fabrication of biodendrimeric β-cyclodextrin via click reaction with potency of anticancer drug delivery agent.

    PubMed

    Toomari, Yousef; Namazi, Hassan; Entezami, Ali Akbar

    2015-08-01

    The aim of this work was the synthesis of biodendrimeric β-cyclodextrin (β-CD) on the secondary face with encapsulation efficacy, with β-CDs moiety to preserve the biocompatibility properties, also particularly growth their loading capacity for drugs with certain size. The new dendrimer, having 14 β-CD residues attached to the core β-CD in secondary face (11), was prepared through click reaction. The encapsulation property of the prepared compound was evaluated by methotrexate (MTX) drug molecule. Characterization of compound 11 was performed with (1)H NMR, (13)C NMR and FTIR and its supramolecular inclusion complex structure was determined using FTIR, DLS, DSC and SEM techniques. In vitro cytotoxicity test results showed that compound 11 has very low or no cytotoxic effect on T47D cancer cells. In vitro drug release study at pHs 3, 5 and 7.4 showed that the release process was noticeably pH dependent and the dendrimer could be used as an appropriate controlled drug delivery system (DDS) for cancer treatment. PMID:26056989

  3. Effective ascorbate-free and photolatent click reactions in water using a photoreducible copper(II)-ethylenediamine precatalyst

    PubMed Central

    Beniazza, Redouane; Bayo, Natalia; Molton, Florian; Duboc, Carole; Massip, Stéphane; McClenaghan, Nathan; Lastécouères, Dominique

    2015-01-01

    Summary The search for copper catalysts able to perform effectively click reactions in water in the absence of sodium ascorbate is an active area of current research with strong potential for applications in bioconjugation. The water-soluble and photoreducible copper(II)–EDA (EDA = ethylenediamine) complex 1, which has two 4-benzoylbenzoates acting as both counterion and photosensitizer, has been synthesized and characterized by different techniques including single crystal X-ray diffraction. Highly efficient photoreduction was demonstrated when solutions of 1 in hydrogen atom donating solvents, such as THF or MeOH, were exposed to UVA radiation (350–400 nm) provided by a low pressure mercury lamp (type TLC = thin-layer chromatography, 365 nm), or by a 23 W fluorescent bulb, or by ambient/sunlight. In water, a much poorer hydrogen atom donating solvent, the photoreduction of 1 proved inefficient. Interestingly, EPR studies revealed that complex 1 could nonetheless be effectively photoreduced in water when alkynes were present in solution. The catalytic activity of 1 for click reactions involving a range of water-soluble alkynes and azides, in particular saccharides, was tested under various illumination conditions. Complex 1 was found to exhibit a photolatent character, the photogenerated copper(I) being very reactive. On irradiating aqueous reaction mixtures containing 1 mol % of 1 at 365 nm (TLC lamp) for 1 h, click reactions were shown to proceed to full conversion. PMID:26664615

  4. Composition controlled synthesis of PCL-PEG Janus nanoparticles: magnetite nanoparticles prepared from one-pot photo-click reaction.

    PubMed

    Khoee, S; Bagheri, Y; Hashemi, A

    2015-03-01

    The aim of this study is to investigate the effect of polymer nature on the morphology of synthesized nanoparticles. Super paramagnetic iron oxide nanoparticles (SPIONs) were prepared by co-precipitation method and then reacted with (3-mercaptopropyl) trimethoxysilane to obtain thiol-decorated SPIONs. Acrylated poly(caprolactone) and methoxy poly(ethylene glycol) were prepared, and then "thiol-ene click" reaction was performed under UV irradiation to attach two types of polymers on the surface of magnetite nanoparticles via the "photo-click" reaction method. Computational modelling was used for the prediction of the self-assembly of polymers on the surface of SPIONs, which determines the morphology of polymer coated nanoparticles. PMID:25666985

  5. Composition controlled synthesis of PCL-PEG Janus nanoparticles: magnetite nanoparticles prepared from one-pot photo-click reaction

    NASA Astrophysics Data System (ADS)

    Khoee, S.; Bagheri, Y.; Hashemi, A.

    2015-02-01

    The aim of this study is to investigate the effect of polymer nature on the morphology of synthesized nanoparticles. Super paramagnetic iron oxide nanoparticles (SPIONs) were prepared by co-precipitation method and then reacted with (3-mercaptopropyl) trimethoxysilane to obtain thiol-decorated SPIONs. Acrylated poly(caprolactone) and methoxy poly(ethylene glycol) were prepared, and then ``thiol-ene click'' reaction was performed under UV irradiation to attach two types of polymers on the surface of magnetite nanoparticles via the ``photo-click'' reaction method. Computational modelling was used for the prediction of the self-assembly of polymers on the surface of SPIONs, which determines the morphology of polymer coated nanoparticles.

  6. Computational studies on the regioselectivity of metal-catalyzed synthesis of 1,2,3 triazoles via click reaction: a review.

    PubMed

    Hosseinnejad, Tayebeh; Fattahi, Bahareh; Heravi, Majid M

    2015-10-01

    Recently, the experimental and computational chemists have been attracted widely to the click synthesis of 1,2,3 triazoles and their derivatives, mainly due to the fact that they are interesting from structural and mechanistic points of view. Moreover, catalyzed click have been well established as a successful strategy showing high regioselectivity and high yield for the synthesis of 1,2,3-triazoles. In this review, we try to highlight the recently reported computational assessments on the origins and predection of regioselectivity in the catalyzed click synthesis of triazoles from the mechanistic and thermodynamical points of view. In this light, density functional theory (DFT) calculations on the free energy profiles of azide-alkyne cycloaddition reactions have been underscored. The stereoelectronic features for the role of copper, ruthenium, and iridium as catalyst on regioselectivity of click reactions have also be discussed. Graphical Abstract Computational origins for the regioselective behavior of 1,2,3 triazoles click synthesis. PMID:26385849

  7. Biodegradable Multiblock Poly[N-(2-hydroxypropyl)methacrylamide] via Reversible Addition-Fragmentation Chain Transfer Polymerization and Click Chemistry

    PubMed Central

    Luo, Kui; Yang, Jiyuan; Kopečková, Pavla; Kopeček, Jindřich

    2011-01-01

    A new bifunctional chain transfer agent (CTA) containing alkyne end groups was designed, synthesized and used for direct synthesis of clickable telechelic polymers. Good control of reversible addition-fragmentation chain transfer (RAFT) polymerization of N-(2-hydroxypropyl)methacrylamide (HPMA) was achieved by using the new CTA, as indicated by a linear increase of number average molecular weight (Mn) with conversion and low polydispersity (PDI) (<1.1). In particular, enzymatically degradable multiblock HPMA polymers were readily prepared by subsequent reaction with αω, -diazido oligopeptide (GFLG) sequence via CuI catalyzed alkyne-azide cycloaddition. Upon exposure of high molecular weight fractions of multiblock polyHPMA to papain or cathepsin B, the polymer was degraded into segments of molecular weight and narrow polydispersity similar to those of the initial telechelic polyHPMA. PMID:21552355

  8. DOTA derivatives for site-specific biomolecule-modification via click chemistry: synthesis and comparison of reaction characteristics.

    PubMed

    Wängler, Carmen; Schäfer, Martin; Schirrmacher, Ralf; Bartenstein, Peter; Wängler, Björn

    2011-06-15

    Due to the high stability of its complexes with many M(2+) and M(3+)-ions, DOTA (1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid) is the most commonly used chelator for the derivatization and radiolabeling of bioactive molecules. Most of the currently used DOTA derivatives comprise amine-reactive functionalities, limiting their application to the derivatization of fully protected molecules or otherwise resulting in randomly distributed conjugation sites of undefined number. Click chemistry reactions are a valuable alternative to this unspecific conjugation as they proceed efficiently and chemoselectively under mild conditions allowing a site-specific derivatization of unprotected biomolecules. In this work, we describe straightforward syntheses of DOTA derivatives containing thiol, maleimide, aminooxy, aldehyde, alkyne, and azide functionalities, amenable to the currently most often used click chemistry reactions. Furthermore, the efficiency of the respective click reactions introducing DOTA into bioactive molecules was investigated. For each of the synthesized DOTA synthons, the site-specific and efficient conjugation to Tyr(3)-octreotate could be shown. Among these, the addition and oxime formation reactions proceeded fast and without side reactions, giving the products in high yields of 64-83% after purification. The copper-catalyzed triazole formation reactions produced some side-products, giving the desired products in lower, but still reasonable overall yields of 19-25%. All synthesized peptide-DOTA-conjugates were labeled with (68)Ga in high radiochemical yields of 96-99% and high specific activities providing compounds of high purity, demonstrating the applicability of all synthons for biomolecule modification and subsequent radiolabeling. PMID:21620712

  9. Curing of polymer thermosets via click reactions and on demand processes

    NASA Astrophysics Data System (ADS)

    Brei, Mark Richard

    In the first project, an azide functional resin and tetra propargyl aromatic diamines were fabricated for use as a composite matrix. These systems take already established epoxy/amine matrices and functionalize them with click moieties. This allows lower temperatures to be used in the production of a thermoset part. These new systems yield many better mechanical properties than their epoxy/amine derivatives, but their Tgs are low in comparison. The second project investigates the characterization of a linear system based off of the above azide functional resin and a difunctional alkyne. Through selectively choosing catalyst, the linear system can show regioselectivity to either a 1,4-disubstituted triazole, or a 1,5-disubstituted triazole. Without the addition of catalyst, the system produces both triazoles in almost an equal ratio. The differently catalyzed systems were cured and then analyzed by 1H and 13C NMR to better understand the structure of the material. The third project builds off of the utility of the aforementioned azide/alkyne system and introduces an on-demand aspect to the curing of the thermoset. With the inclusion of copper(II) within the azide/alkyne system, UV light is able to catalyze said reaction and cure the material. It has been shown that the copper(II) loading levels can be extremely small, which helps in reducing the copper's effect on mechanical properties The fourth project takes a look at polysulfide-based sealants. These sealants are normally cured via an oxidative reaction. This project took thiol-terminated polysulfides and fabricated alkene-terminated polysulfides for use as a thiol-ene cured material. By changing the mechanism for cure, the polysulfide can be cured via UV light with the use of a photoinitiator within the thiol/alkene polysulfide matrix. The final chapter will focus on a characterization technique, MALDI-TOF, which was used to help characterize the above materials as well as many others. By using MALDI-TOF, the

  10. Non-Catalyzed Click Reactions of ADIBO Derivatives with 5-Methyluridine Azides and Conformational Study of the Resulting Triazoles

    PubMed Central

    Smyslova, Petra; Popa, Igor; Lyčka, Antonín; Tejral, Gracian; Hlavac, Jan

    2015-01-01

    Copper-free click reactions between a dibenzoazocine derivative and azides derived from 5-methyluridine were investigated. The non-catalyzed reaction yielded both regioisomers in an approximately equivalent ratio. The NMR spectra of each regioisomer revealed conformational isomery. The ratio of isomers was dependent on the type of regioisomer and the type of solvent. The synthesis of various analogs, a detailed NMR study and computational modeling provided evidence that the isomery was dependent on the interaction of the azocine and pyrimidine parts. PMID:26673606

  11. Aptamer-based organic-silica hybrid affinity monolith prepared via "thiol-ene" click reaction for extraction of thrombin.

    PubMed

    Wang, Zheng; Zhao, Jin-cheng; Lian, Hong-zhen; Chen, Hong-yuan

    2015-06-01

    A novel strategy for preparing aptamer-based organic-silica hybrid monolithic column was developed via "thiol-ene" click chemistry. Due to the large specific surface area of the hybrid matrix and the simplicity, rapidness and high efficiency of "thiol-ene" click reaction, the average coverage density of aptamer on the organic-silica hybrid monolith reached 420 pmol μL(-1). Human α-thrombin can be captured on the prepared affinity monolithic column with high specificity and eluted by NaClO4 solution. N-p-tosyl-Gly-Pro-Arg p-nitroanilide acetate was used as the sensitive chromogenic substrate of thrombin. The thrombin enriched by this affinity column was detected with a detection of limit of 0.01 μM by spectrophotometry. Furthermore, the extraction recovery of thrombin at 0.15 μM in human serum was 91.8% with a relative standard deviation of 4.0%. These results indicated that "thiol-ene" click chemistry provided a promising technique to immobilize aptamer on organic-inorganic hybrid monolith and the easily-assembled affinity monolithic material could be used to realize highly selective recognition of trace proteins. PMID:25863371

  12. Azide functional monolayers grafted to a germanium surface: model substrates for ATR-IR studies of interfacial click reactions.

    PubMed

    Zhang, Shuo; Koberstein, Jeffrey T

    2012-01-10

    High-quality azide-functional substrates are prepared by a low temperature reaction of 11-bromoundecyltrichlorosilane with UV-ozone-treated germanium ATR-IR plates followed by nucleophilic substitution of the terminal bromine by addition of sodium azide. The resulting monolayer films are characterized by atomic force microscopy (AFM), contact angle analysis, X-ray photoelectron spectroscopy (XPS), attenuated total reflectance infrared spectroscopy (ATR-IR), and ellipsometry. XPS and ellipsometric thickness data correspond well to the results of molecular model calculations confirming the formation of a densely packed azide-functional monolayer. These azide-functional substrates enable interfacial "click" reactions with complementary alkyne-functional molecules to be studied in situ by ATR-IR. To illustrate their potential utility for kinetic studies we show that, in the presence of copper(I) catalyst, the azide-modified surfaces react rapidly and quantitatively with 5-chloro-pentyne to form triazoles via a 1,3-dipolar cycloaddition reaction. Time-resolved ATR-IR measurements indicate that the interfacial click reaction is initially first order in azide concentration as expected from the reaction mechanism, with a rate constant of 0.034 min(-1), and then transitions to apparent second order dependence, with a rate constant of 0.017 min(-1)/(chains/nm(2)), when the surface azide and triazole concentrations become similar, as predicted by Oyama et al. The reaction achieves an ultimate conversion of 50% consistent with the limit expected due to steric hindrance of the 5-chloro-pentyne reactant at the surface. PMID:22081885

  13. Copper Granule-Catalyzed Microwave-Assisted Click Synthesis of Polyphenol Dendrimers

    PubMed Central

    Lee, Choon Young; Held, Rich; Sharma, Ajit; Baral, Rom; Nanah, Cyprien; Dumas, Dan; Jenkins, Shannon; Upadhaya, Samik; Du, Wenjun

    2013-01-01

    Syringaldehyde and vanillin-based antioxidant dendrimers were synthesized via microwave-assisted alkyne-azide 1,3-dipolar cycloaddition using copper granules as a catalyst. The use of Cu(I) as a catalyst resulted in copper contaminated dendrimers. In order to produce copper-free antioxidant dendrimers for biological applications, Cu(I) was substituted with copper granules. Copper granules were ineffective at both room temperature and under reflux conditions (< 5% yield). However, it was an excellent catalyst when dendrimer synthesis was performed under microwave irradiation, giving yields up to 94% within 8 h. ICP-mass analysis of the antioxidant dendrimers obtained with this method showed virtually no copper contamination (9 ppm), which was the same as background level. The synthesized antioxidants, free from copper contamination, demonstrated potent radical scavenging with IC50 values of less than 3 µM in the DPPH assay. In comparison, dendrimers synthesized from Cu(I)-catalyzed Click chemistry showed a high level of copper contamination (4800 ppm) and no detectable antioxidant activity. PMID:24127771

  14. Copper-granule-catalyzed microwave-assisted click synthesis of polyphenol dendrimers.

    PubMed

    Lee, Choon Young; Held, Rich; Sharma, Ajit; Baral, Rom; Nanah, Cyprien; Dumas, Dan; Jenkins, Shannon; Upadhaya, Samik; Du, Wenjun

    2013-11-15

    Syringaldehyde- and vanillin-based antioxidant dendrimers were synthesized via microwave-assisted alkyne-azide 1,3-dipolar cycloaddition using copper granules as a catalyst. The use of Cu(I) as a catalyst resulted in copper contaminated dendrimers. To produce copper-free antioxidant dendrimers for biological applications, Cu(I) was substituted with copper granules. Copper granules were ineffective at both room temperature and under reflux conditions (<5% yield). However, they were an excellent catalyst when dendrimer synthesis was performed under microwave irradiation, giving yields up to 94% within 8 h. ICP-mass analysis of the antioxidant dendrimers obtained with this method showed virtually no copper contamination (9 ppm), which was the same as the background level. The synthesized antioxidants, free from copper contamination, demonstrated potent radical scavenging with IC50 values of less than 3 μM in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In comparison, dendrimers synthesized from Cu(I)-catalyzed click chemistry showed a high level of copper contamination (4800 ppm) and no detectable antioxidant activity. PMID:24127771

  15. Quantitative fluorine NMR to determine carbohydrate density on glyconanomaterials synthesized from perfluorophenyl azide-functionalized silica nanoparticles by click reaction.

    PubMed

    Kong, Na; Zhou, Juan; Park, JaeHyeung; Xie, Sheng; Ramström, Olof; Yan, Mingdi

    2015-09-15

    A quantitative fluorine NMR ((19)F qNMR) method was developed to determine the carbohydrate density on glyconanomaterials. Mannose (Man)- and galactose (Gal)-conjugated silica nanoparticles (SNPs) were synthesized from perfluorophenyl azide (PFPA)-functionalized SNPs and propargylated Man or Gal by copper-catalyzed azide-alkyne cycloaddition (click reaction). After treating PFPA-SNPs or Man-SNPs with hydrofluoric acid followed by lyophilization, the remaining residues were directly subjected to (19)F NMR analysis. The density of PFPA on PFPA-SNP was determined to be 7.7 ± 0.2 × 10(-16) nmol/nm(2) and Man on Man-SNP to be 6.4 ± 0.2 × 10(-16) nmol/nm(2) giving a yield of ∼83% for the click coupling reaction. The apparent dissociation constant (Kd) of Man-SNPs with fluorescein isothiocyanate (FITC)-concanavalin A (Con A) was determined using a fluorescence competition assay to be 0.289 ± 0.003 μM, which represents more than 3 orders of magnitude affinity increase compared to free Man with Con A. PMID:26280598

  16. Click Reaction on Solid Phase Enables High Fidelity Synthesis of Nucleobase-Modified DNA.

    PubMed

    Tolle, Fabian; Rosenthal, Malte; Pfeiffer, Franziska; Mayer, Günter

    2016-03-16

    The post-synthetic functionalization of nucleic acids via click chemistry (CuAAC) has seen tremendous implementation, extending the applicability of nucleobase-modified nucleic acids in fields like fluorescent labeling, nanotechnology, and in vitro selection. However, the production of large quantities of high-density functionalized material via solid phase synthesis has been hampered by oxidative by-product formation associated with the alkaline workup conditions. Herein, we describe a rapid and cost-effective protocol for the high fidelity large-scale production of nucleobase-modified nucleic acids, exemplified with a recently described nucleobase-modified aptamer. PMID:26850226

  17. Initiator and Photocatalyst-Free Visible Light Induced One-Pot Reaction: Concurrent RAFT Polymerization and CuAAC Click Reaction.

    PubMed

    Wang, Jie; Wang, Xinbo; Xue, Wentao; Chen, Gaojian; Zhang, Weidong; Zhu, Xiulin

    2016-05-01

    A new, visible light-catalyzed, one-pot and one-step reaction is successfully employed to design well-controlled side-chain functionalized polymers, by the combination of ambient temperature revisible addtion-fragmentation chain transfer (RAFT) polymerization and click chemistry. Polymerizations are well controlled in a living way under the irradiation of visible light-emitting diode (LED) light without photocatalyst and initiator, using the trithiocarbonate agent as iniferter (initiator-transfer agent-terminator) agent at ambient temperature. Fourier transfer infrared spectroscopy (FT-IR), NMR, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) data confirm the successful one-pot reaction. Compared to the reported zero-valent metal-catalyzed one-pot reaction, the polymerization rate is much faster than that of the click reaction, and the visible light-catalyzed one-pot reaction can be freely and easily regulated by turning on and off the light. PMID:27029002

  18. Crosslinked Matrix-free Nanocomposites

    NASA Astrophysics Data System (ADS)

    Dach, Benjamin; Rengifo, Hernan; Turro, Nicholas; Koberstein, Jeffrey

    2010-03-01

    Matrix-free polymer-silica nanocomposites are formed by crosslinking polymer coated nanoparticles via the `click' reaction. The `click' reaction is also known as H"uisgen 1, 3-dipolar cycloaddition of terminal alkyne and azide functional groups to give 1, 2, 3-triazoles. Silica nanoparticles are functionalized with alkyne and azide moieties. Heterobifunctional α,φ-trimethylsilane-alkyne,azide-poly(styrene) (TMS-PS-N3) and α,φ-trimethylsilane-alkyne,azide--poly(tert-butyl acrylate) (TMS-PtBA-N3) are then covalently bound to the surfaces of the nanoparticles via the `click' reaction. The bare and modified nanoparticles are analyzed by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The thermal, morphological, and mechanical properties of the systems are investigated by thermogravimetric analysis (TGA), transmission electron microscopy (TEM), and dynamic rheology, respectively. .

  19. Sunlight-driven copper-catalyst activation applied to photolatent click chemistry.

    PubMed

    Beniazza, Rédouane; Lambert, Romain; Harmand, Lydie; Molton, Florian; Duboc, Carole; Denisov, Sergey; Jonusauskas, Gedeminas; McClenaghan, Nathan D; Lastécouères, Dominique; Vincent, Jean-Marc

    2014-10-01

    The synthesis, full characterization, photoreduction properties, and catalytic activity for the copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction of a copper(II)-DMEDA (N,N'-dimethylethylendiamine) complex is reported. Spectroscopic studies (UV/Vis, EPR) demonstrated that under daylight illumination highly effective copper(II) to copper(I) reduction occurs in this complex. These findings are in agreement with a high photoreduction quantum yield value of 0.22 in MeOH, and a value approaching unity as determined in THF. The reduction process, which can also be conducted by irradiation at 365 nm by using a standard TLC (thin layer chromatography) lamp, is ascribed to a highly efficient photoinduced electron transfer (PET) process mediated by the benzophenone photosensitizer present in the carboxylate counterion. Having deaerated the reaction mixture, the photogenerated copper(I) species proved to be highly active for the CuAAC reaction, demonstrated by reactions conducted with low catalyst loading (0.5 mol %) on a range of clickable protected and non-protected mono- and disaccharides. Once initiated, the reaction can be stopped at any time on introducing air into the reaction medium. Deoxygenation followed by irradiation restores the activity, making the copper(II)-DMEDA complex a switchable catalyst of practical value. PMID:25171758

  20. Rapid approach to biobased telechelics through two one-pot thiol-ene click reactions.

    PubMed

    Lluch, Cristina; Ronda, Joan C; Galià, Marina; Lligadas, Gerard; Cádiz, Virginia

    2010-06-14

    The application of environmentally friendly thiol-ene chemistry to the preparation of biobased telechelics is presented in this work. This methodology is based on two one-pot photoinitiated thiol-ene click processes: step-growth polymerization using a 3,6-dioxa-1,8-octanedithiol and end-group postpolymerization modification with three functional thiols: 2-mercaptoethanol, 3-mercaptopropionic acid, and 3-mercaptopropyltrimethoxysilane. We applied this approach to a potentially 100% biomass-derived monomer, allyl ester of 10-undecenoic acid (UDA). To show the generality and scope of this methodology, a series of well-defined telechelics with molecular weight ranging from 1000-3000 g/mol and hydroxyl, carboxyl, or trimethoxysilyl groups at the polymer terminus were prepared. An exhaustive (1)H NMR and MALDI-TOF MS analyses demonstrates the highly end-group fidelity of this methodology being an interesting procedure for the accelerated preparation of telechelics derived from divinyl monomers. UDA-based thelechelic diol prepared using this methodology was reacted with 4,4'-methylenebis(phenylisocyanate) and 1,4-butanediol as the chain extender to obtain multiblock poly(ester urethane). PMID:20462176

  1. 64Cu-labeled somatostatin analogues conjugated with cross-bridged phosphonate-based chelators via strain-promoted click chemistry for PET imaging: in silico through in vivo studies.

    PubMed

    Cai, Zhengxin; Ouyang, Qin; Zeng, Dexing; Nguyen, Kim N; Modi, Jalpa; Wang, Lirong; White, Alexander G; Rogers, Buck E; Xie, Xiang-Qun; Anderson, Carolyn J

    2014-07-24

    Somatostatin receptor subtype 2 (sstr2) is a G-protein-coupled receptor (GPCR) that is overexpressed in neuroendocrine tumors. The homology model of sstr2 was built and was used to aid the design of new somatostatin analogues modified with phosphonate-containing cross-bridged chelators for evaluation of using them as PET imaging radiopharmaceuticals. The new generation chelators were conjugated to Tyr3-octreotate (Y3-TATE) through bioorthogonal, strain-promoted alkyne azide cycloaddition (SPAAC) to form CB-TE1A1P-DBCO-Y3-TATE (AP) and CB-TE1K1P-PEG4-DBCO-Y3-TATE (KP) in improved yields compared to standard direct conjugation methods of amide bond formation. Consistent with docking studies, the clicked bioconjugates showed high binding affinities to sstr2, with Kd values ranging from 0.6 to 2.3 nM. Selected isomers of the clicked products were used in biodistribution and PET/CT imaging. Introduction of the bulky dibenzocyclooctyne group in AP decreased clearance rates from circulation. However, the additional carboxylate group and PEG linker from the KP conjugate significantly improved labeling conditions and in vivo stability of the copper complex and ameliorated the slower pharmacokinetics of the clicked somatostatin analogues. PMID:24983404

  2. The synthesis and characterization of nonperipherally tetra terminal alkynyl substituted phthalocyanines and glycoconjugation via the click reaction.

    PubMed

    Kanat, Zeliha; Dinçer, Hatice

    2014-06-21

    In order to obtain nonperipherally tetra terminal alkynyl substituted phthalocyanines (Pcs), new 3-pent-4-ynyloxy phthalonitrile (3) was prepared by the nucleophilic displacement reaction of 3-nitrophthalonitrile (1) and 4-pentyn-1-ol (2) and then cyclotetramerization was attained in the presence of zinc acetate, cobalt acetate, and/or DBU in n-pentanol without protection/deprotection. For the first time, the glycoconjugation of the nonperipherally tetra terminal alkynyl substituted zinc phthalocyanine (ZnPc) (6) can be easily achieved via the click reaction in a high yield. The electronic absorption spectrum of the glucopyranosyl substituted ZnPc (10) derivative showed a red-shifted Q band at 751 nm in dichloromethane due to the protonation of the meso nitrogens of the Pc macrocycle. Deacylation yielded ZnPc (11) bearing glucose substituents at nonperipheral positions with an improved water-solubility and non-aggregation in DMSO. The chemical structures of the new compounds were characterized by (1)H NMR, (13)C NMR, FT-IR, UV-Vis, mass spectrometry and elemental analysis. Moreover, the phthalonitrile compound was characterized using X-ray. PMID:24763524

  3. New Bio-Based Materials From Vegetable Oil: Amination and Click Reactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    For some time we have been interested in utilizing vegetable oils as cheap and bio-renewable raw materials. We have found derivatization reactions with nitrogen-containing reagents to be good pathways to achieve a range of new vegetable oil-based products. One of our approaches is to derivatize ep...

  4. Cellular consequences of copper complexes used to catalyze bioorthogonal click reactions.

    PubMed

    Kennedy, David C; McKay, Craig S; Legault, Marc C B; Danielson, Dana C; Blake, Jessie A; Pegoraro, Adrian F; Stolow, Albert; Mester, Zoltan; Pezacki, John Paul

    2011-11-01

    Copper toxicity is a critical issue in the development of copper-based catalysts for copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions for applications in living systems. The effects and related toxicity of copper on mammalian cells are dependent on the ligand environment. Copper complexes can be highly toxic, can induce changes in cellular metabolism, and can be rapidly taken up by cells, all of which can affect their ability to function as catalysts for CuAAC in living systems. Herein, we have evaluated the effects of a number of copper complexes that are typically used to catalyze CuAAC reactions on four human cell lines by measuring mitochondrial activity based on the metabolism of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to study toxicity, inductively coupled plasma mass spectrometry to study cellular uptake, and coherent anti-Stokes Raman scattering (CARS) microscopy to study effects on lipid metabolism. We find that ligand environment around copper influences all three parameters. Interestingly, for the Cu(II)-bis-L-histidine complex (Cu(his)(2)), cellular uptake and metabolic changes are observed with no toxicity after 72 h at micromolar concentrations. Furthermore, we show that under conditions where other copper complexes kill human hepatoma cells, Cu(I)-L-histidine is an effective catalyst for CuAAC labeling of live cells following metabolic incorporation of an alkyne-labeled sugar (Ac(4)ManNAl) into glycosylated proteins expressed on the cell surface. This result suggests that Cu(his)(2) or derivatives thereof have potential for in vivo applications where toxicity as well as catalytic activity are critical factors for successful bioconjugation reactions. PMID:21970470

  5. Triazolyl-Based Molecular Gels as Ligands for Autocatalytic 'Click' Reactions.

    PubMed

    Araújo, Marco; Díaz-Oltra, Santiago; Escuder, Beatriu

    2016-06-13

    The catalytic performance of triazolyl-based molecular gels was investigated in the Huisgen 1,3-dipolar cycloaddition of alkynes and azides. Low-molecular-weight gelators derived from l-valine were synthesized and functionalized with a triazole fragment. The resultant compounds formed gels either with or without copper, in a variety of solvents of different polarity. The gelators coordinated Cu(I) and exhibited a high catalytic activity in the gel phase for the model reaction between phenylacetylene and benzylazide. Additionally, the gels were able to participate in autocatalytic synthesis and the influence of small structural changes on their performance was observed. PMID:27168408

  6. Biocompatible Azide-Alkyne "Click" Reactions for Surface Decoration of Glyco-Engineered Cells.

    PubMed

    Gutmann, Marcus; Memmel, Elisabeth; Braun, Alexandra C; Seibel, Jürgen; Meinel, Lorenz; Lühmann, Tessa

    2016-05-01

    Bio-orthogonal copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) has been widely used to modify azide- or alkyne-bearing monosaccharides on metabolic glyco-engineered mammalian cells. Here, we present a systematic study to elucidate the design space for the cytotoxic effects of the copper catalyst on NIH 3T3 fibroblasts and on HEK 293-F cells. Monitoring membrane integrity by flow cytometry and RT-PCR analysis with apoptotic and anti-apoptotic markers elucidated the general feasibility of CuAAC, with exposure time of the CuAAC reaction mixture having the major influence on biocompatibility. A high labeling efficiency of HEK 293-F cells with a fluorescent alkyne dye was rapidly achieved by CuAAC in comparison to copper free strain-promoted azide-alkyne cycloaddition (SPAAC). The study details effective and biocompatible conditions for CuAAC-based modification of glyco-engineered cells in comparison to its copper free alternative. PMID:26818821

  7. AutoClickChem: Click Chemistry in Silico

    PubMed Central

    Durrant, Jacob D.; McCammon, J. Andrew

    2012-01-01

    Academic researchers and many in industry often lack the financial resources available to scientists working in “big pharma.” High costs include those associated with high-throughput screening and chemical synthesis. In order to address these challenges, many researchers have in part turned to alternate methodologies. Virtual screening, for example, often substitutes for high-throughput screening, and click chemistry ensures that chemical synthesis is fast, cheap, and comparatively easy. Though both in silico screening and click chemistry seek to make drug discovery more feasible, it is not yet routine to couple these two methodologies. We here present a novel computer algorithm, called AutoClickChem, capable of performing many click-chemistry reactions in silico. AutoClickChem can be used to produce large combinatorial libraries of compound models for use in virtual screens. As the compounds of these libraries are constructed according to the reactions of click chemistry, they can be easily synthesized for subsequent testing in biochemical assays. Additionally, in silico modeling of click-chemistry products may prove useful in rational drug design and drug optimization. AutoClickChem is based on the pymolecule toolbox, a framework that may facilitate the development of future python-based programs that require the manipulation of molecular models. Both the pymolecule toolbox and AutoClickChem are released under the GNU General Public License version 3 and are available for download from http://autoclickchem.ucsd.edu. PMID:22438795

  8. Synthesis of Well-Defined Miktoarm Star Copolymer composed of Poly(3-hexylthiophene) and Poly(methyl methacrylate) via combining anionic polymerization and click reaction

    NASA Astrophysics Data System (ADS)

    Park, Jicheol; Moon, Hong Chul; Kim, Jin Kon

    2013-03-01

    We synthesized well-defined miktoarm star copolymer composed of regioregular poly(3-hexylthiophene) and poly(methyl methacrylate) ((P3HT)2- b-PMMA) by combining anionic polymerization and click reaction. First, we synthesized PMMA terminated with 1,3,5-tris(bromomethy)lbenzene (PMMA-(br)2) by anionic polymerization. Then, the bromide end groups transformed to azide group (PMMA-(N3)2) . For the synthesis (P3HT)2- b-PMMA, click reaction between ethynyl-capped P3HT and PMMA-(N3)2 was performed. The optical property and thin film morphology of (P3HT)2- b-PMMA were investigated by using UV-Vis spectra and atomic force microscopy, respectively.

  9. Synthesis of a Nanostructured Composite: Octakis(1-propyl-1H-1,2,3-triazole-4-yl(methyl 2-chlorobenzoate))octasilsesquioxane via Click Reaction.

    PubMed

    Ghodsi, Mohammadi Ziarani; Shakiba Nahad, Monireh; Lashgari, Negar; Alireza, Badiei

    2015-01-01

    Octakis(1-propyl-1H-1,2,3-triazole-4-yl(methyl 2-chlorobenzoate))octasilsesquioxanes as functionalized silsesquioxanes were synthesized via click reaction (copper-catalyzed Huisgen 1,3-dipolar cycloaddition reaction) between azidemoiety functionalized silsesquioxane and prop-2-ynyl 2-chlorobenzoate. The latter one was synthesized via the condensation reaction of propargyl alcohol and 2-chlorobenzoyl chloride in the presence of SBA-Pr-NH(2) (Santa Barbara Amorphous type material) as a nano basic catalyst. This approach provides a simple and convenient route to efficiently functionalize a wide range of new structures on the surface of silsesquioxanes. PMID:26454606

  10. The Diels-Alder-Reaction with inverse-Electron-Demand, a very efficient versatile Click-Reaction Concept for proper Ligation of variable molecular Partners

    PubMed Central

    Wiessler, Manfred; Waldeck, Waldemar; Kliem, Christian; Pipkorn, Ruediger; Braun, Klaus

    2010-01-01

    The ligation of active pharmaceutical ingredients (API) for working with image processing systems in diagnostics (MRT) attracts increasing notice and scientific interest. The Diels-Alder ligation Reaction with inverse electron demand (DARinv) turns out to be an appropriate candidate. The DARinv is characterized by a specific distribution of electrons of the diene and the corresponding dienophile counterpart. Whereas the reactants in the classical Diels-Alder Reaction feature electron-rich diene and electron-poor dienophile compounds, the DARinv exhibits exactly the opposite distribution of electrons. Substituents with pushing electrones increase and, with pulling electrons reduce the electron density of the dienes as used in the DARinv. We report here that the DARinv is an efficient route for coupling of multifunctional molecules like active peptides, re-formulated drugs or small molecules like the alkyalting agent temozolomide (TMZ). This is an example of our contribution to the "Click chemistry" technology. In this case TMZ is ligated by DARinv as a cargo to transporter molecules facilitating the passage across the cell membranes into cells and subsequently into subcellular components like the cell nucleus by using address molecules. With such constructs we achieved high local concentrations at the desired target site of pharmacological action. The DARinv ligation was carried out using the combination of several technologies, namely: the organic chemistry and the solid phase peptide synthesis which can produce 'tailored' solutions for questions not solely restricted to the medical diagnostics or therapy, but also result in functionalizations of various surfaces qualified amongst others also for array development. We like to acquaint you with the DARinv and we like to exemplify that all ligation products were generated after a rapid and complete reaction in organic solutions at room temperature, in high purity, but also, hurdles and difficulties on the way to the

  11. Functionalization of multi-walled carbon nanotubes with thermo-responsive azide-terminated poly(N-isopropylacrylamide) via click reactions.

    PubMed

    Su, Xin; Shuai, Ya; Guo, Zanru; Feng, Yujun

    2013-01-01

    Covalently functionalized multi-walled carbon nanotubes (MWNTs) were prepared by grafting well-defined thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) via click reactions. First, azide-terminated poly(N-isopropylacrylamide) (N3-PNIPAM) was synthesized by reversible addition fragmentation chain-transfer (RAFT) polymerization, and then the N₃-PNIPAM moiety was connected onto MWNTs by click chemistry. The products were characterized by means of FT-IR, TGA and TEM. The results show that the modification of MWNTs is very successful and MWNTs functionalized by N₃-PNIPAM (MWNTs-PNIPAM) have good solubility and stability in water. TEM images show the functionalized MWNTs are dispersed individually, indicating that the bundles of original MWNTs are separated into individual tubes by surface modification with polymer chains. These MWNTs modified with PNIPAM represent a potential nano-material for preparation of hydrophilic composite materials. PMID:23599017

  12. Determination of copper(II) in the dairy product by an electrochemical sensor based on click chemistry.

    PubMed

    Qiu, Suyan; Xie, Lidan; Gao, Sen; Liu, Qida; Lin, Zhenyu; Qiu, Bin; Chen, Guonan

    2011-11-30

    Herein, a novel sensitive electrochemical sensor for copper(II) based on Cu(I) catalyzed alkyne-azide cycloaddition reaction (CuAAC) is described. The catalyst of Cu(I) species is derived from electrochemical reduction of Cu(II) through bulk electrolysis (BE) with coulometry technique. The propargyl-functionalized ferrocene (propargyl-functionalized Fc) is covalently coupled onto the electrode surface via CuAAC reaction and forms propargyl-functionalized Fc modified gold electrode, which allows a good and stable electrochemical signal. The change of current at peak (dI), detected by differential pulse voltammetry (DPV), exhibits a linear response to the logarithm of Cu(II) concentration in the range of 1.0×10(-14)-1.0×10(-9) mol L(-1). It is also found that the proposed sensor has a good selectivity for copper(II) assay even in the presence of other common metal ions. Additionally, the proposed method has been applied to determine copper(II) in the dairy product (yoghurt) with satisfactory results. PMID:22027119

  13. Nanoplasmonics tuned ``click chemistry''

    NASA Astrophysics Data System (ADS)

    Tijunelyte, I.; Guenin, E.; Lidgi-Guigui, N.; Colas, F.; Ibrahim, J.; Toury, T.; Lamy de La Chapelle, M.

    2016-03-01

    Nanoplasmonics is a growing field of optical condensed matter science dedicated to optical phenomena at the nanoscale level in metal systems. Extensive research on noble metallic nanoparticles (NPs) has emerged within the last two decades due to their ability to keep the optical energy concentrated in the vicinity of NPs, in particular, the ability to create optical near-field enhancement followed by heat generation. We have exploited these properties in order to induce a localised ``click'' reaction in the vicinity of gold nanostructures under unfavourable experimental conditions. We demonstrate that this reaction can be controlled by the plasmonic properties of the nanostructures and we propose two physical mechanisms to interpret the observed plasmonic tuning of the ``click'' chemistry.Nanoplasmonics is a growing field of optical condensed matter science dedicated to optical phenomena at the nanoscale level in metal systems. Extensive research on noble metallic nanoparticles (NPs) has emerged within the last two decades due to their ability to keep the optical energy concentrated in the vicinity of NPs, in particular, the ability to create optical near-field enhancement followed by heat generation. We have exploited these properties in order to induce a localised ``click'' reaction in the vicinity of gold nanostructures under unfavourable experimental conditions. We demonstrate that this reaction can be controlled by the plasmonic properties of the nanostructures and we propose two physical mechanisms to interpret the observed plasmonic tuning of the ``click'' chemistry. Electronic supplementary information (ESI) available: NMR study on reaction initiation, SERS spectra and temperature calculations. See DOI: 10.1039/c5nr09018k

  14. Chiroptical Probing of Lanthanide-Directed Self-Assembly Formation Using btp Ligands Formed in One-Pot Diazo-Transfer/Deprotection Click Reaction from Chiral Amines.

    PubMed

    Byrne, Joseph P; Martínez-Calvo, Miguel; Peacock, Robert D; Gunnlaugsson, Thorfinnur

    2016-01-11

    A series of enantiomeric 2,6-bis(1,2,3-triazol-4-yl)pyridines (btp)-containing ligands was synthesized by a one-pot two-step copper-catalyzed amine/alkyne click reaction. The Eu(III) - and Tb(III) -directed self-assembly formation of these ligands was studied in CH3 CN by monitoring their various photophysical properties, including their emerging circular dichroism and circularly polarized luminescence. The global analysis of the former enabled the determination of both the stoichiometry and the stability constants of the various chiral supramolecular species in solution. PMID:26555573

  15. Rapid grafting of azido-labeled oligo(ethylene glycol)s onto an alkynyl-terminated monolayer on nonoxidized silicon via microwave-assisted "click" reaction.

    PubMed

    Li, Yan; Wang, Jun; Cai, Chengzhi

    2011-03-15

    Microwave (MW) irradiation was used for the grafting of azido-labeled oligo(ethylene oxide) (OEG) on alkynyl-terminated nonoxidized silicon substrates via copper-catalyzed "click" reaction. The "clickable" monolayers were prepared by photografting of an α,ω-alkynene, where the alkynyl terminus was protected by a trimethylgermanyl (TMG) group, onto hydrogen-terminated Si(111) surfaces. X-ray photoelectron spectroscopy (XPS) was primarily employed to characterize the monolayers, and the data obtained were utilized to calculate the surface density of the TMG-alkynyl-functionalized substrate. MW-assisted one-pot deprotection/click reaction was optimized on the surfaces using azido-tagged OEG derivatives. Using MW instead of conventional heating led to a substantial improvement in the rate of the reaction while suppressing the oxidation of the silicon interface and OEG degradation. The antifouling property of the resulting substrates was evaluated using fibrinogen as a model protein. Results show that the OEG-modification reduced the protein adsorption by >90%. PMID:21306165

  16. Nanoplasmonics tuned "click chemistry".

    PubMed

    Tijunelyte, I; Guenin, E; Lidgi-Guigui, N; Colas, F; Ibrahim, J; Toury, T; Lamy de la Chapelle, M

    2016-04-01

    Nanoplasmonics is a growing field of optical condensed matter science dedicated to optical phenomena at the nanoscale level in metal systems. Extensive research on noble metallic nanoparticles (NPs) has emerged within the last two decades due to their ability to keep the optical energy concentrated in the vicinity of NPs, in particular, the ability to create optical near-field enhancement followed by heat generation. We have exploited these properties in order to induce a localised "click" reaction in the vicinity of gold nanostructures under unfavourable experimental conditions. We demonstrate that this reaction can be controlled by the plasmonic properties of the nanostructures and we propose two physical mechanisms to interpret the observed plasmonic tuning of the "click" chemistry. PMID:26961136

  17. In vivo click reaction between Tc-99m-labeled azadibenzocyclooctyne-MAMA and 2-nitroimidazole-azide for tumor hypoxia targeting.

    PubMed

    Sun, Wenjing; Chu, Taiwei

    2015-10-15

    The bioactivity of nitroimidazole in Tc-99m-labeled 2-nitroimidazole, a traditional solid tumor hypoxia-imaging agent for single photon emission computed tomography (SPECT), is reduced by the presence of large ligand and metallic radionuclide, exhibiting lower tumor-to-nontumor ratios. In an effort to solve this general problem, a pretargeting strategy based on click chemistry (strain-promoted cyclooctyne-azide cycloaddition) was applied. The functional click synthons were synthesized as pretargeting components: an azide group linked to 2-nitroimidazole (2NIM-Az) serves for tumor hypoxia-targeting and azadibenzocyclooctyne conjugated with monoamine monoamide dithiol ligand (AM) functions as radiolabeling and binding group to azides in vivo. 2NIM-triazole-MAMA was obtained from in vitro click reaction with a reaction rate constant of 0.98M(-1)s(-1). AM and 2NIM-triazole-MAMA were radiolabeled with Tc-99m. The hypoxia-pretargeting biodistribution was studied in Kunming mice bearing S180 tumor; (99m)Tc-AM and (99m)Tc-triazole-2NIM were used as blank control and conventional control. Compared to the control groups, the pretargeting experiment exhibits the best radio-uptake and retention in tumor, with higher tumor-to-muscle and tumor-to-blood ratios (up to 8.55 and 1.44 at 8h post-(99m)Tc-complex-injection, respectively). To some extent, the pretargeting strategy protects the bioactivity of nitroimidazole and therefore provides an innovative approach for the development of tumor hypoxia-SPECT imaging agents. PMID:26358160

  18. Application of the Huisgen cycloaddition and 'click' reaction toward various 1,2,3-triazoles as HIV non-nucleoside reverse transcriptase inhibitors.

    PubMed

    Pribut, Nicole; Veale, Clinton G L; Basson, Adriaan E; van Otterlo, Willem A L; Pelly, Stephen C

    2016-08-01

    The development of novel anti-HIV agents remains an important medicinal chemistry challenge given that no cure for the disease is imminent, and the continued use of current NNRTIs inevitably leads to problems associated with resistance. Inspired by the pyrazole-containing NNRTI lersivirine (LSV), we embarked upon a study to establish whether 1,2,3-triazole heterocycles could be used as a new scaffold for the creation of novel NNRTIs. An especially attractive feature of triazoles used for this purpose is the versatility in accessing variously functionalised systems using either the thermally regulated Huisgen cycloaddition, or the related 'click' reaction. Employing three alternative forms of these reactions, we were able to synthesise a range of triazole compounds and evaluate their efficacy in a phenotypic HIV assay. To our astonishment, even compounds closely mimicking LSV were only moderately effective against HIV. PMID:27287366

  19. Thiol-ene "click" reaction triggered by neutral ionic liquid: the "ambiphilic" character of [hmim]Br in the regioselective nucleophilic hydrothiolation.

    PubMed

    Kumar, Rajesh; Saima; Shard, Amit; Andhare, Nitin H; Richa; Sinha, Arun K

    2015-01-12

    Thiol-ene "click" chemistry has emerged as a powerful strategy to construct carbon-heteroatom (C-S) bonds, which generally results in the formation of two regioisomers. To this end, the neutral ionic liquid [hmim]Br has been explored as a solvent cum catalyst for the synthesis of linear thioethers from activated and inactivated styrene derivatives or secondary benzyl alcohols and thiols without the requirement of using a metal complex, base, or free radical initiator. Furthermore, detailed mechanistic investigations using (1)H NMR spectroscopy and quadrupole time-of-flight electrospray ionization mass spectrometry (Q-TOF ESI-MS) revealed that the "ambiphilic" character of the ionic liquid promotes the nucleophilic addition of thiol to styrene through an anti-Markovnikov pathway. The catalyst recyclability and the extension of the methodology for thiol-yne click chemistry are additional benefits. A competitive study among thiophenol, styrene, and phenyl acetylene revealed that the rate of reaction is in the order of thiol-yne>thiol-ene>dimerization of thiol in [hmim]Br. PMID:25430704

  20. A Mechanochemically Triggered "Click" Catalyst.

    PubMed

    Michael, Philipp; Binder, Wolfgang H

    2015-11-16

    "Click" chemistry represents one of the most powerful approaches for linking molecules in chemistry and materials science. Triggering this reaction by mechanical force would enable site- and stress-specific "click" reactions--a hitherto unreported observation. We introduce the design and realization of a homogeneous Cu catalyst able to activate through mechanical force when attached to suitable polymer chains, acting as a lever to transmit the force to the central catalytic system. Activation of the subsequent copper-catalyzed "click" reaction (CuAAC) is achieved either by ultrasonication or mechanical pressing of a polymeric material, using a fluorogenic dye to detect the activation of the catalyst. Based on an N-heterocyclic copper(I) carbene with attached polymeric chains of different flexibility, the force is transmitted to the central catalyst, thereby activating a CuAAC in solution and in the solid state. PMID:26420664

  1. Synthesis, click reaction, molecular structure, spectroscopic and DFT computational studies on 3-(2,6-bis(trifluoromethyl)phenoxy)-6-(prop-2-yn-1-yloxy)phthalonitrile

    NASA Astrophysics Data System (ADS)

    Hasan, Muhammad; Shalaby, Mona

    2016-06-01

    The compound 3-(2,6-bis(trifluoromethyl)phenoxy)-6-(prop-2-yn-1-yloxy)phthalonitrile has been synthesized and confirmed by different characterization techniques such as elemental analysis, IR, UV-vis spectroscopy, and X-ray single-crystal determination. The molecular geometry from X-ray determination of this compound in the ground state has been compared using the Hartree-Fock (HF) and density functional theory (DFT) with the 6-31G(d) basis set. This compound reacted with sugar azide via click reaction to form triazol ring. The synergy between carbohydrate molecule and fluorinated organic compound achieved novel synthetic pathways, properties, and applications in chemistry science.

  2. Preparation of polyhedral oligomeric silsesquioxane-based hybrid monolith by ring-opening polymerization and post-functionalization via thiol-ene click reaction.

    PubMed

    Liu, Zhongshan; Ou, Junjie; Lin, Hui; Wang, Hongwei; Dong, Jing; Zou, Hanfa

    2014-05-16

    A polyhedral oligomeric silsesquioxane (POSS) hybrid monolith was simply prepared by using octaglycidyldimethylsilyl POSS (POSS-epoxy) and cystamine dihydrochloride as monomers via ring-opening polymerization. The effects of composition of prepolymerization solution and polycondensation temperature on the morphology and permeability of monolithic column were investigated in detail. The obtained POSS hybrid monolithic column showed 3D skeleton morphology and exhibited high column efficiency of ∼71,000 plates per meter in reversed-phase mechanism. Owing to this POSS hybrid monolith essentially possessing a great number of disulfide bonds, the monolith surface would expose thiol groups after reduction with dithiothreitol (DTT), which supplied active sites to functionalize with various alkene monomers via thiol-ene click reaction. The results indicated that the reduction with DTT could not destroy the 3D skeleton of hybrid monolith. Both stearyl methylacrylate (SMA) and benzyl methacrylate (BMA) were selected to functionalize the hybrid monolithic columns for reversed-phase liquid chromatography (RPLC), while [2-(methacryloyloxy)ethyl]-dimethyl-(3-sulfopropyl)-ammonium hydroxide (MSA) was used to modify the hybrid monolithic column in hydrophilic interaction chromatography (HILIC). These modified hybrid monolithic columns could be successfully applied for separation of small molecules with high efficiency. It is demonstrated that thiol-ene click reaction supplies a facile way to introduce various functional groups to the hybrid monolith possessing thiol groups. Furthermore, due to good permeability of the resulting hybrid monoliths, we also prepared long hybrid monolithic columns in narrow-bore capillaries. The highest column efficiency reached to ∼70,000 plates using a 1-m-long column of 75μm i.d. with a peak capacity of 147 for isocratic chromatography, indicating potential application in separation and analysis of complex biosamples. PMID:24725471

  3. In situ construction of three anion-dependent cu(i) coordination networks as promising heterogeneous catalysts for azide-alkyne "click" reactions.

    PubMed

    Xu, Zhenghu; Han, Lu Lu; Zhuang, Gui Lin; Bai, Jing; Sun, Di

    2015-05-18

    Three Cu(I) coordination networks, namely, {[Cu2(bpz)2(CN)X]·CH3CN}n, (X = Cl, 1; I, 3), {[Cu6(bpz)6(CH3CN)3(CN)3Br]·2OH·14CH3CN}n, (2, bpz = 3,3',5,5'-tetramethyl-4,4'-bipyrazole), were prepared by using solvothermal method. The cyanide ligands in these networks were generated in situ by cleavage of C-C bond of MeCN under solvothermal condition. The structures of these networks are dependent on halogen anions. Complex 1 is a ladderlike structure with μ2-CN(-) as rung and μ2-bpz as armrest. The Cl(-) in 1 is at terminal position but does not extend the one-dimensional (1D) ladder to higher dimensionalities. Complex 2 is a three-dimensional (3D) framework comprised of novel planar [Cu3Br] triangle and single Cu nodes, which are extended by μ2-bpz and μ2-CN(-) to form a novel (3,9)-connected gfy network. Density functional theory calculations showed that single-electron delocalization of Br atom induces the plane structure of [Cu3Br]. Complex 3 also possesses a similar ladderlike subunit as in 1, but the I(-) acts as bidentate bridge to extend the ladder to 3D framework with a four-connected sra topology. The three networks show notable catalytic activity on the click reaction. The compared catalytic results demonstrate that complex 2 possesses the best catalysis performance among three complexes, which is ascribed to the largest solvent-accessible void (porosity: 2 (29.4%) > 1 (25.7%) > 3 (17.6%)) and the more Cu(I) active sites in 2. The present combined structure-property studies provide not only a new synthetic route to obtain a new kind of catalyst for click reaction but also the new insights on catalyst structure-function relationships. PMID:25941881

  4. Cu (I) catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC): Synthesis of 17α-[1-(substituted phenyl)-1,2,3-triazol-4-yl]-19-nor-testosterone-17β-yl acetates targeting progestational and antipro-liferative activities.

    PubMed

    Mohamed, Z H; El-Koussi, Nawal A; Mahfouz, Nadia M; Youssef, Adel F; Abdel Jaleel, Gehad A; Shouman, Samia A

    2015-06-01

    The progestational potency and selectivity of synthetic steroidal agonists can be enhanced by even larger chemical moieties at 17α-position of the steroid backbones. Hereby a series 5a-c and 6a-c of novel 17α-[1-(substituted phenyl)-1,2,3-triazol-4-yl]-19-nortestosterone-17β-yl acetates were designed and synthesized using click chemistry approach searching progestogenic derivatives with potential anticancer activity. Compounds 5a,b and 6a,c have affected to different extents the three histopatho-logical parameters considered for evaluation of their progestational activity. The compounds 5a,b and 6a,c showed modifications in rat uterus at 35.7-34.8 nM levels with privileged endometrial thickening effect and least change of uterine weight relative to NEA at 52.9 nM level. Up to 40 mg/kg dose compounds 5b and 6c were non-toxic. Molecular docking of the ligands in PR showed in the majority of cases a conformational fitting into the active site different from that of the reference steroid NEA. Compound 6b revealed about 46.4% growth inhibition of CNS cancer SNB-75 cell line, 56% growth inhibition of renal cancer A498 cell line and 56.7% growth inhibition of prostate cancer PC-3 cell line which was mediated by cell cycle arrest. Drugability of the screened compounds showed tolerated results after being challenged to diverse physicochemical parameters. PMID:25942354

  5. Regioselective Sequential Modification of Chitosan via Azide-Alkyne Click Reaction: Synthesis, Characterization, and Antimicrobial Activity of Chitosan Derivatives and Nanoparticles

    PubMed Central

    Sarwar, Atif; Katas, Haliza; Samsudin, Siti Noradila; Zin, Noraziah Mohamad

    2015-01-01

    Recently, the attention of researchers has been drawn toward the synthesis of chitosan derivatives and their nanoparticles with enhanced antimicrobial activities. In this study, chitosan derivatives with different azides and alkyne groups were synthesized using click chemistry, and these were further transformed into nanoparticles by using the ionotropic gelation method. A series of chitosan derivatives was successfully synthesized by regioselective modification of chitosan via an azide-alkyne click reaction. The amino moieties of chitosan were protected during derivatization by pthaloylation and subsequently unblocked at the end to restore their functionality. Nanoparticles of synthesized derivatives were fabricated by ionic gelation to form complexes of polyanionic penta-sodium tripolyphosphate (TPP) and cationic chitosan derivatives. Particle size analysis showed that nanoparticle size ranged from 181.03 ± 12.73 nm to 236.50 ± 14.32 nm and had narrow polydispersity index and positive surface charge. The derivatives and corresponding nanoparticles were evaluated in vitro for antibacterial and antifungal activities against three gram-positive and gram-negative bacteria and three fungal strains, respectively. The minimum inhibitory concentration (MIC) of all derivatives ranged from 31.3 to 250 µg/mL for bacteria and 188 to1500 µg/mL for fungi and was lower than that of native chitosan. The nanoparticles with MIC ranging from 1.56 to 25 µg/mLfor bacteria and 94 to 750 µg/mL for fungi exhibited higher activity than the chitosan derivatives. Chitosan O-(1-methylbenzene) triazolyl carbamate and chitosan O-(1-methyl phenyl sulfide) triazolyl carbamate were the most active against the tested bacterial and fungal strains. The hemolytic assay on erythrocytes and cell viability test on two different cell lines (Chinese hamster lung fibroblast cells V79 and Human hepatic cell line WRL68) demonstrated the safety; suggesting that these derivatives could be used in future

  6. Facile Synthesis of Prussian Blue Derivate-Modified Mesoporous Material via Photoinitiated Thiol-Ene Click Reaction for Cesium Adsorption.

    PubMed

    Qian, Jun; Ma, Jiaqi; He, Weiwei; Hua, Daoben

    2015-08-01

    A novel strategy to synthesize a functional mesoporous material for efficient removal of cesium is reported. Specifically, Prussian blue derivate-modified SBA-15 (SBA-15@FC) was prepared by photoinitiated thiol-ene reaction between thiol-modified SBA-15 and pentacyano(4-vinyl pyridine)ferrate complex. The effects of weight percentage of the Prussian blue derivate, pH, adsorbent dose, co-existing ions, and initial concentration were evaluated on the adsorption of cesium ions. The adsorption kinetically follows a pseudo-second-order model and reaches equilibrium within 2 h with a high adsorption capacity of about 13.90 mg Cs g(-1) , which indicates that SBA-15@FC is a promising adsorbent to effectively remove cesium from aqueous solutions. PMID:25965318

  7. Mechanochemical click reaction as a tool for making carbohydrate-based triazole-linked self-assembling materials (CTSAMs).

    PubMed

    Tyagi, Mohit; Taxak, Nikhil; Bharatam, Prasad V; Nandanwar, Hemraj; Kartha, K P Ravindranathan

    2015-04-30

    Various glycosides in which glycosylated triazole residues are anchored on to a central phenyl ring have been prepared under green reaction conditions by a solvent-free mechanochemical method. Some of the glycosides exhibited the ability to form gels when in contact with long chain hydrocarbons, e.g. hexane, heptane and octane, and this property was phase-selective. Thus, from a mixture of hexane-water, the compounds preferably absorbed the alkane to form a gel. The gelation ability was found to increase with an increasing number of substituents on the phenyl ring but only up to tetra-substitution. The hexa-substituted phenyl derivative did not swell in the hydrocarbon solvents investigated. The spontaneous self-assembling properties of these compounds in hexane have been investigated by transmission electron microscopy (TEM). Molecular modelling was used to optimize the structural geometry of these carbohydrate-based triazole-linked self-assembling materials (CTSAMs) and to rationalize their behaviour. PMID:25771296

  8. 'Click chemistry' synthesis of a library of 1,2,3-triazole-substituted galactose derivatives and their evaluation against Trypanosoma cruzi and its cell surface trans-sialidase.

    PubMed

    Carvalho, Ivone; Andrade, Peterson; Campo, Vanessa L; Guedes, Paulo M M; Sesti-Costa, Renata; Silva, João S; Schenkman, Sergio; Dedola, Simone; Hill, Lionel; Rejzek, Martin; Nepogodiev, Sergey A; Field, Robert A

    2010-04-01

    Trypanosoma cruzi trans-sialidase (TcTS) plays a key role in the recognition and invasion of host cells and in enabling the parasite to escape the human immune response. To explore this potential drug target, we have synthesized a small library of substrate analogues based on 1,4-disubstituted 1,2,3-triazole derivatives of galactose modified at either the C-1 or C-6 positions. This was achieved by coupling the appropriate azido-sugars with a panel of 23 structurally diverse terminal alkynes by using the copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction, giving a library of 46 derivatives in good to excellent yield and with complete regioselectivity. The sugar triazoles showed weak inhibition towards TcTS-catalyzed hydrolysis of 2'-(4-methylumbelliferyl)-alpha-d-N-acetylneuraminic acid in vitro (<40% inhibition at 1mM concentration); many of the compounds assessed proved to be acceptor substrates for the enzyme. Despite this modest inhibitory activity, in vitro trypanocidal activity assays against the trypomastigote form of T. cruzi Y strain revealed several compounds active in the low 100s of muM range. Further assessment of these compounds against cultured mouse spleen cells suggests a specific mode of anti-parasite action rather than a generic cytotoxic effect. PMID:20335038

  9. Photoswitchable click amino acids: light control of conformation and bioactivity.

    PubMed

    Hoppmann, Christian; Schmieder, Peter; Heinrich, Nadja; Beyermann, Michael

    2011-11-25

    Click the switch: By using a photoswitchable click amino acid (PSCaa) a light-induced intramolecular thiol-ene click reaction with a neighboring cysteine under very mild conditions results in an azobenzene bridge. By expanding the genetic code for PSCaa the specific incorporation of photoswitch units into proteins in living cells can result in an exciting approach for studying light-controllable activity, in vivo. PMID:21998087

  10. Copper Nanoparticles in Click Chemistry.

    PubMed

    Alonso, Francisco; Moglie, Yanina; Radivoy, Gabriel

    2015-09-15

    The challenges of the 21st century demand scientific and technological achievements that must be developed under sustainable and environmentally benign practices. In this vein, click chemistry and green chemistry walk hand in hand on a pathway of rigorous principles that help to safeguard the health of our planet against negligent and uncontrolled production. Copper-catalyzed azide-alkyne cycloaddition (CuAAC), the paradigm of a click reaction, is one of the most reliable and widespread synthetic transformations in organic chemistry, with multidisciplinary applications. Nanocatalysis is a green chemistry tool that can increase the inherent effectiveness of CuAAC because of the enhanced catalytic activity of nanostructured metals and their plausible reutilization capability as heterogeneous catalysts. This Account describes our contribution to click chemistry using unsupported and supported copper nanoparticles (CuNPs) as catalysts prepared by chemical reduction. Cu(0)NPs (3.0 ± 1.5 nm) in tetrahydrofuran were found to catalyze the reaction of terminal alkynes and organic azides in the presence of triethylamine at rates comparable to those achieved under microwave heating (10-30 min in most cases). Unfortunately, the CuNPs underwent dissolution under the reaction conditions and consequently could not be recovered. Compelling experimental evidence on the in situ generation of highly reactive copper(I) chloride and the participation of copper(I) acetylides was provided. The supported CuNPs were found to be more robust and efficient catalyst than the unsupported counterpart in the following terms: (a) the multicomponent variant of CuAAC could be applied; (b) the metal loading could be substantially decreased; (c) reactions could be conducted in neat water; and (d) the catalyst could be recovered easily and reutilized. In particular, the catalyst composed of oxidized CuNPs (Cu2O/CuO, 6.0 ± 2.0 nm) supported on carbon (CuNPs/C) was shown to be highly versatile and very

  11. Click Chemistry Mediated Functionalization of Vertical Nanowires for Biological Applications.

    PubMed

    Vutti, Surendra; Schoffelen, Sanne; Bolinsson, Jessica; Buch-Månson, Nina; Bovet, Nicolas; Nygård, Jesper; Martinez, Karen L; Meldal, Morten

    2016-01-11

    Semiconductor nanowires (NWs) are gaining significant importance in various biological applications, such as biosensing and drug delivery. Efficient and controlled immobilization of biomolecules on the NW surface is crucial for many of these applications. Here, we present for the first time the use of the Cu(I) -catalyzed alkyne-azide cycloaddition and its strain-promoted variant for the covalent functionalization of vertical NWs with peptides and proteins. The potential of the approach was demonstrated in two complementary applications of measuring enzyme activity and protein binding, which is of general interest for biological studies. The attachment of a peptide substrate provided NW arrays for the detection of protease activity. In addition, green fluorescent protein was immobilized in a site-specific manner and recognized by antibody binding to demonstrate the proof-of-concept for the use of covalently modified NWs for diagnostic purposes using minute amounts of material. PMID:26601641

  12. Selective Cell Adhesion and Biosensing Applications of Bio-Active Block Copolymers Prepared by CuAAC/Thiol-ene Double Click Reactions.

