A Terminal,Fluxional η4‐Benzene Complex with a Thermally Accessible Triplet State is the Primary Photoproduct in the Intercyclobutadiene Haptotropism of (CpCo)phenylenes

Low‐temperature irradiation of linear [3]‐ and [4]phenylene cyclopentadienylcobalt complexes generates labile, fluxional η⁴‐arene complexes, in which the metal resides on the terminal ring. Warming induces a haptotropic shift to the neighboring cyclobutadiene rings, followed by the previously reported intercyclobutadiene migration. NMR scrutiny of the primary photoproduct reveals a thermally accessible 16‐electron cobalt η²‐triplet species, which, according to DFT computations, is responsible for the rapid symmetrization of the molecules along their long axes. Calculations indicate that the entire haptotropic manifold along the phenylene frame is governed by dual‐state reactivity of alternating 18‐electron singlets and 16‐electron triplets.     

Quantification of plasma phospholipids by ultra performance liquid chromatography tandem mass spectrometry

We describe a fast and robust ultra performance liquid chromatography tandem mass spectrometry method for the quantification of phospholipid (PL) species in EDTA-plasma samples. We quantified total phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylcholine (LPC), and sphingomyelin (SM) and several species within these classes using one or two external calibrators and one internal standard for each class. Inter-assay coefficients of variation were <10% for the most abundant species and <20% for all quantified PC, LPC, and SM species and the three most abundant PE species. Coefficients of linear regression were R ² > 0.98. Mean recoveries were between 83% and 123%. The limits of detection were 0.37 μmol/L for PC, 4.02 μmol/L for LPC, 3.75 μmol/L for PE, and 0.86 μmol/L for SM. Quantification was linear over the physiological ranges for PE, LPC, and SM and up to 500 μmol/L for PC. The concentrations of PLs in the plasma of healthy donors yielded results that were comparable with those of previous works.     

Development and Validation of the UPLC-DAD Methodology for the Detection of Triterpenoids and Phytosterols in Fruit Samples of Vaccinium macrocarpon Aiton and Vaccinium oxycoccos L.

Cranberries are used in the production of medicinal preparations and food supplements, which highlights the importance of triterpene compounds determination in cranberry fruit raw material. The aim of our study was to develop and validate for routine testing suitable UPLC-DAD methodology for the evaluation of triterpene acids, neutral triterpenoids, phytosterols, and squalene content in cranberry samples. The developed and optimized UPLC-DAD methodology was validated according to the guidelines of the International Council for Harmonization (ICH), evaluating the following parameters: range, specificity, linearity (R² > 0.999), precision, LOD (0.27–1.86 µg/mL), LOQ (0.90–6.18 µg/mL), and recovery (80–110%). The developed and validated technique was used for the evaluation of triterpenic compounds in samples of Vaccinium macrocarpon and Vaccinium oxycoccos fruits, and their peels, pulp and seeds. The studied chromatogram profiles of Vaccinium macrocarpon and Vaccinium oxycoccos were identical but differed in the areas of the analytical peaks. Ursolic acid was the dominant compound in fruit samples of Vaccinium macrocarpon and Vaccinium oxycoccos. The highest amounts of triterpenic compounds were detected in the cranberry peels samples. The developed method for the detection of triterpene compounds can be applied in further studies for routine testing on the qualitative and quantitative composition of fruit samples of Vaccinium macrocarpon and Vaccinium oxycoccos species and cultivars.     

Radioprotective activity of metalladithioacetals derived from N‐substituted naphthylethylimidazoline

A number of organosilicon and organogermanium derivatives of N‐substituted 2‐[1‐(1‐naphthyl)ethyl]‐2‐imidazoline have been reported and the toxicity of these compounds has been determined in mice. In this paper we report the evaluation of the radioprotective activity of new sila‐ and germa‐dithioacetals derived from N‐substituted 2‐[1‐(1‐naphthyl)ethyl]‐2‐imidazoline. Copyright © 2003 John Wiley & Sons, Ltd.     

Identification of Non-Macrocyclic Small Molecule Inhibitors against the NS3/4A Serine Protease of Hepatitis C Virus through in Silico Screening

Drug discovery and design for inhibition of the Hepatitis C Virus (HCV) NS3/4A serine protease is a major challenge. The broad, shallow, and generally featureless nature of the active site makes it a difficult target for "hit" selection especially using standard docking programs. There are several macrocyclic NS3/4A protease inhibitors that have been approved or are in clinical trials to treat chronic HCV (alone or as combination therapy), but most of the current therapies for HCV infection have untoward side effects, indicating a continuing medical need for the discovery of novel therapeutics with improved efficacy. In this study, we designed and implemented a two-tiered and progressive docking regime that successfully identified five non-macrocyclic small molecules that show inhibitory activity in the low micromolar range. Of these, four compounds show varying inhibition against HCV subgenotypes 1b, 1a, 2a, and 4d. The top inhibitor (3) has an IC(50) value of 15 μM against both subgenotypes 1b and 2a of the NS3/4A protease enzyme. Another inhibitor, 1, inhibits all four subgenotypes with moderate activity, showing highest activity for genotype 2a (24 μM). The five inhibitors presented in this study could be valuable candidates for future hit to lead optimization. Additionally, enzyme-inhibitor interaction models presented herein provide key information regarding structural differences between the active sites of the NS3/4A protease of the HCV subgenotype 1a and 1b that might explain the variable inhibitory activity between subgenotypes of the small molecule inhibitors identified here.     

