7-Benz[c] acridinemethanols as tetracyclic analogs of the 2-phenyl-4-quinolinemethanol antimalarials

A series of new 7-benz[c]acridinemethanols and 5,6-dihydro-7-benz[c]acridinemethanols was prepared as rigid, tetracyclic analogs of the antimalarial 2-phenyl-4-quinolinemethanols. Condensation of 5,7-dichloroisatin with 6-chloro-, 7-chloro-, and 6,7-dichloro-1-tetralone furnished halogenated 5,6-dihydro-7-benz[c]acridinecarboxylic acids, which were transformed into the corresponding acid chlorides, acyl malonates, α-bromomethyl ketones, and epoxides. Fully aromatic members of the series obtained via dehydrogenation of the 5,6-dihydro acids were likewise converted into epoxides via the acylmalonate route. Although all the epoxides studied proved to be exceptionally resistant to ring-opening by di-n-butylamine, probably on account of steric effects, they could be cleaved readily with piperidine or morpholine. Nmr spectra of the resulting amino alcohols suggest that these compounds exist in a single preferred conformation stabilized by internal O-H····N hydrogen bonding, and that free rotation about the side chain C-C bond does not occur at room temperature.     

Neutral pi-associated porphyrin [2]catenanes

A series of neutral porphyrin-containing catenanes has been synthesised, consisting of a zinc porphyrin strapped by a polyethylene glycol chain containing four or six ethylenoxy-units and incorporating a central naphthoquinol unit, interlinked with a naphthalene diimide macrocycle. The napthalene diimide precursor units exhibit only weak binding with the strapped porphyrins (Ka between 8 and 0.02 M(-1)), but good yields of the catenanes were obtained by Glaser coupling of the alkynyl napthalene diimide precursors in the presence of the porphyrins. Structures and solution conformations were determined by mass spectral and detailed 1H NMR studies. For the longer strapped porphyrins, the diimide macrocycle rotates around the central naphthoquinol unit at 420-450 times per second, while rotation is virtually prevented in the tighter strapped derivatives. A second dynamic process occurring in both sets of catenanes and described as 'yawing' leads to inequivalence in the naphthalene moieties. UV-Visible spectra indicate charge transfer interactions and electronic communication between the two components of the catenane.     

Benchmarking of ruthenium initiators for the ROMP of a norbornenedicarboxylic acid ester

The kinetic study of ring-opening metathesis polymerization (ROMP) of a diester functionalised norbornene derivative, (±)-exo,endo-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid diethyl ester, with a series of ruthenium benzylidene complexes revealed the applicability of these initiators for well defined polymerization reactions. Values for the rate of initiation as well as the rate of propagation of the initiators were determined and correlated to the molecular weight and polydispersity of the isolated polymers. As the only initiator providing an entry to virtually monodisperse polymers the classical “first generation Grubbs-catalyst” was identified, while N-heterocyclic carbene based initiators polymerized with a rate of propagation much higher than the rate of initiation yielding polymers with a broader molecular weight distribution.     

Straightforward synthesis of sphinganines via a serine-derived Weinreb amide

Sphinganines can be synthesized in just three steps from easily prepared serine-derived Weinreb amide 4. Pre-deprotonation of the acidic (N-H and O-H) protons of 4 allows for its efficient conversion to amino ketones 5. Such ketones can be selectively reduced to either erythro- or threo-sphinganines. Partially protected sphinganines 11 are also readily accessible in five steps from 4. Thus, Weinreb amide 4 represents one of the most versatile templates described to date for sphinganine synthesis.     

Circular‐Dichroism Studies on Artemisinin and Epiartemisinin and Their β‐Cyclodextrin Complexes in Solution

The circular dichroism (CD) spectra of the powerful antimalarian active principle artemisinin (ART; 1 ) from Artemisia annua, and of epiartemisinin (EPI, 2), its C(7) epimer, were studied in solution in the presence and absence of β‐cyclodextrin (β‐cd). A significant inversion of sign in the region of the second electronic transition was detected. The rotational strengths were successfully calculated within the time‐dependent density functional theory (DFT), which enabled us to establish a correlation between the molecular recognition and the biological acitivities of the two isomers.     

Analysis of free fatty acids and fatty acid phenacyl esters in vegetable oils and margarine by capillary electrochromatography

Capillary electrochromatography (CEC) has been utilized to analyze free fatty acids (FFAs) and fatty acid phenacyl esters (FAPEs) originating from vegetable oils and margarine. The analyses were performed on capillaries 25 and 40 cm long, 100 microm ID, and packed with 3 microm Hypersil ODS. Isocratic elution was achieved with the mobile phase acetonitrile/50 mM 2-(N-morpholino)ethane sulfonic acid (MES), pH 6, at a ratio of 9:1. For quantitative analysis, the formation of FAPE derivatives is preferred. Moreover, the number of double bonds in the FAPEs can be elucidated by measuring the UV absorbance ratio of 240:210 nm. For the determination of the oleate/elaidate ratio in margarines, the FFAs are analyzed because of overlap of elaidate/palmitate in FAPE analysis. Data obtained with CEC and micro liquid chromatography (LC) were compared and CEC was found to be far superior in terms of efficiency and speed of analysis. Important selectivity differences were noted between micro LC on highly endcapped ODS and CEC on the silanol-rich Hypersil ODS.     

