New synthetic approach to paullones and characterization of their SIRT1 inhibitory activity

A series of 7,12-dihydroindolo[3,2-d][1]benzazepine-6(5H)-ones (paullones) substituted at C9/C10 (Br) and C2 (Me, CF(3), CO(2)Me) have been synthesized by a one-pot Suzuki-Miyaura cross-coupling of an o-aminoarylboronic acid and methyl 2-iodoindoleacetate followed by intramolecular amide formation. Other approaches to the paullone scaffold based on Pd-catalyzed C-H activation were unsuccessful. In vitro enzymatic assay with recombinant human SIRT-1 indicated a strong inhibitory profile for the series, in particular the analogue with a methoxycarbonyl group at C2 and a bromine at C9. These compounds are, in general, inducers of granulocyte differentiation of the U937 acute leukemia cell line and cause a marked increase in pre-G1 of the cell cycle.     

Searching for new cell-penetrating agents: hybrid cyclobutane-proline γ,γ-peptides

Two generations of hybrid γ,γ-peptides containing cyclobutane amino acids and cis-γ-amino-L-proline joined in alternation have been synthesized and their capacity to cross the eukaryotic cell membrane has been evaluated. The first generation consists of di-, tetra- and hexapeptides, and their properties have been analyzed as well as the influence of peptide length and chirality of the cyclobutane residues. Results have shown that the absolute configuration of the cyclobutane amino acid does not have a relevant influence. The second generation consists of hybrid γ,γ-hexapeptides with a common backbone and distinct side chains introduced with different linkage types through the α-amino group (N(α)) of the proline monomers. These peptides have been shown to be non-toxic towards HeLa cells and to internalize them effectively, the best results being obtained for the peptides with a spacer of five carbons between the N(α) atom and the guanidinium group. The introduction of cyclobutane residues inside the sequence affords a good balance between charge and hydrophobicity, reducing the number of positive charges. This results in lower toxicity and similar cell-uptake properties when compared to previously described peptide agents.     

Synthesis, characterisation, and biodistribution of radioiodinated C-hydroxy-carboranes

The synthesis, radiolabelling and biodistribution of iodinated C-hydroxy-nido-carborane ligands is described. Microwave heating by using NaF in aqueous ethanol was used to prepare {sodium [7-hydroxy-7,8-dicarba-nido-undecaborate], nido-carboranol} and {sodium [7-hydroxy-7,8-dicarba-nido-undecaborate-8-carboxylic acid], nido-salborin} in 97 and 90?% yield, respectively. Radioiodination of these nido-carboranes was completed by using both (125) I and (123) I, and the products were obtained in high radiochemical purity (>99?%) and yield (72 to 87?%). The structures of the radiolabelled products were validated through comparison to authentic standards. Biodistribution studies in BALB/c mice showed low accumulation of the labelled compounds in the liver and intestines, which are sites where labelled carboranes typically localise. The labelled cluster bearing hydroxy and carboxylic acid groups on the two carbon vertices demonstrated preferential clearance through the kidneys and low thyroid uptake. This compound had substantially reduced non-specific binding than the deshydroxy analogue making it an attractive bifunctional ligand for preparing targeted molecular imaging and therapy agents.     

Bioactivity and Viscoelastic Characterization of Chitosan/Bioglass® Composite Membranes

Membranes of chitosan (CTS) and composite membranes of CTS with bioglass are prepared by solvent casting. The composite membranes are shown to induce the precipitation of apatite upon immersion in SBF. The biomineralization process is followed by measuring the variation of the viscoelastic properties of the membranes immersed in SBF, both online and offline. Non‐conventional DMA is used to measure the change in the storage modulus, E′, and the loss factor, tan δ, as a function of the immersion in SBF. A simple model is used to estimate the E′ of the apatite layer formed in vitro that is about 130 MPa. This work shows that innovate mechanical tests can be useful to characterize the mechanical performance of composites under physiological conditions.

     

A simple gas chromatography method for the analysis of monoethanolamine in air

A simple method determining airborne monoethanolamine has been developed. Monoethanolamine determination has traditionally been difficult due to analytical separation problems. Even in recent sophisticated methods, this difficulty remains as the major issue often resulting in time-consuming sample preparations. Impregnated glass fiber filters were used for sampling. Desorption of monoethanolamine was followed by capillary GC analysis and nitrogen phosphorous selective detection. Separation was achieved using a specific column for monoethanolamines (35% diphenyl and 65% dimethyl polysiloxane). The internal standard was quinoline. Derivatization steps were not needed. The calibration range was 0.5-80 μg/mL with a good correlation (R(2) = 0.996). Averaged overall precisions and accuracies were 4.8% and -7.8% for intraday (n = 30), and 10.5% and -5.9% for interday (n = 72). Mean recovery from spiked filters was 92.8% for the intraday variation, and 94.1% for the interday variation. Monoethanolamine on stored spiked filters was stable for at least 4 weeks at 5°C. This newly developed method was used among professional cleaners and air concentrations (n = 4) were 0.42 and 0.17 mg/m(3) for personal and 0.23 and 0.43 mg/m(3) for stationary measurements. The monoethanolamine air concentration method described here was simple, sensitive, and convenient both in terms of sampling and analytical analysis.     

Bis-trifluoromethyl Effect: Doubled Transitions in the Rotational Spectra of Hexafluoroisobutene, (CF(3))(2)C═CH(2)

Rotational spectra for hexafluoroisobutene, and its (13)C isotopologues, have been recorded between 8 and 16 GHz using a chirped pulse, Fourier transform microwave spectrometer. Notably, all spectra observed are doubled with separations between the doublets being between 1 and 60 MHz. We propose that the bis-trifluoromethyl groups of the target molecule are staggered in the equilibrium configuration, and that a novel, out-of-phase rotation through a F-CCC-F planar configuration with low barrier (<100 cm(-1)), leads to the observed doubled rotational spectra.     

Enhancement of the Kondo effect through Rashba spin-orbit interactions

We study a one-orbital Anderson impurity in a two-dimensional electron bath with Rashba spin-orbit interactions in the Kondo regime. The spin SU(2) symmetry-breaking term couples the impurity to a two-band electron gas. A Schrieffer-Wolff transformation shows the existence of the Dzyaloshinsky-Moriya interaction away from the particle-hole symmetric impurity state. A renormalization group analysis reveals a two-channel Kondo model with ferro- and antiferromagnetic couplings. The parity-breaking Dzyaloshinsky-Moriya term renormalizes the antiferromagnetic Kondo coupling with an exponential enhancement of the Kondo temperature.     

Optical measurement of acoustic pressure amplitudes-at the sensitivity limits of Rayleigh scattering

Rayleigh scattering is a measurement technique applicable for the determination of density distributions in various technical or natural flows. The current sensitivity limits of the Rayleigh scattering technique were investigated experimentally. It is shown that it is possible to measure density oscillations caused by acoustic pressure oscillations noninvasively and directly. Acoustical standing waves in a rectangular duct were investigated using Rayleigh scattering and compared to microphone measurements. The comparison showed a sensitivity of the Rayleigh scattering technique of 75 Pa (7·10(-4) kg/m(3)) and a precision of 14 Pa (1·10(-4) kg/m(3)). Therefore, it was also shown that Rayleigh scattering is applicable for acoustic measurements.     

Chain transfer to aluminium in MAO-activated metallocene-catalyzed polymerization reactions

Chemical trapping of metal-bound oligomeric chains during the MAO-activated, metallocene-catalyzed polymerization of ethylene identify the two observed chain-bearing species to be alkylzirconocenium species and higher alkyl aluminiums, consistent with a proposed mechanism.