Novel route to the synthesis of 4-quinolyl isothiocyanates

4-Quinolyl isothiocyanates were synthesized in a regiospecific fashion from the corresponding 4-chloroquinolines and silver thiocyanate in refluxing toluene. The products were isolated in quantitative yield and high purity (>95%) by simple filtration and concentration. Reactivity and mechanism of the reaction are discussed. The new approach would provide a new mean which had been lacking for the synthesis of functionalized 4-quinolinyl isothiocyanate.     

Effect of n-alkyl chain length on the complexation of phenanthrene and 9-alkyl-phenanthrene with beta-cyclodextrin

The characteristics of host-guest complexation between beta-cyclodextrin (beta-CD) and phenanthrene derivatives (phenanthrene, n-propyl, n-butyl and n-hexyl-phenanthrene) were investigated by fluorescence spectrometry. Linear and non-linear regression methods were used to estimate the formation constants (K1). A 1:1 stoichiometric ratio and an effect of n-alkyl chain length on the formation constant were observed for the binary inclusion complex between guest and beta-CD. The formation constant dramatically increases with the length of n-alkyl, it starts from the value of 140 l mol(-1) for the phenanthrene to reach the value of 580 l mol(-1) for hexyl-phenanthrene. The effect of the temperature on the fluorescence intensity of each complex (guest-host) was also studied; and then the thermodynamic parameters were calculated. The main inclusion site seems to be aromatic moiety for short chain molecules, and it moves toward the alkyl chain part, as the chain becomes longer.     

C2-Cyanomethyl (CNMe) Ether-Protected Glycosyl Trichloroacetimidate Donors for Stereoselective β-O-Glycosylations

Stereoselective construction of glycosidic linkages have emerged as one of the pivotal aspects for the synthesis of complex oligosaccharide assemblies. We herein report C2-cyanomethyl (CNMe) ether as a strong stereodirecting group on trichloroacetimidate glycosyl donors for the synthesis of 1,2-trans-β-O-glycosides. The developed donors bearing various arming and disarming protections along with C2-CNMe ether delivered the glycosides in short reaction time, moderate to good yields and high to excellent stereoselectivities. Gluco- and galacto- configured donors were found compatible with an array of alcohols having varied reactivities. The orthogonality of the CNMe ether protection with silyl ether group has been further explored for sequential glycosylations.     

The use of amidoximated cellulose for the removalof metal ions and dyes from waste waters

The adsorption of metal ions such as Cu(II), Cr(III), Cd(II) and Ni(II)and dyes such as Acid Blue 25, Calmagite and Eriochrome Blue Black Bis performed onto amidoximated cellulose (Am-Cell). Different ways are possible for theadsorption of these pollutants onto Am-Cell : adsorption of each pollutantaloneon the support, or cumulative adsorption of both metal ions and dyes on the samesupport. In the last case, the pollutants may be adsorbed simultaneously from aunique solution, or successively from two different solutions, whatever theorder. Am-Cell loaded or not with metal ions shows a high capacity for dyeadsorption. Ternary complexes involving metal/dye/amidoxime are formed. Theobserved stoichiometries are 1/1/1 with Cu(II), Cr(III) and Cd(II) ions and1/1/2with Ni(II) ion. A quasi-total and specific desorption of either metal ions (bytreatment with ethylenediaminetetracetic salt) or of dyes (by heating inaqueoussolution) is possible from these ternary complexes. Concerning the dyes, manysuccessive adsorption/desorption cycles are possible without a noticeablechange in the adsorption capacity.     

Synthetic approaches to indolo[6,7-a]pyrrolo[3,4-c]carbazoles: potent cyclin D1/CDK4 inhibitors

Synthesis of indolo[6,7-a]pyrrolo[3,4-c]carbazoles 1, a new class of cyclin D1/CDK4 inhibitors, by oxidation of the corresponding aryl indolylmaleimides 2, will be described. Two approaches to the synthesis of 2 were identified that required new methods for the synthesis of 7-substituted indole acetamides 3 and N-methyl (indol-7-yl)oxoacetates 6. The chemistry developed enabled introduction of functionality (-OR, NR(2)) at C(12) and N(13) facilitating structure-activity relationship (SAR) evaluation of this indolocarbazole platform.