Oxalate-bridged complexes of dimolybdenum and ditungsten supported by pivalate ligands: ((t)BuCO(2))(3)M(2)(mu-O(2)CCO(2))M(2)(O(2)C(t)Bu)(3). Correlation of the solid-state, molecular, and electronic structures with Raman, resonance Raman, and electronic spectral data

The compounds ((t)BuCO(2))(3)M(2)(mu-O(2)CCO(2))M(2)(O(2)C(t)Bu)(3) (M(4)OXA), where M = Mo or W, are shown by analysis of powder X-ray diffraction data to have extended lattice structures wherein oxygen atoms from the oxalate and pivalate ligands of one M(4)OXA molecule are linked to metal atoms of neighboring molecules. Raman, resonance Raman, electronic absorption (2-325 K in 2-MeTHF), and emission spectra are reported, together with corresponding spectra of the mu-O(2)(13)C(13)CO(2) isotopomers. To aid in the assignment, the Raman spectra of K(2)C(2)O(4).H(2)O and K(2)(13)C(2)O(4).H(2)O have also been recorded. The visible region of the electronic spectra is dominated by intense, fully allowed MLCT transitions, M(2) delta to oxalate pi*, which show pronounced thermochromism and extensive vibronic progressions associated with the oxalate ligand at low temperatures. With excitation into these charge-transfer bands, strong resonance enhancement is seen for Raman bands assigned to the oxalate nu(1)(a(g)) and, to a lesser extent, nu(2)(a(g)) modes. Electronic structure calculations for the model compounds (HCO(2))(3)M(2)(mu-O(2)CCO(2))M(2)(O(2)CH)(3), employing density functional theory (gradient corrected and time-dependent) with the Gaussian 98 and ADF 2000 packages, predict the planar oxalate D(2h) configuration to be favored, which maximizes M(2) delta to oxalate pi* back-bonding, and indicate low barriers (<8 kcal mol(-1)) to rotation about the oxalate C-C bonds.     

THE GENERATION OF HYDROXYL RADICALS IN BIOLOGIC SYSTEMS: TOXICOLOGICAL ASPECTS

Abstract— The formation of hydroxyl radicals in vitro was studied through their reaction with 2-keto-4-thiomethylbutyric acid to form ethylene gas. The autoxidation reaction of 6-aminodopamine served as a model source of hydroxyl radicals. Ethylene production was suppressed by catalase and by superoxide dismutase, indicating that both hydrogen peroxide and superoxide were involved in the reaction. Hydroxyl radical scavengers (thiourea > benzoate > ethanol) suppressed ethylene production in good agreement with their respective rate constants for reaction with hydroxyl radicals. Urea served as a negative control. Several substituted thiourea derivatives also suppressed ethylene production to a similar degree as thiourea itself. Biologic studies centered on several cytotoxic agents whose mechanisms of action are thought to involve hydroxyl radicals. These agents included alloxan, which destroys the beta cells of the pancreas, and 6-hydroxy- and 6-aminodopamine, which destroy sympathetic nerves. Damage to tissues in vivo was blocked to varying degrees by pretreatment of animals with hydroxyl radical scavengers such as ethanol or the thiourea derivatives. In addition, hydroxyl radical scavengers blocked the action of 5,7-dihydroxytryptamine, a neurotoxin whose effects on noradrenaline neurons were previously shown to be blocked by inhibitors of monoamine oxidase. The data indicate that these cell toxins produce their damaging actions on specific target cells through the intracellular generation of hydroxyl radicals.     

Proteome analysis of conditioned medium from cultured adult hippocampal progenitors

It is known that proliferation and survival of neural stem/progenitor cells in vitro not only depend on exogenous factors, but also on autocrine factors secreted into the conditioned medium. It is also well known that the identification of bioactive proteins secreted into the conditioned medium poses a substantial challenge. Recently, neural stem/progenitor cells were shown to secrete a survival factor, cystatin C, into the conditioned medium. Here, we demonstrate an approach to identify other low molecular weight proteins in conditioned medium from cultured adult rat hippocampal progenitor cells. A combination of preparative two-dimensional gel electrophoresis (2-DE) and mass spectrometry was utilized in the analysis. We were able to identify a number of proteins, which include Rho-guanine nucleotide dissociation inhibitor 1, phosphatidylethanolamine binding protein (PEBP), also termed Raf-1 kinase interacting protein, polyubiquitin, immunophilin FK506 binding protein 12 (FKBP12) and cystatin C. The presence of PEBP and FKBP12 in conditioned medium was confirmed immunologically. All nestin-positive progenitor cells showed immunoreactivity for antibodies against PEBP and FKBP12. To our knowledge we are the first to use this preparative proteomic approach to search for stem cell factors in conditioned medium. The method could be used to identify novel bioactive proteins secreted by stem/progenitor cells in vitro. Identification of bioactive proteins in vitro is of potential importance for the understanding of the regulatory mechanisms of the cells in vivo.     

An algorithm for convex constrained minimax optimization based on duality

We consider the problem of finding the minimum value of the upper hull ofn convex functionals on a Hilbert space, subject to convex constraints. The problem is reformulated as that of finding the minimum of the worst convex combination of these functionals, which eventually yields a saddle-point problem. We propose a new algorithm to solve this problem that simplifies the task of updating the dual variables. Simultaneously, the constraints can be dualized by introducing other dual multipliers. Convergence proofs are given and a concrete example shows the practical and computational advantages of the proposed algorithm and approach.This research has been supported by the Centre National de la Recherche Scientifique (CNRS-France) under Contract No. ATP-2340.     