    PubMed

    Oyman Eyrilmez, Gizem; Doran, Sean; Murtezi, Eljesa; Demir, Bilal; Odaci Demirkol, Dilek; Coskunol, Hakan; Timur, Suna; Yagci, Yusuf

    2015-09-01

    N-Acetyl-l-cysteine (NAC)-capped poly(methyl methacrylate)-b-polycaprolactone block copolymer (PMMA-b-PCL-NAC) was prepared using the previously described one-pot photoinduced sequential CuAAC/thiol-ene double click procedure. PMMA-b-PCL-NAC had previously shown good applicability as a matrix for cell adhesion of cells from the Vero cell line (African green monkey kidney epithelial). Here, in this work, PMMA-b-PCL-NAC served as an excellent immobilization matrix for biomolecule conjugation. Covalent binding of RGD (R: arginine, G: glycine, and D: aspartic acid) peptide sequence onto the PMMA-b-PCL-NAC-coated surface was performed via EDC chemistry. RGD-modified PMMA-b-PCL-NAC (PMMA-b-PCL-NAC-RGD) as a non-toxic cell proliferation platform was used for selective "integrin αvβ3-mediated cell adhesion and biosensing studies. Both optical and electrochemical techniques were used to monitor the adhesion differences between "integrin αvβ3" receptor positive and negative cell lines on to the designed biofunctional surfaces. PMID:25974890

  13. Nucleotidyl transferase assisted DNA labeling with different click chemistries

    PubMed Central

    Winz, Marie-Luise; Linder, Eva Christina; André, Timon; Becker, Juliane; Jäschke, Andres

    2015-01-01

    Here, we present a simple, modular and efficient strategy that allows the 3′-terminal labeling of DNA, regardless of whether it has been chemically or enzymatically synthesized or isolated from natural sources. We first incorporate a range of modified nucleotides at the 3′-terminus, using terminal deoxynucleotidyl transferase. In the second step, we convert the incorporated nucleotides, using either of four highly efficient click chemistry-type reactions, namely copper-catalyzed azide-alkyne cycloaddition, strain-promoted azide-alkyne cycloaddition, Staudinger ligation or Diels-Alder reaction with inverse electron demand. Moreover, we create internal modifications, making use of either ligation or primer extension, after the nucleotidyl transferase step, prior to the click reaction. We further study the influence of linker variants on the reactivity of azides in different click reactions. We find that different click reactions exhibit distinct substrate preferences, a fact that is often overlooked, but should be considered when labeling oligonucleotides or other biomolecules with click chemistry. Finally, our findings allowed us to extend our previously published RNA labeling strategy to the use of a different copper-free click chemistry, namely the Staudinger ligation. PMID:26013812

  14. Recent advances in click chemistry applied to dendrimer synthesis.

    PubMed

    Arseneault, Mathieu; Wafer, Caroline; Morin, Jean-François

    2015-01-01

    Dendrimers are monodisperse polymers grown in a fractal manner from a central point. They are poised to become the cornerstone of nanoscale devices in several fields, ranging from biomedicine to light-harvesting. Technical difficulties in obtaining these molecules has slowed their transfer from academia to industry. In 2001, the arrival of the "click chemistry" concept gave the field a major boost. The flagship reaction, a modified Hüisgen cycloaddition, allowed researchers greater freedom in designing and building dendrimers. In the last five years, advances in click chemistry saw a wider use of other click reactions and a notable increase in the complexity of the reported structures. This review covers key developments in the click chemistry field applied to dendrimer synthesis from 2010 to 2015. Even though this is an expert review, basic notions and references have been included to help newcomers to the field. PMID:26007183

  15. Growth of Thin, Anisotropic, π-Conjugated Molecular Films by Stepwise "Click" Assembly of Molecular Building Blocks: Characterizing Reaction Yield, Surface Coverage, and Film Thickness versus Addition Step Number.

    PubMed

    Demissie, Abel T; Haugstad, Greg; Frisbie, C Daniel

    2015-07-15

    We report the systematic characterization of anisotropic, π-conjugated oligophenyleneimine (OPI) films synthesized using stepwise imine condensation, or "click" chemistry. Film synthesis began with a self-assembled monolayer (SAM) of 4-formylthiophenol or 4-aminothiophenol on Au, followed by repetitive, alternate addition of terephthalaldehyde (benzene-1,4-dicarbaldehyde) or 1,4-benzenediamine to form π-conjugated films ranging from 0.6-5.5 nm in thickness. By systematically capping the OPI films with a redox or halogen label, we were able to measure the relative surface coverage after each monomer addition via Rutherford backscattering spectrometry, X-ray photoelectron spectroscopy, spectroscopic ellipsometry, reflection-absorption infrared spectroscopy, and cyclic voltammetry. Nuclear reaction analysis was also employed for the first time on a SAM to calculate the surface coverage of carbon atoms after each stepwise addition. These six different analysis methods indicate that the average extent of reaction is 99% for each addition step. The high yield and molecular surface coverage confirm the efficacy of Schiff base chemistry, at least with the terephthalaldehyde and 1,4-benzenediamine monomers, for preparing high-quality molecular films with π conjugation normal to the substrate. PMID:26098519

  16. An integrated approach for enhanced protein conjugation and capture with viral nanotemplates and hydrogel microparticle platforms via rapid bioorthogonal reactions.

    PubMed

    Jung, Sukwon; Yi, Hyunmin

    2014-07-01

    We demonstrate significantly enhanced protein conjugation and target protein capture capacity by exploiting tobacco mosaic virus (TMV) templates assembled with hydrogel microparticles. Protein conjugation results with a red fluorescent protein R-Phycoerythrin (R-PE) show significantly enhanced protein conjugation capacity of TMV-assembled particles (TMV-particles) compared to planar substrates or hydrogel microparticles. In-depth examination of protein conjugation kinetics via tetrazine (Tz)-trans-cyclooctene (TCO) cycloaddition and strain-promoted alkyne-azide cycloaddition (SPAAC) reaction demonstrates that TMV-particles provide a less hindered environment for protein conjugation. Target protein capture results using an anti-R-PE antibody (R-Ab)-R-PE pair also show substantially improved capture capacity of R-Ab conjugated TMV-particles over R-Ab conjugated hydrogel microparticles. We further demonstrate readily controlled protein and antibody conjugation capacity by simply varying TMV concentrations, which show negligible negative impact of densely assembled TMVs on protein conjugation and capture capacity. Combined, these results illustrate a facile postfabrication protein conjugation approach with TMV templates assembled onto hydrogel microparticles for improved and controlled protein conjugation and sensing platforms. We anticipate that our approach can be readily applied to various protein sensing applications. PMID:24937661

  17. Pseudo-Ligandless Click Chemistry for Oligonucleotide Conjugation.

    PubMed

    Mack, Stephanie; Fouz, Munira F; Dey, Sourav K; Das, Subha R

    2016-01-01

    Particularly for its use in bioconjugations, the copper-catalyzed (or copper-promoted) azide-alkyne cycloaddition (CuAAC) reaction or 'click chemistry', has become an essential component of the modern chemical biologist's toolbox. Click chemistry has been applied to DNA, and more recently, RNA conjugations, and the protocols presented here can be used for either. The reaction can be carried out in aqueous buffer, and uses acetonitrile as a minor co-solvent that serves as a ligand to stabilize the copper. The method also includes details on the analysis of the reaction product. © 2016 by John Wiley & Sons, Inc. PMID:27258688

  18. A carborane-derivative "click" reaction under heterogeneous conditions for the synthesis of a promising lipophilic MRI/GdBNCT agent.

    PubMed

    Toppino, Antonio; Bova, Maria Elena; Geninatti Crich, Simonetta; Alberti, Diego; Diana, Eliano; Barge, Alessandro; Aime, Silvio; Venturello, Paolo; Deagostino, Annamaria

    2013-01-01

    In this study, the Huisgen reaction has been used to functionalise a carborane cage with a lipophilic moiety and a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) ligand to obtain a new Gd boron neutron-capture therapy (BNCT)/magnetic resonance imaging (MRI) agent. The introduction of the triazole units has been accomplished under both heterogeneous conditions, by the use of a Cu-supported ionic-liquid catalyst, and homogeneous conditions. The ability of the Gd complex of the synthesised ligand to form stable adducts with low-density lipoproteins (LDLs) has been evaluated and then MRI has been performed on tumour melanoma cells incubated in the presence of a Gd-complex/LDL imaging probe. It has been concluded that the high amount of intracellular boron necessary to perform BNCT can be reached even in the presence of a relatively low-boron-containing LDL concentration. PMID:23154917

  19. Double clicking for site-specific coupling of multiple enzymes.

    PubMed

    Lim, Sung In; Cho, Jinhwan; Kwon, Inchan

    2015-09-14

    A method to site-specifically couple multiple enzymes is reported. The approach is based on the site-specific incorporation of a clickable non-natural amino acid into enzymes and two compatible click reactions. The multi-enzyme reaction system exhibited enhanced catalytic efficiency over the respective free enzymes. PMID:26191550

  20. Facile "one-pot" synthesis of poly(methacrylic acid)-based hybrid monolith via thiol-ene click reaction for hydrophilic interaction chromatography.

    PubMed

    Lv, Xumei; Tan, Wangming; Chen, Ye; Chen, Yingzhuang; Ma, Ming; Chen, Bo; Yao, Shouzhuo

    2016-07-01

    A novel sol-gel "one-pot" approach in tandem with a radical-mediated thiol-ene reaction for the synthesis of a methacrylic acid-based hybrid monolith was developed. The polymerization monomers, tetramethoxysilane (TMOS) and 3-mercaptopropyl trimethoxysilane (MPTS), were hydrolyzed in high-concentration methacrylic acid solution that also served as a hydrophilic functional monomer. The resulting solution was then mixed with initiator (2, 2'-azobis (2-methylpropionamide) dihydrochloride) and porogen (urea, polyethylene glycol 20,000) in a capillary column and polymerized in water bath. The column had a uniform porous structure and a good permeability. The evaluation of the monolith was performed by separation of small molecules including nucleosides, phenols, amides, bases and Triton X-100. The calibration curves for uridine, inosine, adenosine and cytidine were determined. All the calibration curves exhibited good linear regressions (R(2)≥0.995) within the test ranges of 0.5-40μg/mL for four nucleosides. Additionaliy, atypical hydrophilic mechanism was proved by elution order from low to high according to polarity retention time increased with increases in the content of the organic solvent in the mobile phase. Further studies indicated that hydrogen bond and electrostatic interactions existed between the polar analytes and the stationary phase. This was the mechanism of retention. The excellent separation of the BSA digest showed good hydrophility of the column and indicated the potential in separation of complex biological samples. PMID:27264742

  1. Preparation of Lanthanide-Polymer Composite Material via Click Chemistry.

    PubMed

    Chen, Bin; Wen, Guian; Wu, Jiajie; Feng, Jiachun

    2015-10-01

    Covalently attaching lanthanide complexes to the polymer backbone can effectively reduce the clustering of lanthanides and thus become an important strategy to fully unleash their potential. In this Communication, a metal-free click reaction is used for the first time to link a lanthanide complex to the polymer matrix. A diene-bearing copolymer with anthracenylmethyl methacrylate as a monomer and a dienophile-bearing lanthanide complex with 5-maleimido-1,10-phenanthroline as the second ligand are synthesized and coupled together through a Diels-Alder cycloaddition (DA). A comparative investigation demonstrates that the composite material prepared by DA click reaction shows the highest quantum yields in the same lanthanide concentration as compared to materials prepared by widely used "directly doping" and "in situ coordinating lanthanide ions with macromolecular ligand" approaches. This work suggests that the "metal-free" DA click reaction can be a promising tool in the synthesis of high efficient lanthanide functionalized polymeric materials. PMID:26248311

  2. 18F-Labeling Using Click Cycloadditions

    PubMed Central

    Ross, Tobias L.

    2014-01-01

    Due to expanding applications of positron emission tomography (PET) there is a demand for developing new techniques to introduce fluorine-18 (t1/2 = 109.8 min). Considering that most novel PET tracers are sensitive biomolecules and that direct introduction of fluorine-18 often needs harsh conditions, the insertion of 18F in those molecules poses an exceeding challenge. Two major challenges during 18F-labeling are a regioselective introduction and a fast and high yielding way under mild conditions. Furthermore, attention has to be paid to functionalities, which are usually present in complex structures of the target molecule. The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) and several copper-free click reactions represent such methods for radiolabeling of sensitive molecules under the above-mentioned criteria. This minireview will provide a quick overview about the development of novel 18F-labeled prosthetic groups for click cycloadditions and will summarize recent trends in copper-catalyzed and copper-free click 18F-cycloadditions. PMID:25003110

  3. Complex surface concentration gradients by stenciled "electro click chemistry".

    PubMed

    Hansen, Thomas S; Lind, Johan U; Daugaard, Anders E; Hvilsted, Søren; Andresen, Thomas L; Larsen, Niels B

    2010-10-19

    Complex one- or two-dimensional concentration gradients of alkynated molecules are produced on azidized conducting polymer substrates by stenciled "electro click chemistry". The latter describes the local electrochemical generation of catalytically active Cu(I) required to complete a "click reaction" between alkynes and azides at room temperature. A stencil on the counter electrode defines the shape and multiplicity of the gradient(s) on the conducting polymer substrate, while the specific reaction conditions control gradient steepness and the maximum concentration deposited. Biologically active ligands including cell binding peptides are patterned in gradients by this method without losing their biological function or the conductivity of the polymer. PMID:20860406

  4. Fluorescence imaging of chromosomal DNA using click chemistry.

    PubMed

    Ishizuka, Takumi; Liu, Hong Shan; Ito, Kenichiro; Xu, Yan

    2016-01-01

    Chromosome visualization is essential for chromosome analysis and genetic diagnostics. Here, we developed a click chemistry approach for multicolor imaging of chromosomal DNA instead of the traditional dye method. We first demonstrated that the commercially available reagents allow for the multicolor staining of chromosomes. We then prepared two pro-fluorophore moieties that served as light-up reporters to stain chromosomal DNA based on click reaction and visualized the clear chromosomes in multicolor. We applied this strategy in fluorescence in situ hybridization (FISH) and identified, with high sensitivity and specificity, telomere DNA at the end of the chromosome. We further extended this approach to observe several basic stages of cell division. We found that the click reaction enables direct visualization of the chromosome behavior in cell division. These results suggest that the technique can be broadly used for imaging chromosomes and may serve as a new approach for chromosome analysis and genetic diagnostics. PMID:27620982

  5. A click chemistry strategy for visualization of plant cell wall lignification.

    PubMed

    Tobimatsu, Yuki; Van de Wouwer, Dorien; Allen, Eric; Kumpf, Robert; Vanholme, Bartel; Boerjan, Wout; Ralph, John

    2014-10-21

    Bioorthogonal click chemistry was commissioned to visualize the plant cell wall lignification process in vivo. This approach uses chemical reporter-tagged monolignol mimics that can be metabolically incorporated into lignins and subsequently derivatized via copper-assisted or copper-free click reactions. PMID:25180250

  6. Cycloadditions for Studying Nucleic Acids.

    PubMed

    Kath-Schorr, Stephanie

    2016-02-01

    Cycloaddition reactions for site-specific or global modification of nucleic acids have enabled the preparation of a plethora of previously inaccessible DNA and RNA constructs for structural and functional studies on naturally occurring nucleic acids, the assembly of nucleic acid nanostructures, therapeutic applications, and recently, the development of novel aptamers. In this chapter, recent progress in nucleic acid functionalization via a range of different cycloaddition (click) chemistries is presented. At first, cycloaddition/click chemistries already used for modifying nucleic acids are summarized, ranging from the well-established copper(I)-catalyzed alkyne-azide cycloaddition reaction to copper free methods, such as the strain-promoted azide-alkyne cycloaddition, tetrazole-based photoclick chemistry and the inverse electron demand Diels-Alder cycloaddition reaction between strained alkenes and tetrazine derivatives. The subsequent sections contain selected applications of nucleic acid functionalization via click chemistry; in particular, site-specific enzymatic labeling in vitro, either via DNA and RNA recognizing enzymes or by introducing unnatural base pairs modified for click reactions. Further sections report recent progress in metabolic labeling and fluorescent detection of DNA and RNA synthesis in vivo, click nucleic acid ligation, click chemistry in nanostructure assembly and click-SELEX as a novel method for the selection of aptamers. PMID:27572987

  7. A Versatile Strategy to Synthesize Perfluoropolyether-Based Thermoplastic Fluoropolymers by Alkyne-Azide Step-Growth Polymerization.

    PubMed

    Lopez, Gérald; Ameduri, Bruno; Habas, Jean-Pierre

    2016-04-01

    Perfluoropolyether (PFPE)-based thermoplastic fluoropolymers are synthesized by A2 + B2 step-growth polymerization between PFPE-diyne and fluorinated diazides. This versatile method allows synthesizing PFPE-based materials with tunable physicochemical properties depending on the exact nature of the fluorinated segment of the diazide precursor. Semicrystalline or amorphous materials endowed with high thermostability (≈300 °C under air) and low glass transition temperature (≈-100 °C) are obtained, as confirmed by differential scanning calorimetry, thermogravimetry, and rheometry. Step-growth polymerizations can be copper-catalyzed but also thermally activated in some cases, thus avoiding the presence of copper residues in the final materials. This strategy opens up new opportunities to easily access PFPE-based materials on an industrial scale. Furthermore, a plethora of developments can be envisioned (e.g., by adding a third trifunctional component to the formulations for the synthesis of PFPE-based elastomers). PMID:26914503

  8. Surface-initiated Polymerization of Azidopropyl Methacrylate and its Film Elaboration via Click Chemistry

    PubMed Central

    Saha, Sampa; Bruening, Merlin L.; Baker, Gregory L.

    2013-01-01

    Azidopropyl methacrylate (AzPMA), a functional monomer with a pendent azido group, polymerizes from surfaces and provides polymer brushes amenable to subsequent elaboration via click chemistry. In DMF at 50 °C, click reactions between poly(AzPMA) brushes and an alkynylated dye proceed with >90% conversion in a few minutes. However, in aqueous solutions, reaction with an alkyne-containing poly(ethylene glycol) methyl ether (mPEG, Mn=5000) gives <10% conversion after a 12-h reaction at room temperature. Formation of copolymers with AzPMA and polyethylene glycol methyl ether methacrylate (mPEGMA) enables control over the hydrophilicity and functional group density in the copolymer to increase the yield of aqueous click reactions. The copolymers show reaction efficiencies as high as 60%. These studies suggest that for aqueous applications such as bioconjugation via click chemistry, control over brush hydrophilicity is vital. PMID:24293702

  9. Multifunctional Surface Manipulation Using Orthogonal Click Chemistry.

    PubMed

    Brooks, Karson; Yatvin, Jeremy; McNitt, Christopher D; Reese, R Alexander; Jung, Calvin; Popik, Vladimir V; Locklin, Jason

    2016-07-01

    Polymer brushes are excellent substrates for the covalent immobilization of a wide variety of molecules due to their unique physicochemical properties and high functional group density. By using reactive microcapillary printing, poly(pentafluorophenyl acrylate) brushes with rapid kinetic rates toward aminolysis can be partially patterned with other click functionalities such as strained cyclooctyne derivatives and sulfonyl fluorides. This trireactive surface can then react locally and selectively in a one pot reaction via three orthogonal chemistries at room temperature: activated ester aminolysis, strain promoted azide-alkyne cycloaddition, and sulfur(VI) fluoride exchange, all of which are tolerant of ambient moisture and oxygen. Furthermore, we demonstrate that these reactions can also be used to create areas of morphologically distinct surface features on the nanoscale, by inducing buckling instabilities in the films and the grafting of nanoparticles. This approach is modular, and allows for the development of highly complex surface motifs patterned with different chemistry and morphology. PMID:27280689

  10. Click-EM for imaging metabolically tagged nonprotein biomolecules.

    PubMed

    Ngo, John T; Adams, Stephen R; Deerinck, Thomas J; Boassa, Daniela; Rodriguez-Rivera, Frances; Palida, Sakina F; Bertozzi, Carolyn R; Ellisman, Mark H; Tsien, Roger Y

    2016-06-01

    EM has long been the main technique for imaging cell structures with nanometer resolution but has lagged behind light microscopy in the crucial ability to make specific molecules stand out. Here we introduce click-EM, a labeling technique for correlative light microscopy and EM imaging of nonprotein biomolecules. In this approach, metabolic labeling substrates containing bioorthogonal functional groups are provided to cells for incorporation into biopolymers by endogenous biosynthetic machinery. The unique chemical functionality of these analogs is exploited for selective attachment of singlet oxygen-generating fluorescent dyes via bioorthogonal 'click chemistry' ligations. Illumination of dye-labeled structures generates singlet oxygen to locally catalyze the polymerization of diaminobenzidine into an osmiophilic reaction product that is readily imaged by EM. We describe the application of click-EM in imaging metabolically tagged DNA, RNA and lipids in cultured cells and neurons and highlight its use in tracking peptidoglycan synthesis in the Gram-positive bacterium Listeria monocytogenes. PMID:27110681

  11. Picazoplatin, an Azide-Containing Platinum(II) Derivative for Target Analysis by Click Chemistry

    PubMed Central

    White, Jonathan D.; Osborn, Maire F.; Moghaddam, Alan D.; Guzman, Lindsay E.; Haley, Michael M.; DeRose, Victoria J.

    2014-01-01

    Despite the broad use of platinum-based chemotherapeutics, identification of their full range of cellular targets remains a significant challenge. In order to identify, visualize, and isolate cellular targets of Pt(II) complexes, we have modified the chemotherapeutic drug picoplatin with an azide moiety for subsequent click reactivity. The new compound picazoplatin readily binds DNA and RNA oligonucleo-tides and undergoes facile post-labeling click reactions to alkyne-fluorophore conjugates. Pt-fluorophore click reactions in ribosomal RNA purified from drug-treated S. cerevisiae demonstrate its potential for future in vivo efforts. PMID:23879391

  12. Low generation polyamine dendrimers bearing flexible tetraethylene glycol as nanocarriers for plasmids and siRNA

    NASA Astrophysics Data System (ADS)

    Sharma, Rishi; Zhang, Issan; Shiao, Tze Chieh; Pavan, Giovanni M.; Maysinger, Dusica; Roy, René

    2016-02-01

    Low G1 generation polyamine dendrimers built around programmable, flexible, and short tetraethyleneglycol branches were readily prepared in a divergent manner using a combination of orthogonal AB3 or AB5 units and highly efficient chemical transformations based on Cu(i) catalyzed alkyne-azide cycloaddition (CUAAC) and thiol-ene click reactions. The constructs showed that the G1 polyamines with only twelve and eighteen amine surface groups can successfully deliver siRNA in human cells, with transfection efficiency comparable to that of Lipofectamine 2000®. Measurements of cell viability following transfection of plasmid DNA and siRNA showed that the dendritic polyamines are less cytotoxic than Lipofectamine 2000® and are thus preferable for biological applications.Low G1 generation polyamine dendrimers built around programmable, flexible, and short tetraethyleneglycol branches were readily prepared in a divergent manner using a combination of orthogonal AB3 or AB5 units and highly efficient chemical transformations based on Cu(i) catalyzed alkyne-azide cycloaddition (CUAAC) and thiol-ene click reactions. The constructs showed that the G1 polyamines with only twelve and eighteen amine surface groups can successfully deliver siRNA in human cells, with transfection efficiency comparable to that of Lipofectamine 2000®. Measurements of cell viability following transfection of plasmid DNA and siRNA showed that the dendritic polyamines are less cytotoxic than Lipofectamine 2000® and are thus preferable for biological applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06757j

  13. Click.

    PubMed

    2016-05-01

    The under-18 conception rate in the UK for 2013 is the lowest since 1969. Despite this, the UK remains among the top five in the EU in terms of live births to women aged 15-17 and 15-19, and reducing teenage pregnancy is high on the government agenda. The following websites offer advice on sex and relationships for children and young people. PMID:27156412

  14. Click.

    PubMed

    2016-03-01

    Agency nurse community Originally the brainchild of Teresa Chinn (@AgencyNurse) to overcome the isolation of being an agency nurse, Wecommunities has developed in a number of different directions. There is a weekly Twitter chat at @wenurses with guest hosts. Audio recordings of these chats are available on the Wecommunities website at http://www.wecommunities.org. PMID:26954636

  15. Modular "Click" Preparation of Bifunctional Polymeric Heterometallic Catalysts.

    PubMed

    Wang, Wenlong; Zhao, Liyuan; Lv, Hui; Zhang, Guodong; Xia, Chungu; Hahn, F Ekkehardt; Li, Fuwei

    2016-06-27

    Heterobimetallic molecular complexes or strictly alternating metallated polymers are obtained by a click reaction between mononuclear metal complexes (secondary building units, SBUs) bearing NHCs functionalized with either p-azidophenyl or p-ethynylphenyl wingtips. With a copper-NHC complex as SBU the formation of molecular or polymeric compounds did not require any additives as the copper complex catalyzes the click reaction. Transmetallation from heterobimetallic Cu/Ag derivatives to Cu/Pd derivatives was achieved. The linker between the SBUs (flexible or rigid) influences the catalytic activity of the heterobimetallic compounds. The polymer with alternating copper-NHC and silver-NHC units and a flexible methylene-triazole bridge between them shows the highest activity in the catalytic alkynylation of trifluoromethyl ketones to give fluorinated propargylic alcohols. PMID:27331787

  16. Unique tetrameric and hexameric mannoside clusters prepared by click chemistry.

    PubMed

    Al-Mughaid, Hussein; Al-Zoubi, Raed M; Paul, Nawal K; Grindley, T Bruce

    2015-11-19

    The synthesis of novel tetrameric and hexameric mannoside clusters bearing 1,2,3-trizole linkages via Cu(I)-catalyzed azide-alkyne cycloaddition reaction ("click chemistry") is described. An attractive feature of these multiarmed mannoside clusters as potential inhibitors of uropathogenic Escherichia coli is the use of an aglycone whose length is designed to fit in the tyrosine gate. The acetylated mannosides were deprotected and the corresponding de-O-acetylated mannosides were found to exhibit good water solubility. PMID:26398914

  17. Click synthesis of a polyamidoamine dendrimer-based camptothecin prodrug

    PubMed Central

    Zolotarskaya, Olga Yu.; Xu, Leyuan; Valerie, Kristoffer; Yang, Hu

    2015-01-01

    In the present work we report on the click synthesis of a new camptothecin (CPT) prodrug based on anionic polyamidoamine (PAMAM) dendrimer intended for cancer therapy. We applied ‘click’ chemistry to improve polymer-drug coupling reaction efficiency. Specifically, CPT was functionalized with a spacer, 1-azido-3,6,9,12,15-pentaoxaoctadecan-18-oic acid (APO), via EDC/DMAP coupling reaction. In parallel, propargylamine (PPA) and methoxypoly(ethylene glycol) amine were conjugated to PAMAM dendrimer G4.5 in sequence using an effective coupling agent 4-(4,6-dimethoxy-(1,3,5)triazin-2-yl)-4-methyl-morpholinium chloride (DMTMM). CPT-APO was then coupled to PEGylated PAMAM dendrimer G4.5-PPA via a click reaction using copper bromide/2,2’-bipyridine/ dimethyl sulfoxide (catalyst/ligand/solvent). Human glioma cells were exposed to the CPT-conjugate to determine toxicity and cell cycle effects using WST-1 assay and flow cytometry. The CPT-conjugate displayed a dose-dependent toxicity with an IC50 of 5 μM, a 185-fold increase relative to free CPT, presumably as a result of slow release. As expected, conjugated CPT resulted in G2/M arrest and cell death while the dendrimer itself had little to no toxicity. Altogether, highly efficient click chemistry allows for the synthesis of multifunctional dendrimers for sustained drug delivery. PMID:26640689

  18. Disruption of the auditory response to a regular click train by a single, extra click.

    PubMed

    Lütkenhöner, Bernd; Patterson, Roy D

    2015-06-01

    It has been hypothesized that the steady-state response to a periodic sequence of clicks can be modeled as the superposition of responses to single clicks. Here, this hypothesis is challenged by presenting an extra click halfway between two consecutive clicks of a regular series, while measuring the auditory evoked field. After a solitary click at time zero, the click series sounded from 100 to 900 ms, with the extra click presented around 500 ms. The silent period between two stimulus sequences was 310-390 ms (uniformly distributed) so that one stimulation cycle lasted, on average, 1250 ms. Five different click rates between 20 and 60 Hz were examined. The disturbance caused by the extra click was revealed by subtracting the estimated steady-state response from the joint response to the click series and the extra click. The early peaks of the single-click response effectively coincide with same-polarity peaks of the 20-Hz steady-state response. Nevertheless, prediction of the latter from the former proved impossible. However, the 40-Hz steady-state response can be predicted reasonably well from the 20-Hz steady-state response. Somewhat surprisingly, the amplitude of the evoked response to the extra click grew when the click rate of the train was increased from 20 to 30 Hz; the opposite effect would have been expected from research on adaptation. The smaller amplitude at lower click rates might be explained by forward suppression. In this case, the apparent escape from suppression at higher rates might indicate that the clicks belonging to the periodic train are being integrated into an auditory stream, possibly in much the same manner as in classical stream segregation experiments. PMID:25814380

  19. The monopulsed nature of sperm whale clicks

    NASA Astrophysics Data System (ADS)

    Møhl, Bertel; Wahlberg, Magnus; Madsen, Peter T.; Heerfordt, Anders; Lund, Anders

    2003-08-01

    Traditionally, sperm whale clicks have been described as multipulsed, long duration, nondirectional signals of moderate intensity and with a spectrum peaking below 10 kHz. Such properties are counterindicative of a sonar function, and quite different from the properties of dolphin sonar clicks. Here, data are presented suggesting that the traditional view of sperm whale clicks is incomplete and derived from off-axis recordings of a highly directional source. A limited number of assumed on-axis clicks were recorded and found to be essentially monopulsed clicks, with durations of 100 μs, with a composite directionality index of 27 dB, with source levels up to 236 dB re: 1 μPa (rms), and with centroid frequencies of 15 kHz. Such clicks meet the requirements for long-range biosonar purposes. Data were obtained with a large-aperture, GPS-synchronized array in July 2000 in the Bleik Canyon off Vestera˚len, Norway (69°28' N, 15°40' E). A total of 14 h of sound recordings was collected from five to ten independent, simultaneously operating recording units. The sound levels measured make sperm whale clicks by far the loudest of sounds recorded from any biological source. On-axis click properties support previous work proposing the nose of sperm whales to operate as a generator of sound.

  20. Just Click It: Undergraduate Procedures for the Copper(I)-Catalyzed Formation of 1,2,3-Triazoles from Azides and Terminal Acetylenes

    ERIC Educational Resources Information Center

    Sharpless, William D.; Peng Wu; Hansen, Trond Vidar; Lindberg, James G.

    2005-01-01

    The click chemistry uses only the most reliable reactions to build complex molecules from olefins, electrophiles and heteroatom linkers. A variation on Huisgen's azide-alkyne 1,2,3-triazole synthesis, the addition of the copper (I), the premium example of the click reaction, catalyst strongly activates terminal acetylenes towards the 1,3-dipole in…

  1. Chemosynthesis of poly(ε-lysine)-analogous polymers by microwave-assisted click polymerization.

    PubMed

    Guo, Jinshan; Wei, Ying; Zhou, Dongfang; Cai, Pingqiang; Jing, Xiabin; Chen, Xue-Si; Huang, Yubin

    2011-03-14

    Poly(ε-lysine) (ε-PL)-analogous click polypeptides with not only similar α-amino side groups but also similar main chain to ε-PL were chemically synthesized for the first time through click polymerization from aspartic (or glutamic)-acid-based dialkyne and diazide monomers. With microwave-assisting, the reaction time of click polymerization was compressed into 30 min. The polymers were fully characterized by NMR, ATR-FTIR, and SEC-MALLS analysis. The deprotected click polypeptides had similar pK(a) value (7.5) and relatively low cytotoxicity as ε-PL and could be used as substitutes of ε-PL in biomedical applications, especially in endotoxin selective removal. Poly(ethylene glycol) (PEG)-containing alternating copolymers with α-amino groups were also synthesized and characterized. After deprotection, the polymers could be used as functional gene vector with PEG shadowing system and NCA initiator to get amphiphilic graft polymers. PMID:21302898

  2. Click chemistry patents and their impact on drug discovery and chemical biology.

    PubMed

    Xu, Hua; Jones, Lyn H

    2015-01-01

    First introduced by K Barry Sharpless in 2001, the term 'click chemistry' soon became a widely used description of chemical reactions that proceed rapidly, cleanly and in a manner that is often compatible with aqueous solutions. Click chemistry is frequently employed throughout the process of drug discovery, and greatly helps advance research programs in the pharmaceutical industry. It facilitates library synthesis to support medicinal chemistry optimization, helps identify the targets and off-targets of drug candidates, and can facilitate the determination of drug efficacy in clinical trials. In the last decade, a large number of patent applications covering the various types and utilities of click chemistry have been filed. In this review, we provide the first analysis of click chemistry applications. PMID:25853470

  3. Triazolinediones enable ultrafast and reversible click chemistry for the design of dynamic polymer systems

    NASA Astrophysics Data System (ADS)

    Billiet, Stijn; de Bruycker, Kevin; Driessen, Frank; Goossens, Hannelore; van Speybroeck, Veronique; Winne, Johan M.; Du Prez, Filip E.

    2014-09-01

    With its focus on synthetic reactions that are highly specific and reliable, ‘click’ chemistry has become a valuable tool for many scientific research areas and applications. Combining the modular, covalently bonded nature of click-chemistry linkages with an ability to reverse these linkages and reuse the constituent reactants in another click reaction, however, is a feature that is not found in most click reactions. Here we show that triazolinedione compounds can be used in click-chemistry applications. We present examples of simple and ultrafast macromolecular functionalization, polymer-polymer linking and polymer crosslinking under ambient conditions without the need for a catalyst. Moreover, when triazolinediones are combined with indole reaction partners, the reverse reaction can also be induced at elevated temperatures, and the triazolinedione reacted with a different reaction partner, reversibly or irreversibly dependent on its exact nature. We have used this ‘transclick’ reaction to introduce thermoreversible links into polyurethane and polymethacrylate materials, which allows dynamic polymer-network healing, reshaping and recycling.

  4. Polymer brushes grafted to "passivated" silicon substrates using click chemistry.

    PubMed

    Ostaci, Roxana-Viorela; Damiron, Denis; Capponi, Simona; Vignaud, Guillaume; Léger, Liliane; Grohens, Yves; Drockenmuller, Eric

    2008-03-18

    We present herein a versatile method for grafting polymer brushes to passivated silicon surfaces based on the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (click chemistry) of omega-azido polymers and alkynyl-functionalized silicon substrates. First, the "passivation" of the silicon substrates toward polymer adsorption was performed by the deposition of an alkyne functionalized self-assembled monolayer (SAM). Then, three tailor-made omega-azido linear brush precursors, i.e., PEG-N3, PMMA-N3, and PS-N3 (Mn approximately 20,000 g/mol), were grafted to alkyne-functionalized SAMs via click chemistry in tetrahydrofuran. The SAM, PEG, PMMA, and PS layers were characterized by ellipsometry, scanning probe microscopy, and water contact angle measurements. Results have shown that the grafting process follows the scaling laws developed for polymer brushes, with a significant dependence over the weight fraction of polymer in the grafting solution and the grafting time. The chemical nature of the brushes has only a weak influence on the click chemistry grafting reaction and morphologies observed, yielding polymer brushes with thickness of ca. 6 nm and grafting densities of ca. 0.2 chains/nm2. The examples developed herein have shown that this highly versatile and tunable approach can be extended to the grafting of a wide range of polymer (pseudo-) brushes to silicon substrates without changing the tethering strategy. PMID:18247640

  5. Clicks counting system for a riflescope

    NASA Astrophysics Data System (ADS)

    Drumea, Andrei; Granciu, Dana

    2015-02-01

    A very useful requirement for a zoom aiming scope with high magnification used for long range rifle shooting is counting and display of knob's clicks number needed for elevation corrections. The paper analyzes one method for clicks counting usable with existing mechanical knobs and describes a microcontroller based system that implements it. Practical aspects like required changes in mechanical construction, influence of perturbations, complexity of electronics or power consumption are also analyzed.

  6. Click hydrogels, microgels and nanogels: emerging platforms for drug delivery and tissue engineering.

    PubMed

    Jiang, Yanjiao; Chen, Jing; Deng, Chao; Suuronen, Erik J; Zhong, Zhiyuan

    2014-06-01

    Hydrogels, microgels and nanogels have emerged as versatile and viable platforms for sustained protein release, targeted drug delivery, and tissue engineering due to excellent biocompatibility, a microporous structure with tunable porosity and pore size, and dimensions spanning from human organs, cells to viruses. In the past decade, remarkable advances in hydrogels, microgels and nanogels have been achieved with click chemistry. It is a most promising strategy to prepare gels with varying dimensions owing to its high reactivity, superb selectivity, and mild reaction conditions. In particular, the recent development of copper-free click chemistry such as strain-promoted azide-alkyne cycloaddition, radical mediated thiol-ene chemistry, Diels-Alder reaction, tetrazole-alkene photo-click chemistry, and oxime reaction renders it possible to form hydrogels, microgels and nanogels without the use of potentially toxic catalysts or immunogenic enzymes that are commonly required. Notably, unlike other chemical approaches, click chemistry owing to its unique bioorthogonal feature does not interfere with encapsulated bioactives such as living cells, proteins and drugs and furthermore allows versatile preparation of micropatterned biomimetic hydrogels, functional microgels and nanogels. In this review, recent exciting developments in click hydrogels, microgels and nanogels, as well as their biomedical applications such as controlled protein and drug release, tissue engineering, and regenerative medicine are presented and discussed. PMID:24674460

  7. Universal dark quencher based on "clicked" spectrally distinct azo dyes.

    PubMed

    Chevalier, Arnaud; Hardouin, Julie; Renard, Pierre-Yves; Romieu, Anthony

    2013-12-01

    The first synthesis of an heterotrifunctional molecular scaffold derived from the popular DABCYL azo dye quencher has been achieved. The sequential derviatization of this trivalent azobenzene derivative with two other nonfluorescent azo dyes (Black Hole Quencher BHQ-1 and BHQ-3) and through effective reactions from the "bioconjugation chemistry" repertoire has led to an universal dark quencher (UDQ). This "clicked" poly azo dye is able to turn off an array of fluorophores covering the UV/NIR (300-750 nm) spectral range. PMID:24215300

  8. Click Chemistry, a Powerful Tool for Pharmaceutical Sciences

    PubMed Central

    Hein, Christopher D.; Liu, Xin-Ming; Wang, Dong

    2008-01-01

    Click chemistry refers to a group of reactions that are fast, simple to use, easy to purify, versatile, regiospecific, and give high product yields. While there are a number of reactions that fulfill the criteria, the Huisgen 1,3-dipolar cycloaddition of azides and terminal alkynes has emerged as the frontrunner. It has found applications in a wide variety of research areas, including materials sciences, polymer chemistry, and pharmaceutical sciences. In this manuscript, important aspects of the Huisgen cycloaddition will be reviewed, along with some of its many pharmaceutical applications. Bioconjugation, nanoparticle surface modification, and pharmaceutical-related polymer chemistry will all be covered. Limitations of the reaction will also be discussed. PMID:18509602

  9. Modification of chemical and conformational properties of natural organic matter by click chemistry as revealed by ESI-Orbitrap mass spectrometry.

    PubMed

    Nebbioso, Antonio; Piccolo, Alessandro

    2015-11-01

    A click reaction is reported here for the first time as a useful technique to control the conformational stability of natural organic matter (NOM) suprastructures. Click conjugates were successfully formed between a previously butynylated NOM hydrophobic fraction and a hydrophilic polyethylene glycol (PEG)-amino chain. The click products were shown by size exclusion chromatography (HPSEC) hyphenated with Orbitrap mass spectrometry (MS) in electrospray ionization (ESI) (+), while precursors were visible in ESI (-). Despite their increase in molecular weight, HPSEC elution of click conjugates occurred after that of precursors, thus showing their departure from the NOM supramolecular association. This indicates that the click-conjugated NOM molecules were varied in their hydrophilic and cationic character and lost the capacity to accommodate in the original hydrophobic suprastructures. The most abundant product had the C16H30O5N4 formula, a click conjugate of butanoic acid, while other products were short-chained (C4-C8) linear unsaturated and hydroxylated carboxylic acids. Tandem MS revealed formation of triazole rings in clicked conjugates and their two fragmentations at the ester and the C-N alkyl-aryl bonds. The behavior of NOM molecules modified by click chemistry confirms that hydrophobicity and ionic charge of humic molecules play a pivotal role in stabilizing intermolecular forces in NOM. Moreover, the versatility of the click reaction may become useful to decorate NOM molecules with a variety of substrates, in order to alter NOM conformational and chemical properties and diversify its applications in the environment. PMID:26363779

  10. Click sounds produced by cod (Gadus morhua)

    NASA Astrophysics Data System (ADS)

    Vester, Heike I.; Folkow, Lars P.; Blix, A. S.

    2004-02-01

    Conspicuous sonic click sounds were recorded in the presence of cod (Gadus morhua), together with either harp seals (Pagophilus groenlandicus), hooded seals (Cystophora cristata) or a human diver in a pool. Similar sounds were never recorded in the presence of salmon (Salmo salar) together with either seal species, or from either seal or fish species when kept separately in the pool. It is concluded that cod was the source of these sounds and that the clicks were produced only when cod were approached by a swimming predatorlike body. The analyzed click sounds (n=377) had the following characteristics (overall averages +/- S.D.): peak frequency=5.95+/-2.22 kHz peak-to-peak duration=0.70+/-0.45 ms sound pressure level (received level)=153.2+/-7.0 dB re 1 μPa at 1 m. At present the mechanism and purpose of these clicks is not known. However, the circumstances under which they were recorded and some observations on the behavior of the seals both suggest that the clicks could have a predator startling function.

  11. Click sounds produced by cod (Gadus morhua).

    PubMed

    Vester, Heike I; Folkow, Lars P; Blix, A S

    2004-02-01

    Conspicuous sonic click sounds were recorded in the presence of cod (Gadus morhua), together with either harp seals (Pagophilus groenlandicus), hooded seals (Cystophora cristata) or a human diver in a pool. Similar sounds were never recorded in the presence of salmon (Salmo salar) together with either seal species, or from either seal or fish species when kept separately in the pool. It is concluded that cod was the source of these sounds and that the clicks were produced only when cod were approached by a swimming predatorlike body. The analyzed click sounds (n = 377) had the following characteristics (overall averages +/- S.D.): peak frequency = 5.95 +/- 2.22 kHz; peak-to-peak duration = 0.70 +/- 0.45 ms; sound pressure level (received level) = 153.2 +/- 7.0 dB re 1 microPa at 1 m. At present the mechanism and purpose of these clicks is not known. However, the circumstances under which they were recorded and some observations on the behavior of the seals both suggest that the clicks could have a predator startling function. PMID:15000203

  12. Expanding iClick to group 9 metals

    DOE PAGESBeta

    Beto, Christopher C.; Yang, Xi; Powers, Andrew R.; Ghiviriga, Ion; Abboud, Khalil A.; Veige, Adam S.

    2015-09-01

    In this study, the iClick (inorganic click) reactions between gold-acetylides and group 9 transition metal-azide complexes are presented. Complexes [Rh(CO)(PPh3)2][PPh3Au](μ-N3C2C6H4NO2) (3), {[Rh(CO)(PPh3)][PPh3Au](μ-N3C2C6H4NO2)}2 (4), and [(CO)(PPh3)2IrAuPPh3](μ-N3C2C6H4NO2) (6) have been synthesized via M-azide/M-acetylide cycloaddition reactions between PPh3Au(Ctriple bond; length of mdashCC6H4NO2) (2) and either Rh(CO)(PPh3)2N3 (1), or Ir(CO)(PPh3)2N3 (5). Complexes 3, 4, and 6 have been characterized by a combination of NMR spectroscopies, crystallography and combustion analysis.

  13. Expanding iClick to group 9 metals

    SciTech Connect

    Beto, Christopher C.; Yang, Xi; Powers, Andrew R.; Ghiviriga, Ion; Abboud, Khalil A.; Veige, Adam S.

    2015-09-01

    In this study, the iClick (inorganic click) reactions between gold-acetylides and group 9 transition metal-azide complexes are presented. Complexes [Rh(CO)(PPh3)2][PPh3Au](μ-N3C2C6H4NO2) (3), {[Rh(CO)(PPh3)][PPh3Au](μ-N3C2C6H4NO2)}2 (4), and [(CO)(PPh3)2IrAuPPh3](μ-N3C2C6H4NO2) (6) have been synthesized via M-azide/M-acetylide cycloaddition reactions between PPh3Au(Ctriple bond; length of mdashCC6H4NO2) (2) and either Rh(CO)(PPh3)2N3 (1), or Ir(CO)(PPh3)2N3 (5). Complexes 3, 4, and 6 have been characterized by a combination of NMR spectroscopies, crystallography and combustion analysis.

  14. Cyclooctyne [60]fullerene hexakis adducts: a globular scaffold for copper-free click chemistry.

    PubMed

    Ramos-Soriano, Javier; Reina, José J; Pérez-Sánchez, Alfonso; Illescas, Beatriz M; Rojo, Javier; Martín, Nazario

    2016-08-18

    The synthesis of a new highly symmetric hexakis adduct of C60 appended with 12 cyclooctyne moieties has been carried out. This compound has been used for the copper-free strain-promoted cycloaddition reaction to a series of azides with excellent yields. This strategy for the obtention of clicked adducts of [60]fullerene is of special interest for biological applications. PMID:27492263

  15. A click chemistry-based microRNA maturation assay optimized for high-throughput screening.

    PubMed

    Lorenz, Daniel A; Garner, Amanda L

    2016-07-01

    Catalytic enzyme-linked click-chemistry assays (cat-ELCCA) are an emerging class of biochemical assay. Herein we report on expanding the toolkit of cat-ELCCA to include the kinetically superior inverse-electron demand Diels-Alder (IEDDA) reaction. The result is a technology with improved sensitivity and reproducibility, enabling automated high-throughput screening. PMID:27284591

  16. Thiol click modification of cyclic disulfide containing biodegradable polyurethane urea elastomers.

    PubMed

    Fang, Jun; Ye, Sang-Ho; Wang, Jing; Zhao, Ting; Mo, Xiumei; Wagner, William R

    2015-05-11

    Although the thiol click reaction is an attractive tool for postpolymerization modification of thiolmers, thiol groups are easily oxidized, limiting the potential for covalent immobilization of bioactive molecules. In this study, a series of biodegradable polyurethane elastomers incorporating stable cyclic disulfide groups was developed and characterized. These poly(ester urethane)urea (PEUU-SS) polymers were based on polycaprolactone diol (PCL), oxidized dl-dithiothreitol (O-DTT), lysine diisocyanate (LDI), or butyl diisocyanate (BDI), with chain extension by putrescine. The ratio of O-DTT:PCL was altered to investigate different levels of potential functionalization. PEG acrylate was employed to study the mechanism and availability of both bulk and surface click modification of PEUU-SS polymers. All synthesized PEUU-SS polymers were elastic with breaking strengths of 38-45 MPa, while the PEUU-SS(LDI) polymers were more amorphous, possessing lower moduli and relatively small permanent deformations versus PEUU-SS(BDI) polymers. Variable bulk click modification of PEUU-SS(LDI) polymers was achieved by controlling the amount of reduction reagent, and rapid reaction rates occurred using a one-pot, two-step process. Likewise, surface click reaction could be carried out quickly under mild, aqueous conditions. Furthermore, a maleimide-modified affinity peptide (TPS) was successfully clicked on the surface of an electrospun PEUU-SS(BDI) fibrous sheet, which improved endothelial progenitor cell adhesion versus corresponding unmodified films. The cyclic disulfide containing biodegradable polyurethanes described provide an option for cardiovascular and other soft tissue regenerative medicine applications where a temporary, elastic scaffold with designed biofunctionality from a relatively simple click chemistry approach is desired. PMID:25891476

  17. Synthesis of Porphyrin, Chlorin and Phthalocyanine Derivatives by Azide-Alkyne Click Chemistry.

    PubMed

    Acherar, Samir; Colombeau, Ludovic; Frochot, Céline; Vanderesse, Régis

    2015-01-01

    The aim of this review is to provide a summary of the use of copper-catalyzed azide-alkyne cycloaddition (CuAAC) in the synthesis of porphyrin, chlorin and phthalocyanine derivatives for different types of therapeutic applications. The click reaction is a powerful and versatile tool for scientists working on the synthesis of various symmetrically and asymmetrically substituted tetrapyrrolic derivatives. For example, click chemistry is widely used for the elaboration of photosensitizer conjugates for photodynamic therapy applications. Other biological applications are also described. PMID:26179994

  18. Multicolor fluorescent labeling of cellulose nanofibrils by click chemistry.

    PubMed

    Navarro, Julien R G; Conzatti, Guillaume; Yu, Yang; Fall, Andreas B; Mathew, Renny; Edén, Mattias; Bergström, Lennart

    2015-04-13

    We have chemically modified cellulose nanofibrils (CNF) with furan and maleimide groups, and selectively labeled the modified CNF with fluorescent probes; 7-mercapto-4-methylcoumarin and fluorescein diacetate 5-maleimide, through two specific click chemistry reactions: Diels-Alder cycloaddition and the thiol-Michael reaction. Characterization by solid-state (13)C NMR and infrared spectroscopy was used to follow the surface modification and estimate the substitution degrees. We demonstrate that the two luminescent dyes could be selectively labeled onto CNF, yielding a multicolor CNF that was characterized by UV/visible and fluorescence spectroscopies. It was demonstrated that the multicolor CNF could be imaged using a confocal laser scanning microscope. PMID:25774999

  19. Functional graphene by thiol-ene click chemistry.

    PubMed

    Luong, Nguyen Dang; Sinh, Le Hoang; Johansson, Leena-Sisko; Campell, Joseph; Seppälä, Jukka

    2015-02-16

    Thiol-ene click reaction was successfully employed for chemical modification of graphene oxide (GO) by one-step synthesis. Herein, 2,2-azobis(2-methylpropionitrile) (AIBN) was used as thermal catalyst and cysteamine hydrochloride (HS-(CH2 )2 -NH2 HCl) was used as thiol-containing compound, which is incorporated to GO surface upon reaction with the C=C bonds. The hydrochloride acts as protecting group for the amine, which is finally eliminated by adding sodium hydroxide. The modified GO contains both S- and N-containing groups (NS-GO). We found that NS-GO sheets form good dispersion in water, ethanol, and ethylene glycol. These graphene dispersions can be processed into functionalized graphene film. Besides, it was demonstrated that NS-GO was proved to be an excellent host matrix for platinum nanoparticles. The developed method paves a new way for graphene modification and its functional nanocomposites. PMID:25580698

  20. Surface modification of nanoporous 1,2-polybutadiene by atom transfer radical polymerization or click chemistry.

    PubMed

    Guo, Fengxiao; Jankova, Katja; Schulte, Lars; Vigild, Martin E; Ndoni, Sokol

    2010-02-01

    Surface-initiated atom transfer radical polymerization (ATRP) and click chemistry were used to obtain functional nanoporous polymers based on nanoporous 1,2-polybutadiene (PB) with gyroid morphology. The ATRP monolith initiator was prepared by immobilizing bromoester initiators onto the pore walls through two different methodologies: (1) three-step chemical conversion of double bonds of PB into bromoisobutyrate, and (2) photochemical functionalization of PB with bromoisobutyrate groups. Azide functional groups were attached onto the pore walls before click reaction with alkynated MPEG. Following ATRP-grafting of hydrophilic polyacrylates and click of MPEG, the originally hydrophobic samples transformed into hydrophilic nanoporous materials. The successful modification was confirmed by infrared spectroscopy, contact angle measurements and measurements of spontaneous water uptake, while the morphology was investigated by small-angle X-ray scattering and transmission electron microscopy. PMID:20099923

  1. Peptidyl Materials Formed Through Click Chemistry Enhanced Coiled-Coil Interactions

    NASA Astrophysics Data System (ADS)

    Koehler, Kenneth

    2014-03-01

    Biologically derived materials offer a level of sophistication synthetically fabricated materials have only attempted to mimic. This level of complexity may be found in materials such as peptides. Implementing new theory and modeling, peptides with the propensity to form coiled-coil (CC) bundles were designed and synthesized. Through the use of this de novo approach, modeling allowed prediction of the feasibility to include non-natural amino acids conducive to click chemistry into the peptide. Amino acids showcasing thiol or alkyne functionalities were considered owing to the ability of these moieties to participate in the thiol-ene and copper click reactions respectively. Once synthesized, the peptides decorated with these clickable motifs were placed in solution and allowed to self-assemble into CC's. CD spectroscopy and DLS experiments confirmed the formation and assembly of CC's. Click reactions were then incited to link the CC assemblies together and form a network with predictable dimensionality and pore size between CC bundles. To incite network formation, click reactions between CC side chain residues and suitably functionalized crosslinkers were implemented. The linking of coiled-coils and material formation were assessed using DLS and TEM.

  2. Learning Clicks: Year End Report 2008/2009

    ERIC Educational Resources Information Center

    Alberta Advanced Education and Technology, 2009

    2009-01-01

    Learning Clicks was developed in 2003 as an interactive, fun way for Alberta students to learn about these opportunities. Learning Clicks is a program designed to support Strategy 2.4 in Alberta Advanced Education and Technology's 2007-10 Business Plan. The 2008/2009 season was the 5th year of the Learning Clicks program. This paper offers a…

  3. One-pot synthesis of 2,5-dihydropyrroles from terminal alkynes, azides, and propargylic alcohols by relay actions of copper, rhodium, and gold.

    PubMed

    Miura, Tomoya; Tanaka, Takamasa; Matsumoto, Kohei; Murakami, Masahiro

    2014-12-01

    Relay actions of copper, rhodium, and gold formulate a one-pot multistep pathway, which directly gives 2,5-dihydropyrroles starting from terminal alkynes, sulfonyl azides, and propargylic alcohols. Initially, copper-catalyzed 1,3-dipolar cycloaddition of terminal alkynes with sulfonyl azides affords 1-sulfonyl-1,2,3-triazoles, which then react with propargylic alcohols under the catalysis of rhodium. The resulting alkenyl propargyl ethers subsequently undergo the thermal Claisen rearrangement to give α-allenyl-α-amino ketones. Finally, a gold catalyst prompts 5-endo cyclization to produce 2,5-dihydropyrroles. PMID:25345587

  4. Preparation of cyclodextrin chiral stationary phases by organic soluble catalytic 'click' chemistry.

    PubMed

    Wang, Yong; Chen, Hui; Xiao, Yin; Ng, Cheong Hengq; Oh, Ting Shan; Tan, Timothy Thatt Yang; Ng, Siu Choon

    2011-07-01

    We describe an effective and simple protocol that uses click chemistry to attach native β-cyclodextrin (β-CD) to silica particles, resulting in a chiral stationary phase (CCNCSP) that can be used for the enantioseparation of chiral drugs by high-performance liquid chromatography (HPLC). Starting from β-CD, the CCNCSP is prepared in several steps: (i) reaction of β-CD with 1-(p-toluenesulfonyl)-imidazole to afford mono-6-toluenesulfonyl-β-CD; (ii) azidolysis of mono-6-toluenesulfonyl-β-CD in dimethylformamide to give mono-6-azido-β-CD (N(3)-CD); (iii) reaction of cuprous iodide with triphenylphosphine to form an organic soluble catalyst CuI(PPh(3)); (iv) preparation of alkynyl-modified silica particles; and (v) click chemistry immobilization of N(3)-CD onto alkynyl-modified silica to afford the desired chiral stationary phase. Synthesis of the stationary phase and column packing takes ∼1 week. PMID:21720308

  5. Instantaneous Click Chemistry by a Copper-Containing Polymeric-Membrane-Installed Microflow Catalytic Reactor.

    PubMed

    Yamada, Yoichi M A; Ohno, Aya; Sato, Takuma; Uozumi, Yasuhiro

    2015-11-23

    The copper(I)-catalyzed Huisgen cycloaddition (azide-alkyne cycloaddition) is an important reaction in click chemistry that ideally proceeds instantaneously. An instantaneous Huisgen cycloaddition has been developed that uses a novel catalytic dinuclear copper complex-containing polymeric membrane-installed microflow device. A polymeric membranous copper catalyst was prepared from poly(4-vinylpyridine), copper(II) sulfate, sodium chloride, and sodium ascorbate at the interface of two laminar flows inside microchannels. Elucidation of the structure by XANES, EXAFS, and elemental analysis, as well as second-order Møller-Plesset perturbation theory (MP2) calculations and density functional theory (DFT) calculations assigned the local structure near Cu as a μ-chloro dinuclear Cu(I) complex. The microflow device promotes the instantaneous click reaction of a variety of alkynes and organic azides to afford the corresponding triazoles in quantitative yield. PMID:26439220

  6. Synthesis and Characterization of Multiwalled Carbon Nanotubes/Poly(HEMA-co-MMA) by Utilizing Click Chemistry.

    PubMed

    Bach, Long Giang; Cao, Xuan Thang; Islam, Md Rafiqul; Jeong, Yeon Tae; Kim, Jong Su; Lim, Kwon Taek

    2016-03-01

    The hybrid material consisting of multi walled carbon nanotubes (MWNTs) and poly(2-hydroxyethylmethacrylate-co-methylmethacrylate) [poly(HEMA-co-MMA)] was synthesized by a combination of RAFT and Click chemistry. In the primary stage, the copolymer poly(HEMA-co-MMA) was prepared by applying RAFT technique. Alkynyl side groups were incorporated onto the poly(HEMA-co-MMA) backbone by esterification reaction. Then, MWNTs-N3 was prepared by treating MWNTs with 4-azidobutylamine. The click coupling reaction between azide-functionalized MWNTs (MWNTs-N3) and the alkyne-functionalized random copolymer ((HEMA-co-MMA)-Alkyne) with the Cu(I)-catalyzed [3+2] Huisgen cycloaddition afforded the hybrid compound. The structure and properties of poly(MMA-co-HEMA)-g-MWNTs were investigated by FT-IR, EDX and TGA measurements. The copolymer brushes were observed to be immobilized onto the functionalized MWNTs by SEM and TEM analysis. PMID:27455744

  7. Immobilization of enzymes on ethynyl-modified electrodes via click chemistry.

    PubMed

    Hayat, Akhtar; Sassolas, Audrey; Rhouati, Amina; Marty, Jean-Louis

    2013-01-01

    This paper describes a novel, simple, and versatile protocol for covalent immobilization of enzyme on electrode. The immobilization method is based on the combination of diazonium salt electrografting and click chemistry. The ethynyl-terminated monolayers are obtained by diazonium salt electrografting, then, in the presence of copper (I) catalyst, the ethynyl modified surfaces reacts efficiently and rapidly with enzyme bearing an azide function (azido-enzyme), thus forming a covalent 1,2,3-triazole linkage by means of click chemistry. The ethynyl-terminated film preserves the activity of the immobilized enzyme. The click chemistry along with binary film of diazonium salts offers a variety of good characteristics including high sensitivity, good repeatability and reusability, rapid response and long term stability of the system. Thus, because of the chemoselective reactivity and quantitative yield of the click reaction, an ethynyl-terminated monolayer can be treated as a general platform for obtaining reliable coverage of a wide range of azido-terminated species of interest for various sensing applications. PMID:23934806

  8. Core-shell morphology and characterization of carbon nanotube nanowires click coupled with polypyrrole

    NASA Astrophysics Data System (ADS)

    Rana, Sravendra; Cho, Jae Whan

    2011-07-01

    Core-shell nanowires having multiwalled carbon nanotubes (MWNT) as a core and polypyrrole (PPy) as a shell were synthesized using Cu(I)-catalyzed azide-alkyne cycloaddition click chemistry. According to transmission electron microscopy measurements, the uniform PPy layers of 10-20 nm in thickness were formed well on the MWNT's surface. In particular 'grafting from' click coupling was more effective in obtaining uniform and stable core-shell nanowires as well as in the reaction yield, compared to 'grafting to' click coupling. This is due to chemical bond formation between PPy and MWNT in equal intervals along the longitudinal direction of the MWNT, achieved by 'grafting from' click coupling. As a result, the core-shell nanowires were very stable even in the sonication of nanowires and showed an enhanced electrical conductivity of 80 S cm - 1, due to the synergetic interaction between MWNTs and PPy, which is higher than the conductivity of pure MWNTs and pure PPy. In addition, the core-shell nanowires could show better NO2 gas sensing properties compared to pure MWNTs and pure PPy as well as MWNT/PPy composites prepared by in situ polymerization. The synthesized core-shell nanowires would play an important role in preparing electrical and sensing devices.

  9. Get the right mix of bricks & clicks.

    PubMed

    Gulati, R; Garino, J

    2000-01-01

    The bright line that once distinguished the dot-com from the incumbent is rapidly fading. Success in the new economy will go to those who can execute clicks-and-mortar strategies that bridge the physical and virtual worlds. But how executives forge such strategies is under considerable debate. Despite the obvious benefits that integration offers--cross-promotion, shared information, purchasing leverage, distribution economies, and the like--many executives now assume that Internet businesses have to be separate to thrive. They believe that the very nature of traditional business--its protectiveness of current customers, its fear of cannibalization, its general myopia--will smother any Internet initiative. Authors Ranjay Gulati and Jason Garino contend that executives don't have to make an either- or choice when it comes to their clicks-and-mortar strategies. The question isn't, "Should we develop our Internet channel in-house or launch a spin-off?" but rather, "What degree of integration makes sense for our company?" To determine the best level of integration for their companies, executives should examine four business dimensions: brand, management, operations, and equity. Drawing on the experiences of three established retailers--Office Depot, KB Toys, and Rite Aid--the authors show the spectrum of strategies available and discuss the trade-offs involved in each choice. By thinking carefully about which aspects of a business to integrate and which to keep distinct, companies can tailor their clicks-and-mortar strategy to their own particular market and competitive situation, dramatically increasing their odds of e-business success. PMID:11183973

  10. Enhancement of TFO Triplex Formation by Conjugation with Pyrene via Click Chemistry.

    PubMed

    Taniguchi, Yosuke; Tomizaki, Akira; Matsueda, Nozomu; Okamura, Hidenori; Sasaki, Shigeki

    2015-01-01

    This paper reports the preparation of 14-mer triplex-forming oligonucleotides (TFOs) containing a 2-O-methyl-1-β-phenyl-α-propargyl-ribose unit, which was conjugated with azide-modified molecules via a click reaction. Modification of these TFOs with pyrene assisted triplex formation, improving the stability of the triplex DNA and the anti-proliferative effects against A549 cells. PMID:26521856

  11. Copper catalyst activation driven by photoinduced electron transfer: a prototype photolatent click catalyst.

    PubMed

    Harmand, Lydie; Cadet, Sarah; Kauffmann, Brice; Scarpantonio, Luca; Batat, Pinar; Jonusauskas, Gediminas; McClenaghan, Nathan D; Lastécouères, Dominique; Vincent, Jean-Marc

    2012-07-16

    PET cat. While the copper(II) tren ketoprofenate precatalyst 1 (see picture) is inactive at room temperature in methanol, it is quantitatively and rapidly reduced to its cuprous state upon light irradiation to provide a highly reactive click catalyst. By simply introducing air into the reaction medium the catalysis can be switched off and then switched on again by bubbling argon followed by irradiation. PMID:22777953

  12. Development of a microfluidic “click chip” incorporating an immobilized Cu(I) catalyst

    PubMed Central

    Li, Hairong; Whittenberg, Joseph J.; Zhou, Haiying; Ranganathan, David; Desai, Amit V.; Koziol, Jan; Zeng, Dexing; Kenis, Paul J. A.; Reichert, David E.

    2015-01-01

    We have developed a microfluidic “click chip” incorporating an immobilized Cu(I) catalyst for click reactions. The microfluidic device was fabricated from polydimethylsiloxane (PDMS) bonded to glass and featured ~14,400 posts on the surface to improve catalyst immobilization. This design increased the immobilization efficiency and reduces the reagents’ diffusion time to active catalyst site. The device also incorporates five reservoirs to increase the reaction volume with minimal hydrodynamic pressure drop across the device. A novel water-soluble tris-(benzyltriazolylmethyl)amine (TBTA) derivative capable of stabilizing Cu(I), ligand 2, was synthesized and successfully immobilized on the chip surface. The catalyst immobilized chip surface was characterized by X-ray photoelectron spectroscopy (XPS). The immobilization efficiency was evaluated via radiotracer methods: the immobilized Cu(I) was measured as 1136±272 nmol and the surface immobilized Cu(I) density was 81±20 nmol cm−2. The active Cu(I)-ligand 2 could be regenerated up to five times without losing any catalyst efficiency. The “click” reaction of Flu568-azide and propargylamine was studied on chip for proof-of-principle. The on-chip reaction yields were ca. 82% with a 50 min reaction time or ca. 55% with a 15 min period at 37 °C, which was higher than those obtained in the conventional reaction. The on-chip “click” reaction involving a biomolecule, cyclo(RGDfK) peptide was also studied and demonstrated a conversion yield of ca. 98%. These encouraging results show promise on the application of the Cu(I) catalyst immobilized “click chip” for the development of biomolecule based imaging agents. PMID:25598970

  13. Facile synthesis of 4-vinyl- and 4-fluorovinyl-1,2,3-triazoles via bifunctional “click-olefination” reagents

    PubMed Central

    Kumar, Rakesh; Pradhan, Padmanava; Zajc, Barbara

    2011-01-01

    Modular synthesis of vinyl and fluorovinyl triazoles can be achieved from bifunctional propargyl and fluoropropargyl sulfones by Cu-catalyzed azide-alkyne ligation and Julia-Kocienski olefination. Competitive click reactions of the protio and fluoropropargyl sulfones show higher reactivity of the latter, and a preliminary DFT analysis was performed. PMID:21336351

  14. Liposome functionalization with copper-free "click chemistry".

    PubMed

    Oude Blenke, Erik; Klaasse, Gruson; Merten, Hannes; Plückthun, Andreas; Mastrobattista, Enrico; Martin, Nathaniel I

    2015-03-28

    The modification of liposomal surfaces is of interest for many different applications and a variety of chemistries are available that makes this possible. A major disadvantage of commonly used coupling chemistries (e.g. maleimide-thiol coupling) is the limited control over the site of conjugation in cases where multiple reactive functionalities are present, leading to heterogeneous products and in some cases dysfunctional conjugates. Bioorthogonal coupling approaches such as the well-established copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction are attractive alternatives as the reaction kinetics are favorable and azide-containing reagents are widely available. In the work described here, we prepared lipids containing a reactive cyclooctyne group and, after incorporation into liposomes, demonstrated successful conjugation of both a small molecule dye (5'-TAMRA-azide) as well as a larger azide-containing model protein based upon a designed ankyrin repeat protein (azido-DARPin). By applying the strain-promoted azido-alkyne cycloaddition (SPAAC) the use of Cu(I) as a catalyst is avoided, an important advantage considering the known deleterious effects associated with copper in cell and protein studies. We demonstrate complete control over the number of ligands coupled per liposome when using a small molecule azide with conjugation occurring at a reasonable reaction rate. By comparison, the conjugation of a larger azide-modified protein occurs more slowly, however the number of protein ligands coupled was found to be sufficient for liposome targeting to cells. Importantly, these results provide a strong proof of concept for the site-specific conjugation of protein ligands to liposomal surfaces via SPAAC. Unlike conventional approaches, this strategy provides for the homogeneous coupling of proteins bearing a single site-specific azide modification and eliminates the chance of forming dysfunctional ligands on the liposome. Furthermore, the absence of

  15. Modular ‘Click-in-Emulsion’ Bone-Targeted Nanogels

    PubMed Central

    Heller, Daniel A.; Levi, Yair; Pelet, Jeisa M.; Doloff, Joshua C.; Wallas, Jasmine; Pratt, George W.; Jiang, Shan; Sahay, Gaurav; Schroeder, Avi; Schroeder, Josh E.; Chyan, Yieu; Zurenko, Christopher; Querbes, William; Manzano, Miguel; Kohane, Daniel S.; Langer, Robert; Anderson, Daniel G.

