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Current methods for the preparation of functional small-molecule fluorophores generally require labor-intensive, multi-step synthetic routes for all the major chromophore groups. In spite of recent significant contributions from numerous laboratories, the paucity of rapid, straightforward and wide-scope synthetic strategies in this field is limiting the development of advanced probes for bioimaging, sensing and therapeutic applications. We describe herein a general and robust methodology for the one-step fluorescent labeling of a wide variety of molecules having C-, N-, P-, O-, S-, or halide-nucleophilic centers, using stable and readily available acetoxymethyl-BODIPYs as reagents in the presence of an acid catalyst. This modular methodology allows a very facile preparation of mono- and di-functional probes incorporating a broad assortment of biomolecules, enzyme cofactors, natural products, and other chromophores, as well as chemical functionalities for a wide range of applications including bioorthogonal conjugation, polymerization, and supramolecular chemistry, among others. The photophysical properties and preliminary applications of the new probes in live-cell imaging were also studied. The described strategy enables the high-throughput engineering of novel BODIPY dyes with diverse functionalities for basic and applied science with potential for innovative technological applications.

[ES] Compuestos para etiquetado fluorescente. La presente invención se refiere a unos compuestos de estructura BODIPY con buenas propiedades para el etiquetado fluorescente específico de C-nucleófilos, así como su procedimiento de obtención que permite de manera eficiente y económica la preparación de una gran diversidad de compuestos de forma directa, rápida, y con buenos rendimientos de reacción. La aplicación de estos compuestos incluye, aunque no exclusivamente, su uso como marcadores biológicos para la tinción selectiva de células y microrganismos vivos, como sondas fluorescentes en biosensores en bioimagen de organismos vivos o los captadores de energía en células solares, o como emisores en láseres de colorante o como emisores en sistemas OLED., [EN] Fluorescent labeling compounds. The present invention refers to compounds with a BODIPY structure with good properties for the specific fluorescent labeling of C-nucleophiles, as well as its obtaining procedure that allows efficiently and economically the preparation of a great diversity of compounds directly, quickly. , and with good reaction yields. The application of these compounds includes, although not exclusively, their use as biological markers for the selective staining of living cells and microorganisms, as fluorescent probes in biosensors in bioimaging of living organisms or energy harvesters in solar cells, or as emitters in lasers. dye or as emitters in OLED systems.

[EN] The present invention relates to compounds of BODIPY structure having good properties for the specific fluorescent labelling of C-nucleophiles and to the process of obtainment thereof, which enables the efficient and economic preparation of a great diversity of compounds in a direct, fast way and with good reaction yields. The application of these compounds includes, but is not limited to, their use as biomarkers for selective staining of living cells and microorganisms, as fluorescent probes in biosensors in bioimaging of living organisms or energy scavengers in solar cells, or as emitters in dye lasers or as emitters in OLED systems., [ES] La presente invención se refiere a unos compuestos de estructura BODIPY con buenas propiedades para el etiquetado fluorescente específico de C-nucleófilos, así como su procedimiento de obtención que permite de manera eficiente y económica la preparación de una gran diversidad de compuestos de forma directa, rápida, y con buenos rendimientos de reacción. La aplicación de estos compuestos incluye, aunque no exclusivamente, su uso como marcadores biológicos para la tinción selectiva de células y microrganismos vivos, como sondas fluorescentes en biosensores en bioimagen de organismos vivos o los captadores de energía en células solares, o como emisores en láseres de colorante o como emisores en sistemas OLED., [FR] La présente invention concerne des composés de structure BODIPY ayant de bonnes propriétés pour l'étiquetage fluorescent spécifique de C-nucléophiles, ainsi que leur procédé d'obtention permettant de manière efficace et économique la préparation d'une grande variété de composés de manière directe, rapide et avec de bons rendements de réaction. L'application de ces composés comprend, même de manière non exclusive, leur utilisation comme marqueurs biologiques pour la coloration sélective de cellules et de micro-organismes vivants, comme sondes fluorescentes dans des biocapteurs en bio-imagerie d'organismes vivants ou capteurs d'énergie dans des cellules solaires ou comme émetteurs dans des lasers à colorant ou comme émetteurs dans des systèmes OLED.

