Organic reactions in supercritical fluids: Continuous, selective and green

Supercritical fluids (SCFs) offer a wide range of opportunities as media for chemical reactions and supercritical CO2, ScCO2, is becoming increasingly important as a benign replacement for more toxic solvents.1 High pressure reactions, however, are more capital intensive than conventional low pressure processes. Therefore, supercritical fluids will only gain widespread acceptance in those areas where the fluids give real chemical advantages as well as environmental benefits. This lecture gives a brief account of the use of flow reactors for continuous reactions in supercritical fluids, particularly those of interest for the manufacture of fine chemicals.

Probing biomolecular interaction forces using an anharmonic acoustic technique for selective detection of bacterial spores.

Receptor-based detection of pathogens often suffers from non-specific interactions, and as most detection techniques cannot distinguish between affinities of interactions, false positive responses remain a plaguing reality. Here, we report an anharmonic acoustic based method of detection that addresses the inherent weakness of current ligand dependant assays. Spores of Bacillus subtilis (Bacillus anthracis simulant) were immobilized on a thickness-shear mode AT-cut quartz crystal functionalized with anti-spore antibody and the sensor was driven by a pure sinusoidal oscillation at increasing amplitude. Biomolecular interaction forces between the coupled spores and the accelerating surface caused a nonlinear modulation of the acoustic response of the crystal. In particular, the deviation in the third harmonic of the transduced electrical response versus oscillation amplitude of the sensor (signal) was found to be significant. Signals from the specifically-bound spores were clearly distinguishable in shape from those of the physisorbed streptavidin-coated polystyrene microbeads. The analytical model presented here enables estimation of the biomolecular interaction forces from the measured response. Thus, probing biomolecular interaction forces using the described technique can quantitatively detect pathogens and distinguish specific from non-specific interactions, with potential applicability to rapid point-of-care detection. This also serves as a potential tool for rapid force-spectroscopy, affinity-based biomolecular screening and mapping of molecular interaction networks.

One possible way to promote the bond-selective chemical-reactions by frequency-modulated lasers

It is proposed in this paper that we can use frequency-modulated (FM) lasers to realize bond-selective chemical reactions or to raise the efficiency of molecular isotope separation. Examples are given for HF molecule and the C–H bond in some hydrocarbons.

Evaluation of bioactive sphingolipids in 4-HPR-resistant leukemia cells

Background -- N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide) is a synthetic retinoid with potent pro-apoptotic activity against several types of cancer, but little is known regarding mechanisms leading to chemoresistance. Ceramide and, more recently, other sphingolipid species (e.g., dihydroceramide and dihydrosphingosine) have been implicated in 4-HPR-mediated tumor cell death. Because sphingolipid metabolism has been reported to be altered in drug-resistant tumor cells, we studied the implication of sphingolipids in acquired resistance to 4-HPR based on an acute lymphoblastic leukemia model. Methods -- CCRF-CEM cell lines resistant to 4-HPR were obtained by gradual selection. Endogenous sphingolipid profiles and in situ enzymatic activities were determined by LC/MS, and resistance to 4-HPR or to alternative treatments was measured using the XTT viability assay and annexin V-FITC/propidium iodide labeling. Results -- No major crossresistance was observed against other antitumoral compounds (i.e. paclitaxel, cisplatin, doxorubicin hydrochloride) or agents (i.e. ultra violet C, hydrogen peroxide) also described as sphingolipid modulators. CCRF-CEM cell lines resistant to 4-HPR exhibited a distinctive endogenous sphingolipid profile that correlated with inhibition of dihydroceramide desaturase. Cells maintained acquired resistance to 4-HPR after the removal of 4-HPR though the sphingolipid profile returned to control levels. On the other hand, combined treatment with sphingosine kinase inhibitors (unnatural (dihydro)sphingosines ((dh)Sph)) and glucosylceramide synthase inhibitor (PPMP) in the presence or absence of 4-HPR increased cellular (dh)Sph (but not ceramide) levels and were highly toxic for both parental and resistant cells. Conclusions -- In the leukemia model, acquired resistance to 4-HPR is selective and persists in the absence of sphingolipid profile alteration. Therapeutically, the data demonstrate that alternative sphingolipid-modulating antitumoral strategies are suitable for both 4-HPR-resistant and sensitive leukemia cells. Thus, whereas sphingolipids may not be critical for maintaining resistance to 4-HPR, manipulation of cytotoxic sphingolipids should be considered a viable approach for overcoming resistance.

Potential applications of reproductive and molecular genetic technologies in the selective breeding of aquaculture species

The use of reproductive and genetic technologies can increase the efficiency of selective breeding programs for aquaculture species. Four technologies are considered, namely: marker-assisted selection, DNA fingerprinting, in-vitro fertilization, and cryopreservation. Marker-assisted selection can result in greater genetic gain, particularly for traits difficult or expensive to measure, than conventional selection methods, but its application is currently limited by lack of high density linkage maps and by the high cost of genotyping. DNA fingerprinting is most useful for genetic tagging and parentage verification. Both in-vitro fertilization and cryopreservation techniques can increase the accuracy of selection while controlling accumulation of inbreeding in long-term selection programs. Currently, the cost associated with the utilization of reproductive and genetic techniques is possibly the most important factor limiting their use in genetic improvement programs for aquatic species.

A Trifluoromethyl Analogue of Celecoxib Exerts Beneficial Effects in Neuroinflammation

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Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

The synthesis of a GSK 2(nd) generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I) and gold(I) catalysts in this reaction was established by working with chiral phosphoramidites or with chiral BINAP. The best reaction conditions were used for the total synthesis of the hepatitis C virus inhibitor by a four step procedure affording this product in 99% ee and in 63% overall yield. The origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial.

Development of catalytic methane reforming systems integrating hydrogen selective PdCu membrane modules

En la presente tesis doctoral se ha estudiado la integración del proceso de producción de hidrógeno con su purificación mediante el empleo de membranas selectivas de hidrógeno. La producción de hidrógeno se realiza empleando catalizadores no convencionales de níquel soportado sobre magnesia y alúmina en un reactor catalítico. Se analiza la actividad de los catalizadores y la producción de hidrógeno mediante distintos procesos con metano como son la oxidación parcial catalítica (OPC), OPC húmeda y reformadoLa purificación de hidrógeno se realiza en un módulo provisto de una membrana selectiva de hidrógeno de PdCu depositado en un soporte poroso cerámico. Una vez optimizada su preparación mediante deposición no electrolítica se caracterizan. Para ello se determina su permeabilidad a distintas temperaturas y realizando ciclos térmicos en atmósferas inerte y de hidrógeno, que puede fragilizar el metal. Una vez preparados los catalizadores y las membranas se integran los dos sistemas y se determinan los parámetros de operación óptimos como la presión de la línea de alimentación y el caudal de gas de arrastre en el módulo de membrana. Ambos parámetros se optimizan para lograr la máxima recuperación de hidrógeno en el módulo de membrana. Por últimos se realizan ensayos completos de producción y purificación, que permiten observar el rendimiento del sistema y también el efecto que los compuestos de la mezcla compleja alimentada a las membranas tienen en su comportamiento. Para concluir la integración de procesos se realizan ensayos añadiendo azufre de forma que el sistema sea más similar al proceso real. Esto permite también analizar el efecto del azufre tanto en los catalizadores como en las membranas.