    2013-01-01

    A new class of nanogel demonstrates modular biodistribution and affinity for bone. Nanogels, 67 nm in diameter and synthesized via an astoichiometric click-chemistry-inemulsion method, controllably display residual, free click-able functional groups. Functionalization with a bisphosphonate ligand results in significant binding to bone on the inner walls of marrow cavities, liver avoidance, and anti-osteoporotic effects. PMID:23280931

  16. Click-crosslinkable and photodegradable gelatin hydrogels for cytocompatible optical cell manipulation in natural environment

    PubMed Central

    Tamura, Masato; Yanagawa, Fumiki; Sugiura, Shinji; Takagi, Toshiyuki; Sumaru, Kimio; Kanamori, Toshiyuki

    2015-01-01

    This paper describes the generation of “click-crosslinkable“ and “photodegaradable“ gelatin hydrogels from the reaction between dibenzocycloctyl-terminated photoclevable tetra-arm polyethylene glycol and azide-modified gelatin. The hydrogels were formed in 30 min through the click-crosslinking reaction. The micropatterned features in the hydrogels were created by micropatterned light irradiation; the minimum resolution of micropatterning was 10-μm widths for line patterns and 20-μm diameters for circle patterns. Cells were successfully encapsulated in the hydrogels without any loss of viability across a wide concentration range of crosslinker. In contrast, an activated-ester-type photocleavable crosslinker, which we previously used to prepare photodegradable gelatin hydrogels, induced a decrease in cell viability at crosslinker concentrations greater than 1.8 mM. We also observed morphology alteration and better growth of cancer cells in the click-crosslinked photodegradable gelatin hydrogels that included matrigel than in the absence of matrigel. We also demonstrated micropatterning of the hydrogels encapsulating cells and optical cell separation. Both of the cells that remained in the non-irradiated area and the cells collected from the irradiated area maintained their viability. PMID:26450015

  17. Sensitive detection of copper(II) by a commercial glucometer using click chemistry.

    PubMed

    Su, Jiao; Xu, Jin; Chen, Ying; Xiang, Yun; Yuan, Ruo; Chai, Yaqin

    2013-07-15

    The commercially available glucometer has been the most successful point-of-care (POC) sensor up to date. However, the glucometer only responds to glucose rather than other species. Extending the use of the glucometer for monitoring different types of targets would potentially revolutionize the applicability of the glucometer. Here we report a new sensing strategy for sensitive and selective detection of Cu(2+) based on multi-invertase conjugated magnetic bead signal amplification labels and a glucometer transducer. The Cu(2+) is in situ reduced to Cu(+) by sodium ascorbate, which catalyzes the click linking between the alkynyl-DNA immobilized on a disposable screen printed carbon electrode and the azido-DNA attached to the invertase/magnetic bead conjugates. The numerous invertase on the magnetic bead labels through Cu(+)-catalyzed click chemistry reaction convert sucrose to glucose, which is monitored by the glucometer and offers amplified digital readings for Cu(2+) detection. By employing the multi-invertase signal amplification, as low as 10nM Cu(2+) can be detected. Our method also shows high selectivity for Cu(2+) against other metal ions owing to the highly specific Cu(+)-catalyzed click chemistry reaction, and is applicable for monitoring Cu(2+) in real river samples. Our strategy can be easily expanded for the monitoring of a wide range of targets when coupled with various recognition events. PMID:23500367

  18. Click-coated, heparinized, decellularized vascular grafts

    PubMed Central

    Dimitrievska, Sashka; Cai, Chao; Weyers, Amanda; Balestrini, Jenna L.; Lin, Tylee; Sundaram, Sumati; Hatachi, Go; Spiegel, David A.; Kyriakides, Themis R.; Miao, Jianjun; Li, Guoyun; Niklason, Laura; Linhardt, Robert J.

    2014-01-01

    A novel method enabling the engineering of a dense and appropriately oriented heparin-containing layer on decellularized aortas has been developed. Amino groups of decellularized aortas were first modified to azido groups using 3-azidobenzoic acid. Azide-clickable dendrons were attached onto the azido groups through “alkyne-azide” click chemistry, affording a ten-fold amplification of adhesions sites. Dendron end groups were finally decorated with end-on modified heparin chains. Heparin chains were oriented like heparan sulfate groups on native endothelial cells surface. XPS, NMR, MS and FTIR were used to characterize the synthesis steps, building the final heparin layered coatings. Continuity of the heparin coating was verified using fluorescent microscopy and histological analysis. Efficacy of heparin linkage was demonstrated with factor Xa antithrombogenic assay and platelet adhesion studies. The results suggest that oriented heparin immobilization to decellularized aortas may improve the in vivo blood compatibility of decellularized aortas and vessels. PMID:25463496

  19. Clicks versus Citations: Click Count as a Metric in High Energy Physics Publishing

    SciTech Connect

    Bitton, Ayelet; /UC, San Diego /SLAC

    2011-06-22

    High-energy physicists worldwide rely on online resources such as SPIRES and arXiv to perform gather research and share their own publications. SPIRES is a tool designed to search the literature within high-energy physics, while arXiv provides the actual full-text documents of this literature. In high-energy physics, papers are often ranked according to the number of citations they acquire - meaning the number of times a later paper references the original. This paper investigates the correlation between the number of times a paper is clicked in order to be downloaded and the number of citations it receives following the click. It explores how physicists truly read what they cite.

  20. Polymer- and Colloid-Functionalization Using a Combination Of ATRP and Click Chemistry

    NASA Astrophysics Data System (ADS)

    Zarafshani, Zoya; Lutz, Jean-François

    A straightforward click reaction (i.e. copper catalyzed 1,3 dipolar Huisgen cycloaddition of azides and terminal alkynes) was used as a complementary tool for functionalizing well-defined polymers prepared by atom transfer radical polymerization (ATRP). The bromine chain-ends of polystyrene or poly(acrylate) backbones were first transformed into azide end-groups via nucleophilic substitution and subsequently involved in “click” cycloaddition reactions with various functional alkynes. This efficient ATRP/“click” dual synthetic strategy was employed for preparing a wide variety of tailor-made functional materials such as telechelics, polymer-bioconjugates or shell-functionalized polymeric micelles.

  1. Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

    PubMed Central

    Wang, Ding; Xu, Zheng

    2015-01-01

    Summary The Cu(I)-catalyzed azide-alkyne cycloaddition reaction, also known as click chemistry, has become a useful tool for the facile formation of 1,2,3-triazoles. Specifically, the utility of this reaction has been demonstrated by the synthesis of structurally diverse bi- and bis-1,2,3-triazoles. The present review focuses on the synthesis of such bi- and bistriazoles and the importance of using copper-promoted click chemistry (CuAAC) for such transformations. In addition, the application of bitriazoles and the related CuAAAC reaction in different fields, including medicinal chemistry, coordination chemistry, biochemistry, and supramolecular chemistry, have been highlighted. PMID:26734102

  2. A new modular approach to nanoassembly: stable and addressable DNA nanoconstructs via orthogonal click chemistries.

    PubMed

    Gerrard, Simon R; Hardiman, Claire; Shelbourne, Montserrat; Nandhakumar, Iris; Nordén, Bengt; Brown, Tom

    2012-10-23

    Thermodynamic instability is a problem when assembling and purifying complex DNA nanostructures formed by hybridization alone. To address this issue, we have used photochemical fixation and orthogonal copper-free, ring-strain-promoted, click chemistry for the synthesis of dimeric, trimeric, and oligomeric modular DNA scaffolds from cyclic, double-stranded, 80-mer DNA nanoconstructs. This particular combination of orthogonal click reactions was more effective for nanoassembly than others explored. The complex nanostructures are stable to heat and denaturation agents and can therefore be purified and characterized. They are addressable in a sequence-specific manner by triplex formation, and they can be reversibly and selectively deconstructed. Nanostructures utilizing this orthogonal, chemical fixation methodology can be used as building blocks for nanomachines and functional DNA nanoarchitectures. PMID:22989197

  3. People’s Ability to Detect Objects Using Click-Based Echolocation: A Direct Comparison between Mouth-Clicks and Clicks Made by a Loudspeaker

    PubMed Central

    Thaler, Lore; Castillo-Serrano, Josefina

    2016-01-01

    Echolocation is the ability to use reflected sound to obtain information about the spatial environment. Echolocation is an active process that requires both the production of the emission as well as the sensory processing of the resultant sound. Appreciating the general usefulness of echo-acoustic cues for people, in particular those with vision impairments, various devices have been built that exploit the principle of echolocation to obtain and provide information about the environment. It is common to all these devices that they do not require the person to make a sound. Instead, the device produces the emission autonomously and feeds a resultant sound back to the user. Here we tested if echolocation performance in a simple object detection task was affected by the use of a head-mounted loudspeaker as compared to active clicking. We found that 27 sighted participants new to echolocation did generally better when they used a loudspeaker as compared to mouth-clicks, and that two blind participants with experience in echolocation did equally well with mouth clicks and the speaker. Importantly, performance of sighted participants’ was not statistically different from performance of blind experts when they used the speaker. Based on acoustic click data collected from a subset of our participants, those participants whose mouth clicks were more similar to the speaker clicks, and thus had higher peak frequencies and sound intensity, did better. We conclude that our results are encouraging for the consideration and development of assistive devices that exploit the principle of echolocation. PMID:27135407

  4. People's Ability to Detect Objects Using Click-Based Echolocation: A Direct Comparison between Mouth-Clicks and Clicks Made by a Loudspeaker.

    PubMed

    Thaler, Lore; Castillo-Serrano, Josefina

    2016-01-01

    Echolocation is the ability to use reflected sound to obtain information about the spatial environment. Echolocation is an active process that requires both the production of the emission as well as the sensory processing of the resultant sound. Appreciating the general usefulness of echo-acoustic cues for people, in particular those with vision impairments, various devices have been built that exploit the principle of echolocation to obtain and provide information about the environment. It is common to all these devices that they do not require the person to make a sound. Instead, the device produces the emission autonomously and feeds a resultant sound back to the user. Here we tested if echolocation performance in a simple object detection task was affected by the use of a head-mounted loudspeaker as compared to active clicking. We found that 27 sighted participants new to echolocation did generally better when they used a loudspeaker as compared to mouth-clicks, and that two blind participants with experience in echolocation did equally well with mouth clicks and the speaker. Importantly, performance of sighted participants' was not statistically different from performance of blind experts when they used the speaker. Based on acoustic click data collected from a subset of our participants, those participants whose mouth clicks were more similar to the speaker clicks, and thus had higher peak frequencies and sound intensity, did better. We conclude that our results are encouraging for the consideration and development of assistive devices that exploit the principle of echolocation. PMID:27135407

  5. Spectrogram analysis of low to mid frequency marine mammal clicks

    NASA Astrophysics Data System (ADS)

    Ioup, George E.; Ioup, Juliette W.; Larue, James P.; Sidorovskaia, Natalia A.; Kuczaj, Stan A.; Rayborn, Grayson H.; Walker, Christopher D.

    2001-05-01

    Previous investigators have proposed explanations for some sperm whale click structure and pointed out that the separation of individual pulses within the click might be used to determine approximately the size of the sperm whales. Recently, Mohl et al. [J. Acoust. Soc. Am. 114, 1124-1154 (2003)] have shown that echo-location click structure is highly dependent on the received angle. In data measured by the Littoral Acoustic Demonstration Center using bottom-moored hydrophones in the northern Gulf of Mexico in the summers of 2001 and 2002, rich click structures were observed in the spectrograms of many click trains, some of which exhibit strikingly consistent spectral nulls across the train. Although this structure in the spectra could be due to propagation effects, investigations to date suggest this possibility is highly unlikely, as discussed in the next abstract. Therefore it is at least plausible that the structure could be used to identify individual animals. This is known to be a difficult problem in the case of sperm whales because of the angle dependence of at least some of their clicks. These difficulties are discussed, as is the possible use of the spectrograms of the clicks to identify individuals. [Research supported by ONR.

  6. Dual-functionalized nanostructured biointerfaces by click chemistry.

    PubMed

    Schenk, Franziska C; Boehm, Heike; Spatz, Joachim P; Wegner, Seraphine V

    2014-06-17

    The presentation of biologically active molecules at interfaces has made it possible to investigate the responses of cells to individual molecules in their matrix at a given density and spacing. However, more sophisticated methods are needed to create model surfaces that present more than one molecule in a controlled manner in order to mimic at least partially the complexity given in natural environments. Herein, we present dual-functionalized surfaces combining quasi-hexagonally arranged gold nanoparticles with defined spacings and a newly developed PEG-alkyne coating to functionalize the glass in the intermediate space. The PEG-alkyne coating provides an inert background for cell interactions but can be modified orthogonally to the gold nanoparticles with numerous azides, including spectroscopically active molecules, peptides, and biotin at controlled densities by the copper(I)-catalyzed azide alkyne click reaction. The simultaneous presentation of cRGD on the gold nanoparticles with 100 nm spacing and synergy peptide PHSRN in the space between has a striking effect on REF cell adhesion; cells adhere, spread, and form mature focal adhesions on the dual-functionalized surfaces, whereas cells cannot adhere on either monofunctional surface. Combining these orthogonal functionalization methods creates a new platform to study precisely the crosstalk and synergy between different signaling molecules and clustering effects in ligand-receptor interactions. PMID:24856250

  7. Click Chemistry Immobilization of Antibodies on Polymer Coated Gold Nanoparticles.

    PubMed

    Finetti, Chiara; Sola, Laura; Pezzullo, Margherita; Prosperi, Davide; Colombo, Miriam; Riva, Benedetta; Avvakumova, Svetlana; Morasso, Carlo; Picciolini, Silvia; Chiari, Marcella

    2016-07-26

    The goal of this work is to develop an innovative approach for the coating of gold nanoparticles (AuNPs) with a synthetic functional copolymer. This stable coating with a thickness of few nanometers provides, at the same time, stabilization and functionalization of the particles. The polymeric coating consists of a backbone of polydimethylacrylamide (DMA) functionalized with an alkyne monomer that allows the binding of azido modified molecules by Cu(I)-catalyzed azide/alkyne 1,3-dipolar cycloaddition (CuAAC, click chemistry). The thin polymer layer on the surface stabilizes the colloidal suspension whereas the alkyne functions pending from the backbone are available for the reaction with azido-modified proteins. The reactivity of the coating is demonstrated by immobilizing an azido modified anti-mouse IgG antibody on the particle surface. This approach for the covalent binding of antibody to a gold-NPs is applied to the development of gold labels in biosensing techniques. PMID:27367748

  8. Dual-Functionalized Nanostructured Biointerfaces by Click Chemistry

    PubMed Central

    2014-01-01

    The presentation of biologically active molecules at interfaces has made it possible to investigate the responses of cells to individual molecules in their matrix at a given density and spacing. However, more sophisticated methods are needed to create model surfaces that present more than one molecule in a controlled manner in order to mimic at least partially the complexity given in natural environments. Herein, we present dual-functionalized surfaces combining quasi-hexagonally arranged gold nanoparticles with defined spacings and a newly developed PEG-alkyne coating to functionalize the glass in the intermediate space. The PEG-alkyne coating provides an inert background for cell interactions but can be modified orthogonally to the gold nanoparticles with numerous azides, including spectroscopically active molecules, peptides, and biotin at controlled densities by the copper(I)-catalyzed azide alkyne click reaction. The simultaneous presentation of cRGD on the gold nanoparticles with 100 nm spacing and synergy peptide PHSRN in the space between has a striking effect on REF cell adhesion; cells adhere, spread, and form mature focal adhesions on the dual-functionalized surfaces, whereas cells cannot adhere on either monofunctional surface. Combining these orthogonal functionalization methods creates a new platform to study precisely the crosstalk and synergy between different signaling molecules and clustering effects in ligand–receptor interactions. PMID:24856250

  9. Click production during breathing in a sperm whale (Physeter macrocephalus)

    NASA Astrophysics Data System (ADS)

    Wahlberg, Magnus; Frantzis, Alexandros; Alexiadou, Paraskevi; Madsen, Peter T.; Møhl, Bertel

    2005-12-01

    A sperm whale (Physeter macrocephalus) was observed at the surface with above- and underwater video and synchronized underwater sound recordings. During seven instances the whale ventilated its lungs while clicking. From this observation it is inferred that click production is achieved by pressurizing air in the right nasal passage, pneumatically disconnected from the lungs and the left nasal passage, and that air flows anterior through the phonic lips into the distal air sac. The capability of breathing and clicking at the same time is unique among studied odontocetes and relates to the extreme asymmetry of the sperm whale sound-producing forehead.

  10. Application of Near-IR Absorption Porphyrin Dyes Derived from Click Chemistry as Third-Order Nonlinear Optical Materials.

    PubMed

    Mi, Yongsheng; Liang, Pengxia; Yang, Zhou; Wang, Dong; Cao, Hui; He, Wanli; Yang, Huai; Yu, Lian

    2016-02-01

    Recently, third-order nonlinear properties of porphyrins and porphyrin polymers and coordination compounds have been extensively studied in relation to their use in photomedicine and molecular photonics. A new functionalized porphyrin dye containing electron-rich alkynes was synthesized and further modified by formal [2+2] click reactions with click reagents tetracyanoethylene (TCNE) and 7, 7, 8, 8-tetracyanoquinodimethane (TCNQ). The photophysical properties of these porphyrin dyes, as well as the click reaction, were studied by UV/Vis spectroscopy. In particular, third-order nonlinear optical properties of the dyes, which showed typical d-π-A structures, were characterized by Z-scan techniques. In addition, the self-assembly properties were investigated through the phase-exchange method, and highly organized morphologies were observed by scanning electron microscopy (SEM). The effects of the click post-functionalization on the properties of the porphyrins were studied, and these functionalized porphyrin dyes represent an interesting set of candidates for optoelectronic device components. PMID:27308215

  11. Application of Near‐IR Absorption Porphyrin Dyes Derived from Click Chemistry as Third‐Order Nonlinear Optical Materials

    PubMed Central

    Mi, Yongsheng; Liang, Pengxia; Cao, Hui; He, Wanli

    2015-01-01

    Abstract Recently, third‐order nonlinear properties of porphyrins and porphyrin polymers and coordination compounds have been extensively studied in relation to their use in photomedicine and molecular photonics. A new functionalized porphyrin dye containing electron‐rich alkynes was synthesized and further modified by formal [2+2] click reactions with click reagents tetracyanoethylene (TCNE) and 7, 7, 8, 8‐tetracyanoquinodimethane (TCNQ). The photophysical properties of these porphyrin dyes, as well as the click reaction, were studied by UV/Vis spectroscopy. In particular, third‐order nonlinear optical properties of the dyes, which showed typical d‐π‐A structures, were characterized by Z‐scan techniques. In addition, the self‐assembly properties were investigated through the phase‐exchange method, and highly organized morphologies were observed by scanning electron microscopy (SEM). The effects of the click post‐functionalization on the properties of the porphyrins were studied, and these functionalized porphyrin dyes represent an interesting set of candidates for optoelectronic device components. PMID:27308215

  12. Iterative In situ Click Chemistry Assembles a Branched Capture Agent and Allosteric Inhibitor for Akt1

    PubMed Central

    Millward, Steven W.; Henning, Ryan K.; Kwong, Gabriel A.; Pitram, Suresh; Agnew, Heather D.; Deyle, Kaycie M.; Nag, Arundhati; Hein, Jason; Lee, Su Seong; Lim, Jaehong; Pfeilsticker, Jessica A.; Sharpless, K. Barry; Heath, James R.

    2011-01-01

    We describe the use of iterative in situ click chemistry to design an Akt-specific branched peptide triligand that is a drop-in replacement for monoclonal antibodies in multiple biochemical assays. Each peptide module in the branched structure makes unique contributions to affinity and/or specificity resulting in a 200 nM affinity ligand that efficiently immunoprecipitates Akt from cancer cell lysates and labels Akt in fixed cells. Our use of a small molecule to pre-inhibit Akt prior to screening resulted in low micromolar inhibitory potency and an allosteric mode of inhibition, which is evidenced through a series of competitive enzyme kinetic assays. To demonstrate the efficiency and selectivity of the protein-templated in situ click reaction, we developed a novel QPCR-based methodology that enabled a quantitative assessment of its yield. These results point to the potential for iterative in situ click chemistry to generate potent, synthetically accessible antibody replacements with novel inhibitory properties PMID:21962254

  13. Click-Based Libraries of SFTI-1 Peptides: New Methods Using Reversed-Phase Silica.

    PubMed

    Cistrone, Philip A; Dawson, Philip E

    2016-03-14

    Performing sequential reactions for the orthogonal derivatization of peptides in solution often requires intermediate handling and purification steps. To solve these problems, we have exploited the distinct adsorption kinetics of peptides toward particulate reversed-phase (RP) C18 silica material, enabling consecutive reactions to be performed without intermediate elution. To illustrate this approach, sequential CuAAC/click reactions were used to modify an analog of the bicyclic peptide sunflower trypsin inhibitor 1 (SFTI-1), a potent scaffold for trypsin and chymotrypsin-like enzyme inhibitors. The SFTI-1 scaffold was synthesized containing both β-azido alanine and propargyl glycine residues. Despite the mutual reactivity of these groups, site isolation on RP silica enabled consecutive click reactions and associated washing steps to be performed while the peptide remained immobilized. Importantly, this approach eliminated side products that could form between two peptides or within a single peptide. These studies suggest a broad utility for RP silica in solving both peptide handling problems and in improving synthetic workflows. PMID:26914614

  14. "Click" Chemistry: Application of Copper Metal in Cu-Catalyzed Azomethine Imine-Alkyne Cycloadditions.

    PubMed

    Pušavec Kirar, Eva; Grošelj, Uroš; Mirri, Giorgio; Požgan, Franc; Strle, Gregor; Štefane, Bogdan; Jovanovski, Vasko; Svete, Jurij

    2016-07-15

    A series of 16 copper-catalyzed azomethine imine-alkyne cycloaddition (CuAIAC) reactions between four pyrazolidinone-1-azomethine imines and four terminal ynones gave the corresponding fluorescent cycloadducts as bimane analogues in very high yields. The applicability of CuAIAC was demonstrated by the fluorescent labeling of functionalized polystyrene and by using Cu-C and Cu-Fe as catalysts. Experimental evidence, kinetic measurements, and correlation between a clean catalyst surface and the reaction rate are in agreement with a homotopic catalytic system with catalytic Cu(I)-acetylide formed from Cu(0) by "in situ" oxidation. The availability of azomethine imines, mild reaction conditions, simple workup, and scalability make CuAIAC a viable supplement to the Cu-catalyzed azide-alkyne cycloaddition reaction in "click" chemistry. PMID:27305104

  15. Click Chemistry-Mediated Nanosensors for Biochemical Assays

    PubMed Central

    Chen, Yiping; Xianyu, Yunlei; Wu, Jing; Yin, Binfeng; Jiang, Xingyu

    2016-01-01

    Click chemistry combined with functional nanoparticles have drawn increasing attention in biochemical assays because they are promising in developing biosensors with effective signal transformation/amplification and straightforward signal readout for clinical diagnostic assays. In this review, we focus on the latest advances of biochemical assays based on Cu (I)-catalyzed 1, 3-dipolar cycloaddition of azides and alkynes (CuAAC)-mediated nanosensors, as well as the functionalization of nanoprobes based on click chemistry. Nanoprobes including gold nanoparticles, quantum dots, magnetic nanoparticles and carbon nanomaterials are covered. We discuss the advantages of click chemistry-mediated nanosensors for biochemical assays, and give perspectives on the development of click chemistry-mediated approaches for clinical diagnosis and other biomedical applications. PMID:27217831

  16. Clicking hyoid: A rare case report and review

    PubMed Central

    Singh, Virendra; Priya, Kannu; Bhagol, Amrish; Kirti, Shruti; Thepra, Manju

    2015-01-01

    Painful conditions of unexplained origin pose a challenging task for the clinician from both the diagnosis and treatment perspective. This might be accounted due to overlapping symptomatology; moreover, nonspecific subjective findings push the diagnostic process to a more perplexing direction. The main loophole in their management lies in difficulty to make an appropriate diagnosis. Clicking hyoid is an extremely rare anomaly of hyoid bone which produces painful clicking in throat. Here, we report a case of a young patient presented with pain and clicking in throat which aggravated on swallowing. After a series of examinations, it was diagnosed as clicking hyoid and was managed successfully by surgical treatment. The objective of this article is not only to increase awareness of the ailment so as to validate its existence but also demonstrate the significant utility of the surgical management. PMID:27390508

  17. Late systolic click in non-obstructive cardiomyopathy

    PubMed Central

    Mercer, Edward N.; Frye, Robert L.; Giuliani, Emilio R.

    1970-01-01

    Two patients with seriously impaired left ventricular function, abnormal left ventricular conduction on the electrocardiogram, mitral regurgitation, and a very late systolic click are reported. Idiopathic non-obstructive cardiomyopathy seemed to be the cause of the left ventricular dysfunction in both cases. The mitral valve was anatomically normal at the time of operation in one patient, except for dilatation of the annulus, and the mitral regurgitation appeared to be secondary to left ventricular failure. The very late timing of the mitral systolic clicks in these two patients may be related to a large left ventricular end-diastolic volume and impaired left ventricular function, or to an abnormal sequence of excitation of the left ventricle. The timing of the late systolic click in these patients is in contrast to that in patients with mid systolic clicks, hearts of normal size, and little cardiac disability. Images PMID:5470052

  18. Click Chemistry-Mediated Nanosensors for Biochemical Assays.

    PubMed

    Chen, Yiping; Xianyu, Yunlei; Wu, Jing; Yin, Binfeng; Jiang, Xingyu

    2016-01-01

    Click chemistry combined with functional nanoparticles have drawn increasing attention in biochemical assays because they are promising in developing biosensors with effective signal transformation/amplification and straightforward signal readout for clinical diagnostic assays. In this review, we focus on the latest advances of biochemical assays based on Cu (I)-catalyzed 1, 3-dipolar cycloaddition of azides and alkynes (CuAAC)-mediated nanosensors, as well as the functionalization of nanoprobes based on click chemistry. Nanoprobes including gold nanoparticles, quantum dots, magnetic nanoparticles and carbon nanomaterials are covered. We discuss the advantages of click chemistry-mediated nanosensors for biochemical assays, and give perspectives on the development of click chemistry-mediated approaches for clinical diagnosis and other biomedical applications. PMID:27217831

  19. Nonecholocating fruit bats produce biosonar clicks with their wings.

    PubMed

    Boonman, Arjan; Bumrungsri, Sara; Yovel, Yossi

    2014-12-15

    Because evolution mostly acts over millions of years, the intermediate steps leading to a functional sensory system remain enigmatic. Accordingly, there is an ongoing debate regarding the evolution of bat echolocation. In search of the origin of bat echolocation, we studied how Old World fruit bats, which have always been classified as nonecholocating, orient in complete darkness. We found that two of these nonecholocating species used click-like sounds to detect and discriminate objects in complete darkness. However, we discovered that this click-based echo sensing is rudimentary and does not allow these bats to estimate distance accurately as all other echolocating bats can. Moreover, unlike all other echolocating bats, which generate pulses using the larynx or the tongue, these bats generated clicks with their wings. We provide evidence suggesting that all Old World fruit bats can click with their wings. Although this click-based echo sensing used by Old World fruit bats may not represent the ancestral form of current (laryngeal) bat echolocation, we argue that clicking fruit bats could be considered behavioral fossils, opening a window to study the evolution of echolocation. PMID:25484290

  20. Design and synthesis of glycoprotein-based multivalent glyco-ligands for influenza hemagglutinin and human galectin-3.

    PubMed

    Wang, Helen; Huang, Wei; Orwenyo, Jared; Banerjee, Aditi; Vasta, Gerardo R; Wang, Lai-Xi

    2013-04-01

    We report a facile synthesis of glycoprotein-based glyco-ligands and their binding with influenza hemagglutinin and human galectin-3. Human serum albumin (HSA) was used as the scaffold and an Asn-linked complex type N-glycan prepared from chicken eggs was used as the glycan building block. It was found that Cu(I)-catalyzed alkyne-azide cycloaddition reaction (click chemistry) between the alkyne-labeled glycan and the azide-tagged HSA led to an efficient formation of the glycoconjugates. The density of glycan ligands on the protein scaffold was readily varied by changing the molar ratios of the two reactants. Binding studies indicated that the sialylated and desialylated multivalent glycoligands could selectively bind to influenza hemagglutinin and human galectin-3, respectively, with high affinity. In the two glycan-lectin interactions, a clear multivalent effect was observed. Moreover, a cell-based assay showed that the synthetic multivalent glyco-ligands could efficiently inhibit the attachment of galectin-3 to human prostate cancer and lung cancer cell lines. This study suggests that the synthetic glycoprotein-based glyco-ligands can be useful for different applications, including blocking the function of galectin-3 in cancer metastasis. PMID:23411399

  1. Novel oligonuclear copper complexes featuring exciting luminescent characteristics

    NASA Astrophysics Data System (ADS)

    Zink, Daniel M.; Volz, Daniel; Bergmann, Larissa; Nieger, Martin; Bräse, Stefan; Yersin, Hartmut; Baumann, Thomas

    2013-09-01

    A series of highly luminescent mono-, di-, and trinuclear copper(I) complexes has been synthesized using modular ligand systems of easily accessible N^N, P^P or P^N ligands in order to show the rich structural diversity of copper(I) compounds. Those systems allow for the design of various emitting materials with desired photophysical properties, such as emission colors and high efficiencies. The complexes were characterized with well-established methods such as X-ray crystallographic studies or elemental analysis and, in addition, due to their interesting photoluminescence characteristics, their emission properties were further investigated by means of spectroscopic methods as well as DFT-calculations. In detail, various cationic and neutral mononuclear complexes have been synthesized in order to investigate the photophysical properties of this these different types of emitting compounds. It has been found that neutral copper(I) complexes show superior emission properties (with PLQY up to 89%) compared to their cationic counterparts. Furthermore, a series of dinuclear and trinuclear copper(I) complexes has been synthesized featuring an easy tunable emission maximum from sky blue to deep red (481 nm to 713 nm) with extraordinary high photoluminescence quantum yields up to 99%. In addition, a new crosslinking-technique has been developed to open up the door for a new way to fully solution processed OLED using these promising emitting compounds: Alkyne-substituted emitting complexes crosslink automatically with azide-polymers in a copper-catalyzed alkyne-azide Click reaction.

  2. Synthesis of clicked imidazolium-containing biosourced copolymers and application in carbon nanotube dispersion.

    PubMed

    Mincheva, Rosica; Meyer, Franck; Verge, Pierre; Raquez, Jean-Marie; Billiet, Leen; Du Prez, Filip; Dubois, Philippe

    2011-12-15

    New polyesters incorporating a variable quantity of imidazolium rings along the backbone are synthesized by Huisgen 1,3-dipolar cycloaddition ("click" reaction). Subsequently, the imidazolium-grafted copolymers reveal an efficient dispersing ability toward the carbon nanotubes (CNTs) through supramolecular interactions in organic media. Interestingly, these compounds offer a simple and reliable strategy to control the quantity of dispersed CNTs as a function of imidazolium content. This approach is particularly suitable for the elaboration of biosourced and biodegradable materials based on poly(butylene succinate) with high-performance properties. PMID:22105987

  3. One-pot synthesis of Au@SiO(2) catalysts: a click chemistry approach.

    PubMed

    Solovyeva, Vera A; Vu, Khanh B; Merican, Zulkifli; Sougrat, Rachid; Rodionov, Valentin O

    2014-10-13

    Using the copper-catalyzed azide-alkyne cycloaddition "click" reaction, a library of triazole amphiphiles with a variety of functional polar "heads" and hydrophobic or superhydrophobic "tails" was synthesized. The amphiphiles were evaluated for their ability to stabilize small Au nanoparticles, and, at the same time, serve as templates for nanocasting porous SiO2. One of the Au@SiO2 materials thus prepared was found to be a highly active catalyst for the Au nanoparticle-catalyzed regioselective hydroamination of alkynes. PMID:25229602

  4. Bioorthogonal Click Chemistry: An Indispensable Tool to Create Multifaceted Cell Culture Scaffolds

    PubMed Central

    2012-01-01

    Over the past decade, bioorthogonal click chemistry has led the field of biomaterial science into a new era of diversity and complexity by its extremely selective, versatile, and biocompatible nature. In this viewpoint, we seek to emphasize recent endeavors of exploiting this versatile chemistry toward the development of poly(ethylene glycol) hydrogels as cell culture scaffolds. In these cell-laden materials, the orthogonality of these reactions has played an effective role in allowing the creation of diverse biochemical patterns in complex biological environments that provide new found opportunities for researchers to delineate and control cellular phenotypes more precisely than ever. PMID:23336091

  5. Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation

    PubMed Central

    McKay, Craig S.; Finn, M.G.

    2014-01-01

    The selective chemical modification of biological molecules drives a good portion of modern drug development and fundamental biological research. While a few early examples of reactions that engage amine and thiol groups on proteins helped establish the value of such processes, the development of reactions that avoid most biological molecules so as to achieve selectivity in desired bond-forming events has revolutionized the field. We provide an update on recent developments in bioorthogonal chemistry that highlights key advances in reaction rates, biocompatibility, and applications. While not exhaustive, we hope this summary allows the reader to appreciate the rich continuing development of good chemistry that operates in the biological setting. PMID:25237856

  6. 'Clickable' ZnO nanocrystals: the superiority of a novel organometallic approach over the inorganic sol-gel procedure.

    PubMed

    Grala, Agnieszka; Wolska-Pietkiewicz, Małgorzata; Danowski, Wojciech; Wróbel, Zbigniew; Grzonka, Justyna; Lewiński, Janusz

    2016-05-31

    We demonstrate for the first time a highly efficient Cu(i)-catalyzed alkyne-azide cycloaddition reaction on the surface of ZnO nanocrystals with retention of their photoluminescence properties. Our comparative studies highlight the superiority of a novel self-supporting organometallic method for the preparation of brightly luminescent and well-passivated ZnO nanocrystals over the traditional sol-gel procedure. PMID:27156855

  7. Water-soluble NHC-Cu catalysts: applications in click chemistry, bioconjugation and mechanistic analysis.

    PubMed

    Díaz Velázquez, Heriberto; Ruiz García, Yara; Vandichel, Matthias; Madder, Annemieke; Verpoort, Francis

    2014-12-14

    Copper(I)-catalyzed 1,3-dipolar cycloaddition of azides and terminal alkynes (CuAAC), better known as "click" reaction, has triggered the use of 1,2,3-triazoles in bioconjugation, drug discovery, materials science and combinatorial chemistry. Here we report a new series of water-soluble catalysts based on N-heterocyclic carbene (NHC)-Cu complexes which are additionally functionalized with a sulfonate group. The complexes show superior activity towards CuAAC reactions and display a high versatility, enabling the production of triazoles with different substitution patterns. Additionally, successful application of these complexes in bioconjugation using unprotected peptides acting as DNA binding domains was achieved for the first time. Mechanistic insight into the reaction mechanism is obtained by means of state-of-the-art first principles calculations. PMID:25251642

  8. The application of click chemistry in the synthesis of agents with anticancer activity

    PubMed Central

    Ma, Nan; Wang, Ying; Zhao, Bing-Xin; Ye, Wen-Cai; Jiang, Sheng

    2015-01-01

    The copper(I)-catalyzed 1,3-dipolar cycloaddition between alkynes and azides (click chemistry) to form 1,2,3-triazoles is the most popular reaction due to its reliability, specificity, and biocompatibility. This reaction has the potential to shorten procedures, and render more efficient lead identification and optimization procedures in medicinal chemistry, which is a powerful modular synthetic approach toward the assembly of new molecular entities and has been applied in anticancer drugs discovery increasingly. The present review focuses mainly on the applications of this reaction in the field of synthesis of agents with anticancer activity, which are divided into four groups: topoisomerase II inhibitors, histone deacetylase inhibitors, protein tyrosine kinase inhibitors, and antimicrotubule agents. PMID:25792812

  9. Medclic: the Mediterranean in one click

    NASA Astrophysics Data System (ADS)

    Troupin, Charles; Frontera, Biel; Sebastián, Kristian; Pau Beltran, Joan; Krietemeyer, Andreas; Gómara, Sonia; Gomila, Mikel; Escudier, Romain; Juza, Mélanie; Mourre, Baptiste; Garau, Angels; Cañellas, Tomeu; Tintoré, Joaquín

    2016-04-01

    "Medclic: the Mediterranean in one click" is a research and dissemination project focused on the scientific, technological and societal approaches of the Balearic Islands Coastal Observing and Forecasting System ({SOCIB}{www.socib.es}) in a collaboration with "la Caixa" Foundation. SOCIB aims at research excellence and the development of technology which enables progress toward the sustainable management of coastal and marine environments, providing solutions to meet the needs of society. Medclic goes one step forward and has two main goals: at the scientific level, to advance in establishing and understanding the mesoscale variability at the regional scale and its interaction, and thus improving the characterisation of the "oceanic weather" in the Mediterranean; at the outreach level: to bring SOCIB and the new paradigm of multi-platform observation in real time closer to society, through scientific outreach. SOCIB Data Centre is the core of the new multi-platform and real time oceanography and is responsible for directing the different stages of data management, ranging from data acquisition to its distribution and visualization through web applications. The system implemented relies on open source solutions and provides data in line with international standards and conventions (INSPIRE, netCDF Climate and Forecast, ldots). In addition, the Data Centre has implemented a REST web service, called Data Discovery. This service allows data generated by SOCIB to be integrated into applications developed by the Data Centre itself or by third parties, as it is the case with Medclic. Relying on this data distribution, the new web Medclic, www.medclic.es, constitutes an interactive scientific and educational area of communication that contributes to the rapprochement of the general public with the new marine and coastal observing technologies. Thanks to the Medclic web, data coming from new observing technologies in oceanography are available in real time and in one clic

  10. Enantioselective copper-catalyzed azide-alkyne click cycloaddition to desymmetrization of maleimide-based bis(alkynes).

    PubMed

    Song, Tao; Li, Li; Zhou, Wei; Zheng, Zhan-Jiang; Deng, Yuan; Xu, Zheng; Xu, Li-Wen

    2015-01-01

    A copper catalyst system derived from TaoPhos and CuF2 was used successfully for catalytic asymmetric Huisgen [3+2] cycloaddition of azides and alkynes to give optically pure products containing succinimide- and triazole-substituted quaternary carbon stereogenic centers. The desired products were obtained in good yields (60-80 %) and 85:15 to >99:1 enantiomeric ratio (e.r.) in this click cycloaddition reaction. PMID:25388524

  11. Ways to suppress click and pop for class D amplifiers

    NASA Astrophysics Data System (ADS)

    Haishi, Wang; Bo, Zhang; Jiang, Sun

    2012-08-01

    Undesirable audio click and pop may be generated in a speaker or headphone. Compared to linear (class A/B/AB) amplifiers, class D amplifiers that comprise of an input stage and a modulation stage are more prone to producing click and pop. This article analyzes sources that generate click and pop in class D amplifiers, and corresponding ways to suppress them. For a class D amplifier with a single-ended input, click and pop is likely to be due to two factors. One is from a voltage difference (VDIF) between the voltage of an input capacitance (VCIN) and a reference voltage (VREF) of the input stage, and the other one is from the non-linear switching during the setting up of the bias and feedback voltages/currents (BFVC) of the modulation stage. In this article, a fast charging loop is introduced into the input stage to charge VCIN to roughly near VREF. Then a correction loop further charges or discharges VCIN, substantially equalizing it with VREF. Dummy switches are introduced into the modulation stage to provide switching signals for setting up BFVC, and the power switches are disabled until the BFVC are set up successfully. A two channel single-ended class D amplifier with the above features is fabricated with 0.5 μm Bi-CMOS process. Road test and fast Fourier transform analysis indicate that there is no noticeable click and pop.

  12. Click- and chirp-evoked human compound action potentials.

    PubMed

    Chertoff, Mark; Lichtenhan, Jeffery; Willis, Marie

    2010-05-01

    In the experiments reported here, the amplitude and the latency of human compound action potentials (CAPs) evoked from a chirp stimulus are compared to those evoked from a traditional click stimulus. The chirp stimulus was created with a frequency sweep to compensate for basilar membrane traveling wave delay using the O-Chirp equations from Fobel and Dau [(2004). J. Acoust. Soc. Am. 116, 2213-2222] derived from otoacoustic emission data. Human cochlear traveling wave delay estimates were obtained from derived compound band action potentials provided by Eggermont [(1979). J. Acoust. Soc. Am. 65, 463-470]. CAPs were recorded from an electrode placed on the tympanic membrane (TM), and the acoustic signals were monitored with a probe tube microphone attached to the TM electrode. Results showed that the amplitude and latency of chirp-evoked N1 of the CAP differed from click-evoked CAPs in several regards. For the chirp-evoked CAP, the N1 amplitude was significantly larger than the click-evoked N1s. The latency-intensity function was significantly shallower for chirp-evoked CAPs as compared to click-evoked CAPs. This suggests that auditory nerve fibers respond with more unison to a chirp stimulus than to a click stimulus. PMID:21117748

  13. Clicking caterpillars: acoustic aposematism in Antheraea polyphemus and other Bombycoidea.

    PubMed

    Brown, Sarah G; Boettner, George H; Yack, Jayne E

    2007-03-01

    Acoustic signals produced by caterpillars have been documented for over 100 years, but in the majority of cases their significance is unknown. This study is the first to experimentally examine the phenomenon of audible sound production in larval Lepidoptera, focusing on a common silkmoth caterpillar, Antheraea polyphemus (Saturniidae). Larvae produce airborne sounds, resembling ;clicks', with their mandibles. Larvae typically signal multiple times in quick succession, producing trains that last over 1 min and include 50-55 clicks. Individual clicks within a train are on average 24.7 ms in duration, often consisting of multiple components. Clicks are audible in a quiet room, measuring 58.1-78.8 dB peSPL at 10 cm. They exhibit a broadband frequency that extends into the ultrasound spectrum, with most energy between 8 and 18 kHz. Our hypothesis that clicks function as acoustic aposematic signals, was supported by several lines of evidence. Experiments with forceps and domestic chicks correlated sound production with attack, and an increase in attack rate was positively correlated with the number of signals produced. In addition, sound production typically preceded or accompanied defensive regurgitation. Bioassays with invertebrates (ants) and vertebrates (mice) revealed that the regurgitant is deterrent to would-be predators. Comparative evidence revealed that other Bombycoidea species, including Actias luna (Saturniidae) and Manduca sexta (Sphingidae), also produce airborne sounds upon attack, and that these sounds precede regurgitation. The prevalence and adaptive significance of warning sounds in caterpillars is discussed. PMID:17337712

  14. Click dendrimers and triazole-related aspects: catalysts, mechanism, synthesis, and functions. A bridge between dendritic architectures and nanomaterials.

    PubMed

    Astruc, Didier; Liang, Liyuan; Rapakousiou, Amalia; Ruiz, Jaime

    2012-04-17

    One of the primary recent improvements in molecular chemistry is the now decade-old concept of click chemistry. Typically performed as copper-catalyzed azide-alkyne (CuAAC) Huisgen-type 1,3-cycloadditions, this reaction has many applications in biomedicine and materials science. The application of this chemistry in dendrimer synthesis beyond the zeroth generation and in nanoparticle functionalization requires stoichiometric use of the most common click catalyst, CuSO(4)·5H(2)O with sodium ascorbate. Efforts to develop milder reaction conditions for these substrates have led to the design of polydentate nitrogen ligands. Along these lines, we have described a new, efficient, practical, and easy-to-synthesize catalytic complex, [Cu(I)(hexabenzyltren)]Br, 1 [tren = tris(2-aminoethyl)amine], for the synthesis of relatively large dendrimers and functional gold nanoparticles (AuNPs). This efficient catalyst can be used alone in 0.1% mol amounts for nondendritic click reactions or with the sodium-ascorbate additive, which inhibits aerobic catalyst oxidation. Alternatively, catalytic quantities of the air-stable compounds hexabenzyltren and CuBr added to the click reaction medium can provide analogously satisfactory results. Based on this catalyst as a core, we have also designed and synthesized analogous Cu(I)-centered dendritic catalysts that are much less air-sensitive than 1 and are soluble in organic solvents or in water (depending on the nature of the terminal groups). These multivalent catalysts facilitate efficient click chemistry and exert positive dendritic effects that mimic enzyme activity. We propose a monometallic CuAAC click mechanism for this process. Although the primary use of click chemistry with dendrimers has been to decorate dendrimers with a large number of molecules for medicinal or materials purposes, we are specifically interested in the formation of intradendritic [1,2,3]-triazole heterocycles that coordinate to transition-metal ions via their

  15. Uncovering Quantum Correlations with Time-Multiplexed Click Detection.

    PubMed

    Sperling, J; Bohmann, M; Vogel, W; Harder, G; Brecht, B; Ansari, V; Silberhorn, C

    2015-07-10

    We report on the implementation of a time-multiplexed click detection scheme to probe quantum correlations between different spatial optical modes. We demonstrate that such measurement setups can uncover nonclassical correlations in multimode light fields even if the single mode reductions are purely classical. The nonclassical character of correlated photon pairs, generated by a parametric down-conversion, is immediately measurable employing the theory of click counting instead of low-intensity approximations with photoelectric detection models. The analysis is based on second- and higher-order moments, which are directly retrieved from the measured click statistics, for relatively high mean photon numbers. No data postprocessing is required to demonstrate the effects of interest with high significance, despite low efficiencies and experimental imperfections. Our approach shows that such novel detection schemes are a reliable and robust way to characterize quantum-correlated light fields for practical applications in quantum communications. PMID:26207467

  16. Uncovering Quantum Correlations with Time-Multiplexed Click Detection

    NASA Astrophysics Data System (ADS)

    Sperling, J.; Bohmann, M.; Vogel, W.; Harder, G.; Brecht, B.; Ansari, V.; Silberhorn, C.

    2015-07-01

    We report on the implementation of a time-multiplexed click detection scheme to probe quantum correlations between different spatial optical modes. We demonstrate that such measurement setups can uncover nonclassical correlations in multimode light fields even if the single mode reductions are purely classical. The nonclassical character of correlated photon pairs, generated by a parametric down-conversion, is immediately measurable employing the theory of click counting instead of low-intensity approximations with photoelectric detection models. The analysis is based on second- and higher-order moments, which are directly retrieved from the measured click statistics, for relatively high mean photon numbers. No data postprocessing is required to demonstrate the effects of interest with high significance, despite low efficiencies and experimental imperfections. Our approach shows that such novel detection schemes are a reliable and robust way to characterize quantum-correlated light fields for practical applications in quantum communications.

  17. Elastin-like recombinamer catalyst-free click gels: characterization of poroelastic and intrinsic viscoelastic properties.

    PubMed

    González de Torre, Israel; Santos, Mercedes; Quintanilla, Luis; Testera, Ana; Alonso, Matilde; Rodríguez Cabello, José Carlos

    2014-06-01

    Elastin-like recombinamer catalyst-free click gels (ELR-CFCGs) have been prepared and characterized by modifying both a structural ELR (VKVx24) and a biofunctionalized ELR-bearing RGD cell-adhesion sequence (HRGD6) to bear the reactive groups needed to form hydrogels via a click reaction. Prior to formation of the ELR-CFCGs, azide-bearing and cyclooctyne-modified ELRs were also synthesized. Subsequent covalent crosslinking was based on the reaction between these azide and cyclooctyne groups, which takes place under physiological conditions and without the need for a catalyst. The correlation among SEM micrographs, porosity, swelling ratio, and rheological measurements have been carried out. The storage and loss moduli at 1Hz are in the range 1-10kPa and 100-1000Pa, respectively. The linear dependence of |G∗| on f(½) and the peak value of tan δ were considered to be consistent with a poroelastic mechanism dominating the frequency range 0.3-70Hz. The discrete relaxation spectrum was obtained from stress relaxation measurements (t>5s). The good fit of the relaxation modulus to decrease exponential functions suggests that an intrinsic viscoelastic mechanism dominates the transients. Several recombinamer concentrations and temperatures were tested to obtain gels with fully tuneable properties that could find applications in the biomedical field. PMID:24530853

  18. Simple Method To Prepare Oligonucleotide-Conjugated Antibodies and Its Application in Multiplex Protein Detection in Single Cells.

    PubMed

    Gong, Haibiao; Holcomb, Ilona; Ooi, Aik; Wang, Xiaohui; Majonis, Daniel; Unger, Marc A; Ramakrishnan, Ramesh

    2016-01-20

    The diversity of nucleic acid sequences enables genomics studies in a highly multiplexed format. Since multiplex protein detection is still a challenge, it would be useful to use genomics tools for this purpose. This can be accomplished by conjugating specific oligonucleotides to antibodies. Upon binding of the oligonucleotide-conjugated antibodies to their targets, the protein levels can be converted to oligonucleotide levels. In this report we describe a simple method for preparing oligonucleotide-conjugated antibodies and discuss this method's application in oligonucleotide extension reaction (OER) for multiplex protein detection. Conjugation is based on strain-promoted alkyne-azide cycloaddition (the Cu-free click reaction), in which the antibody is activated with a dibenzocyclooctyne (DBCO) moiety and subsequently linked covalently with an azide-modified oligonucleotide. In the functional test, the reaction conditions and purification processes were optimized to achieve maximum yield and best performance. The OER assay employs a pair of antibody binders (two antibodies, each conjugated with its own oligonucleotide) developed for each protein target. The two oligonucleotides contain unique six-base complementary regions at their 3' prime ends to allow annealing and extension by DNA synthesis enzymes to form a DNA template. Following preamplification, the DNA template is detected by qPCR. Distinct oligonucleotide sequences are assigned to different antibody binders to enable multiplex protein detection. When tested using recombinant proteins, some antibody binders, such as those specific to CSTB, MET, EpCAM, and CASP3, had dynamic ranges of 5-6 logs. The antibody binders were also used in a multiplexed format in OER assays, and the binders successfully detected their protein targets in cell lysates, and in single cells in combination with the C1 system. This click reaction-based antibody conjugation procedure is cost-effective, needs minimal hands-on time, and

  19. Hearing sensation levels of emitted biosonar clicks in an echolocating Atlantic bottlenose dolphin.

    PubMed

    Li, Songhai; Nachtigall, Paul E; Breese, Marlee; Supin, Alexander Ya

    2012-01-01

    Emitted biosonar clicks and auditory evoked potential (AEP) responses triggered by the clicks were synchronously recorded during echolocation in an Atlantic bottlenose dolphin (Tursiops truncatus) trained to wear suction-cup EEG electrodes and to detect targets by echolocation. Three targets with target strengths of -34, -28, and -22 dB were used at distances of 2 to 6.5 m for each target. The AEP responses were sorted according to the corresponding emitted click source levels in 5-dB bins and averaged within each bin to extract biosonar click-related AEPs from noise. The AEP amplitudes were measured peak-to-peak and plotted as a function of click source levels for each target type, distance, and target-present or target-absent condition. Hearing sensation levels of the biosonar clicks were evaluated by comparing the functions of the biosonar click-related AEP amplitude-versus-click source level to a function of external (in free field) click-related AEP amplitude-versus-click sound pressure level. The results indicated that the dolphin's hearing sensation levels to her own biosonar clicks were equal to that of external clicks with sound pressure levels 16 to 36 dB lower than the biosonar click source levels, varying with target type, distance, and condition. These data may be assumed to indicate that the bottlenose dolphin possesses effective protection mechanisms to isolate the self-produced intense biosonar beam from the animal's ears during echolocation. PMID:22238654

  20. Hearing Sensation Levels of Emitted Biosonar Clicks in an Echolocating Atlantic Bottlenose Dolphin

    PubMed Central

    Li, Songhai; Nachtigall, Paul E.; Breese, Marlee; Supin, Alexander Ya.

    2012-01-01

    Emitted biosonar clicks and auditory evoked potential (AEP) responses triggered by the clicks were synchronously recorded during echolocation in an Atlantic bottlenose dolphin (Tursiops truncatus) trained to wear suction-cup EEG electrodes and to detect targets by echolocation. Three targets with target strengths of −34, −28, and −22 dB were used at distances of 2 to 6.5 m for each target. The AEP responses were sorted according to the corresponding emitted click source levels in 5-dB bins and averaged within each bin to extract biosonar click-related AEPs from noise. The AEP amplitudes were measured peak-to-peak and plotted as a function of click source levels for each target type, distance, and target-present or target-absent condition. Hearing sensation levels of the biosonar clicks were evaluated by comparing the functions of the biosonar click-related AEP amplitude-versus-click source level to a function of external (in free field) click-related AEP amplitude-versus-click sound pressure level. The results indicated that the dolphin's hearing sensation levels to her own biosonar clicks were equal to that of external clicks with sound pressure levels 16 to 36 dB lower than the biosonar click source levels, varying with target type, distance, and condition. These data may be assumed to indicate that the bottlenose dolphin possesses effective protection mechanisms to isolate the self-produced intense biosonar beam from the animal's ears during echolocation. PMID:22238654

  1. 'Click' preparation of CuPt nanorod-anchored graphene oxide as a catalyst in water.

    PubMed

    Yang, Hyunseung; Kwon, Yongwoo; Kwon, Taegyun; Lee, Hyunjoo; Kim, Bumjoon J

    2012-10-22

    In this paper, a simple and powerful method of producing nanoparticle-anchored graphene oxide (GO) composites using a 'click' reaction is demonstrated. This method affords a facile means of anchoring of nanoparticles with various shapes and sizes on the GO. CuPt nanorods with controlled size, aspect ratio (from 1 to 11), and uniformity are synthesized. Transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy measurements are made to monitor the formation and characterize the properties of the CuPt nanorod-grafted GO composites. Their catalytic properties in the water phase are investigated using an o-phenylenediamine oxidation reaction. The results of this study clearly demonstrate that nonpolar CuPt nanorods immobilized on GO can function as a catalyst in an aqueous solution and that GO can be used as a catalytic nanorod support. PMID:22821640

  2. Polyisobutylene chain end transformations: Block copolymer synthesis and click chemistry functionalizations

    NASA Astrophysics Data System (ADS)

    Magenau, Andrew Jackson David

    The primary objectives of this research were twofold: (1) development of synthetic procedures for combining quasiliving carbocationic polymerization (QLCCP) of isobutylene (IB) and reversible addition fragmentation chain transfer (RAFT) polymerization for block copolymer synthesis; (2) utilization of efficient, robust, and modular chemistries for facile functionalization of polyisobutylene (PIB). In the first study block copolymers consisting of PIB, and either PMMA or PS block segments, were synthesized by a site transformation approach combining living cationic and reversible addition-fragmentation chain transfer (RAFT) polymerizations. The initial PIB block was synthesized via quasiliving cationic polymerization using the TMPCl/TiCl4 initiation system and was subsequently converted into a hydroxylterminated PIB. Site transformation of the hydroxyl-terminated PIB into a macro chain transfer agent (PIB-CTA) was accomplished by N,N'-dicyclohexylcarbodiimide/dimethylaminopyridine-catalyzed esterification with 4-cyano-4-(dodecylsulfanylthiocarbonylsulfanyl)pentanoic acid. In the second study another site transformation approach was developed to synthesize a novel block copolymer, composed of PIB and PNIPAM segments. The PIB block was prepared via quasiliving cationic polymerization and end functionalized by in-situ quenching to yield telechelic halogen-terminated PIB. Azido functionality was obtained by displacement of the terminal halogen through nucleophilic substitution, which was confirmed by both 1H and 13C NMR. Coupling of an alkyne-functional chain transfer agent (CTA) to azido PIB was successfully accomplished through a copper catalyzed click reaction. Structure of the resulting PIB-based macro-CTA was verified with 1H NMR, FTIR, and GPC; whereas coupling reaction kinetics were monitored by real time variable temperature (VT) 1H NMR. In a third study, a click chemistry functionalization procedure was developed based upon the azide-alkyne 1,3-dipolar

  3. Synthesis of Zwitterionic Polymer Particles via Combined Distillation Precipitation Polymerization and Click Chemistry for Highly Efficient Enrichment of Glycopeptide.

    PubMed

    Liu, Jianxi; Yang, Kaiguang; Shao, Wenya; Li, Senwu; Wu, Qi; Zhang, Shen; Qu, Yanyan; Zhang, Lihua; Zhang, Yukui

    2016-08-31

    Because of the low abundance of glycopeptide in natural biological samples, methods for efficient and selective enrichment of glycopeptides play a significant role in mass spectrometry (MS)-based glycoproteomics. In this study, a novel kind of zwitterionic hydrophilic interaction chromatography polymer particles, namely, poly(N,N-methylenebisacrylamide-co-methacrylic acid)@l-Cys (poly(MBAAm-co-MAA)@l-Cys), for the enrichment of glycopeptides was synthesized by a facile and efficient approach that combined distillation precipitation polymerization (DPP) and "thiol-ene" click reaction. In the DPP approach, residual vinyl groups explored outside the core with high density, then the functional ligand cysteine was immobilized onto the surface of core particles by highly efficient thiol-ene click reaction. Taking advantage of the unique structure of poly(MBAAm-co-MAA)@l-Cys, the resulting particles possess remarkable enrichment selectivity for glycopeptides from the tryptic digested human immunoglobulin G. The polymer particles were successfully employed for the analysis of human plasma, and 208 unique glycopeptides corresponding to 121 glycoproteins were reliably identified in triple independent nano-LC-MS/MS runs. The selectivity toward glycopeptides of these particles poly(MBAAm-co-MAA)@l-Cys is ∼2 times than that of the commercial beads. These results demonstrated that these particles had great potential for large-scale glycoproteomics research. Moreover, the strategy with the combination of DPP and thiol-ene click chemistry might be a facile method to produce functional polymer particles for bioenrichment application. PMID:27498760

  4. Tandem diazonium salt electroreduction and click chemistry as a novel, efficient route for grafting macromolecules to gold surface

    NASA Astrophysics Data System (ADS)

    Mahouche, Samia; Mekni, Nejib; Abbassi, Leila; Lang, Philippe; Perruchot, Christian; Jouini, Mohamed; Mammeri, Fayna; Turmine, Mireille; Romdhane, Hatem Ben; Chehimi, Mohamed M.

    2009-11-01

    Bis-alkynylated oligoethyleneglycol (OEG) and a monopropargyl-functionalized perfluorinated ethylene glycol (FEG) were clicked to azide-functionalized gold surface (Au-N 3) at room temperature via the well known 1,3 cycloaddition click chemical reaction. The Au-N 3 substrate was obtained by nucleophilic attack of NaN 3 on gold substrates modified by the electrochemical reduction of the BF4-, +N 2-C 6H 4-CH 2Br diazonium salt. This electrochemical process yields aryl layer-modified gold of the type Au-C 6H 4-CH 2Br (hereafter Au-Br). The untreated and modified gold plates were examined by XPS, PMIRRAS and contact angle measurements. XPS brought evidence for electrografting aryl layers by the detection of Br3d; azide functionalization by the increase of the N/Br atomic ratio; and click reaction of OEG with Au-N 3 by the increase of O/N ratio. In addition, the perfluorinated plate (Au-FEG) exhibited F1s and characteristic C1s peaks from -(CF 2) 7- chain and terminal CF 3. Infra red spectroscopy (PMIRRAS) evidenced (i) grafting N 3 to Au-Br; (ii) characteristic stretching bands, from ethylene glycol units, C-O-C (1100-1300 cm -1); CF 2 (1000-1100 cm -1) and CF 3 (1100-1350 cm -1) from FEG grafts; and (iii) suppression of alkynyl bands from OEG and FEG after surface click chemistry. More importantly, PMIRRAS results support an important bridging of the bispropargyl oligoethylene glycol at the gold surface. Water drop contact angles were found to be 48.7° and 83.0° for Au-OEG and Au-FEG, respectively, therefore highlighting the control over the hydrophilic/hydrophobic character of the clicked substrate. This work shows that clicking macromolecules to grafted, diazonium salt-derived aryl layers is a novel, simple and valuable approach for designing robust, functional surface organic coatings.

  5. The use of azide-alkyne click chemistry in recent syntheses and applications of polytriazole-based nanostructured polymers

    NASA Astrophysics Data System (ADS)

    Shi, Yi; Cao, Xiaosong; Gao, Haifeng

    2016-02-01

    The rapid development of efficient organic click coupling reactions has significantly facilitated the construction of synthetic polymers with sophisticated branched nanostructures. This Feature Article summarizes the recent progress in the application of efficient copper-catalyzed and copper-free azide-alkyne cycloaddition (CuAAC and CuFAAC) reactions in the syntheses of dendrimers, hyperbranched polymers, star polymers, graft polymers, molecular brushes, and cyclic graft polymers. Literature reports on the interesting properties and functions of these polytriazole-based nanostructured polymers are also discussed to illustrate their potential applications as self-healing polymers, adhesives, polymer catalysts, opto-electronic polymer materials and polymer carriers for drug and imaging molecules.

  6. A study on the AMACR catalysed elimination reaction and its application to inhibitor testing† †Electronic supplementary information (ESI) available: 1H NMR spectra of synthesised compounds; details of X-ray crystal structure determination of compound 35; original data for Table 1; plots of fluorescence resulting from reaction of sensors 33 and 34 with fluoride solutions. CCDC 1408401. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ob01541c Click here for additional data file. Click here for additional data file.

    PubMed Central

    Yevglevskis, Maksims; Lee, Guat L.; Sun, Jenny; Zhou, Shiyi; Sun, Xiaolong; Kociok-Köhn, Gabriele; James, Tony D.; Woodman, Timothy J.

