Pharmacophore model for bile acids recognition by the FPR receptor

Formyl-peptide receptors (FPRs) belong to the family A of the G-protein coupled receptor superfamily and include three subtypes: FPR, FPR-like-1 and FPR-like-2. They have been involved in the control of␣many inflammatory processes promoting the recruitment and infiltration of leukocytes in regions of inflammation through the molecular recognition of chemotactic factors. A large number of structurally diverse chemotypes modulate the activity of FPRs. Newly identified antagonists include bile acids deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). The molecular recognition of these compounds at FPR receptor was computationally investigated using both ligand- and structure-based approaches. Our findings suggest that all antagonists bind at the first third of the seven helical bundles. A closer inspection of bile acid interaction reveals a number of unexploited anchor points in the binding site that may be used to aid the design of new potent and selective bile acids derivatives at FPR.     

Determination of herbicides by solid phase extraction gas chromatography-mass spectrometry in drinking waters

A solid phase extraction (SPE) method has been optimized for the gas chromatography-mass spectrometry (GC-MS) simultaneous determination of herbicides belonging to the following different families: carbamate (molinate), atrazines (atrazine, propazine, simazine, ametryne, cyanazine, terbutylazine, deethylterbutylazine, deethylatrazine), dinitroaniline (trifluralin, pendimethalin), chloroacetamide (alachlor, metolachlor). Different solid substrates have been compared (C18, cyano, styrene-divinylbenzene, phenyl, graphitic carbon). The type of conditioning and elution solvent, its volume, and the sample flow rate have been considered as variables affecting the recovery yields of the herbicides.The optimized experimental conditions are C18 phase conditioned with 3 mL acetone, loaded with 1 L water sample at 5 mL min⁻¹, and eluted with 3 mL acetone. Good recoveries (included between 79% and 99%) and R.S.D. (included between 2% and 12%) have been obtained for all analytes, except for deethylatrazine whose recovery was 46 ± 7%. The recovery of deethylatrazine increases up to 94 ± 17% if a non-porous graphitic carbon is coupled to the C18 phase, keeping the other parameters constant as optimized. The optimized method has been successfully checked for the identification and quantitation of the selected herbicides in raw and drinking water samples, with quantitation limits as low as 0.01 μg L⁻¹, fully in agreement with the current legislation. The method is easily routinable. After development, the method is currently routinely applied for the analysis of herbicides in waters and, up today, more than one thousand samples have been analysed at the “Laboratorio della Società Metropolitana Acque di Torino” (Laboratory of the Municipal Waterworks of Turin) in charge of the control of drinking water quality in Torino.     

Metal atoms and clusters in fullerene cages

Fullerenes containing metal atoms and clusters can be formed by the arc-vaporization method. The electronic structure of these metallofullerenes can be probed using magnetic resonance techniques. Electron paramagnetic resonance (EPR) spectra of LaC₈₂, YC₈₂, ScC₈₂ and Sc₃C₈₂ have been obtained. Metallofullerenes containing a single metal atom (MC₈₂ with M = La, Y, or Sc), have small hyperfine couplings and g-values close to 2, implying that they can be described as + 3 metal cations within — 3 fullerene radical anion cages. In the La and Y cases, additional EPR active MC₈₂ species have been found. The EPR spectrum of Sc₃C₈₂ shows that the metal atoms are equivalent, suggesting that they may form a triangular molecule. No EPR spectrum is found for Y₂C₈₂ or for Sc₂C_2n species (with 2n = 82,84,86), suggesting that they are diamagnetic. Sc NMR spectra of a solution containing Sc₂C_2n species have been obtained which confirm the diamagnetism of the discandium metallofullerenes.     

Reinforcement of polystyrene by covalently bonded oxo-titanium clusters

Oxo-metallic clusters are employed as inorganic nanobuilding blocks in order to obtain new organic–inorganic hybrid materials. Nanobuilding blocks are well-defined preformed entities which allow a better control of the inorganic domains for the elaboration of hybrid compounds. The oxo-alcoxo cluster Ti₁₆O₁₆(OEt)₃₂ presents a shell of labile ethoxy groups which can be selectively exchanged with the preservation of the oxo-core in order to introduce polymerizable ligands at the surface of this nanobrick. Three different new clusters, Ti₁₆O₁₆(OEt)_32−x(OPhCHCH₂)_x, have been synthesised, each cluster bears exactly 4, 8 and 16 styrenic groups. These functional clusters were copolymerized with styrene leading to three dimensional networks where the inorganic nano-fillers are covalently linked to the organic polymer. Thus new hybrid materials can be obtained and these nanobricks are good models to correlate the structure of hybrid materials and their physical properties especially their mechanical and thermal properties. The structure of the materials in function of the organic–inorganic ratio and in function of the cluster functionalities was investigated by SAXS, and the formation of the different levels of aggregation is reported.     