Current methods for the preparation of functional small-molecule fluorophores generally require labor-intensive, multi-step synthetic routes for all the major chromophoric groups. In spite of recent significant contributions from numerous laboratories, the paucity of rapid, straightforward and wide-scope synthetic strategies in this field is limiting the development of advanced probes for bioimaging, sensing and therapeutic applications. We describe herein a general and robust methodology for the one-step fluorescent labeling of a wide variety of molecules having C-, N-, P-, O-, S-, or halide-nucleophilic centers, using stable and readily available acetoxymethyl-BODIPYs as reagents in the presence of an acid catalyst. This modular methodology allows a very facile preparation of mono- and di-functional probes incorporating a broad assortment of biomolecules, enzyme cofactors, natural products, and other chromophores, as well as chemical functionalities for a wide range of applications including bioorthogonal conjugation, polymerization, and supramolecular chemistry, among others. The photophysical properties and preliminary applications of the new probes in live-cell imaging were also studied. The described strategy enables the high-throughput engineering of novel BODIPY dyes with diverse functionalities for basic and applied science with potential for innovative technological applications.

Current methods for the preparation of functional small-molecule fluorophores generally require labor-intensive, multi-step synthetic routes for all the major chromophore groups. In spite of recent significant contributions from numerous laboratories, the paucity of rapid, straightforward and wide-scope synthetic strategies in this field is limiting the development of advanced probes for bioimaging, sensing and therapeutic applications. We describe herein a general and robust methodology for the one-step fluorescent labeling of a wide variety of molecules having C-, N-, P-, O-, S-, or halide-nucleophilic centers, using stable and readily available acetoxymethyl-BODIPYs as reagents in the presence of an acid catalyst. This modular methodology allows a very facile preparation of mono- and di-functional probes incorporating a broad assortment of biomolecules, enzyme cofactors, natural products, and other chromophores, as well as chemical functionalities for a wide range of applications including bioorthogonal conjugation, polymerization, and supramolecular chemistry, among others. The photophysical properties and preliminary applications of the new probes in live-cell imaging were also studied. The described strategy could enable the high-throughput engineering of novel BODIPY dyes with diverse functionalities for basic and applied research with potential for innovative technological applications.

Glycosyl sulfoxides have gained recognition in the total synthesis of complex oligosaccharides and as model substrates for dissecting the mechanisms involved. Reactions of these donors are usually performed under pre-activation conditions, but an experimentally more convenient single-step protocol has also been reported, whereby activation is performed in the presence of the acceptor alcohol; yet, the nature and prevalence of the reaction intermediates formed in this more complex scenario have comparatively received minimal attention. Herein, a systematic NMR-based study employing both C-labelled and unlabelled glycosyl sulfoxide donors for the detection and monitoring of marginally populated intermediates is reported. The results conclusively show that glycosyl triflates play a key role in these glycosylations despite the presence of the acceptor alcohol. Importantly, the formation of covalent donor/acceptor sulfonium adducts was identified as the main competing reaction, and thus a non-productive consumption of the acceptor that could limit the reaction yield was revealed.

Rechargeable lithium-ion batteries are excellent candidates for the next generation power sources because of their high gravimetric and volumetric energy compared to other cell chemistries. Conventional LIB¿s, based on organic carbonate liquid electrolytes, suffer from potential thermal and chemical threats associated with the thermal runaway hazard, low thermal stability, low flash points, toxicity, high volatility and flammability. Aprotic ionic liquids, represent a safe alternative to organic carbonates, due to their negligible vapor pressure, wide liquid range, high thermal stability, non-flammability, high ionic conductivity and wide electrochemical stability window. However, problems associated to their high viscosity, especially when lithium salts have been added, low stability of the solid electrolyte interphase (SEI), and high cost need to be solved. In this work, we report on the synthesis and characterization of a series of novel room temperature dicationic ionic liquid electrolytes, based on pyrrolidinium and piperidinium cation moieties linked by short oligo(ethylene glycol) chains. Electrochemical performance of Li-half cells assembled using LiMn2O4 spinel (LMO) as cathode material and 1M LiTFSI doped dicationic ionic liquid electrolytes have been tested.

