β-Carbolines as agonistic or antagonistic benzodiazepine receptor ligands. 1. Synthesis of some 5-, 6- and 7-amino derivatives of 3-methoxycarbonyl-β-carboline (β-CCM) and of 3-ethoxycarbonyl-β-carboline (β-CCE)

Condensation of diethyl formylamino- or diethyl acetylaminomalonate with 4-, 5- or 6-nitrogramine 1 afforded the diethyl formylamino- or the diethyl acetylamino[(nitroindol)-3-ylmethyl]malonates 2 ; reduction of the nitro group followed by N-formylation or acetylation of the resulting amino compounds 3 , led to the 4-, 5-and 6-acylamino derivatives 4 . Cyclization of 4 in the presence of polyphosphoric esters gave the 3,3-bis(ethoxycarbonyl)-3,4-dihydro-β-carbolines 5 , which underwent lithium chloride/water catalyzed monodeethoxycarbonylation to the corresponding 5-, 6- and 7-acylamino-3-ethoxycarbonyl-β-carbolines 6 , whose acidic hydrolysis led finally to the 5-, 6- and 7-amino-3-ethoxycarbonyl-β-carbolines 9 . The 6-amino compounds 9b-e were obtained also by direct nitration of 3-methoxycarbonyl-β-carboline 7a and of 3-ethoxycarbonyl-β-carboline 7c , followed by the nitro group reduction of the resulting nitro carbolines 8 . Preliminary studies of the binding to rabbit brain benzodiazepine receptor sites indicate compounds 9b and 9c to inhibit the ³H-diazepam binding at 10^?8 M concentrations.     

Solvent scales comparison by using α-nitrocyclohexanone as probe in ionic liquids,organic solvents and CH3CN/CHCl3 mixtures

The UV–vis spectra of α-nitrocyclohexanone were determined at 25 °C in a series of solvents, including room-temperature ionic liquids, water and CH₃CN/CHCl₃ binary mixtures. A multiple linear regression analysis was performed by applying the Catalán empirical multiparameter solvent approach. Polarizability plays the major role in the solute-solvent interactions, as demonstrated by the quantification of the single solvent contributions, while an excellent linear correlation was found between the experimental and calculated solvent-dependent maxima adsorption bands. The solvatochromic trend of α-nitrocyclohexanone in the investigated media was confirmed by applying the Spange empirical solvent parameters for the ionic liquids in the Kamlet–Taft scale.     

Pyrolysis/gas chromatography/ion-trap detection of polyphenols (vegetable tannins): Preliminary results

Tannins from sorghum grains with high and low tannin content, from grape skins and seeds and from apple pomace were analysed by pyrolysis/gas chromatography/ion-trap detector mass spectrometry. Pyrolysis at 600°C produced catechol as a characteristic fragment of condensed tannins, and other phenolic compounds related to the lignified tissues. Catechol was also the main fragment in the pyrogram of catechin, a monomeric constituent of condensed tannins. Mass spectral data and relative quantifications of the pyrograms of several samples are provided. Quantitative data are discussed in terms of reproducibility and linearity of response and are compared with the results of a spectrophotometric assay for tannins.     

Formation of dense self-assembled monolayers of (n-decyl)trichlorosilanes on Ta/Ta2O5

Tantalum pentoxide (Ta2O5) is a promising material for the realization of biological interfaces because of its high dielectric constant, its high chemical stability, and its excellent passivating properties. Nevertheless, the deposition of highly organized silane SAMs to realize well-defined and tailored Ta2O5-based (bio)interfaces, has not been studied in great detail as of yet. In this work, we have investigated the formation of a highly ordered, dense monolayer of trichlorosilanes on Ta2O5 surfaces. Specifically, two different cleaning procedures for Ta2O5 were compared and (n-decyl)trichlorosilane (DTS) was used to study the effect of both cleaning methods on the silanization of Ta2O5. Both types of cleaning allowed the formation of complete and crystalline DTS monolayers on Ta2O5, in contrast with the incomplete, disordered silane layer assembled on uncleaned Ta2O5. The deposited self-assembled monolayers were studied by means of contact angle goniometry, Brewster angle FTIR, X-ray photoelectron spectroscopy, cyclic voltammetry, and ellipsometry. Infrared analysis exhibited a highly ordered DTS silane film on Ta2O5 and indicated a larger tilt angle of the alkyl chains on this substrate by comparison to DTS on SiO2. Furthermore, with use of ellipsometry and XPS, the silane film thickness on Ta2O5 was determined to be substantially smaller than that reported in the literature for DTS on SiO2, supporting the observations of an increased tilt angle (approximately 45 degrees ) on Ta2O5 than on SiO2 (approximately 10 degrees ). By means of cyclic voltammetry, the formation of a dense, essentially pinhole-free, silane film was observed on the cleaned samples. In conclusion, the fully characterized and optimized procedure for the silanization of Ta2O5 surfaces with trichlorosilanes will allow the formation of well-defined, reproducible, and controllable chemical interfaces on Ta2O5.     

Comparison of the Wetting Properties of Three Commonly Used Simulated Intestinal Fluids Used as Dissolution Media in the Characterization of Drugs

Simulated intestinal fluids (SIFs) are described in the United States Pharmacopoeia (USP) and the International Pharmacopoeia (IntPh) as recommended dissolution media for the characterization of solid drugs. This study was carried out to compare their wettability properties. Six different model substrates were used as surrogates for solid drugs. These surrogate solid substrates were characterized by the Lifshitz-van der Waals, electron donor and electron acceptor terms, which are the three components of the total surface energy obtained by the van Oss model, which is based upon Young’s equation. Contact angles of the SIFs on the surrogate solid-substrates were determined dynamically by image analysis up to five minutes after applying a drop of the fluid on the solid surface. Observed time-dependent spreading behavior was accounted for by a linear extrapolation of the experimental data to zero contact time to obtain the apparent equilibrium contact angle at zero time. Additionally, the pH, osmolality and buffer capacity of the SIFs were experimentally determined. Although some differences in osmolality and buffer capacity were observed, no statistically significant differences in the wetting properties of the three SIFs were detected. This confirms recent findings that there are no observed differences in dissolution behavior among these simulated intestinal fluids. Harmonization of these SIFs is thus recommended.     

