Synthesis of 1-(4-substituted)benzyl-6-hydroxyisoquinolines with potential activity on NA+,K+-atpase

The synthesis of 1-(4-substituted)benzyl-6-hydroxyisoquinolines, to be evaluated in the displacement of the specific ³H-ouabain binding to Na⁺,K⁺-ATPase, is described. The key step involved a cyclization to the isoquinoline ring under Pictet-Gams conditions which was best performed with the 6-hydroxy group protected as the benzyl ether. When an unsaturated ester group was present in position 4 of the 1-benzyl group, this was best introduced before the cyclization step, since the IIeck reaction on 1-(4-bromobenzyl)-6-hydroxyisoquinoline ( 8 ) with acrylic acid derivatives was not successful in all cases.     

Mechanically-based approach to non-local elasticity: Variational principles

The mechanically-based approach to non-local elastic continuum, will be captured through variational calculus, based on the assumptions that non-adjacent elements of the solid may exchange central body forces, monotonically decreasing with their interdistance, depending on the relative displacement, and on the volume products. Such a mechanical model is investigated introducing primarily the dual state variables by means of the virtual work principle. The constitutive relations between dual variables are introduced defining a proper, convex, potential energy. It is proved that the solution of the elastic problem corresponds to a global minimum of the potential energy functional. Moreover, the Euler–Lagrange equations together with the natural boundary conditions associated to the total potential energy functional are established with variational calculus and they coincide with analogous relations already obtained by means of mechanical considerations. Numerical analysis of a tensile specimen has been introduced to show the capabilities of the proposed approach.     

Understanding the mechanism of direct visible-light-activated [2 + 2] cycloadditions mediated by Rh and Ir photocatalysts: combined computational and spectroscopic studies

The mechanism of [2 + 2] cycloadditions activated by visible light and catalyzed by bis-cyclometalated Rh(iii) and Ir(iii) photocatalysts was investigated, combining density functional theory calculations and spectroscopic techniques. Experimental observations show that the Rh-based photocatalyst produces excellent yield and enantioselectivity whereas the Ir-photocatalyst yields racemates. Two different mechanistic features were found to compete with each other, namely the direct photoactivation of the catalyst–substrate complex and outer-sphere triplet energy transfer. Our integrated analysis suggests that the direct photocatalysis is the inner working of the Rh-catalyzed reaction, whereas the Ir catalyst serves as a triplet sensitizer that activates cycloaddition via an outer-sphere triplet excited state energy transfer mechanism.

The mechanism of [2 + 2] cycloadditions activated by visible light and catalyzed by bis-cyclometalated Rh(iii) and Ir(iii) photocatalysts was investigated, combining density functional theory calculations and spectroscopic techniques.     

Optimisation of analytical procedures for the quantification of ionic and carbonaceous fractions in the atmospheric aerosol and applications to ambient samples

In the last decade, our research group set up and optimised analytical techniques for the characterisation of the major components of atmospheric aerosol (i.e. secondary inorganic ions and carbonaceous material) and source markers (e.g. levoglucosan, carbonates). In this study, we present a complete overview on the most problematic aspects that can be encountered during the quantification of the two main components of aerosol, i.e. the ionic and carbonaceous fractions. More in detail, different liquid chromatographic approaches were set up for main ions and anhydrosugars determination. Quality assurance procedures (i.e. tests on data reliability) were applied during the set-up phase and they are presented in this work. As regards the carbonaceous component characterisation, two evolved gas analysis techniques were set up and applied: the thermogravimetric technique coupled to the Fourier transformed infrared spectroscopy (TGA/FTIR) and the thermal–optical transmittance method (TOT). A suitable protocol for organic and elemental carbon separation was set up for the TGA/FTIR system and a comparison with the results obtained by the TOT method was carried out. Studies on the impact of filter load, field blanks, and sample composition on OC/EC quantification by the TOT method were performed. Moreover, approaches for carbonate carbon quantification on different kinds of filters were developed. It was demonstrated that this approach allows to reach the ionic balance in samples impacted by carbonate compounds. The optimised methods have been applied for the analysis of thousands of PM filters allowing the obtainment of reliable results.     

