Synthesis and cytotoxic activity of benzophenanthrolinone analogues of acronycine

Condensation of either 2-bromobenzoic acid (4) or 2-chloro-3-nitrobenzoic acid (5) with suitable aminoquinolines 6-8 afforded phenylquinolylamines 9-13. Acid mediated cyclization gave the corresponding 12H-benzo[b][1,7]phenanthrolin-7-ones 14 and 15, and 12H-benzo[b][1,10]phenanthrolin-7-ones 16-18. Compounds 14, 16, and 17 were subsequently N-methylated to 6-demethoxyacronycine and acronycine analogues 19-21, whereas reduction of the aromatic nitro group of 18 gave the amino derivative 22. Unsubstituted 12H-benzo[b][1,10]phenanthrolin-7-ones 16, 17, 20, and 21 were devoid of significant cytotoxic activity, whereas 18 and 22, bearing a nitrogen substituent at position 11, were significantly active. Unsubstituted 12H-benzo[b][1,7]phenanthrolin-7-ones 14 and 19, which include a pyridine nitrogen in the same 4-position as the pyran oxygen of acronycine exhibited cytotoxic activities within the same range of magnitude as acronycine itself.     

Selenium speciation by coupling vesicle mediated HPLC with off-line ETAAS and on-line focused microwave digestion HG-AAS detection

A novel High Performance Liquid Chromatography (HPLC) method for the separation of selenium species with specific detection by off-line Electrothermal Atomization Atomic Absorption Spectrometry (ETAAS) or on-line focused microwave digestion (MW) Hydride Generation Atomic Absorption Spectrometry (HG-AAS) is described. Vesicular mobile phases of the cationic surfactant didodecyldimethylammonium bromide (DDAB) have been evaluated for the liquid chromatographic separation of inorganic selenium (selenite and selenate) and different selenoaminoacids (selenocystine, selenomethionine and selenoethionine) on a C(18) reversed-phase column modified by DDAB molecules. The effects of different parameters (pH, buffer and vesicle concentrations) of the mobile phase on the retention times have been determined. The detection limit for selenium with the proposed off-line HPLC-ETAAS method has been found to be 5 microg/L of Se. The detection limit using HPLC-"on line" focused microwave digestion-HG-AAS has been found to be 1 microg/L of Se, with a precision (repeatability) better than +/- 5%. The latter proved to be an exceptional on-line real-time chromatographic detector for selenium speciation purposes.     

Some results on the geometry of Choquet simplices

In this paper, we give some properties of Choquet simplices which lead to the characterization of the closed Choquet simplices of ⁿ.The results of this paper were presented at the Conference on Convexity and Foundation of Geometry held in Haifa (10–14 March 1975).     

Preparation of trout liver microsomes for iron speciation in P-450 enzymes by AE–FPLC with ICP–(ORS)MS detection

Cytochromes P-450 are members of a superfamily of hemoproteins involved in the oxidative metabolism of various physiological and xenobiotic compounds in eukaryotes and prokaryotes. The multiplicity of this group of enzymes has been widely studied by chromatographic techniques, mainly high-performance liquid chromatography (HPLC). Because these enzymes are membrane-bound proteins, sample preparation for chromatographic separation of P-450 enzymes requires a solubilization step. The sample-preparation procedures are critical, because detergents affect not only the efficiency of protein solubilization but also their further chromatographic resolution. Trout liver microsomes have been taken here as a model sample to investigate iron speciation in cytochrome P-450. Trouts were treated intraperitoneally with -naphthoflavone, a potent inducer of some P-450 enzymes, and a microsomal suspension containing 7.4±0.1 nmol mL^–1 P-450 enzymes was obtained by ultracentrifugation. Lubrol PX was selected as detergent for solubilization, resulting in about 90% solubilization recovery. The solubilized cytochromes P-450 were further separated by AE–FPLC, with UV detection, or coupled to ICP–MS with an octapole reaction system, ICP–(ORS)MS (monitoring Fe signals at masses 54, 56, and 57). A sampling procedure and chromatographic conditions are developed and were successfully applied to iron speciation in trout liver P-450 enzymes. ICP–(ORS)MS detection of P-450 enzymes is Fe-specific and so will give accurate information on the prosthetic group of the protein, which can constitute an advantageous alternative to classical methods for detection of these hemoproteins.     

Un nouveau type d'alcaloïdes isoquinoleiques,les bisaporphines

The structures of Beccapoline and Beccapolinium, two new isoquinoline alkaloids from $\text{Polyathia beccarii}$, Annonaceae, have been elucidated by spectroscopic analysis. They are the first examples of natural bisaporphines.     

The complete symmetrization of quantum operators: new thoughts on an old problem

The complete symmetrization with respect to x, p _x,... of the operators associated with dynamical properties can sometimes lead to results different from those obtained by the conventional quantum formalism based on the rule op (A ²)=(op A)². For example, angular momentum operators M _z ² and M ² are modified by the additive constants ²/2 and 3 ²/2 respectively (M ²0 for electron in the ground state of H atom, rotator never at rest, but spectra unchanged); the average quadratic dispersion of energy is different from zero. These results can be interpreted by assuming that the system is never strictly isolated but communicates with the other systems of the universe by means of electromagnetic interactions. Quantum mechanics would give only average values over a sufficiently long time and would exhibit a quasi-ergodic character. Examples supporting this possibility are given, in particular that of arsines for which quantum forecasts correspond to average values over one year.Dedicated to Professor J. Koutecký on the occasion of his 65th birthday     

Fungicidal properties of meso-arylglycosylporphyrins: influence of sugar substituents on photoinduced damage in the yeast Saccharomyces cerevisiae

A series of neutral meso-arylglycosylporphyrins has been tested in order to evaluate their potency as antifungal agents against the yeast Saccharomyces cerevisiae. Photodynamic activity of these molecules results in intracellular damage as evidenced by the loss of clonogenicity and DNA fragmentation. The ability of these photosensitizers to permeate yeast cells is determined by microspectrofluorimetry and is correlated with their antifungal potency. Amphiphilic porphyrin derivatives are shown to exhibit the more pronounced photoactivity.     

