Synthesis, characterization of dihydrolipoic acid capped gold nanoparticles, and functionalization by the electroluminescent luminol

The use of gold nanoparticles as biological probes requires the improvement of colloidal stability. Dihydrolipoic acid (DHLA), a dithiol obtained by the reduction of thioctic acid, appears therefore very attractive for the stabilization and the further functionalization of gold nanoparticles because DHLA is characterized by a carboxylic acid group and two thiol functions. The ionizable carboxylic acid groups ensure, for pH > or = 8, the water solubility of DHLA-capped gold (Au@DHLA) nanoparticles, prepared by the Brust protocol, and the stability of the resulting colloid by electrostatic repulsions. Moreover almost all DHLA, adsorbed onto gold, adopts a conformation allowing their immobilization by both sulfur ends. It is proved by sulfur K-edge X-ray absorption near edge structure spectroscopy, which appears as an appropriate tool for determining the chemical form of sulfur atoms present in the organic monolayer. Such a grafting renders the DHLA monolayers more resistant to displacement by dithiothreitol than mercaptoundecanoic acid monolayers. The presence of DHLA on gold particles allows their functionalization by the electroluminescent luminol through amine coupling reactions assisted by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide. As a luminol-functionalized particle is nine times as bright as a single luminol molecule, the use of the particles as a biological probe with a lower threshold of detection is envisaged.     

Regio- and stereoselective alkylation at the 3′-terminal end of ribonucleotides by N-2-methyl-9-hydroxyellipticinium acetate : an antitumor agent

The regio- and stereoselective alkylation at the 3′-terminal end of ribonucleotides by N-2-methyl-9-hydroxyellipticinium acetate under oxidative conditions is reported.     

Amyloid binding and beyond: a new approach for Alzheimer's disease drug discovery targeting Aβo–PrPC binding and downstream pathways

Amyloid β oligomers (Aβo) are the main toxic species in Alzheimer''s disease, which have been targeted for single drug treatment with very little success. In this work we report a new approach for identifying functional Aβo binding compounds. A tailored library of 971 fluorine containing compounds was selected by a computational method, developed to generate molecular diversity. These compounds were screened for Aβo binding by a combined ¹⁹F and STD NMR technique. Six hits were evaluated in three parallel biochemical and functional assays. Two compounds disrupted Aβo binding to its receptor PrP^C in HEK293 cells. They reduced the pFyn levels triggered by Aβo treatment in neuroprogenitor cells derived from human induced pluripotent stem cells (hiPSC). Inhibitory effects on pTau production in cortical neurons derived from hiPSC were also observed. These drug-like compounds connect three of the pillars in Alzheimer''s disease pathology, i.e. prion, Aβ and Tau, affecting three different pathways through specific binding to Aβo and are, indeed, promising candidates for further development.

A new approach combining virtual screening, ¹⁹F and STD NMR, and biochemical assays using hiPSC and targetting multiple pathways involving Aβ, PrP^C and Tau provides a more effective strategy for Alzheimer''s disease drug discovery than Aβ only approach.     

Identification and simultaneous determination of non-steroidal anti-inflammatory drugs using high-performance liquid chromatography

An isocratic high-performance liquid chromatographic procedure is presented for the screening of plasma samples for the presence of sixteen non-steroidal anti-inflammatory drugs. Detection was achieved simultaneously at two wavelengths (254 and 370 nm) and the purity of the eluted peaks was tested using absorbance ratios at the two wavelengths; identification could thus be effective without interferences from substances of other pharmacological classes. The drugs were extracted simultaneously with diethyl ether after acidification and separated from each other on an octadecyl reversed-phase column using only one eluent, acetonitrile-0.3% acetic acid-tetrahydrofuran (36:63.1:0.9, v/v). The recovery, precision and reproducibility of the method were satisfactory as it allowed the determination of the drugs from infra- to supratherapeutic concentrations.     

The holonomy of the determinant of cohomology of an algebraic bundle

The purpose of this note is to remark that Theorem 3.7 in [1], when combined with the work of Bismut and Freed [2], leads, in the algebraic case, to an improvement of both results concerning the holonomy of determinant line bundles.     

Analytic torsion and holomorphic determinant bundles

In this paper, we derive the main properties of Kähler fibrations. We introduce the associated Levi-Civita superconnection to construct analytic torsion forms for holomorphic direct images. These forms generalize in any degree the analytic torsion of Ray and Singer. In the case of acyclic complexes of holomorphic Hermitian vector bundles, such forms are calculated by means of Bott-Chern classes.Supported by NSF Grant DMS 850248 and by the Sloan Foundation     

Dosage spectrophotométrique de traces de chrome,concentrées a l'oxine fondue

A method is described for the determination of Cr in aqueous solutions. It is based on the formation of Cr(III) oxinate, its extraction by means of molten oxine and the spectrophotometric measurement of the chloroform solution at 420 nm. The method is relatively specific and the sensitivity is about 10^?3 ppm. Several examples of application to sodium compounds are presented.