Simultaneous determination of optical and chemical purities of a drug with two chiral centers by liquid chromatography-circular dichroism detection on a non-chiral stationary phase

The need for a rapid and cheap chromatographic technique for the simultaneous determination of diastereoisomeric and chemical purities of a drug has led to develop a non-enantioselective HPLC method on a porous graphitic carbon (PGC) sorbent and by using circular dichroism (CD) detection. Among a lot of non-chiral chromatographic supports tested, PGC was the only one allowing the separation of all benzoxathiepin diastereoisomers. After optimization of the chromatographic conditions, a mobile phase composed of chloroform, acetonitrile and methanol was suitable to elute the diastereoisomers with their related chemical impurities in less than 20 min by gradient mode. CD detection was found to be compatible with elution gradient and both the UV, CD and g anisotropy factor signals were recorded without disturbance. The determination of chemical purity was achieved with UV detection (254 nm) whereas the diastereoisomeric purity was determined using CD detection (258 nm) by plotting the anisotropy factors (R,S-S,R and R,R-S,S) versus the enantiomeric excess of each couple of enantiomers. A mathematic model was developed in order to express the diastereoisomeric excess versus the enantiomeric excess of each couple of enantiomers. Hence, the HPLC-UV/CD method was convenient to give access simultaneously to the optical and chemical purities of a chiral drug.     

Ruthenium catalysts supported on TiO<Subscript>2</Subscript> prepared by sol–gel way for <Emphasis Type="Italic">p</Emphasis>-hydroxybenzoic acid wet air oxidation

The wet air oxidation of p-hydroxybenzoic acid, chosen as a model compound of olive mills wastewaters was carried out at 140 °C and 50 bar air over Ru catalysts supported on TiO₂ prepared by sol–gel method. These catalysts were characterized by means of N₂ adsorption–desorption, XRD and TEM. Optimization of the catalytic performances was obtained by studying some parameters such as the catalyst preparation method, the solvent evacuation way, the nature of the hydrolysis agent, the influence of the ruthenium salt used as the metal precursor (Ru(NO)(NO₃)₃ or Ru(acac)₃) and the catalyst pretreatment. The pre-calcination of the catalyst precursor at 300 °C under oxygen, before the reduction step under hydrogen, was detrimental to the activity. The results showed that the use of nitric acid as hydrolysis agent, drying under supercritical conditions and the use of Ru(NO)(NO₃)₃ leads to the more efficient catalyst with high TOC abatement.     

New chromogenic substrates for feruloyl esterases

Indolyl and nitrophenyl 5-O-hydroxycinnamoyl-alpha-L-arabinofuranosides were prepared by chemo-enzymatic syntheses. These probes were designed as substrates to be used in assays of feruloyl esterase activity (EC 3.1.1.77). Color development in the assays only occurs when feruloyl esterase activity releases an intermediate chromogenic arabinoside that is a suitable substrate for alpha-L-arabinofuranosidase (EC 3.2.1.55), which in turn releases the free chromogenic group. The usefulness of these compounds was evaluated in both qualitative solid media-based assays and quantitative liquid assays that can be performed in microtiter plates using feruloyl esterases and arabinofuranosidases from various origins.     

Use of electrowetting to measure dynamic interfacial tensions of a microdrop

The adsorption of surface active species to liquid-liquid and to solid-liquid interfaces can have dramatic effects in microfluidics. In this paper we show how electrowetting on dielectric can be used to monitor a dynamic liquid-liquid interfacial tension (IFT) with a time resolution of O(1 s) using amplitude modulation of the AC voltage. This straightforward method, which requires less than a microlitre of sample, is demonstrated for aqueous drops containing Triton X-100 surfactant on a Teflon AF-coated substrate and with heptane as the immiscible oil ambient. Under these conditions, next to extracting the oil-water IFT (γ(ow)), also the effective water-substrate IFT difference (Δγ(ws)) can be obtained from the oil-water IFT and the Young's angle. Both γ(ow) and γ(ws) decrease over time due to adsorption. The measured dynamic oil-water IFT compares well to results of pendant drop experiments.     