Dicationic ionic liquids are promising solvents for safe high performance Li-ion battery applications. In this work, we report on the synthesis and characterization of new electrolytes based on geminal dicationic pyrrolidinium and piperidinium bis(trifluoromethane)sulfonimide ionic liquids, where the two cations are linked by variable length oxyethylene chain spacers. All 1 M LiTFSI doped synthesized electrolytes are thermally stable up to 300 °C, and they exhibited remarkable electrochemical stability window up to 6.0 V vs. Li/Li. Electrolytes were assembled with LiMnO (LMO) spinel in lithium half-cells. Electrochemical cell performance in terms of cyclic voltammetry, rate capability and galvanostatic cycling studies have been studied at 60 °C. Results obtained indicate that both the cationic structure and the length of the oxyethylene chain spacer has a significant influence on the electrochemical performance of LMO-cells. The cell based on the pyrrolidinium electrolyte with the two cationic structures linked by two oxyethylene units exhibit the faster rate capability, with a capacity retention of 45% at 5C, and the highest reversible capacity (ca. 80 mAhg).

This paper reports on the synthesis and characterization of novel dicationic ionic liquid electrolytes based on asymmetrical imidazolium-trialkylammonium ionic liquids. The results obtained indicate that the length of the alkyl chain attached to the nitrogen atom has a significant influence on the thermal and electrochemical properties of the electrolytes, as well as on parameters such as lithium ion coordination number and lithium ion transport number. All synthesized dicationic ionic liquids and the corresponding electrolytes are liquid at room temperature being thermally stable up to 300 °C; well above battery operation temperature. Room temperature ionic conductivities of the electrolytes are in the range of 0.8–7.2 × 10 S cm, with an electrochemical stability window of 1.5 V–5.0 V vs. Li/Li. Synthesized electrolytes have been tested in Li half-cells using LiMnO (LMO) spinel as cathode material. Cyclic voltammetry, rate capability and galvanostatic cycling studies at 60 °C have been performed. Again, the alkyl chain length attached to the nitrogen atom plays a significantly role in the electrochemical performance of the LMO cells. Among the cells studied, the one assembled with the electrolyte 1M LITFSI doped IMI-TEA exhibits the best rate capability and the high cycling performance.

The synthesis and characterization of novel ionic liquid (ILs) based gel polymer electrolytes for application in sodium-ion (Na) batteries is reported. It comprises a 0.2 M solution of NaN(CFSO) (sodium bis(trifluoromethylsulfonyl) imide) in mono and dicationic imidazolium-based ionic liquids immobilized in a poly(vinylidene fluoride)-hexafluoropropylene copolymer matrix. The membranes offer acceptable ionic conductivity, up to 2.2 × 10 S cm at room temperature, with excellent thermal and electrochemical stabilities. The useful thermal stability reached up 150 °C and decomposition only starts at about 400 °C, while electrochemical stability window comprises from 1.5 V to 5.0 V vs. Na/Na. Na transference values (t) are in the range of 0.1 to 0.5, indicating a contribution of anionic transport (TFSI anion) and component ions of ionic liquid to the total ionic conductivity. The nature of Na coordination and the formation of Na-complexes were elucidated through Raman spectroscopy. The average number of TFSI coordinated to Na (n) allowed to know the contribution of the formed complexes in ionic mobility mechanism in the gel electrolytes. The effect of side chain length in oxyethylene-functionalized imidazolium mono and dicationic RTILs on both structural and electrochemical properties were discussed. Results obtained demonstrate promising characteristics of the membranes, being suitable candidates to be used in rechargeable sodium batteries.

[EN] The invention relate to graphite materials, and more specifically to the exfoliation of graphite using deep eutectic solvents, to methods related thereto, to polymer composite materials containing graphene and the methods for the production thereof, and to graphene/metal, exfoliated graphite/metal, graphene/metal oxide and exfoliated graphite/metal oxide composite materials and the methods for the production thereof., [ES] La presente invención se refiere a materiales grafíticos, y más específicamente a la exfoliación de grafito usando disolventes eutécticos profundos, métodos relacionados con ello, a materiales compuestos poliméricos que contienen grafeno y los métodos para su preparación, materiales compuestos grafeno/metal, grafito exfoliado/metal, grafeno/óxido metálico y grafito exfoliado/óxido metálicoy los métodos para su preparación.

La presente invención se refiere a materiales grafíticos, y más específicamente a la exfoliación de grafito usando disolventes eutécticos profundos, métodos relacionados con ello, a materiales compuestos poliméricos que contienen grafeno y los métodos para su preparación, materiales compuestos grafeno/metal, grafito exfoliado/metal, grafeno/óxido metálico y grafito exfoliado/óxido metálicoy los métodos para su preparación.

