Complexes d'or(I) et de platine(II) portant des ligands phospholes : synthèse et applications dans l'activation d'alcynes

L'activation homogène d'alcynes par des complexes d'or(I) et de platine(II) a connu un important essor ces 10 dernières années. Initialement, les sels métalliques, AuCl ou PtCl2, étaient utilisés. La conception de nouveaux ligands est primordiale afin d'améliorer l'activité, la sélectivité, mais aussi la stabilité des catalyseurs. Historiquement, des ligands phospholes sont utilisés au laboratoire pour développer des nouveaux outils catalytiques. C'est dans ce contexte que nous nous sommes intéressés aux applications des ligands phospholes dans l'activation d'alcyne. Des complexes d'or(I), [Au(L)Cl], et de platine(II), [Pt(L)2Cl2], portant des ligands phospholes ont été synthétisés. La caractérisation de ces complexes et l'étude de leurs structures ont permis de déterminer les propriétés stéréo-électroniques de ces ligands. Les complexes d'or(I) ont été engagés dans des réactions de cycloisomérisation d'1,6-énynes et de cyclopropanation d'oléfines. Le complexe portant le ligand 1-phényl-2,3,4,5-tétraméthylphosphole, [Au(TMP)Cl], s'est montré supérieur en activité, sélectivité, et stabilité. Un complexe cationique [Au(TMP)(CH3CN)]SbF6, particulièrement actif en cycloisomérisation d'1,6-énynes a aussi été isolé. Les complexes de platine(II) ont été testés dans les réactions de cycloisomérisation, d'alcoxy-cyclisation et d'hydroarylation cyclisante d'1,6-énynes. Le ligand TMP a permis ici aussi d'obtenir un catalyseur [Pt(TMP)2Cl2] d'activité supérieure. Une nouvelle réaction d'addition d'aldéhydes sur les 1,6-énynes catalysée au platine(II) a également été découverte donnant un accès direct à des structures hétérocycliques comportant trois cycles accolés. Nos travaux démontrent l'intérêt et la spécificité des ligands monophospholes et de leurs complexes d'Au(I) et de Pt(II) dans les réactions mettant en jeu une étape d'activation d'un alcyne, suivie d'une attaque nucléophile d'un alcène, d'un alcool, d'un aryle ou d'un aldéhyde. Ils tendent à rationaliser l'influence de la nature du ligand sur l'activité et la sélectivité du catalyseur, et ouvrent la voie au design de nouveaux outils de synthèse performants pour la préparation en une seule étape de structures polycycliques élaboréesHomogeneous alkyne activation by gold(I) and platinum(II) has witnesses an important growth in the past decade. Simple salts AuCl and PtCl2 have been initially used but the design of new ligands is essential to improve the activity, selectivity and stability of the catalysts. Phosphole ligands, and their application in catalysis is currently an important area of research in the team. In this context we decided to study these ligands in gold(I) and platinum(II) catalytic activation of alkynes. Gold(I) complexes [Au(L)Cl], and platinum(II) complexes,[Pt(L)2Cl2] bearing phosphole ligands have been synthesized. Their characterization, as well as the study of their structures, has allowed us to evaluate their stereo-electronical properties. Gold(I) complexes have been tested in 1,6-enyne cycloisomerization and olefin cyclopropanation reaction. 1-phenyl-2,3,4,5-tetramethylphosphole, TMP gave the best catalyst [Au(TMP)Cl]. It could also be isolated in its cationic form [Au(TMP)CH3CN]SbF6, which was found to be very active in 1,6-enyne cycloisomérisation. Platinum(II) complexes have been tested in cycloisomerization, alkoxy and hydroarylative cyclization of 1,6-enynes. The TMP ligand gave again the best catalyst [Pt(TMP)2Cl2]. During these catalytic trials, we also discovered a new platinum(II) catalyzed addition of aldehydes on 1,6-enynes. Our work shows how phosphole ligands and their gold(I) and platinum(II) complexes are specifics. In this study we also tried to rationalize ligand influence during the catalysis. This study allowed us to develop a new class of catalysts, which has opened to the design of new tools for p-acid catalysi

