Palladium-catalyzed oxidative cyclizations: synthesis of dihydropyranones and furanones

A boron-mediated syn- and anti-stereoselective aldol reaction giving rise to various beta-hydroxyenones was coupled to a Pd((II))-mediated oxidative cyclization to give 2,3,6-trisubstituted syn- and anti-dihydropyranones in good yields. The Pd((II))-mediated oxidative cyclization was expanded to alpha-hydroxyenones leading to furan-3(2H)-one derivatives, which include natural product bullatenone and a known precursor of geiparvarin. The sole product of the oxidative cyclization of alpha,beta-dihydroxyenone was a five-membered furan-3(2H)-one derivative, suggesting that the ring closure of these diols is both chemo- and regioselective.     

Control of lysine reactivity in four-helix bundle proteins by site-selective pKa depression: expanding the versatility of proteins by postsynthetic functionalization

Five 42-residue polypeptides have been designed to fold into hairpin helix-loop-helix motifs that dimerize to form four-helix bundles, and to serve as protein scaffolds for the elucidation at the molecular level of the principles that control and fine-tune lysine and ornithine reactivities in a protein context. Site-selective control of Lys and Orn reactivity provides a mechanism for addressing directly individual residues and is a prerequisite for the site-selective functionalization of folded proteins. Several lysine and one ornithine residues were introduced on the surface and in the hydrophobic core of the folded motif. The reactivity of each residue was determined by measuring the degree of acylation of the trypsin cleaved fragments by HPLC and mass spectrometry. The most reactive residues were Orn34 and Lys19, both of which were located in d positions in the heptad repeat, and therefore in hydrophobic environments. Upon reaction of the helix-loop-helix dimer KA-I with one equivalent of mono-p-nitrophenyl fumarate, Orn34 was acylated approximately three times more efficiently than Lys19, whereas Lys10 (b position), Lys15 (g position), and Lys33 (c position) remained unmodified. In the sequence KA-I-A(15) Lys15 was replaced by an alanine residue and the selectivity of Orn34 over Lys19 increased to approximately a factor of six, probably because Lys15 had the capacity to reduce the pK(a) value of Lys19 and 85 % of site-selectively monoacylated product was obtained. The pH dependence of the acylation reaction was determined and showed that the pK(a) of the reactive residues were 9.3, more than a pK(a) unit below the magnitude of the corresponding residue in a solvent exposed position. Introducing Lys and Orn residues into a or d positions of the heptad repeat therefore serves as a mechanism of depressing their pK(a) to increase their reactivity site selectively. Extensive NMR and CD spectroscopic analyses showed that the sequences fold according to prediction.     

Quaterthiophene-based dimers containing an ethylene bridge: molecular design,synthesis, and optoelectronic properties

Two quaterthiophene-based dimers including an ethylene bridge have been designed and efficiently prepared; experimental and computational studies show a promising potential as semiconducting material with a charge transport of higher dimensionality compared to quaterthiophene.     

Direct measurement of tilt angle in smectic mesophases by neutron diffraction

We report the results of a direct measurement of the tilt angle of the molecules with respect to the normal layer in the different smectic phases and in the crystalline phase of the TBBA liquid crystal. The values of the tilt angles are obtained by using a new simple method that consists of direct reading of the angular distance between two Bragg peaks in a single neutron rocking curve. The results on the smectic phases are in good agreement with the existing experimental values obtained with other techniques.     

Surfactant-free synthesis of amphiphilic diblock copolymer nanoparticles via nitroxide-mediated emulsion polymerization

Amphiphilic hairy nanoparticles are prepared in a one step, batch, heterogeneous polymerization of styrene or n-butyl acrylate, using a water-soluble poly(sodium acrylate) alkoxyamine macroinitiator based on the SG1 nitroxide.     

Parametric inference for discrete observations of diffusion processes with mixed effects

Stochastic differential equations with mixed effects provide means to model intra-individual and inter-individual variability in repeated experiments leading to longitudinal data. We consider N i.i.d. stochastic processes defined by a stochastic differential equation with linear mixed effects which are discretely observed. We study a parametric framework with distributions leading to explicit approximate likelihood functions and investigate the asymptotic behavior of estimators under the asymptotic framework : the number N of individuals (trajectories) and the number n of observations per individual tend to infinity within a fixed time interval. The estimation method is assessed on simulated data for various models.     

Structured Hybrid Nanoparticles via Surface‐Initiated ATRP of Methyl Methacrylate from Ordered Mesoporous Silica

Structured hybrid nanoparticles were synthesized via surface‐initiated atom transfer radical polymerization of MMA from ordered mesoporous silica (OMS) nanoparticles with various morphologies. The design of the OMS particles was adjusted to target either spherical core‐shell or cylindrical morphologies with a mean diameter below 400 nm. The polymer growth via ATRP from the silica surface was well‐controlled as demonstrated by the macromolecular characteristics of the grafted chains. Original hybrid multilayered nanoparticles composed of either a dense silica core or hollow core; an inner OMS shell showing radial orientation of the mesopores and an outer PMMA shell with controlled thickness were successfully prepared.

     

Elaboration of monodisperse spherical hollow particles with ordered mesoporous silica shells via dual latex/surfactant templating: radial orientation of mesopore channels

Monodisperse spherical hollow nanoparticles of mesoporous silica featuring mesopores with a radial orientation in the silica shell were synthesized via a dual-templating method. Specifically designed polystyrene latexes with anionic or cationic surface charges acted as the core templates, while cetyltrimethylammonium bromide served as a co-template to structure the mesopore formation during tetraethoxysilane hydrolysis/condensation. The particles were well-separated and presented homogeneous mesoporous silica shells. Average particle diameters were less than 200 nm, and the particles displayed high values of specific surface area and pore volume. The shell thickness and the hollow core diameter could be tuned independently while the radial pore structure was preserved. A detailed analysis of the nitrogen adsorption-desorption isotherms proved that the central cavity was completely isolated from the external medium, that is, only accessible through the radial mesopores of the shell. Consequently, our particles gather the advantages of a well-defined structure, straight penetrating channels across the silica shell, and a high accessible porous volume of the central core. These properties make them far better candidates than simple mesoporous particles for any storage and/or controlled release applications.