Líquidos iónicos, procedimiento de preparación y su uso como electrolitos para dispositivos electroquímicos de almacenamiento de energía. La presente invención se refiere a líquidos iónicos de formula general (1) , su síntesis y al uso de los dichos líquidos iónicos como electrolitos en dispositivos electroquímicos de almacenamiento de energía eléctrica. ,....

[EN] The invention relates to ionic liquids of general formula (I), to the synthesis thereof, and to the use of said ionic liquids as electrolytes in electrochemical electrical energy storage devices., [ES] La presente invención se refiere a líquidos iónicos de formula general (I), su síntesis y al uso de los dichos líquidos iónicos como electrolitos en dispositivos electroquímicos de almacenamiento de energía eléctrica. (I)

Staphylococcal enterotoxin B (SEB) exposure triggers an exaggerated pro-inflammatory cytokine response that often leads to toxic shock syndrome (TSS) associated with organ failure and death. MyD88 mediates pro-inflammatory cytokine signaling induced by SEB exposure and MyD88-/- mice are resistant to SEB intoxication, suggesting that MyD88 may be a potential target for therapeutic intervention. We targeted the BB loop region of the Toll/IL-1 receptor (TIR) domain of MyD88 to develop small-molecule therapeutics. Here, we report that a synthetic compound (EM-163), mimic to dimeric form of BB-loop of MyD88 attenuated tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1Beta, IL-2 and IL-6 production in human primary cells, whether administered pre- or post-SEB exposure. Results from a direct binding assay and from MyD88 co-transfection/co-immunoprecipitation experiments, suggest that EM-163 inhibits TIR-TIR domain interaction. Additional results indicate that EM-163 prevents MyD88 from mediating downstream signaling. In an NF-kB-driven reporter assay of lipopolysaccharide-stimulated MyD88 signaling, EM-163 demonstrated a dose-dependent inhibition of reporter activity as well as TNF-alpha and IL-1Beta production. Importantly, administration of EM-163 pre- or post exposure to a lethal dose of SEB abrogated pro-inflammatory cytokine responses and protected mice from toxic shock-induced death. Taken together, our results suggest that EM-163 exhibits a potential for therapeutic use against SEB intoxication., Published in PLoS ONE, v7 n7 e40773, July 27, 2012. The original document contains color images.

The first total synthesis of the natural alkaloid amphorogynine C is reported (2.9 % overall yield in 20 steps). The key steps include a Claisen-Johnson rearrangement and an intramolecular azide-olefin cycloaddition, followed by a reduction of the resulting imine. The construction of the pyrrolizidine skeleton was achieved by an alkoxide-mediatedlactone ring opening and subsequent cyclization of a conveniently functionalized bicyclic amine. Finally, the proposed structure of amphorogynine C was confirmed by single-crystal X-ray diffraction analysis. The first synthesis of the representative pyrrolizidine alkaloid amphorogynine C is described. The key step includes an intramolecular azide-olefin cycloaddition reaction. The proposed structure of the natural product was confirmed by single-crystal X-ray diffraction analysis. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Toxic shock syndrome (TSS) is a clinical consequence of the profound amplification of host pro-inflammatory cytokine signaling that results from staphylococcal enterotoxin (SE) exposure. We recently reported that MyD88-/- mice were resistant to SEA or SEB toxic shock and displayed reduced levels of pro-inflammatory cytokines in their serum. Here we report that SEB stimulation of total mononuclear cells up-regulated MyD88 in monocytes and T cells. Further, MyD88 gene silencing in primary human cells using siRNA prevented SEB or SEB plus lipopolyaccharide (LPS) induction of interleukin-1 Beta (IL-1 Beta) transcriptional activation, suggesting that MyD88-mediated signaling is an essential component of SEB toxicity. We synthesized small molecules that mimic the conserved BBloop in the Toll/IL-1 receptor (TIR) domain of MyD88. In primary human cells, these mimetics attenuated SEB-induced proinflammatory cytokine production. SEB stimulation of primary cells with mimetic affected newly synthesized MyD88 and downstream signaling components. Furthermore, LPS-induced MyD88 signaling was likewise inhibited in a cell-based reporter assay. More importantly, administration of mimetic reduced cytokine responses and increased survivability in a murine SEB challenge model. Collectively, these results suggest that MyD88 BB-loop mimetics interfere with SEB-induced proinflammatory signaling and toxicity, thus offering a potential approach in the therapy of toxic shock., Published in Journal of Biological Chemistry, 21 June 2011.