A new selective approach to 1,1-bis(silyl)-2-arylethenes and 1,1-bis(silyl)-1,3-butadienes via sequential silylative coupling-Heck coupling reactions

A novel selective route to 1,1-bis(silyl)-1-alkenes has been developed. Sequential one-pot silylative coupling exo-cyclization of 1,2-bis(dimethylvinylsiloxy)ethane followed by the reaction with Grignard reagents leads to the desired 1,1-bis(silyl)ethenes, which are then efficiently coupled in the presence of silver nitrate and palladium acetate with aryl or alkenyl idodides to give the corresponding 1,1-bis(silyl)-2-arylethenes or 1,1,4-trisubstituted 1,3-butadienes with high yield.     

A fluorescent broad-spectrum proteasome inhibitor for labeling proteasomes in vitro and in vivo

The proteasome is an essential evolutionary conserved protease involved in many regulatory systems. Here, we describe the synthesis and characterization of the activity-based, fluorescent, and cell-permeable inhibitor Bodipy TMR-Ahx(3)L(3)VS (MV151), which specifically targets all active subunits of the proteasome and immunoproteasome in living cells, allowing for rapid and sensitive in-gel detection. The inhibition profile of a panel of commonly used proteasome inhibitors could be readily determined by MV151 labeling. Administration of MV151 to mice allowed for in vivo labeling of proteasomes, which correlated with inhibition of proteasomal degradation in the affected tissues. This probe can be used for many applications ranging from clinical profiling of proteasome activity, to biochemical analysis of subunit specificity of inhibitors, and to cell biological analysis of the proteasome function and dynamics in living cells.     

Superparamagnetic Composites Based on Ionic Resin Beads/CaCO3/Magnetite

The preparation of superparamagnetic composites obtained by CaCO₃ mineralization from supersaturate aqueous solutions is presented. The preparation was conducted in the presence of oleic acid stabilized magnetite nanoparticles as a water‐based magnetic fluid and insoluble templates as gel‐like cross‐linked polymeric beads. The presence of the magnetic particles in the composites provides a facile way for external manipulation using a permanent magnet, thus allowing the separation and extraction of magnetically modified materials. Two ion exchangers based on divinylbenzene/ethyl acrylate/acrylonitrile cross‐linked copolymer—a cation ion exchanger (CIE) and an amphoteric ion exchanger (AIE)—were used, as well as different addition orders of magnetite and CaCO₃ crystals growth precursors. The morphology of the composites was investigated by SEM, the polymorphs content by X‐ray diffraction, and the thermal stability by thermogravimetric analysis. Polymer, CaCO₃, and magnetite in the composite particles were shown to be present by energy dispersive X‐ray (EDX), XPS, and TEM. The sorption capacity for Cu^II ions was tested, as compared to samples prepared without magnetite.     

Specific cell-permeable inhibitor of proteasome trypsin-like sites selectively sensitizes myeloma cells to bortezomib and carfilzomib

Proteasomes degrade the majority of proteins in mammalian cells, are involved in the regulation of multiple physiological functions, and are established targets of anticancer drugs. The proteasome has three types of active sites. Chymotrypsin-like sites are the most important for protein breakdown and have long been considered the only suitable targets for antineoplastic drugs; however, our recent work demonstrated that inhibitors of caspase-like sites sensitize malignant cells to inhibitors of the chymotrypsin-like sites. Here, we describe the development of specific cell-permeable inhibitors and an activity-based probe of the trypsin-like sites. These compounds selectively sensitize multiple myeloma cells to inhibitors of the chymotrypsin-like sites, including antimyeloma agents bortezomib and carfilzomib. Thus, trypsin-like sites are cotargets for anticancers drugs. Together with inhibitors of chymotrypsin- and caspase-like sites developed earlier, we provide the scientific community with a complete set of tools to separately modulate proteasome active sites in living cells.     

Rotational and translational self-diffusion in concentrated suspensions of permeable particles

In our recent work on concentrated suspensions of uniformly porous colloidal spheres with excluded volume interactions, a variety of short-time dynamic properties were calculated, except for the rotational self-diffusion coefficient. This missing quantity is included in the present paper. Using a precise hydrodynamic force multipole simulation method, the rotational self-diffusion coefficient is evaluated for concentrated suspensions of permeable particles. Results are presented for particle volume fractions up to 45% and for a wide range of permeability values. From the simulation results and earlier results for the first-order virial coefficient, we find that the rotational self-diffusion coefficient of permeable spheres can be scaled to the corresponding coefficient of impermeable particles of the same size. We also show that a similar scaling applies to the translational self-diffusion coefficient considered earlier. From the scaling relations, accurate analytic approximations for the rotational and translational self-diffusion coefficients in concentrated systems are obtained, useful to the experimental analysis of permeable-particle diffusion. The simulation results for rotational diffusion of permeable particles are used to show that a generalized Stokes-Einstein-Debye relation between rotational self-diffusion coefficient and high-frequency viscosity is not satisfied.     