Enantiospecific synthesis of the (9S,18R)-diastereomer of the leukocyte adhesion inhibitor cyclamenol A

Cyclamenol A is one of the very few non-carbohydrate and non-peptide natural products that inhibit leukocyte adhesion to endothelial cells. We report on the first enantioselective total synthesis of the (9S, 18R)-diastereomer of this macrocyclic polyene lactam. Key elements of the synthesis are i) the synthesis of the required chiral building blocks by employing readily accessible building blocks from the chiral pool, that is, (S)-malic acid and (R)-hydroxyisobutyric acid, ii) assembly of a linear polyene precursor by means of Wittig and Horner olefination reactions as key C-C bond-forming transformations, iii) ring closure by means of a vanadium-mediated pinacolisation reaction and iv) conversion of the generated cis-diol into a (Z)-olefin to complete the entire polyene system of the natural product. Attempts to close the macrocyclic ring by a macrolactamisation, a double Stille coupling or direct olefination in a McMurry reaction failed. Crucial to the successful completion of the synthesis was the correct orchestration of the final steps. It was necessary to first deprotect the intermediate formed after macrocycle formation and to generate the sensitive heptaene system in the last step by means of a Corey-Hopkins sequence.     

Synthesis and X-ray crystal structure determination of first examples of donor-functionalized terphenyl lanthanide complexes

The molecular structures of novel donor-functionalized terphenyl derivatives of trivalent ytterbium, yttrium, and samarium of composition [DanipYb(mu2-Cl)2(mu3-Cl)Li(THF)]2 (1) and [DanipLn(mu2-Cl)2(mu2-Cl)Li(THF)2]2 (Ln = Y, 2; Ln = Sm, 3) are reported [Danip = 2,6-di(o-anisol)phenyl]. The complexes are obtained from the reaction of equimolar amounts of DanipLi and LnCl3 (Ln = Yb, Y, Sm) in tetrahydrofuran at room temperature in 60% yield. 1-2 toluene crystallizes in the monoclinic space group Ponebar. Crystal data for 1-2 toluene at 203 K: a = 9.7281(9) A; b = 12.7989(12) A; c = 13.4870(12) A; alpha = 91.553(2) degrees; beta = 103.957(2) degrees; gamma = 109.916(2) degrees; V = 1521.2(2) A(3); Z' = 1; D(calcd) = 1.615 g cm(-3); R1 = 3.43%. 2-toluene crystallizes in the monoclinic space group Ponebar. Crystal data for 2-toluene at 203 K: a = 10.4152(10) A; b = 12.5783(12) A; c = 14.4640(14) A; alpha = 69.963(2) degrees; beta = 80.900(2) degrees; gamma = 66.603(2) degrees; V = 1633.3(3) A(3); Z' = 1; D(calcd) = 1.386 g cm(-3); R1 = 4.07%. 3-toluene crystallizes in the monoclinic space group Ponebar. Crystal data for 3-toluene at 203 K: a = 10.3457(8) A; b = 12.5658(10) A; c = 14.4365(11) A; alpha = 70.2250(10) degrees; beta = 81.2820(10) degrees; gamma = 66.8330(10) degrees; V = 1623.3(2) A(3); Z' = 1; D(calcd) = 1.521 g cm(-3); R1 = 3.40%. Complexes 1-3 represent first examples of donor-functionalized terphenyl complexes of the elements ytterbium, yttrium, and samarium, respectively. The molecular structures of 1-3 feature a "constraint geometry" type arrangement of the Danip ligand at the lanthanide atom. The complexes reported are dimeric and composed of lithium chloride bridged DanipLnCl(2) moieties (Ln = Yb, Y, Sm), stabilized through additional coordination of two methoxy functions to the lanthanide atom.     

Influence of reduction conditions on H2 adsorption in high-surface Rh/CeO2 catalysts as deduced by volumetry, calorimetry, and 1H NMR techniques

1H NMR spectra corresponding to H2 adsorption on high-surface Rh/CeO2 catalysts (S(BET) approximately 55 m2/g) are formed by two lines, attributed to hydrogen adsorbed on ceria (resonance line A) and rhodium-metal particles (upfield-shifted line B). The evolution of 1H NMR spectra as a function of temperature, time, and type of reduction (static or dynamic) allows the study of the progressive establishment of the strong metal-support interaction (SMSI) in Rh/CeO2 catalysts. As the reduction progresses, the mean adsorption heat and the amount of hydrogen adsorbed on the metal, deduced from volumetry, NMR, and calorimetry techniques, decrease considerably. As a consequence of the decrease in metal activity, the amount of hydrogen transferred to the support CeO2 is also reduced (spill-over processes). Outgassing of samples at 773 K eliminates hydrogen species retained at the metal-support surface, and oxidation treatments at 473 and 673 K eliminate the electronic effect and physical blocking of metal particles. The oxidation at 673 K recuperates the total adsorption capacity of metal particles. On the basis of these treatments, the contribution of different processes to the SMSI effect is analyzed. Electronic perturbation of rhodium particles is higher when reductions are performed in dynamic conditions; however, the importance of physical blocking of metal particles increases in static reductions. High reducibility of ceria strengthens electronic effects in Rh/CeO2 compared to those observed in Rh/TiO2 catalysts.