Solid-phase synthesis and biological evaluation of a teleocidin library--discovery of a selective PKCdelta down regulator

Protein kinaseC (PKC) is linked to the signal-induced modulation of a wide variety of cellular processes, such as growth, differentiation, secretion, apoptosis, and tumor development. The design and synthesis of small molecules that regulate these different cellular signaling systems is at the forefront of modern drug design. Herein we report a) an efficient method for the synthesis of indolactamV (6), a PKC activator, and its N13-des(methyl) analogues (19) using a regioselective organometallic transformation, a convenient aminomalonate derivative (10) to introduce the appropriate functionality and an enantiospecific enzymic hydrolysis as key steps; b) the use of this method in the first solid-phase synthesis of a teleocidin library modifying the N-13, C-12 and C-7 alkyl chains, and, therefore, producing a library of potential activators and/or inhibitors of PKC of the general structure (32); c) the activation of PKC by selected members of the library using a MARCKS translocation in vivo assay system; d) the observation that some of these analogues are nearly as effective as the natural PKC activators phorbol dibutyrate and (-)-indolactam V (6), and e) the observation that some of these analogues have different potential to induce down-regulation of members of the PKC gene family after chronic stimulation.     

Poly(2-hydroxyethyl acrylate) hydrogel confined in a hydrophobous porous matrix

A series of interpenetrated polymer networks (IPNs) in which the first component is a porous poly(ethyl methacrylate) (PEMA) hydrophobic network and the second one is a poly(2-hydroxyethyl acrylate) (PHEA) hydrophilic network were synthesized. Equilibrium sorption isotherms can be reduced to a single master curve for all the IPNs when the water absorbed is expressed per gram of PHEA in them. The equilibrium water sorption in immersion is always much smaller than that of pure PHEA. This feature is due to the confining effect of the stiff PEMA matrix. The plasticizing effect of the absorbed water on the PHEA phase was characterized using thermally stimulated depolarization currents, dynamic-mechanical analysis and dielectric relaxation spectroscopy. The results show that the shift of the main relaxation peak towards lower temperatures is unaffected by the presence of the PEMA matrix, and only depends on the water content per gram of PHEA in the IPN.     

Application of a Laplace Transform Method to the Study of Binary Mixtures of Spherical and Rod-Like Particles for Low Intensity Levels.

A Laplace Transform (LT) method is used to improve the results obtained in a quasi-elastic scattering (QELS) experiment. This is designed to determine the characteristic parameters of a bimodal solution of spherical and rod-like macromolecules. The theoretical study and the experimental simulation are carried out for low light levels and the results show that the LT technique provides a real alternative to the second order correlation function, g⁽²⁾(τ), in QELS measurements for these particularly difficult experimental conditions.     

Arsenic Speciation in Marine Sediments: Effects of Redox Potential and Reducing conditions

Abstract

The speciation of arsenic in the environment is among others controlled by reduction, methylation and oxidation processes and therefore influenced by the prevailing redox conditions. In this study we have analyzed sediments taken from La Coruña estuary in the north west of Spain. Inorganic (trivalent and pentavalent) and the organic (MMA and DMA) arsenic speciation is related to Eh, Fe and Mn load. The various of the arsenic species concentration and other parameters was analyzed at different depths in some of the sampling points. Low arsenic concentrations (1–10 μg·g^–1) were found. In spite of oxidising conditions (Eh values between 31–96 mV), most of the samples showed a higher As(V) percentage than As (III). Principal component analysis was made to see a sample groups and the results showed that speciation depends on reducing conditions (Eh and Mn).     

Unexpected reactivity of pyridinium salts toward alkynyl Fischer complexes to produce oxo‐heterocycles

The unprecedented reaction of ketone‐containing aromatic pyridinium salts 3a ‐ e and alkynyl Fischer complexes 1a ‐ f proceeds via a mild domino process to provide 4,6‐disubstituted pyran‐2‐ones 5a ‐ k and 2,3,5‐trisubstituted furans 6a ‐ h (45‐97%). According of the results of isotopic labeling experiments, a mechanism involving an initial Michael addition appears to be the key step, obtaining a mesomeric structure responsible for the formation of both products.     