Evaluation of docking performance in a blinded virtual screening of fragment-like trypsin inhibitors

In this study, we have "blindly" assessed the ability of several combinations of docking software and scoring functions to predict the binding of a fragment-like library of bovine trypsine inhibitors. The most suitable protocols (involving Gold software and GoldScore scoring function, with or without rescoring) were selected for this purpose using a training set of compounds with known biological activities. The selected virtual screening protocols provided good results with the SAMPL3-VS dataset, showing enrichment factors of about 10 for Top 20 compounds. This methodology should be useful in difficult cases of docking, with a special emphasis on the fragment-based virtual screening campaigns.     

Theory of filters

We consider the following statistical problem: suppose we have a light beam and a collection of semi-transparent windows which can be placed in the way of the beam. Assume that we are colour blind and we do not possess any colour sensitive detector. The question is, whether by only measurements of the decrease in the beam intensity in various sequences of windows we can recognize which among our windows are light beam filters absorbing photons according to certain definite rules? To answer this question a definition of physical systems is formulated independent of “quantum logic” and lattice theory, and a new idea of quantization is proposed. An operational definition of filters is given: in the framework of this definition certain nonorthodox classes of filters are admissible with a geometry incompatible to that assumed in orthodox quantum mechanics. This leads to an extension of the existing quantum mechanical structure generalizing the schemes proposed by Ludwig [10] and the present author [13]. In the resulting theory, the quantum world of orthodox quantum mechanics is not the only possible but is a special member of a vast family of “quantum worlds” mathematically admissible. An approximate classification of these worlds is given, and their possible relation to the quantization of non-linear fields is discussed. It turns out to be obvious that the convex set theory has a similar significance for quantum physics as the Riemannian geometry for space-time physics.     

The influence of the dispersion of metals on the activity of Pt/C and Pd/C catalysts in the dehydrogenation of perhydroterphenyl

The activity of Pt/C and Pd/C catalysts in the dehydrogenation of perhydroterphenyl was studied at conversions lower than 30% depending on the dispersion of platinum and palladium metals, which was estimated by two independent methods (adsorption of CO and X-ray diffraction).     

Synthesis of Monofunctionalized Silsesquioxanes (RSiMe2O)(iBu)7Si8O12 via Alkene Hydrosilylation

The research presented in this work comprehensively describes hydrosilylation of a wide spectrum of alkenes which contain one or more reactive groups with (HSiMe₂O)(iBu)₇Si₈O₁₂, in the presence of different types of catalysts. Special attention is paid to the influence of alkene, catalyst, and reaction conditions on process effectiveness and selectivity by the precise monitoring of the experiments with in situ FTIR and NMR spectroscopies. More than twenty silsesquioxanes bearing reactive groups (OH, Br, NR₂, CO, COOR, NCO, epoxy, SiR₃) commonly used in organic and polymer chemistry, were obtained, isolated and characterized by ¹H, ¹³C, ²⁹Si NMR and MALDI TOF. Importantly, in the presented syntheses, commercially available reagents and catalysts were used, meaning that the presented methods could be easily repeated, rapidly scaled up, and widely applied.     

A New Spark Plug to Improve the Performances of Combustion Engines: Study and Analysis of Unburned Exhaust Gases

The ignition sparks provided by the conventional spark plug do not always ensure a fast and complete combustion of the hydrocarbon-air mixture. For this reason, we offer a new type of plug with a double spark using two simultaneous discharges generated by a pulsed high voltage-power supply. This work presents the comparison of two spark plugs, a classical one and a double spark plug, by analyzing the unburned hydrocarbon gases from the exhaust pipe of the engine. For a first gasoline engine, we measure the oxygen concentration in the exhaust gases with a lambda probe and the unburned hydrocarbon by the use of GC–MS coupled with SPME extraction technique. We can observe a clear decrease of total unburned hydrocarbon (THC). For a second motor test bench, powered with propane, we complete measures in function of air/fuel ratio of the THC, NO_x, CO₂ and CO. These results confirm that we obtained a better combustion especially for leaner mixtures.