Assessing the effect of latex particle size and distribution on the rheological and adhesive properties of model waterborne acrylic pressure-sensitive adhesives films

The adhesive and rheological properties of model acrylic pressure-sensitive adhesive (PSA) films prepared from high solid emulsions with different particle sizes and distributions have been investigated with a customized probe tack apparatus. For each emulsion, the monomer composition and gel content were kept constant but different average particle sizes and distributions were used. Adhesive films 100 microm thick were then prepared from these emulsions and their rheological properties in the linear regime and adhesive properties were systematically characterized. Surprisingly, both the rheological and adhesive properties were found to be very dependent on the initial latex particle size distribution. A series of experiments were carried out to assess the adhesive properties of films made from blends of small- and large-particle-size latexes. Using the probe tack test, a maximum in adhesion energy of the dry films was found for 60% of small particles in the blend, a composition clearly different from that giving a minimum viscosity of the latex implying that optimizing for properties may not be equivalent to optimizing for processing in these adhesive applications. Finally, the adhesive properties of two multimodal latexes with different particle size distributions were investigated. Both gave significantly higher adhesion energies and clear evidence of a fibrillar detachment process. This important result suggests that the spatial distribution of gel domains in the dry film and the molecular connectivity between those gel domains also play an important role in controlling its adhesive properties.     

On the existence of pyrophosphates of tetravalent metals having a layered structure

After an accurate investigation of the thermal behaviour (TG and DTA curves) of several samples of α-Zr(HPO₄)₂·H₂O and α-Ti(HPO₄)₂·H₂O, prepared both by the refluxing and HF procedures, γ-Zr(HPO₄)₂·2 H₂O and γ-Ti(HPO₄)₂·2 H₂O, new pyrophosphate phases of tetravalent metals have been isolated.The structure of these compounds, deduced from X-ray diffraction data, density measurements and considerations of bond length and angles, arises from the packing of layers of α and γ type, identical to those present in the starting materials and held together by POP bridges.These layered M(IV)P₂O₇ are obtained after the condensation process of the HPO₄ groups present in α and γ-M(IV)(HPO₄)₂ and are stable until the transition to the respective cubic pyrophosphates takes place.The range of stability of these phases changes on going from the α to the γ phase and in part depends on the degree of crystallinity and/or the crystal size of the starting layered exchanger. The chemical implications of α- and γ-L-M(IV)P₂O₇ are examined and discussed.     

Spiro[2.2]pentane as a dissymmetric scaffold for conformationally constrained analogues of glutamic acid: focus on racemic 1-aminospiro[2.2]pentyl-1,4-dicarboxylic acids

In search for novel conformationally constrained analogues of L-glutamic acid, a diastereodivergent synthesis of the four 1-aminospiro[2.2]pentyl-1,4-dicarboxylic acid racemic pairs is reported along with their stereochemical assignment, conformational analysis, and preliminary biological evaluation as potential glutamate (ionotropic and metabotropic) ligands.     

A series of diarylsubstituted oximes as potential substrate for new aldose reductase inhibitors

In the course of our research aimed at the discovery of new compounds acting as aldose reductase inhibitors, we tested a series of some (E)‐ and (Z)‐ω‐[[(aryldiazinylmethylene)amino]oxy]alkanoic acids, which were found to have moderate in vitro inhibitory activity. On this basis we have now prepared several new derivatives modified both at the length of the chain and at its terminal carboxylic group, together with compounds carrying various substituents at the phenyl ring. This paper describes their synthesis and biological properties.     

A critical local energy release rate criterion for fatigue fracture of elastomers

Using Digital Image Correlation on high‐resolution images, the full strain field near the tip of a crack propagating under cyclic loading in an elastomer was characterized. We show unambiguously, and for the first time, the existence of a strongly localized and highly oriented process zone close to the crack tip and propose a simple physical model introducing a local energy release rate g_local = W_unloadingH₀, where W_unloading is the unloading strain energy density in uniaxial tension at the maximum strain measured at the crack tip, and H₀ is the undeformed size of the highly stretched zone in the loading direction. Remarkably, the crack growth rate under cyclic loading is found to fall on a master curve as a function of g_local for three elastomers with different filler contents and crosslinking densities, while the same crack growth rate as a function of the applied macroscopic energy release rate G, differs by two orders of magnitude for the same three elastomers. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 49: 1518–1524, 2011