Reactivity of TpMe2-containing hydride-iridafurans with alkenes, alkynes, and H2

The TpMe2-containing hydride-iridafurans 2a,b (TpMe2 = hydrotris(3,5-dimethylpyrazolyl)borate) cleanly reacted with ethylene to give the bicyclic derivatives 6a,b. Formation of the latter complexes is a reversible process, and it is proposed to occur by an electrocyclic ring closure that takes place between C2H4 and the 16e unsaturated intermediates A, resulting from hydride migration to the α carbon of the metallacycle. Similar reactions were observed with a variety of alkynes RC≡CR (R = H, Ph, CO2Me) and R′C≡CH (R′= CO2Me, Ph, CMe3), with the regioselectivity observed for the latter substrates depending on the nature of R′. In the case of Me3SiC≡CH the structure of an unexpected byproduct indicates that an alkyne–vinylidene rearrangement has taken place on the metal coordination sphere during the reaction, and this observation suggests that in the mechanism of all these coupling processes the corresponding π adducts are active intermediates. Finally, complexes 2a,b reacted with H2 to give products derived from the hydrogenation of their alkenyl arms.Ministerio de Ciencia e Innovación CTQ2010-17476. Consolider Ingenio 2010 CSD 2007-0006Junta de Andalucía FQM-119, P09-FQM-483

Docetaxel-Loaded Nanoparticles Assembled from β-Cyclodextrin/Calixarene Giant Surfactants: Physicochemical Properties and Cytotoxic Effect in Prostate Cancer and Glioblastoma Cells

Giant amphiphiles encompassing a hydrophilic β-cyclodextrin (βCD) component and a hydrophobic calix[4]arene (CA4) module undergo self-assembly in aqueous media to afford core-shell nanospheres or nanocapsules, depending on the nanoprecipitation protocol, with high docetaxel (DTX) loading capacity. The blank and loaded nanoparticles have been fully characterized by dynamic light scattering (DLS), ζ-potential measurements and cryo-transmission electron microscopy (cryo-TEM). The data are compatible with the distribution of the drug between the nanoparticle core and the shell, where it is probably anchored by inclusion of the DTX aromatic moieties in βCD cavities. Indeed, the release kinetics profiles evidenced an initial fast release of the drug, which likely accounts for the fraction hosted on the surface, followed by a slow and sustained release rate, corresponding to diffusion of DTX in the core, which can be finely tuned by modification of the giant amphiphile chemical structure. The ability of the docetaxel-loaded nanoparticles to induce cellular death in different prostate (human LnCap and PC3) and glioblastoma (human U87 and rat C6) cells was also explored. Giant amphiphile-based DTX formulations surpassing or matching the antitumoral activity of the free DTX formulation were identified in all cases with no need to employ any organic co-solvent, thus overcoming the DTX water solubility problems. Moreover, the presence of the βCD shell at the surface of the assemblies is intended to impart stealth properties against serum proteins while permitting nanoparticle surface decoration by supramolecular approaches, paving the way for a new generation of molecularly well-defined antitumoral drug delivery systems with improved specificity and efficiency. Altogether, the results provide a proof of concept of the suitability of the approach based on βCD-CA4 giant amphiphiles to access DTX carriers with tunable properties

MULTICUBE: Multi-objective design space exploration of multi-core architectures

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Combining biotechnology with circular bioeconomy: from poultry, swine, cattle, brewery, dairy and urban wastewaters to biohydrogen