    2016-01-01

    α-Methylacyl-CoA racemase (AMACR; P504S) catalyses a key step in the degradation of branched-chain fatty acids and is important for the pharmacological activation of Ibuprofen and related drugs. Levels of AMACR are increased in prostate and other cancers, and it is a drug target. Development of AMACR as a drug target is hampered by lack of a convenient assay. AMACR irreversibly catalyses the elimination of HF from 3-fluoro-2-methylacyl-CoA substrates, and this reaction was investigated for use as an assay. Several known inhibitors and alternative substrates reduced conversion of 3-fluoro-2-methyldecanoyl-CoA by AMACR, as determined by 1H NMR. The greatest reduction of activity was observed with known potent inhibitors. A series of novel acyl-CoA esters with aromatic side chains were synthesised for testing as chromophoric substrates. These acyl-CoA esters were converted to unsaturated products by AMACR, but their use was limited by non-enzymatic elimination. Fluoride sensors were also investigated as a method of quantifying released fluoride and thus AMACR activity. These sensors generally suffered from high background signal and lacked reproducibility under the assay conditions. In summary, the elimination reaction can be used to characterise inhibitors, but it was not possible to develop a convenient colorimetric or fluorescent assay using 3-fluoro-2-methylacyl-CoA substrates. PMID:26537174

  7. Throat clicking as the initial symptom of Parkinson's disease.

    PubMed

    Iyer, Sanjay S; Morgan, John C; Glover, Andrea L; Sethi, Kapil D

    2005-10-01

    The presenting manifestations of Parkinson's disease (PD) are variable, but a majority of patients note tremor as the initial symptom. Others complain of slowing of movements, loss of dexterity, fatigue, or changes in handwriting as initial symptoms. We describe a patient who developed an unusual clicking sound emanating from his throat as the initial manifestation of PD. PMID:16001408

  8. Click, Clack, Move: Facilitation of the Arts as Transformative Pedagogy

    ERIC Educational Resources Information Center

    Vettraino, Elinor; Linds, Warren; Goulet, Linda

    2013-01-01

    This article explores the arts' potential to transform the relationships between students and teachers, so that education becomes an "as if" world, where education is an act of social justice. Interweaving themes from the children's book "Click Clack Moo, Cows that Type" with theories of transformative pedagogy and their own…

  9. Click chemistry promoted by graphene supported copper nanomaterials.

    PubMed

    Shaygan Nia, Ali; Rana, Sravendra; Döhler, Diana; Noirfalise, Xavier; Belfiore, Alice; Binder, Wolfgang H

    2014-12-18

    A facile and robust approach is provided for the synthesis of highly dispersed copper nanoparticles immobilized onto graphene nanosheets, useful as a recyclable and reusable heterogeneous catalyst with excellent catalytic activity to achieve Cu(I)-catalyzed [3+2] cycloaddition 'click' chemistry. PMID:25350638

  10. DNA Barcoding of Japanese Click Beetles (Coleoptera, Elateridae)

    PubMed Central

    Oba, Yuichi; Ôhira, Hitoo; Murase, Yukio; Moriyama, Akihiko; Kumazawa, Yoshinori

    2015-01-01

    Click beetles (Coleoptera: Elateridae) represent one of the largest groups of beetle insects. Some click beetles in larval form, known as wireworms, are destructive agricultural pests. Morphological identification of click beetles is generally difficult and requires taxonomic expertise. This study reports on the DNA barcoding of Japanese click beetles to enable their rapid and accurate identification. We collected and assembled 762 cytochrome oxidase subunit I barcode sequences from 275 species, which cover approximately 75% of the common species found on the Japanese main island, Honshu. This barcode library also contains 20 out of the 21 potential pest species recorded in Japan. Our analysis shows that most morphologically identified species form distinct phylogenetic clusters separated from each other by large molecular distances. This supports the general usefulness of the DNA barcoding approach for quick and reliable identification of Japanese elaterid species for environmental impact assessment, agricultural pest control, and biodiversity analysis. On the other hand, the taxonomic boundary in dozens of species did not agree with the boundary of barcode index numbers (a criterion for sequence-based species delimitation). These findings urge taxonomic reinvestigation of these mismatched taxa. PMID:25636000

  11. Making It CLICK: Planning, Creating, and Using CPCC Libraries' Logo

    ERIC Educational Resources Information Center

    Moore, Gena

    2005-01-01

    The Central Piedmont Community College Libraries have been successful in creating positive expectations from the CPCC community by connecting an official library logo with quality library service. The creation of the CPCC Libraries' logo CLICK was a process that spanned several months. A history of this process details the meetings and design work…

  12. Decoration of silk fibroin by click chemistry for biomedical application.

    PubMed

    Zhao, Hongshi; Heusler, Eva; Jones, Gabriel; Li, Linhao; Werner, Vera; Germershaus, Oliver; Ritzer, Jennifer; Luehmann, Tessa; Meinel, Lorenz

    2014-06-01

    Silkfibroin (SF) has an excellent biocompatibility and its remarkable structure translates into exciting mechanical properties rendering this biomaterial particularly fascinating for biomedical application. To further boost the material's biological/preclinical impact, SF is decorated with biologics, typically by carbodiimide/N-hydroxysuccinimide coupling (EDC/NHS). For biomedical application, this chemistry challenges the product risk profile due to the formation of covalent aggregates, particularly when decoration is with biologics occurring naturally in humans as these aggregates may prime for autoimmunity. Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC; click chemistry) provides the necessary specificity to avoid such intermolecular, covalent aggregates. We present a blueprint outlining the necessary chemistry rendering SF compatible with CuAAC and with a particular focus on structural consequences. For that, the number of SF carboxyl groups (carboxyl-SF; required for EDC/NHS chemistry) or azido groups (azido-SF; required for click chemistry) was tailored by means of diazonium coupling of the SF tyrosine residues. Structural impact on SF and decorated SF was characterized by Fourier transform infrared spectroscopy (FTIR). The click chemistry yielded a better controlled product as compared to the EDC/NHS chemistry with no formation of inter- and intramolecular crosslinks as demonstrated for SF decorated with fluorescent model compounds or a biologic, fibroblast growth factor 2 (FGF2), respectively. In conclusion, SF can readily be translated into a scaffold compatible with click chemistry yielding decorated products with a better risk profile for biomedical application. PMID:24576682

  13. Expanding the chemical scope of RNA:methyltransferases to site-specific alkynylation of RNA for click labeling

    PubMed Central

    Motorin, Yuri; Burhenne, Jürgen; Teimer, Roman; Koynov, Kaloian; Willnow, Sophie; Weinhold, Elmar; Helm, Mark

    2011-01-01

    This work identifies the combination of enzymatic transfer and click labeling as an efficient method for the site-specific tagging of RNA molecules for biophysical studies. A double-activated analog of the ubiquitous co-substrate S-adenosyl-l-methionine was employed to enzymatically transfer a five carbon chain containing a terminal alkynyl moiety onto RNA. The tRNA:methyltransferase Trm1 transferred the extended alkynyl moiety to its natural target, the N2 of guanosine 26 in tRNAPhe. LC/MS and LC/MS/MS techniques were used to detect and characterize the modified nucleoside as well as its cycloaddition product with a fluorescent azide. The latter resulted from a labeling reaction via Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition click chemistry, producing site-specifically labeled RNA whose suitability for single molecule fluorescence experiments was verified in fluorescence correlation spectroscopy experiments. PMID:21037259

  14. ClickDiary: Online Tracking of Health Behaviors and Mood

    PubMed Central

    Chan, Ta-Chien; Yen, Tso-Jung; Fu, Yang-Chih

    2015-01-01

    Background Traditional studies of health behaviors are typically conducted using one-shot, cross-sectional surveys. Thus, participants’ recall bias may undermine the reliability and validity of the data. To capture mood changes and health behaviors in everyday life, we designed an online survey platform, ClickDiary, which helped collect more complete information for comprehensive data analyses. Objective We aim to understand whether daily mood changes are related to one’s personal characteristics, demographic factors, and daily health behaviors. Methods The ClickDiary program uses a Web-based platform to collect data on participants’ health behaviors and their social-contact networks. The name ClickDiary comes from the platform’s interface, which is designed to allow the users to respond to most of the survey questions simply by clicking on the options provided. Participants were recruited from the general population and came from various backgrounds. To keep the participants motivated and interested, the ClickDiary program included a random drawing for rewards. We used descriptive statistics and the multilevel proportional-odds mixed model for our analysis. Results We selected 130 participants who had completed at least 30 days of ClickDiary entries from May 1 to October 31, 2014 as our sample for the study. According to the results of the multilevel proportional-odds mixed model, a person tended to be in a better mood on a given day if he or she ate more fruits and vegetables, took in more sugary drinks, ate more fried foods, showed no cold symptoms, slept better, exercised longer, and traveled farther away from home. In addition, participants were generally in a better mood during the weekend than on weekdays. Conclusions Sleeping well, eating more fruits and vegetables, and exercising longer each day all appear to put one in a better mood. With the online ClickDiary survey, which reduces the recall biases that are common in traditional one-shot surveys

  15. Planning for Post-Secondary Is Just a Click Away! Learning Clicks Final Report. 2007/2008 School Year

    ERIC Educational Resources Information Center

    Alberta Advanced Education and Technology, 2008

    2008-01-01

    Learning Clicks is a program under the provincial department of Advanced Education and Technology's "Raising Awareness about Planning for Post-Secondary" (RAPPS) umbrella; an initiative that supports Strategy 2.4 in Alberta Advanced Education and Technology's 2007-10 Business Plan to enhance parents' and learners' knowledge and awareness of…

  16. Click chemistry approach to conventional vegetable tanning process: accelerated method with improved organoleptic properties.

    PubMed

    Krishnamoorthy, Ganesan; Ramamurthy, Govindaswamy; Sadulla, Sayeed; Sastry, Thotapalli Parvathaleswara; Mandal, Asit Baran

    2014-09-01

    Click chemistry approaches are tailored to generate molecular building blocks quickly and reliably by joining small units together selectively and covalently, stably and irreversibly. The vegetable tannins such as hydrolyzable and condensed tannins are capable to produce rather stable radicals or inhibit the progress of radicals and are prone to oxidations such as photo and auto-oxidation, and their anti-oxidant nature is well known. A lot remains to be done to understand the extent of the variation of leather stability, color variation (lightening and darkening reaction of leather), and poor resistance to water uptake for prolonged periods. In the present study, we have reported click chemistry approaches to accelerated vegetable tanning processes based on periodates catalyzed formation of oxidized hydrolysable and condensed tannins for high exhaustion with improved properties. The distribution of oxidized vegetable tannin, the thermal stability such as shrinkage temperature (T s) and denaturation temperature (T d), resistance to collagenolytic activities, and organoleptic properties of tanned leather as well as the evaluations of eco-friendly characteristics were investigated. Scanning electron microscopic analysis indicates the cross section of tightness of the leather. Differential scanning calorimetric analysis shows that the T d of leather is more than that of vegetable tanned or equal to aldehyde tanned one. The leathers exhibited fullness, softness, good color, and general appearance when compared to non-oxidized vegetable tannin. The developed process benefits from significant reduction in total solids and better biodegradability in the effluent, compared to non-oxidized vegetable tannins. PMID:24888617

  17. (99m)Tc-bioorthogonal click chemistry reagent for in vivo pretargeted imaging.

    PubMed

    García, María Fernanda; Zhang, Xiuli; Shah, Manankumar; Newton-Northup, Jessica; Cabral, Pablo; Cerecetto, Hugo; Quinn, Thomas

    2016-03-15

    Metal-free click chemistry has become an important tool for pretargeted approaches in the molecular imaging field. The application of bioorthogonal click chemistry between a pretargeted trans-cyclooctene (TCO) derivatized monoclonal antibody (mAb) and a (99m)Tc-modified 1,2,4,5-tetrazine for tumor imaging was examined in vitro and in vivo. The HYNIC tetrazine compound was synthesized and structurally characterized, confirming its identity. Radiolabeling studies demonstrated that the HYNIC tetrazine was labeled with (99m)Tc at an efficiency of >95% and was radiochemically stable. (99m)Tc-HYNIC tetrazine reacted with the TCO-CC49 mAb in vitro demonstrating its selective reactivity. In vivo biodistribution studies revealed non-specific liver and GI uptake due to the hydrophobic property of the compound, however pretargeted SPECT imaging studies demonstrated tumor visualization confirming the success of the cycloaddition reaction in vivo. These results demonstrated the potential of (99m)Tc-HYNIC-tetrazine for tumor imaging with pretargeted mAbs. PMID:26875936

  18. A clickable UTP analog for the posttranscriptional chemical labeling and imaging of RNA.

    PubMed

    Sawant, Anupam A; Mukherjee, Progya P; Jangid, Rahul K; Galande, Sanjeev; Srivatsan, Seergazhi G

    2016-06-28

    The development of robust tools and practical RNA labeling strategies that would facilitate the biophysical analysis of RNA in both cell-free and cellular systems will have profound implications in the discovery of new RNA diagnostic tools and therapeutic strategies. In this context, we describe the development of a new alkyne-modified UTP analog, 5-(1,7-octadinyl)uridine triphosphate (ODUTP), which serves as an efficient substrate for the introduction of a clickable alkyne label into RNA transcripts by bacteriophage T7 RNA polymerase and mammalian cellular RNA polymerases. The ODU-labeled RNA is effectively used by reverse transcriptase to produce cDNA, a property which could be utilized in expanding the chemical space of a RNA library in the aptamer selection scheme. Further, the alkyne label on RNA provides a convenient tool for the posttranscriptional chemical functionalization with a variety of biophysical tags (fluorescent, affinity, amino acid and sugar) by using alkyne-azide cycloaddition reaction. Importantly, the ability of endogenous RNA polymerases to specifically incorporate ODUTP into cellular RNA transcripts enabled the visualization of newly transcribing RNA in cells by microscopy using click reactions. In addition to a clickable alkyne group, ODU contains a Raman scattering label (internal disubstituted alkyne), which exhibits characteristic Raman shifts that fall in the Raman-silent region of cells. Our results indicate that an ODU label could potentially facilitate two-channel visualization of RNA in cells by using click chemistry and Raman spectroscopy. Taken together, ODU represents a multipurpose ribonucleoside tool, which is expected to provide new avenues to study RNA in cell-free and cellular systems. PMID:27173127

  19. A novel protocol for the one-pot borylation/Suzuki reaction provides easy access to hinge-binding groups for kinase inhibitors† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ob01915j Click here for additional data file.

    PubMed Central

    Hooper, A.; Zambon, A.

    2016-01-01

    The one-pot borylation/Suzuki reaction is a very efficient means of accessing cross-coupling products of two aryl-halide partners that generally requires the use of specific catalysts or ligands and/or relatively long reaction times. This new microwave-assisted method provides a quick one-pot borylation/Suzuki reaction protocol that we applied to the synthesis of various bi- or poly-aryl scaffolds, including a variety of aryl and heteroaryl ring systems and the core frameworks of kinase inhibitors vemurafenib and GDC-0879. PMID:26620576

  20. Carbohydrate CuAAC click chemistry for therapy and diagnosis.

    PubMed

    He, Xiao-Peng; Zeng, Ya-Li; Zang, Yi; Li, Jia; Field, Robert A; Chen, Guo-Rong

    2016-06-24

    Carbohydrates are important as signaling molecules and for cellular recognition events, therefore offering scope for the development of carbohydrate-mimetic diagnostics and drug candidates. As a consequence, the construction of carbohydrate-based bioactive compounds and sensors has become an active research area. While the advent of click chemistry has greatly accelerated the progress of medicinal chemistry and chemical biology, recent literature has seen an extensive use of such approaches to construct functionally diverse carbohydrate derivatives. Here we summarize some of the progress, covering the period 2010 to mid-2015, in Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition CuAAC "click chemistry" of carbohydrate derivatives, in the context of potential therapeutic and diagnostic tool development. PMID:27085906

  1. Flexible Piezoelectric Energy Harvesting from Mouse Click Motions.

    PubMed

    Cha, Youngsu; Hong, Jin; Lee, Jaemin; Park, Jung-Min; Kim, Keehoon

    2016-01-01

    In this paper, we study energy harvesting from the mouse click motions of a robot finger and a human index finger using a piezoelectric material. The feasibility of energy harvesting from mouse click motions is experimentally and theoretically assessed. The fingers wear a glove with a pocket for including the piezoelectric material. We model the energy harvesting system through the inverse kinematic framework of parallel joints in a finger and the electromechanical coupling equations of the piezoelectric material. The model is validated through energy harvesting experiments in the robot and human fingers with the systematically varying load resistance. We find that energy harvesting is maximized at the matched load resistance to the impedance of the piezoelectric material, and the harvested energy level is tens of nJ. PMID:27399705

  2. Flexible Piezoelectric Energy Harvesting from Mouse Click Motions

    PubMed Central

    Cha, Youngsu; Hong, Jin; Lee, Jaemin; Park, Jung-Min; Kim, Keehoon

    2016-01-01

    In this paper, we study energy harvesting from the mouse click motions of a robot finger and a human index finger using a piezoelectric material. The feasibility of energy harvesting from mouse click motions is experimentally and theoretically assessed. The fingers wear a glove with a pocket for including the piezoelectric material. We model the energy harvesting system through the inverse kinematic framework of parallel joints in a finger and the electromechanical coupling equations of the piezoelectric material. The model is validated through energy harvesting experiments in the robot and human fingers with the systematically varying load resistance. We find that energy harvesting is maximized at the matched load resistance to the impedance of the piezoelectric material, and the harvested energy level is tens of nJ. PMID:27399705

  3. Sperm whale clicks: directionality and source level revisited.

    PubMed

    Møhl, B; Wahlberg, M; Madsen, P T; Miller, L A; Surlykke, A

    2000-01-01

    In sperm whales (Physeter catodon L. 1758) the nose is vastly hypertrophied, accounting for about one-third of the length or weight of an adult male. Norris and Harvey [in Animal Orientation and Navigation, NASA SP-262 (1972), pp. 397-417] ascribed a sound-generating function to this organ complex. A sound generator weighing upward of 10 tons and with a cross-section of 1 m is expected to generate high-intensity, directional sounds. This prediction from the Norris and Harvey theory is not supported by published data for sperm whale clicks (source levels of 180 dB re 1 microPa and little, if any, directionality). Either the theory is not borne out or the data is not representative for the capabilities of the sound-generating mechanism. To increase the amount of relevant data, a five-hydrophone array, suspended from three platforms separated by 1 km and linked by radio, was deployed at the slope of the continental shelf off Andenes, Norway, in the summers of 1997 and 1998. With this system, source levels up to 223 dB re 1 microPa peRMS were recorded. Also, source level differences of 35 dB for the same click at different directions were seen, which are interpreted as evidence for high directionality. This implicates sonar as a possible function of the clicks. Thus, previously published properties of sperm whale clicks underestimate the capabilities of the sound generator and therefore cannot falsify the Norris and Harvey theory. PMID:10641672

  4. Au-iClick mirrors the mechanism of copper catalyzed azide–alkyne cycloaddition (CuAAC)

    SciTech Connect

    Powers, Andrew R.; Ghiviriga, Ion; Abboud, Khalil A.; Veige, Adam S.

    2015-07-20

    This report outlines the investigation of the iClick mechanism between gold(I)-azides and gold(I)-acetylides to yield digold triazolates. Isolation of digold triazolate complexes offer compelling support for the role of two copper(I) ions in CuAAC. In addition, a kinetic investigation reveals the reaction is first order in both Au(I)-N3 and Au(I)-C≡C-R equivalent to C-R, thus second order overall. A Hammett plot with a ρ = 1.02(5) signifies electron-withdrawing groups accelerate the cycloaddition by facilitating the coordination of the second gold ion in a π-complex. Rate inhibition by the addition of free triphenylphosphine to the reaction indicates that ligand dissociation is a prerequisite for the reaction. The mechanistic conclusions mirror those proposed for the CuAAC reaction.

  5. Au-iClick mirrors the mechanism of copper catalyzed azide–alkyne cycloaddition (CuAAC)

    DOE PAGESBeta

    Powers, Andrew R.; Ghiviriga, Ion; Abboud, Khalil A.; Veige, Adam S.

    2015-07-20

    This report outlines the investigation of the iClick mechanism between gold(I)-azides and gold(I)-acetylides to yield digold triazolates. Isolation of digold triazolate complexes offer compelling support for the role of two copper(I) ions in CuAAC. In addition, a kinetic investigation reveals the reaction is first order in both Au(I)-N3 and Au(I)-C≡C-R equivalent to C-R, thus second order overall. A Hammett plot with a ρ = 1.02(5) signifies electron-withdrawing groups accelerate the cycloaddition by facilitating the coordination of the second gold ion in a π-complex. Rate inhibition by the addition of free triphenylphosphine to the reaction indicates that ligand dissociation is amore » prerequisite for the reaction. The mechanistic conclusions mirror those proposed for the CuAAC reaction.« less

  6. Conjugating folate on superparamagnetic Fe3O4@Au nanoparticles using click chemistry

    NASA Astrophysics Data System (ADS)

    Shen, Xiaofang; Ge, Zhaoqiang; Pang, Yuehong

    2015-02-01

    Gold-coated magnetic core@shell nanoparticles, which exhibit magneto-optical properties, not only enhance the chemical stability of core and biocompatibility of surface, but also provide a combination of multimodal imaging and therapeutics. The conjugation of these tiny nanoparticles with specific biomolecules allows researchers to target the desired location. In this paper, superparamagnetic Fe3O4@Au nanoparticles were synthesized and functionalized with the azide group on the surface by formation of self-assembled monolayers. Folate (FA) molecules, non-immunogenic target ligands for cancer cells, are conjugated with alkyne and then immobilized on the azide-terminated Fe3O4@Au nanoparticles through copper(I)-catalyzed azide-alkyne cycloaddition (click reaction). Myelogenous leukemia K562 cells were used as a folate receptor (FR) model, which can be targeted and extracted by magnetic field after interaction with the Fe3O4@Au-FA nanoparticles.

  7. Synthesis and application of a new cleavable linker for "click"-based affinity chromatography.

    PubMed

    Landi, Felicetta; Johansson, Conny M; Campopiano, Dominic J; Hulme, Alison N

    2010-01-01

    A new chemically-cleavable linker has been synthesised for the affinity-independent elution of biomolecules by classical affinity chromatography. This azo-based linker is shown to couple efficiently with "click" derivatised ligands such as biotin propargyl amide through a copper(I)-catalysed Huisgen 1,3-dipolar cycloaddition reaction. Binding to Affi-Gel matrices displaying ligands coupled to the new linker is both efficient and selective. The captured material may be readily released from the resin upon treatment with sodium dithionite. These mild elution conditions have allowed for the efficient isolation of the affinity partner from complex protein mixtures such as those found in fetal bovine serum. PMID:20024132

  8. Solvent-Free Click-Mechanochemistry for the Preparation of Cancer Cell Targeting Graphene Oxide.

    PubMed

    Rubio, Noelia; Mei, Kuo-Ching; Klippstein, Rebecca; Costa, Pedro M; Hodgins, Naomi; Wang, Julie Tzu-Wen; Festy, Frederic; Abbate, Vincenzo; Hider, Robert C; Chan, Ka Lung Andrew; Al-Jamal, Khuloud T

    2015-09-01

    Polyethylene glycol-functionalized nanographene oxide (PEGylated n-GO) was synthesized from alkyne-modified n-GO, using solvent-free click-mechanochemistry, i.e., copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The modified n-GO was subsequently conjugated to a mucin 1 receptor immunoglobulin G antibody (anti-MUC1 IgG) via thiol-ene coupling reaction. n-GO derivatives were characterized with Fourier-transformed infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), Bradford assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and atomic force microscopy (AFM). Cell targeting was confirmed in vitro in MDA-MB-231 cells, either expressing or lacking MUC1 receptors, using flow cytometry, confocal laser scanning microscopy (CLSM) and multiphoton (MP) fluorescence microscopy. Biocompatibility was assessed using the modified lactate dehydrongenase (mLDH) assay. PMID:26278410

  9. Solvent-Free Click-Mechanochemistry for the Preparation of Cancer Cell Targeting Graphene Oxide

    PubMed Central

    2015-01-01

    Polyethylene glycol-functionalized nanographene oxide (PEGylated n-GO) was synthesized from alkyne-modified n-GO, using solvent-free click-mechanochemistry, i.e., copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC). The modified n-GO was subsequently conjugated to a mucin 1 receptor immunoglobulin G antibody (anti-MUC1 IgG) via thiol–ene coupling reaction. n-GO derivatives were characterized with Fourier-transformed infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), Bradford assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and atomic force microscopy (AFM). Cell targeting was confirmed in vitro in MDA-MB-231 cells, either expressing or lacking MUC1 receptors, using flow cytometry, confocal laser scanning microscopy (CLSM) and multiphoton (MP) fluorescence microscopy. Biocompatibility was assessed using the modified lactate dehydrongenase (mLDH) assay. PMID:26278410

  10. Click chemistry modification of natural keratin fibers for sustained shrink-resist performance.

    PubMed

    Yu, Dan; Cai, Jackie Y; Church, Jeffrey S; Wang, Lijing

    2015-01-01

    This paper introduces a novel chemical treatment for achieving sustained shrink-resist performance on natural keratin fibers. The new treatment involves the controlled reduction of keratin in the cuticle region of the fiber, and the application of a water soluble diacrylate, namely glycerol 1,3-diglycerolate diacrylate (GDA), on the reduced keratin substrate. The acrylate groups of the GDA react with cysteine residues in the reduced keratin through thiol-ene click reactions at room temperature, leading to GDA grafting and the formation of GDA crosslinks in the keratin structure. The modified substrates were characterized by infrared spectroscopy and scanning electron microscopy, and assessed for its shrink-resistance and wet burst strength. This chemical modification has shown to alter the fiber surface morphology and hydrophilicity, resulting in substantially improved shrink-resistance with good fiber strength retention. Possible shrink-resistance mechanisms were also discussed. PMID:25840149

  11. The photochemical thiol–ene reaction as a versatile method for the synthesis of glutathione S-conjugates targeting the bacterial potassium efflux system Kef† †Electronic supplementary information (ESI) available: Further experimental details and NMR spectra. See DOI: 10.1039/c5qo00436e Click here for additional data file.

    PubMed Central

    Rasmussen, Tim; Miller, Samantha; Booth, Ian R.

    2016-01-01

    The thiol–ene coupling reaction is emerging as an important conjugation reaction that is suitable for use in a biological setting. Here, we explore the utility of this reaction for the synthesis of glutathione-S-conjugates (GSX) and present a general, operationally simple, protocol with a wide substrate scope. The GSX afforded are an important class of compounds and provide invaluable molecular tools to study glutathione-binding proteins. In this study we apply the diverse library of GSX synthesised to further our understanding of the structural requirements for binding to the glutathione-binding protein, Kef, a bacterial K+ efflux system, found in many bacterial pathogens. This system is vital to the survival of bacteria upon exposure to electrophiles, and plays an essential role in the maintenance of intracellular pH and K+ homeostasis. Consequently, Kef is an appealing target for the development of novel antibacterial drugs. PMID:27110363

  12. Conjugating folate on superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles using click chemistry

    SciTech Connect

    Shen, Xiaofang Ge, Zhaoqiang; Pang, Yuehong

    2015-02-15

    Gold-coated magnetic core@shell nanoparticles, which exhibit magneto-optical properties, not only enhance the chemical stability of core and biocompatibility of surface, but also provide a combination of multimodal imaging and therapeutics. The conjugation of these tiny nanoparticles with specific biomolecules allows researchers to target the desired location. In this paper, superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles were synthesized and functionalized with the azide group on the surface by formation of self-assembled monolayers. Folate (FA) molecules, non-immunogenic target ligands for cancer cells, are conjugated with alkyne and then immobilized on the azide-terminated Fe{sub 3}O{sub 4}@Au nanoparticles through copper(I)-catalyzed azide-alkyne cycloaddition (click reaction). Myelogenous leukemia K562 cells were used as a folate receptor (FR) model, which can be targeted and extracted by magnetic field after interaction with the Fe{sub 3}O{sub 4}@Au–FA nanoparticles. - Graphical abstract: Self-assembled azide-terminated group on superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles followed by click reaction with alkyne-functionalized folate, allowing the nanoparticles target folate receptor of cancer cells. - Highlights: • Azidoundecanethiol was coated on the superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles by forming self-assembled monolayers. • Alkyne-terminated folate was synthesized from a reaction between the amine and the carboxylic acid. • Conjugation of Fe{sub 3}O{sub 4}@Au nanoparticles with folate was made by copper-catalyzed azide-alkyne cycloaddition click chemistry.

  13. Deuterated carbohydrate probes as ‘label-free’ substrates for probing nutrient uptake in mycobacteria by nuclear reaction analysis† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c4cc09588j Click here for additional data file.

    PubMed Central

    Lowery, R.; Gibson, M. I.; Thompson, R. L.

    2015-01-01

    Understanding and probing small molecule uptake in cells is challenging, requiring sterically large chemical labels, or radioactive isotopes. Here, the uptake of deuterated sugars by Mycobacterium smegmatis, a non-pathogenic model of Mycobacterium tuberculosis, has been investigated using ion-beam (nuclear reaction) analysis demonstrating a new technique for label-free nutrient acquisition measurement. PMID:25695462

  14. Click rates and silences of sperm whales at Kaikoura, New Zealand

    NASA Astrophysics Data System (ADS)

    Douglas, Lesley A.; Dawson, Stephen M.; Jaquet, Nathalie

    2005-07-01

    Analysis of the usual click rates of sperm whales (Physeter macrocephalus) at Kaikoura, New Zealand, confirms the potential for assessing abundance via ``click counting.'' Usual click rates over three dive cycles each of three photographically identified whales showed that 5 min averages of usual click rate did not differ significantly within dives, among dives of the same whale or among whales. Over the nine dives (n=13 728 clicks) mean usual click rate was 1.272 clicks s-1 (95% CI=0.151). On average, individual sperm whales at Kaikoura spent 60% of their time usual clicking in winter and in summer. There was no evidence that whale identity or stage of the dive recorded affects significantly the percentage of time spent usual clicking. Differences in vocal behavior among sperm whale populations worldwide indicate that estimates of abundance that are based on click rates need to based on data from the population of interest, rather than from another population or some global average.

  15. Azidopropylvinylsulfonamide as a New Bifunctional Click Reagent for Bioorthogonal Conjugations: Application for DNA-Protein Cross-Linking.

    PubMed

    Dadová, Jitka; Vrábel, Milan; Adámik, Matej; Brázdová, Marie; Pohl, Radek; Fojta, Miroslav; Hocek, Michal

    2015-11-01

    N-(3-Azidopropyl)vinylsulfonamide was developed as a new bifunctional bioconjugation reagent suitable for the cross-linking of biomolecules through copper(I)-catalyzed azide-alkyne cycloaddition and thiol Michael addition reactions under biorthogonal conditions. The reagent is easily clicked to an acetylene-containing DNA or protein and then reacts with cysteine-containing peptides or proteins to form covalent cross-links. Several examples of bioconjugations of ethynyl- or octadiynyl-modified DNA with peptides, p53 protein, or alkyne-modified human carbonic anhydrase with peptides are given. PMID:26377361

  16. Simple thiol-ene click chemistry modification of SBA-15 silica pores with carboxylic acids.

    PubMed

    Bordoni, Andrea V; Lombardo, M Verónica; Regazzoni, Alberto E; Soler-Illia, Galo J A A; Wolosiuk, Alejandro

    2015-07-15

    A straightforward approach for anchoring tailored carboxylic groups in mesoporous SiO2 colloidal materials is presented. The thiol-ene photochemical reaction between vinyltrimethoxysilane precursors and various thiocarboxylic acids which has, click chemistry features (i.e. high conversion yields, insensitivity to oxygen, mild reaction conditions), results in carboxylated silane precursors that can be readily used as surface modifiers. The carboxylic groups of acetic, undecanoic and succinic acid were immobilized on the silica mesopore walls of SBA-15 powders employing the synthesized silane precursors. Post-grafting has been confirmed through infrared spectrometry (FTIR), energy dispersive X-ray spectroscopy (EDS), elemental analysis (EA) and zeta potential measurements. Detailed field-emission gun scanning electron microscopy (FESEM) images and small angle X-ray scattering (SAXS) data revealed parallel mesopores and ordered mesostructures. It is shown that the immobilized COOH groups are chemically accessible for acid-base reactions as well as copper adsorption. Immobilization of easily synthesized tailored carboxylic modified alkoxide precursors within mesoporous systems provides a unique chemical nanoenvironment within these ordered frameworks. PMID:25845883

  17. Electrochemical impedance spectroscopy sensor for ascorbic acid based on copper(I) catalyzed click chemistry.

    PubMed

    Qiu, Suyan; Gao, Sen; Liu, Qida; Lin, Zhenyu; Qiu, Bin; Chen, Guonan

    2011-07-15

    Copper(I) species can be acquired from the reduction of copper(II) by ascorbic acid (AA) in situ, and which in turn quantitative catalyze the azides and alkynes cycloaddition reaction. In this study, propargyl-functionalized ferrocene (propargyl-functionalized Fc) has been modified on the electrode through reacting with azide terminal modified Au electrode via copper(I) catalyzed azides and alkynes cycloaddition (CuAAC) reaction. The electrochemical impedance spectroscopy (EIS) measurement has been applied to test the electron transfer resistance of the Au electrode before and after click reaction. The changes of the fractional surface coverage (θ) with different AA concentrations are characterized. It is found that the θ value has a linear response to the logarithm of AA concentration in the range of 5.0 pmol/L to 1.0 nmol/L with the detection limits of 2.6 pmol/L. The sensor shows a good stability and selectivity. And it has been successfully applied to the AA detection in the real samples (urine) with satisfactory results. PMID:21596552

  18. A multi-hypothesis tracker for clicking whales.

    PubMed

    Baggenstoss, Paul M

    2015-05-01

    This paper describes a tracker specially designed to track clicking beaked whales using widely spaced bottom-mounted hydrophones, although it can be adapted to different species and sensors. The input to the tracker is a sequence of static localization solutions obtained using time difference of arrival information at widely spaced hydrophones. To effectively handle input localizations with high ambiguity, the tracker is based on multi-hypothesis tracker concepts, so it considers all potential association hypotheses and keeps a large number of potential tracks in memory. The method is demonstrated on actual data and shown to successfully track multiple beaked whales at depth. PMID:25994688

  19. Middle ear myoclonus: a new technique for suppression of spontaneous clicking tinnitus.

    PubMed

    Chan, Chung; Palaniappan, Rudrapathy

    2010-01-01

    Middle ear myoclonus is one of the causes of clicking tinnitus and can be psychologically distressing. Current management of intractable clicking includes medication or tenotomy. Two cases with spontaneous intrusive irregular clicking are presented where relief and a sense of control were obtained using non-invasive self - administered zygomatic pressure. This technique may be useful in selected patients before resorting to medication or tenotomy. PMID:21609914

  20. Redox-Responsive Micelles with Cores Crosslinked via Click Chemistry.

    PubMed

    Zhang, Xiaojin; Dong, Hui; Fu, Shuangli; Zhong, Zhenlin; Zhuo, Renxi

    2016-06-01

    Redox-responsive micelles with cores crosslinked via click chemistry are developed to improve the stability of polymer micelles. Amphiphilic block copolymer mPEG-b-P(DTC-ADTC) with pendant azido groups on the hydrophobic chains is synthesized by the ring-opening polymerization of 2,2-bis(azidomethyl)trimethylene carbonate (ADTC) and 2,2-dimethyltrimethylene carbonate (DTC) with monomethoxy poly(ethylene glycol) (mPEG) as an initiator. mPEG-b-P(DTC-ADTC) self-assemble to form the micelles in aqueous solution and the cores of the micelles are crosslinked via click chemistry to afford redox-responsive core-crosslinked micelles. Core-crosslinking enhances the stability of the micelles in aqueous solution and improve the drug-loading property. The redox-responsive core-crosslinked micelles can be reduced by the addition of reducing agents such as dithiothreitol (DTT), and thus release the loaded drug quickly in the presence of DTT. PMID:27150437

  1. Binding-regulated click ligation for selective detection of proteins.

    PubMed

    Cao, Ya; Han, Peng; Wang, Zhuxin; Chen, Weiwei; Shu, Yongqian; Xiang, Yang

    2016-04-15

    Herein, a binding-regulated click ligation (BRCL) strategy for endowing selective detection of proteins is developed with the incorporation of small-molecule ligand and clickable DNA probes. The fundamental principle underlying the strategy is the regulating capability of specific protein-ligand binding against the ligation between clickable DNA probes, which could efficiently combine the detection of particular protein with enormous DNA-based sensing technologies. In this work, the feasibly of the BRCL strategy is first verified through agarose gel electrophoresis and electrochemical impedance spectroscopy measurements, and then confirmed by transferring it to a nanomaterial-assisted fluorescence assay. Significantly, the BRCL strategy-based assay is able to respond to target protein with desirable selectivity, attributing to the specific recognition between small-molecule ligand and its target. Further experiments validate the general applicability of the sensing method by tailoring the ligand toward different proteins (i.e., avidin and folate receptor), and demonstrate its usability in complex biological samples. To our knowledge, this work pioneers the practice of click chemistry in probing specific small-molecule ligand-protein binding, and therefore may pave a new way for selective detection of proteins. PMID:26599478

  2. Site-Specific Labeling of Protein Kinase CK2: Combining Surface Display and Click Chemistry for Drug Discovery Applications.

    PubMed

    Nienberg, Christian; Retterath, Anika; Becher, Kira-Sophie; Saenger, Thorsten; Mootz, Henning D; Jose, Joachim

    2016-01-01

    Human CK2 is a heterotetrameric constitutively active serine/threonine protein kinase and is an emerging target in current anti-cancer drug discovery. The kinase is composed of two catalytic CK2α subunits and two regulatory CK2β subunits. In order to establish an assay to identify protein-protein-interaction inhibitors (PPI) of the CK2α/CK2β interface, a bioorthogonal click reaction was used to modify the protein kinase α-subunit with a fluorophore. By expanding the genetic code, the unnatural amino acid para azidophenylalanine (pAzF) could be incorporated into CK2α. Performing the SPAAC click reaction (Strain-Promoted Azide-Alkyne Cycloaddition) by the use of a dibenzylcyclooctyne-fluorophore (DBCO-fluorophore) led to a specifically labeled human protein kinase CK2α. This site-specific labeling does not impair the phosphorylation activity of CK2, which was evaluated by capillary electrophoresis. Furthermore a dissociation constant (KD) of 631 ± 86.2 nM was determined for the substrate αS1-casein towards CK2α. This labeling strategy was also applied to CK2β subunit on Escherichia coli, indicating the site-specific modifications of proteins on the bacterial cell surface when displayed by Autodisplay. PMID:27355959

  3. Facile preparation of organic-silica hybrid monolith for capillary hydrophilic liquid chromatography based on "thiol-ene" click chemistry.

    PubMed

    Chen, Ming-Luan; Zhang, Jun; Zhang, Zheng; Yuan, Bi-Feng; Yu, Qiong-Wei; Feng, Yu-Qi

    2013-04-01

    In this work, a one-step approach to facile preparation of organic-inorganic hybrid monoliths was successfully developed. After vinyl-end organic monomers and azobisisobutyronitrile (AIBN) were mixed with hydrolyzed tetramethoxysilane (TMOS) and 3-mercaptopropyltrimethoxysilane (MPTMS), the homogeneous mixture was introduced into a fused-silica capillary for simultaneous polycondensation and "thiol-ene" click reaction to form the organic-silica hybrid monoliths. By employing this strategy, two types of organic-silica hybrid monoliths with positively charged quaternary ammonium and amide groups were prepared, respectively. The functional groups were successfully introduced onto the monoliths during the sol-gel process with "thiol-ene" click reaction, which was demonstrated by ζ-potential assessment, energy dispersive X-ray spectroscopy (EDX), and Fourier transform infrared (FT-IR) spectroscopy. The porous structure of the prepared monolithic columns was examined by scanning electron microscopy (SEM), nitrogen adsorption-desorption measurement, and mercury intrusion porosimetry. These results indicate the prepared organic-silica hybrid monoliths possess homogeneous column bed, large specific surface area, good mechanical stability, and excellent permeability. The prepared monolithic columns were then applied for anion-exchange/hydrophilic interaction liquid chromatography. Different types of analytes, including benzoic acids, inorganic ions, nucleosides, and nucleotides, were well separated with high column efficiency around 80,000-130,000 plates/m. Taken together, we present a facile and universal strategy to prepare organic-silica hybrid monoliths with a variety of organic monomers using one-step approach. PMID:23434082

  4. Degradable polymeric nanoparticles by aggregation of thermoresponsive polymers and ``click'' chemistry

    NASA Astrophysics Data System (ADS)

    Dworak, Andrzej; Lipowska, Daria; Szweda, Dawid; Suwinski, Jerzy; Trzebicka, Barbara; Szweda, Roza

    2015-10-01

    This study describes a novel approach to the preparation of crosslinked polymeric nanoparticles of controlled sizes that can be degraded under basic conditions. For this purpose thermoresponsive copolymers containing azide and alkyne functions were obtained by ATRP of di(ethylene glycol) monomethyl ether methacrylate (D) and 2-aminoethyl methacrylate (A) followed by post polymerization modification. The amino groups of A were reacted with propargyl chloroformate or 2-azido-1,3-dimethylimidazolinium hexafluorophosphate, which led to two types of copolymers. Increasing the temperature of aqueous solutions of the mixed copolymers caused their aggregation into spherical nanoparticles composed of both types of chains. Their dimensions could be controlled by changing the concentration and heating rate of the solutions. Covalent stabilization of aggregated chains was performed by a ``click'' reaction between the azide and alkyne groups. Due to the presence of a carbamate bond the nanoparticles undergo pH dependent degradation under mild basic conditions. The proposed procedure opens a route to new carriers for the controlled release of active species.This study describes a novel approach to the preparation of crosslinked polymeric nanoparticles of controlled sizes that can be degraded under basic conditions. For this purpose thermoresponsive copolymers containing azide and alkyne functions were obtained by ATRP of di(ethylene glycol) monomethyl ether methacrylate (D) and 2-aminoethyl methacrylate (A) followed by post polymerization modification. The amino groups of A were reacted with propargyl chloroformate or 2-azido-1,3-dimethylimidazolinium hexafluorophosphate, which led to two types of copolymers. Increasing the temperature of aqueous solutions of the mixed copolymers caused their aggregation into spherical nanoparticles composed of both types of chains. Their dimensions could be controlled by changing the concentration and heating rate of the solutions. Covalent

  5. Click Cross-Linking-Improved Waterborne Polymers for Environment-Friendly Coatings and Adhesives.

    PubMed

    Hu, Jianqing; Peng, Kaimei; Guo, Jinshan; Shan, Dingying; Kim, Gloria B; Li, Qiyao; Gerhard, Ethan; Zhu, Liang; Tu, Weiping; Lv, Weizhong; Hickner, Michael A; Yang, Jian

    2016-07-13

    Waterborne polymers, including waterborne polyurethanes (WPU), polyester dispersions (PED), and polyacrylate emulsions (PAE), are employed as environmentally friendly water-based coatings and adhesives. An efficient, fast, stable, and safe cross-linking strategy is always desirable to impart waterborne polymers with improved mechanical properties and water/solvent/thermal and abrasion resistance. For the first time, click chemistry was introduced into waterborne polymer systems as a cross-linking strategy. Click cross-linking rendered waterborne polymer films with significantly improved tensile strength, hardness, adhesion strength, and water/solvent resistance compared to traditional waterborne polymer films. For example, click cross-linked WPU (WPU-click) has dramatically improved the mechanical strength (tensile strength increased from 0.43 to 6.47 MPa, and Young's modulus increased from 3 to 40 MPa), hardness (increased from 59 to 73.1 MPa), and water resistance (water absorption percentage dropped from 200% to less than 20%); click cross-linked PED (PED-click) film also possessed more than 3 times higher tensile strength (∼28 MPa) than that of normal PED (∼8 MPa). The adhesion strength of click cross-linked PAE (PAE-click) to polypropylene (PP) was also improved (from 3 to 5.5 MPa). In addition, extra click groups can be preserved after click cross-linking for further functionalization of the waterborne polymeric coatings/adhesives. In this work, we have demonstrated that click modification could serve as a convenient and powerful approach to significantly improve the performance of a variety of traditional coatings and adhesives. PMID:27326894

  6. Aqueous Modification of Nano- and Microfibrillar Cellulose with a Click Synthon.

    PubMed

    Hettegger, Hubert; Beaumont, Marco; Potthast, Antje; Rosenau, Thomas

    2016-01-01

    The modification of cellulose as a renewable resource has received wide attention in research and industry. A major problem regarding chemical modification, including heating and drying, is related to hornification that causes pore-system collapse and results in decreased reactivity and changes in the 3D structure of the material. A mild and green approach for the modification of different never-dried and thus wet cellulose substrates (pulp, nanostructured celluloses, and viscose fibers) by an alkoxysilane-azide in water is presented. A kinetic study of the silanization reaction demonstrates that alkoxy-trans-silanization of the cellulose surface is accomplished in water as a suspension medium within a few hours at room temperature. The resulting, azido-equipped celluloses are widely applicable precursor materials for subsequent functionalization by so-called click chemistry, for example, with a fluorescent Rhodamine derivative as a representative reagent. Successful covalent bonding was shown by GPC and a model reaction. The 3D structure of the materials remained intact, as was inter alia visualized by optical and fluorescence microscopy. PMID:26612209

  7. Click chemistry functionalization improving the wideband optical-limiting performance of fullerene derivatives.

    PubMed

    Liu, Xiong; Wang, Dong; Gao, Hong; Yang, Zhou; Xing, Yan; Cao, Hui; He, Wanli; Wang, Huihui; Gu, Jianming; Hu, Huiying

    2016-03-14

    A novel kind of monodonor-bisacceptor (D-A-A) C60 charge-transfer complex was synthesized by the high-yielding [2+2] click chemistry reaction and the Prato reaction. Both electrochemical and UV-vis spectra studies were carried out and they proved that the side groups of the fullerene derivatives played an important role in the energy gaps, and also affected the third-order non-linear optical response. The experimental investigation on the third-order non-linear optical phenomena of the fullerene derivatives was measured using the Z-scan technique at different wavelengths (532 nm and 1064 nm). All the compounds exhibited very special non-linear optical properties when pumped by 21 ps pulses at 532 nm which suggested that there were two different types of reversible photo-isomerization. The optical-limiting performance has also been studied which proved indirectly the mechanism models of the reversible photo-isomerization. PMID:26899312

  8. Characterization of peptide immobilization on an acetylene terminated surface via click chemistry

    NASA Astrophysics Data System (ADS)

    Shamsi, Fahimeh; Coster, Hans; Jolliffe, Katrina A.

    2011-10-01

    Peptide (A-A-A-A-G-G-G-E-R-G-D)1A: Alanine; D: Glutamic acid; E: Aspartic acid; G: Glycine; R: Arginine. conjugated surfaces were prepared on silicon surfaces through click chemistry. The amino acid sequence RGD is the cellular attachment site of a large number of extracellular matrices such as blood and cell surface proteins. Recent research has focused on developing RGD peptides which mimic cell adhesion proteins and integrins [1,2].The steps involved the formation of an alkyne-terminated monolayer on Si(111), followed by linking the peptide to 4-azidophenyl isothiocyanate via a specific and gentle reaction. This was followed by the attachment of the azido peptide to the surface-bound alkynes using the Cu (I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction. The surface structures of the alkyne terminated monolayer and the attached peptide were characterized using high resolution impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS) and Fourier Transform Infrared (ATR-FTIR) Spectroscopy. EIS characterization revealed the alkyne layer and the hydrophobic and polar regions of the attached peptide. XPS analysis showed a high surface coverage of the peptide on the silicon substrates and this was confirmed by FTIR.Our results confirmed a specific covalent attachment of the peptide on the silicon surfaces. This approach offers a versatile, experimentally simple, method for the specific attachment of peptide ligands. This approach would have applications for cell attachment and biosensors.

  9. Multiple shape memory polymers based on laminates formed from thiol-click chemistry based polymerizations.

    PubMed

    Podgórski, M; Wang, C; Bowman, C N

    2015-09-14

    This investigation details the formation of polymer network trilayer laminates formed by thiol-X click chemistries, and their subsequent implementation and evaluation for quadruple shape memory behavior. Thiol-Michael addition and thiol-isocyanate-based crosslinking reactions were employed to fabricate each of the laminate's layers with independent control of the chemistry and properties of each layer and outstanding interlayer adhesion and stability. The characteristic features of step-growth thiol-X reactions, such as excellent network uniformity and narrow thermal transitions as well as their stoichiometric nature, enabled fabrication of trilayer laminates with three distinctly different glass transition temperatures grouped within a narrow range of 100 °C. Through variations in the layer thicknesses, a step-wise modulus drop as a function of temperature was achieved. This behavior allowed multi-step programming and the demonstration and quantification of quadruple shape memory performance. As is critical for this performance, the interface connecting the layers was evaluated in stoichiometric as well as off-stoichiometric systems. It was shown that the laminated structures exhibit strong interfacial binding and hardly suffer any delamination during cyclic material testing and deformation. PMID:26234205

  10. Sex and Ear Differences in Spontaneous and Click-Evoked Otoacoustic Emissions in Young Adults

    ERIC Educational Resources Information Center

    Snihur, Adrian W. K.; Hampson, Elizabeth

    2011-01-01

    Effects of sex and handedness on the production of spontaneous and click-evoked otoacoustic emissions (OAEs) were explored in a non-hearing impaired population (ages 17-25 years). A sex difference in OAEs, either produced spontaneously (spontaneous OAEs or SOAEs) or in response to auditory stimuli (click-evoked OAEs or CEOAEs) has been reported in…

  11. Selective Bifunctional Modification of a Non-catenated Metal-Organic Framework Material via 'Click' Chemistry

    SciTech Connect

    Gadzikwa, Tendai; Farha, Omar K.; Malliakas, Christos D.; Kanatzidis, Mercouri G.; Hupp, Joseph T.; Nguyen, SonBinh T.; NWU

    2009-12-01

    A noncatenated, Zn-based metal-organic framework (MOF) material bearing silyl-protected acetylenes was constructed and postsynthetically modified using 'click' chemistry. Using a solvent-based, selective deprotection strategy, two different organic azides were 'clicked' onto the MOF crystals, resulting in a porous material whose internal and external surfaces are differently functionalized.

  12. Clicking in a Killer Whale Habitat: Narrow-Band, High-Frequency Biosonar Clicks of Harbour Porpoise (Phocoena phocoena) and Dall’s Porpoise (Phocoenoides dalli)

    PubMed Central

    Kyhn, Line A.; Tougaard, Jakob; Beedholm, Kristian; Jensen, Frants H.; Ashe, Erin; Williams, Rob; Madsen, Peter T.

    2013-01-01

    Odontocetes produce a range of different echolocation clicks but four groups in different families have converged on producing the same stereotyped narrow band high frequency (NBHF) click. In microchiropteran bats, sympatric species have evolved the use of different acoustic niches and subtly different echolocation signals to avoid competition among species. In this study, we examined whether similar adaptations are at play among sympatric porpoise species that use NBHF echolocation clicks. We used a six-element hydrophone array to record harbour and Dall’s porpoises in British Columbia (BC), Canada, and harbour porpoises in Denmark. The click source properties of all porpoise groups were remarkably similar and had an average directivity index of 25 dB. Yet there was a small, but consistent and significant 4 kHz difference in centroid frequency between sympatric Dall’s (137±3 kHz) and Canadian harbour porpoises (141±2 kHz). Danish harbour porpoise clicks (136±3 kHz) were more similar to Dall’s porpoise than to their conspecifics in Canada. We suggest that the spectral differences in echolocation clicks between the sympatric porpoises are consistent with evolution of a prezygotic isolating barrier (i.e., character displacement) to avoid hybridization of sympatric species. In practical terms, these spectral differences have immediate application to passive acoustic monitoring. PMID:23723996

  13. Clicking in a killer whale habitat: narrow-band, high-frequency biosonar clicks of harbour porpoise (Phocoena phocoena) and Dall's porpoise (Phocoenoides dalli).

    PubMed

    Kyhn, Line A; Tougaard, Jakob; Beedholm, Kristian; Jensen, Frants H; Ashe, Erin; Williams, Rob; Madsen, Peter T

    2013-01-01

    Odontocetes produce a range of different echolocation clicks but four groups in different families have converged on producing the same stereotyped narrow band high frequency (NBHF) click. In microchiropteran bats, sympatric species have evolved the use of different acoustic niches and subtly different echolocation signals to avoid competition among species. In this study, we examined whether similar adaptations are at play among sympatric porpoise species that use NBHF echolocation clicks. We used a six-element hydrophone array to record harbour and Dall's porpoises in British Columbia (BC), Canada, and harbour porpoises in Denmark. The click source properties of all porpoise groups were remarkably similar and had an average directivity index of 25 dB. Yet there was a small, but consistent and significant 4 kHz difference in centroid frequency between sympatric Dall's (137±3 kHz) and Canadian harbour porpoises (141±2 kHz). Danish harbour porpoise clicks (136±3 kHz) were more similar to Dall's porpoise than to their conspecifics in Canada. We suggest that the spectral differences in echolocation clicks between the sympatric porpoises are consistent with evolution of a prezygotic isolating barrier (i.e., character displacement) to avoid hybridization of sympatric species. In practical terms, these spectral differences have immediate application to passive acoustic monitoring. PMID:23723996

  14. Stealth polymeric vesicles via metal-free click coupling.

    PubMed

    Isaacman, Michael J; Corigliano, Eleonora M; Theogarajan, Luke S

    2013-09-01

    The strain-promoted azide-alkyne cycloaddition represents an optimal metal-free method for the modular coupling of amphiphilic polymer blocks. Hydrophilic poly(oxazoline) (PMOXA) or poly(ethylene glycol) (PEG) A-blocks were coupled with a hydrophobic poly(siloxane) B-block to provide triblock copolymers capable of self-assembling into vesicular nanostructures. Stealth properties investigated via a complement activation assay revealed the superior in vitro stealth attributes of polymeric vesicles synthesized via a metal-free approach to those coupled via the widely used copper-catalyzed click method. Furthermore, the ability to change a single parameter, such as the hydrophilic block, allowed the direct comparison of the biocompatibility properties of triblock copolymers containing PMOXA or PEG. Our studies convincingly demonstrate the need for a metal-free approach, both in preventing cytotoxicity while imparting optimal stealth properties for potential biomedical applications. PMID:23952743

  15. Bioorthogonal Click Chemistry-Based Synthetic Cell Glue.

    PubMed

    Koo, Heebeom; Choi, Myunghwan; Kim, Eunha; Hahn, Sei Kwang; Weissleder, Ralph; Yun, Seok Hyun

    2015-12-22

    Artificial methods of cell adhesion can be effective in building functional cell complexes in vitro, but methods for in vivo use are currently lacking. Here, a chemical cell glue based on bioorthogonal click chemistry with high stability and robustness is introduced. Tetrazine (Tz) and trans-cyclooctene (TCO) conjugated to the cell surface form covalent bonds between cells within 10 min in aqueous conditions. Glued, homogeneous, or heterogeneous cell pairs remain viable and stably attached in a microfluidic flow channel at a shear stress of 20 dyn cm(-2) . Upon intravenous injection of assembled Jurkat T cells into live mice, fluorescence microscopy shows the trafficking of cell pairs in circulation and their infiltration into lung tissues. These results demonstrate the promising potential of chemically glued cell pairs for various applications ranging from delivering therapeutic cells to studying cell-cell interactions in vivo. PMID:26768353

  16. BLINK: Billion Lines INdexing in a clicK

    NASA Astrophysics Data System (ADS)

    Kamennoff, N.; Foucaud, S.; Reybier, S.; Tsai, M.-F.; Tang, C.-H.

    2012-09-01

    The coming generation of sky surveys are going to provide measurements for properties of a number of objects like never have been reached before. Astronomical databases will have to deal with requests on several billions of entries at once, and therefore a new computational framework is vital for the next generation of Data-Centers. As part of the efforts linked to the setting up of the Taiwan Extragalactic Astronomical Data Center (TWEA-DC), Billion Lines INdexing in a clicK (BLINK) is developed to satisfy this role. BLINK is a framework that aims to ease access to large amount of data and share analysis software amongst users. BLINK is also designed to be parallelized and distributed on large amount of heterogeneous resources. BLINK will propose at first a very fast indexing algorithm and cross-matching capability, enabling to gather multiwavelength information of large chunk of the sky in a very limited period of time.

  17. X-Ray Photoelectron Spectroscopy and Scanning Electrochemical Microscopy Studies of Branched Multiwalled Carbon Nanotube Paper Modified by Electrochemical Grafting and Click Chemistry

    NASA Astrophysics Data System (ADS)

    Coates, Megan; Nyokong, Tebello

    2013-06-01

    Modification of nanomaterials through electrochemical grafting is a useful approach to introduce linking groups on to the surface of these structures. This work shows the possibility of applying electrochemical grafting to branched multiwalled carbon nanotube paper with an electrical resistance of 0.1 ohm-cm, and subsequent reaction of the grafted 4-azidobenzenediazonium with ethynylferrocene through the Sharpless click chemistry reaction. A comparison is made between this paper electrode and adsorbed single-walled carbon nanotubes on a glassy carbon electrode, with electrochemistry, X-ray photoelectron spectroscopy and scanning electrochemical microscopy used for characterization.

  18. Evoked-potential recovery during double click stimulation in a whale: a possibility of biosonar automatic gain control.

    PubMed

    Supin, Alexander Ya; Nachtigall, Paul E; Breese, Marlee

    2007-01-01

    False killer whale Pseudorca crassidens auditory brainstem responses (ABR) were recorded using a double-click stimulation paradigm specifically measuring the recovery of the second response (to the test click) as a function of the inter-click interval (ICI) at various levels of the conditioning and test click. At all click intensities, the slopes of recovery functions were almost constant: 0.6-0.8 microV per ICI decade. Therefore, even when the conditioning-to-test-click level ratio was kept constant, the duration of recovery was intensity-dependent: The higher intensity the longer the recovery. The conditioning-to-test-click level ratio strongly influenced the recovery time: The higher the ratio, the longer the recovery. The dependence was almost linear using a logarithmic ICI scale with a rate of 25-30 dB per ICI decade. These data were used for modeling the interaction between the emitted click and the echo during echolocation, assuming that the two clicks simulated the transmitted and echo clicks. This simulation showed that partial masking of the echo by the preceding emitted click may explain the independence of echo-response amplitude of target distance. However, the distance range where this mechanism is effective depends on the emitted click level: The higher the level, the greater the range. @ 2007 Acoustical Society of America. PMID:17297815

  19. Effect of electron donating groups on polyphenol-based antioxidant dendrimers.

    PubMed

    Lee, Choon Young; Nanah, Cyprien N; Held, Rich A; Clark, Amanda R; Huynh, Uyen G T; Maraskine, Marina C; Uzarski, Rebecca L; McCracken, John; Sharma, Ajit

    2015-04-01

    Numerous studies have reported the beneficial effects of antioxidants in human diseases. Among their biological effects, a majority of antioxidants scavenge reactive radicals in the body, thereby reducing oxidative stress that is associated with the pathogenesis of many diseases. Antioxidant dendrimers are a new class of potent antioxidant compounds reported recently. In this study, six polyphenol-based antioxidant dendrimers with or without electron donating groups (methoxy group) were synthesized in order to elucidate the influence of electron donating groups (EDG) on their antioxidant activities. Syringaldehyde (2 ortho methoxy groups), vanillin (1 ortho methoxy group), and 4-hydroxybenzaldehyde (0 methoxy group) were derivatized with propargylamine to form building blocks for the dendrimers. All the six dendrimers contain polyether cores, which were synthesized by attaching pentaerythritol and methyl α-d-glucopyranoside to in-house prepared spacer units. To prepare generation 1 antioxidant dendrimers, microwave energy and granulated metallic copper catalyst were used to link the cores and building blocks together via alkyne-azide 1,3-cycloaddition click chemistry. These reaction conditions resulted in high yields of the target dendrimers that were free from copper contamination. Based on DPPH antioxidant assay, antioxidant dendrimers decorated with syringaldehyde and vanillin exhibited over 70- and 170-fold increase in antioxidant activity compared to syringaldehyde and vanillin, respectively. The antioxidant activity of dendrimers increased with increasing number of EDG groups. Similar results were obtained when the dendrimers were used to protect DNA and human LDL against organic carbon and nitrogen-based free radicals. In addition, the antioxidant dendrimers did not show any pro-oxidant activity on DNA in the presence of physiological amounts of copper. Although the dendrimers showed potent antioxidant activities against carbon and nitrogen free radicals

  20. Effect of Electron Donating Groups on Polyphenol-based Antioxidant Dendrimers

    PubMed Central

    Lee, Choon Young; Nanah, Cyprien; Held, Rich; Clark, Amanda; Huynh, Uyen; Maraskine, Marina C.; Uzarski, Rebecca L.; McCracken, John; Sharma, Ajit

    2015-01-01

    Numerous studies have reported the beneficial effects of antioxidants in human diseases. Among their biological effects, a majority of antioxidants scavenge reactive radicals in the body, thereby reducing oxidative stress that is associated with the pathogenesis of many diseases. Antioxidant dendrimers are a new class of potent antioxidant compounds reported recently. In this study, six polyphenol-based antioxidant dendrimers with or without electron donating groups (methoxy group) were synthesized in order to elucidate the influence of electron donating groups (EDG) on their antioxidant activities. Syringaldehyde (2 ortho methoxy groups), vanillin (1 ortho methoxy group), and 4-hydroxybenzaldehyde (0 methoxy group) were derivatized with propargylamine to form building blocks for the dendrimers. All the six dendrimers contain polyether cores, which were synthesized by attaching pentaerythritol and methyl α-D-glucopyranoside to in-house prepared spacer units. To prepare generation 1 antioxidant dendrimers, microwave energy and granulated metallic copper catalyst were used to link the cores and building blocks together via alkyne-azide 1,3-cycloaddition click chemistry. These reaction conditions resulted in high yields of the target dendrimers that were free from copper contamination. Based on DPPH antioxidant assay, antioxidant dendrimers decorated with syringaldehyde and vanillin exhibited over 70- and 170-fold increase in antioxidant activity compared to syringaldehyde and vanillin, respectively. The antioxidant activity of dendrimers increased with increasing number of EDG groups. Similar results were obtained when the dendrimers were used to protect DNA and human LDL against organic carbon and nitrogen-based free radicals. In addition, the antioxidant dendrimers did not show any pro-oxidant activity on DNA in the presence of physiological amounts of copper. Although the dendrimers showed potent antioxidant activities against carbon and nitrogen free radicals

  1. Rapidly Polymerizing Injectable Click Hydrogel Therapy to Delay Bone Growth in a Murine Re-synostosis Model

    PubMed Central

    Hermann, Christopher D.; Wilson, David S.; Lawrence, Kelsey A.; Ning, Xinghai; Olivares-Navarrete, Rene; Williams, Joseph K.; Guldberg, Robert E.; Murthy, Niren; Schwartz, Zvi; Boyan, Barbara D.

    2014-01-01

    Craniosynostosis is the premature fusion of cranial sutures, which can result in progressive cranial deformations, increased intracranial pressure, and restricted brain growth. Most cases of craniosynostosis require surgical reconstruction of the cranial vault with the goal of increasing the intracranial volume and correcting the craniofacial deformities. However, patients often experience rapid post-operative bone re-growth, known as re-synostosis, which necessitates additional surgical intervention. Bone morphogenic protein (BMP) inhibitors have tremendous potential to treat re-synostosis, but the realization of a clinically viable inhibitor-based therapeutic requires the development of a delivery vehicle that can localize the release to the site of administration. Here, we present an in situ rapidly crosslinking injectable hydrogel that has the properties necessary to encapsulate co-administered proteins and demonstrate that the delivery of rmGremlin1 via our hydrogel system delays bone re-growth in a weanling mouse model of re-synostosis. Our hydrogel is composed of two mutually reactive poly(ethylene glycol) macromolecules, which when mixed crosslink via a bio-orthogonal Cu free click reaction. Hydrogels containing Gremlin caused a dose-dependent inhibition of bone regrowth. In addition to craniofacial applications, our injectable click hydrogel has the potential to provide customizable protein, small molecule, and cell delivery to any site accessible via needle or catheter. PMID:25176067

  2. Rapidly polymerizing injectable click hydrogel therapy to delay bone growth in a murine re-synostosis model.

    PubMed

    Hermann, Christopher D; Wilson, David S; Lawrence, Kelsey A; Ning, Xinghai; Olivares-Navarrete, Rene; Williams, Joseph K; Guldberg, Robert E; Murthy, Niren; Schwartz, Zvi; Boyan, Barbara D

    2014-12-01

    Craniosynostosis is the premature fusion of cranial sutures, which can result in progressive cranial deformations, increased intracranial pressure, and restricted brain growth. Most cases of craniosynostosis require surgical reconstruction of the cranial vault with the goal of increasing the intracranial volume and correcting the craniofacial deformities. However, patients often experience rapid post-operative bone regrowth, known as re-synostosis, which necessitates additional surgical intervention. Bone morphogenetic protein (BMP) inhibitors have tremendous potential to treat re-synostosis, but the realization of a clinically viable inhibitor-based therapeutic requires the development of a delivery vehicle that can localize the release to the site of administration. Here, we present an in situ rapidly crosslinking injectable hydrogel that has the properties necessary to encapsulate co-administered proteins and demonstrate that the delivery of rmGremlin1 via our hydrogel system delays bone regrowth in a weanling mouse model of re-synostosis. Our hydrogel is composed of two mutually reactive poly(ethylene glycol) macromolecules, which when mixed crosslink via a bio-orthogonal Cu free click reaction. Hydrogels containing Gremlin caused a dose dependent inhibition of bone regrowth. In addition to craniofacial applications, our injectable click hydrogel has the potential to provide customizable protein, small molecule, and cell delivery to any site accessible via needle or catheter. PMID:25176067

  3. Synthesis and antioxidant property of novel 1,2,3-triazole-linked starch derivatives via 'click chemistry'.

    PubMed

    Tan, Wenqiang; Li, Qing; Li, Wancong; Dong, Fang; Guo, Zhanyong

    2016-01-01

    Based on the copper (I) catalyzed Huisgen azide-alkyne cycloaddition (click chemistry), the novel synthesis of a variety of 1,2,3-triazole-linked starch derivatives was developed, including 6-hydroxymethyltriazole-6-deoxy starch (HMTST), 6-hydroxyethyltriazole-6-deoxy starch (HETST), 6-hydroxypropyltriazole-6-deoxy starch (HPTST), and 6-hydroxybutyltriazole-6-deoxy starch (HBTST). Their antioxidant properties against hydroxyl-radical, DPPH-radical, and superoxide-radical were evaluated in vitro, respectively. The antioxidant activity of the obtained novel amphiprotic starch derivatives via 'click reaction' exhibited remarkable improvement over starch. And the scavenging effect indices of most of the products were higher than 60% at 1.6 mg/mL against hydroxyl-radical and DPPH-radical. Moreover, the scavenging effect of the products against superoxide-radical attained 90% above at 0.1mg/mL. Generally, the antioxidant activity decreased in the order: HBTST>HPTST>HETST>HMTST>starch. Furthermore, the order of their antioxidant activity was consistent with the electron-donating ability of different substituted groups of the 1,2,3-triazoles. The substituted groups with stronger electron supplying capacity provided more electrons to the various radicals, which relatively enhanced the capacity for scavenging free radicals. PMID:26449530

  4. In situ-forming click-crosslinked gelatin based hydrogels for 3D culture of thymic epithelial cells.

    PubMed

    Truong, Vinh X; Hun, Michael L; Li, Fanyi; Chidgey, Ann P; Forsythe, John S

    2016-07-21

    Hydrogels prepared from naturally derived gelatin can provide a suitable environment for cell attachment and growth, making them favourable materials in tissue engineering. However, physically crosslinked gelatin hydrogels are not stable under physiological conditions while chemical crosslinking of gelatin by radical polymerization may be harmful to cells. In this study, we attached the norbornene functional group to gelatin, which was subsequently crosslinked with a polyethylene glycol (PEG) linker via the nitrile oxide-norbornene click reaction. The rapid crosslinking process allows the hydrogel to be formed within minutes of mixing the polymer solutions under physiological conditions, allowing the gels to be used as injectable materials. The hydrogels properties including mechanical strength, swelling and degradation, can be tuned by changing either the ratio of the reacting groups or the total concentration of the polymer precursors. Murine embryonic fibroblastic cells cultured in soft gels (2 wt% of gelatin and 1 wt% of PEG linker) demonstrated high cell viability as well as similar phenotypic profiles (PDGFRα and MTS15) to Matrigel cultures over 5 days. Thymic epithelial cell and fibroblast co-cultures produced epithelial colonies in these gels following 7 days incubation. These studies demonstrate that gelatin based hydrogels, prepared using "click" crosslinking, provide a robust cell culture platform with retained benefits of the gelatin material, and are therefore suitable for use in various tissue engineering applications. PMID:27217071

  5. Modification of fluorous substrates with oligo(ethylene glycol) via "click" chemistry for long-term resistance of cell adhesion.

