Dérivés de la dihydro-2,4 triazole-1,2,4 thione-3 et de l'amino-2 thiadiazole-1,3,4 à partir de nouvelles thiosemicarbazones d'esters

A new general synthesis of 4,5-disubstituted 2,4-dihydro-1,2,4-triazole-3-thiones is proposed. These heterocycles are obtained by the action of primary amines, arylhydrazines or aroylhydrazines on the thiosemicarbazones of eaters. These last compounds are prepared by action of chlorhydrates of iminoethers on thiosemicarbazide in dimethylformamide. These thiosemicarbazones react also with strong acids, acid anhydrides and chlorides; by thermolysis and they give 2-amino-1,3,4-thiadiazole derivatives. Also, two derivatives of 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole have been prepared.     

An insight into the mechanisms of the phototoxic response induced by cyamemazine in cultured fibroblasts and keratinocytes

The phototoxicity of cyamemazine (CMZ, Tercian), a neuroleptic of the phenothiazine family, has recently been reported in humans. CMZ has an absorbance maximum at 267 nm (molar absorptivity, 25,800 M(-1) cm(-1)) but a weaker molar absorptivity in the ultraviolet A (UV-A) region. CMZ exhibits a fluorescence with maximum emission at 535 nm and a quantum yield of 0.11. CMZ is a powerful photosensitizing agent toward HS 68 human skin fibroblasts and NCTC 2544 keratinocytes. At a UV-A radiation dose of 10 J/cm2, innocuous to cells in the absence of CMZ, the LD50 (lethal dose corresponding to 50% killing) are 0.5 and 1 microM for the fibroblasts and the keratinocytes, respectively, after overnight incubation with the drug. Short incubation times do not significantly alter the LD50. The CMZ-induced phototoxicity is accompanied by lipid membrane peroxidation consistent with the amphiphilic character of this photosensitizer. Keratinocytes are an order of magnitude less sensitive to the photosensitized lipid peroxidation than fibroblasts. Microspectrofluorometry reveals that lysosomal membranes are major sites of CMZ incorporation into the two cell lines because a Forster-type resonance energy transfer process occurs from CMZ to LysoTracker Red DND99 (LTR), a specific fluorescent probe of lysosomal membranes. The CMZ-photosensitized destruction of LTR demonstrates that CMZ retains its photosensitizing capacity after its lysosomal uptake.     

First enantioselective total synthesis of (-)-Centrolobine

[structure: see text] The first enantioselective total synthesis of (-)-Centrolobine is described. The key reaction is the synthesis of the cis-disubstituted tetrahydropyran framework by intramolecular cyclization of the enantiopure hydroxyketone 3 with Et3SiH and TMSOTf. The stereoselective reduction of the beta-ketosulfoxide 4 is the source of chirality. Revision of the absolute configuration of (-)-Centrolobine is proposed.     

Effects of Alkylamines on the Percolation Phenomena in Water/AOT/Isooctane Microemulsions

We carried out an investigation on the influence of several alkylamines, frequently present in reactions carried out in microemulsions, on the properties of the water/AOT/isooctane system. The presence of alkylamines has an important effect on the electrical percolation phenomena. This effect of amines on the electrical percolation of microemulsions of AOT/isooctane/water can be explained by taking into account the ability of these substrates to associate with the AOT film in the microemulsion, the basicity of the amine, and the different solubility of the amine in the three pseudophases of the system. Copyright 2000 Academic Press.     

Influence of glymes upon percolative phenomena in AOT-based microemulsions

A study was carried out on the influence of different polyethylene glycol dimethyl ethers (glymes) on the conductance percolation of AOT/isooctane/water microemulsions. The glymes used were chosen on the basis of this chain length (the number of polymeric units). In all cases we observed a decrease in the percolation threshold on increasing the amount of a glyme added to the microemulsion. We observed a correlation between the effect exerted by the glyme and its chain length, which shows the importance of including them in the interface for the percolative phenomenon. Such inclusion modifies the properties of the AOT film, facilitating the exchange of matter between droplets.     

Multilayer adsorption of alcohols from benzene/n-heptane mixtures on silica gel

An equation for multilayer adsorption from multicomponent liquid mixtures on solid surfaces¹ has been examined. For this purpose experimental adsorption data for four alcohols from benzene/n-heptane mixture on silica gel have been measured. Average number of the adsorbed layers, heterogeneity parameter and capacity of the surface phase have been evaluated by using the equation mentioned above.