ABSTRACT: The ability of microalgae to grow in nutrient-rich environments and to accumulate nutrients from wastewaters (WW) makes them attractive for the sustainable and low-cost treatment of WW. The valuable biomass produced can be further used for the generation of bioenergy, animal feed, fertilizers, and biopolymers, among others. In this study, Scenedesmus obliquus was able to remove nutrients from different wastewaters (poultry, swine and cattle breeding, brewery and dairy industries, and urban) with removal ranges of 95-100% for nitrogen, 63-99% for phosphorus and 48-70% for chemical oxygen demand. The biomass productivity using wastewaters was higher (except for poultry) than in synthetic medium (Bristol), the highest value being obtained in brewery wastewater (1025 mg/(L.day) of freeze-dried biomass). The produced biomass contained 31-53% of proteins, 12-36% of sugars and 8-23% of lipids, regardless of the type of wastewater. The potential of the produced Scenedesmus obliquus biomass for the generation of BioH(2) through batch dark fermentation processes with Enterobacter aerogenes was evaluated. The obtained yields ranged, in mL H-2/g Volatile Solids (VS), from 50.1 for biomass from anaerobically digested cattle WW to 390 for swine WW, whereas the yield with biomass cultivated in Bristol medium was 57.6 mL H-2/gvs.info:eu-repo/semantics/publishedVersio

A Randomized Placebo-Controlled Trial of Varenicline for Smoking Cessation Allowing Flexible Quit Dates

Introduction: Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication. Methods: In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were instructed to quit between Days 8 and 35 after starting medication. The primary endpoint was carbon monoxide-confirmed continuous abstinence during Weeks 9-12, and a key secondary endpoint was continuous abstinence during Weeks 9-24. Results: Overall, 493 subjects were randomized to varenicline and 166 to placebo. Continuous abstinence was higher for varenicline than for placebo subjects at the end of treatment (Weeks 9-12: 53.1% vs. 19.3%; odds ratio [OR] 5.9; 95% CI, 3.7-9.4; p < .0001) and through 24 weeks follow-up (Weeks 9-24: 34.7% vs. 12.7%; OR 4.4; 95% CI, 2.6-7.5; p < .0001). Serious adverse events occurred in 1.2% varenicline (none were psychiatric) and 0.6% placebo subjects. Fewer varenicline than placebo subjects reported depression-related adverse events (2.3% vs. 6.7%, respectively). Conclusions: Varenicline 1 mg b.i.d. using a flexible quit date paradigm had similar efficacy and safety compared with previous fixed quit date studies. © The Author 2011. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco

Docetaxel-Loaded Nanoparticles Assembled from β-Cyclodextrin/Calixarene Giant Surfactants: Physicochemical Properties and Cytotoxic Effect in Prostate Cancer and Glioblastoma Cells

Giant amphiphiles encompassing a hydrophilic β-cyclodextrin (βCD) component and a hydrophobic calix[4]arene (CA4) module undergo self-assembly in aqueous media to afford core-shell nanospheres or nanocapsules, depending on the nanoprecipitation protocol, with high docetaxel (DTX) loading capacity. The blank and loaded nanoparticles have been fully characterized by dynamic light scattering (DLS), ζ-potential measurements and cryo-transmission electron microscopy (cryo-TEM). The data are compatible with the distribution of the drug between the nanoparticle core and the shell, where it is probably anchored by inclusion of the DTX aromatic moieties in βCD cavities. Indeed, the release kinetics profiles evidenced an initial fast release of the drug, which likely accounts for the fraction hosted on the surface, followed by a slow and sustained release rate, corresponding to diffusion of DTX in the core, which can be finely tuned by modification of the giant amphiphile chemical structure. The ability of the docetaxel-loaded nanoparticles to induce cellular death in different prostate (human LnCap and PC3) and glioblastoma (human U87 and rat C6) cells was also explored. Giant amphiphile-based DTX formulations surpassing or matching the antitumoral activity of the free DTX formulation were identified in all cases with no need to employ any organic co-solvent, thus overcoming the DTX water solubility problems. Moreover, the presence of the βCD shell at the surface of the assemblies is intended to impart stealth properties against serum proteins while permitting nanoparticle surface decoration by supramolecular approaches, paving the way for a new generation of molecularly well-defined antitumoral drug delivery systems with improved specificity and efficiency. Altogether, the results provide a proof of concept of the suitability of the approach based on βCD-CA4 giant amphiphiles to access DTX carriers with tunable properties.This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO, grants no. BFU2014-59009-P, SAF2016-76083-R and CTQ2015-64425-C2-1-R), CYTED (grant no. 214RT0482); the Junta de Andalucía (grant no. FQM2012-1467), the European Union (FEDER and FSE) the CSIC and the MIUR (PRIN 2010 JMAZML, MultiNanoIta).Peer Reviewe