The incoherent scattering function and related correlation functions in hard sphere fluids at short times

For a classical fluid of hard spheres and hard disks exact expressions for all densities and wave vectors are derived for the coefficients oft ⁿ in the short-time expansion of the incoherent intermediate scattering function (n = 0, 1,..., 4) and the velocity correlation function (n=0,1,2). Similarly, we obtain the coefficient of the leading term in the short-time behavior of the cumulants of the displacements. Furthermore,S(k, ) has a high-frequency tail ^–4, characteristic for the hard-sphere fluid, which leads to a modification of the standard sum rules. We present estimates for the frequency range, in which this tail may be observed in neutron scattering off noble gases. The results are also compared with Enskog's theory and molecular dynamics calculations.     

SPECTROSCOPIC STUDIES OF CUTANEOUS PHOTOSENSITIZING AGENTS–VIII. A SPIN-TRAPPING STUDY OF LIGHT INDUCED FREE RADICALS FROM CHLORPROMAZINE and PROMAZINE

Abstract— The clinically important phenothiazine drugs, particularly chlorpromazine, often elicit phototoxic and photoallergic reactions. We have used the spin traps 2-methyl-2-nitrosopropane (MNP) and 5,5-dimethyl-pyrroline-N-oxide (DMPO) to define the radical photolysis pathways of chlorpromazine and promazine. In the absence of oxygen the dechlorination product of chlorpromazine is trapped by MNP. The reactivity of the dechlorination product is similar to that of the phenyl radical as shown by its ability to extract hydrogen atoms from donors. Our results suggest that the dechlorination product is sufficiently reactive to account for the observation that chlorpromazine is more phototoxic than its parent promazine. In the presence of oxygen both chlorpromazine and promazine form a superoxide-dismutase-insensitive oxygen-centered intermediate which, when trapped by DMPO, rapidly decays to DMPO-OOH and subsequently to DMPO-OH. In addition, chlorpromazine readily undergoes photoelectron ejection only when it is excited into the second excited singlet state (Δ < 280 nra). This previously unknown wavelength dependence of photoionization should be considered in establishing the mechanism of chlorpromazine photosensitization.     

Processing studies and thermal stability of addition polymers from 1,4,5,8-tetrahydro-1,4;5,8-diepoxyanthracene and Bis-dienes

1,4,5,8-Tetrahydro-1,4;5,8-diepoxyanthracene reacts with various anthracene end-capped polymide oligomers to form Diels-Alder cycloaddition copolymers. The polymers are soluble in common organic solvents, and dehydrate thermally at temperatures of 300–350°C to give thermal oxidatively stable pentiptycene units along the polymer backbone. Because of their high softening points and good thermal oxidative stability, the polymers are candidates for matrix resins for high temperature composite applications. To assess their usefulness for such applications, several parameters have been studied affecting the properties of the final polymer. These parameters include varying the formulated molecular weight of the end-capped prepolymers, and use of meta-substituted aromatic diamine in place of some of the para-substituted diamine. Processability of the resins was studied using rheometric spectrometry, and a processing scheme was devised. Finally, several formulations of neat resins were compression molded into coupons, and evaluated for longterm stability in air at 315 and 371°C. The best combination of good processability and thermal oxidative stability was obtained from polymers synthesized with small amounts of meta-diamine substitution and higher formulated molecular weight prepolymers.     

Redox reactions involving rhenium and uranium hexafluorides,a convenient synthesis of β-uranium pentafluoride

Rhenium and uranium hexafluorides oxidise elemental iodine in iodine pentafluoride at ambient temperature to give the I₂⁺ cation. With UF₆ an additional reaction occurs to give β-uranium pentafluoride as one product, β-UF₅ is soluble in acetonitrile without disproportionation and is also formed from the reduction of UF₆ by MeCN. Copper, cadmium, and thallium metals are oxidised by ReF₆ in MeCN giving Cu^I, Cd^II, and Tl^I hexafluororhenates(V) but the reactions are complicated by reaction between ReF₆ and the solvent.     

Chiral capillary electrophoretic method for quantification of apomorphine

A new method for chiral determination of apomorphine enantiomers was developed and validated. Seven different neutral and charged cyclodextrins were tested for enantioselectivity on R,S-apomorphine. Sulfobutylether-beta-cyclodextrin was found to offer the best resolution, but with this system, four peaks were detected from a solution of the two enantiomers, which was suggested to be the result of different forms of the complex between the selector and apomorphine. A complexation constant was estimated for a complex of 1:1 ratio for the second and the fourth peak, whereas the other two peaks were fitted to a model ratio of 1:2 (analyte-selector). To avoid this phenomenon, hydroxypropyl-beta-cyclodextrin was then chosen as the chiral selector. An optimisation study was performed on three factors: concentration of the chiral selector, pH of the buffer, and applied voltage. Optimum conditions were: 14 mM of hydroxypropyl-beta-cyclodextrin, pH 3.0, and 16 kV. UV detection was at 200 nm. The method was validated at the chosen conditions, offering a limit of detection of 0.2 microM and a limit of quantification of 0.5 microM. The validated method was applied for the determination of R,S-apomorphine in a transport study with an in vitro cell culture model of the intestinal mucosa (Caco-2).