Multifunctional redox catalysts as selective enhancers of oxidative stress

Certain cancer cells proliferate under conditions of oxidative stress (OS) and might therefore be selectively targeted by redox catalysts. Among these catalysts, compounds containing a chalcogen and a quinone redox centre are particularly well suited to respond to the presence of OS. These catalysts combine the specific electrochemical features of quinones and chalcogens. They exhibit high selectivity and efficiency against oxidatively stressed rat PC12, human Jurkat and human Daudi cells in cell culture, where their mode of action most likely involves the catalytic activation of existent and the generation of new reactive oxygen species. The high efficiency and selectivity shown by these catalysts makes them interesting for the development of anti-cancer drugs.     

Magnetic resonance study on lamellar phases of ammonium perfluorooctanoate

The aggregation properties of ammonium perfluorooctanoate (NH₄-PFO) in concentrated aqueous phases have been investigated by magnetic resonance techniques and have been compared with the aggregation properties in dilute solutions. Magnetic resonance methods indicated that NH₄-PFO—water systems with surfactant concentrations below 45% (w/w) behaved as isotropic purely micellar solutions in the temperature range 285–340 K. For higher concentrations the system exhibited a rather complex structure, having both isotropic and anisotropic components. The nematic nature of the anisotropic fraction was demonstrated by ¹⁹F NMR studies. The ¹⁹F NMR and EPR of nitroxides (TempTMA⁺, 5- and 16-DXSA) inserted as paramagnetic probes into the concentrated NH₄-PFO—water systems allowed us to establish that the lamellar phase could be mechanically oriented between quartz slides. The EPR investigation also gave details concerning the dynamics of both the oriented and non-oriented structures.     

Targeting cell surface receptors with ligand-conjugated nanocrystals

To explore the potential for use of ligand-conjugated nanocrystals to target cell surface receptors, ion channels, and transporters, we explored the ability of serotonin-labeled CdSe nanocrystals (SNACs) to interact with antidepressant-sensitive, human and Drosophila serotonin transporters (hSERT, dSERT) expressed in HeLa and HEK-293 cells. Unlike unconjugated nanocrystals, SNACs were found to dose-dependently inhibit transport of radiolabeled serotonin by hSERT and dSERT, with an estimated half-maximal activity (EC(50)) of 33 (dSERT) and 99 microM (hSERT). When serotonin was conjugated to the nanocrystal through a linker arm (LSNACs), the EC(50) for hSERT was determined to be 115 microM. Electrophysiology measurements indicated that LSNACs did not elicit currents from the serotonin-3 (5HT(3)) receptor but did produce currents when exposed to the transporter, which are similar to those elicited by antagonists. Moreover, fluorescent LSNACs were found to label SERT-transfected cells but did not label either nontransfected cells or transfected cells coincubated with the high-affinity SERT antagonist paroxetine. These findings support further consideration of ligand-conjugated nanocrystals as versatile probes of membrane proteins in living cells.     

Sample preparation improvement in polycyclic aromatic hydrocarbons determination in olive oils by gel permeation chromatography and liquid chromatography with fluorescence detection

The determination of 15 polycyclic aromatic hydrocarbons (PAHs) in olive oil samples has been improved in order to obtain a fast methodology with a low limit of detection through the combination of liquid-liquid extraction with acetonitrile and preparative gel permeation chromatography (GPC) prior to the injection of purified extracts into a C18 column. Acetonitrile-water was used as the mobile phase with a gradient from 50 to 95%, w/w, acetonitrile in 30 min. The oven temperature was maintained at 15 degrees C, and fluorometric detection was made at a fixed excitation wavelength of 264 nm and variable, optimal emission wavelength for each analyte ranging from 352 nm for 11-H-benzo(b)fluorene to 500 nm for indeno(1,2,3-cd)pyrene. Recovery for all the compounds studied varied from 75 to 111%, and limit of detection values from 0.05 ng/g for benzo(k)fluoranthene to 0.48 ng/g for indeno(1,2,3-cd)pyrene, corresponding to 0.09 ng/g benzo(a)pyrene. Results were compared with those obtained by liquid-liquid extraction followed by a cleanup on silica and a direct GPC treatment of oil samples diluted in dichloromethane, 2 other methodologies that are appropriate for quantifying PAHs in olive oils. However, the proposed method improves the determination limits, reduces the time of analysis, and provides a highly stable baseline for sample chromatograms.