Profiling and quantifying polar lipids in milk by hydrophilic interaction liquid chromatography coupled with evaporative light-scattering and mass spectrometry detection

In this work, a high-performance liquid chromatography with evaporative light scattering detection method has been developed and applied for quantification of the polar content of the lipid fraction in milk samples of different origin. From a chromatographic stand-point, a 4.6-mm I.D. hydrophilic interaction liquid chromatography column was employed to attain a baseline separation of major phospholipid classes contained in the various milk samples tested. Quantitative analysis was performed by the external calibration method using reference material solutions in the 5–100 mg/L concentration range. Analytical recoveries ranging from 57 to 100 %, and repeatability data lower than 8.04 % were obtained on a skimmed cow’s milk sample. The crude cow milk was the most abundant (0.04 %) in phospholipids and donkey milk was the poorest (0.004 %). Quantitative differences were determined in the phospholipid content of the milk samples tested. Finally, characterization of phospholipid profile and fatty acid composition of the different samples was carried out by an ion trap-time of flight mass spectrometer and gas chromatography coupled to flame ionization and mass spectrometry detection. A thorough screening of the polar lipid composition of milk samples of different origin is here outlined, for the first time.     

Absolute configuration assignment made easier by the VCD of coupled oscillating carbonyls: the case of (−)-propanedioic acids, 2-(2,3)-dihydro-3-oxo-1H-isoindol-1-yl)-1,3-dimethyl ester

Depending on their relative orientation, coupled oscillating carbonyl groups provide a VCD spectrum with a characteristic CO bond stretching region showing a strong bisignate VCD feature, which can be readily predicted adopting long available semiempirical methods. The extended coupled oscillator (ECO) formalism has been used to assign the absolute configuration of a recently synthesized chiral 3-substituted isoindolinone. The prediction of (S) configuration for the (−) enantiomer has been confirmed by quantum mechanical calculations.     

Modified surface chemistry of activated carbons

In this study, immersion calorimetry was used to characterise different samples of commercial granular activated carbon (GAC) which undergo oxidation with HNO₃ (GACOxN) and thermal treatments to modify its superficial group contents, as well as to determine the textural characteristics of the materials through nitrogen adsorption at 77 K and its superficial chemistry by Boehm titration and zero point of charge. Correlations between the immersion enthalpies and the results of the other techniques of characterisation were established. The immersion enthalpies in dichloromethane obtained were greater, which were found to be between ?88.36 and ?155.6 J g^?1, in contrast to those in carbon tetrachloride, which were found to be between ?50.21 and ?94.29 J g^?1. The dependence of the immersion enthalpies in water on the contents of total acidity and basicity surface groups was also established, and a good correlation between the accessible surface area determined by calorimetric technique and the BET area was found.     

Palladium-arene interactions in catalytic intermediates: an experimental and theoretical investigation of the soft rearrangement between eta1 and eta2 coordination modes