The Effect of Auxiliary Nitrogenated Linkers on the Design of New Cadmium-Based Coordination Polymers as Sensors for the Detection of Explosive Materials

Three new cadmium-based coordination polymers, denoted [Cd(hfipbb)(4,4’-bipy)] ( CdPF-1 ), [Cd(hfipbb)(2,2’-bipy)] ( CdPF-2 ), and [Cd(hfipbb)(1,10-phen)] ( CdPF-3 ), have been hydrothermally synthesized by using the well-known V-shaped organic linker 4,4’-(hexafluoroisopropylidene)bis(benzoic acid) (H₂hfipbb), together with different nitrogenated auxiliary linkers. Considering the d¹⁰ configuration of the transition metal selected, the luminescent properties for these CdPF-n materials were explored, finding that materials CdPF-2 and CdPF-3 act as excellent sensors in the detection of explosive nitro aromatic compounds. The photoluminescence properties of CdPF-2 and CdPF-3 revealed that significant and sensitive fluorescence quenching was observed toward NP (nitrophenol) for CdPF-2 and PA (picric acid) for CdPF-3 in MeOH suspensions.     

Contribution of thermal imaging to fertigation in soilless culture

Thermography is a tool used in many scientific disciplines, including agriculture. This paper describes the application of thermography as a rapid diagnostic method of adequate watering. Two experiments were conducted. In experiment 1, Philodendron erubescens and Anthurium andraeum were transplanted to pots in a greenhouse in Almeria (Spain). The vegetative growth parameters of these plants were measured. In experiment 2, two areas of vegetative cover were established on green walls: one with a combination of aromatic plants and another with ornamental indoor plants. The thermographic images were recorded using a compact infrared camera, which had a spectral infrared range of 7.3–13 μm, microbolometer of 320 × 240 pixels, and the resolution was 0.01 °C at 30 °C. Three irrigation treatments were applied in both experiments, consisting of a control treatment (CT), a deficit irrigation [1/3 less volume, deficient irrigation (DI)] treatment, and an excess irrigation [1/3 greater volume, excess irrigation (EI)] treatment. In both experiments, the sample temperatures were recorded by thermography for each irrigation treatment. In experiment 1, the vegetative growth parameters were greater under CT than under DI or EI. The data of the reference thermographs over the leaves of the potted plants were significantly correlated with the superior growth parameters under the optimal irrigation treatment. A continuous vegetative canopy was formed on both of the green walls in experiment 2, and the average temperatures were correlated with the irrigation treatments in this experiment. The temperatures reflected in the reference thermographs allowed for the determination of the most appropriate irrigation treatment. These results suggest that thermography can be a useful method to provide an early diagnosis of water stress in potted plants and green walls.     

An Adjustable Cleft Based on an 8-Sulfonamide-2-Naphthoic Acid with Oxyanion Hole Geometry

Cleft type receptors showing the oxyanion hole motif have been prepared in a straightforward synthesis starting from the commercial 3,7-dihidroxy-2-naphthoic acid. The double H-bond donor pattern is achieved by the introduction of a sulfonamide group in the C-8 position of naphthalene and a carboxamide at the C-2 position. This cleft, for which the geometry resembles that of an oxyanion hole, is able to adjust to different guests, as shown by the analysis of the X-ray crystal structures of associates with methanol or acetic acid. Combination of hydrogen bonds and charge-transfer interactions led to further stabilization of the complexes, in which the electron-rich aromatic ring of the receptor was close in space to the electron-deficient dinitroaromatic guests. Modelling studies and bidimensional NMR experiments have been carried out to provide additional information.