    PubMed

    Contreras-Caceres, Rafael; Santos, Catherine M; Li, Siheng; Kumar, Amit; Zhu, Zhiling; Kolar, Satya S; Casado-Rodriguez, Miguel A; Huang, Yongkai; McDermott, Alison; Lopez-Romero, Juan Manuel; Cai, Chengzhi

    2015-11-15

    In this work perfluorinated substrates fabricated from SiO2 glass slides are modified with oligo(ethylene glycol) (OEG) units for long-term resistance of cell adhesion purposes, based on fluorous interactions and click chemistry. Specifically, fluorous substrates, prepared by treatment of glass slides with 1H, 1H, 2H, 2H-perfluorodecyltrimethoxysilane (FAS17), were coated with ethynyl-OEG-C8F17, followed by covalent attachment of an azido-OEG via copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction. We demonstrate that the resultant surface avoid fibrinogen adsorption and resisted cell adhesion for over 14days. X-ray photoemission spectroscopy (XPS) analysis and contact angle goniometry measurements confirm the presence of the OEG molecules on the fluorous substrates. Bright field optical images show total absence of 3T3 fibroblast cells on the OEG modified fluorinated substrate for 1 and 5days, and a remarkably decrease of cell adhesion at 14days. PMID:26210101

  6. Click synthesis of quaternized poly(dimethylaminoethyl methacrylate) functionalized graphene oxide with improved antibacterial and antifouling ability.

    PubMed

    Tu, Qin; Tian, Chang; Ma, Tongtong; Pang, Long; Wang, Jinyi

    2016-05-01

    A quaternized poly(dimethylaminoethyl methacrylate) functionalized graphene oxide (GO-QPDMAEMA) was successfully prepared in this study via click chemistry. Alkyne-functionalized graphene oxide (GO-alkyne) was first synthesized through a two-step amidation reaction of GO-COOH. Meanwhile, azide-terminated poly(dimethylaminoethyl methacrylate) (PDMAEMA-N3) was prepared via the atom-transfer radical-polymerization of dimethylaminoethyl methacrylate (DMAEMA). Subsequently, PDMAEMA-N3 was grafted onto the GO-alkyne through click chemistry to obtain PDMAEMA modified graphene oxide (GO-PDMAEMA). Finally, the tertiary amino groups of GO-PDMAEMA were quaternized by ethyl bromide to provide a quaternized poly(dimethylaminoethyl methacrylate) functionalized graphene oxide (GO-QPDMAEMA). Various characterization techniques, including Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, UV-vis spectrometry, ζ potential, Raman, contact angle analyses and field emission scanning electron microscope were used to ascertain the successful preparation of the quaternized GO-QPDMAEMA. Furthermore, antibacterial and antifouling activities of GO-QPDMAEMA were investigated via protein adsorption, as well as bacterial and cell adhesion studies. The results suggest that the GO-QPDMAEMA surface exhibited significant antibacterial and antifouling properties, compared with the GO-COOH and GO-PDMAEMA surfaces. PMID:26852103

  7. Changes in parameters of auditory evoked magnetic fields with click train patterns

    NASA Astrophysics Data System (ADS)

    Nakagawa, Seiji; Ueno, Shoogo; Imada, Toshiaki

    1999-04-01

    N1m is an auditory evoked brain magnetic field with a magnitude of 100 fT order observed over the auditory cortex, 100 ms after the onset of auditory stimuli. The N1m is often used as a landmark of functional localization in the cortex. However, the mechanism of the N1m has not yet been clarified. The N1m peak amplitude and latency are dependent on the specifics of the stimulus; duration, intensity, and sequence of stimuli. In this study, we examined the dependency of the N1m peak amplitude and latency on the stimulus duration and frequency. Trains of 0.2 ms clicks were used for auditory stimuli by changing the number of clicks and the click interval. Auditory brain magnetic responses evoked by the click trains were recorded from seven human adult subjects by a dc superconducting quantum interference device magnetometer. In the results of this study, the N1m amplitudes significantly increased as the stimulus duration increased and the amplitudes leveled when the stimulus duration reached 32 ms. The amplitudes produced by the trains with the same number of clicks showed greater values for 4-ms-interval trains. The N1m latencies significantly decreased as the stimulus duration increased and leveled at 32 ms. It is concluded that all clicks received within 32 ms were integrated and that this integration mechanism is dependent upon the click interval. Increased synchrony of neuronal cells at the cortical level can explain this integration mechanism.

  8. Click-based echolocation in bats: not so primitive after all.

    PubMed

    Yovel, Yossi; Geva-Sagiv, Maya; Ulanovsky, Nachum

    2011-05-01

    Echolocating bats of the genus Rousettus produce click sonar signals, using their tongue (lingual echolocation). These signals are often considered rudimentary and are believed to enable only crude performance. However, the main argument supporting this belief, namely the click's reported long duration, was recently shown to be an artifact. In fact, the sonar clicks of Rousettus bats are extremely short, ~50-100 μs, similar to dolphin vocalizations. Here, we present a comparison between the sonar systems of the 'model species' of laryngeal echolocation, the big brown bat (Eptesicus fuscus), and that of lingual echolocation, the Egyptian fruit bat (Rousettus aegyptiacus). We show experimentally that in tasks, such as accurate landing or detection of medium-sized objects, click-based echolocation enables performance similar to laryngeal echolocators. Further, we describe a sophisticated behavioral strategy for biosonar beam steering in clicking bats. Finally, theoretical analyses of the signal design--focusing on their autocorrelations and wideband ambiguity functions--predict that in some aspects, such as target ranging and Doppler-tolerance, click-based echolocation might outperform laryngeal echolocation. Therefore, we suggest that click-based echolocation in bats should be regarded as a viable echolocation strategy, which is in fact similar to the biosonar used by most echolocating animals, including whales and dolphins. PMID:21465138

  9. Point-and-Click Cursor Control With an Intracortical Neural Interface System by Humans With Tetraplegia

    PubMed Central

    Kim, Sung-Phil; Simeral, John D.; Hochberg, Leigh R.; Donoghue, John P.; Friehs, Gerhard M.; Black, Michael J.

    2012-01-01

    We present a point-and-click intracortical neural interface system (NIS) that enables humans with tetraplegia to volitionally move a 2-D computer cursor in any desired direction on a computer screen, hold it still, and click on the area of interest. This direct brain–computer interface extracts both discrete (click) and continuous (cursor velocity) signals from a single small population of neurons in human motor cortex. A key component of this system is a multi-state probabilistic decoding algorithm that simultaneously decodes neural spiking activity of a small population of neurons and outputs either a click signal or the velocity of the cursor. The algorithm combines a linear classifier, which determines whether the user is intending to click or move the cursor, with a Kalman filter that translates the neural population activity into cursor velocity. We present a paradigm for training the multi-state decoding algorithm using neural activity observed during imagined actions. Two human participants with tetraplegia (paralysis of the four limbs) performed a closed-loop radial target acquisition task using the point-and-click NIS over multiple sessions. We quantified point-and-click performance using various human-computer interaction measurements for pointing devices. We found that participants could control the cursor motion and click on specified targets with a small error rate (<3% in one participant). This study suggests that signals from a small ensemble of motor cortical neurons (~40) can be used for natural point-and-click 2-D cursor control of a personal computer. PMID:21278024

  10. Novel antifouling surface with improved hemocompatibility by immobilization of polyzwitterions onto silicon via click chemistry

    NASA Astrophysics Data System (ADS)

    Zheng, Sunxiang; Yang, Qian; Mi, Baoxia

    2016-02-01

    A novel procedure is presented to develop an antifouling silicon surface with improved hemocompatibility by using a zwitterionic polymer, poly(sulfobetaine methacrylate) (polySBMA). Functionalization of the silicon surface with polySBMA involved the following three steps: (1) an alkyne terminated polySBMA was synthesized by RAFT polymerization; (2) a self-assembled monolayer with bromine end groups was constructed on the silicon surface, and then the bromine end groups were replaced by azide groups; and (3) the polySBMA was attached to the silicon surface by azide-alkyne cycloaddition click reaction. Membrane characterization confirmed a successful silicon surface modification with almost 100% coverage by polySBMA and an extremely hydrophilic surface after such modification. The polySBMA-modified silicon surface was found to have excellent anti-nonspecific adsorption properties for both bovine serum albumin (BSA) protein and model bacterial cells. Whole blood adsorption experiments showed that the polySBMA-modified silicon surface exhibited excellent hemocompatibility and effective anti-adhesion to blood cells. Silicon membranes with such antifouling and hemocompatible surfaces can be advantageously used to drastically extend the service life of implantable medical devices such as artificial kidney devices.

  11. The number of consecutive clicks in the train as positive or differential conditioned stimulus in dogs.

    PubMed

    Varga, M E

    1982-01-01

    Conditioned reflexes were elaborated to trains of identical signals (clicks) of a constant number with variable interstimulus interval. The negative conditioned stimulus differed from the positive one only by the number of elements in the train. In classical defensive conditioned reflexes the latent period of motor conditioned responses to the positive stimulus was shorter than to the negative one. There were differences in the latent periods and in the speed of running to the feeding box to the positive and negative stimuli when alimentary instrumental reflexes were elaborated. The dogs ran faster to the feeding box after the positive stimuli. In 30 percent of the total number of negative stimulus presentations they did not run to the feeding box at all. There was no correlation between the reaction parameters and duration of the trains. These parameters correlate only with the number of elements in the train. Experimental data suggest that the quantitative assessment of signal trains effected in the dogs’ central nervous system, i.e. the simple count of elements may be used in its adaptive behavior. PMID:7180592

  12. Cell Proliferation Method: Click Chemistry Based on BrdU Coupling for Multiplex Antibody Staining.

    PubMed

    Cappella, Paolo; Gasparri, Fabio; Pulici, Maurizio; Moll, Jürgen

    2015-01-01

    Determination of incorporation of the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) into DNA is a widely used method to analyze the cell cycle. However, DNA denaturation is required for BrdU detection with the consequence that most protein epitopes are destroyed and their immunocytochemical detection for multiplex analysis is not possible. A novel assay is presented for identifying cells in active S-phase that does not require the DNA denaturation step but nevertheless detects BrdU. For this purpose, cells were pulsed for a short time by 5-ethynyl-2'-deoxyuridine (EdU) which is incorporated into DNA. The nucleotide-exposed ethynyl residue was then derivatized by a copper-catalyzed cycloaddition reaction ("click chemistry" coupling) using a BrdU azide probe. The resulting DNA-bound bromouracil moieties were then detected by commercial anti-BrdU monoclonal antibodies without the need for a denaturation step. This method has been tested using several cell lines and is more sensitive than traditional BrdU and allows multicolor and multiplex analysis in flow cytometry (FCM) and image-based cytometry. PMID:25827484

  13. A portable chemical sensor for histidine based on the strategy of click chemistry.

    PubMed

    Zhou, Jin; Xu, Kefeng; Zhou, Ping; Zheng, Ou; Lin, Zhenyu; Guo, Longhua; Qiu, Bin; Chen, Guonan

    2014-01-15

    A novel portable chemical sensor is developed in combination of the personal glucose meters (PGM) with click chemistry for sensitive and selective determination of histidine. Invertase-labeled alkynyl-DNA can be modified onto the surfaces of Streptavidin Magnespheres Paramagnetic Particles (PMPs) through copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) reaction and formed invertase-functionalized PMPs, which can be separated easily. The presence of invertase can convert sucrose to glucose and can be monitored by the PGM easily. The presence of histidine can inhibit the CuAAC, so the read-out signal of PGM decreased. The difference in signals from the PGM before and after addition of histidine has a good linear correlation with the logarithm of the histidine concentrations in the range of 0.01~100 μM with a detection limit of 3.4 nM, which is lower than those of many other chemical sensors. Moreover, the assay of histidine in milk samples is demonstrated with satisfactory results. PMID:24007674

  14. Incorporation of Methionine Analogues Into Bombyx mori Silk Fibroin for Click Modifications.

    PubMed

    Teramoto, Hidetoshi; Kojima, Katsura

    2015-05-01

    Bombyx mori silk fibroin incorporating three methionine (Met) analogues-homopropargylglycine (Hpg), azidohomoalanine (Aha), and homoallylglycine (Hag)-can be produced simply by adding them to the diet of B. mori larvae. The Met analogues are recognized by methionyl-tRNA synthetase, bound to tRNA(Met), and used for the translation of adenine-uracil-guanine (AUG) codons competitively with Met. In the presence of the standard amount of Met in the diet, incorporation of these analogues remains low. Lowering the amount of Met in the diet drastically improves incorporation efficiencies. Alkyne and azide groups in Hpg and Aha incorporated into silk fibroin can be selectively modified with Cu-catalyzed azide-alkyne cycloaddition reactions (click chemistry). Since Met residues exist only at the N-terminal domain of the fibroin heavy chain and in the fibroin light chain, good access to the reactive sites is expected and domain-selective modifications are possible without perturbing other major domains, including repetitive domains. PMID:25644632

  15. Cell proliferation method: click chemistry based on BrdU coupling for multiplex antibody staining.

    PubMed

    Cappella, Paolo; Gasparri, Fabio; Pulici, Maurizio; Moll, Jürgen

    2008-07-01

    Determination of incorporation of the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) into DNA is a widely used method to analyze the cell cycle (see UNIT 7.7). However, DNA denaturation is required for BrdU detection with the consequence that most protein epitopes are destroyed and their immunocytochemical detection for multiplex analysis is not possible. A novel assay is presented for identifying cells in active S-phase that does not require the DNA denaturation step but nevertheless detects BrdU. For this purpose, cells were pulsed for a short time by an alkenyl deoxyuridine (5-ethynyl-2'-deoxyuridine, EdU), which is incorporated into DNA. The nucleotide exposed ethynyl residue was then derivatized by a copper-catalyzed cycloaddition reaction ("click chemistry" coupling) using a BrdU azide probe. The resulting DNA-bound bromouracil moieties were then detected by commercial anti-BrdU monoclonal antibodies without the need for a denaturation step. This method has been tested using several cell lines and is preferred over traditional BrdU detection since it is more sensitive and allows multicolor and multiplex analysis in FCM and imaging. PMID:18770651

  16. Affinity Induced Surface Functionalization of Liposomes Using Cu-Free Click Chemistry.

    PubMed

    Bak, Martin; Jølck, Rasmus I; Eliasen, Rasmus; Andresen, Thomas L

    2016-07-20

    Functionalization of nanoparticles is a key element for improving specificity of drug delivery systems toward diseased tissue or cells. In the current study we report a highly efficient and chemoselective method for post-functionalization of liposomes with biomacromolecules, which equally well can be used for functionalization of other nanoparticles or solid surfaces. The method exploits a synergistic effect of having both affinity and covalent anchoring tags on the surface of the liposome. This was achieved by synthesizing a peptide linker system that uses Cu-free strain-promoted click chemistry in combination with histidine affinity tags. The investigation of post-functionalization of PEGylated liposomes was performed with a cyclic RGDfE peptide. By exploring both affinity and covalent tags a 98 ± 2.0% coupling efficiency was achieved, even a diluted system showed a coupling efficiency of 87 ± 0.2%. The reaction kinetics and overall yield were quantified by HPLC. The results presented here open new possibilities for constructing complex nanostructures and functionalized surfaces. PMID:27269516

  17. Fabrication of PEG-carboxymethylcellulose hydrogel by thiol-norbornene photo-click chemistry.

    PubMed

    Lee, Sora; Park, Young Hwan; Ki, Chang Seok

    2016-02-01

    Both poly(ethylene glycol) (PEG) and carboxymethylcellulose (CMC) are biocompatible polymers, which have been widely utilized in biomedical fields. In this study, we demonstrated the fabrication of pH-sensitive PEG-CMC hydrogels based on thiol-norbornene photo-click reaction and characterized their properties, such as swelling ratio, stiffness, degradation, and protein drug release. For the hydrogel fabrication, tetra-arm PEG and CMC were functionalized with norbornene groups and thiol groups, respectively. The hydrogels fabricated with varying concentration (0-3%) of CMCSH and a fixed concentration (4%) of PEG4NB by orthogonal step-growth photopolymerization showed high gel fractions (∼0.85). The presence of CMCSH in hydrogel did not affected gel point (∼4 s) but significantly prolonged completion time of gelation. Swelling ratios of PEG-CMC increased from ∼32 to ∼60 and the shear elastic modulus decreased from ∼3000 to ∼600 Pa with an increase of CMCSH content (0-3%). PEG-CMC hydrogel containing more CMCSH not only underwent slower hydrolytic bulk degradation but also showed a slower BSA release in acidic condition. These results indicate thiol-norbornene PEG-CMC hydrogel has potential as pH-sensitive protein drug carrier. PMID:26616448

  18. Luminescent Iridium(III) Cyclometalated Complexes with 1,2,3-Triazole "Click" Ligands.

    PubMed

    Connell, Timothy U; White, Jonathan M; Smith, Trevor A; Donnelly, Paul S

    2016-03-21

    A series of cyclometalated iridium(III) complexes with either 4-(2-pyridyl)-1,2,3-triazole or 1-(2-picolyl)-1,2,3-triazole ancillary ligands to give complexes with either 5- or 6-membered chelate rings were synthesized and characterized by a combination of X-ray crystallography, electron spin ionization-high-resolution mass spectroscopy (ESI-HRMS), and nuclear magnetic resonance (NMR) spectroscopy. The electronic properties of the complexes were probed using absorption and emission spectroscopy, as well as cyclic voltammetry. The relative stability of the complexes formed from each ligand class was measured, and their excited-state properties were compared. The emissive properties are, with the exception of complexes that contain a nitroaromatic substituent, insensitive to functionalization of the ancillary pyridyl-1,2,3-triazole ligand but tuning of the emission maxima was possible by modification of the cyclometalating ligands. It is possible to prepare a wide range of optimally substituted pyridyl-1,2,3-triazoles using copper Cu(I)-catalyzed azide alkyne cycloaddition, which is a commonly used "click" reaction, and this family of ligands represent an useful alternative to bipyridine ligands for the preparation of luminescent iridium(III) complexes. PMID:26938838

  19. Biodegradable DNA-enabled poly(ethylene glycol) hydrogels prepared by copper-free click chemistry.

    PubMed

    Barker, Karolyn; Rastogi, Shiva K; Dominguez, Jose; Cantu, Travis; Brittain, William; Irvin, Jennifer; Betancourt, Tania

    2016-01-01

    Significant research has focused on investigating the potential of hydrogels in various applications and, in particular, in medicine. Specifically, hydrogels that are biodegradable lend promise to many therapeutic and biosensing applications. Endonucleases are critical for mechanisms of DNA repair. However, they are also known to be overexpressed in cancer and to be present in wounds with bacterial contamination. In this work, we set out to demonstrate the preparation of DNA-enabled hydrogels that could be degraded by nucleases. Specifically, hydrogels were prepared through the reaction of dibenzocyclooctyne-functionalized multi-arm poly(ethylene glycol) with azide-functionalized single-stranded DNA in aqueous solutions via copper-free click chemistry. Through the use of this method, biodegradable hydrogels were formed at room temperature in buffered saline solutions that mimic physiological conditions, avoiding possible harmful effects associated with other polymerization techniques that can be detrimental to cells or other bioactive molecules. The degradation of these DNA-cross-linked hydrogels upon exposure to the model endonucleases Benzonase(®) and DNase I was studied. In addition, the ability of the hydrogels to act as depots for encapsulation and nuclease-controlled release of a model protein was demonstrated. This model has the potential to be tailored and expanded upon for use in a variety of applications where mild hydrogel preparation techniques and controlled material degradation are necessary including in drug delivery and wound healing systems. PMID:26541212

  20. Click conjugation of peptide to hydrogel nanoparticles for tumor-targeted drug delivery.

    PubMed

    Qin, Ming; Zong, Hong; Kopelman, Raoul

    2014-10-13

    Here we introduce a modified peptide-decorated polymeric nanoparticle (NP) for cancer cell targeting, which can deliver drugs, such as doxorubicin (Dox), to several kinds of cancer cells. Specifically, we employ a nucleolin-targeting NP, with a matrix based on a copolymer of acrylamide (AAm) and 2-carboxyethyl acrylate (CEA). The negatively charged co(CEA-AAm) NP was conjugated with a nucleolin-targeting F3 peptide using a highly efficient and specific copper(I) catalyzed azide-alkyne click reaction. F3 peptide binds to angiogenic tumor vasculatures and other nucleolin overexpressing tumor cells. Attaching F3 peptide onto the NP increases the NP uptake by the nucleolin-expressing glioma cell line 9L and the breast cancer cell line MCF-7. Notably, the F3-conjugated NPs show much higher uptake by the nucleolin-overexpressing glioma cell line 9L than that by the breast cancer cell line MCF-7, the latter having a lower expression of nucleolin on its plasma membrane surface. Moreover, the F3 peptide also dramatically enhances the uptake of co(CEA-AAm) NPs by the drug-resistant cell line NCI/ADR-RES. Also, with this F3-conjugated co(CEA-AAm) NP, a high loading and slow release of doxorubicin were achieved. PMID:25162488

  1. Chemoselective modification of viral surfaces via bioorthogonal click chemistry.

    PubMed

    Rubino, Frederick A; Oum, Yoon Hyeun; Rajaram, Lakshmi; Chu, Yanjie; Carrico, Isaac S

    2012-01-01

    The modification of virus particles has received a significant amount of attention for its tremendous potential for impacting gene therapy, oncolytic applications and vaccine development. Current approaches to modifying viral surfaces, which are mostly genetics-based, often suffer from attenuation of virus production, infectivity and cellular transduction. Using chemoselective click chemistry, we have developed a straightforward alternative approach which sidesteps these issues while remaining both highly flexible and accessible. The goal of this protocol is to demonstrate the effectiveness of using bioorthogonal click chemistry to modify the surface of adenovirus type 5 particles. This two-step process can be used both therapeutically or analytically, as it allows for chemoselective ligation of targeting molecules, dyes or other molecules of interest onto proteins pre-labeled with azide tags. The three major advantages of this method are that (1) metabolic labeling demonstrates little to no impact on viral fitness, (2) a wide array of effector ligands can be utilized, and (3) it is remarkably fast, reliable and easy to access. In the first step of this procedure, adenovirus particles are produced bearing either azidohomoalanine (Aha, a methionine surrogate) or the unnatural sugar O-linked N-azidoacetylglucosamine (O-GlcNAz), both of which contain the azide (-N3) functional group. After purification of the azide-modified virus particles, an alkyne probe containing the fluorescent TAMRA moiety is ligated in a chemoselective manner to the pre-labeled proteins or glycoproteins. Finally, an SDS-PAGE analysis is performed to demonstrate the successful ligation of the probe onto the viral capsid proteins. Aha incorporation is shown to label all viral capsid proteins (Hexon, Penton and Fiber), while O-GlcNAz incorporation results in labeling of Fiber only. In this evolving field, multiple methods for azide-alkyne ligation have been successfully developed; however only the

  2. Directionality of sperm whale sonar clicks and its relation to piston radiation theory.

    PubMed

    Beedholm, Kristian; Møhl, Bertel

    2006-02-01

    This paper investigates the applicability to sperm whales of the theory of sound radiating from a piston. The theory is applied to a physical model and to a series of sperm whale clicks. Results show that wave forms of off-axis signals can be reproduced by convolving an on-axis signal with the spatial impulse response of a piston. The angle of a recorded click can be estimated as the angle producing the spatial impulse response that gives the best match with the observation when convolved with the on-axis wave form. It is concluded that piston theory applies to sperm whale sonar click emission. PMID:16521791

  3. Comparative analysis of click chemistry mediated activity-based protein profiling in cell lysates.

    PubMed

    Yang, Yinliang; Yang, Xiaomeng; Verhelst, Steven H L

    2013-01-01

    Activity-based protein profiling uses chemical probes that covalently attach to active enzyme targets. Probes with conventional tags have disadvantages, such as limited cell permeability or steric hindrance around the reactive group. A tandem labeling strategy with click chemistry is now widely used to study enzyme targets in situ and in vivo. Herein, the probes are reacted in live cells, whereas the ensuing detection by click chemistry takes place in cell lysates. We here make a comparison of the efficiency of the activity-based tandem labeling strategy by using Cu(I)-catalyzed and strain-promoted click chemistry, different ligands and different lysis conditions. PMID:24126377

  4. Click reaction based synthesis, antimicrobial, and cytotoxic activities of new 1,2,3-triazoles.

    PubMed

    El Sayed Aly, Mohamed Ramadan; Saad, Hosam Ali; Mohamed, Mosselhi Abdelnabi Mosselhi

    2015-07-15

    Three-motif pharmacophoric models 20a-e and 21-25 were prepared in good yields by CuAAC of two azido substrates 2 and 11 with seven terminal acetylenic derivatives including chalcones 17a-e, theophylline 18 and cholesterol 19. The structure of these compounds was elucidated by NMR, MS, IR spectroscopy and micro analyses. This series was screened as antimicrobial and cytotoxic agents in vitro. Most derivatives showed appreciable antibacterial activity, but they displayed weak cytotoxic, and antifungal activities. Notably, conjugate 25 (cream of the crop) was found to be more active than Ampicillin against Escherichia coli and Staphylococcus aureus and showed appreciable antifungal and cytotoxic activities as well. PMID:26025874

  5. Surface modification via strain-promoted click reaction facilitates targeted lentiviral transduction.

    PubMed

    Chu, Yanjie; Oum, Yoon Hyeun; Carrico, Isaac S

    2016-01-01

    As a result of their ability to integrate into the genome of both dividing and non-dividing cells, lentiviruses have emerged as a promising vector for gene delivery. Targeted gene transduction of specific cells and tissues by lentiviral vectors has been a major goal, which has proven difficult to achieve. We report a novel targeting protocol that relies on the chemoselective attachment of cancer specific ligands to unnatural glycans on lentiviral surfaces. This strategy exhibits minimal perturbation on virus physiology and demonstrates remarkable flexibility. It allows for targeting but can be more broadly useful with applications such as vector purification and immunomodulation. PMID:26499046

  6. Harnessing click detectors for the genuine characterization of light states

    PubMed Central

    Heilmann, René; Sperling, Jan; Perez-Leija, Armando; Gräfe, Markus; Heinrich, Matthias; Nolte, Stefan; Vogel, Werner; Szameit, Alexander

    2016-01-01

    The key requirement for harnessing the quantum properties of light is the capability to detect and count individual photons. Of particular interest are photon-number-resolving detectors, which allow one to determine whether a state of light is classical or genuinely quantum. Existing schemes for addressing this challenge rely on a proportional conversion of photons to electrons. As such, they are capable of correctly characterizing small photon fluxes, yet are limited by uncertainties in the conversion rate. In this work, we employ a divide-and-conquer approach to infallibly discerning non-classicality of states of light. This is achieved by transforming the incident fields into uniform spatial distributions that readily lend themselves for characterization by standard on-off detectors. Since the exact statistics of the light stream in multiplexed on-off detectors are click statistics, our technique is freely scalable to accommodate–in principle–arbitrarily large photon fluxes. Our experiments pave the way towards genuine integrated photon-number-resolving detection for advanced on-chip photonic quantum networks. PMID:26771053

  7. Harnessing click detectors for the genuine characterization of light states.

    PubMed

    Heilmann, René; Sperling, Jan; Perez-Leija, Armando; Gräfe, Markus; Heinrich, Matthias; Nolte, Stefan; Vogel, Werner; Szameit, Alexander

    2016-01-01

    The key requirement for harnessing the quantum properties of light is the capability to detect and count individual photons. Of particular interest are photon-number-resolving detectors, which allow one to determine whether a state of light is classical or genuinely quantum. Existing schemes for addressing this challenge rely on a proportional conversion of photons to electrons. As such, they are capable of correctly characterizing small photon fluxes, yet are limited by uncertainties in the conversion rate. In this work, we employ a divide-and-conquer approach to infallibly discerning non-classicality of states of light. This is achieved by transforming the incident fields into uniform spatial distributions that readily lend themselves for characterization by standard on-off detectors. Since the exact statistics of the light stream in multiplexed on-off detectors are click statistics, our technique is freely scalable to accommodate-in principle-arbitrarily large photon fluxes. Our experiments pave the way towards genuine integrated photon-number-resolving detection for advanced on-chip photonic quantum networks. PMID:26771053

  8. Harnessing click detectors for the genuine characterization of light states

    NASA Astrophysics Data System (ADS)

    Heilmann, René; Sperling, Jan; Perez-Leija, Armando; Gräfe, Markus; Heinrich, Matthias; Nolte, Stefan; Vogel, Werner; Szameit, Alexander

    2016-01-01

    The key requirement for harnessing the quantum properties of light is the capability to detect and count individual photons. Of particular interest are photon-number-resolving detectors, which allow one to determine whether a state of light is classical or genuinely quantum. Existing schemes for addressing this challenge rely on a proportional conversion of photons to electrons. As such, they are capable of correctly characterizing small photon fluxes, yet are limited by uncertainties in the conversion rate. In this work, we employ a divide-and-conquer approach to infallibly discerning non-classicality of states of light. This is achieved by transforming the incident fields into uniform spatial distributions that readily lend themselves for characterization by standard on-off detectors. Since the exact statistics of the light stream in multiplexed on-off detectors are click statistics, our technique is freely scalable to accommodate-in principle-arbitrarily large photon fluxes. Our experiments pave the way towards genuine integrated photon-number-resolving detection for advanced on-chip photonic quantum networks.

  9. Predicting user click behaviour in search engine advertisements

    NASA Astrophysics Data System (ADS)

    Daryaie Zanjani, Mohammad; Khadivi, Shahram

    2015-10-01

    According to the specific requirements and interests of users, search engines select and display advertisements that match user needs and have higher probability of attracting users' attention based on their previous search history. New objects such as user, advertisement or query cause a deterioration of precision in targeted advertising due to their lack of history. This article surveys this challenge. In the case of new objects, we first extract similar observed objects to the new object and then we use their history as the history of new object. Similarity between objects is measured based on correlation, which is a relation between user and advertisement when the advertisement is displayed to the user. This method is used for all objects, so it has helped us to accurately select relevant advertisements for users' queries. In our proposed model, we assume that similar users behave in a similar manner. We find that users with few queries are similar to new users. We will show that correlation between users and advertisements' keywords is high. Thus, users who pay attention to advertisements' keywords, click similar advertisements. In addition, users who pay attention to specific brand names might have similar behaviours too.

  10. Evaluating Search Engine Relevance with Click-Based Metrics

    NASA Astrophysics Data System (ADS)

    Radlinski, Filip; Kurup, Madhu; Joachims, Thorsten

    Automatically judging the quality of retrieval functions based on observable user behavior holds promise for making retrieval evaluation faster, cheaper, and more user centered. However, the relationship between observable user behavior and retrieval quality is not yet fully understood. In this chapter, we expand upon, Radlinski et al. (How does clickthrough data reflect retrieval quality, In Proceedings of the ACM Conference on Information and Knowledge Management (CIKM), 43-52, 2008), presenting a sequence of studies investigating this relationship for an operational search engine on the arXiv.org e-print archive. We find that none of the eight absolute usage metrics we explore (including the number of clicks observed, the frequency with which users reformulate their queries, and how often result sets are abandoned) reliably reflect retrieval quality for the sample sizes we consider. However, we find that paired experiment designs adapted from sensory analysis produce accurate and reliable statements about the relative quality of two retrieval functions. In particular, we investigate two paired comparison tests that analyze clickthrough data from an interleaved presentation of ranking pairs, and find that both give accurate and consistent results. We conclude that both paired comparison tests give substantially more accurate and sensitive evaluation results than the absolute usage metrics in our domain.

  11. Paint and Click: Unified Interactions for Image Boundaries

    SciTech Connect

    Summa, B.; Gooch, A. A.; Scorzelli, G.; Pascucci, V.

    2015-06-22

    Image boundaries are a fundamental component of many interactive digital photography techniques, enabling applications such as segmentation, panoramas, and seamless image composition. Interactions for image boundaries often rely on two complementary but separate approaches: editing via painting or clicking constraints. In this work, we provide a novel, unified approach for interactive editing of pairwise image boundaries that combines the ease of painting with the direct control of constraints. Rather than a sequential coupling, this new formulation allows full use of both interactions simultaneously, giving users unprecedented flexibility for fast boundary editing. To enable this new approach, we provide technical advancements. In particular, we detail a reformulation of image boundaries as a problem of finding cycles, expanding and correcting limitations of the previous work. Our new formulation provides boundary solutions for painted regions with performance on par with state-of-the-art specialized, paint-only techniques. In addition, we provide instantaneous exploration of the boundary solution space with user constraints. Finally, we provide examples of common graphics applications impacted by our new approach.

  12. Detection of systolic ejection click using time growing neural network.

    PubMed

    Gharehbaghi, Arash; Dutoit, Thierry; Ask, Per; Sörnmo, Leif

    2014-04-01

    In this paper, we present a novel neural network for classification of short-duration heart sounds: the time growing neural network (TGNN). The input to the network is the spectral power in adjacent frequency bands as computed in time windows of growing length. Children with heart systolic ejection click (SEC) and normal children are the two groups subjected to analysis. The performance of the TGNN is compared to that of a time delay neural network (TDNN) and a multi-layer perceptron (MLP), using training and test datasets of similar sizes with a total of 614 normal and abnormal cardiac cycles. From the test dataset, the classification rate/sensitivity is found to be 97.0%/98.1% for the TGNN, 85.1%/76.4% for the TDNN, and 92.7%/85.7% for the MLP. The results show that the TGNN performs better than do TDNN and MLP when frequency band power is used as classifier input. The performance of TGNN is also found to exhibit better immunity to noise. PMID:24613501

  13. Pitch strength of regular-interval click trains with different length “runs” of regular intervals

    PubMed Central

    Yost, William A.; Mapes-Riordan, Dan; Shofner, William; Dye, Raymond; Sheft, Stanley

    2009-01-01

    Click trains were generated with first- and second-order statistics following Kaernbach and Demany [J. Acoust. Soc. Am. 104, 2298–2306 (1998)]. First-order intervals are between successive clicks, while second-order intervals are those between every other click. Click trains were generated with a repeating alternation of fixed and random intervals which produce a pitch at the reciprocal of the duration of the fixed interval. The intervals were then randomly shuffled and compared to the unshuffled, alternating click trains in pitch-strength comparison experiments. In almost all comparisons for the first-order interval stimuli, the shuffled-interval click trains had a stronger pitch strength than the unshuffled-interval click trains. The shuffled-interval click trains only produced stronger pitches for second-order interval stimuli when the click trains were unfiltered. Several experimental conditions and an analysis of runs of regular and random intervals in these click trains suggest that the auditory system is sensitive to runs of regular intervals in a stimulus that contains a mix of regular and random intervals. These results indicate that fine-structure regularity plays a more important role in pitch perception than randomness, and that the long-term autocorrelation function or spectra of these click trains are not good predictors of pitch strength. PMID:15957774

  14. 'Click Chemistry' in the preparation of porous polymer-basedparticulate stationary phases for mu-HPLC separation of peptides andproteins

    SciTech Connect

    Slater, Michael; Snauko, Marian; Svec, Frantisek; Frechet, JeanM.J.

    2006-01-02

    With the use of the copper(I)-catalyzed (3 + 2) azide-alkynecycloaddition, an element of "click chemistry," stationary phasescarrying long alkyl chains or soybean trypsin inhibitor have beenprepared for use in HPLC separations in the reversed-phase and affinitymodes, respectively. The ligands were attached via a triazole ring tosize monodisperse porous beads containing either alkyne or azide pendantfunctionalities. Alkyne-containing beads prepared by directcopolymerization of propargyl acrylate with ethylene dimethacrylate wereallowed to react with azidooctadecane to give a reversed-phase sorbent.Azide-functionalized beads were prepared by chemical modification ofglycidyl methacrylate particles. Subsequent reaction with a terminalaliphatic alkyne produced a reversed-phase sorbent similar to thatobtained from the alkyne beads. Soybean trypsin inhibitor wasfunctionalized with N-(4-pentynoyloxy) succinimide to carry alkyne groupsand then allowed to react with the azide-containing beads to produce anaffinity sorbent for trypsin. The performance of these stationary phaseswas demonstrated with the HPLC separations of a variety of peptides andproteins.

  15. Source parameter estimates of echolocation clicks from wild pygmy killer whales (Feresa attenuata) (L)

    NASA Astrophysics Data System (ADS)

    Madsen, P. T.; Kerr, I.; Payne, R.

    2004-10-01

    Pods of the little known pygmy killer whale (Feresa attenuata) in the northern Indian Ocean were recorded with a vertical hydrophone array connected to a digital recorder sampling at 320 kHz. Recorded clicks were directional, short (25 μs) transients with estimated source levels between 197 and 223 dB re. 1 μPa (pp). Spectra of clicks recorded close to or on the acoustic axis were bimodal with peak frequencies between 45 and 117 kHz, and with centroid frequencies between 70 and 85 kHz. The clicks share characteristics of echolocation clicks from similar sized, whistling delphinids, and have properties suited for the detection and classification of prey targeted by this odontocete. .

  16. Hierachical assembly of collagen mimetic peptides into biofunctional materials

    NASA Astrophysics Data System (ADS)

    Gleaton, Jeremy W.

    Collagen is a remarkably strong and prevalent protein distributed throughout nature and as such, collagen is an ideal material for a variety of medical applications. Research efforts for the development of synthetic collagen biomaterials is an area of rapid growth. Here we present two methods for the assembly of collagen mimetic peptides (CMPs). The initial approach prompts assembly of CMPs which contain modifications for metal ion-triggered assembly. Hierarchical assembly into triple helices, followed by formation of disks via hydrophobic interactions has been demonstrated. Metal-ion mediated assembly of these disks, using iron (II)-bipyrdine interactions, has been shown to form micron-sized cages. The nature of the final structures that form depends on the number of bipyridine moieties incorporated into the CMP. These hollow spheres encapsulate a range of molecular weight fluorescently labeled dextrans. Furthermore, they demonstrate a time dependent release of contents under a variety of thermal conditions. The second approach assembles CMPs via the copper-catalyzed alkyne-azide cycloaddition (CuAAC) and the strain-promoted alkyne-azide cycloaddition (SPAAC) reactions. CMPs that incorporate the unnatural amino acids L-propargylglycine and L-azidolysine form triple helices and demonstrate higher order assembly when reacted via CuAAC. Reaction of the alkyne/azide modified CMPs under CuAAC conditions was found to produce an crosslinked 3-dimensional network. Moreover, we demonstrate that polymers, such as, PEG, can be reacted with alkyne and azide CMP triple helices via CuAAC and SPAAC. This designed covalent CMP chemistry allows for high flexibility in integrating various chemical cues, such as cell growth and differentiation within the higher order structures.

  17. Polystyrene or Magnetic Nanoparticles as Support in Enantioselective Organocatalysis? A Case Study in Friedel-Crafts Chemistry.

    PubMed

    Ranjbar, Sara; Riente, Paola; Rodríguez-Escrich, Carles; Yadav, Jagjit; Ramineni, Kishore; Pericàs, Miquel A

    2016-04-01

    Heterogenized versions of the second-generation MacMillan imidazolidin-4-one are described for the first time. This versatile organocatalyst has been supported on 1% DVB Merrifield resin and Fe3O4 magnetic nanoparticles through a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The resulting catalytic materials have been successfully applied to the asymmetric Friedel-Crafts alkylation of indoles with α,β-unsaturated aldehydes. While both catalytic systems can be easily recovered and admit repeated recycling, the polystyrene-based catalyst shows higher stability and provides better stereoselectivities. PMID:27010999

  18. Click-words: learning to predict document keywords from a user perspective

    PubMed Central

    Islamaj Doğan, Rezarta; Lu, Zhiyong

    2010-01-01

    Motivation: Recognizing words that are key to a document is important for ranking relevant scientific documents. Traditionally, important words in a document are either nominated subjectively by authors and indexers or selected objectively by some statistical measures. As an alternative, we propose to use documents' words popularity in user queries to identify click-words, a set of prominent words from the users' perspective. Although they often overlap, click-words differ significantly from other document keywords. Results: We developed a machine learning approach to learn the unique characteristics of click-words. Each word was represented by a set of features that included different types of information, such as semantic type, part of speech tag, term frequency–inverse document frequency (TF–IDF) weight and location in the abstract. We identified the most important features and evaluated our model using 6 months of PubMed click-through logs. Our results suggest that, in addition to carrying high TF–IDF weight, click-words tend to be biomedical entities, to exist in article titles, and to occur repeatedly in article abstracts. Given the abstract and title of a document, we are able to accurately predict the words likely to appear in user queries that lead to document clicks. Contact: luzh@ncbi.nlm.nih.gov Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20810602

  19. Interrelationships between intranarial pressure and biosonar clicks in the bottlenose dolphin (Tursiops truncatus)

    NASA Astrophysics Data System (ADS)

    Elsberry, Wesley R.; Cranford, Ted W.; Ridgway, Sam H.; Carder, Donald A.; Vanbonn, William G.; Blackwood, Diane J.; Carr, Jennifer A.; Evans, William E.

    2002-05-01

    Three Atlantic bottlenose dolphins (Tursiops truncatus) were given a target recognition biosonar task. During their performance of the task, both acoustic data in the far field and pressure within the bony nasal passages were digitally recorded (Elsberry et al., 1999). Analysis of over 15000 biosonar clicks provided new insights into odontocete biosonar sound production and is consistent with acoustic and pressure data taken from white whales (Delphinapterus leucas) during biosonar (Ridgway and Carder, 1988). Our work provides the first evidence for a minimum intranarial pressure during biosonar click production for any odontocete (11.8+/-0.5 kPascals over basal pressure). All three subjects exhibited nearly the same minimum tranarial pressure difference during biosonar click production. Clicks produced at or near this minimum intranarial pressure exhibited a wide range of acoustic power values. The acoustic power of a biosonar click was not highly correlated with intranarial pressure (R2=0.116). The radiated acoustic energy in biosonar clicks ranged from 1 to 1370 microJoules. Estimates of mechanical work during pressurization events were produced using a piston/cylinder model and intranarial volume data from prepared specimens and computed tomography scans. Mechanical work during pressurization events ranged from 2.74 to 23.0 Joules, with an average of 10.3 Joules.

  20. Polysiloxane-Based Autonomic Self-Healing Elastomers Obtained through Dynamic Boronic Ester Bonds Prepared by Thiol-Ene "Click" Chemistry.

    PubMed

    Zuo, Yujing; Gou, Zhiming; Zhang, Changqiao; Feng, Shengyu

    2016-07-01

    Cross-linked silicone elastomers constructed with dynamic-covalent boronic esters are first synthesized by photoinitiated radical thiol-ene "click" chemistry. The resultant samples can be cut with a sharp knife into two pieces and then healed via the reversibility of the boronic ester cross-linkages to restore the original silicone sample within 30 min. Regulation of luminescent properties is achieved by incorporating organic dye into the elastomers through a "one-pot" thiol-ene reaction. The proposed synthesis procedure demonstrates a new strategy to produce boronic acid silicone materials capable of self-healing without external forces. PMID:27159536

  1. Synthesis of 1,2,3-triazol-1-yl-methaneboronic acids via click chemistry: an easy access to a new potential scaffold for protease inhibitors

    PubMed Central

    Romagnoli, Chiara; Caselli, Emilia; Prati, Fabio

    2015-01-01

    Stereoselective synthesis of previously unreported 1,2,3-triazol-1-yl-methaneboronic acids has been achieved from azidomethaneboronates by Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC). The proximity of the cycloaddition reaction center to the boronic group is not detrimental for the stability of the sp3-carbon-boron bond nor to the stereoisomeric composition, further expanding the field of application of click chemistry to new boronate substrates and offering a new potential scaffold for protease inhibitors. PMID:26257579

  2. Copper-Catalyzed Azide–Alkyne Click Chemistry for Bioconjugation

    PubMed Central

    Presolski, Stanislav I.; Hong, Vu Phong; Finn, M.G.

    2012-01-01

    The copper-catalyzed azide-alkyne cycloaddition reaction is widely used for the connection of molecular entities of all sizes. A protocol is provided here for the process with biomolecules. Ascorbate is used as reducing agent to maintain the required cuprous oxidation state. Since these convenient conditions produce reactive oxygen species, five equivalents of a copper-binding ligand is used with respect to metal. The ligand both accelerates the reaction and serves as a sacrificial reductant, protecting the biomolecules from oxidation. A procedure is also described for testing the efficiency of the reaction under desired conditions for purposes of optimization, before expensive biological reagents are used. PMID:22844652

  3. Thiol-norbornene photo-click hydrogels for tissue engineering applications

    PubMed Central

    Lin, Chien-Chi; Ki, Chang Seok; Shih, Han

    2014-01-01

    Thiol-norbornene (thiol-ene) photo-click hydrogels have emerged as a diverse material system for tissue engineering applications. These hydrogels are cross-linked through light mediated orthogonal reactions between multi-functional norbornene-modified macromers (e.g., poly(ethylene glycol), hyaluronic acid, gelatin) and sulfhydryl-containing linkers (e.g., dithiothreitol, PEG-dithiol, bis-cysteine peptides) using low concentration of photoinitiator. The gelation of thiol-norbornene hydrogels can be initiated by long-wave UV light or visible light without additional co-initiator or co-monomer. The cross-linking and degradation behaviors of thiol-norbornene hydrogels are controlled through material selections, whereas the biophysical and biochemical properties of the gels are easily and independently tuned owing to the orthogonal reactivity between norbornene and thiol moieties. Uniquely, the cross-linking of step-growth thiol-norbornene hydrogels is not oxygen-inhibited, therefore the gelation is much faster and highly cytocompatible compared with chain-growth polymerized hydrogels using similar gelation conditions. These hydrogels have been prepared as tunable substrates for 2D cell culture, as microgels or bulk gels for affinity-based or protease-sensitive drug delivery, and as scaffolds for 3D cell culture. Reports from different laboratories have demonstrated the broad utility of thiol-norbornene hydrogels in tissue engineering and regenerative medicine applications, including valvular and vascular tissue engineering, liver and pancreas-related tissue engineering, neural regeneration, musculoskeletal (bone and cartilage) tissue regeneration, stem cell culture and differentiation, as well as cancer cell biology. This article provides an up-to-date overview on thiol-norbornene hydrogel cross-linking and degradation mechanisms, tunable material properties, as well as the use of thiol-norbornene hydrogels in drug delivery and tissue engineering applications. PMID

  4. Investigating Biochemical and Developmental Dependencies of Lignification with a Click-Compatible Monolignol Analog in Arabidopsis thaliana Stems

    PubMed Central

    Pandey, Jyotsna L.; Kiemle, Sarah N.; Richard, Tom L.; Zhu, Yimin; Cosgrove, Daniel J.; Anderson, Charles T.

    2016-01-01

    Lignin is a key structural component of plant cell walls that provides rigidity, strength, and resistance against microbial attacks. This hydrophobic polymer also serves a crucial role in water transport. Despite its abundance and essential functions, several aspects of lignin biosynthesis and deposition remain cryptic. Lignin precursors are known to be synthesized in the cytoplasm by complex biosynthetic pathways, after which they are transported to the apoplastic space, where they are polymerized via free radical coupling reactions into polymeric lignin. However, the lignin deposition process and the factors controlling it are unclear. In this study, the biochemical and developmental dependencies of lignification were investigated using a click-compatible monolignol analog, 3-O-propargylcaffeyl alcohol (3-OPC), which can incorporate into both in vitro polymerized lignin and Arabidopsis thaliana tissues. Fluorescence labeling of 3-OPC using click chemistry followed by confocal fluorescence microscopy enabled the detection and imaging of 3-OPC incorporation patterns. These patterns were consistent with endogenous lignification observed in different developmental stages of Arabidopsis stems. However, the concentration of supplied monolignols influenced where lignification occurred at the subcellular level, with low concentrations being deposited in cell corners and middle lamellae and high concentrations also being deposited in secondary walls. Experimental inhibition of multiple lignification factors confirmed that 3-OPC incorporation proceeds via a free radical coupling mechanism involving peroxidases/laccases and reactive oxygen species (ROS). Finally, the presence of peroxide-producing enzymes determined which cell walls lignified: adding exogenous peroxide and peroxidase caused cells that do not naturally lignify in Arabidopsis stems to lignify. In summary, 3-OPC accurately mimics natural lignification patterns in different developmental stages of Arabidopsis

  5. Bottlenose dolphin (Tursiops truncatus) detection of simulated echoes from normal and time-reversed clicks.

    PubMed

    Finneran, James J; Wu, Teri; Borror, Nancy; Tormey, Megan; Brewer, Arial; Black, Amy; Bakhtiari, Kimberly

    2013-12-01

    In matched filter processing, a stored template of the emitted sonar pulse is compared to echoes to locate individual replicas of the emitted pulse embedded in the echo stream. A number of experiments with bats have suggested that bats utilize matched filter processing for target ranging, but not for target detection. For dolphins, the few available data suggest that dolphins do not utilize matched filter processing. In this study, the effect of time-reversing a dolphin's emitted click was investigated. If the dolphin relied upon matched filter processing, time-reversal of the click would be expected to reduce the correlation between the (unaltered) click and the echoes and therefore lower detection performance. Two bottlenose dolphins were trained to perform a phantom echo detection task. On a small percentage of trials ("probe trials"), a dolphin's emitted click was time-reversed before interacting with the phantom echo system. Data from the normal and time-reversed trials were then analyzed and compared. There were no significant differences in detection performance or click emissions between the normal and time-reversed conditions for either subject, suggesting that the dolphins did not utilize matched filter processing for this echo detection task. PMID:25669264

  6. Iterated intracochlear reflection shapes the envelopes of basilar-membrane click responses.

    PubMed

    Shera, Christopher A

    2015-12-01

    Multiple internal reflection of cochlear traveling waves has been argued to provide a plausible explanation for the waxing and waning and other temporal structures often exhibited by the envelopes of basilar-membrane (BM) and auditory-nerve responses to acoustic clicks. However, a recent theoretical analysis of a BM click response measured in chinchilla concludes that the waveform cannot have arisen via any equal, repetitive process, such as iterated intracochlear reflection [Wit and Bell (2015), J. Acoust. Soc. Am. 138, 94-96]. Reanalysis of the waveform contradicts this conclusion. The measured BM click response is used to derive the frequency-domain transfer function characterizing every iteration of the loop. The selfsame transfer function that yields waxing and waning of the BM click response also captures the spectral features of ear-canal stimulus-frequency otoacoustic emissions measured in the same animal, consistent with the predictions of multiple internal reflection. Small shifts in transfer-function phase simulate results at different measurement locations and reproduce the heterogeneity of BM click response envelopes observed experimentally. PMID:26723327

  7. A Study of Functional Polymer Colloids Prepared Using Thiol-Ene/Yne Click Chemistry

    NASA Astrophysics Data System (ADS)

    Durham, Olivia Z.

    This project demonstrates the first instance of thiol-ene chemistry as the polymerization method for the production of polymer colloids in two-phase heterogeneous suspensions, miniemulsions, and emulsions. This work was also expanded to thiol-yne chemistry for the production of polymer particles containing increased crosslinking density. The utility of thiol-ene and thiol-yne chemistries for polymerization and polymer modification is well established in bulk systems. These reactions are considered 'click' reactions, which can be defined as processes that are both facile and simple, offering high yields with nearly 100% conversion, no side products, easy product separation, compatibility with a diverse variety of commercially available starting materials, and orthogonality with other chemistries. In addition, thiol-ene and thiol-yne chemistry follow a step-growth mechanism for the development of highly uniform polymer networks, where polymer growth is dependent on the coupling of functional groups. These step-growth polymerization systems are in stark contrast to the chain-growth mechanisms of acrylic and styrenic monomers that have dominated the field of conventional heterogeneous polymerizations. Preliminary studies evaluated the mechanism of particle production in suspension and miniemulsion systems. Monomer droplets were compared to the final polymer particles to confirm that particle growth occurred through the polymerization of monomer droplets. Additional parameters examined include homogenization energy (mechanical mixing), diluent species and concentration, and monomer content. These reactions were conducted using photoinitiation to yield particles in a matter of minutes with diameters in the size range of several microns to hundreds of microns in suspensions or submicron particles in miniemulsions. Improved control over the particle size and size distribution was examined through variation of reaction parameters. In addition, a method of seeded suspension

  8. A Study of Functional Polymer Colloids Prepared Using Thiol-Ene/Yne Click Chemistry

    NASA Astrophysics Data System (ADS)

    Durham, Olivia Z.

    This project demonstrates the first instance of thiol-ene chemistry as the polymerization method for the production of polymer colloids in two-phase heterogeneous suspensions, miniemulsions, and emulsions. This work was also expanded to thiol-yne chemistry for the production of polymer particles containing increased crosslinking density. The utility of thiol-ene and thiol-yne chemistries for polymerization and polymer modification is well established in bulk systems. These reactions are considered 'click' reactions, which can be defined as processes that are both facile and simple, offering high yields with nearly 100% conversion, no side products, easy product separation, compatibility with a diverse variety of commercially available starting materials, and orthogonality with other chemistries. In addition, thiol-ene and thiol-yne chemistry follow a step-growth mechanism for the development of highly uniform polymer networks, where polymer growth is dependent on the coupling of functional groups. These step-growth polymerization systems are in stark contrast to the chain-growth mechanisms of acrylic and styrenic monomers that have dominated the field of conventional heterogeneous polymerizations. Preliminary studies evaluated the mechanism of particle production in suspension and miniemulsion systems. Monomer droplets were compared to the final polymer particles to confirm that particle growth occurred through the polymerization of monomer droplets. Additional parameters examined include homogenization energy (mechanical mixing), diluent species and concentration, and monomer content. These reactions were conducted using photoinitiation to yield particles in a matter of minutes with diameters in the size range of several microns to hundreds of microns in suspensions or submicron particles in miniemulsions. Improved control over the particle size and size distribution was examined through variation of reaction parameters. In addition, a method of seeded suspension

  9. Neglect of bandwidth of Odontocetes echo location clicks biases propagation loss and single hydrophone population estimates.

    PubMed

    Ainslie, Michael A

    2013-11-01

    Passive acoustic monitoring with a single hydrophone has been suggested as a cost-effective method to monitor population density of echolocating marine mammals, by estimating the distance at which the hydrophone is able to intercept the echolocation clicks and distinguish these from the background. To avoid a bias in the estimated population density, this method relies on an unbiased estimate of the detection range and therefore of the propagation loss (PL). When applying this method, it is common practice to estimate PL at the center frequency of a broadband echolocation click and to assume this narrowband PL applies also to the broadband click. For a typical situation this narrowband approximation overestimates PL, underestimates the detection range and consequently overestimates the population density by an amount that for fixed center frequency increases with increasing pulse bandwidth and sonar figure of merit. PMID:24180761

  10. Synthesis and characterization of photoluminescent hybrids of poly( ɛ-caprolactone)-grafted-polyhedral oligosilsesquioxane by using a combination of ring-opening polymerization and click chemistry

    NASA Astrophysics Data System (ADS)

    Cao, Xuan Thang; Showkat, Ali Md; Bach, Long Giang; Jeong, Yeon Tae; Kim, Jong Soo; Lim, Kwon Taek; Gal, Yeong-Soon

    2015-01-01

    Photoluminescent hybrids of poly( ɛ-caprolactone) (PCL), polyhedral oligosilsesquioxane (POSS) and terbium ions (Tb3+) were synthesized by using a combination of ring-opening polymerization (ROP), click chemistry and coordination chemistry. Initially, acetylene functionalized PCL (alkyne-PCL-COOH) was prepared by using ROP of ɛ-caprolactone with propargyl alcohol, and azide-substituted POSS (POSS-N3) was prepared by using the reaction of chloropropyl-heptaisobutyl-substituted POSS with NaN3. The click reaction between alkyne-PCL-COOH and POSS-N3 afforded POSS-g-PCL, which was subsequently coordinated with Tb3+ ions in the presence of 1,10-phenanthroline to produce POSS-g-PCL-Tb3+-Phen. The structures and compositions of the hybrids were investigated by using 1H nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), Field emission scanning electron microscope (FE-SEM), Transmission electron microscopy (TEM), and Thermogravimetric analysis (TGA). The optical properties of POSS-g-PCL-Tb3+-Phen complexes were characterized by using photoluminescence spectroscopy, which showed four high emission bands centered at 489, 545, 584, and 620 nm with excitation at 330 nm. The emission spectra of the europium-ion-coordinated hybrids, POSS-g-PCL-Eu3+-Phen, had four high-intensity peaks, 594, 617, 652 and 686 nm, for an excitation wavelength of 352 nm.

  11. Layer-by-layer assembly of graphene oxide on polypropylene macroporous membranes via click chemistry to improve antibacterial and antifouling performance

    NASA Astrophysics Data System (ADS)

    Zhang, Zhen-Bei; Wu, Jing-Jing; Su, Yu; Zhou, Jin; Gao, Yong; Yu, Hai-Yin; Gu, Jia-Shan

    2015-03-01

    Polypropylene is an extensively used membrane material; yet, polypropylene membranes exhibit extremely poor resistance to protein fouling. To ameliorate this issue, graphene oxide (GO) nanosheets were used to modify macroporous polypropylene membrane (MPPM) via layer-by-layer assembly technique through click reaction. First, alkyne-terminated GO was prepared through esterification between carboxyl groups in GO and amide groups in propargylamine; azide-terminated GO was synthesized by the ring-opening reaction of epoxy groups in GO with sodium azide. Second, GO was introduced to the membrane by click chemistry. Characterizations of infrared spectra and X-ray photoelectron spectroscopy confirmed the modification. The sharply decreasing of static water contact angle indicated the improvement of the surface hydrophilicity for GO modified membrane. Introducing GO to the membrane results in a dramatic increase of water flux, improvements in the antifouling characteristics and antibacterial property for the membranes. The pure water flux through the 5-layered GO modified membrane is 1.82 times that through the unmodified one. The water flux restores to 43.0% for the unmodified membrane while to 79.8% for the modified membrane. The relative flux reduction decreases by 32.1% due to GO modification. The antibacterial property was also enhanced by two-thirds. These results demonstrate that the antifouling and antibacterial characteristics can be raised by tethering GO to the membrane surface.

  12. Palladium Nanoparticles Embedded in a Layer-by-Layer Nanoreactor Built with Poly(Acrylic Acid) Using "Electro-Click Chemistry".

    PubMed

    Villalba, Matias; Bossi, Mariano; Pozo, Maria Del; Calvo, Ernesto J

    2016-07-12

    Palladium nanoparticles (Pd NPs) were formed by electrochemical reduction of Pd(NH3)4(3+) ions entrapped by ion exchange in poly(acrylic acid) (PAA) multilayer films grown by the Sharpless "click reaction." The alkyne (PAAalk) and azide (PAAaz) groups were covalently bound to the PAA, and the catalyzed buildup of the multilayer film was performed by electrochemical reduction of Cu(2+) to Cu(+). The size of the Pd NPs formed in Au/(PAAalk)3(PAAaz)2 multilayer films by the click reaction, that is, 50 nm, is larger than that of similar Pd NPs formed in electrostatically bound Au/(PAA)3(PAH)2 nanoreactors, that is, 6-9 nm, under similar conditions. A combination of electrochemical methods and electrochemical quartz crystal microbalance, polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS), ellipsometry, and scanning electron microscopy has been used to follow these processes. Cyclic voltammetry of the resulting Pd NPs in a 0.1 M H2SO4 solution at 0.1 V·s(-1) shows the PdO reduction peak at the same potential as that on the clean Pd surface unlike the NPs formed in electrostatically self-assembled Au/(PAA)3(PAH)2 nanoreactors with a 0.2 V shift in the cathodic direction most probably because of the strong adsorption of amino groups on the Pd NP surfaces. PMID:27308840

  13. Azide Tripodal Dendrons from Behera's Amine and Their Clicked Dendrimers.

    PubMed

    Barmare, Farhana; Abadjian, Marie-Caline Z; Wiener, Erik C; Grotjahn, Douglas B

    2016-08-01

    Diazo transfer reactions on Behera's amine and its next-generation analogue formed G0 and G1 azide dendrons bearing three and nine tert-butyl-protected esters, respectively. The utility of the new dendrons was demonstrated by copper-catalyzed azide-alkyne cycloaddition, with 1,3,5-triethynylbenzene, forming two novel dendrimers in a convergent manner. Acid-mediated dendrimer deprotection was successful, and the resulting carboxy-terminated dendrimers were analyzed by NMR and DOSY experiments. PMID:27454340

  14. OSU-6: A Highly Efficient, Metal-Free, Heterogeneous Catalyst for the Click Synthesis of 5-Benzyl and 5-Aryl-1H-tetrazoles.

    PubMed

    Nammalwar, Baskar; Muddala, Nagendra Prasad; Pitchimani, Rajasekar; Bunce, Richard A

    2015-01-01

    OSU-6, an MCM-41 type hexagonal mesoporous silica with mild Brönsted acid properties, has been used as an efficient, metal-free, heterogeneous catalyst for the click synthesis of 5-benzyl and 5-aryl-1H-tetrazoles from nitriles in DMF at 90 °C. This catalyst offers advantages including ease of operation, milder conditions, high yields, and reusability. Studies are presented that demonstrate the robust nature of the catalyst under the optimized reaction conditions. OSU-6 promotes the 1,3-dipolar addition of azides to nitriles without significant degradation or clogging of the nanoporous structure. The catalyst can be reused up to five times without a significant reduction in yield, and it does not require treatment with acid between reactions. PMID:26703538

  15. Interaction of BODIPY dyes with bovine serum albumin: a case study on the aggregation of a click-BODIPY dye.

    PubMed

    Jameson, Laramie P; Smith, Nicholas W; Annunziata, Onofrio; Dzyuba, Sergei V

    2016-06-01

    The fluorescence of BODIPY and click-BODIPY dyes was found to substantially increase in the presence of bovine serum albumin (BSA). BSA acted as a solubilizer for dye aggregates, in addition to being a conventional binding scaffold for the click-BODIPY dyes, indicating that disaggregation of fluorophores should be considered when evaluating dye-protein interactions. PMID:27173791

  16. The function of male sperm whale slow clicks in a high latitude habitat: communication, echolocation, or prey debilitation?