---

Mehrschichten-Adsorption von Alkoholen aus Benzol/n-Heptan-Mischung an Silica Gel

Zusammenfassung Eine Gleichung für Mehrschichten-Adsorption an festen Oberflächen¹ aus Mehrkomponentenlösungen wurde getestet. Zu diesem Zweck wurden experimentelle Daten für die Adsorption von vier Alkoholen aus Benzol/n-Heptan-Mischung an Silica Gel herangezogen. Der Mittelwert für die Anzahl der Adsorptionsschichten, der Heterogenitätsparameter und die Kapazität der Oberflächenphase wurde aus dieser Gleichung berechnet.

     

Interaction and lipid-induced conformation of two cecropin-melittin hybrid peptides depend on peptide and membrane composition

The interaction of two hybrid peptides of cecropin A and melittin [CA(1-8)M(1-18) and CA(1-7)M(2-9)] with liposomes was studied by differential scanning calorimetry (DSC), circular dichroism (CD), and quasi-elastic light scattering (QELS). The study was carried out with large unilamellar vesicles (LUVs) of three different lipid compositions: 1,2-dimyristoil-sn-glycero-3-phosphocholine (DMPC), 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and a binary mixture of DMPC/DMPG, in a wide range of peptide-to-lipid (P:L) molar ratios (0 to 1:7). DSC results indicate that, for both peptides, the interaction depends on membrane composition, with very different behavior for zwitterionic and anionic membranes. CD data show that, although the two peptides have different secondary structures in buffer (random coil for CA(1-7)M(2-9) and predominantly beta-sheet for CA(1-8)M(1-18)), they both adopt an alpha-helical structure in the presence of the membranes. Overall, results are compatible with a model involving a strong electrostatic surface interaction between the peptides and the negatively charged liposomes, which gives place to aggregation in the gel phase and precipitation after a threshold peptide concentration. In the case of zwitterionic membranes, a progressive surface coverage with peptide molecules destabilizes the membrane, eventually leading to membrane disruption. Moreover, delicate modulations in behavior were observed depending on the peptide.     

Chemiluminometric determination of carvedilol in a multi-pumping flow system

In this work a simple, fast, sensitive and selective flow-based procedure for the chemiluminometric determination of carvedilol, a recent non-cardioselective β-blocker with noteworthy antioxidant activity, is proposed. The developed methodology takes advantage of the antioxidant capacity of carvedilol to inhibit the chemiluminescence response resulting from the oxidation of luminol by hypochlorite, by acting as a hypochlorite scavenger. The analytical process was implemented in a multi-pumping flow system that employs multiple solenoid actuated micro-pumps as the only active components. These acted as solution insertion, propelling and commuting units assuring an easily controlled, low cost, compact and reliable analytical system.A linear working range for carvedilol concentrations ranging from 1.2 × 10⁻⁷ to 3.0 × 10⁻⁶ mol l⁻¹ (r > 0.999, n = 6), was obtained, with a detection limit of 8.7 × 10⁻⁹ mol l⁻¹. The system handles about 65 samples per hour yielding precise results (R.S.D. < 1.3%, n = 10). Recoveries within 95 and 104% were obtained.     

DFT and NMR parameterized conformation of valeranone

A Monte Carlo random search using molecular mechanics, followed by geometry optimization of each minimum energy structure employing density functional theory (DFT) calculations at the B3LYP/6-31G* level and a Boltzmann analysis of the total energies, generated accurate molecular models which describe the conformational behavior of the antispasmodic bicyclic sesquiterpene valeranone (1). The theoretical H-C-C-H dihedral angles gave the corresponding 1H, 1H vicinal coupling constants using a generalized Karplus-type equation. In turn, the 3J(H,H) values were used as initial input data for the spectral simulation of 1, which after iteration provided an excellent correlation with the experimental 1H NMR spectrum. The calculated 3J(H,H) values closely predicted the experimental values, excepting the coupling constant between the axial hydrogen alpha to the carbonyl group and the equatorial hydrogen beta to the carbonyl group (J(2beta, 3beta)). The difference is explained in terms of the electron density distribution found in the highest occupied molecular orbital (HOMO) of 1. The simulated spectrum, together with 2D NMR experiments, allowed the total assignment of the 1H and 13C NMR spectra of 1.