Reaction of [TpRh(C2H4)2] with dimethyl acetylenedicarboxylate: identification of intermediates of the [2+2+2] alkyne and alkyne-ethylene cyclo(co)trimerizations

The reaction between the bis(ethylene) complex [TpRh(CH)], 1, (Tp=hydrotris(pyrazolyl)borate), and dimethyl acetylenedicarboxylate (DMAD) has been studied under different experimental conditions. A mixture of products was formed, in which TpRh species were prevalent, whereas the presence of trapping agents, like water or acetonitrile, allowed for the stabilization and isolation of octahedral TpRh compounds. An excess of DMAD gave rise to a small amount of the [2+2+2] cyclotrimerization product hexamethyl mellitate (6). Although no catalytic application of 1 was achieved, mechanistic insights shed light on the formation of stable rhodium species representing the resting state of the catalytic cycle of rhodium-mediated [2+2+2] cyclo(co)trimerization reactions. Metallacyclopentene intermediate species, generated from the activation of one alkyne and one ethylene molecule from 1, and metallacyclopentadiene species, formed by oxidative coupling of two alkynes to the rhodium centre, are crucial steps in the pathways leading to the final organometallic and organic products.Financial support (FEDER contribution) from the Spanish Ministerio de Economía y Competitividad (grants CSD2007‐0006 and CTQ2014‐51912‐REDC) and the Junta de Andalucía (Grant FQM‐119) is acknowledged.Peer Reviewe

Formation of unusual iridabenzene and metallanaphthalene containing electron-withdrawing substituents

A new route to irida-aromatic derivatives which consists of the oxidation of bicyclic compounds has been disclosed. The iridanaphthalene 3 experiences hydrolytic cleavage of the Ir-carboxylate moiety regenerating the bicyclic structure 5, whereas treatment of 5 with ClC(O)CO2Me yields back the metalla-aromatic 3. Copyright © 2003 American Chemical Society.Financial support from the DGI (Project BQU2001-1995, FEDER support) and from the Junta de Andalucía, EU COST Action WG-D17-003, and cooperation project CSICCONACyT 2001MX0003-E130.0337 are gratefully acknowledged. C.M.P. and N.R. thank the Junta de Andalucía and the MECD for research grants.Peer Reviewe

Aldehyde-Assisted Hydrogen Transfer during the Formation of Hydride-Iridafurans from Alkynes and Aldehydes

The bis(ethylene) IrI complex [Tpmath imageIr(C2H4)2] (1; Tpmath image=hydrotris(3,5-dimethylpyrazolyl)borate) reacts with two equivalents of aromatic or aliphatic aldehydes in the presence of one equivalent of dimethyl acetylenedicarboxylate (DMAD) with ultimate formation of hydride iridafurans of the formula [Tpmath imageIr(H){C(R1)[DOUBLE BOND]C(R2)C(R3)O}] (R1=R2=CO2Me; R3=alkyl, aryl; 3). Several intermediates have been observed in the course of the reaction. It is proposed that the key step of metallacycle formation is a C[BOND]C coupling process in the undetected IrI species [Tpmath imageIr{η1-O-R3C([DOUBLE BOND]O)H}(DMAD)] (A) to give the trigonal-bipyramidal 16 e− IrIII intermediates [Tpmath imageIr{C(CO2Me)[DOUBLE BOND]C(CO2Me)C(R3)(H)O}] (C), which have been trapped by NCMe to afford the adducts 11 (R3=Ar). If a second aldehyde acts as the trapping reagent for these species, this ligand acts as a shuttle in transfering a hydrogen atom from the γ- to the α-carbon atom of the iridacycle through the formation of an alkoxide group. Methyl propiolate (MP) can be used instead of DMAD to regioselectively afford the related iridafurans. These reactions have also been studied by DFT calculations.Peer Reviewe