Gold(I) complexes bearing phosphole ligands: Synthesis and antimalarial activity

AbstractA series of gold(I)-monophosphole complexes have been synthesized and characterized. The introduction of a nitrogen moiety in the complex structure was envisioned either by choosing the bis(trifluoromethanesulfonyl)imidate ligand as the X-ligand or by preparing a new pyrrolidinophosphole ligand as the L-ligand. All the complexes have been evaluated in vitro for their antimalarial activity. These gold–phosphole complexes showed moderate activities with IC50 values ranging from 9.7 to 24 μM against Plasmodium falciparum chloroquine-resistant strains

WOLF: A modular estimation framework for robotics based on factor graphs

© 2022 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes,creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.This paper introduces WOLF, a C++ estimation framework based on factor graphs and targeted at mobile robotics. WOLF can be used beyond SLAM to handle self-calibration, model identification, or the observation of dynamic quantities other than localization. The architecture of WOLF allows for a modular yet tightly-coupled estimator. Modularity is enhanced via reusable plugins that are loaded at runtime depending on application setup. This setup is achieved conveniently through YAML files, allowing users to configure a wide range of applications without the need of writing or compiling code. Most procedures are coded as abstract algorithms in base classes with varying levels of specialization. Overall, all these assets allow for coherent processing and favor code re-usability and scalability. WOLF can be used with ROS, and is made publicly available and open to collaboration.Peer ReviewedPostprint (author's final draft

Targeted Magnetic Intra-Lysosomal Hyperthermia produces lysosomal reactive oxygen species and causes Caspase-1 dependent cell death

Therapeutic strategies using drugs which cause Lysosomal Cell Death have been proposed for eradication of resistant cancer cells. In this context, nanotherapy based on Magnetic Intra-Lysosomal Hyperthermia (MILH) generated by magnetic nanoparticles (MNPs) that are grafted with ligands of receptors overexpressed in tumors appears to be a very promising therapeutic option. However, mechanisms whereby MILH induces cell death are still elusive. Herein, using Gastrin-grafted MNPs specifically delivered to lysosomes of tumor cells from different cancers, we provide evidences that MILH causes cell death through a non-apoptotic signaling pathway. The mechanism of cell death involves a local temperature elevation at the nanoparticle periphery which enhances the production of reactive oxygen species through the lysosomal Fenton reaction. Subsequently, MILH induces lipid peroxidation, lysosomal membrane permeabilization and leakage of lysosomal enzymes into the cytosol, including Cathepsin-B which activates Caspase-1 but not apoptotic Caspase-3. These data highlight the clear potential of MILH for the eradication of tumors overexpressing receptors

Development of immunoassays for the detection of kanamycin in veterinary fields

Monoclonal antibody against kanamycin was prepared, and competitive direct ELISA and immunochromatographic assay were developed using the antibody to detect kanamycin in animal plasma and milk. The monoclonal antibody produced was identified to be IgG1, which has a kappa light chain. No cross-reactivity of the antibody was detected with other aminoglycosides, indicating that the monoclonal antibody was highly specific for kanamycin. Based on competitive direct ELISA, the detection limits of kanamycin were determined to be 1.1 ng/ml in PBS, 1.4 ng/ml in plasma, and 1.0 ng/ml in milk. The concentration of intramuscularly injected kanamycin was successfully monitored in rabbit plasma with competitive direct ELISA. Based on the colloidal gold-based immunochromatographic assay, the detection limits of kanamycin were estimated to be about 6-8 ng/ml in PBS, plasma, and milk. The immunochromatographic assay would be suitable for rapid and simple screening of kanamycin residues in veterinary medicine. Screened positives can be confirmed using a more sensitive laboratory method such as competitive direct ELISA. Therefore, the assays developed in this study could be used to complement each other as well as other laboratory findings. Moreover, instead of slaughtering the animals to obtain test samples, these methods could be applied to determine kanamycin concentration in the plasma of live animals