Marine natural products

This review covers the literature published in 2004 for marine natural products, with 693 citations (491 for the period January to December 2004) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates and echinoderms. The emphasis is on new compounds (716 for 2004), together with their relevant biological activities, source organisms and country of origin. Biosynthetic studies (8), and syntheses (80), including those that lead to the revision of structures or stereochemistries, have been included.     

Thioindigo dyes: highly accurate visible spectra with TD-DFT

The structure and visible spectra of a large panel of thioindigo dyes and derivatives have been evaluated using a TD-PBE0/6-311+G(2d,p)//PBE0/6-311G(d,p) approach explicitly taking bulk solvent effects into account by means of the polarizable continuum model. The influence of the solvent characteristics, the trans-cis isomerization, and the chemical substitution on the benzene rings have been investigated. In addition, hemi-thioindigo dyes, thiazine-indigo, chromophore-like molecules, and selenoindigo have been considered. Though the relative oscillator strengths of the two allowed visible transitions in the nonplanar cis isomers are not always correctly reproduced by theory, the agreement between theoretical and experimental results is far above expectations. For the 170 cases studied, we obtained a mean unsigned error on the predicted lambda(max) limited to 6.9 nm or 0.03 eV, with only 6 (4) cases for which the difference exceeds 20 nm (0.10 eV). These errors are 1 order of magnitude smaller than what has previously been reported for indigoids. A linear correlation between the central double bond length and the lambda(max) has been established, while the bond length and vibrational frequency of the carbonyl groups do not correlate with the thioindigo color. The higher excitation energies of the cis conformers, compared to the trans structures, result from a less stabilized LUMO in the former case. Indeed, for cis thioindigo, the two electron-rich (in the excited state) carbonyl units lie close to each other.     

Prenylated xanthone derivatives with antiplasmodial activity from Allanblackia monticola STANER L.C

Further study of the methanol extract of the stem bark of Allanblackia monticola STANER L.C. resulted in the isolation of a new prenylated xanthenedione, designated allanxanthone C, together with the five known xanthones, garciniafuran, tovophyllin A, rubraxanthone, norcowanin and mangostin and one saponin, stigmasterol-3-O-beta-D-glucopyranoside. The structure of the new compound was established by detailed spectroscopic analysis to be 1,2-dihydro-3,6,8-trihydroxy-1,1,7-tri(3-methylbut-2-enyl)xanthen-2,9-dione (3-hydroxyapetalinone C). The methanol extract and pure compounds were tested on two strains of Plasmodium falciparum, F32 (chloroquine sensitive) and FcM29 (chloroquine resistant). The IC50 values obtained ranged from 0.6 to 8.9 microg/ml. Their cytotoxicity was estimated on human melanoma cells (A375) and the cytotoxicity/antiplasmodial ratio was found to be between 15.45 and 30.46. The antimicrobial activities against a range of microorganisms of the crude extract and some of these compounds are also reported.     

Total synthesis of ecteinascidin 743

A convergent total synthesis of ecteinascidin 743 is realized from five building blocks of almost equal size. It takes 23 steps from l-3-hydroxy-4-methoxy-5-methyl phenylalanol (5) with an overall yield of 3%.     

Glycosylated VCAM-1 isoforms revealed in 2D western blots of HUVECs treated with tumoral soluble factors of breast cancer cells

Background  

Several common aspects of endothelial phenotype, such as the expression of cell adhesion molecules, are shared between metastasis and inflammation. Here, we analyzed VCAM-1 variants as biological markers of these two types of endothelial cell activation. With the combination of 2-DE and western blot techniques and the aid of tunicamycin, we analyzed N-glycosylation variants of VCAM-1 in primary human endothelial cells stimulated with either TNF or tumoral soluble factors (TSF's) derived from the human breast cancer cell line ZR75.30.