A series of dichloro-bridged arylbicycloheptylpalladium complexes have been synthesized and characterized by means of NMR spectroscopy. The compound [(C16H19)PdCl]2*CH2Cl2 with ortho and para methyl substituents at the arene has been characterized by means of X-ray diffraction techniques. The C(ipso) atom of the arene lies almost at the fourth planar coordination site of the metal [Pd-C(ipso) = 2.22(1) A (average)], and due to the arene's tilting, the substituted C(ortho) atom is relatively close to the metal atom [2.54(1) A (average)]. The coordinated C(ipso)-C(ortho) linkage, in a seemingly dihapto coordination, is anti with respect to the CH2 bridge of the bicycloheptyl unit. Variable-temperature NMR experiments for the para-substituted dimer 9 reveal restricted rotation of the two aryl groups about the corresponding C-C(ipso) bonds (DeltaE < or =17 kcal x mol(-1)). DFT-B3LYP calculations have been carried out on the known and similar monomer (phenylbicycloheptenyl)Pd(PPh3)I (4) and its related substituted derivatives. The essential results are as follows: (i) The potential energy surface for twisting the phenyl ring away from the symmetric eta(1) coordination in 4 is very flat (DeltaE < or = 1 kcal x mol(-1)) whereas an Atoms in Molecules analysis excludes the existence of an actual Pd-C(ortho) bond in the seemingly eta2-type conformer. (ii) Complete rotation of the unsubstituted phenyl ring is not facile but feasible. A significant strain affects the transition-state structure featuring a Pd-HC(aryl) agostic-type bond. The calculated destabilization of 10.3 kcal x mol(-1), with respect to the ground state, can be compared to the experimental barrier of the dimer 9. (iii) Various methyl-substituted derivatives of 4 have been optimized, and their structural and energetic trends are discussed. An almost ideal eta1 coordination is shown by the anti conformer of the C(ortho)-substituted complex due steric effects. For all of the other cases, a slipped eta2 coordination may be described. As a general conclusion, the unsaturated metal center receives pi electron density of the arene mainly through its C(ipso) atom. The effect may be slightly improved if the C(ortho) atom also gets closer to the metal, but in no case, does the slipped eta2 coordination seem to be crucial for the stability of the system.     

High-density lipoproteins contribute to the alpha-1-globulin zone in capillary electrophoresis of human serum proteins

Alpha-1-antitrypsin (AAT) and alpha-1-acid glycoprotein (AAG) are reported to be the main proteins contributing to the alpha-1-globulin capillary zone electrophoresis (CZE) zone, but the sum (AAT + AAG) showed lower than the alpha-1-globulin. We investigated the role of high-density lipoprotein (HDL), an additional protein migrating in the alpha-1-globulin zone, as a possible cause for such a gap. In a set of 98 sera we measured the alpha-1-globulin with a dedicated clinical capillary electrophoresis system, and AAT, AAG and apolipoprotein A-1 (ApoA) by immunonephelometry. The alpha-1-globulin were consistently higher than the sum (AAT + AAG), by (mean value +/- standard deviation) 1.70 +/- 0.88 g/L in 49 sera with low ApoA, and by 3.59 +/- 0.75 g/L in 49 sera with high ApoA. Corresponding figures in the comparison alpha-1-globulin/(AAT + AAG + ApoA) were reduced to 1.08 +/- 0.77 g/L and 1.67 +/- 0.70 g/L. It is concluded that HDL significantly contribute to the CZE alpha-1-globulin zone, but do not completely explain the differences between the electrophoretic and the immunochemical measurements. However, CZE alpha-1-globulin measurements give information about increases of the two major acute phase proteins comparable to specific protein measurements.     

Cholesterol oxidation in meat-based baby foods

Cholesterol oxidation in commercial meat-based homogenized and freeze-dried baby foods was examined. The 7 major products of this reaction were determined by gas chromatography coupled with mass spectrometry (GC-MS). As far as single cholesterol oxidation products (COP) are concerned, 7-ketocholesterol was the major product of direct cholesterol oxidation in the 2 groups of analyzed samples, and this study confirmed that it is a useful marker of the whole cholesterol oxidation process. Nevertheless, the amounts of cholesterol-5beta,6beta-epoxide were often similar to and sometimes higher than the amounts of 7-ketocholesterol, thus showing a strong development of both direct and indirect cholesterol oxidation pathways. Total COP content was significantly higher in freeze-dried than in homogenized products. Moreover, in freeze-dried samples, the COP content per serving was quite variable and, in 2 samples, it was close to or even higher than 500 microg. The greater development of cholesterol oxidation in the freeze-dried samples was confirmed by their highest total COP/cholesterol percent ratios. A constant correlation between the fatty acid composition and the development of cholesterol oxidation was not found, although a positive correlation between unsaturated fatty acid content and total COP content occasionally exists in samples of the same brand.