Preparation and characterisation of hydroxide stabilised ZnO(0001)-Zn-OH surfaces

Two different approaches under ambient conditions were developed for the preparation of clean, non-reconstructed, single crystalline ZnO(0001)-Zn surfaces. The surface preparation by a wet chemical etching procedure was compared with the same treatment in combination with a subsequent heat treatment in humidified oxygen atmosphere. Depending on the preparation technique, atomically flat terraces with a width of 100 nm to several micrometers were observed using an atomic force microscope (AFM). The obtained surface structures were further characterized by means of angle resolved X-ray photoelectron spectroscopy (AR-XPS), time-of-flight secondary ion mass spectroscopy (ToF-SIMS), Auger electron spectroscopy (AES) and low energy electron diffraction (LEED) measurements. Based on these results it is shown that the obtained surfaces are, in contrast to surfaces prepared under UHV conditions, stabilised by the adsorption of a monolayer of hydroxides. The important role of H(2)O during the heat treatment is pointed out by comparing the results of the same heat treatment in the absence of water. H(2)O turned out to play an important role in the reorganization process of the surface at elevated temperatures, thereby yielding extremely large atomically flat terraces. The terminating edges of these terraces were found to include 120 degrees and 60 degrees angles, thus perfectly reflecting the hexagonal surface structure.     

Reactivity of niobium(v) and tantalum(v) halides with carbonyl compounds: synthesis of simple coordination adducts, C-H bond activation, C=O protonation, and halide transfer

The metal halides of Group 5 MX(5) (M = Nb, Ta; X = F, Cl, Br) react with ketones and acetylacetones affording the octahedral complexes [MX(5)(ketone)] () and [TaX(4){kappa(2)(O)-OC(Me)C(R)C(Me)O}] (R = H, Me, ), respectively. The adducts [MX(5)(acetone)] are still reactive towards acetone, acetophenone or benzophenone, giving the aldolate species [MX(4){kappa(2)(O)-OC(Me)CH(2)C(R)(R')O}] (). The syntheses of (M = Ta, X = F, R = R' = Ph) and (M = Ta, X = Cl, R = Me, R' = Ph) take place with concomitant formation of [(Ph(2)CO)(2)-H][TaF(6)], and [(MePhCO)(2)-H][TaCl(6)], respectively. The compounds [acacH(2)][TaF(6)], and [TaF{OC(Me)C(Me)C(Me)O}(3)][TaF(6)], have been isolated as by-products in the reactions of TaF(5) with acacH and 3-methyl-2,4-pentanedione, respectively. The molecular structures of, and have been ascertained by single crystal X-ray diffraction studies.     

1-H2N-CB11F11]---synthesis and reactions of a functionalized fluorinated carbadodecaborate anion

In anhydrous hydrogen fluoride, K[1-H2N-CB11H11] is fluorinated with elemental fluorine to produce K[1-H2N-CB11F11]. Under strong alkaline conditions, two fluorine atoms of the [1-H2N-CB11F11]- anion are regioselectively exchanged, yielding the [1-H2N-4,6-(HO)2-CB11F9]- anion via [1-H2N-6-HO-CB11F10]- as an intermediate. Both hydroxycarborate anions were isolated as [Ph4P]+ salts. All of the species were characterized by IR, Raman, and multi-NMR spectroscopy, thermal analysis (DSC) as well as by mass spectrometry (MALDI). The assignment of the NMR signals was supported by DFT calculations. Solid-state structures of K[1-H2N-CB11F11], [BzPh3P][1-H2N-CB11F11], [Ph4P][1-H2N-4,6-(HO)2-CB11F9], [Ph4P][1-H2N-6-HO-CB11F10], and [BzPh3P][1-H2N-CB11H11] were determined by single-crystal X-ray diffraction.     

Validation of a fast screening method for the detection of cocaine in hair by MALDI-MS

The sensitivity and specificity of a novel method of screening for cocaine in hair, based on matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry (MS), have been evaluated. The method entails a rapid extraction procedure consisting of shaking 2.5 mg pulverised hair at high frequency in the presence of an acidic solution (160 μL of water, 20 μL of acetonitrile and 20 μL of 1 M trifluoroacetic acid) and a stainless-steel bullet. Following centrifugation, the supernatant is dried under a nitrogen stream, and the residue is reconstituted in 10 μL of methanol/trifluoroacetic acid (7:3; v/v). One microlitre of the extract is deposed on a MALDI sample holder previously scrubbed with graphite; an α-cyano-4-hydroxycinnamic acid (matrix) solution is electrosprayed over the dried sample surface to achieve a uniform distribution of matrix crystals. The identification of cocaine is obtained by post-source decay experiments performed on its MH⁺ ion (m/z 304), with a limit of detection of 0.1 ng/mg of cocaine. A total of 304 hair samples were analysed in parallel by MALDI-MS and a reference gas chromatography-MS method. The obtained results demonstrate specificity and sensitivity of 100% for MALDI-MS. Evidence of cocaine presence was easily obtained even when hair samples exhibiting particularly low cocaine levels (<0.5 ng/mg) were analysed.