    PubMed

    Oliveira, Cláudia; Wahlberg, Magnus; Johnson, Mark; Miller, Patrick J O; Madsen, Peter T

    2013-05-01

    Sperm whales produce different click types for echolocation and communication. Usual clicks and buzzes appear to be used primarily in foraging while codas are thought to function in social communication. The function of slow clicks is less clear, but they appear to be produced by males at higher latitudes, where they primarily forage solitarily, and on the breeding grounds, where they roam between groups of females. Here the behavioral context in which these vocalizations are produced and the function they may serve was investigated. Ninety-nine hours of acoustic and diving data were analyzed from sound recording tags on six male sperm whales in Northern Norway. The 755 slow clicks detected were produced by tagged animals at the surface (52%), ascending from a dive (37%), and during the bottom phase (11%), but never during the descent. Slow clicks were not associated with the production of buzzes, other echolocation clicks, or fast maneuvering that would indicate foraging. Some slow clicks were emitted in seemingly repetitive temporal patterns supporting the hypothesis that the function for slow clicks on the feeding grounds is long range communication between males, possibly relaying information about individual identity or behavioral states. PMID:23654416

  17. Semiconducting organic-inorganic nanocomposites by intimately tethering conjugated polymers to inorganic tetrapods.

    PubMed

    Jung, Jaehan; Yoon, Young Jun; Lin, Zhiqun

    2016-04-28

    Semiconducting organic-inorganic nanocomposites were judiciously crafted by placing conjugated polymers in intimate contact with inorganic tetrapods via click reaction. CdSe tetrapods were first synthesized by inducing elongated arms from CdSe zincblende seeds through seed-mediated growth. The subsequent effective inorganic ligand treatment, followed by reacting with short bifunctional ligands, yielded azide-functionalized CdSe tetrapods (i.e., CdSe-N3). Finally, the ethynyl-terminated conjugated polymer poly(3-hexylthiophene) (i.e., P3HT-[triple bond, length as m-dash]) was tethered to CdSe-N3 tetrapods via a catalyst-free alkyne-azide cycloaddition, forming intimate semiconducting P3HT-CdSe tetrapod nanocomposites. Intriguingly, the intimate contact between P3HT and CdSe tetrapod was found to not only render the effective dispersion of CdSe tetrapods in the P3HT matrix, but also facilitate the efficient electronic interaction between these two semiconducting constituents. The successful anchoring of P3HT chains onto CdSe tetrapods was substantiated through Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy measurements. Moreover, the absorption and photoluminescence studies further corroborated the intimate tethering between P3HT and CdSe tetrapods. The effect of the type of bifunctional ligands (i.e., aryl vs. aliphatic ligands) and the size of tetrapods on the device performance of hybrid organic-inorganic solar cells was also scrutinized. Interestingly, P3HT-CdSe tetrapod nanocomposites produced via the use of an aryl bifunctional ligand (i.e., 4-azidobenzoic acid) exhibited an improved photovoltaic performance compared to that synthesized with their aliphatic ligand counterpart (i.e., 5-bromovaleric acid). Clearly, the optimal size of CdSe tetrapods ensuring the effective charge transport in conjunction with the good dispersion of CdSe tetrapods rendered an improved device performance. We envision that the click-reaction

  18. Number and duration of echolocation click trains produced by a harbor porpoise (Phocoena phocoena) in relation to target and performance.

    PubMed

    Kastelein, Ronald A; Verlaan, Mariska; Jennings, Nancy

    2008-07-01

    Echolocation effort (number and duration of echolocation click trains produced) by a harbor porpoise is described in relation to target presence, strength and distance, and performance of the detection task. The porpoise was presented with two target sizes at five distances (12-20 m), or no target, and had to indicate whether it could detect the target. Small, distant targets required long and multiple click trains. Multiple click trains mostly occurred when the small target was far away and not detected, and during target-absent trials in which the animal correctly responded. In target-absent trials, an incorrect response was linked to short click trains. Click train duration probably increased until the animal's certainty about the target's presence or absence exceeded a certain level, after which the porpoise responded. PMID:18646952

  19. Brick & Click Libraries: An Academic Library Conference (14th, Maryville, Missouri, November 7, 2014)

    ERIC Educational Resources Information Center

    Baudino, Frank, Ed.; Johnson, Carolyn, Ed.

    2014-01-01

    Eighteen scholarly papers and twelve abstracts comprise the content of the fourteenth annual Brick and Click Libraries Symposium, held annually at Northwest Missouri State University in Maryville, Missouri. The proceedings, authored by academic librarians and presented at the symposium, portray the contemporary and future face of librarianship.…

  20. "Just Clicks": An Interpretive Phenomenological Analysis of Professional Dancers' Experience of Flow

    ERIC Educational Resources Information Center

    Hefferon, Kate M.; Ollis, Stewart

    2006-01-01

    The subjective experience of flow in professional dancers was analyzed using interpretive phenomenological analysis (IPA). Flow is believed to be a psychological state in which the mind and body "just click", creating optimal performance. Unfortunately, sport and performance research have severely neglected reviewing the flow experience in…

  1. Brick and Click Libraries: An Academic Library Symposium (12th, Maryville, Missouri, October 26, 2012)

    ERIC Educational Resources Information Center

    Baudino, Frank, Ed.; Johnson, Carolyn, Ed.

    2012-01-01

    Twenty scholarly papers and fifteen abstracts comprise the content of the twelfth annual Brick and Click Libraries Symposium, held at Northwest Missouri State University in Maryville, Missouri. The peer-reviewed proceedings, authored by academic librarians and presented at the symposium, portray the contemporary and future face of librarianship.…

  2. Brick & Click Libraries: An Academic Library Symposium (13th, Maryville, Missouri, November 1, 2013)

    ERIC Educational Resources Information Center

    Baudino, Frank, Ed.; Johnson, Carolyn, Ed.; Park, Sarag G., Ed.

    2013-01-01

    Twenty-six scholarly papers and ten abstracts comprise the content of the thirteenth annual Brick and Click Libraries Symposium, held annually at Northwest Missouri State University in Maryville, Missouri. The proceedings, authored by academic librarians and presented at the symposium, portray the contemporary and future face of librarianship. The…

  3. Echolocation clicks of free-ranging Cuvier's beaked whales (Ziphius cavirostris).

    PubMed

    Zimmer, Walter M X; Johnson, Mark P; Madsen, Peter T; Tyack, Peter L

    2005-06-01

    Strandings of beaked whales of the genera Ziphius and Mesoplodon have been reported to occur in conjunction with naval sonar use. Detection of the sounds from these elusive whales could reduce the risk of exposure, but descriptions of their vocalizations are at best incomplete. This paper reports quantitative characteristics of clicks from deep-diving Cuvier's beaked whales (Ziphius cavirostris) using a unique data set. Two whales in the Ligurian Sea were simultaneously tagged with sound and orientation recording tags, and the dive tracks were reconstructed allowing for derivation of the range and relative aspect between the clicking whales. At depth, the whales produced trains of regular echolocation clicks with mean interclick intervals of 0.43 s (+/- 0.09) and 0.40 s (+/- 0.07). The clicks are frequency modulated pulses with durations of approximately 200 micros and center frequencies around 42 kHz, -10 dB bandwidths of 22 kHz, and Q(3 dB) of 4. The sound beam is narrow with an estimated directionality index of more than 25 dB, source levels up to 214 dB(pp) re: 1 microPa at 1 m, and energy flux density of 164 dB re: 1 microPa2 s. As the spectral and temporal properties are different from those of nonziphiid odontocetes the potential for passive detection is enhanced. PMID:16018493

  4. Brick and Click Libraries: Proceedings of an Academic Library Symposium (Maryville, Missouri, October 22, 2004)

    ERIC Educational Resources Information Center

    Baudino, Frank, Ed.; Mardis, Lori, Ed.; Park, Sarah G., Ed.; Ury, Connie J., Ed.

    2004-01-01

    The Brick & Click Libraries Symposium is a one-day conference that focuses on providing library resources and services for students who are either on-campus learners or off-campus learners. It is sponsored by Northwest Missouri State University in order to offer academic librarians a forum for sharing practical information. The subjects and…

  5. High-frequency click-evoked otoacoustic emissions and behavioral thresholds in humans1

    PubMed Central

    Goodman, Shawn S.; Fitzpatrick, Denis F.; Ellison, John C.; Jesteadt, Walt; Keefe, Douglas H.

    2009-01-01

    Relationships between click-evoked otoacoustic emissions (CEOAEs) and behavioral thresholds have not been explored above 5 kHz due to limitations in CEOAE measurement procedures. New techniques were used to measure behavioral thresholds and CEOAEs up to 16 kHz. A long cylindrical tube of 8 mm diameter, serving as a reflectionless termination, was used to calibrate audiometric stimuli and design a wideband CEOAE stimulus. A second click was presented 15 dB above a probe click level that varied over a 44 dB range, and a nonlinear residual procedure extracted a CEOAE from these click responses. In some subjects (age 14–29 years) with normal hearing up to 8 kHz, CEOAE spectral energy and latency were measured up to 16 kHz. Audiometric thresholds were measured using an adaptive yes-no procedure. Comparison of CEOAE and behavioral thresholds suggested a clinical potential of using CEOAEs to screen for high-frequency hearing loss. CEOAE latencies determined from the peak of averaged, filtered temporal envelopes decreased to 1 ms with increasing frequency up to 16 kHz. Individual CEOAE envelopes included both compressively growing longer-delay components consistent with a coherent-reflection source and linearly or expansively growing shorter-delay components consistent with a distortion source. Envelope delays of both components were approximately invariant with level. PMID:19206876

  6. The Jonker-Volgenant algorithm applied to click-train separation.

    PubMed

    Baggenstoss, Paul M

    2014-05-01

    The problem of click-train separation is cast as a linear assignment problem to obtain a faster solution guaranteed to achieve the global minimum error. It is shown how the problem can be cast in a compact matrix form that is solvable by an off-the-shelf algorithm, the Jonker-Volgenant algorithm. PMID:24815231

  7. Localization of click trains and speech by cats: the negative level effect.

    PubMed

    Gai, Yan; Ruhland, Janet L; Yin, Tom C T

    2014-10-01

    Although localization of sound in elevation is believed to depend on spectral cues, it has been shown with human listeners that the temporal features of sound can also greatly affect localization performance. Of particular interest is a phenomenon known as the negative level effect, which describes the deterioration of localization ability in elevation with increasing sound level and is observed only with impulsive or short-duration sound. The present study uses the gaze positions of domestic cats as measures of perceived locations of sound targets varying in azimuth and elevation. The effects of sound level on localization in terms of accuracy, precision, and response latency were tested for sound with different temporal features, such as a click train, a single click, a continuous sound that had the same frequency spectrum of the click train, and speech segments. In agreement with previous human studies, negative level effects were only observed with click-like stimuli and only in elevation. In fact, localization of speech sounds in elevation benefited significantly when the sound level increased. Our findings indicate that the temporal continuity of a sound can affect the frequency analysis performed by the auditory system, and the variation in the frequency spectrum contained in speech sound does not interfere much with the spectral coding for its location in elevation. PMID:24942705

  8. Brick & Click Libraries: An Academic Library Conference (15th, Maryville, Missouri, November 6, 2015)

    ERIC Educational Resources Information Center

    Baudino, Frank, Ed.; Johnson, Carolyn, Ed.

    2015-01-01

    Nineteen scholarly papers and seventeen abstracts comprise the content of the fifteenth annual Brick and Click Libraries Conference, held annually at Northwest Missouri State University in Maryville, Missouri. The proceedings, authored by academic librarians and presented at the symposium, portray the contemporary and future face of librarianship.…

  9. A `Clicked' Tetrameric Hydroxamic Acid Glycopeptidomimetic Antagonizes Sugar-Lectin Interactions On The Cellular Level

    NASA Astrophysics Data System (ADS)

    Zhang, Hai-Lin; Zang, Yi; Xie, Juan; Li, Jia; Chen, Guo-Rong; He, Xiao-Peng; Tian, He

    2014-07-01

    A tetrameric N-acetyl galactosaminyl (GalNAc) peptidomimetic was constructed by N-acetylation of repeating proline-based hydroxamic acid units, followed by a convergent `click chemistry' coupling. This novel glycopeptidomimetic was determined to effectively antagonize the interaction between a transmembrane hepatic lectin and GalNAc on the cellular level.

  10. Extraction of pulse repetition intervals from sperm whale click trains for ocean acoustic data mining.

    PubMed

    Zaugg, Serge; van der Schaar, Mike; Houégnigan, Ludwig; André, Michel

    2013-02-01

    The analysis of acoustic data from the ocean is a valuable tool to study free ranging cetaceans and anthropogenic noise. Due to the typically large volume of acquired data, there is a demand for automated analysis techniques. Many cetaceans produce acoustic pulses (echolocation clicks) with a pulse repetition interval (PRI) remaining nearly constant over several pulses. Analyzing these pulse trains is challenging because they are often interleaved. This article presents an algorithm that estimates a pulse's PRI with respect to neighboring pulses. It includes a deinterleaving step that operates via a spectral dissimilarity metric. The sperm whale (SW) produces trains with PRIs between 0.5 and 2 s. As a validation, the algorithm was used for the PRI-based identification of SW click trains with data from the NEMO-ONDE observatory that contained other pulsed sounds, mainly from ship propellers. Separation of files containing SW clicks with a medium and high signal to noise ratio from files containing other pulsed sounds gave an area under the receiver operating characteristic curve value of 0.96. This study demonstrates that PRI can be used for the automated identification of SW clicks and that deinterleaving via spectral dissimilarity contributes to algorithm performance. PMID:23363108

  11. Synthesis of double-clickable functionalised graphene oxide for biological applications† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5cc05412e Click here for additional data file.

    PubMed Central

    Mei, Kuo-Ching; Rubio, Noelia; Costa, Pedro M.; Kafa, Houmam; Abbate, Vincenzo; Festy, Frederic; Bansal, Sukhvinder S.; Hider, Robert C.

    2015-01-01

    Azide- and alkyne-double functionalised graphene oxide (Click2 GO) was synthesised and characterised with attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), thermogravimetric analysis (TGA) and Raman spectroscopy. Fourteen-percentage increase in azide content was found, after pre-treatment of GO with meta-chloroperoxybenzoic acid (mCPBA), determined with elemental analysis. No effect on A549 cell viability was found, up to 100 μg mL–1 and 72 h of incubation, determined with the modified lactate dehydrogenase (mLDH) assay. Two sequential copper(i) catalysed azide–alkyne cycloaddition (CuAAC) reactions were performed to conjugate the propargyl-modified blood–brain barrier targeting peptide Angiopep-2, and a bis-azide polyethylene glycol (M W = 3500), to the Click2 GO. The final conjugate was characterised with ATR-FTIR and TGA. PMID:26295072

  12. Lateralization of High-Frequency Clicks Based on Interaural Time: Additivity of Information across Frequency

    NASA Astrophysics Data System (ADS)

    Wenzel, Elizabeth Marie

    Lateralization performance based on interaural differences of time (IDTs) was measured for trains of Gaussian clicks which varied in spectral content. In the first experiment, thresholds ((DELTA)IDTs) were measured as a function of the number of clicks in the train (n = 1 to 32), the interclick interval (ICI = 2.5 or 5 ms), and the spectral content (1 vs. 2 or 4 carriers). Subjects' performance was compared to perfect statistical summation which predicts slopes of -.50 when log-(DELTA)IDT vs. long -n is plotted. The results showed that increasing the spectral content of the clicks decreased the intercepts of the log -log functions (decreased thresholds) while having little effect on their slopes. Shortening the ICIs caused the slopes of the functions to decrease in absolute value. To estimate the bandwidth of frequency-interaction in lateralization, d's were measured for clicks with constant IDTs (n = 1) with a fixed carrier (FF = 4000, 5200, 6000 or 7200 Hz), both alone and combined with a second click whose carrier (F) varied from 3500 to 8500 Hz. Performance in combined conditions was compared to independent summation of the information carried by the two frequency-bands. Performance improved as the separation between F and FF increased until the level predicted by independence was reached. The final experiment investigated the interaction of frequency content with IDT. d's were measured as a function of the IDT in clicks with carriers of 5200, 6000 or 7200 Hz, both alone and combined with a 4000-Hz click with a fixed IDT. Performance in combined conditions was again compared to independent additivity. The improvement with frequency was explained by an increase in the number of samples of the IDT reaching the binaural centers due to spread of excitation along the basilar membrane. Less than independent summation was explained by correlation between overlapping bands which reduced the amount of information exciting independent channels. The data also suggest that

  13. Single "click" synthesis of a mixed-mode silica sorbent and application in matrix solid-phase dispersion extraction of β-agonists from porcine liver.

    PubMed

    Zhu, Yuling; Yang, Siwen; Chen, Gang; Xing, Jun

    2014-08-01

    A single "click" strategy is proposed for the preparation of a reversed-phase/weak cation-exchange mixed-mode silica-based sorbent (silica-WCX). Upon this strategy, both 1-dodecyne and 5-hexynoic acid were simultaneously immobilized onto azide-silica in varied ratio via Cu (I)-catalyzed azide-alkyne cycloaddition click reaction. The chemical compositions of silica-WCXs were characterized by elemental analysis, acid-base titration and Fourier transform-infrared spectroscopy. The results indicated that the actual mole ratio of n-dodecyl to carboxylic group on the sorbent is almost the same as the reactant ratio of 1-dodecyne to 5-hexynoic acid, and the repeatability of synthesis method is good. After that, two β-agonists, clenbuterol and ractopamine, were selected as model drug residues to evaluate the applicability of silica-WCX in matrix solid-phase dispersion extraction for the determination of basic drug residues in porcine liver by HPLC/UV. In comparison with some commercial sorbents, silica-WCX exhibited higher recoveries and better purification capability. Under the optimized conditions, linearity ranges were between 0.04 and 8.0μg/g for both analytes with coefficients of determination (R(2)) higher than 0.9997. The average recoveries at three spiked levels ranged from 92.5% to 105.0% with RSDs less than 6.6%. PMID:24929910

  14. Integration of Bioorthogonal Probes and Q-FRET for the Detection of Histone Acetyltransferase Activity.

    PubMed

    Han, Zhen; Luan, Yepeng; Zheng, Yujun George

    2015-12-01

    Histone acetyltransferases (HATs) are key players in the epigenetic regulation of gene function. The recent discovery of diverse HAT substrates implies a broad spectrum of cellular functions of HATs. Many pathological processes are also intimately associated with the dysregulation of HAT levels and activities. However, detecting the enzymatic activity of HATs has been challenging, and this has significantly impeded drug discovery. To advance the field, we developed a convenient one-pot, mix-and-read strategy that is capable of directly detecting the acylated histone product through a fluorescent readout. The strategy integrates three technological platforms-bioorthogonal HAT substrate labeling, alkyne-azide click chemistry, and quenching FRET-into one system for effective probing of HAT enzyme activity. PMID:26455821

  15. Spray assembled, cross-linked polyelectrolyte multilayer membranes for salt removal.

    PubMed

    Cho, Kwun Lun; Lomas, Hannah; Hill, Anita J; Caruso, Frank; Kentish, Sandra E

    2014-07-29

    The present study reports the synthesis of spray-coated cross-linked polyelectrolyte multilayer membranes. Membrane cross-linking was performed using alkyne-azide "click" chemistry, where alkyne and azide functional groups were used to modify the poly(acrylic acid) (PAA) and the poly(allylamine) hydrochloride (PAH) polyelectrolytes. The results demonstrate that deposition at lower ionic strength produced smoother and denser membrane structures. Pore size analysis using neutral poly(ethylene glycol) revealed a decrease in the membrane pore size as the degree of cross-linking was increased, resulting in the membrane rejecting divalent CaCl2 at levels of up to 80%, and 50% rejection of monovalent NaCl. When poly(sodium-4-styrenesulfonate) (PSS) was combined with small amounts of cross-linkable PAA, significant flux increases were observed in the multilayer membranes with no observable reduction in ion rejection. PMID:25036367

  16. Asymmetric AB3 Miktoarm Star Polymers: Synthesis, Self-Assembly, and Study of Micelle Stability Using AF4 for Efficient Drug Delivery.

    PubMed

    Moquin, Alexandre; Sharma, Anjali; Cui, Yiming; Lau, Anthony; Maysinger, Dusica; Kakkar, Ashok

    2015-12-01

    A simple and versatile methodology, which employs a combination of ring-opening polymerization and alkyne-azide click chemistry to synthesize amphiphilic AB3 miktoarm stars, is reported. Their aqueous self-assembly behavior was studied using dynamic light scattering, fluorescence, and asymmetrical flow field-flow fractionation (AF4). AB3 miktoarm stars form micelles which incorporate curcumin with high efficiency, and significantly reduce the viability of glioblastoma cells in spheroids. We demonstrate that AF4 is an effective technique to determine the size distribution of self-assembled structures exposed to a biological medium. The ease, with which asymmetric AB3 miktoarm polymers are constructed, provides a platform that can be widely employed to deliver a variety of lipophilic drugs. PMID:26259625

  17. Influence of metallocene substitution on the antibacterial activity of multivalent peptide conjugates.

    PubMed

    Hoffknecht, Barbara C; Prochnow, Pascal; Bandow, Julia E; Metzler-Nolte, Nils

    2016-07-01

    Peptide dendrimers and derivatisation of peptides with metallocenes showed promising results in the search for new antibacterial agents. The two concepts are combined in this work leading to multivalent, metallocene-containing peptide derivates. These new peptides were synthesised utilising microwave assisted, copper(I) catalyzed alkyne-azide cycloaddition (CuAAC, "click" chemistry). Twelve new peptide conjugates, containing either a ferrocenoyl group or a ruthenocenoyl group on so-called ultrashort (i.e. < 5 amino acids) peptides, and ranging from monovalent to trivalent conjugates, were synthesised and their antibacterial activity was investigated by minimal inhibitory concentration (MIC) assays on five different bacterial strains. The antibacterial activity was compared to the same peptide conjugates without metallocenes. The resulting MIC values showed a significant enhancement of the antibacterial activity of these peptide conjugates against Gram-positive bacteria by the metallocenoyl groups. Additionally, the compounds with two metallocenoyl groups presented the best antibacterial activities overall. PMID:26988572

  18. In situ assembly of porous Au-paper electrode and functionalization of magnetic silica nanoparticles with HRP via click chemistry for Microcystin-LR immunoassay.

    PubMed

    Ge, Shenguang; Liu, Weiyan; Ge, Lei; Yan, Mei; Yan, Jixian; Huang, Jiadong; Yu, Jinghua

    2013-11-15

    A simple, low-cost and sensitive origami electrochemical immunoassay-device was developed based on a novel gold nanoparticle modified porous paper working electrode (Au-PWE) for point-of-care testing. Azide-functionalized Au-PWE was prepared by the functionalization of Au-PWE with 1-azidoundecan-11-thiol. Alkyne end-terminated antibody was prepared with 4-pentynoic acid and antibody by the 1-ethyl-3-(3-(dimethylamino) propyl) carbodiimide hydrochloride and N-hydroxysuccinimide activation reaction. Alkyne-antibody was coupled to azido-Au-PWE by click reaction as a recognition element. Nearly monodispersed sphere-like silica-coated ferroferric oxide (Fe3O4@SiO2) nanoparticles were prepared via the reverse microemulsion method. Azide-functionalized Fe3O4@SiO2 was prepared by the functionalization of silica shell with 3-bromopropyltrichlorosilane followed by substitution with sodium azide. Alkyne-functionalized antibody and horse radish peroxidase were coupled to azide-functionalized Fe3O4@SiO2 by click reaction as signal label. Horse radish peroxidase and ferroferric oxide could catalyze the oxidation of thionine in the presence of hydrogen peroxide. After the sandwich immunoreaction, the current was proportional to the logarithm of the Microcystin-LR. The linear regression equation was i(μA)=119.89+46.27 log cMC-LR (μg/mL) in the range from 0.01 to 200 μg/mL. The limit of detection was 0.004 μg/mL. This immunoassay would provide a universal immunoassay method in environmental monitoring and public health. PMID:23728196

  19. Tetrathiafulvalene mono- and bis-1,2,3-triazole precursors by click chemistry: structural diversity and reactivity.

    PubMed

    Biet, Thomas; Avarvari, Narcis

    2014-05-28

    The donor ortho-dimethyl-TTF-(N-n-Bu-1,2,3-triazole) 1,5-isomer has been synthesized by click chemistry following a ruthenium-catalyzed azide-alkyne cycloaddition procedure. The single crystal X-ray analysis showed a planar conformation between the TTF and triazole units and a set of intermolecular interactions at the supramolecular level in the solid state. The same procedure allowed the preparation of the corresponding ortho-dimethyl-TTF-bis(triazole) which was also structurally characterized. Because of the steric hindrance, the triazole units are no longer planar with the TTF backbone. The reactivity of the triazole ring has been investigated in protonation and alkylation reactions, monitored by UV-visible spectroscopy, which clearly showed the red shift of the intramolecular charge transfer band. A TTF-methyl-triazolium salt has been isolated and analyzed by single crystal X-ray analysis. All of the TTF-triazoles and triazolium salts are valuable precursors for radical cation salts due to their oxidation potentials and variety of possible intermolecular interactions. PMID:24682102

  20. Site-specific labeling of RNA by combining genetic alphabet expansion transcription and copper-free click chemistry.

    PubMed

    Someya, Tatsuhiko; Ando, Ami; Kimoto, Michiko; Hirao, Ichiro

    2015-08-18

    Site-specific labeling of long-chain RNAs with desired molecular probes is an imperative technique to facilitate studies of functional RNA molecules. By genetic alphabet expansion using an artificial third base pair, called an unnatural base pair, we present a post-transcriptional modification method for RNA transcripts containing an incorporated azide-linked unnatural base at specific positions, using a copper-free click reaction. The unnatural base pair between 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds) and pyrrole-2-carbaldehyde (Pa) functions in transcription. Thus, we chemically synthesized a triphosphate substrate of 4-(4-azidopentyl)-pyrrole-2-carbaldehyde (N3-PaTP), which can be site-specifically introduced into RNA, opposite Ds in templates by T7 transcription. The N3-Pa incorporated in the transcripts was modified with dibenzocyclooctyne (DIBO) derivatives. We demonstrated the transcription of 17-, 76- and 260-mer RNA molecules and their site-specific labeling with Alexa 488, Alexa 594 and biotin. This method will be useful for preparing RNA molecules labeled with any functional groups of interest, toward in vivo experiments. PMID:26130718

  1. Click labeling of unnatural sugars metabolically incorporated into viral envelope glycoproteins enables visualization of single particle fusion.

    PubMed

    Oum, Yoon Hyeun; Desai, Tanay M; Marin, Mariana; Melikyan, Gregory B

    2016-07-01

    Enveloped viruses infect target cells by fusing their membrane with cellular membrane through a process that is mediated by specialized viral glycoproteins. The inefficient and highly asynchronous nature of viral fusion complicates studies of virus entry on a population level. Single virus imaging in living cells has become an important tool for delineating the entry pathways and for mechanistic studies of viral fusion. We have previously demonstrated that incorporation of fluorescent labels into the viral membrane and trapping fluorescent proteins in the virus interior enables the visualization of single virus fusion in living cells. Here, we implement a new approach to non-invasively label the viral membrane glycoproteins through metabolic incorporation of unnatural sugars followed by click-reaction with organic fluorescent dyes. This approach allows for efficient labeling of diverse viral fusion glycoproteins on the surface of HIV pseudoviruses. Incorporation of a content marker into surface-labeled viral particles enables sensitive detection of single virus fusion with live cells. PMID:27033181

  2. Thiol-ene click chemistry derived cationic cyclodextrin chiral stationary phase and its enhanced separation performance in liquid chromatography.

    PubMed

    Yao, Xiaobin; Tan, Timothy Thatt Yang; Wang, Yong

    2014-01-24

    This work is the first demonstration of a simple thiol-ene click chemistry to anchor vinyl imidazolium β-CD onto thiol silica to form a novel cationic native cyclodextrin (CD) chiral stationary phase (CSP). The CSP afforded high enantioseparation ability towards dansyl (Dns) amino acids, carboxylic aryl compounds and flavonoids in chiral HPLC. The current CSP demonstrates the highest resolving ability (selectivity >1.1, resolution >1.5) towards Dns amino acids in a mobile phase buffered at pH=6.5, with the resolution of Dns-dl-leucine as high as 6.97. 2,4-dichloride propionic acid (2,4-ClPOPA) was well resolved with the selectivity and resolution of 1.37 and 4.88, respectively. Compared to a previously reported native CD-CSP based on a triazole linkage, the current cationic CD-CSP shows a stronger retention and higher resolution towards acidic chiral compounds, ascribed to the propitious strong electrostatic attraction. Stability evaluation results indicated that thiol-ene reaction can provide a facile and robust approach for the preparation of positively charged CD CSPs. PMID:24411138

  3. Facile Synthesis of DendriMac Polymers via the Combination of Living Anionic Polymerization and Highly Efficient Coupling Reactions.

    PubMed

    Ma, Hongwei; Wang, Qiuyun; Sang, Wei; Han, Li; Liu, Pibo; Sheng, Heyu; Wang, Yurong; Li, Yang

    2016-01-01

    Two DendriMac polymers (Dendri-hydr and Dendri-click) are efficiently and conveniently synthesized via the combination of living anionic polymerization (LAP) and hydrosilylation/click chemistry. Based on the end-capping of DPE derivatives (DPE-SiH and DPE-DA) toward polymeric anions, the polymeric core and arms are effectively synthesized, and the base polymers can be regarded as polymeric bricks. Hydrosilylation and click chemistry are used as coupling reactions to construct the DendriMac polymers with high efficiency and convenience. The numbers of branched arms are calculated by SEC as 5.84 and 6.08 for Dendri-hydr and Dendri-click, respectively, which indicate that the DendriMac architectures exhibit high structural integrity. Because of its independence, high efficiency, and convenience, the whole construction can be regarded as the "building of polymeric bricks." PMID:26501193

  4. Three-Dimensional Polypeptide Architectures Through Tandem Catalysis and Click Chemistry

    NASA Astrophysics Data System (ADS)

    Rhodes, Allison Jane

    -defined, high-density brushes for applications in drug delivery and imaging. Here, we also report a method for the synthesis of soluble, well-defined, azido functionalized polypeptides in a straightforward, 3-step synthesis. Homo and diblock azidopolypeptides were prepared with controlled segment lengths via living polymerization using Co(PMe3)4 initiator. Through copper azide alkyne click chemistry (CuAAC) in organic solvent, azidopolypeptides were regioselectively and quantitatively modified with carboxylic acid (pH-responsive), amino acid and sugar functional groups. Finally, the advances towards well-defined hyperbranched polypeptides through alpha-amino-acid-N-thiocarboxyanhydrides (NTAs) will be discussed. Within the past 10 years, controlled NCA (alpha-amino acid-N-carboxyanhydride) ring-opening polymerization (ROP) has emerged, expanding the application of copolypeptide polymers in various drug delivery and tissue engineering motifs. Modification of NCA monomers to the corresponding alpha-amino-acid-N-thiocarboxyanhydride (NTA) will diversify ROP reactions, leading to more complex polypeptides (such as hyperbranched polymers), in addition to the possibility of performing these polymerizations under ambient conditions, which would greatly expand their potential utility. The project focuses on the preparation of hyperbranched polypeptides with well-defined architectures and controlled branching density in a one-pot reaction. This will be accomplished by taking advantage of the different selectivities of Co(PMe3)4 and depeNi(COD) polymerization initiators, and by exploiting the reactivity difference between NCA and the more stable NTA monomers.

  5. Assessing the Delivery of Molecules to the Mitochondrial Matrix Using Click Chemistry.

    PubMed

    Hoogewijs, Kurt; James, Andrew M; Smith, Robin A J; Gait, Michael J; Murphy, Michael P; Lightowlers, Robert N

    2016-07-15

    Mitochondria are central to health and disease, hence there is considerable interest in developing mitochondria-targeted therapies that require the delivery of peptides or nucleic acid oligomers. However, progress has been impeded by the lack of a measure of mitochondrial import of these molecules. Here, we address this need by quantitatively detecting molecules within the mitochondrial matrix. We used a mitochondria- targeted cyclooctyne (MitoOct) that accumulates several- hundredfold in the matrix, driven by the membrane potential. There, MitoOct reacts through click chemistry with an azide on the target molecule to form a diagnostic product that can be quantified by mass spectrometry. Because the membrane potential-dependent MitoOct concentration in the matrix is essential for conjugation, we can now determine definitively whether a putative mitochondrion-targeted molecule reaches the matrix. This "ClickIn" approach will facilitate development of mitochondria-targeted therapies. PMID:27124570

  6. Assessing the Delivery of Molecules to the Mitochondrial Matrix Using Click Chemistry

    PubMed Central

    Hoogewijs, Kurt; James, Andrew M.; Smith, Robin A. J.

    2016-01-01

    Abstract Mitochondria are central to health and disease, hence there is considerable interest in developing mitochondria‐targeted therapies that require the delivery of peptides or nucleic acid oligomers. However, progress has been impeded by the lack of a measure of mitochondrial import of these molecules. Here, we address this need by quantitatively detecting molecules within the mitochondrial matrix. We used a mitochondria‐ targeted cyclooctyne (MitoOct) that accumulates several‐ hundredfold in the matrix, driven by the membrane potential. There, MitoOct reacts through click chemistry with an azide on the target molecule to form a diagnostic product that can be quantified by mass spectrometry. Because the membrane potential‐dependent MitoOct concentration in the matrix is essential for conjugation, we can now determine definitively whether a putative mitochondrion‐targeted molecule reaches the matrix. This “ClickIn” approach will facilitate development of mitochondria‐targeted therapies. PMID:27124570

  7. Automated Delineation of Lung Tumors from CT Images Using a Single Click Ensemble Segmentation Approach

    PubMed Central

    Gu, Yuhua; Kumar, Virendra; Hall, Lawrence O; Goldgof, Dmitry B; Li, Ching-Yen; Korn, René; Bendtsen, Claus; Velazquez, Emmanuel Rios; Dekker, Andre; Aerts, Hugo; Lambin, Philippe; Li, Xiuli; Tian, Jie; Gatenby, Robert A; Gillies, Robert J

    2012-01-01

    A single click ensemble segmentation (SCES) approach based on an existing “Click&Grow” algorithm is presented. The SCES approach requires only one operator selected seed point as compared with multiple operator inputs, which are typically needed. This facilitates processing large numbers of cases. Evaluation on a set of 129 CT lung tumor images using a similarity index (SI) was done. The average SI is above 93% using 20 different start seeds, showing stability. The average SI for 2 different readers was 79.53%. We then compared the SCES algorithm with the two readers, the level set algorithm and the skeleton graph cut algorithm obtaining an average SI of 78.29%, 77.72%, 63.77% and 63.76% respectively. We can conclude that the newly developed automatic lung lesion segmentation algorithm is stable, accurate and automated. PMID:23459617

  8. Engineering Cyclodextrin Clicked Chiral Stationary Phase for High-Efficiency Enantiomer Separation

    PubMed Central

    Tang, Jian; Zhang, Shapopeng; Lin, Yuzhou; Zhou, Jie; Pang, Limin; Nie, Xuemei; Zhou, Baojing; Tang, Weihua

    2015-01-01

    The separation of racemic molecules is of crucial significance not only for fundamental research but also for technical application. Enantiomers remain challenging to be separated owing to their identical physical and chemical properties in achiral environments. Chromatographic techniques employing chiral stationary phases (CSPs) have been developed as powerful tools for the chiral analysis and preparation of pure enantiomers, most of which are of biological and pharmaceutical interests. Here we report our efforts in developing high-performance phenylcarbamated cyclodextrin (CD) clicked CSPs. Insights on the impact of CD functionalities in structure design are provided. High-efficiency enantioseparation of a range of aryl alcohols and flavanoids with resolution values (Rs) over 10 were demonstrated by per(3-chloro-4-methyl)phenylcarbamated CD clicked CSP. Comparison study and molecular simulations suggest the improved enantioselectivity was attributed to higher interactions energy difference between the complexes of enantiomers and CSPs with phenylcarbamated CD bearing 3-chloro and 4-methyl functionalities. PMID:26235204

  9. 1Click1View: Interactive Visualization Methodology for RNAi Cell-Based Microscopic Screening

    PubMed Central

    Zwolinski, Lukasz; Kozak, Marta; Kozak, Karol

    2013-01-01

    Technological advancements are constantly increasing the size and complexity of data resulting from large-scale RNA interference screens. This fact has led biologists to ask complex questions, which the existing, fully automated analyses are often not adequate to answer. We present a concept of 1Click1View (1C1V) as a methodology for interactive analytic software tools. 1C1V can be applied for two-dimensional visualization of image-based screening data sets from High Content Screening (HCS). Through an easy-to-use interface, one-click, one-view concept, and workflow based architecture, visualization method facilitates the linking of image data with numeric data. Such method utilizes state-of-the-art interactive visualization tools optimized for fast visualization of large scale image data sets. We demonstrate our method on an HCS dataset consisting of multiple cell features from two screening assays. PMID:23484084

  10. Engineering Cyclodextrin Clicked Chiral Stationary Phase for High-Efficiency Enantiomer Separation

    NASA Astrophysics Data System (ADS)

    Tang, Jian; Zhang, Shapopeng; Lin, Yuzhou; Zhou, Jie; Pang, Limin; Nie, Xuemei; Zhou, Baojing; Tang, Weihua

    2015-08-01

    The separation of racemic molecules is of crucial significance not only for fundamental research but also for technical application. Enantiomers remain challenging to be separated owing to their identical physical and chemical properties in achiral environments. Chromatographic techniques employing chiral stationary phases (CSPs) have been developed as powerful tools for the chiral analysis and preparation of pure enantiomers, most of which are of biological and pharmaceutical interests. Here we report our efforts in developing high-performance phenylcarbamated cyclodextrin (CD) clicked CSPs. Insights on the impact of CD functionalities in structure design are provided. High-efficiency enantioseparation of a range of aryl alcohols and flavanoids with resolution values (Rs) over 10 were demonstrated by per(3-chloro-4-methyl)phenylcarbamated CD clicked CSP. Comparison study and molecular simulations suggest the improved enantioselectivity was attributed to higher interactions energy difference between the complexes of enantiomers and CSPs with phenylcarbamated CD bearing 3-chloro and 4-methyl functionalities.

  11. Propagation modeling for sperm whale acoustic clicks in the northern Gulf of Mexico

    NASA Astrophysics Data System (ADS)

    Sidorovskaia, Natalia A.; Udovydchenkov, Ilya A.; Rypina, Irina I.; Ioup, George E.; Ioup, Juliette W.; Caruthers, Jerald W.; Newcomb, Joal; Fisher, Robert

    2001-05-01

    Simulations of acoustic broadband (500-6000 Hz) pulse propagation in the northern Gulf of Mexico, based on environmental data collected as a part of the Littoral Acoustic Demonstration Center (LADC) experiments in the summers of 2001 and 2002, are presented. The results of the modeling support the hypothesis that consistent spectrogram interference patterns observed in the LADC marine mammal phonation data cannot be explained by the propagation effects for temporal analysis windows corresponding to the duration of an animal click, and may be due to a uniqueness of an individual animal phonation apparatus. The utilization of simulation data for the development of an animal tracking algorithm based on the acoustic recordings of a single bottom-moored hydrophone is discussed. The identification of the bottom and surface reflected clicks from the same animal is attempted. The critical ranges for listening to a deep-water forging animal by a surface receiving system are estimated. [Research supported by ONR.

  12. Genetically encoding photoswitchable click amino acids in Escherichia coli and mammalian cells.

    PubMed

    Hoppmann, Christian; Lacey, Vanessa K; Louie, Gordon V; Wei, Jing; Noel, Joseph P; Wang, Lei

    2014-04-01

    The ability to reversibly control protein structure and function with light would offer high spatiotemporal resolution for investigating biological processes. To confer photoresponsiveness on general proteins, we genetically incorporated a set of photoswitchable click amino acids (PSCaas), which contain both a reversible photoswitch and an additional click functional group for further modifications. Orthogonal tRNA-synthetases were evolved to genetically encode PSCaas bearing azobenzene with an alkene, keto, or benzyl chloride group in E. coli and in mammalian cells. After incorporation into calmodulin, the benzyl chloride PSCaa spontaneously generated a covalent protein bridge by reacting with a nearby cysteine residue through proximity-enabled bioreactivity. The resultant azobenzene bridge isomerized in response to light, thereby changing the conformation of calmodulin. These genetically encodable PSCaas will prove valuable for engineering photoswitchable bridges into proteins for reversible optogenetic regulation. PMID:24615769

  13. Announcement: Click It or Ticket Campaign - May 23-June 5, 2016.

    PubMed

    2016-01-01

    Click It or Ticket is a national campaign coordinated annually by the National Highway Traffic Safety Administration to increase the proper use of seat belts. In 2014, more than 21,000 passenger vehicle occupants died in motor vehicle crashes in the United States; 49% were unrestrained at the time of the crash (1). An additional 2.4 million occupants (restrained and unrestrained) were treated in emergency departments for nonfatal crash-related injuries (2). PMID:27196941

  14. The adaptive function of tiger moth clicks against echolocating bats: an experimental and synthetic approach.

    PubMed

    Ratcliffe, John M; Fullard, James H

    2005-12-01

    We studied the efficiency and effects of the multiple sensory cues of tiger moths on echolocating bats. We used the northern long-eared bat, Myotis septentrionalis, a purported moth specialist that takes surface-bound prey (gleaning) and airborne prey (aerial hawking), and the dogbane tiger moth, Cycnia tenera, an eared species unpalatable to bats that possesses conspicuous colouration and sound-producing organs (tymbals). This is the first study to investigate the interaction of tiger moths and wild-caught bats under conditions mimicking those found in nature and to demand the use of both aerial hawking and gleaning strategies by bats. Further, it is the first to report spectrograms of the sounds produced by tiger moths while under aerial attack by echolocating bats. During both aerial hawking and gleaning trials, all muted C. tenera and perched intact C. tenera were attacked by M. septentrionalis, indicating that M. septentrionalis did not discriminate C. tenera from palatable moths based on potential echoic and/or non-auditory cues. Intact C. tenera were attacked significantly less often than muted C. tenera during aerial hawking attacks: tymbal clicks were therefore an effective deterrent in an aerial hawking context. During gleaning attacks, intact and muted C. tenera were always attacked and suffered similar mortality rates, suggesting that while handling prey this bat uses primarily chemical signals. Our results also show that C. tenera temporally matches the onset of click production to the ;approach phase' echolocation calls produced by aerial hawking attacking bats and that clicks themselves influence the echolocation behaviour of attacking bats. In the context of past research, these findings support the hypotheses that the clicks of arctiid moths are both an active defence (through echolocation disruption) and a reliable indicator of chemical defence against aerial-hawking bats. We suggest these signals are specialized for an aerial context. PMID

  15. A fluorosurfactant and photoreducible Cu(II)-tren click catalyst: surfactant and catalytic properties at liquid/liquid interfaces.

    PubMed

    Jochyms, Quentin; Guillot, Pierre; Mignard, Emmanuel; Vincent, Jean-Marc

    2015-12-01

    The fluorous copper(ii) complex [Cu(II)(trenRf6)3-benzoylbenzoate]3-benzoylbenzoate 2, composed of a highly fluorophilic tris(2-aminoethyl)amine ligand and two 3-benzoylbenzoates as counterions and photosensitizers, was synthesized from the dinuclear complex [Cu(3-benzoylbenzoate)4(H2O)2] 1 which was characterized by X-ray analysis. Complex 2, which is highly soluble in perfluorocarbons, moderately soluble in organic solvents while insoluble in water, was found to be a very effective fluorosurfactant. At the air/water interface it formed a Langmuir film, which upon compression slowly collapsed at about 28 mN m(-1), which corresponds to a surface area of about 220 Å(2) per molecule. Tensiometric measurements revealed that 2 is more rapidly adsorbed at the diisopropyl ether (DIPE)/water interface than the perfluorodecalin (PFD)/water one, leading to a decrease of the interfacial tensions of about 14 mN m(-1) and 40 mN m(-1), respectively. Photoreduction of 2 occurs effectively in H-donating solvents such as THF and DIPE, or even in PFD ensuring that an electron donor, such as propargyl alcohol, is present in a separate aqueous phase. Complex 2, when combined with light (365 nm), catalyzes the click reaction between the azide 3 and alkyne 4 under homogeneous conditions (methanol), to afford the disaccharide 5. Under emulsified biphasic DIPE/water or PFD/water conditions, the reactions proceeded well. However, it was shown that a fast and significant amount of copper and 3-benzoylbenzoate counterion was transferred into the aqueous phase, and that most of the catalysis could be ascribed to a copper species solubilised in the aqueous phase, and not to the fluorous copper complex accumulated at the interface. PMID:26489534

  16. Multimerization of cRGD peptides by click chemistry: synthetic strategies, chemical limitations, and influence on biological properties.

    PubMed

    Wängler, Carmen; Maschauer, Simone; Prante, Olaf; Schäfer, Martin; Schirrmacher, Ralf; Bartenstein, Peter; Eisenhut, Michael; Wängler, Björn

    2010-10-18

    Integrin α(ν)β(3) is overexpressed on endothelial cells of growing vessels as well as on several tumor types, and so integrin-binding radiolabeled cyclic RGD pentapeptides have attracted increasing interest for in vivo imaging of α(ν)β(3) integrin expression by positron emission tomography (PET). Of the cRGD derivatives available for imaging applications, systems comprising multiple cRGD moieties have recently been shown to exhibit highly favorable properties in relation to monomers. To assess the synthetic limits of the cRGD-multimerization approach and thus the maximum multimer size achievable by using different efficient conjugation reactions, we prepared a variety of multimers that were further investigated in vitro with regard to their avidities to integrin α(ν)β(3.) The synthesized peptide multimers containing increasing numbers of cRGD moieties on PAMAM dendrimer scaffolds were prepared by different click chemistry coupling strategies. A cRGD hexadecimer was the largest construct that could be synthesized under optimized reaction conditions, thus identifying the current synthetic limitations for cRGD multimerization. The obtained multimeric systems were conjugated to a new DOTA-based chelator developed for the derivatization of sterically demanding structures and successfully labeled with (68)Ga for a potential in vivo application. The evaluated multimers showed very high avidities-increasing with the number of cRGD moieties-in in vitro studies on immobilized α(ν)β(3) integrin and U87MG cells, of up to 131- and 124-fold, respectively, relative to the underivatized monomer. PMID:20827791

  17. Immobilization of poly(acrylamide) brushes onto poly(caprolactone) surface by combining ATRP and "click" chemistry: Synthesis, characterization and evaluation of protein adhesion

    NASA Astrophysics Data System (ADS)

    Ma, Yuhao; Bian, Xinxiu; He, Liu; Cai, Mengtan; Xie, Xiaoxiong; Luo, Xianglin

    2015-02-01

    Developments of poly(caprolactone) in blood-contacting applications are often restricted due to its intrinsic hydrophobicity. One common way to improve its hemocompatibility is to attach hydrophilic polymers. Here we developed a non-destructive method to graft hydrophilic poly(acrylamide) (PAAm) onto poly(caprolactone) (PCL) surface. In this strategy, azido-ended PCL with low molecular weights was synthesized and blended with PCL to create a surface with "clickable" property. Alkyne-ended poly(acrylamide)s with controlled chain lengths were then synthesized by atom transfer radical polymerization (ATRP), and finally were immobilized onto PCL surface by "click" reaction. The occurrence of immobilization was verified qualitatively by water contact angle measurement and quantitatively by X-ray photoelectron spectroscopy (XPS). The PAAm grafted surface exhibited fouling resistant properties, as demonstrated by reduced bovine serum albumin (BSA) and fibrinogen (Fg) adhesion.

  18. Synthesis and cytotoxic activities of 2-substituted (25R)-spirostan-1,4,6-triene-3-ones via ring-opening/elimination and 'click' strategy.

    PubMed

    Lu, Xiao-Feng; Yang, Zheng; Huang, Nian-Yu; He, Hai-Bo; Deng, Wei-Qiao; Zou, Kun

    2015-09-01

    To develop more effective antitumor steroidal drugs, we synthesized a library including twenty-two novel cytotoxic 2-alkyloxyl substituted (25R)-spirostan-1,4,6-triene-3-ones and corresponding 1,2,3-triazoles through an abnormal monoepoxide ring-opening/elimination and 'click' reactions. After the cytotoxic evaluations against HepG2, Caski and HeLa cell lines, three steroidal triazoles 5b, 5f and 5m in this library were found to possess potent anti-proliferative effects against Caski cells with the half-inhibitory concentrations (IC50) of 9.4-11.8 μM. The high-efficient and straightforward process was attractive feature for facile preparation of anti-tumor steroidal triazoles. PMID:26141770

  19. The Use of Microwave-Assisted Solid-Phase Peptide Synthesis and Click Chemistry for the Synthesis of Vaccine Candidates Against Hookworm Infection.

    PubMed

    Fuaad, Abdullah A H Ahmad; Skwarczynski, Mariusz; Toth, Istvan

    2016-01-01

    A protein-based vaccine approach against hookworm infection has failed to deliver the expected outcome, due to a problem with an allergic response in the patient or difficulties in the proteins' production. This implication could be overcome by using a chemically synthesized peptide-based vaccine approach. This approach utilizes minimal pathogenic components that are necessary for the stimulation of the immune response without triggering adverse side effects. To boost the peptide's immunogenicity, a lipid core peptide (LCP) system can be utilized as a carrier molecule/immunostimulant. This chapter describes in detail the synthesizing of protected lipoamino acid, the self-adjuvanting moiety (LCP core), the peptide epitope, and the final vaccine candidate. The subunit peptide and the LCP core were synthesized using microwave-assisted solid-phase peptide synthesis (SPPS). Then the final hookworm vaccine construct was assembled using the copper-catalyzed azide-alkyne cycloaddition, or "click," reaction. PMID:27076158

  20. Clicks, whistles and pulses: Passive and active signal use in dolphin communication

    NASA Astrophysics Data System (ADS)

    Herzing, Denise L.

    2014-12-01

    The search for signals out of noise is a problem not only with radio signals from the sky but in the study of animal communication. Dolphins use multiple modalities to communicate including body postures, touch, vision, and most elaborately sound. Like SETI radio signal searches, dolphin sound analysis includes the detection, recognition, analysis, and interpretation of signals. Dolphins use both passive listening and active production to communicate. Dolphins use three main types of acoustic signals: frequency modulated whistles (narrowband with harmonics), echolocation (broadband clicks) and burst pulsed sounds (packets of closely spaced broadband clicks). Dolphin sound analysis has focused on frequency-modulated whistles, yet the most commonly used signals are burst-pulsed sounds which, due to their graded and overlapping nature and bimodal inter-click interval (ICI) rates are hard to categorize. We will look at: 1) the mechanism of sound production and categories of sound types, 2) sound analysis techniques and information content, and 3) examples of lessons learned in the study of dolphin acoustics. The goal of this paper is to provide perspective on how animal communication studies might provide insight to both passive and active SETI in the larger context of searching for life signatures.

  1. Short-term enhancement and suppression of dolphin auditory evoked responses following echolocation click emission.

    PubMed

    Finneran, James J; Echon, Roxanne; Mulsow, Jason; Houser, Dorian S

    2016-07-01

    Biosonar gain control mechanisms in a bottlenose dolphin were investigated by measuring the auditory steady-state response (ASSR) to an external tone while the animal echolocated. The dolphin performed an echo change-detection task that utilized electronically synthesized echoes with echo delays corresponding to 25- and 50-m target range. During the task, amplitude modulated tones with carrier frequencies from 25 to 125 kHz were continuously presented and the instantaneous electroencephalogram stored for later analysis. ASSRs were extracted from the electroencephalogram by synchronously averaging time epochs temporally aligned with the onset of the external tone modulation cycle nearest to each of the dolphin's echolocation clicks. Results showed an overall suppression of the ASSR amplitude for tones with frequencies near the click center frequencies. A larger, temporary suppression of the ASSR amplitude was also measured at frequencies above 40-50 kHz, while a temporary enhancement was observed at lower frequencies. Temporal patterns for ASSR enhancement or suppression were frequency-, level-, and range-dependent, with recovery to pre-click values occurring within the two-way travel time. Suppressive effects fit the patterns expected from forward masking by the emitted biosonar pulse, while the specific mechanisms responsible for the frequency-dependent enhancement are unknown. PMID:27475154

  2. Multifractal detrended fluctuation analysis to characterize phase couplings in seahorse (Hippocampus kuda) feeding clicks.

    PubMed

    Haris, K; Chakraborty, Bishwajit; Menezes, A; Sreepada, R A; Fernandes, W A

    2014-10-01

    Nonlinear phenomena in animal vocalizations fundamentally includes known features, namely, frequency jump, subharmonics, biphonation, and deterministic chaos. In the present study, the multifractal detrended fluctuation analysis (MFDFA) has been employed to characterize the phase couplings revealed in the feeding clicks of Hippocampus kuda yellow seahorse. The fluctuation function Fq(s), generalized Hurst exponent h(q), multifractal scaling exponent τ(q), and the multifractal spectrum f(α) calculated in the procedure followed were analyzed to comprehend the underlying nonlinearities in the seahorse clicks. The analyses carried out reveal long-range power-law correlation properties in the data, substantiating the multifractal behavior. The resulting h(q) spectrum exhibits a distinct characteristic pattern in relation to the seahorse sex and size, and reveals a spectral blind spot in the data that was not possible to detect by conventional spectral analyses. The corresponding multifractal spectrum related width parameter Δh(q) is well clustered, defining the individual seahorse clicks. The highest degree of multifractality is evident in the 18 cm male seahorse, signifying greater heterogeneity. A further comparison between the seahorse body size and weight (wet) with respect to the width parameter Δh(q) and the second-order Hurst exponent h(q=2) underscores the versatility of MFDFA as a robust statistical tool to analyze bioacoustic observations. PMID:25324096

  3. Detecting sperm whale clicks in the presence of ambient and shipping noise using higher order moments

    NASA Astrophysics Data System (ADS)

    Larue, James P.; Ioup, George E.; Ioup, Juliette W.

    2001-05-01

    The single-receiver detection of various sources using higher order moments is demonstrated. The data for this study come from the Littoral Acoustic Demonstration Center experiment in the northern Gulf of Mexico in the summer of 2001. Results show that in a time-varying environment it may be more meaningful to use non-normalized statistics (e.g., using the fourth central moment rather than the kurtosis). A whale click is detected over a 35-ms window, i.e., with a sampling rate of 11718 samples per second, 40 samples are used to produce a statistic. In the past, energy and related detectors have been used for the single receiver detection of broadband signals produced by whale clicks. The presence of loud shipping noise, which is also broadband, tends to mask the clicks and make their detection difficult. Using short-time statistics may help mitigate this problem. Analysis with fractal exponents will be shown as well. [Research supported by ONR.

  4. Determining the detection thresholds for harbor porpoise clicks of autonomous data loggers, the Timing Porpoise Detectors.

    PubMed

    Verfuß, Ursula K; Dähne, Michael; Gallus, Anja; Jabbusch, Martin; Benke, Harald

    2013-09-01

    Timing Porpoise Detectors (T-PODs, Chelonia Ltd.) are autonomous passive acoustic devices for monitoring odontocetes. They register the time of occurrence and duration of high frequency pulsed sounds as possible odontocetes echolocation clicks. Because of evolution, five T-POD versions exist. Although the manufacturer replaced those by a digital successor, the C-POD, T-PODs are still used, and data from many field studies exist. Characterizing the acoustic properties of T-PODs enables the interpretation of data obtained with different devices. Here, the detection thresholds of different T-POD versions for harbor porpoise clicks were determined. While thresholds among devices were quite variable in the first T-POD generations, they became more standardized in newer versions. Furthermore, the influence of user-controlled settings on the threshold was investigated. From version 3 on, the detection threshold was found to be easily adjustable with version-dependent setting options "minimum intensity" and "sensitivity," enabling the presetting of standard thresholds. In version 4, the setting "click bandwidth" had a strong influence on the detection threshold, while "selectivity" in version 3 and "noise adaptation = ON" or "OFF" in version 4 hardly influenced thresholds obtained in the tank tests. Nevertheless, the latter setting may influence thresholds in a complex acoustic environment like the sea. PMID:23968043

  5. In situ click chemistry: from small molecule discovery to synthetic antibodies

    PubMed Central

    Agnew, Heather D.; Lai, Bert; Lee, Su Seong; Lim, Jaehong; Nag, Arundhati; Pitram, Suresh; Rohde, Rosemary; Heath, James R.

    2013-01-01

    Advances in the fields of proteomics, molecular imaging, and therapeutics are closely linked to the availability of affinity reagents that selectively recognize their biological targets. Here we present a review of Iterative Peptide In Situ Click Chemistry (IPISC), a novel screening technology for designing peptide multiligands with high affinity and specificity. This technology builds upon in situ click chemistry, a kinetic target-guided synthesis approach where the protein target catalyzes the conjugation of two small molecules, typically through the azide–alkyne Huisgen cycloaddition. Integrating this methodology with solid phase peptide libraries enables the assembly of linear and branched peptide multiligands we refer to as Protein Catalyzed Capture Agents (PCC Agents). The resulting structures can be thought of as analogous to the antigen recognition site of antibodies and serve as antibody replacements in biochemical and cell-based applications. In this review, we discuss the recent progress in ligand design through IPISC and related approaches, focusing on the improvements in affinity and specificity as multiligands are assembled by target-catalyzed peptide conjugation. We compare the IPISC process to small molecule in situ click chemistry with particular emphasis on the advantages and technical challenges of constructing antibody-like PCC Agents. PMID:22836343

  6. On the dynamic behaviour of the "click" mechanism in dipteran flight.

    PubMed

    Tang, Bin; Brennan, M J

    2011-11-21

    In this paper, the dynamic behaviour of the "click" mechanism is analysed. A more accurate model is used than in the past, in which the limits of movement due to the geometry of the flight mechanism are imposed. Moreover, the effects of different damping models are investigated. In previous work, the damping model was assumed to be of the linear viscous type for simplicity, but it is likely that the damping due to drag forces is nonlinear. Accordingly, a model of damping in which the damping force is proportional to the square of the velocity is used, and the results are compared with the simpler model of linear viscous damping. Because of the complexity of the model an analytical approach is not possible so the problem has been cast in terms of non-dimensional variables and solved numerically. The peak kinetic energy of the wing root per energy input in one cycle is chosen to study the effectiveness of the "click" mechanism compared with a linear resonant mechanism. It is shown that, the "click" mechanism has distinct advantages when it is driven below its resonant frequency. When the damping is quadratic, there are some further advantages compared to when the damping is linear and viscous, provided that the amplitude of the excitation force is large enough to avoid the erratic behaviour of the mechanism that occurs for small forces. PMID:21907214

  7. Off-axis effects on the multipulse structure of sperm whale usual clicks with implications for sound production.

    PubMed

    Zimmer, Walter M X; Madsen, Peter T; Teloni, Valeria; Johnson, Mark P; Tyack, Peter L

    2005-11-01

    Sperm whales (Physeter macrocephalus) produce multipulsed clicks with their hypertrophied nasal complex. The currently accepted view of the sound generation process is based on the click structure measured directly in front of, or behind, the whale where regular interpulse intervals (IPIs) are found between successive pulses in the click. Most sperm whales, however, are recorded with the whale in an unknown orientation with respect to the hydrophone where the multipulse structure and the IPI do not conform to a regular pulse pattern. By combining far-field recordings of usual clicks with acoustic and orientation information measured by a tag on the clicking whale, we analyzed clicks from known aspects to the whale. We show that a geometric model based on the bent horn theory for sound production can explain the varying off-axis multipulse structure. Some of the sound energy that is reflected off the frontal sac radiates directly into the water creating an intermediate pulse p1/2 seen in off-axis recordings. The powerful p1 sonar pulse exits the front of the junk as predicted by the bent-horn model, showing that the junk of the sperm whale nasal complex is both anatomically and functionally homologous to the melon of smaller toothed whales. PMID:16334703

  8. Off-axis effects on the multipulse structure of sperm whale usual clicks with implications for sound production

    NASA Astrophysics Data System (ADS)

    Zimmer, Walter M. X.; Madsen, Peter T.; Teloni, Valeria; Johnson, Mark P.; Tyack, Peter L.

    2005-11-01

    Sperm whales (Physeter macrocephalus) produce multipulsed clicks with their hypertrophied nasal complex. The currently accepted view of the sound generation process is based on the click structure measured directly in front of, or behind, the whale where regular interpulse intervals (IPIs) are found between successive pulses in the click. Most sperm whales, however, are recorded with the whale in an unknown orientation with respect to the hydrophone where the multipulse structure and the IPI do not conform to a regular pulse pattern. By combining far-field recordings of usual clicks with acoustic and orientation information measured by a tag on the clicking whale, we analyzed clicks from known aspects to the whale. We show that a geometric model based on the bent horn theory for sound production can explain the varying off-axis multipulse structure. Some of the sound energy that is reflected off the frontal sac radiates directly into the water creating an intermediate pulse p1/2 seen in off-axis recordings. The powerful p1 sonar pulse exits the front of the junk as predicted by the bent-horn model, showing that the junk of the sperm whale nasal complex is both anatomically and functionally homologous to the melon of smaller toothed whales.

  9. The energy ratio mapping algorithm: a tool to improve the energy-based detection of odontocete echolocation clicks.

    PubMed

    Klinck, Holger; Mellinger, David K

    2011-04-01

    The energy ratio mapping algorithm (ERMA) was developed to improve the performance of energy-based detection of odontocete echolocation clicks, especially for application in environments with limited computational power and energy such as acoustic gliders. ERMA systematically evaluates many frequency bands for energy ratio-based detection of echolocation clicks produced by a target species in the presence of the species mix in a given geographic area. To evaluate the performance of ERMA, a Teager-Kaiser energy operator was applied to the series of energy ratios as derived by ERMA. A noise-adaptive threshold was then applied to the Teager-Kaiser function to identify clicks in data sets. The method was tested for detecting clicks of Blainville's beaked whales while rejecting echolocation clicks of Risso's dolphins and pilot whales. Results showed that the ERMA-based detector correctly identified 81.6% of the beaked whale clicks in an extended evaluation data set. Average false-positive detection rate was 6.3% (3.4% for Risso's dolphins and 2.9% for pilot whales). PMID:21476637

  10. Echolocation in sympatric Peale's dolphins (Lagenorhynchus australis) and Commerson's dolphins (Cephalorhynchus commersonii) producing narrow-band high-frequency clicks.

    PubMed

    Kyhn, L A; Jensen, F H; Beedholm, K; Tougaard, J; Hansen, M; Madsen, P T

    2010-06-01

    An increasing number of smaller odontocetes have recently been shown to produce stereotyped narrow-band high-frequency (NBHF) echolocation clicks. Click source parameters of NBHF clicks are very similar, and it is unclear whether the sonars of individual NBHF species are adapted to specific habitats or the presence of other NBHF species. Here, we test whether sympatric NBHF species sharing the same habitat show similar adaptations in their echolocation clicks and whether their clicks display signs of character displacement. Wide-band sound recordings were obtained with a six-element hydrophone array from wild Peale's (Lagenorhynchus australis) and Commerson's (Cephalorhynchus commersonii) dolphins off the Falkland Islands. The centroid frequency was different between Commerson's (133+/-2 kHz) and Peale's (129+/-3 kHz) dolphins. The r.m.s. bandwidth was 12+/-3 kHz for both species. The source level was higher for Peale's dolphin (185+/-6 dB re 1 muPa p.-p.) than for Commerson's (177+/-5 dB re 1 muPa p.-p.). The mean directivity indexes were 25 dB for both species. The relatively low source levels in combination with the high directivity index may be an adaptation to reduce clutter when foraging in a coastal environment. We conclude that the small species-specific shifts in distribution of centroid frequencies around 130 kHz may reflect character displacement in otherwise-stereotyped NBHF clicks. PMID:20472781

  11. Efficient 18F-Labeling of Large 37-Amino Acid pHLIP Peptide Analogues and their Biological Evaluation

    PubMed Central

    Daumar, Pierre; Wanger-Baumann, Cindy A.; Pillarsetty, NagaVaraKishore; Fabrizio, Laura; Carlin, Sean D.; Andreev, Oleg A.; Reshetnyak, Yana K.; Lewis, Jason S.

