Selective double Suzuki cross-coupling reactions. Synthesis of unsymmetrical diaryl (or heteroaryl) methanes

Using a double Suzuki cross-coupling reaction ortho- or para-bromobenzyl bromides are easily transformed into unsymmetrical diaryl (or heteroaryl) methanes     

trans-Bis-[(−)ephedrinate]-palladium complex: synthesis, molecular modeling and use as catalyst

The reaction between palladium acetate, (−)-ephedrine and potassium acetate led to bis-chelate complex Pd[OCH(Ph)NH(Me)]₂ whose the trans-structure is obtained from calculations. The use of this complex to catalyze either the 1,4-hydrogenation of (E)-2-benzyliden-1-tetralone or Heck reaction of phenyl iodide with 3-methyl-3-buten-2-ol led to a low enantiomeric excess.     

Novel fluorinated amphiphilic cyclodextrin derivatives: Synthesis of mono-, di- and heptakis-(6-deoxy-6-perfluoroalkylthio)-β-cyclodextrins

A new series of fluorinated amphiphilic β-cyclodextrin derivatives has been synthesized. The strategy is based on the modification of the C-6 position of the mono-6-deoxy-6^A-para-tolylsulfonyl, di-6^A, 6^D-deoxy-6^A, 6^D-(para-tolylsulfonyl) and heptakis-(6-deoxy-6-iodo)-β-cyclodextrin precursors. The synthesis lead to mono-perfluoroalkylthio-, di-perfluoroalkylthio- and heptakis-perfluoroalkylthio-β-cyclodextrin in excellent yields (90-99%).     

An improved capillary electrophoresis method for in vitro monitoring of the challenging early steps of Aβ1–42 peptide oligomerization: Application to anti‐Alzheimer's drug discovery

We report an improved CE method to monitor in vitro the self‐assembly of monomeric amyloid β‐peptide (42 amino acids amyloid β‐peptide, Aβ_1–42) and in particular the crucial early steps involved in the formation of the neurotoxic oligomers. In order to start the kinetics from the beginning, sample preparation was optimized to provide samples containing exclusively the monomeric form. The CE method was also improved using a dynamic coating and by reducing the separation distance. Using this method, the disappearance of the monomer as well as the progressive formation of four species during the self‐assembly process can now be monitored and quantified over time. The hydrodynamic radius of the species present at the initial kinetics step was estimated around 1.8 nm by Taylor dispersion analysis while SDS‐PAGE analyses showed the predominance of the monomer. These results confirmed that the Aβ_1–42 species present at this initial time was the monomer. Methylene blue, an anti‐Alzheimer disease candidate, was then evaluated. In spite of an oligomerization inhibition, the enhanced disappearance of the Aβ_1–42 monomer provoked by methylene blue was demonstrated for the first time. This method, allowing the monomeric and smallest oligomeric species to be monitored, represents a new accurate and precise way to evaluate compounds for drug discovery.     

Synthesis of partially fluorinated poly(arylene ether sulfone) multiblock copolymers bearing perfluorosulfonic functions

Partially fluorinated poly(arylene ether sulfone) multiblock copolymers bearing perfluorosulfonic functions (ps‐PES‐FPES), with ionic exchange capacity (IEC) ranging between 0.9 and 1.5 meq H⁺/g, are synthesized by regioselective bromination of partially fluorinated poly(arylene ether sulfone) multiblock copolymers (PES‐FPES), followed by Ullman coupling reaction with lithium 1,1,2,2‐tetrafluoro‐2‐(1,1,2,2‐tetrafluoro‐2‐iodoethoxy)ethanesulfonate. The PES‐FPES are prepared by aromatic nucleophilic substitution reaction by an original approach, that is, “one pot two reactions synthesis.” The chemical structures of polymers are analyzed by ¹H and ¹⁹F NMR spectroscopy. The resulted ionomers present two distinct glass transitions and α relaxations revealing phase separation between the hydrophilic and the hydrophobic domains. The phase separation is observed at much lower block lengths of ps‐PES‐FPES as compared with the literature. AFM and SANS observations supported the phase separation, the hydrophilic domains are well dispersed but the connectivity to each other depends on the ps‐PES block lengths. The thermomechanical behavior, the water up‐take, and the conductivity of the ps‐PES‐FPES membranes are compared with those of Nafion 117^® and randomly functionalized polysulfone (ps‐PES). Conductivities close or higher to those of Nafion 117^® are obtained. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1941–1956     

Non-denaturating isoelectric focusing gel electrophoresis for uranium–protein complexes quantitative analysis with LA-ICP MS

A non-denaturating isoelectric focusing (ND-IEF) gel electrophoresis protocol has been developed to study and identify uranium (U)–protein complexes with laser ablation–inductively coupled plasma mass spectrometry (LA-ICP MS) and electrospray ionization mass spectrometry (ESI-MS). The ND-IEF-LA-ICP MS methodology set-up was initiated using in vitro U–protein complex standards (i.e., U–bovine serum albumin and U–transferrin) allowing the assessment of U recovery to 64.4?±?0.4 %. This methodology enabled the quantification of U–protein complexes at 9.03?±?0.23, 15.27?±?0.36, and 177.31?±?25.51 nmol U L^?1 in digestive gland cytosols of the crayfish, Procambarus clarkii, exposed respectively to 0, 0.12, and 2.5 μmol of waterborne depleted U L^?1 during 10 days. ND-IEF-LA-ICP MS limit of detection was 19.3 pmol U L^?1. Elemental ICP MS signals obtained both in ND-IEF electropherograms and in size exclusion chromatograms of in vivo U–protein complexes revealed interactions between U- and Fe- and Cu-proteins. Moreover, three proteins (hemocyanin, pseudohemocyanin-2, and arginine kinase) out of 42 were identified as potential uranium targets in waterborne-exposed crayfish cytosols by microbore reversed phase chromatography coupled to molecular mass spectrometry (µRPC-ESI-MS/MS) after ND-IEF separation.

Optimization of Experimental Parameters to Explore Small‐Ligand/Aptamer Interactions through Use of 1H NMR Spectroscopy and Molecular Modeling

Aptamers constitute an emerging class of molecules designed and selected to recognize any given target that ranges from small compounds to large biomolecules, and even cells. However, the underlying physicochemical principles that govern the ligand‐binding process still have to be clarified. A major issue when dealing with short oligonucleotides is their intrinsic flexibility that renders their active conformation highly sensitive to experimental conditions. To overcome this problem and determine the best experimental parameters, an approach based on the design‐of‐experiments methodology has been developed. Here, the focus is on DNA aptamers that possess high specificity and affinity for small molecules, L ‐tyrosinamide, and adenosine monophosphate. Factors such as buffer, pH value, ionic strength, Mg²⁺‐ion concentration, and ligand/aptamer ratio have been considered to find the optimal experimental conditions. It was then possible to gain new insight into the conformational features of the two ligands by using ligand‐observed NMR spectroscopic techniques and molecular mechanics.