Library of second-generation cycloruthenated compounds and evaluation of their biological properties as potential anticancer drugs: passing the nanomolar barrier

A library of 32 organoruthenium compounds has been synthesised. Known and novel C-N cyclometalated compounds as well as N-C-N and N-N-C pincer derivatives of this metal have been used in this purpose. Most of the compounds have been tested for their in vitro antitumoral behaviours, good to excellent activities have thus been found. Several of the newly synthesized compounds pass the symbolic barrier of the nanomolar range for their IC(50) indicating a critical improvement. The level of activity is tentatively correlated to physicochemical properties of the compounds such as their Ru(III/II) redox potential and their lipophilicity (log P).     

Numerical study of shear band instability and effect of cavitation on the response of a specimen under undrained biaxial loading

This paper presents an extension of the local second gradient model to multiphasic materials (solids particles, air, water) and including the cavitation phenomenon. This new development was made in order to model the response of saturated dilatant materials under deviatoric stress and undrained conditions and possibly, in future, the behavior of unsaturated soils. Some experiments have showed the significance of cavitation for the hydromechanical response of materials. However, to date and as far as we are aware, no attempt was made to implement the cavitation as a phase change mechanism with a control of pore pressure. The first part of the results section explores the effects of permeability, dilation angle and loading rate on the stability of shear bands during a localization event. The reasons underlying the band instability are discussed in detail, which helps defining the conditions required to maintain stability and investigating the effects of cavitation without parasite effect of materials parameters or loading rate. The model showed that, if a uniform response is obtained, cavitation triggers localization. However, in case of a localized solution, cavitation follows the formation of the shear band, with the two events being quite distinct.     

Polysulfide chalcogels with ion-exchange properties and highly efficient mercury vapor sorption

We report the synthesis of metal-chalcogenide aerogels from Pt(2+) and polysulfide clusters ([S(x)](2-), x = 3-6). The cross-linking reaction of these ionic building blocks in formamide solution results in spontaneous gelation and eventually forms a monolithic dark brown gel. The wet gel is transformed into a highly porous aerogel by solvent exchanging and subsequent supercritical drying with CO(2). The resulting platinum polysulfide aerogels possess a highly porous and amorphous structure with an intact polysulfide backbone. These chalcogels feature an anionic network that is charged balanced with potassium cations, and hosts highly accessible S-S bonding sites, which allows for reversible cation exchange and mercury vapor capture that is superior to any known material.     

Capillary electrophoresis/visible‐LED induced fluorescence of tryptophan: What's new?

Tryptophane (Trp) labelled by 3‐(4‐carboxybenzoyl)‐2‐quinolinecarboxaldehyde (CBQCA) is very difficult to identify using CE and fluorescence detection (480 nm). Why in this article some mass spectrometry experiments show that Trp is really labelled by CBQCA as Leucine (Leu)? If the maximum of UV absorption (λ_max) is the same between Leu‐CBQCA and Trp‐CBQCA, the molar extinction coefficient is around 2 fold higher for Trp‐CBQCA. The fluorescence of the Leu‐CBQCA derivative is 50 times more important than for Trp‐CBQCA. The addition of 7.5 mM of β‐cyclodextrin (β‐CD) was found to be a good mean to improve 2.1 fold the sensitivity of the Trp‐CBQCA fluorescence. Using a buffer containing SDS and β‐CD in CE, a LOD of 0.7 µM of L‐Trp can be reached and the ratio of the intensities between Leu, Isoleucine, Valine, Trp is 100, 21, 15, 1. Negative ESI^/MS and MS/MS of the labeled amino acids show that a loss of the carboxylate function takes place. In the presence of two enantiomers of Trp‐CBQCA, we have shown that this decarboxylation is not due to the derivatization process in the solution but rather occurs in the source of the mass spectrometer.     

Structure de La2Fe2S5 et de La2Fe1.87S5

The compound La₂Fe₂S₅ is orthorhombic. Cell parameters are: a = 3.997(2)Å; b = 16.485(5)Å; c = 11.394(4)Å. Space group is Cmc2₁ (Z = 4. In the cell, chains of polyedra comprised of sulfur atoms tetrahedrally or octahedrally coordinating centrally located iron atoms give a monodimensional character to the structure. This one is refined to R = 0.037. To complete the study of these chains, in the La₂Fe_2?xS₅ system, vacancies are introduced on iron atom sites. The ordered compound, La₂Fe_1.87S₅, having such vacancies, is an orthorhombic superstructure of the stoechiometric compound. Cell parameters are: a = 3.9996(5)Å; b = 49.508(3)Å; c = 11.308(3)Å. Space group is Cmc2₁ and Z = 12. The structure is refined to R = 0.068. Only two iron atom sites have vacancies. One is tetrahedral, the other octahedral. In this last case the chain deformations are the more important. The chain becomes a sort of tunnel made of atoms of sulfur, with in its center the short iron-iron separation of 2.82 Å.     

Zirconium deficiency in nasicon-type compounds: Crystal structure of Na5Zr(PO4)3

Single crystals of Na₅Zr(PO₄)₃ have been prepared using a flux method. At high temperature (200|MoC), the crystal structure can be described as a 3D network of PO₄ tetrahedra corner shared with ZrO₆ and NaO₆ octahedra. In fact, this compound belongs to the Nasicon-type class which exhibits a large nonstoichiometry range by zirconium deficiency.     

The multi-copy simultaneous search methodology: a fundamental tool for structure-based drug design

Fragment-based ligand design approaches, such as the multi-copy simultaneous search (MCSS) methodology, have proven to be useful tools in the search for novel therapeutic compounds that bind pre-specified targets of known structure. MCSS offers a variety of advantages over more traditional high-throughput screening methods, and has been applied successfully to challenging targets. The methodology is quite general and can be used to construct functionality maps for proteins, DNA, and RNA. In this review, we describe the main aspects of the MCSS method and outline the general use of the methodology as a fundamental tool to guide the design of de novo lead compounds. We focus our discussion on the evaluation of MCSS results and the incorporation of protein flexibility into the methodology. In addition, we demonstrate on several specific examples how the information arising from the MCSS functionality maps has been successfully used to predict ligand binding to protein targets and RNA.     

Near‐Infrared‐Emitting BODIPY‐trisDOTA111In as a Monomolecular Multifunctional Imaging Probe: From Synthesis to In Vivo Investigations

A new generation of monomolecular imaging probes (MOMIP) based on a distyryl‐BODIPY (BODIPY=boron‐dipyrromethene) coupled with three DOTA macrocycles has been prepared (DOTA=1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid). The MOMIP presents good fluorescence properties and is very stable in serum. The bimodal probe was conjugated to trastuzumab, and an optical in vivo study showed high accumulation of the imaging agent at the tumor site. ¹¹¹In radiometallation of the bioconjugate was performed in high radiochemical yield, highlighting the potential of this new BODIPY‐chelators derivative as a bimodal imaging probe.     

Strong Convergence Results for the Asymptotic Behavior of the 3D-Shell Model

We revisit the asymptotic convergence properties—with respect to the thickness parameter—of the earlier-proposed 3D-shell model. This shell model is very attractive for engineering applications, in particular due to the possibility of directly using a general 3D constitutive law in the corresponding finite element formulations. We establish strong convergence results for the 3D-shell model in the two main types of asymptotic regimes, namely, bending- and membrane-dominated behavior. This is an important achievement, as it completely substantiates the asymptotic consistency of the 3D-shell model with 3D linearized isotropic elasticity.