    2012-01-01

    Solid tumors often develop an acidic microenvironment, which plays a critical role in tumor progression and is associated with increased level of invasion and metastasis. The 37-residue pH (low) insertion peptide (pHLIP®) is under study as an imaging platform because of its unique ability to insert into cell membranes at a low extracellular pH (pHe<7). Labeling of peptides with [18F]-fluorine is usually performed via prosthetic groups using chemoselective coupling reactions. One of the most successful procedures involves the alkyne-azide copper(I) catalyzed cycloaddition (CuAAC). However, none of the known “click” methods have been applied to peptides as large as pHLIP. We designed a novel prosthetic group and extended the use of the CuAAC “click chemistry” for the simple and efficient 18F-labeling of large peptides. For the evaluation of this labeling approach, a D-amino acid analogue of WT-pHLIP and a L-amino acid control peptide K-pHLIP, both functionalized at the N-terminus with 6-azidohexanoic acid, were used. The novel 6-[18F]fluoro-2-ethynylpyridine prosthetic group, was obtained via nucleophilic substitution on the corresponding bromo-precursor after 10 min at 130 °C with a radiochemical yield of 27.5 ± 6.6% (decay corrected) with high radiochemical purity ≥ 98%. The subsequent CuI catalyzed “click” reaction with the azido functionalized pHLIP peptides was quantitative within 5 min at 70 °C in a mixture of water and ethanol using Cu-acetate and sodium L-ascorbate. [18F]-D-WT-pHLIP and [18F]-L-K-pHLIP were obtained with total radiochemical yields of 5–20% after HPLC purification. The total reaction time was only 85 min including formulation. In vitro stability tests revealed high stability of the [18F]-D-WT-pHLIP in human and mouse plasma after 120 min, with the parent tracer remaining intact at 65 and 85%, respectively. PET imaging and biodistribution studies in LNCaP and PC-3 xenografted mice with the [18F]-D-WT-pHLIP and the negative

  12. Semiconducting organic-inorganic nanocomposites by intimately tethering conjugated polymers to inorganic tetrapods

    NASA Astrophysics Data System (ADS)

    Jung, Jaehan; Yoon, Young Jun; Lin, Zhiqun

    2016-04-01

    Semiconducting organic-inorganic nanocomposites were judiciously crafted by placing conjugated polymers in intimate contact with inorganic tetrapods via click reaction. CdSe tetrapods were first synthesized by inducing elongated arms from CdSe zincblende seeds through seed-mediated growth. The subsequent effective inorganic ligand treatment, followed by reacting with short bifunctional ligands, yielded azide-functionalized CdSe tetrapods (i.e., CdSe-N3). Finally, the ethynyl-terminated conjugated polymer poly(3-hexylthiophene) (i.e., P3HT-&z.tbd;) was tethered to CdSe-N3 tetrapods via a catalyst-free alkyne-azide cycloaddition, forming intimate semiconducting P3HT-CdSe tetrapod nanocomposites. Intriguingly, the intimate contact between P3HT and CdSe tetrapod was found to not only render the effective dispersion of CdSe tetrapods in the P3HT matrix, but also facilitate the efficient electronic interaction between these two semiconducting constituents. The successful anchoring of P3HT chains onto CdSe tetrapods was substantiated through Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy measurements. Moreover, the absorption and photoluminescence studies further corroborated the intimate tethering between P3HT and CdSe tetrapods. The effect of the type of bifunctional ligands (i.e., aryl vs. aliphatic ligands) and the size of tetrapods on the device performance of hybrid organic-inorganic solar cells was also scrutinized. Interestingly, P3HT-CdSe tetrapod nanocomposites produced via the use of an aryl bifunctional ligand (i.e., 4-azidobenzoic acid) exhibited an improved photovoltaic performance compared to that synthesized with their aliphatic ligand counterpart (i.e., 5-bromovaleric acid). Clearly, the optimal size of CdSe tetrapods ensuring the effective charge transport in conjunction with the good dispersion of CdSe tetrapods rendered an improved device performance. We envision that the click-reaction strategy enabled by

  13. Reactive Surfaces and Interfaces utilizing 2-Vinyl-4,4-Dimethylazlactone (VDMA): An Example of ??Click?? Chemistry

    SciTech Connect

    Messman, Jamie M; Kilbey, II, S Michael; Lokitz, Bradley S; Hinestrosa Salazar, Juan Pablo; Ankner, John Francis

    2009-01-01

    Creating polymer-modified interfaces decorated with biologically-relevant materials V so-called bio-interfaces V with precise control over the nanoscale structure and properties is of increasing technological importance for a large number of advanced materials applications, including adaptive and/or lubricious biomaterial coatings, electro-actuators (synthetic muscles), biosensors with amplified response, coatings for stealth drug delivery, supports for enzymatic catalysts, protein or antibody arrays, and high affinity separation agents. The ability to design and decorate interfaces with biologically-relevant molecules and understand synthesis-structure-function relationships remains a significant challenge. The overarching objective of this research program is to investigate the polymerization and functionalization of a new class of polymeric materials that are capable of serving as a versatile platform from which bio-interfaces for specific applications can be created and evaluated. Stimuli-responsive (co)polymers containing vinyl dimethyl azlactone (VDMA) have been prepared using free radical polymerization techniques (controlled and conventional). Subsequent immobilization of biomolecules (e.g., dansylcadaverine, N ,N -bis(carboxymethyl)-L-lysine hydrate) on PVDMA-containing surface scaffolds affords bio-interfaces. Reaction of nucleophiles with the azlactone moiety proceeds rapidly, quantitatively, and in the absence of byproducts, which are essential criteria governing the click-type nature of this procedure. The conversion of these materials into polyelectrolytes and bioconjugates can be monitored in real-time using infrared spectroscopy. Additionally, pVDMA polymers prepared using reversible addition fragmentation chain transfer (RAFT) polymerization are the basis for creating polymer brushes by a grafting to approach. We will describe how compositional differences and changes in molecular weight affect the solubility and responsiveness of p

  14. Continued Maturation of the Click-Evoked Auditory Brainstem Response in Preschoolers

    PubMed Central

    Spitzer, Emily; White-Schwoch, Travis; Carr, Kali Woodruff; Skoe, Erika; Kraus, Nina

    2016-01-01

    Background Click-evoked auditory brainstem responses (ABRs) are a valuable tool for probing auditory system function and development. Although it has long been thought that the human auditory brainstem is fully mature by age 2 yr, recent evidence indicates a prolonged developmental trajectory. Purpose The purpose of this study was to determine the time course of ABR maturation in a preschool population and fill a gap in the knowledge of development. Research Design Using a cross-sectional design, we investigated the effect of age on absolute latencies, interwave latencies, and amplitudes (waves I, III, V) of the click-evoked ABR. Study Sample A total of 71 preschoolers (ages 3.12–4.99 yr) participated in the study. All had normal peripheral auditory function and IQ. Data Collection and Analysis ABRs to a rarefaction click stimulus presented at 31/sec and 80 dB SPL (73 dB nHL) were recorded monaurally using clinically-standard recording and filtering procedures while the participant sat watching a movie. Absolute latencies, interwave latencies, and amplitudes were then correlated to age. Results Developmental changes were restricted to absolute latencies. Wave V latency decreased significantly with age, whereas wave I and III latencies remained stable, even in this restricted age range. Conclusions The ABR does not remain static after age 2 yr, as seen by a systematic decrease in wave V latency between ages 3 and 5 yr. This finding suggests that the human brainstem has a continued developmental time course during the preschool years. Latency changes in the age 3–5 yr range should be considered when using ABRs as a metric of hearing health. PMID:25597458

  15. Evaluating and Optimizing Online Advertising: Forget the Click, but There Are Good Proxies.

    PubMed

    Dalessandro, Brian; Hook, Rod; Perlich, Claudia; Provost, Foster

    2015-06-01

    Online systems promise to improve advertisement targeting via the massive and detailed data available. However, there often is too few data on exactly the outcome of interest, such as purchases, for accurate campaign evaluation and optimization (due to low conversion rates, cold start periods, lack of instrumentation of offline purchases, and long purchase cycles). This paper presents a detailed treatment of proxy modeling, which is based on the identification of a suitable alternative (proxy) target variable when data on the true objective is in short supply (or even completely nonexistent). The paper has a two-fold contribution. First, the potential of proxy modeling is demonstrated clearly, based on a massive-scale experiment across 58 real online advertising campaigns. Second, we assess the value of different specific proxies for evaluating and optimizing online display advertising, showing striking results. The results include bad news and good news. The most commonly cited and used proxy is a click on an ad. The bad news is that across a large number of campaigns, clicks are not good proxies for evaluation or for optimization: clickers do not resemble buyers. The good news is that an alternative sort of proxy performs remarkably well: observed visits to the brand's website. Specifically, predictive models built based on brand site visits-which are much more common than purchases-do a remarkably good job of predicting which browsers will make a purchase. The practical bottom line: evaluating and optimizing campaigns using clicks seems wrongheaded; however, there is an easy and attractive alternative-use a well-chosen site-visit proxy instead. PMID:27447433

  16. Three-dimensional beam pattern of regular sperm whale clicks confirms bent-horn hypothesis

    NASA Astrophysics Data System (ADS)

    Zimmer, Walter M. X.; Tyack, Peter L.; Johnson, Mark P.; Madsen, Peter T.

    2005-03-01

    The three-dimensional beam pattern of a sperm whale (Physeter macrocephalus) tagged in the Ligurian Sea was derived using data on regular clicks from the tag and from hydrophones towed behind a ship circling the tagged whale. The tag defined the orientation of the whale, while sightings and beamformer data were used to locate the whale with respect to the ship. The existence of a narrow, forward-directed P1 beam with source levels exceeding 210 dBpeak re: 1 μPa at 1 m is confirmed. A modeled forward-beam pattern, that matches clicks >20° off-axis, predicts a directivity index of 26.7 dB and source levels of up to 229 dBpeak re: 1 μPa at 1 m. A broader backward-directed beam is produced by the P0 pulse with source levels near 200 dBpeak re: 1 μPa at 1 m and a directivity index of 7.4 dB. A low-frequency component with source levels near 190 dBpeak re: 1 μPa at 1 m is generated at the onset of the P0 pulse by air resonance. The results support the bent-horn model of sound production in sperm whales. While the sperm whale nose appears primarily adapted to produce an intense forward-directed sonar signal, less-directional click components convey information to conspecifics, and give rise to echoes from the seafloor and the surface, which may be useful for orientation during dives..

  17. Underwater Ambient Noise and Sperm Whale Click Detection during Extreme Wind Speed Conditions

    NASA Astrophysics Data System (ADS)

    Newcomb, Joal J.; Wright, Andrew J.; Kuczaj, Stan; Thames, Rachel; Hillstrom, Wesley R.; Goodman, Ralph

    2004-11-01

    The Littoral Acoustic Demonstration Center (LA DC) deployed three Environmental Acoustic Recording System (EARS) buoys in the northern Gulf of Mexico during the summers of 2001 (LADC 01) and 2002 (LADC 02). The hydrophone of each buoy was approximately 50m from the bottom in water depths of 645m to 1034m. During LADC 01 Tropical Storm Barry passed within 93nmi east of the EARS buoys. During LADC 02 Tropical Storm Isidore and Hurricane Lili passed within approximately 73nmi and 116nmi, respectively, west of the EARS buoys. The proximity of these storm systems to the EARS buoys, in conjunction with wind speed data from three nearby NDBC weather buoys, allows for the direct comparison of underwater ambient noise levels with high wind speeds. These results are compared to the G. M. Wenz spectra at frequencies from 1kHz to 5.5kHz. In addition, the impact of storm conditions on sperm whale clicks was assessed. In particular, although the time period during the closest approach of TS Barry tended to produce lower click rates, this time period did not have the greatest incidence of non-detection at all the EARS buoys. It follows that storm-related masking noise could not have been responsible for all the observed trends. The data suggest that sperm whales may have left the vicinity of the deepest EARS buoy (nearest TS Barry's storm track) during the storm and possibly moved into the shallower waters around the other EARS buoys. It also appears that sperm whales may not have returned to the deepest EARS area, or did not resume normal behavior immediately after the storm, as the click rate did not recover to pre-storm levels during the period after TS Barry had dissipated. Results of these analyses and the ambient noise analysis will be presented. (Research supported by ONR).

  18. High-yield clicking and dissociation of doxorubicin nanoclusters exhibiting differential cellular uptakes and imaging.

    PubMed

    Kim, Hye Sung; Yoon, Sujin; Son, Young Ju; Park, Yeonju; Jung, Young Mee; Yoo, Hyuk Sang

    2015-11-10

    Gold nanoparticles (AuNPs) and quantum dots (Qdots) were clicked into doxorubicin nanoclusters that showed enzyme-dependent dissociation behaviors for differential cellular uptakes and imaging. The AuNPs were co-functionalized with doxorubicin (DOX) and azide-terminated polymer (DOX/azide@AuNP), while an enzyme-cleavable peptide and alkyne-terminated polymer were sequentially conjugated on Qdot surface (Alkyne-MMP@Qdot). Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, and fluorescence imaging detected the azide and alkyne groups on DOX/azide@AuNP and Alkyne-MMP@Qdot, respectively, and the click-reactivity was also confirmed. In the presence of the catalyst, two nanoparticles were clicked to doxorubicin nanoclusters, which increased the volume of the particles ca. 343-fold within 30min. Upon matrix metalloproteinase-2 (MMP-2) digestion, the nanoclusters were clearly dissociated into smaller particles, and the fluorescence of the quenched Qdot was also recovered, which suggests that the nanoclusters respond to MMP-2 concentrations and can thus be employed for cancer imaging. Confocal microscopy and an elemental analysis of the cancer cells revealed that the cellular uptakes of doxorubicin nanoclusters significantly increased at higher MMP-2 concentrations, and doxorubicin could also be cleaved for anti-cancer effects. In vivo and in vitro cytotoxicity assay accordingly showed that the cytotoxicity of doxorubicin nanoclusters against cancer cells increased in MMP-2-rich environments such as tumor site. Thus, these nanoclusters containing DOX/azide@AuNP and Alkyne-MMP@Qdot are expected to be multifunctional carriers for targeted anti-cancer treatments and imaging. PMID:26315815

  19. Target Identification by Diazirine Photo-Cross-linking and Click Chemistry

    PubMed Central

    MacKinnon, Andrew L.; Taunton, Jack

    2013-01-01

    Target identification of biologically active small-molecules is often the rate-determining step in forward chemical genetics. Photo-affinity labeling (PAL) represents a useful biochemical strategy for target identification in complex protein mixtures. This unit describes the use of alkyl diazirine-based photo-affinity probes and Cu(I)-catalyzed click chemistry to covalently label and visualize the targets of biologically active small-molecules. A general method for affinity purification of probe-modified proteins, useful for identification of protein targets, is also described. PMID:23667793

  20. Juicer Provides a One-Click System for Analyzing Loop-Resolution Hi-C Experiments.

    PubMed

    Durand, Neva C; Shamim, Muhammad S; Machol, Ido; Rao, Suhas S P; Huntley, Miriam H; Lander, Eric S; Aiden, Erez Lieberman

    2016-07-01

    Hi-C experiments explore the 3D structure of the genome, generating terabases of data to create high-resolution contact maps. Here, we introduce Juicer, an open-source tool for analyzing terabase-scale Hi-C datasets. Juicer allows users without a computational background to transform raw sequence data into normalized contact maps with one click. Juicer produces a hic file containing compressed contact matrices at many resolutions, facilitating visualization and analysis at multiple scales. Structural features, such as loops and domains, are automatically annotated. Juicer is available as open source software at http://aidenlab.org/juicer/. PMID:27467249

  1. Cathepsin B Inhibitors: Combining Dipeptide Nitriles with an Occluding Loop Recognition Element by Click Chemistry.

    PubMed

    Schmitz, Janina; Li, Tianwei; Bartz, Ulrike; Gütschow, Michael

    2016-03-10

    An active site mapping of human cathepsin B with dipeptide nitrile inhibitors was performed for a combinatorial approach by introducing several points of diversity and stepwise optimizing the inhibitor structure. To address the occluding loop of cathepsin B by a carboxylate moiety, click chemistry to generate linker-connected molecules was applied. Inhibitor 17 exhibited K i values of 41.3 nM, 27.3 nM, or 19.2 nM, depending on the substrate and pH of the assay. Kinetic data were discussed with respect to the conformational selection and induced fit models. PMID:26985300

  2. Quantitation of Protein Translation Rate In Vivo with Bioorthogonal Click-Chemistry.

    PubMed

    Belda-Palazón, Borja; Ferrando, Alejandro; Farràs, Rosa

    2016-01-01

    The development of novel bioorthogonal reactives that can be used to tag biomolecules in vivo has revolutionized the studies of cellular and molecular biology. Among those novel reactive substances, amino acid analogs can be used to label nascent proteins, thus opening new avenues for measuring protein translation rates in vivo with a limited manipulation of the sample. Here, we describe the use of Click-chemistry to tag and separate newly synthesized proteins in mammalian cells that can be used, coupled with western analysis, to estimate the translation rate of any protein of interest. PMID:27613050

  3. Comparison of the auditory systems of heterosexuals and homosexuals: Click-evoked otoacoustic emissions

    PubMed Central

    McFadden, Dennis; Pasanen, Edward G.

    1998-01-01

    Click-evoked otoacoustic emissions (CEOAEs) are echo-like waveforms emitted by normal-hearing cochleas in response to a brief transient. CEOAEs are known to be stronger in females than in males. In this experiment, the CEOAEs of homosexual and bisexual females were found to be intermediate to those of heterosexual females and heterosexual males. A parsimonious explanation is that the auditory systems of homosexual and bisexual females, and the brain structures responsible for their sexual orientation, have been partially masculinized by exposure to high levels of androgens prenatally. No difference in CEOAEs was observed between homosexual and heterosexual males. PMID:9482952

  4. Carbonic Anhydrase Inhibition with Benzenesulfonamides and Tetrafluorobenzenesulfonamides Obtained via Click Chemistry

    PubMed Central

    2014-01-01

    A series of novel benzene- and 2,3,5,6-tetrafluorobenzenesulfonamide was synthesized by using a click chemistry approach starting from azido-substituted sulfonamides and alkynes, incorporating aryl, alkyl, cycloalkyl, and amino-/hydroxy-/halogenoalkyl moieties. The new compounds were medium potency inhibitors of the cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isoforms I and II and low nanomolar/subnanomolar inhibitors of the tumor-associated hCA IX and XII isoforms. The X-ray crystal structure of two such sulfonamides in adduct with hCA II allowed us to understand the factors governing inhibitory power. PMID:25147616

  5. Temporal resolution in the dolphin's auditory system revealed by double-click evoked potential study.

    PubMed

    Supin AYa; Popov, V V

    1995-04-01

    Temporal resolution of hearing in two bottlenosed dolphins was estimated by measuring auditory brain-stem response (ABR) recovery in conditions of double-click stimuli. From these data, temporal transfer function of the supposed integrator was derived assuming nonlinear transform of the integrator output to ABR amplitude. The obtained temporal transfer function showed a nearly constant level up to 200 microseconds. then decay to approximately -3 dB at 300 microseconds (as presented in the sound intensity domain), and subsequent decay of 10-11 dB per time doubling (about 35 dB/decade). PMID:7598764

  6. Star-Shaped Polyacrylates: Highly Functionalized Architectures via CuAAC Click Conjugation.

    PubMed

    Lammens, Mieke; Fournier, David; Fijten, Martin W M; Hoogenboom, Richard; Prez, Filip Du

    2009-12-01

    Well-defined functional star-shaped polymer structures with up to 29 arms have been successfully synthesized by the combination of atom transfer radical polymerization (ATRP) and click chemistry. First, azide end-functionalized poly(isobornyl acrylate) (PiBA) star-shaped polymers were prepared by successive ATRP and bromine substitution. Subsequently, alkyne end-functionalized molecules and polymers were introduced onto the star-shaped PiBA bearing pendant azide moieties by copper-catalyzed azide-alkyne cycloaddition (CuAAC). The possibilities and limits for the CuAAC on such highly branched polyacrylates are described. PMID:21638494

  7. Surface Modification of Polydivinylbenzene Microspheres with a Fluorinated Glycopolymer Using Thiol-Halogen Click Chemistry.

    PubMed

    Song, Wentao; Granville, Anthony M

    2016-01-01

    Distillation-precipitation polymerization of divinylbenzene was applied to obtain uniform-sized polymeric microspheres. The microspheres were then modified with polypentafluorostyrene chains utilizing surface-initiated atom transfer radical polymerization techniques. The hydrophobic fluoropolymer-coated microsphere was then converted to a hydrophilic biopolymer by performing thiol-halogen click chemistry between polypentafluorostyrene and 1-thio-β-D-glucose sodium salt. The semi-fluorinated glycopolymer showed good binding ability with Concanavalin A as determined by confocal microscopy and turbidity experiments. PMID:26537469

  8. Modifying the 5'-Cap for Click Reactions of Eukaryotic mRNA and To Tune Translation Efficiency in Living Cells.

    PubMed

    Holstein, Josephin M; Anhäuser, Lea; Rentmeister, Andrea

    2016-08-26

    The 5'-cap is a hallmark of eukaryotic mRNAs and plays fundamental roles in RNA metabolism, ranging from quality control to export and translation. Modifying the 5'-cap may thus enable modulation of the underlying processes and investigation or tuning of several biological functions. A straightforward approach is presented for the efficient production of a range of N7-modified caps based on the highly promiscuous methyltransferase Ecm1. We show that these, as well as N(2) -modified 5'-caps, can be used to tune translation of the respective mRNAs both in vitro and in cells. Appropriate modifications allow subsequent bioorthogonal chemistry, as demonstrated by intracellular live-cell labeling of a target mRNA. The efficient and versatile N7 manipulation of the mRNA cap makes mRNAs amenable to both modulation of their biological function and intracellular labeling, and represents a valuable addition to the chemical biology toolbox. PMID:27511141

  9. Site-specific antibody-liposome conjugation through copper-free click chemistry: a molecular biology approach for targeted photodynamic therapy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Obaid, Girgis; Wang, Yucheng; Kuriakose, Jerrin; Broekgaarden, Mans; Alkhateeb, Ahmed; Bulin, Anne-Laure; Hui, James; Tsourkas, Andrew; Hasan, Tayyaba

    2016-03-01

    Nanocarriers, such as liposomes, have the ability to potentiate photodynamic therapy (PDT) treatment regimens by the encapsulation of high payloads of photosensitizers and enhance their passive delivery to tumors through the enhanced permeability and retention effect. By conjugating targeting moieties to the surface of the liposomal nanoconstructs, cellular selectivity is imparted on them and PDT-based therapies can be performed with significantly higher dose tolerances, as off-target toxicity is simultaneously reduced.1 However, the maximal benefits of conventional targeted nanocarriers, including liposomes, are hindered by practical limitations including chemical instability, non-selective conjugation chemistry, poor control over ligand orientation, and loss of ligand functionality following conjugation, amongst others.2 We have developed a robust, physically and chemically stable liposomal nanoplatform containing benzoporphyrin derivative photosensitizer molecules within the phospholipid bilayer and an optimized surface density of strained cyclooctyne moieties for `click' conjugation to azido-functionalized antibodies.3 The clinical chimeric anti-EGFR antibody Cetuximab is site-specifically photocrosslinked to a recombinant bioengineered that recognizes the antibody's Fc region, containing a terminal azide.4 The copper-free click conjugation of the bioengineered Cetuximab derivative to the optimized photosensitizing liposome provides exceptional control over the antibody's optimal orientation for cellular antigen binding. Importantly, the reaction occurs rapidly under physiological conditions, bioorthogonally (selectively in the presence of other biomolecules) and without the need for toxic copper catalysis.3 Such state-of-the-art conjugation strategies push the boundaries of targeted photodynamic therapy beyond the limitations of traditional chemical coupling techniques to produce more robust and effective targeted therapeutics with applications beyond

  10. 1,2,3-Triazole-Functionalized Polysulfone Synthesis through Microwave-Assisted Copper-Catalyzed Click Chemistry: A Highly Proton Conducting High Temperature Membrane.

    PubMed

    Sood, Rakhi; Donnadio, Anna; Giancola, Stefano; Kreisz, Aurélien; Jones, Deborah J; Cavaliere, Sara

    2016-07-01

    Microwave heating holds all the aces regarding development of effective and environmentally friendly methods to perform chemical transformations. Coupling the benefits of microwave-enhanced chemistry with highly reliable copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry paves the way for a rapid and efficient synthesis procedure to afford high performance thermoplastic materials. We describe herein fast and high yielding synthesis of 1,2,3-triazole-functionalized polysulfone through microwave-assisted CuAAC as well as explore their potential as phosphoric acid doped polymer electrolyte membranes (PEM) for high temperature PEM fuel cells. Polymers with various degrees of substitution of the side-chain functionality of 1,4-substituted 1,2,3-triazole with alkyl and aryl pendant structures are prepared by sequential chloromethylation, azidation, and microwave-assisted CuAAC using a range of alkynes (1-pentyne, 1-nonyne, and phenylacetylene). The completeness of reaction at each step and the purity of the clicked polymers were confirmed by (1)H-(13)C NMR, DOSY-NMR and FTIR-ATR spectroscopies. The thermal and thermochemical properties of the modified polymers were characterized by differential scanning calorimetry and thermogravimetric analysis coupled with mass spectroscopy (TG-MS), respectively. TG-MS analysis demonstrated that the commencement of the thermal degradation takes place with the decomposition of the triazole ring while its substituents have critical influence on the initiation temperature. Polysulfone functionalized with 4-phenyl-1,2,3-triazole demonstrates significantly higher Tg, Td, and elastic modulus than the ones bearing 4-propyl-1,2,3-triazole and 4-heptyl-1,2,3-triazole groups. After doping with phosphoric acid, the functionalized polymers with acid doping level of 5 show promising performance with high proton conductivity in anhydrous conditions (in the range of 27-35 mS/cm) and satisfactorily high elastic modulus (in the range

  11. Azide vs Alkyne Functionalization in Pt(II) Complexes for Post-treatment Click Modification: Solid-State Structure, Fluorescent Labeling, and Cellular Fate.

    PubMed

    Wirth, Regina; White, Jonathan D; Moghaddam, Alan D; Ginzburg, Aurora L; Zakharov, Lev N; Haley, Michael M; DeRose, Victoria J

    2015-12-01

    Tracking of Pt(II) complexes is of crucial importance toward understanding Pt interactions with cellular biomolecules. Post-treatment fluorescent labeling of functionalized Pt(II)-based agents using the bioorthogonal Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has recently been reported as a promising approach. Here we describe an azide-functionalized Pt(II) complex, cis-[Pt(2-azidobutyl)amido-1,3-propanediamine)Cl2] (1), containing the cis geometry and difunctional reactivity of cisplatin, and present a comparative study with its previously described alkyne-functionalized congener. Single-crystal X-ray diffraction reveals a dramatic change in the solid-state arrangement with exchange of the alkyne for an azide moiety wherein 1 is dominated by a pseudo-chain of Pt-Pt dimers and antiparallel alignment of the azide substituents, in comparison with a circular arrangement supported by CH/π(C≡C) interactions in the alkyne version. In vitro studies indicate similar DNA binding and click reactivity of both congeners observed by fluorescent labeling. Interestingly, complex 1 shows in vitro enhanced click reactivity in comparison to a previously reported azide-appended Pt(II) complex. Despite their similar behavior in vitro, preliminary in cellulo HeLa studies indicate a superior imaging potential of azide-functionalized 1. Post-treatment fluorescent labeling of 1 observed by confocal fluorescence microscopy shows nuclear and intense nucleolar localization. These results demonstrate the potential of 1 in different cell line localization studies and for future isolation and purification of Pt-bound targets. PMID:26512733

  12. On the performance of automated porpoise-click-detectors in experiments with captive harbor porpoises (Phocoena phocoena)

    NASA Astrophysics Data System (ADS)

    Thomsen, Frank; Elk, Niels Van; Brock, Vilmut; Piper, Werner

    2005-07-01

    Recently, automated porpoise-click-detectors (T-PODs, Chelonia-Marine-Research) have been used intensively in monitoring harbor porpoises (Phocoena phocoena) in the wild. However, the automated click-detection-mechanism of the T-POD leads to questions on the characteristics of the detection process. We undertook experiments with six captive harbor porpoises (four subadult males in one pool, two adult males in another) at the Dolfinarium Harderwijk (Netherlands). One T-POD was placed for over a week in each pool, while the behavior of the porpoises was logged by visual observation. Data were analyzed using the T-POD software. A total of 725 431 clicks in 30 090 trains were recorded with 32% of the trains classified as CET HI, 27% as CET LO, and 41% as DOUBTFUL. All three train classes differed significantly in all parameters, except for click duration. We conclude that T-PODs perform generally well in detecting click trains of harbor porpoises but that in any future study trains classified as being of lower probability should be investigated very carefully to avoid the risk of losing valuable information.

  13. The Source Parameters of Echolocation Clicks from Captive and Free-Ranging Yangtze Finless Porpoises (Neophocaena asiaeorientalis asiaeorientalis).

    PubMed

    Fang, Liang; Wang, Ding; Li, Yongtao; Cheng, Zhaolong; Pine, Matthew K; Wang, Kexiong; Li, Songhai

    2015-01-01

    The clicks of Yangtze finless porpoises (Neophocaena asiaeorientalis asiaeorientalis) from 7 individuals in the tank of Baiji aquarium, 2 individuals in a netted pen at Shishou Tian-e-zhou Reserve and 4 free-ranging individuals at Tianxingzhou were recorded using a broadband digital recording system with four element hydrophones. The peak-to-peak apparent source level (ASL_pp) of clicks from individuals at the Baiji aquarium was 167 dB re 1 μPa with mean center frequency of 133 kHz, -3dB bandwidth of 18 kHz and -10 dB duration of 58 μs. The ASL_pp of clicks from individuals at the Shishou Tian-e-zhou Reserve was 180 dB re 1 μPa with mean center frequency of 128 kHz, -3dB bandwidth of 20 kHz and -10 dB duration of 39 μs. The ASL_pp of clicks from individuals at Tianxingzhou was 176 dB re 1 μPa with mean center frequency of 129 kHz, -3dB bandwidth of 15 kHz and -10 dB duration of 48 μs. Differences between the source parameters of clicks among the three groups of finless porpoises suggest these animals adapt to their echolocation signals depending on their surroundings. PMID:26053758

  14. The Source Parameters of Echolocation Clicks from Captive and Free-Ranging Yangtze Finless Porpoises (Neophocaena asiaeorientalis asiaeorientalis)

    PubMed Central

    Fang, Liang; Wang, Ding; Li, Yongtao; Cheng, Zhaolong; Pine, Matthew K.; Wang, Kexiong; Li, Songhai

    2015-01-01

    The clicks of Yangtze finless porpoises (Neophocaena asiaeorientalis asiaeorientalis) from 7 individuals in the tank of Baiji aquarium, 2 individuals in a netted pen at Shishou Tian-e-zhou Reserve and 4 free-ranging individuals at Tianxingzhou were recorded using a broadband digital recording system with four element hydrophones. The peak-to-peak apparent source level (ASL_pp) of clicks from individuals at the Baiji aquarium was 167 dB re 1 μPa with mean center frequency of 133 kHz, -3dB bandwidth of 18 kHz and -10 dB duration of 58 μs. The ASL_pp of clicks from individuals at the Shishou Tian-e-zhou Reserve was 180 dB re 1 μPa with mean center frequency of 128 kHz, -3dB bandwidth of 20 kHz and -10 dB duration of 39 μs. The ASL_pp of clicks from individuals at Tianxingzhou was 176 dB re 1 μPa with mean center frequency of 129 kHz, -3dB bandwidth of 15 kHz and -10 dB duration of 48 μs. Differences between the source parameters of clicks among the three groups of finless porpoises suggest these animals adapt to their echolocation signals depending on their surroundings. PMID:26053758

  15. The effects of preceding lead-alone and lag-alone click trains on the buildup of echo suppression

    PubMed Central

    Bishop, Christopher W.; Yadav, Deepak; London, Sam; Miller, Lee M.

    2014-01-01

    Spatial perception in echoic environments is influenced by recent acoustic history. For instance, echo suppression becomes more effective or “builds up” with repeated exposure to echoes having a consistent acoustic relationship to a temporally leading sound. Four experiments were conducted to investigate how buildup is affected by prior exposure to unpaired lead-alone or lag-alone click trains. Unpaired trains preceded lead-lag click trains designed to evoke and assay buildup. Listeners reported how many sounds they heard from the echo hemifield during the lead-lag trains. Stimuli were presented in free field (experiments 1 and 4) or dichotically through earphones (experiments 2 and 3). In experiment 1, listeners reported more echoes following a lead-alone train compared to a period of silence. In contrast, listeners reported fewer echoes following a lag-alone train; similar results were observed with earphones. Interestingly, the effects of lag-alone click trains on buildup were qualitatively different when compared to a no-conditioner trial type in experiment 4. Finally, experiment 3 demonstrated that the effects of preceding click trains on buildup cannot be explained by a change in counting strategy or perceived click salience. Together, these findings demonstrate that echo suppression is affected by prior exposure to unpaired stimuli. PMID:25096114

  16. Validity and Reliability of GraphClick and DataThief III for Data Extraction.

    PubMed

    Flower, Andrea; McKenna, John William; Upreti, Gita

    2016-05-01

    Researchers frequently rely on meta-analyses of prior research studies to efficiently evaluate a broad spectrum of results on a particular topic. In the realm of single-subject experimental designs (SSEDs), meta-analyses have a particular cachet: retaining the rigor of single-subject designs with the added robustness of replication to more fully determine the strength of a given approach or intervention. Until recently, researchers wishing to undertake meta-analytic research themselves have had limited options for synthesizing the intervention effects of a collection of studies. Researchers consistently use two software programs, DataThief III and GraphClick, to conduct meta-analytic work using SSEDs. The purpose of this study was to evaluate and compare the validity and reliability of the results yielded by each of these programs when evaluating the results of multiple research studies on the Good Behavior Game, a classroom-based intervention that has been in practice since 1969. Study findings suggest that both GraphClick and DataThief III provide valid methods of data extraction. In addition, both programs allow for reliable extraction of data between raters and between software programs. Limitations and directions for future research are explored. PMID:26611466

  17. Music, clicks, and their imaginations favor differently the event-based timing component for rhythmic movements.

    PubMed

    Bravi, Riccardo; Quarta, Eros; Del Tongo, Claudia; Carbonaro, Nicola; Tognetti, Alessandro; Minciacchi, Diego

    2015-06-01

    The involvement or noninvolvement of a clock-like neural process, an effector-independent representation of the time intervals to produce, is described as the essential difference between event-based and emergent timing. In a previous work (Bravi et al. in Exp Brain Res 232:1663-1675, 2014a. doi: 10.1007/s00221-014-3845-9 ), we studied repetitive isochronous wrist's flexion-extensions (IWFEs), performed while minimizing visual and tactile information, to clarify whether non-temporal and temporal characteristics of paced auditory stimuli affect the precision and accuracy of the rhythmic motor performance. Here, with the inclusion of new recordings, we expand the examination of the dataset described in our previous study to investigate whether simple and complex paced auditory stimuli (clicks and music) and their imaginations influence in a different way the timing mechanisms for repetitive IWFEs. Sets of IWFEs were analyzed by the windowed (lag one) autocorrelation-wγ(1), a statistical method recently introduced for the distinction between event-based and emergent timing. Our findings provide evidence that paced auditory information and its imagination favor the engagement of a clock-like neural process, and specifically that music, unlike clicks, lacks the power to elicit event-based timing, not counteracting the natural shift of wγ(1) toward positive values as frequency of movements increase. PMID:25837726

  18. Synthesis of Water Soluble Camptothecin-Polyoxetane Conjugates via Click Chemistry

    PubMed Central

    Zolotarskaya, Olga Yu.; Wagner, Alison F.; Beckta, Jason M.; Valerie, Kristoffer; Wynne, Kenneth J.; Yang, Hu

    2012-01-01

    Water soluble camptothecin (CPT)-polyoxetane conjugates were synthesized using a clickable polymeric platform P(EAMO) that was made by polymerization of acetylene-functionalized 3-ethyl-3-hydroxymethyl oxetane (i.e., EAMO). CPT was first modified with a linker 6-azidohexanoic acid via an ester linkage to yield CPT-azide. CPT-azide was then click coupled to P(EAMO) in dichloromethane using bromotris(triphenylphosphine) copper(I)/N,N-diisopropylethylamine. For water solubility and cytocompatibility improvement, methoxypolyethylene glycol azide (mPEG-azide) was synthesized from mPEG 750 gmol−1 and click grafted using copper(II) sulfate and sodium ascorbate to P(EAMO)-g-CPT. 1H NMR spectroscopy confirmed synthesis of all intermediates and the final product P(EAMO)-g-CPT/PEG. CPT was found to retain its therapeutically active lactone form. The resulting P(EAMO)-g-CPT/PEG conjugates were water soluble and produced dose-dependent cytotoxicity to human glioma cells and increased γ-H2AX foci formation, indicating extensive cell cycle-dependent DNA damage. Altogether, we have synthesized CPT-polymer conjugates able to induce controlled toxicity to human cancer cells. PMID:23051100

  19. Small polyanion recognition of a triazolium cyclodextrin click cluster in water.

    PubMed

    Le, Hoa Thi; Park, Seung Cheol; Kang, Chulhun; Lim, Choon Woo; Kim, Tae Woo

    2015-08-14

    In order to detect small polyanions (sPAs), which play important roles in many biological systems, a triazolium cyclodextrin click cluster (5, hexakis{6-(3-methyl-4-hydroxymethyl-1H-1,2,3-triazolium-1-yl)-6-deoxy}-α-cyclodextrin iodide) was synthesized and characterized. The competition binding to 5 occupied by 5-carboxyfluorescein of inositol-1,4,5-trisphosphate (IP3), phytic acid, adenosine triphosphate (ATP), ethylenediaminetetraacetic acid (EDTA), glucose, and glucose-6-phosphate was evaluated by UV/vis titration in HEPES (10 mM, pH 7.4) : methanol (1 : 1, v/v). We obtained the binding constants of IP3 and phytic acid to 5 (1.4 × 10(6) and 1.9 × 10(6) M(-1), respectively); however, the binding constants of ATP and EDTA were significantly lower (2.1 × 10(5) and 4.5 × 10(4) M(-1), respectively). Moreover, glucose and glucose-6-phosphate did not show any detectable binding. In addition, the sPA recognition of the triazolium cyclodextrin click cluster in water was confirmed by fluorescence titration. PMID:26140361

  20. Fast assessment of canine hearing using high click-rate BAER.

    PubMed

    Wilson, Wayne J; Mills, Paul C; Bradley, Andrew P; Petoe, Matthew A; Smith, Andrew W B; Dzulkarnain, Ahmad Aidil

    2011-01-01

    The aim of this study was to determine if high stimulus repetition rates could reduce the time taken to obtain brainstem auditory evoked response (BAER) waveforms of equivalent quality in dogs. Click-evoked BAER waveforms were obtained from nine healthy, adult, mixed-breed dogs at stimulus intensities of 70, 60, 50 and 40 decibels (normal hearing level) (dBnHL) and stimulus repetition rates of 11, 33 and 91 clicks-per-second (cps). The quality of the BAER waveforms was kept constant by ensuring all waveforms achieved the same signal-to-noise (SNR), as shown by their F(sp) value of 3.1. Increasing the stimulus repetition rate from 11 to 91Hz significantly (P<0.01) reduced the median time to obtain BAER waveforms of equivalent quality by 3.29-14.07s per waveform, or alternatively, increased the recording speed by 4.6-13.7 times per waveform (depending on the stimulus intensity). The use of high stimulus repetition rate BAER shows significant promise for the rapid assessment of auditory function in dogs. PMID:19900825

  1. Click chemistry armed enzyme-linked immunosorbent assay to measure palmitoylation by hedgehog acyltransferase

    PubMed Central

    Lanyon-Hogg, Thomas; Masumoto, Naoko; Bodakh, George; Konitsiotis, Antonio D.; Thinon, Emmanuelle; Rodgers, Ursula R.; Owens, Raymond J.; Magee, Anthony I.; Tate, Edward W.

    2015-01-01

    Hedgehog signaling is critical for correct embryogenesis and tissue development. However, on maturation, signaling is also found to be aberrantly activated in many cancers. Palmitoylation of the secreted signaling protein sonic hedgehog (Shh) by the enzyme hedgehog acyltransferase (Hhat) is required for functional signaling. To quantify this important posttranslational modification, many in vitro Shh palmitoylation assays employ radiolabeled fatty acids, which have limitations in terms of cost and safety. Here we present a click chemistry armed enzyme-linked immunosorbent assay (click–ELISA) for assessment of Hhat activity through acylation of biotinylated Shh peptide with an alkyne-tagged palmitoyl-CoA (coenzyme A) analogue. Click chemistry functionalization of the alkyne tag with azido-FLAG peptide allows analysis through an ELISA protocol and colorimetric readout. This assay format identified the detergent n-dodecyl β-d-maltopyranoside as an improved solubilizing agent for Hhat activity. Quantification of the potency of RU-SKI small molecule Hhat inhibitors by click–ELISA indicated IC50 values in the low- or sub-micromolar range. A stopped assay format was also employed that allows measurement of Hhat kinetic parameters where saturating substrate concentrations exceed the binding capacity of the streptavidin-coated plate. Therefore, click–ELISA represents a nonradioactive method for assessing protein palmitoylation in vitro that is readily expandable to other classes of protein lipidation. PMID:26334609

  2. Neural point-and-click communication by a person with incomplete locked-in syndrome

    PubMed Central

    Bacher, Daniel; Jarosiewicz, Beata; Masse, Nicolas Y.; Stavisky, Sergey D.; Simeral, John D.; Newell, Katherine; Oakley, Erin M.; Cash, Sydney S.; Friehs, Gerhard; Hochberg, Leigh R.

    2015-01-01

    A goal of Brain-Computer Interface (BCI) research is to develop fast and reliable means of communication for individuals with paralysis and anarthria. We evaluated the ability of an individual with incomplete locked-in syndrome enrolled in the BrainGate Neural Interface System pilot clinical trial (IDE) to communicate using neural point-and-click control. A general-purpose interface was developed to provide control of a computer cursor in tandem with one of two on-screen virtual keyboards. The novel BrainGate Radial Keyboard was compared to a standard QWERTY keyboard in a balanced copy-spelling task. The Radial Keyboard yielded a significant improvement in typing accuracy and speed – enabling typing rates over 10 correct characters per minute. The participant used this interface to communicate face-to-face with research staff by using text-to-speech conversion, and remotely using an internet chat application. This study demonstrates the first use of an intracortical BCI for neural point-and-click communication by an individual with incomplete locked-in syndrome. PMID:25385765

  3. Automatic detection of echolocation clicks based on a Gabor model of their waveform.

    PubMed

    Madhusudhana, Shyam; Gavrilov, Alexander; Erbe, Christine

    2015-06-01

    Prior research has shown that echolocation clicks of several species of terrestrial and marine fauna can be modelled as Gabor-like functions. Here, a system is proposed for the automatic detection of a variety of such signals. By means of mathematical formulation, it is shown that the output of the Teager-Kaiser Energy Operator (TKEO) applied to Gabor-like signals can be approximated by a Gaussian function. Based on the inferences, a detection algorithm involving the post-processing of the TKEO outputs is presented. The ratio of the outputs of two moving-average filters, a Gaussian and a rectangular filter, is shown to be an effective detection parameter. Detector performance is assessed using synthetic and real (taken from MobySound database) recordings. The detection method is shown to work readily with a variety of echolocation clicks and in various recording scenarios. The system exhibits low computational complexity and operates several times faster than real-time. Performance comparisons are made to other publicly available detectors including pamguard. PMID:26093399

  4. Climatic, Edaphic Factors and Cropping History Help Predict Click Beetle (Coleoptera: Elateridae) (Agriotes spp.) Abundance

    PubMed Central

    Kozina, A.; Lemic, D.; Bazok, R.; Mikac, K. M.; Mclean, C. M.; Ivezić, M.; Igrc Barčić, J.

    2015-01-01

    It is assumed that the abundance of Agriotes wireworms (Coleoptera: Elateridae) is affected by agro-ecological factors such as climatic and edaphic factors and the crop/previous crop grown at the sites investigated. The aim of this study, conducted in three different geographic counties in Croatia from 2007 to 2009, was to determine the factors that influence the abundance of adult click beetle of the species Agriotes brevis Cand., Agriotes lineatus (L.), Agriotes obscurus (L.), Agriotes sputator (L.), and Agriotes ustulatus Schall. The mean annual air temperature, total rainfall, percentage of coarse and fine sand, coarse and fine silt and clay, the soil pH, and humus were investigated as potential factors that may influence abundance. Adult click beetle emergence was monitored using sex pheromone traps (YATLORf and VARb3). Exploratory data analysis was preformed via regression tree models and regional differences in Agriotes species’ abundance were predicted based on the agro-ecological factors measured. It was found that the best overall predictor of A. brevis abundance was the previous crop grown. Conversely, the best predictor of A. lineatus abundance was the current crop being grown and the percentage of humus. The best predictor of A. obscurus abundance was soil pH in KCl. The best predictor of A. sputator abundance was rainfall. Finally, the best predictors of A. ustulatus abundance were soil pH in KCl and humus. These results may be useful in regional pest control programs or for predicting future outbreaks of these species. PMID:26175463

  5. Selective conjugation of proteins by mining active proteomes through click-functionalized magnetic nanoparticles.

    PubMed

    Ilyas, Shaista; Ilyas, Muhammad; van der Hoorn, Renier A L; Mathur, Sanjay

    2013-11-26

    Superparamagnetic iron oxide nanoparticles (SPIONs) coated with azide groups were functionalized at the surface with biotin (biotin@SPIONs) and cysteine protease inhibitor E-64 (E-64@SPIONs) with the purpose of developing nanoparticle-based assays for identifying cysteine proteases in proteomes. Magnetite particles (ca. 6 nm) were synthesized by microwave-assisted thermal decomposition of iron acetylacetonate and subsequently functionalized following a click chemistry protocol to obtain biotin and E-64 labeled particulate systems. Successful surface modification and covalent attachment of functional groups and molecules were confirmed by FT-IR spectroscopy and thermal gravimetric analysis. The ability of the surface-grafted biotin terminal groups to specifically interact with streptavidin (either horseradish peroxidase [(HRP)-luminol-H2O2] or rhodamine) was confirmed by chemiluminescent assay. A quantitative assessment showed a capture limit of 0.55-1.65 μg protein/100 μg particles. Furthermore, E-64@SPIONs were successfully used to specifically label papain-like cysteine proteases from crude plant extracts. Owing to the simplicity and versatility of the technique, together with the superparamagnetic behavior of FeOx-nanoparticles, the results demonstrate that click chemistry on surface anchored azide group is a viable approach toward bioconjugations that can be extended to other nanoparticles surfaces with different functional groups to target specific therapeutic and diagnostic applications. PMID:24143894

  6. Targeted Ultrasound-Assisted Cancer-Selective Chemical Labeling and Subsequent Cancer Imaging using Click Chemistry.

    PubMed

    Wang, Hua; Gauthier, Marianne; Kelly, Jamie R; Miller, Rita J; Xu, Ming; O'Brien, William D; Cheng, Jianjun

    2016-04-25

    Metabolic sugar labeling followed by the use of reagent-free click chemistry is an established technique for in vitro cell targeting. However, selective metabolic labeling of the target tissues in vivo remains a challenge to overcome, which has prohibited the use of this technique for targeted in vivo applications. Herein, we report the use of targeted ultrasound pulses to induce the release of tetraacetyl N-azidoacetylmannosamine (Ac4 ManAz) from microbubbles (MBs) and its metabolic expression in the cancer area. Ac4 ManAz-loaded MBs showed great stability under physiological conditions, but rapidly collapsed in the presence of tumor-localized ultrasound pulses. The released Ac4 ManAz from MBs was able to label 4T1 tumor cells with azido groups and significantly improved the tumor accumulation of dibenzocyclooctyne (DBCO)-Cy5 by subsequent click chemistry. We demonstrated for the first time that Ac4 ManAz-loaded MBs coupled with the use of targeted ultrasound could be a simple but powerful tool for in vivo cancer-selective labeling and targeted cancer therapies. PMID:27010510

  7. Synthesis and amylin receptor activity of glycomimetics of pramlintide using click chemistry.

    PubMed

    Yule, Lauren R; Bower, Rebekah L; Kaur, Harveen; Kowalczyk, Renata; Hay, Debbie L; Brimble, Margaret A

    2016-06-21

    Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. AMY1(a) receptor activity was retained by incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide. Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting. PMID:27139251

  8. Why are there no long distance jumpers among click-beetles (Elateridae)?

    PubMed

    Ribak, Gal; Mordechay, Oded; Weihs, Daniel

    2013-09-01

    Click-beetles jump from an inverted position without using their legs. This unique mechanism results in high vertical jumps with the jump angle restricted by the rigid morphology of the exoskeleton. We explored the option to exploit this jumping mechanism for application to small mechanical devices having to extricate themselves from rough terrain. We combined experiments on a biomimetic jumping device with a physical-mathematical model of the jump to assess the effect of morphological variation on the jumping performance. We found that through morphological change of two non-dimensional (size independent) parameters, the propulsive force powering the jump can be directed at angles as small as 40°. However, in practice jumping at such angles is precluded by loss of traction with the ground during the push-off phase. This limitation to steep jump angles is inherent to the jumping mechanism which is based on rotation of body parts about a single hinge. Such a rotation dictates a curvilinear trajectory for the center of mass during takeoff so that the vertical and horizontal accelerations occur out of phase, implying loss of traction with the ground before substantial horizontal acceleration can be reached. Thus click-beetle inspired jumping is effective mainly for making steep-angle righting jumps. PMID:23837996

  9. Propagation of narrow-band-high-frequency clicks: measured and modeled transmission loss of porpoise-like clicks in porpoise habitats.

    PubMed

    DeRuiter, Stacy L; Hansen, Michael; Koopman, Heather N; Westgate, Andrew J; Tyack, Peter L; Madsen, Peter T

    2010-01-01

    Estimating the range at which harbor porpoises can detect prey items and environmental objects is integral to understanding their biosonar. Understanding the ranges at which they can use echolocation to detect and avoid obstacles is particularly important for strategies to reduce bycatch. Transmission loss (TL) during acoustic propagation is an important determinant of those detection ranges, and it also influences animal detection functions used in passive acoustic monitoring. However, common assumptions regarding TL have rarely been tested. Here, TL of synthetic porpoise clicks was measured in porpoise habitats in Canada and Denmark, and field data were compared with spherical spreading law and ray-trace (Bellhop) model predictions. Both models matched mean observations quite well in most cases, indicating that a spherical spreading law can usually provide an accurate first-order estimate of TL for porpoise sounds in porpoise habitat. However, TL varied significantly (+/-10 dB) between sites and over time in response to variability in seafloor characteristics, sound-speed profiles, and other short-timescale environmental fluctuations. Such variability should be taken into account in estimates of the ranges at which porpoises can communicate acoustically, detect echolocation targets, and be detected via passive acoustic monitoring. PMID:20059001

  10. Application of a water-soluble pyridyl disulfide amine linker for use in Cu-free click bioconjugation

    PubMed Central

    Thomas, Joshua D.; Burke, Terrence R.

    2011-01-01

    Described herein is the design and synthesis of a discrete heterobifunctional PEG-based pyridyl disulfide/amine-containing linker that can be used in the Cu-free click preparation of bioconjugates. The title PEG-based pyridyl disulfide amine linker is a potentially useful reagent for preparing water-soluble disulfide-linked cargos. It may be particularly valuable in expanding the field of Cu-free click-based bioconjugations to include reductively labile antibody, polymer, or nanoparticle-based drug conjugates. PMID:21826118

  11. Engineering single-molecule, nanoscale, and microscale bio-functional materials via click chemistry

    NASA Astrophysics Data System (ADS)

    Daniele, Michael Angelo-Anthony

    To expand the design envelope and supplement the materials library available to biomaterials scientists, the copper(I)-catalyzed azide-alkyne cycloaddition (CuCAAC) was explored as a route to design, synthesize and characterize bio-functional small-molecules, nanoparticles, and microfibers. In each engineered system, the use of click chemistry provided facile, bio-orthogonal control for materials synthesis; moreover, the results provided a methodology and more complete, fundamental understanding of the use of click chemistry as a tool for the synergy of biotechnology, polymer and materials science. Fluorophores with well-defined photophysical characteristics (ranging from UV to NIR fluorescence) were used as building blocks for small-molecule, fluorescent biosensors. Fluorophores were paired to exhibit fluorescence resonant energy transfer (FRET) and used to probe the metabolic activity of carbazole 1,9a-dioxygenase (CARDO). The FRET pair exhibited a significant variation in PL response with exposure to the lysate of Pseudomonas resinovorans CA10, an organism which can degrade variants of both the donor and acceptor fluorophores. Nanoparticle systems were modified via CuCAAC chemistry to carry affinity tags for CARDO and were subsequently utilized for affinity based bioseparation of CARDO from crude cell lysate. The enzymes were baited with an azide-modified carbazolyl-moiety attached to a poly(propargyl acrylate) nanoparticle. Magnetic nanocluster systems were also modified via CuCAAC chemistry to carry fluorescent imaging tags. The iron-oxide nanoclusters were coated with poly(acrylic acid-co-propargyl acrylate) to provide a clickable surface. Ultimately, alternate Cu-free click chemistries were utilized to produce biohybrid microfibers. The biohybrid microfibers were synthesized under benign photopolymerization conditions inside a microchannel, allowing the encapsulation of viable bacteria. By adjusting pre-polymer solutions and laminar flow rates within the

  12. The Blue Button Project: Engaging Patients in Healthcare by a Click of a Button

    PubMed Central

    Mohsen, Mona Omar; Aziz, Hassan A.

    2015-01-01

    The Blue Button project has become a way for many Americans to download their health records by just a click in any way that suits them, such as in print, on a thumb drive, or on their mobile devices and smartphones. Several organizations have developed and applied Blue Buttons on their websites to allow beneficiaries to securely access and view personal medical information and claims. The purpose of this literature review is to highlight the significance of the Blue Button project in the field of health information management. Findings suggest that the project could empower and engage consumers and patients in a healthcare system by allowing access to medical records, thereby promoting better management and overall improvement of their healthcare. To date, the project has gained wide support from insurers, technology companies, and health providers despite the challenges of standardization and interoperability. PMID:26755898

  13. Monitoring Protein O-GlcNAc Status via Metabolic Labeling and Copper-free Click Chemistry

    PubMed Central

    Teo, Chin Fen; Wells, Lance

    2014-01-01

    O-GlcNAc modification found on the serine and threonine residues of intracellular proteins is an inducible post-translational modification that regulates numerous biological processes. In combination with other cell biological and biochemical approaches, a robust and streamlined strategy for detecting the number and stoichiometry of O-GlcNAc modification can provide valuable insights for decoding the functions of O-GlcNAc at the molecular level. Herein, we report an optimized workflow for evaluating the O-GlcNAc status of proteins using a combination of metabolic labeling and click chemistry based mass tagging. This method is strategically complementary to the chemoenzymatic-based mass-tagging method. PMID:24995865

  14. Photophysical and nonlinear optical studies of tetraakynyl zincphthalocyanine and its "clicked" analogue

    NASA Astrophysics Data System (ADS)

    Bankole, Owolabi M.; Nyokong, Tebello

    2015-06-01

    We report here for the first time on the photophysical and nonlinear optical behavior of tetra-substituted alkynyl zinc phthalocyanine and its "clicked" analogue (4 and 5). The compounds exhibited high triplet quantum yields in dimethylsulphoxide (DMSO). Nonlinear optical (NLO) properties were also evaluated for the two compounds at 532 nm and 10 ns in DMSO. We observed two-photon absorption (2PA) and strong reverse saturable absorption (RSA) as the dominant mechanisms at nanosecond laser excitation. The presence of electron acceptor groups fused with triazole linkers in the peripheral positions of 4 provide excellent coexistent features, such as enhanced triplet quantum yields and lifetimes compared to 5. Large third-order susceptibility (2.09 × 10-11 and 3.53 × 10-9 esu) and hyperpolarizability (1.09 × 10-30 and 9.13 × 10-29 esu) were estimated for complexs 4 and 5, respectively.

  15. Development of red-shifted mutants derived from luciferase of Brazilian click beetle Pyrearinus termitilluminans.

    PubMed

    Nishiguchi, Tomoki; Yamada, Toshimichi; Nasu, Yusuke; Ito, Mashiho; Yoshimura, Hideaki; Ozawa, Takeaki

    2015-10-01

    Luciferase, a bioluminescent protein, has been used as an analytical tool to visualize intracellular phenomena. Luciferase with red light emission is particularly useful for bioluminescence imaging because of its high transmittance in mammalian tissues. However, the luminescence intensity of existing luciferases with their emission over 600 nm is insufficient for imaging studies because of their weak intensities. We developed mutants of Emerald luciferase (Eluc) from Brazilian click beetle (Pyrearinus termitilluminans), which emits the strongest bioluminescence among beetle luciferases. We successively introduced four amino acid mutations into the luciferase based on a predicted structure of Eluc using homology modeling. Results showed that quadruple mutations R214K/H241K/S246H/H347A into the beetle luciferase emit luminescence with emission maximum at 626 nm, 88-nm red-shift from the wild-type luciferase. This mutant luciferase is anticipated for application in in vivo multicolor imaging in living samples. PMID:26313214

  16. A recyclable and reusable supported Cu(I) catalyzed azide-alkyne click polymerization

    NASA Astrophysics Data System (ADS)

    Wu, Haiqiang; Li, Hongkun; Kwok, Ryan T. K.; Zhao, Engui; Sun, Jing Zhi; Qin, Anjun; Tang, Ben Zhong

    2014-05-01

    The azide-alkyne click polymerization (AACP) has emerged as a powerful tool for the synthesis of functional polytriazoles. While, for the Cu(I)-catalyzed AACP, the removal of the catalytic Cu(I) species from the resulting polytriazoles is difficult, and the research on the recyclability and reusability of the catalyst remains intact. Herein, we reported the first example of using recyclable and reusable supported Cu(I) catalyst of CuI@A-21 for the AACP. CuI@A-21 could not only efficiently catalyze the AACP but also be reused for at least 4 cycles. Moreover, pronounced reduction of copper residues in the products was achieved. Apart from being a green and cost-effective polymer synthesis strategy, this method will also broaden the application of AACP in material and biological sciences and provide guidelines for other polymerizations with metal catalysts.

  17. A recyclable and reusable supported Cu(I) catalyzed azide-alkyne click polymerization

    PubMed Central

    Wu, Haiqiang; Li, Hongkun; Kwok, Ryan T. K.; Zhao, Engui; Sun, Jing Zhi; Qin, Anjun; Tang, Ben Zhong

    2014-01-01

    The azide–alkyne click polymerization (AACP) has emerged as a powerful tool for the synthesis of functional polytriazoles. While, for the Cu(I)-catalyzed AACP, the removal of the catalytic Cu(I) species from the resulting polytriazoles is difficult, and the research on the recyclability and reusability of the catalyst remains intact. Herein, we reported the first example of using recyclable and reusable supported Cu(I) catalyst of CuI@A-21 for the AACP. CuI@A-21 could not only efficiently catalyze the AACP but also be reused for at least 4 cycles. Moreover, pronounced reduction of copper residues in the products was achieved. Apart from being a green and cost-effective polymer synthesis strategy, this method will also broaden the application of AACP in material and biological sciences and provide guidelines for other polymerizations with metal catalysts. PMID:24875854

  18. Bioconjugation of biotin to the interfaces of polymeric micelles via in situ click chemistry.

    PubMed

    Wang, Xiaojuan; Liu, Li; Luo, Yan; Zhao, Hanying

    2009-01-20

    Azido-containing amphiphilic triblock copolymer poly(ethylene glycol)-b-poly(azidoethyl methacrylate)-b-poly(methyl methacrylate) (PEG-b-PAzEMA-b-PMMA) was prepared by postpolymerization functionalization of poly(ethylene glycol)-b-poly(hydroxyethyl methacrylate)-b-poly(methyl methacrylate) (PEG-b-PHEMA-b-PMMA). In aqueous media, PEG-b-PAzEMA-b-PMMA self-assembled into spherical micelles with the azide groups at the hydrophobic/hydrophilic interface due to the molecular architecture. Biotin was conjugated to the micelles by in situ click chemistry between azide groups and alkynated biotin, resulting in the formation of a functional interface between the hydrophilic shell and the hydrophobic core. The bioavailability of biotin to avidin was demonstrated by an avidin/4'-hydroxyazobenzene-2-carboxylic acid (avidin/HABA) assay, transmission electron microscopy, and dynamic light scattering investigations. PMID:19105785

  19. Directional Materials—Nanoporous Organosilica Monoliths with Multiple Gradients Prepared Using Click Chemistry.

    PubMed

    Schachtschneider, Andreas; Wessig, Martin; Spitzbarth, Martin; Donner, Adrian; Fischer, Christian; Drescher, Malte; Polarz, Sebastian

    2015-09-01

    The existence of more than one functional entity is fundamental for materials, which are desired of fulfilling complementary or succeeding tasks. Whereas it is feasible to make materials with a homogeneous distribution of two different, functional groups, cases are extremely rare exhibiting a smooth transition from one property to the next along a defined distance. We present a new approach leading to high-surface area solids with functional gradients at the microstructural level. Periodically ordered mesoporous organosilicas (PMOs) and aerogel-like monolithic bodies with a maximum density of azide groups were prepared from a novel sol-gel precursor. The controlled and fast conversion of the azide into numerous functions by click chemistry is the prerequisite for the implementation of manifold gradient profiles. Herein we discuss materials with chemical, optical and structural gradients, which are interesting for all applications requiring directionality, for example, chromatography. PMID:26190518

  20. Post-synthetic Spin-Labeling of RNA through Click Chemistry for PELDOR Measurements.

    PubMed

    Kerzhner, Mark; Abdullin, Dinar; Więcek, Jennifer; Matsuoka, Hideto; Hagelueken, Gregor; Schiemann, Olav; Famulok, Michael

    2016-08-16

    Site-directed spin labeling of RNA based on click chemistry is used in combination with pulsed electron-electron double resonance (PELDOR) to benchmark a nitroxide spin label, called here dŲ. We compare this approach with another established method that employs the rigid spin label Çm for RNA labeling. By using CD spectroscopy, thermal denaturation measurements, CW-EPR as well as PELDOR we analyzed and compared the influence of dŲ and Çm on a self-complementary RNA duplex. Our results demonstrate that the conformational diversity of dŲ is significantly reduced near the freezing temperature of a phosphate buffer, resulting in strongly orientation-selective PELDOR time traces of the dŲ-labeled RNA duplex. PMID:27412453

  1. Novel types of carborane-carrier hyaluronan derivatives via "click chemistry".

    PubMed

    Di Meo, Chiara; Panza, Luigi; Campo, Federica; Capitani, Donatella; Mannina, Luisa; Banzato, Alessandra; Rondina, Maria; Rosato, Antonio; Crescenzi, Vittorio

    2008-07-01

    Two new HA derivatives bearing carborane rings were synthesized by click chemistry. The optimal conditions were assessed for the preparation of biocompatible boron carriers, potentially suitable for application in BNCT and capable of targeting the CD44 antigen. The new polymeric samples were characterized by means of NMR-spectroscopy techniques that gave degrees of 17 and 8% for HAAACB and HapACB, respectively. Both HAAACB and HApACB turned out to be nontoxic for colorectal, ovarian and bladder tumor cell lines, to disclose a specific interaction with the CD44 antigen as the native hyaluronan moiety, and to deliver boron-atom concentrations largely sufficient for BNCT therapy when accumulated in cancer cells. PMID:18412288

  2. "Click" chemistry mildly stabilizes bifunctional gold nanoparticles for sensing and catalysis.

    PubMed

    Li, Na; Zhao, Pengxiang; Liu, Na; Echeverria, María; Moya, Sergio; Salmon, Lionel; Ruiz, Jaime; Astruc, Didier

    2014-07-01

    A large family of bifunctional 1,2,3-triazole derivatives that contain both a polyethylene glycol (PEG) chain and another functional fragment (e.g., a polymer, dendron, alcohol, carboxylic acid, allyl, fluorescence dye, redox-robust metal complex, or a β-cyclodextrin unit) has been synthesized by facile "click" chemistry and mildly coordinated to nanogold particles, thus providing stable water-soluble gold nanoparticles (AuNPs) in the size range 3.0-11.2 nm with various properties and applications. In particular, the sensing properties of these AuNPs are illustrated through the detection of an analogue of a warfare agent (i.e., sulfur mustard) by means of a fluorescence "turn-on" assay, and the catalytic activity of the smallest triazole-AuNPs (core of 3.0 nm) is excellent for the reduction of 4-nitrophenol in water. PMID:24891131

  3. Synthesis and characterization of modified Schiff base silatranes (MSBS) via 'Click Silylation'

    NASA Astrophysics Data System (ADS)

    Singh, Gurjaspreet; Arora, Aanchal; Mangat, Satinderpal Singh; Singh, Jandeep; Chaudhary, Sunita; Kaur, Navneet; Choquesillo-Lazarte, Duane

    2015-01-01

    Schiff bases (1a-1d) were modified into terminal alkynes (2a-2d) which on Click Silylation with 3-azidopropyltriethoxysilane (AzPTES) yielded 1,2,3-triazole capped triethoxysilanes (3a-3d). These triethoxysilanes on transesterification with triethanolamine afforded corresponding modified Schiff base silatranes (MSBS) (4a-4d) in high yield and purity. All the synthesized compounds were well characterized by IR, NMR (1H, 13C), mass spectroscopy, elemental analysis and complete structure elucidation by X-ray diffraction studies for 2b and 4b. Starting alkynes and final silatranes are further compared by their absorption spectra and TGA analysis. Synthesized MSBS are the first compounds of their kind which being hydrolytically stable can be put to further use in the field of medical and material research.

  4. The Blue Button Project: Engaging Patients in Healthcare by a Click of a Button.

    PubMed

    Mohsen, Mona Omar; Aziz, Hassan A

    2015-01-01

    The Blue Button project has become a way for many Americans to download their health records by just a click in any way that suits them, such as in print, on a thumb drive, or on their mobile devices and smartphones. Several organizations have developed and applied Blue Buttons on their websites to allow beneficiaries to securely access and view personal medical information and claims. The purpose of this literature review is to highlight the significance of the Blue Button project in the field of health information management. Findings suggest that the project could empower and engage consumers and patients in a healthcare system by allowing access to medical records, thereby promoting better management and overall improvement of their healthcare. To date, the project has gained wide support from insurers, technology companies, and health providers despite the challenges of standardization and interoperability. PMID:26755898

  5. Development of red-shifted mutants derived from luciferase of Brazilian click beetle Pyrearinus termitilluminans

    NASA Astrophysics Data System (ADS)

    Nishiguchi, Tomoki; Yamada, Toshimichi; Nasu, Yusuke; Ito, Mashiho; Yoshimura, Hideaki; Ozawa, Takeaki

    2015-10-01

    Luciferase, a bioluminescent protein, has been used as an analytical tool to visualize intracellular phenomena. Luciferase with red light emission is particularly useful for bioluminescence imaging because of its high transmittance in mammalian tissues. However, the luminescence intensity of existing luciferases with their emission over 600 nm is insufficient for imaging studies because of their weak intensities. We developed mutants of Emerald luciferase (Eluc) from Brazilian click beetle (Pyrearinus termitilluminans), which emits the strongest bioluminescence among beetle luciferases. We successively introduced four amino acid mutations into the luciferase based on a predicted structure of Eluc using homology modeling. Results showed that quadruple mutations R214K/H241K/S246H/H347A into the beetle luciferase emit luminescence with emission maximum at 626 nm, 88-nm red-shift from the wild-type luciferase. This mutant luciferase is anticipated for application in in vivo multicolor imaging in living samples.

