Mechanisms of reduced human vascular cell migration after photodynamic therapy

Restenosis results from intimal hyperplasia and constrictive remodeling following cardiovascular interventions. Photodynamic therapy (PDT) has been shown to inhibit intimal hyperplasia in vivo by preventing neointimal repopulation of the treated vessel. This study was undertaken in an attempt to further dissect the mechanisms by which PDT acts on secreted and extracellular matrix proteins to inhibit migration of cultured human vascular cells. PDT of three-dimensional collagen gels inhibited invasive human smooth muscle cell (SMC) migration, whereas cell-derived matrix metalloproteinase production remained unaltered. Additionally, PDT generated cross-links in the collagen gels, a result substantiated in an ex vivo model whereby PDT rendered the treated vessels resistant to pepsin digestion and inhibited invasive migration of SMC and fibroblasts. These data support the premise that by inducing matrix protein cross-links, rendering the vessel resistant to degradation, in vivo PDT inhibits repopulation of the vessel and therefore intimal hyperplasia.     

Profiling fatty acids in vegetable oils by reactive pyrolysis-gas chromatography with dimethyl carbonate and titanium silicate

A novel methodology in on-line pyrolysis-gas chromatography (Py-GC) for the fast analysis of fatty acids in vegetable oils with minimal sample treatment and the use of non-toxic reagents is described. Pyrolysis at 500 degrees C for 10 s of sub-microgram quantity of vegetable oil dissolved in dimethyl carbonate (DMC) and in the presence of nanopowder titanium silicon oxide resulted in the production of fatty acid methyl esters (FAMEs) as unique products. Pyrolysis performed by means of a resistively heated filament pyrolyser interfaced to a GC-MS apparatus enabled the direct analysis of evolved FAMEs. The DMC/Py-GC-MS analysis was tested on soybean, coconut, linseed, walnut and olive oil and the results compared to the classical BF(3)-methanol as reference methodology. The DMC method exhibited a lower precision and was biased towards lower levels of polyunsaturated fatty acids (PUFA) in comparison to the BF(3)-methanol method, but was more advantageous in terms of reduced sample treatment, waste generation and risk factors of employed chemicals.     

QUENCHING OF CHEMICALLY and ENZYMICALLY-GENERATED TRIPLET ACETONE BY TYROSINE and 3,5-DIHALOGENODERIVATIVES

Tyrosine and especially its 3,5-dihalogenoderivatives quench acetone triplets. When the excited acetone is generated free in solution, the Stern-Volmer plots for the quenching by these species, monitored via the sensitized emission of the 9,10-dibromoanthracene-2-sulfonate ion, are linear. When triplet acetone is generated enzymically by the peroxidase-catalyzed aerobic oxidation of isobutyral-dehyde, the Stern-Volmer plots for the quenching of the acetone phosphorescence curve upwards in the case of 3,5-dibromotyrosine and even more markedly with 3,5-diiodotyrosine. Quenching appears likely to occur by triplet-triplet energy transfer and especially in the case of the phenoxide form, also by electron transfer. The curvature denotes a static contribution to quenching favoured by the enzyme.     

Diastereoselective synthesis of α-amino-β-hydroxyacids

threo-α-Dibenzylamino-?-hydroxyesters (2) have been synthesised with high diastereoselectivity through the NaBH₄ reduction of α-dibenzylamino-β-oxoesters (4) and then tranformed into threo-α-amino-β-hydroxyacids.     

Reactivity of peroxo forms of the vanadium haloperoxidase cofactor. A DFT investigation

Density functional theory has been used to investigate structural, electronic and reactivity properties of complexes related to the peroxo forms of vanadium haloperoxidases (VHPO). In particular, the reactivity of the cofactor as a function of protonation state and environment, which are two factors thought to be crucial in modulating the activity of the enzyme, has been examined. In full agreement with experimental data, results highlight the role of protonation in the activation of the peroxo-vanadium complexes and show that the oxo-transfer step involves the unprotonated axial peroxo oxygen atom, which is easily accessible to substrates in the peroxo form of the enzyme. The role of Lys353, which in the X-ray structure of the peroxide-bound form of vanadium chloroperoxidase is hydrogen bonded to the equatorial oxygen atom of the peroxo group, has been also explored. It is concluded that Lys353 can play a role similar to a H+ in the activation of the peroxo form of the cofactor.     

A palladium-catalyzed synthetic approach to new Huperzine A analogues modified at the pyridone ring

The synthesis of two new Huperzine A analogues is reported. Both products present an amino substituted benzo-fused system in place of the pyridone ring of the natural alkaloid. The synthetic strategy to the two analogues is based on three different key palladium-catalyzed steps, namely a carbonylation reaction, an epoxide isomerization and a bicycloannulation reaction.     

Unusual and unexpected reactivity of t-butyl dicarbonate (Boc2O) with alcohols in the presence of magnesium perchlorate. A new and general route to t-butyl ethers

[reaction: see text] A new mild method for protecting alcohols as t-butyl ethers is reported. The reaction proceeds with Mg(ClO4)2 and Boc2O and shows general applicability. The deprotection of t-butyl ethers has also been revisited. Preliminary results indicate the CeCl3 x 7H2O/NaI system is a very suitable catalyst for their removal.     

Nanoporous thermosetting polymers

Potential applications of nanoporous thermosetting polymers include polyelectrolytes in fuel cells, separation membranes, adsorption media, and sensors. Design of nanoporous polymers for such applications entails controlling permeability by tailoring pore size, structure, and interface chemistry. Nanoporous thermosetting polymers are often synthesized via free radical mechanisms using solvents that phase separate during polymerization. In this work, a novel technique for the synthesis of nanoporous thermosets is presented that is based on the reactive encapsulation of an inert solvent using step-growth cross-linking polymerization without micro/macroscopic phase separation. The criteria for selecting such a monomer-polymer-solvent system are discussed based on FTIR analysis, observed micro/macroscopic phase separation, and thermodynamics of swelling. Investigation of resulting network pore structures by scanning electron microscopy (SEM) and small-angle X-ray scattering following extraction and supercritical drying using carbon dioxide showed that nanoporous polymeric materials with pore sizes ranging from 1 to 50 nm can be synthesized by varying the solvent content. The differences in the porous morphology of these materials compared to more common free radically polymerized analogues that exhibit phase separation were evident from SEM imaging. Furthermore, it was demonstrated that the chemical activity of the nanoporous materials obtained by our method could be tailored by grafting appropriate functional groups at the pore interface.     

Reaction of N,N'-dialkyldithiodianilines with β-ketoesters. A new synthesis of N-alkyl-2-acyl-3-oxo-3,4-dihydro-1,4-benzothiazines

The title compounds 3a-j together with the N-alkylacylketene S,N-acetals 12a-j were obtained by reaction of N,N'-dialkyldithiodianilines with β-ketoesters compounds. A possible reaction pathway is suggested.     

Mononuclear heterocyclic rearrangement. Note I. Kinetic study of the rearrangement of the phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole into 2,5-diphenyl-4-benzoylamino-1,2,3-triazole

The rates of the mononuclear heterocyclic rearrangement of the phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole (1) into 2,5-diphenyl-4-benzoylamino-1,2,3-triazole (II) have heen measured in dioxane/water (50:50, v:v) in the range of pS⁺ 3.8–12.2 at various temperatures and the activation parameters determined. On the basis of the results obtained, we present evidence for the occurrence of two different types of reaction: the first, base-catalyzed; the second, pS⁺ -independent. In the base-catalyzed range the catalysis is of the general type.