Solution structure of a let-7 miRNA:lin-41 mRNA complex from C. elegans

let-7 microRNA (miRNA) regulates heterochronic genes in developmental timing of the nematode Caenorhabditis elegans. Binding of miRNA to messenger RNA (mRNA) and structural features of the complex are crucial for gene silencing. We herein present the NMR solution structure of a model mimicking the interaction of let-7 miRNA with its complementary site (LCS 2) in the 3′ untranslated region (3′-UTR) of the lin-41 mRNA. A structural study was performed by NMR spectroscopy using NOE restraints, torsion angle restraints and residual dipolar couplings. The 33-nt RNA construct folds into a stem–loop structure that features two stem regions which are separated by an asymmetric internal loop. One of the stems comprises a GU wobble base pair, which does not alter its overall A-form RNA conformation. The asymmetric internal loop adopts a single, well-defined structure in which three uracils form a base triple, while two adenines form a base pair. The 3D structure of the construct gives insight into the structural aspects of interactions between let-7 miRNA and lin-41 mRNA

Systematic analysis of the entire second extracellular loop of the V 1a vasopressin receptor :Key residues, conserved throughout a G-protein-coupled receptor family, identified

The roles of extracellular residues of G-protein-coupled receptors (GPCRs) are not well defined compared with residues in transmembrane helices. Nevertheless, it has been established that extracellular domains of both peptide-GPCRs and amine-GPCRs incorporate functionally important residues. Extracellular loop 2 (ECL2) has attracted particular interest, because the x-ray structure of bovine rhodopsin revealed that ECL2 projects into the binding crevice within the transmembrane bundle. Our study provides the first comprehensive investigation into the role of the individual residues comprising the entire ECL2 domain of a small peptide-GPCR. Using the V1a vasopressin receptor, systematic substitution of all of the ECL2 residues by Ala generated 30 mutant receptors that were characterized pharmacologically. The majority of these mutant receptor constructs (24 in total) had essentially wild-type ligand binding and intracellular signaling characteristics, indicating that these residues are not critical for normal receptor function. However, four aromatic residues Phe189, Trp206, Phe209, and Tyr218 are important for agonist binding and receptor activation and are highly conserved throughout the neurohypophysial hormone subfamily of peptide-GPCRs. Located in the middle of ECL2, juxtaposed to the highly conserved disulfide bond, Trp206 and Phe209 project into the binding crevice. Indeed, Phe209 is part of the Cys-X-X-X-Ar (where Ar is an aromatic residue) motif, which is well conserved in both peptide-GPCRs and amine-GPCRs. In contrast, Phe189 and Tyr218, located at the extreme ends of ECL2, may be important for determining the position of the ECL2 cap over the binding crevice. This study provides mechanistic insight into the roles of highly conserved ECL2 residues

Competence in Streptococcus pneumoniae Is Regulated by the Rate of Ribosomal Decoding Errors

Competence for genetic transformation in Streptococcus pneumoniae develops in response to accumulation of a secreted peptide pheromone and was one of the initial examples of bacterial quorum sensing. Activation of this signaling system induces not only expression of the proteins required for transformation but also the production of cellular chaperones and proteases. We have shown here that activity of this pathway is sensitively responsive to changes in the accuracy of protein synthesis that are triggered by either mutations in ribosomal proteins or exposure to antibiotics. Increasing the error rate during ribosomal decoding promoted competence, while reducing the error rate below the baseline level repressed the development of both spontaneous and antibiotic-induced competence. This pattern of regulation was promoted by the bacterial HtrA serine protease. Analysis of strains with the htrA (S234A) catalytic site mutation showed that the proteolytic activity of HtrA selectively repressed competence when translational fidelity was high but not when accuracy was low. These findings redefine the pneumococcal competence pathway as a response to errors during protein synthesis. This response has the capacity to address the immediate challenge of misfolded proteins through production of chaperones and proteases and may also be able to address, through genetic exchange, upstream coding errors that cause intrinsic protein folding defects. The competence pathway may thereby represent a strategy for dealing with lesions that impair proper protein coding and for maintaining the coding integrity of the genome