  6. Sugar microarray via click chemistry: molecular recognition with lectins and amyloid β (1-42)

    NASA Astrophysics Data System (ADS)

    Matsumoto, Erino; Yamauchi, Takahiro; Fukuda, Tomohiro; Miura, Yoshiko

    2009-06-01

    Sugar microarrays were fabricated on various substrates via click chemistry. Acetylene-terminated substrates were prepared by forming self-assembled monolayers (SAMs) on a gold substrate with alkyl-disulfide and on silicon, quartz and glass substrates with a silane-coupling reagent. The gold substrates were subjected to surface plasmon resonance measurements, and the quartz and glass substrates were subjected to spectroscopy measurements and optical microscopy observation. The saccharide-immobilized substrate on the gold substrate showed specific interaction with the corresponding lectin, and the saccharides showed inert surface properties to other proteins with a high signal-to-noise ratio. We also focused on the saccharide-protein interaction on protein amyloidosis of Alzheimer amyloid β. Amyloid β peptide showed conformation transition on the saccharide-immobilization substrate into a β-sheet, and fibril formation and amyloid aggregates were found on the specific saccharides.

  7. Time-frequency decomposition of click evoked otoacoustic emissions in children.

    PubMed

    Mishra, Srikanta K; Biswal, Milan

    2016-05-01

    Determining the time-frequency distributions of click-evoked otoacoustic emissions (CEOAEs) are scientifically and clinically relevant because of their relationship with cochlear mechanisms. This study investigated the time-frequency properties of CEOAEs in 5-10 year old children. In the first part, we examined the feasibility of the S transform to characterize the time-frequency features of CEOAEs. A synthetic signal with known gammatones was analyzed using the S transform, as well as a wavelet transform with the basis function used traditionally for CEOAE analysis. The S and wavelet transforms provided similar representations of the gammatones of the synthetic signal in the mid and high frequencies. However, the S transform yielded a slightly more precise time-frequency representation at low frequencies (500 and 707 Hz). In the second part, we applied the S transform to compare the time-frequency distribution of CEOAEs between adults and children. Several confounding variables, such as spontaneous emissions and potential efferent effects from the use of higher click rates, were considered for obtaining reliable CEOAE recordings. The results revealed that the emission level, level versus frequency plot, latency, and latency versus frequency plot in 5-10 year old children are adult-like. The time-frequency characteristics of CEOAEs in 5-10 year old children are consistent with the maturation of various aspects of cochlear mechanics, including the basal to apical transition. In sum, the description of the time-frequency features in children and the use of the S transform to decompose CEOAEs, are novel aspects of this study. The S transform can be used as an alternative approach to characterize the time-frequency distribution of CEOAEs. PMID:26976693

  8. Click Chemistry Finds Its Way in Constructing an Ionic Highway in Anion-Exchange Membrane.

    PubMed

    Ge, Qianqian; Ran, Jin; Miao, Jibin; Yang, Zhengjin; Xu, Tongwen

    2015-12-30

    To find the way to construct an ionic highway in anion-exchange membranes (AEMs), a series of side-chain-type alkaline polymer electrolytes (APEs) based on poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) polymer backbones were synthesized via Cu(I)-catalyzed click chemistry. The resulting triazole groups and quaternary ammonium (QA) groups facilitate the formation of a continuous hydrogen bond network, which will lead to high hydroxide conductivity according to Grotthuss-type mechanism. Microphase separation induced by long alkyl side chains contributes at the same time to further improving the hydroxide conductivity of the resultant AEMs. Hydroxide conductivity as high as 52.8 mS/cm is obtained for membrane TA-14C-1.21 (IEC = 1.21 mmol/g) with the longest pendant chain at 30 °C, and the conductivity can be increased to 140 mS/cm when the temperature was increased to 80 °C. Moreover, the corresponding water uptake is only 8.6 wt % at 30 °C. In the meantime, the membrane properties can be tuned by precisely regulating the hydrophilic/hydrophobic ratio in the cationic head groups. Compared with AEMs containing triazole and quaternized trimethylammonium head groups, enhanced dimensional stability and mechanical properties are obtained by tuning side-chain chemistry. However, the alkaline stability of the membrane is not as stable as anticipated, probably because of the existence of the triazole ring. Further study will be focused on increasing the alkali stability of the membrane. We envisage that the side-chain-type APEs meditated by click chemistry bearing long hydrophobic side chains pendant to the cationic head groups hold promise as a novel AEMs material. PMID:26645427

  9. Brick and Click Libraries: Proceedings of an Academic Library Symposium (9th, Maryville, Missouri, November 6, 2009)

    ERIC Educational Resources Information Center

    Ury, Connie Jo, Ed.; Baudino, Frank, Ed.; Park, Sarah G., Ed.

    2009-01-01

    Twenty-one scholarly papers and fourteen abstracts comprise the content of the ninth annual "Brick and Click Libraries Symposium," held annually at Northwest Missouri State University in Maryville, Missouri. The peer-reviewed proceedings, authored by academic librarians and presented at the symposium, portray the contemporary and future face of…

  10. Assessing the Mitochondrial Membrane Potential in Cells and In Vivo using Targeted Click Chemistry and Mass Spectrometry.

    PubMed

    Logan, Angela; Pell, Victoria R; Shaffer, Karl J; Evans, Cameron; Stanley, Nathan J; Robb, Ellen L; Prime, Tracy A; Chouchani, Edward T; Cochemé, Helena M; Fearnley, Ian M; Vidoni, Sara; James, Andrew M; Porteous, Carolyn M; Partridge, Linda; Krieg, Thomas; Smith, Robin A J; Murphy, Michael P

    2016-02-01

    The mitochondrial membrane potential (Δψm) is a major determinant and indicator of cell fate, but it is not possible to assess small changes in Δψm within cells or in vivo. To overcome this, we developed an approach that utilizes two mitochondria-targeted probes each containing a triphenylphosphonium (TPP) lipophilic cation that drives their accumulation in response to Δψm and the plasma membrane potential (Δψp). One probe contains an azido moiety and the other a cyclooctyne, which react together in a concentration-dependent manner by "click" chemistry to form MitoClick. As the mitochondrial accumulation of both probes depends exponentially on Δψm and Δψp, the rate of MitoClick formation is exquisitely sensitive to small changes in these potentials. MitoClick accumulation can then be quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This approach enables assessment of subtle changes in membrane potentials within cells and in the mouse heart in vivo. PMID:26712463

  11. Brick and Click Libraries: Proceedings of a Regional Academic Library Symposium (Missouri State University, Maryville, Missouri, October 10, 2003)

    ERIC Educational Resources Information Center

    Ury, Connie Jo, Ed.; Baudino, Frank, Ed.

    2003-01-01

    The 2003 Brick and Click is a one-day conference that focuses on providing library resources and services for students who are either on-campus learners or off-campus learners. The conference theme was "The Shape of Tomorrow". It is sponsored by the Northwest Missouri State University in order to offer academic librarians a forum for sharing…

  12. Integrating the Visual Arts Back into the Classroom with Mobile Applications: Teaching beyond the "Click and View" Approach

    ERIC Educational Resources Information Center

    Katz-Buonincontro, Jen; Foster, Aroutis

    2013-01-01

    Teachers can use mobile applications to integrate the visual arts back into the classroom, but how? This article generates recommendations for selecting and using well-designed mobile applications in the visual arts beyond a "click and view " approach. Using quantitative content analysis, the results show the extent to which a sample of…

  13. Brick and Click Libraries: Proceedings of an Academic Library Symposium (10th, Maryville, Missouri, November 5, 2010)

    ERIC Educational Resources Information Center

    Baudino, Frank, Ed.; Ury, Connie Jo, Ed.; Park, Sarah G., Ed.

    2010-01-01

    Twenty-one scholarly papers and fifteen abstracts comprise the content of the tenth annual Brick and Click Libraries Symposium, held annually at Northwest Missouri State University in Maryville, Missouri. The peer-reviewed proceedings, authored by academic librarians and presented at the symposium, portray the contemporary and future face of…

  14. Brick and Click Libraries: Proceedings of an Academic Library Symposium (11th, Maryville, Missouri, November 4, 2011)

    ERIC Educational Resources Information Center

    Baudino, Frank, Ed.

    2011-01-01

    Twenty-three scholarly papers and twelve abstracts comprise the content of the eleventh annual Brick and Click Libraries Symposium, held at Northwest Missouri State University in Maryville, Missouri. The peer-reviewed proceedings, authored by academic librarians and presented at the symposium, portray the contemporary and future face of…

  15. Brick and Click Libraries: Proceedings of an Academic Libraries Symposium (7th, Maryville, Missouri, November 2, 2007)

    ERIC Educational Resources Information Center

    Ury, Connie Jo, Ed.; Baudino, Frank, Ed.; Park, Sarah G., Ed.

    2007-01-01

    Twenty-three scholarly papers and eleven abstracts reflect the content of the seventh "Brick and Click Libraries Symposium," held annually at Northwest Missouri State University in Maryville, Missouri. The proceedings, authored by academic librarians and presented at the symposium, portray the contemporary and future face of librarianship. Many of…

  16. Compensating for the effects of site and equipment variation on delphinid species identification from their echolocation clicks.

    PubMed

    Roch, Marie A; Stinner-Sloan, Johanna; Baumann-Pickering, Simone; Wiggins, Sean M

    2015-01-01

    A concern for applications of machine learning techniques to bioacoustics is whether or not classifiers learn the categories for which they were trained. Unfortunately, information such as characteristics of specific recording equipment or noise environments can also be learned. This question is examined in the context of identifying delphinid species by their echolocation clicks. To reduce the ambiguity between species classification performance and other confounding factors, species whose clicks can be readily distinguished were used in this study: Pacific white-sided and Risso's dolphins. A subset of data from autonomous acoustic recorders located at seven sites in the Southern California Bight collected between 2006 and 2012 was selected. Cepstral-based features were extracted for each echolocation click and Gaussian mixture models were used to classify groups of 100 clicks. One hundred Monte-Carlo three-fold experiments were conducted to examine classification performance where fold composition was determined by acoustic encounter, recorder characteristics, or recording site. The error rate increased from 6.1% when grouped by acoustic encounter to 18.1%, 46.2%, and 33.2% for grouping by equipment, equipment category, and site, respectively. A noise compensation technique reduced error for these grouping schemes to 2.7%, 4.4%, 6.7%, and 11.4%, respectively, a reduction in error rate of 56%-86%. PMID:25618035

  17. How Users Take Advantage of Different Forms of Interactivity on Online News Sites: Clicking, E-Mailing, and Commenting

    ERIC Educational Resources Information Center

    Boczkowski, Pablo J.; Mitchelstein, Eugenia

    2012-01-01

    This study examines the uptake of multiple interactive features on news sites. It looks at the thematic composition of the most clicked, most e-mailed, and most commented stories during periods of heightened and routine political activity. Results show that (a) during the former period, the most commented stories were more likely to be focused on…

  18. Brick and Click Libraries: Changes and Challenges. Proceedings of a Regional Academic Library Symposium (Maryville, Missouri, October 18, 2002).

    ERIC Educational Resources Information Center

    Ury, Connie Jo, Ed.; Wainscott, Vicki, Ed.

    This proceedings of the Brick and Click Libraries Symposium contains the following papers: (1) "Electronic Journals: Vendor Solutions to Access Issues" (Nona Barton); (2) "Tips on Funding" (Janice Borey); (3) "Why Are So Many Web Pages Still So Hard To Use?" (Jerry R. Brown); (4) "The Secrets of Full-Text Databases: The Overlap between a Same…

  19. Brick and Click Libraries: Proceedings of an Academic Libraries Symposium (8th, Maryville, Missouri, November 7, 2008)

    ERIC Educational Resources Information Center

    Baudino, Frank, Ed.; Ury, Connie Jo, Ed.; Park, Sarah G., Ed.

    2008-01-01

    Eighteen scholarly papers and eighteen abstracts comprise the content of the 8th "Brick and Click Libraries Symposium," held annually at Northwest Missouri State University in Maryville, Missouri. The proceedings, authored by academic librarians and presented at the symposium, portray the contemporary and future face of librarianship. Many of the…

  20. Brick and Click Libraries: Proceedings of an Academic Library Symposium (Northwest Missouri State University, Maryville, Missouri, October 14, 2005)

    ERIC Educational Resources Information Center

    Ury, Connie Jo., Ed.; Baudino, Frank, Ed.

    2005-01-01

    These proceedings document the fifth year of the "Brick and Click Libraries Symposium", held annually at Northwest Missouri State University in Maryville, Missouri. Thirty five peer-reviewed papers and abstracts, written by academic librarians, and presented at the symposium are included in this volume. Many of the entries have references and…

  1. Brick and Click Libraries: Proceedings of an Academic Library Symposium (6th, Maryville, Missouri, November 3, 2006)

    ERIC Educational Resources Information Center

    Baudino, Frank, Ed.; Ury, Connie Jo, Ed.; Park, Sarah G., Ed.

    2006-01-01

    These proceedings document the sixth year of the "Brick and Click Libraries Symposium," held annually at Northwest Missouri State University in Maryville, Missouri, on November 3, 2006. Thirty-four peer-reviewed papers and abstracts, written by academic librarians, and presented at the symposium are included in this volume. Many of the entries…

  2. Mixed-methods analytic approach for determining potential impacts of vessel noise on sperm whale click behavior.

    PubMed

    Azzara, Alyson J; von Zharen, Wyndylyn M; Newcomb, Joal J

    2013-12-01

    The Gulf of Mexico is a center of marine activities from seismic exploration to shipping, drilling, platform installation, lightering, and construction, among others. This analysis explored whether sperm whales respond to the passage of vessels using changes in total number of clicks during vessel passages as a proxy for potential variation in behavior. The data for this analysis were collected in 2001 as part of a larger Littoral Acoustic Demonstration Center project using the Environmental Acoustics Recording System buoys. These buoys were bottom moored, autonomous, and self-recording systems consisting of an omni-directional hydrophone and instrument package. Data from 36 days of continuous acoustic monitoring were recorded at a sampling rate of 11.725 kHz, and produced reliable recordings from 5 Hz to ∼5.8 kHz. Multiple preparatory steps were executed including calibration of an automatic click detector. Results indicate a significant decrease (32%) in the number of clicks detected as a ship approached an area. There were also significantly fewer clicks detected after the vessel passed than before (23%). PMID:25669266

  3. Effect of High-Pass Filtering on the Neonatal Auditory Brainstem Response to Air- and Bone-Conducted Clicks.

    ERIC Educational Resources Information Center

    Stuart, Andrew; Yang, Edward Y.

    1994-01-01

    Simultaneous 3- channel recorded auditory brainstem responses (ABR) were obtained from 20 neonates with various high-pass filter settings and low intensity levels. Results support the advocacy of less restrictive high-pass filtering for neonatal and infant ABR screening to air-conducted and bone-conducted clicks. (Author/JDD)

  4. Are Occlusal Characteristics, Headache, Parafunctional Habits and Clicking Sounds Associated with the Signs and Symptoms of Temporomandibular Disorder in Adolescents?

    PubMed Central

    Lauriti, Leandro; Motta, Lara Jansiski; Silva, Paula Fernanda da Costa; Leal de Godoy, Camila Haddad; Alfaya, Thays Almeida; Fernandes, Kristianne Porta Santos; Mesquita-Ferrari, Raquel Agnelli; Bussadori, Sandra Kalil

    2013-01-01

    [Purpose] To assess the association between the oclusal characteristics, headache, parafunctional habits and clicking sounds and signs/symptoms of TMD in adolescents. [Subjects] Adolescents between 14 and 18 years of age. [Methods] The participants were evaluated using the Helkimo Index and a clinical examination to track clicking sounds, parafunctional habits and other signs/symptoms of temporomandibular disorder (TMD). Subjects were classified according to the presence or absence of headache, type of occlusion, facial pattern and type of bite. In statistical analyse we used the chi-square test and Fisher's exact test, with a level of significance of 5%. [Results] The sample was made up of 81 adolescents with a mean age of 15.64 years; 51.9% were male. The prevalence of signals/symptoms of TMD was 74.1%, predominantly affecting females. Signals/symptoms of TMD were significantly associated with clicking sounds, headache and nail biting. No associations were found between signals/symptoms of TMD and angle classification, type of bite and facial pattern. [Conclusion] Headache is one of the most closely associated symptoms of TMD. Clicking sounds were found in the majority of cases. Therefore, the sum of two or more factors may be necessary for the onset and perpetuation of TMD. PMID:24259787

  5. Vitamin B12 Phosphate Conjugation and Its Effect on Binding to the Human B12 -Binding Proteins Intrinsic Factor and Haptocorrin.

    PubMed

    Ó Proinsias, Keith; Ociepa, Michał; Pluta, Katarzyna; Chromiński, Mikołaj; Nexo, Ebba; Gryko, Dorota

    2016-06-01

    The binding of vitamin B12 derivatives to human B12 transporter proteins is strongly influenced by the type and site of modification of the cobalamin original structure. We have prepared the first cobalamin derivative modified at the phosphate moiety. The reaction conditions were fully optimized and its limitations examined. The resulting derivatives, particularly those bearing terminal alkyne and azide groups, were isolated and used in copper-catalyzed alkyne-azide cycloaddition reactions (CuAAC). Their sensitivity towards light revealed their potential as photocleavable molecules. The binding abilities of selected derivatives were examined and compared with cyanocobalamin. The interaction of the alkylated derivatives with haptocorrin was less affected than the interaction with intrinsic factor. Furthermore, the configuration of the phosphate moiety was irrelevant to the binding process. PMID:27120016

  6. Plant cell wall imaging by metabolic click-mediated labelling of rhamnogalacturonan II using azido 3-deoxy-D-manno-oct-2-ulosonic acid.

    PubMed

    Dumont, Marie; Lehner, Arnaud; Vauzeilles, Boris; Malassis, Julien; Marchant, Alan; Smyth, Kevin; Linclau, Bruno; Baron, Aurélie; Mas Pons, Jordi; Anderson, Charles T; Schapman, Damien; Galas, Ludovic; Mollet, Jean-Claude; Lerouge, Patrice

    2016-02-01

    In plants, 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) is a monosaccharide that is only found in the cell wall pectin, rhamnogalacturonan-II (RG-II). Incubation of 4-day-old light-grown Arabidopsis seedlings or tobacco BY-2 cells with 8-azido 8-deoxy Kdo (Kdo-N3 ) followed by coupling to an alkyne-containing fluorescent probe resulted in the specific in muro labelling of RG-II through a copper-catalysed azide-alkyne cycloaddition reaction. CMP-Kdo synthetase inhibition and competition assays showing that Kdo and D-Ara, a precursor of Kdo, but not L-Ara, inhibit incorporation of Kdo-N3 demonstrated that incorporation of Kdo-N3 occurs in RG-II through the endogenous biosynthetic machinery of the cell. Co-localisation of Kdo-N3 labelling with the cellulose-binding dye calcofluor white demonstrated that RG-II exists throughout the primary cell wall. Additionally, after incubating plants with Kdo-N3 and an alkynated derivative of L-fucose that incorporates into rhamnogalacturonan I, co-localised fluorescence was observed in the cell wall in the elongation zone of the root. Finally, pulse labelling experiments demonstrated that metabolic click-mediated labelling with Kdo-N3 provides an efficient method to study the synthesis and redistribution of RG-II during root growth. PMID:26676799

  7. A Chemical Proteomics Approach for the Search of Pharmacological Targets of the Antimalarial Clinical Candidate Albitiazolium in Plasmodium falciparum Using Photocrosslinking and Click Chemistry

    PubMed Central

    Penarete-Vargas, Diana Marcela; Boisson, Anaïs; Urbach, Serge; Chantelauze, Hervé; Peyrottes, Suzanne; Fraisse, Laurent; Vial, Henri J.

    2014-01-01

    Plasmodium falciparum is responsible for severe malaria which is one of the most prevalent and deadly infectious diseases in the world. The antimalarial therapeutic arsenal is hampered by the onset of resistance to all known pharmacological classes of compounds, so new drugs with novel mechanisms of action are critically needed. Albitiazolium is a clinical antimalarial candidate from a series of choline analogs designed to inhibit plasmodial phospholipid metabolism. Here we developed an original chemical proteomic approach to identify parasite proteins targeted by albitiazolium during their native interaction in living parasites. We designed a bifunctional albitiazolium-derived compound (photoactivable and clickable) to covalently crosslink drug–interacting parasite proteins in situ followed by their isolation via click chemistry reactions. Mass spectrometry analysis of drug–interacting proteins and subsequent clustering on gene ontology terms revealed parasite proteins involved in lipid metabolic activities and, interestingly, also in lipid binding, transport, and vesicular transport functions. In accordance with this, the albitiazolium-derivative was localized in the endoplasmic reticulum and trans-Golgi network of P. falciparum. Importantly, during competitive assays with albitiazolium, the binding of choline/ethanolamine phosphotransferase (the enzyme involved in the last step of phosphatidylcholine synthesis) was substantially displaced, thus confirming the efficiency of this strategy for searching albitiazolium targets. PMID:25470252

  8. Post-synthetic modification of metal-organic framework thin films using click chemistry: the importance of strained C-C triple bonds.

    PubMed

    Wang, Zhengbang; Liu, Jinxuan; Arslan, Hasan K; Grosjean, Sylvain; Hagendorn, Tobias; Gliemann, Hartmut; Bräse, Stefan; Wöll, Christof

    2013-12-23

    In this work, we demonstrate that strain-promoted azide-alkyne cycloaddition (SPAAC) yields virtually complete conversion in the context of the post-synthetic modification (PSM) of metal-organic frameworks (MOFs). We use surface-anchored MOF (SURMOF) thin films, [Zn2(N3-bdc)2(dabco)], grown on modified Au substrates using liquid-phase epitaxy (LPE) as a model system to first show that, with standard click chemistry, presently, the most popular method for rendering additional functionality to MOFs via PSM, quantitative conversion yields, cannot be reached. In addition, it is virtually impossible to avoid contaminations of the product by the cytotoxic Cu(I) ions used as a catalyst, a substantial problem for applications in life sciences. Both problems could be overcome by SPAAC, where a metal catalyst is not needed. After optimization of reaction conditions, conversion yields of nearly 100% could be achieved. The consequences of these results for various applications of PSM-modified SURMOFs in the fields of membranes, optical coatings, catalysis, selective gas separation, and chemical sensing are briefly discussed. PMID:24283622

  9. Engineering Thiol-Ene Click Chemistry for the Fabrication of Novel Structurally Well-Defined Multifunctional Cyclodextrin Separation Materials for Enhanced Enantioseparation.

    PubMed

    Yao, Xiaobin; Zheng, Hao; Zhang, Yang; Ma, Xiaofei; Xiao, Yin; Wang, Yong

    2016-05-01

    The preparation of two novel multifunctional cyclodextrin (CD) separation materials and their ultimate enantioseparation performances in high performance liquid chromatography are reported. A mild thiol-ene click reaction was used to anchor 1-allylimidazolium-per(p-methyl)phenylcarbamoylated-β-CD and 1-allylimidazolium-per(p-chloride)phenylcarbamoylated-β-CD onto thiol-modified porous silica giving structurally well-defined stable cationic multifunctional CD chiral stationary phases (CSP1 and CSP2 respectively). These covalently bonded CD phases have typical interaction modes such as H-bonding, π-π effect, electrostatic and dipole-dipole interactions as well as steric effects which result in superior chiral resolution for a variety of chiral compounds in different separation modes. In a reverse-phase mode, both CSPs exhibited excellent separation abilities for isoxazolines, flavonoids, β-blockers, and some other neutral and basic racemates. In a polar-organic mode, isoxazolines and flavonoids were well resolved. CSP1 with an electron-rich phenyl substitution on the CD rims gave a better resolution for isoxazolines whereas CSP2 with an electron-deficient phenyl substitution on the CD rims gave better resolution for flavonoids. Among isoxazolines, 4ClPh-OPr gained a high selectivity and resolution up to 18.6 and 38.7, respectively, which is an amazing result for CD enantioseparation materials. PMID:27058612

  10. A chemical proteomics approach for the search of pharmacological targets of the antimalarial clinical candidate albitiazolium in Plasmodium falciparum using photocrosslinking and click chemistry.

    PubMed

    Penarete-Vargas, Diana Marcela; Boisson, Anaïs; Urbach, Serge; Chantelauze, Hervé; Peyrottes, Suzanne; Fraisse, Laurent; Vial, Henri J

    2014-01-01

    Plasmodium falciparum is responsible for severe malaria which is one of the most prevalent and deadly infectious diseases in the world. The antimalarial therapeutic arsenal is hampered by the onset of resistance to all known pharmacological classes of compounds, so new drugs with novel mechanisms of action are critically needed. Albitiazolium is a clinical antimalarial candidate from a series of choline analogs designed to inhibit plasmodial phospholipid metabolism. Here we developed an original chemical proteomic approach to identify parasite proteins targeted by albitiazolium during their native interaction in living parasites. We designed a bifunctional albitiazolium-derived compound (photoactivable and clickable) to covalently crosslink drug-interacting parasite proteins in situ followed by their isolation via click chemistry reactions. Mass spectrometry analysis of drug-interacting proteins and subsequent clustering on gene ontology terms revealed parasite proteins involved in lipid metabolic activities and, interestingly, also in lipid binding, transport, and vesicular transport functions. In accordance with this, the albitiazolium-derivative was localized in the endoplasmic reticulum and trans-Golgi network of P. falciparum. Importantly, during competitive assays with albitiazolium, the binding of choline/ethanolamine phosphotransferase (the enzyme involved in the last step of phosphatidylcholine synthesis) was substantially displaced, thus confirming the efficiency of this strategy for searching albitiazolium targets. PMID:25470252

  11. Utilization of intrachain 4'-C-azidomethylthymidine for preparation of oligodeoxyribonucleotide conjugates by click chemistry in solution and on a solid support.

    PubMed

    Kiviniemi, Anu; Virta, Pasi; Lönnberg, Harri

    2008-08-01

    4'-C-Azidomethylthymidine 3'-(H-phosphonate) monomer (10) was synthesized in high yield and three such monomers were incorporated by the H-phosphonate coupling into a 15-mer oligodeoxyribonucleotide. The unmodified 2'-deoxynucleosides could be coupled by either the H-phosphonate or phosphoramidite chemistry, indicating that the Staudinger reaction between the azido group and the phosphoramidite reagent severely hampered the coupling only when it took place intramolecularly. After chain assembly, three alkynyl group bearing ligands, viz., propargyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranoside (2), N-{4-[N-(trifluoroacetyl)aminomethyl]benzyl}-4-pentynamide (3) and N (1), N (3), N (2')-tris(trifluoroacetyl)-N (6')-(4-pentynoyl)neamine (4), were conjugated to the azido groups of the oligonucleotide by click chemistry both on a solid support and in solution. The products were deprotected by conventional ammonolysis and purified by HPLC chromatography. Melting temperature studies revealed that the mannose conjugated oligonucleotides formed more stable duplexes with 2'-O-methyl RNA than with DNA strand. With 2'-O-methyl RNA, a slight destabilization compared to an unmodified sequence was observed at low ionic strength, while at high salt content, the manno-conjugation was stabilizing. PMID:18671421

  12. Click-based synthesis and antitubercular evaluation of novel dibenzo[b,d]thiophene-1,2,3-triazoles with piperidine, piperazine, morpholine and thiomorpholine appendages.

    PubMed

    Pulipati, Lokesh; Yogeeswari, Perumal; Sriram, Dharmarajan; Kantevari, Srinivas

    2016-06-01

    A series of novel piperidine, piperazine, morpholine and thiomorpholine appended dibenzo[b,d]thiophene-1,2,3-triazoles were designed and synthesized utilizing azide-alkyne click chemistry in the penultimate step. The required azide building block 6a-e was synthesized from commercial dibenzo[b,d]thiophene in good yields following five step reaction sequence. All the new analogues 8a-f, 9a-f, 10a-f, 11a-f &12a-f were characterized by their NMR and mass spectral analysis. Screening all thirty new compounds for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv, resulted 8a, 8f and 11e as potent analogues with MIC 0.78μg/mL, 0.78μg/mL & 1.56μg/mL, respectively, and has shown lower cytotoxicity. Interestingly, all six piperazine appended dibenzo[b,d]thiophene-1,2,3-triazoles 11a-f exhibited Mtb inhibition activity with MIC 1.56-12.5μg/mL. To some extent, the data observed here indicated Mycobacterium tuberculosis inhibition among the appendages is in the order, piperazine>thiomorpholine>morpholine. PMID:27101894

  13. IntentSearch: Capturing User Intention for One-Click Internet Image Search.

    PubMed

    Tang, Xiaoou; Liu, Ke; Cui, Jingyu; Wen, Fang; Wang, Xiaogang

    2012-07-01

    Web-scale image search engines (e.g., Google image search, Bing image search) mostly rely on surrounding text features. It is difficult for them to interpret users' search intention only by query keywords and this leads to ambiguous and noisy search results which are far from satisfactory. It is important to use visual information in order to solve the ambiguity in text-based image retrieval. In this paper, we propose a novel Internet image search approach. It only requires the user to click on one query image with minimum effort and images from a pool retrieved by text-based search are reranked based on both visual and textual content. Our key contribution is to capture the users' search intention from this one-click query image in four steps. 1) The query image is categorized into one of the predefined adaptive weight categories which reflect users' search intention at a coarse level. Inside each category, a specific weight schema is used to combine visual features adaptive to this kind of image to better rerank the text-based search result. 2) Based on the visual content of the query image selected by the user and through image clustering, query keywords are expanded to capture user intention. 3) Expanded keywords are used to enlarge the image pool to contain more relevant images. 4) Expanded keywords are also used to expand the query image to multiple positive visual examples from which new query specific visual and textual similarity metrics are learned to further improve content-based image reranking. All these steps are automatic, without extra effort from the user. This is critically important for any commercial web-based image search engine, where the user interface has to be extremely simple. Besides this key contribution, a set of visual features which are both effective and efficient in Internet image search are designed. Experimental evaluation shows that our approach significantly improves the precision of top-ranked images and also the user

  14. Cyclodextrin-clicked silica/CdTe fluorescent nanoparticles for enantioselective recognition of amino acids

    NASA Astrophysics Data System (ADS)

    Zhou, Jie; Liu, Yun; Zhang, Zhixing; Yang, Sha; Tang, Jian; Liu, Wei; Tang, Weihua

    2016-03-01

    Fluorescent sensors based on semiconductor quantum dots (QDs) have been immensely investigated for achiral molecular recognition. For chiral discrimination of amino acids (AAs), we herein report a versatile fluorescent sensor, i.e., CdTe QDs encapsulated with cyclodextrin (CD) clicked silica via layer-by-layer modification. The as-obtained hybrid molecular recognition platform exhibited excellent chirality sensing of AAs at micromolar concentrations in water. By taking advantage of the inclusion complexation of CD and the optical properties of the QD core, chiral discrimination was realized on the basis of the different binding energies of the CD-AA enantiomer complexes, as revealed using density-functional theory calculation. The fluorescent probe exhibited linearly enhanced photoluminescence with increased concentration of d-histidine at 0-60 μM and l-histidine at 0-20 μM. These water-soluble fluorescent sensors using a chiral host with a covalently linked chromophore may find applications in the robust sensing of a wide range of achiral and chiral molecules in water.Fluorescent sensors based on semiconductor quantum dots (QDs) have been immensely investigated for achiral molecular recognition. For chiral discrimination of amino acids (AAs), we herein report a versatile fluorescent sensor, i.e., CdTe QDs encapsulated with cyclodextrin (CD) clicked silica via layer-by-layer modification. The as-obtained hybrid molecular recognition platform exhibited excellent chirality sensing of AAs at micromolar concentrations in water. By taking advantage of the inclusion complexation of CD and the optical properties of the QD core, chiral discrimination was realized on the basis of the different binding energies of the CD-AA enantiomer complexes, as revealed using density-functional theory calculation. The fluorescent probe exhibited linearly enhanced photoluminescence with increased concentration of d-histidine at 0-60 μM and l-histidine at 0-20 μM. These water

  15. Drug Reactions

    MedlinePlus

    Most of the time, medicines make our lives better. They reduce aches and pains, fight infections, and control problems such as high blood pressure or diabetes. But medicines can also cause unwanted reactions. One problem is ...

  16. Multiple representations of information in the primary auditory cortex of cats. I. Stability and change in slow components of unit activity after conditioning with a click conditioned stimulus.

    PubMed

    Woody, C D; Zotova, E; Gruen, E

    2000-06-16

    Recordings of activity were made from 647 single units of the A(I) cortex of awake cats to evaluate behavioral state-dependent changes in the population response to a 70-dB click. Averages of PST histograms of unit activity were used to assess the changes in response. This report focuses on slow components of the responses disclosed by averages employing bin widths of 16 ms. Responses were compared before and after a Pavlovian blink CR was produced by forward pairing of click conditioned stimuli (CSs) with USs. A backward-paired 70-dB hiss was presented as a discriminative stimulus. Studies were also done after backward pairing of the click CSs (backward conditioning) that produced weak sensitization instead of a conditioned response. There were four main findings. First, components of activity elicited 32-160 ms after presenting the hiss decreased significantly after conditioning and after backward conditioning. The decreases after conditioning represented the most pronounced changes in activity evoked by either clicks or hisses in this behavioral state. Second, baseline firing decreased after both conditioning and backward conditioning. The direction of baseline change was opposite that found in adjacent cortical regions and in A(I) cortex after operant conditioning employing an acoustic cue. Third, prior to conditioning, unit activity in response to the hiss declined before the sound of the hiss reached its peak or terminated. This decrease was thought to represent a habituatory adaptation of response to a prolonged acoustic stimulus. This type of habituation to a lengthy stimulus has been recognized, behaviorally, but has not been observed previously in the activity of units of the auditory receptive cortex. Fourth, the percentage of click responsive units did not change significantly after the click was used as a CS for conditioning, and despite the accompanying changes in baseline activity, the absolute levels of activity summed in the first 16 ms after click

  17. Synthetic Strategies Toward DNA-Coated Colloids that Crystallize.

    PubMed

    Wang, Yufeng; Wang, Yu; Zheng, Xiaolong; Ducrot, Étienne; Lee, Myung-Goo; Yi, Gi-Ra; Weck, Marcus; Pine, David J

    2015-08-26

    We report on synthetic strategies to fabricate DNA-coated micrometer-sized colloids that, upon thermal annealing, self-assemble into various crystal structures. Colloids of a wide range of chemical compositions, including poly(styrene), poly(methyl methacrylate), titania, silica, and a silica-methacrylate hybrid material, are fabricated with smooth particle surfaces and a dense layer of surface functional anchors. Single-stranded oligonucleotides with a short sticky end are covalently grafted onto particle surfaces employing a strain-promoted alkyne-azide cycloaddition reaction resulting in DNA coatings with areal densities an order of magnitude higher than previously reported. Our approach allows the DNA-coated colloids not only to aggregate upon cooling but also to anneal and rearrange while still bound together, leading to the formation of colloidal crystal compounds when particles of different sizes or different materials are combined. PMID:26192470

  18. Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel-Crafts alkylations.

    PubMed

    Pecchioli, Tommaso; Muthyala, Manoj Kumar; Haag, Rainer; Christmann, Mathias

    2015-01-01

    The first immobilization of a MacMillan's first generation organocatalyst onto dendritic support is described. A modified tyrosine-based imidazolidin-4-one was grafted to a soluble high-loading hyperbranched polyglycerol via a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction and readily purified by dialysis. The efficiency of differently functionalized multivalent organocatalysts 4a-c was tested in the asymmetric Friedel-Crafts alkylation of N-methylpyrrole with α,β-unsaturated aldehydes. A variety of substituted enals was investigated to explore the activity of the catalytic system which was also compared with monovalent analogues. The catalyst 4b showed excellent turnover rates and no loss of activity due to immobilization, albeit moderate enantioselectivities were observed. Moreover, easy recovery by selective precipitation allowed the reuse of the catalyst for three cycles. PMID:26150897

  19. Synthesis and structural characterization of the individual diastereoisomers of a cross-stapled alkene-bridged nisin DE-ring mimic.

    PubMed

    Slootweg, Jack C; Kemmink, Johan; Liskamp, Rob M J; Rijkers, Dirk T S

    2013-11-21

    Herein, we describe the synthesis, structural characterization, and synthetic use as an advanced intermediate of a cross-stapled alkene-bridged hexapeptide to mimic the DE-ring of the lantibiotic nisin. The linear precursor was cyclized by ring-closing metathesis to give the correctly folded bicyclic hexapeptide in a single step, and the four individual diastereoisomers were isolated, structurally assigned and characterized by HPLC, NMR and MS, respectively. The bicyclic hexapeptide was used as a versatile advanced synthon and was modified at its C- and N-terminus, among others, with an azide moiety to access a building block suitable for Cu(I)-catalyzed alkyne-azide cycloaddition-based ligation reactions. PMID:24081149

  20. Hydrophilic and amphiphilic polyethylene glycol-based hydrogels with tunable degradability prepared by "click" chemistry.

    PubMed

    Truong, Vinh; Blakey, Idriss; Whittaker, Andrew K

    2012-12-10

    Hydrogels with tunable degradability have potential uses in a range of applications including drug delivery and tissue scaffolds. A series of poly(ethylene glycol) (PEG) hydrogels and amphiphilic PEG-poly(trimethylene carbonate ) (PTMC) hydrogels were prepared using copper-catalyzed Huisgen's 1,3-dipolar cycloaddition, or "click" chemistry as the coupling chemistry. The fidelity of the coupling chemistry was confirmed using Fourier transform infrared (FTIR) and 1H magic angle spinning (MAS) NMR spectroscopy while thorough swelling and degradation studies of the hydrogels were performed to relate network structure to the physical properties. The cross-linking efficiency calculated using the Flory-Rehner equation varied from 0.90 to 0.99, which indicates that the networks are close to "ideal" at a molecular level. However, at the microscopic level cryogenic scanning electron microscopy (cryo-SEM) indicated that some degree of phase separation was occurring during cross-linking. At 37 °C and pH 7.4, the degradation rate of the hydrogels increased with decreasing cross-link density in the network. Introduction of PTMC as the cross-linker produced an amphiphilic gel with higher cross-link density and a longer degradation time. The degradability of the resultant hydrogels could thus be tuned through control of molecular weight and structure of the precursors. PMID:23134321

  1. Click-generated triazole ureas as ultrapotent, in vivo-active serine hydrolase inhibitors

    PubMed Central

    Adibekian, Alexander; Martin, Brent R.; Wang, Chu; Hsu, Ku-Lung; Bachovchin, Daniel A.; Niessen, Sherry; Hoover, Heather; Cravatt, Benjamin F.

    2011-01-01

    Serine hydrolases (SHs) are a diverse enzyme class representing > 1% of all human proteins. The biological functions for most SHs remain poorly characterized due to a lack of selective inhibitors to probe their activity in living systems. Here, we show that a substantial number of SHs can be irreversibly inactivated by 1,2,3-triazole ureas, which exhibit negligible cross-reactivity with other protein classes. Rapid lead optimization by click chemistry-enabled synthesis and competitive activity-based profiling identified 1,2,3-triazole ureas that selectively inhibit enzymes from diverse branches of the SH superfamily, including peptidases (acyl-peptide hydrolase or APEH), lipases (platelet-activating factor acetylhyrolase-2 or PAFAH2), and uncharacterized hydrolases (α, β-hydrolase 11 or ABHD11), with exceptional potency in cells (sub-nM) and mice (< 1 mg/kg). We show that APEH inhibition leads to accumulation of N-acetylated proteins and promotes proliferation in T-cells. These data designate 1,2,3-triazole ureas as a pharmacologically privileged chemotype for SH inhibition that shows broad activity across the SH class coupled with tunable selectivity for individual enzymes. PMID:21572424

  2. Click-generated triazole ureas as ultrapotent in vivo-active serine hydrolase inhibitors.

    PubMed

    Adibekian, Alexander; Martin, Brent R; Wang, Chu; Hsu, Ku-Lung; Bachovchin, Daniel A; Niessen, Sherry; Hoover, Heather; Cravatt, Benjamin F

    2011-07-01

    Serine hydrolases are a diverse enzyme class representing ∼1% of all human proteins. The biological functions of most serine hydrolases remain poorly characterized owing to a lack of selective inhibitors to probe their activity in living systems. Here we show that a substantial number of serine hydrolases can be irreversibly inactivated by 1,2,3-triazole ureas, which show negligible cross-reactivity with other protein classes. Rapid lead optimization by click chemistry-enabled synthesis and competitive activity-based profiling identified 1,2,3-triazole ureas that selectively inhibit enzymes from diverse branches of the serine hydrolase class, including peptidases (acyl-peptide hydrolase, or APEH), lipases (platelet-activating factor acetylhydrolase-2, or PAFAH2) and uncharacterized hydrolases (α,β-hydrolase-11, or ABHD11), with exceptional potency in cells (sub-nanomolar) and mice (<1 mg kg(-1)). We show that APEH inhibition leads to accumulation of N-acetylated proteins and promotes proliferation in T cells. These data indicate 1,2,3-triazole ureas are a pharmacologically privileged chemotype for serine hydrolase inhibition, combining broad activity across the serine hydrolase class with tunable selectivity for individual enzymes. PMID:21572424

  3. AWclust: point-and-click software for non-parametric population structure analysis

    PubMed Central

    Gao, Xiaoyi; Starmer, Joshua D

    2008-01-01

    Background Population structure analysis is important to genetic association studies and evolutionary investigations. Parametric approaches, e.g. STRUCTURE and L-POP, usually assume Hardy-Weinberg equilibrium (HWE) and linkage equilibrium among loci in sample population individuals. However, the assumptions may not hold and allele frequency estimation may not be accurate in some data sets. The improved version of STRUCTURE (version 2.1) can incorporate linkage information among loci but is still sensitive to high background linkage disequilibrium. Nowadays, large-scale single nucleotide polymorphisms (SNPs) are becoming popular in genetic studies. Therefore, it is imperative to have software that makes full use of these genetic data to generate inference even when model assumptions do not hold or allele frequency estimation suffers from high variation. Results We have developed point-and-click software for non-parametric population structure analysis distributed as an R package. The software takes advantage of the large number of SNPs available to categorize individuals into ethnically similar clusters and it does not require assumptions about population models. Nor does it estimate allele frequencies. Moreover, this software can also infer the optimal number of populations. Conclusion Our software tool employs non-parametric approaches to assign individuals to clusters using SNPs. It provides efficient computation and an intuitive way for researchers to explore ethnic relationships among individuals. It can be complementary to parametric approaches in population structure analysis. PMID:18237431

  4. Auditory Cortex Responses to Clicks and Sensory Modulation Difficulties in Children with Autism Spectrum Disorders (ASD)

    PubMed Central

    Orekhova, Elena V.; Tsetlin, Marina M.; Butorina, Anna V.; Novikova, Svetlana I.; Gratchev, Vitaliy V.; Sokolov, Pavel A.; Elam, Mikael; Stroganova, Tatiana A.

    2012-01-01

    Auditory sensory modulation difficulties are common in autism spectrum disorders (ASD) and may stem from a faulty arousal system that compromises the ability to regulate an optimal response. To study neurophysiological correlates of the sensory modulation difficulties, we recorded magnetic field responses to clicks in 14 ASD and 15 typically developing (TD) children. We further analyzed the P100m, which is the most prominent component of the auditory magnetic field response in children and may reflect preattentive arousal processes. The P100m was rightward lateralized in the TD, but not in the ASD children, who showed a tendency toward P100m reduction in the right hemisphere (RH). The atypical P100m lateralization in the ASD subjects was associated with greater severity of sensory abnormalities assessed by Short Sensory Profile, as well as with auditory hypersensitivity during the first two years of life. The absence of right-hemispheric predominance of the P100m and a tendency for its right-hemispheric reduction in the ASD children suggests disturbance of the RH ascending reticular brainstem pathways and/or their thalamic and cortical projections, which in turn may contribute to abnormal arousal and attention. The correlation of sensory abnormalities with atypical, more leftward, P100m lateralization suggests that reduced preattentive processing in the right hemisphere and/or its shift to the left hemisphere may contribute to abnormal sensory behavior in ASD. PMID:22768163

  5. A versatile click-compatible monolignol probe to study lignin deposition in plant cell walls.

    PubMed

    Pandey, Jyotsna L; Wang, Bo; Diehl, Brett G; Richard, Tom L; Chen, Gong; Anderson, Charles T

    2015-01-01

    Lignin plays important structural and functional roles in plants by forming a hydrophobic matrix in secondary cell walls that enhances mechanical strength and resists microbial decay. While the importance of the lignin matrix is well documented and the biosynthetic pathways for monolignols are known, the process by which lignin precursors or monolignols are transported and polymerized to form this matrix remains a subject of considerable debate. In this study, we have synthesized and tested an analog of coniferyl alcohol that has been modified to contain an ethynyl group at the C-3 position. This modification enables fluorescent tagging and imaging of this molecule after its incorporation into plant tissue by click chemistry-assisted covalent labeling with a fluorescent azide dye, and confers a distinct Raman signature that could be used for Raman imaging. We found that this monolignol analog is incorporated into in vitro-polymerized dehydrogenation polymer (DHP) lignin and into root epidermal cell walls of 4-day-old Arabidopsis seedlings. Incorporation of the analog in stem sections of 6-week-old Arabidopsis thaliana plants and labeling with an Alexa-594 azide dye revealed the precise locations of new lignin polymerization. Results from this study indicate that this molecule can provide high-resolution localization of lignification during plant cell wall maturation and lignin matrix assembly. PMID:25884205

  6. High Frequency Click-Evoked Otoacoustic Emission Measurements Using Maximum Length Sequences

    NASA Astrophysics Data System (ADS)

    Lineton, B.; Sohal, R.; Harvey, E.; Thornton, A. R. D.

    2011-11-01

    The aim of the study was to compare high-frequency components (4-8 kHz) of click-evoked otoacoustic emissions (CEOAEs) recorded using two different stimulus paradigms: the double-evoked (DE) paradigm, which uses two earphones, and the rate-derived nonlinear (RDNL) paradigm, which uses maximum length sequences (MLS) in a single ear-phone. Recordings were made in 20 otologically normal ears, and the results compared in terms of the apparent stimulus artefacts, and the presence of high-frequency CEOAEs. The correlation between CEOAEs amplitudes and DPOAE amplitudes from 4-8 kHz were also calculated. The results showed that, for both paradigms, the stimulus artefacts were of similar amplitudes and had largely decayed by around 1.5-2 ms post stimulus. Though similar in amplitude, the morphology of the artefacts in the two paradigms showed some differences, suggesting a possible means of identification. The CEOAE waveforms (post 2 ms) were very similar in both paradigms, and contained significant energy from 4-8 kHz. The amplitude correlated with the mean DPOAE amplitude from 4-8 kHz (R = 0.7; p<0.001).

  7. A Versatile Click-Compatible Monolignol Probe to Study Lignin Deposition in Plant Cell Walls

    PubMed Central

    Pandey, Jyotsna L.; Wang, Bo; Diehl, Brett G.; Richard, Tom L.; Chen, Gong; Anderson, Charles T.

    2015-01-01

    Lignin plays important structural and functional roles in plants by forming a hydrophobic matrix in secondary cell walls that enhances mechanical strength and resists microbial decay. While the importance of the lignin matrix is well documented and the biosynthetic pathways for monolignols are known, the process by which lignin precursors or monolignols are transported and polymerized to form this matrix remains a subject of considerable debate. In this study, we have synthesized and tested an analog of coniferyl alcohol that has been modified to contain an ethynyl group at the C-3 position. This modification enables fluorescent tagging and imaging of this molecule after its incorporation into plant tissue by click chemistry-assisted covalent labeling with a fluorescent azide dye, and confers a distinct Raman signature that could be used for Raman imaging. We found that this monolignol analog is incorporated into in vitro-polymerized dehydrogenation polymer (DHP) lignin and into root epidermal cell walls of 4-day-old Arabidopsis seedlings. Incorporation of the analog in stem sections of 6-week-old Arabidopsis thaliana plants and labeling with an Alexa-594 azide dye revealed the precise locations of new lignin polymerization. Results from this study indicate that this molecule can provide high-resolution localization of lignification during plant cell wall maturation and lignin matrix assembly. PMID:25884205

  8. Azidoethoxyphenylalanine as a Vibrational Reporter and Click Chemistry Partner in Proteins.

    PubMed

    Tookmanian, Elise M; Phillips-Piro, Christine M; Fenlon, Edward E; Brewer, Scott H

    2015-12-21

    An unnatural amino acid, 4-(2-azidoethoxy)-L-phenylalanine (AePhe, 1), was designed and synthesized in three steps from known compounds in 54% overall yield. The sensitivity of the IR absorption of the azide of AePhe was established by comparison of the frequency of the azide asymmetric stretch vibration in water and dimethyl sulfoxide. AePhe was successfully incorporated into superfolder green fluorescent protein (sfGFP) at the 133 and 149 sites by using the amber codon suppression method. The IR spectra of these sfGFP constructs indicated that the azide group at the 149 site was not fully solvated despite the location in sfGFP and the three-atom linker between the azido group and the aromatic ring of AePhe. An X-ray crystal structure of sfGFP-149-AePhe was solved at 1.45 Å resolution and provides an explanation for the IR data as the flexible linker adopts a conformation which partially buries the azide on the protein surface. Both sfGFP-AePhe constructs efficiently undergo a bioorthogonal strain-promoted click cycloaddition with a dibenzocyclooctyne derivative. PMID:26608683

  9. Design, Synthesis and Cytotoxicity of Novel Dihydroartemisinin-Coumarin Hybrids via Click Chemistry.

    PubMed

    Tian, Ye; Liang, Zhen; Xu, Hang; Mou, Yanhua; Guo, Chun

    2016-01-01

    In order to develop novel chemotherapeutic agents with potent anticancer activities, we designed four series of novel compounds employing hybridization strategy. Twenty novel dihydroartemisinin-coumarin hybrids, 10a-e, 11a-e, 12a-e, 13a-e, were synthesized via click chemistry in this study and their structures were characterized by HRMS and NMR. The cytotoxic activities were measured by MTT assay against three cancer cell lines (HCT-116, MDA-MB-231, and HT-29) under normoxic or anoxic conditions, respectively. The target compounds exhibited moderate activity with IC50 values in the 0.05-125.40 μM range, and these compounds exhibited better activity against HT-29 cell line under anoxic condition. The cytotoxic activities of most compounds under anoxic condition displayed one- to 10-fold greater activity than under normoxic condition. Compounds 10a-e showed better selectivity against the HT-29 cell line than the other two cell lines. These results indicated that our design of CA IX inhibitors does correspond with its action mode to some degree and deserves further investigation. PMID:27294901

  10. Click beetle luciferases as dual reporters of gene expression in Candida albicans.

    PubMed

    Kapitan, Mario; Eichhof, Isabel; Lagadec, Quentin; Ernst, Joachim F

    2016-08-01

    Synthetic genes encoding functional luciferases of the click beetle (CB) Pyrophorus plagiophthalamus have been expressed in the human fungal pathogen Candida albicans. Both green- and red-emitting CB luciferases (CaCBGluc and CaCBRluc) were produced with high efficiency in transformants under transcriptional control of the growth-dependent ACT1 promoter, as well as by the HWP1 and UME6 promoters, which are upregulated during hyphal morphogenesis, as well as by the YWP1 and EFG1 promoters, which are downregulated. For all hyphally regulated genes, relative bioluminescence values derived from promoter fusions approximated relative transcript levels of native genes, although downregulation of YWP1 promoter activity required correction for the stability of CB luciferases (approximate half-lives 30 min for CaCBRluc and 80 min for CaCBGluc, as determined by immunoblotting). Importantly, the activity of both luciferases could be separately monitored in a single strain, in intact cells, in lysed cells or in cell extracts using luciferin as single substrate and inhibition of hypha formation by farnesol could be easily detected by the HWP1p-CaCBRluc fusion. The results suggest that CB luciferases are convenient tools to measure gene expression in C. albicans and may facilitate screenings for antifungal compounds. PMID:27339610

  11. Biological hydrogel synthesized from hyaluronic acid, gelatin and chondroitin sulfate by click chemistry.

    PubMed

    Hu, Xiaohong; Li, Dan; Zhou, Feng; Gao, Changyou

    2011-04-01

    In order to mimic the natural cartilage extracellular matrix, which is composed of core proteins and glycosaminoglycans, a biological hydrogel was synthesized from the biopolymers hyaluronic acid (HA), chondroitin sulfate (CS) and gelatin via click chemistry. HA and CS were modified with 11-azido-3,6,9-trioxaundecan-1-amine (AA) and gelatin was modified with propiolic acid (PA). The molecular structures were verified by (1)H nuclear magnetic resonance, infrared spectroscopy and elemental analysis, giving substitution degrees of 29%, 89% and 44% for HA-AA, CS-AA and gelatin-PA (G-PA), respectively. The -N(3) groups of HA-AA and CS-AA were reacted with the acetylene groups of G-PA, catalyzed by Cu(I), to form triazole rings, thereby forming a cross-linked hydrogel. The gelation time was decreased monotonically with increasing Cu(I) concentration up to 0.95 mg ml(-1). The hydrogel obtained was in a highly swollen state and showed the characteristics of an elastomer. Incubation in phosphate-buffered saline for 4 weeks resulted in a weight loss of up to 45%. Moreover, about 20% gelatin and 10% CS were released from the hydrogel in 2 weeks. In vitro cell culture showed that the hydrogel could support the adhesion and proliferation of chondrocytes. PMID:21145437

  12. Click chemistry inspired synthesis and bioevaluation of novel triazolyl derivatives of osthol as potent cytotoxic agents.

    PubMed

    Farooq, Saleem; Shakeel-u-Rehman; Hussain, Aashiq; Hamid, Abid; Qurishi, Mushtaq A; Koul, Surrinder

    2014-09-12

    A new series of diverse triazoles linked through the hydroxyl group of lactone ring opened osthol (1) were synthesized using click chemistry approach. All the derivatives were subjected to 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) cytotoxicity screening against a panel of seven different human cancer cell lines viz. colon (colo-205), colon (HCT-116), breast (T47D), lung (NCI-H322), lung (A549), prostate (PC-3) and Skin (A-431) to check their cytotoxic potential. Interestingly, among the tested molecules, most of the analogs displayed better cytotoxic activity than the parent osthol (1). Of the synthesized triazoles, compounds 8 showed the best activity with IC50 of 1.3, 4.9, 3.6, 41.0, 35.2, 26.4 and 7.2 μM against colon (Colo-205 and HCT-116), breast (T47D), lung (NCI-H322 and A549), prostate (PC-3) and Skin (A-431) cancer lines respectively. Compound 8 induced potent apoptotic effects in Colo-205 cells. The population of apoptotic cells increased from 11.4% in case of negative control to 24.1% at 25 μM of 8. Compound 8 also induced a remarkable decrease in mitochondrial membrane potential (ΛΨm) leading to apoptosis of cancer cells used. The present study resulted in identification of broad spectrum cytotoxic activity of analogs bearing electron withdrawing substituents, besides the enhanced selective activity of analogs with electron donating moieties. PMID:25062005

  13. DNA-modified Electrodes Fabricated using Copper-Free Click Chemistry for Enhanced Protein Detection

    PubMed Central

    Furst, Ariel L.; Hill, Michael G.; Barton, Jacqueline K.

    2014-01-01

    A method of DNA monolayer formation has been developed using copper-free click chemistry that yields enhanced surface homogeneity and enables variation in the amount of DNA assembled; extremely low-density DNA monolayers, with as little as 5% of the monolayer being DNA, have been formed. These DNA-modified electrodes (DMEs) were characterized visually, with AFM, and electrochemically, and were found to facilitate DNA-mediated reduction of a distally bound redox probe. These low-density monolayers were found to be more homogeneous than traditional thiol-modified DNA monolayers, with greater helix accessibility through an increased surface area-to-volume ratio. Protein binding efficiency of the transcriptional activator TATA-binding protein (TBP) was also investigated on these surfaces and compared to that on DNA monolayers formed with standard thiol-modified DNA. Our low-density monolayers were found to be extremely sensitive to TBP binding, with a signal decrease in excess of 75% for 150 nM protein. This protein was detectable at 4 nM, on the order of its dissociation constant, with our low-density monolayers. The improved DNA helix accessibility and sensitivity of our low-density DNA monolayers to TBP binding reflects the general utility of this method of DNA monolayer formation for DNA-based electrochemical sensor development. PMID:24328347

  14. Label-free electrochemical DNA sensor using "click"-functionalized PEDOT electrodes.

    PubMed

    Galán, Teresa; Prieto-Simón, Beatriz; Alvira, Margarita; Eritja, Ramón; Götz, Günther; Bäuerle, Peter; Samitier, Josep

    2015-12-15

    Here we describe a label-free electrochemical DNA sensor based on poly(3,4-ethylenedioxythiophene)-modified (PEDOT-modified) electrodes. An acetylene-terminated DNA probe, complementary to a specific "Hepatitis C" virus sequence, was immobilized onto azido-derivatized conducting PEDOT electrodes using "click" chemistry. DNA hybridization was then detected by differential pulse voltammetry, evaluating the changes in the electrochemical properties of the polymer produced by the recognition event. A limit of detection of 0.13 nM was achieved using this highly selective PEDOT-based genosensor, without the need for labeling techniques or microelectrode fabrication processes. These results are promising for the development of label-free and reagentless DNA hybridization sensors based on conducting polymeric substrates. Biosensors can be easily prepared using any DNA sequence containing an alkyne moiety. The data presented here reveal the potential of this DNA sensor for diagnostic applications in the screening of diseases, such as "Hepatitis C", and genetic mutations. PMID:26210592

  15. Cyclodextrin-clicked silica/CdTe fluorescent nanoparticles for enantioselective recognition of amino acids.

    PubMed

    Zhou, Jie; Liu, Yun; Zhang, Zhixing; Yang, Sha; Tang, Jian; Liu, Wei; Tang, Weihua

    2016-03-14

    Fluorescent sensors based on semiconductor quantum dots (QDs) have been immensely investigated for achiral molecular recognition. For chiral discrimination of amino acids (AAs), we herein report a versatile fluorescent sensor, i.e., CdTe QDs encapsulated with cyclodextrin (CD) clicked silica via layer-by-layer modification. The as-obtained hybrid molecular recognition platform exhibited excellent chirality sensing of AAs at micromolar concentrations in water. By taking advantage of the inclusion complexation of CD and the optical properties of the QD core, chiral discrimination was realized on the basis of the different binding energies of the CD-AA enantiomer complexes, as revealed using density-functional theory calculation. The fluorescent probe exhibited linearly enhanced photoluminescence with increased concentration of d-histidine at 0-60 μM and L-histidine at 0-20 μM. These water-soluble fluorescent sensors using a chiral host with a covalently linked chromophore may find applications in the robust sensing of a wide range of achiral and chiral molecules in water. PMID:26893164

  16. Use of thiol-ene click chemistry to modify mechanical and thermal properties of polyhydroxyalkanoates (PHAs).

    PubMed

    Levine, Alex C; Heberlig, Graham W; Nomura, Christopher T

    2016-02-01

    In order to diversify the number of applications for poly[(R)-3-hydroxyalkanoates] (PHAs), methods must be developed to alter their physical properties so they are not limited to aliphatic polyesters. Recently we developed Escherichia coli LSBJ as a living biocatalyst with the ability to control the repeating unit composition of PHA polymers, including the ability to incorporate unsaturated repeating units into the PHA polymer at specific ratios. The incorporation of repeating units with terminal alkenes in the side chain of the polymer allowed for the production of random PHA copolymers with defined repeating unit ratios that can be chemically modified for the purpose of tailoring the physical properties of these materials beyond what are available in current PHAs. In this study, unsaturated PHA copolymers were chemically modified via thiol-ene click chemistry to contain an assortment of new functional groups, and the mechanical and thermal properties of these materials were measured. Results showed that cross-linking the copolymer resulted in a unique combination of improved strength and pliability and that the addition of polar functional groups increased the tensile strength, Young's modulus, and hydrophilic profile of the materials. This work demonstrates that unsaturated PHAs can be chemically modified to extend their physical properties to distinguish them from currently available PHA polymers. PMID:26616449

  17. Capturing the Direct Binding of CFTR Correctors to CFTR by Using Click Chemistry.

    PubMed

    Sinha, Chandrima; Zhang, Weiqiang; Moon, Chang Suk; Actis, Marcelo; Yarlagadda, Sunitha; Arora, Kavisha; Woodroofe, Koryse; Clancy, John P; Lin, Songbai; Ziady, Assem G; Frizzell, Raymond; Fujii, Naoaki; Naren, Anjaparavanda P

    2015-09-21

    Cystic fibrosis (CF) is a lethal genetic disease caused by the loss or dysfunction of the CF transmembrane conductance regulator (CFTR) channel. F508del is the most prevalent mutation of the CFTR gene and encodes a protein defective in folding and processing. VX-809 has been reported to facilitate the folding and trafficking of F508del-CFTR and augment its channel function. The mechanism of action of VX-809 has been poorly understood. In this study, we sought to answer a fundamental question underlying the mechanism of VX-809: does it bind CFTR directly in order to exert its action? We synthesized two VX-809 derivatives, ALK-809 and SUL-809, that possess an alkyne group and retain the rescue capacity of VX-809. By using Cu(I) -catalyzed click chemistry, we provide evidence that the VX-809 derivatives bind CFTR directly in vitro and in cells. Our findings will contribute to the elucidation of the mechanism of action of CFTR correctors and the design of more potent therapeutics to combat CF. PMID:26227551

  18. Dissociation between distortion-product and click-evoked otoacoustic emissions in sheep (Ovis aries)

    PubMed Central

    McFadden, Dennis; Pasanen, Edward G.; Valero, Michelle D.; Roberts, Eila K.; Lee, Theresa M.

    2008-01-01

    Distortion-product otoacoustic emissions (DPOAEs) were weak or absent in about one-third of sheep (Ovis aries) of both sexes tested for otoacoustic emissions (OAEs) even though their click-evoked OAEs (CEOAEs) seemingly were typical of other sheep of the same sex. Various pieces of evidence suggest that the absence of measurable DPOAEs was unlikely to be attributable to anesthetic effects, a poorly located probe tip, a pressure differential between middle and outer ears, season of the year, body position during testing, temperature effects, or previous medical history. Sheep apparently can exhibit a marked dissociation between DPOAEs and CEOAEs. In those sheep having measurable DPOAEs, the DPOAEs were stronger in males than in females, which is the opposite direction of effect from the CEOAEs measured in these same sheep and in humans. In female sheep exposed to higher-than-normal levels of androgens during gestation, the measurable DPOAEs were stronger than in untreated females. Although this also was the opposite direction of effect from expected, it still was a shift in the male direction, in accord with past findings about the masculinizing effects of androgens on OAEs. In sheep, androgen exposure appears to have different effects on the mechanisms underlying DPOAEs from those underlying CEOAEs. PMID:19206800

  19. DNA-modified electrodes fabricated using copper-free click chemistry for enhanced protein detection.

    PubMed

    Furst, Ariel L; Hill, Michael G; Barton, Jacqueline K

    2013-12-31

    A method of DNA monolayer formation has been developed using copper-free click chemistry that yields enhanced surface homogeneity and enables variation in the amount of DNA assembled; extremely low-density DNA monolayers, with as little as 5% of the monolayer being DNA, have been formed. These DNA-modified electrodes (DMEs) were characterized visually, with AFM, and electrochemically, and were found to facilitate DNA-mediated reduction of a distally bound redox probe. These low-density monolayers were found to be more homogeneous than traditional thiol-modified DNA monolayers, with greater helix accessibility through an increased surface area-to-volume ratio. Protein binding efficiency of the transcriptional activator TATA-binding protein (TBP) was also investigated on these surfaces and compared to that on DNA monolayers formed with standard thiol-modified DNA. Our low-density monolayers were found to be extremely sensitive to TBP binding, with a signal decrease in excess of 75% for 150 nM protein. This protein was detectable at 4 nM, on the order of its dissociation constant, with our low-density monolayers. The improved DNA helix accessibility and sensitivity of our low-density DNA monolayers to TBP binding reflects the general utility of this method of DNA monolayer formation for DNA-based electrochemical sensor development. PMID:24328347

  20. Jumping without using legs: the jump of the click-beetles (Elateridae) is morphologically constrained.

    PubMed

    Ribak, Gal; Weihs, Daniel

    2011-01-01

    To return to their feet, inverted click-beetles (Elateridae) jump without using their legs. When a beetle is resting on its dorsal side, a hinge mechanism is locked to store elastic energy in the body and releases it abruptly to launch the beetle into the air. While the functional morphology of the jumping mechanism is well known, the level of control that the beetle has over this jumping technique and the mechanical constraints governing the jumps are not entirely clear. Here we show that while body rotations in air are highly variable, the jumps are morphologically constrained to a constant "takeoff" angle (79.9°±1.56°, n = 9 beetles) that directs 98% of the jumping force vertically against gravity. A physical-mathematical model of the jumping action, combined with measurements from live beetle, imply that the beetle may control the speed at takeoff but not the jumping angle. In addition, the model shows that very subtle changes in the exact point of contact with the ground can explain the vigorous rotations of the body seen while the beetle is airborne. These findings suggest that the evolution of this unique non-legged jumping mechanism resulted in a jumping technique that is capable of launching the body high into the air but it is too constrained and unstable to allow control of body orientation at landing. PMID:21698194