Polylutidines: Multifunctional Surfaces through Vaporâ Based Polymerization of Substituted Pyridinophanes

We report a new class of functionalized polylutidine polymers that are prepared by chemical vapor deposition polymerization of substituted [2](1,4)benzeno[2](2,5)pyridinophanes. To prepare sufficient amounts of monomer for CVD polymerization, a new synthesis route for ethynylpyridinophane has been developed in three steps with an overall yield of 59â %. Subsequent CVD polymerization yielded wellâ defined films of poly(2,5â lutidinyleneâ coâ pâ xylylene) and poly(4â ethynylâ 2,5â lutidinyleneâ coâ pâ xylylene). All polymers were characterized by infrared reflectionâ absorption spectroscopy, ellipsometry, contact angle studies, and Xâ ray photoelectron spectroscopy. Moreover, ζâ potential measurements revealed that polylutidine films have higher isoelectric points than the corresponding polyâ xylylene surfaces owing to the nitrogen atoms in the polymer backbone. The availability of reactive alkyne groups on the surface of poly(4â ethynylâ 2,5â lutidinyleneâ coâ pâ xylylene) coatings was confirmed by spatially controlled surface modification by means of Huisgen 1,3â dipolar cycloaddition. Compared to the more hydrophobic polyâ pâ xylylyenes, the presence of the heteroatom in the polymer backbone of polylutidine polymers resulted in surfaces that supported an increased adhesion of primary human umbilical vein endothelial cells (HUVECs). Vaporâ based polylutidine coatings are a new class of polymers that feature increased hydrophilicity and increased cell adhesion without limiting the flexibility in selecting appropriate functional side groups.Coat of many nitrogens! Chemical vapor deposition based polymers have been widely used as biomedical interfaces, but all of these coatings are restricted to simple allâ carbon backbones. For the first time, a class of functionalized lutidine polymers has been prepared by chemical vapor deposition (see figure). This reactive coating opens new perspectives for the design of new cell biomedical applications.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138923/1/chem201700901.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138923/2/chem201700901_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138923/3/chem201700901-sup-0001-misc_information.pd

Marine Biodiversity in South Africa: An Evaluation of Current States of Knowledge

Continental South Africa has a coastline of some 3,650 km and an Exclusive Economic Zone (EEZ) of just over 1 million km2. Waters in the EEZ extend to a depth of 5,700 m, with more than 65% deeper than 2,000 m. Despite its status as a developing nation, South Africa has a relatively strong history of marine taxonomic research and maintains comprehensive and well-curated museum collections totaling over 291,000 records. Over 3 million locality records from more than 23,000 species have been lodged in the regional AfrOBIS (African Ocean Biogeographic Information System) data center (which stores data from a wider African region). A large number of regional guides to the marine fauna and flora are also available and are listed

Continuous-flow synthesis of branched macromolecular architectures in microsystems : towards biomedical applications

Des architectures macromoléculaires branchées ont été synthétisées dans le but de développer des matériaux vecteurs de principes actifs. Dans un premier temps, une étude mécanistique a été réalisée en réacteur fermé afin de mieux comprendre la formation de ces architectures selon une technique de polymérisation contrôlée/’vivante’. L’efficacité de branchement présentait des limites, ce qui fut à l’origine du développement d’un microprocédé continu. Ce procédé microfluidique a permis d’accroître significativement la densité de l’architecture macromoléculaire. De plus, des bibliothèques de polymères, aux caractéristiques modulables, ont été générées et analysées grâce à une chromatographie d’exclusion stérique en ligne. Ce microprocédé, complété par un dispositif de nanoprécipitation du polymère synthétisé, a permis d’obtenir en continu une suspension colloïdale de nanoparticules d’environ 100 nm. La taille des nanoparticules pouvait être ajustée par les paramètres opératoires, notamment grâce à l’utilisation d’un micromélangeur, au sein duquel une étude de simulation numérique de l’hydrodynamique a aussi été réalisée. Ce procédé de nanoprécipitation, réalisé à haut débit, a ensuite été transposé à l’encapsulation d’un principe actif, les nanoparticules formulées constituant un système de délivrance de principe actif à diffusion contrôlée. Enfin, la synthèse de polymères sensibles au pH a été adaptée du précédent travail afin de développer des systèmes de délivrance localisée. Les caractéristiques macromoléculaires, telles que la masse molaire et l’architecture, ont montré un effet sur les propriétés de piégeage et libération d’un principe actif.Branched macromolecular architectures have been synthesized for the development of drug delivery systems. A mechanistic study has first been performed in batch reactors in order to understand the formation of branched polymers, conducted through a controlled polymerization technique, adapted from ATRP. Branching efficiency limitations led to the development of a continuous-flow microprocess, which enabled the production of denser branched architectures. In addition, polymer libraries have been conveniently generated and characterized, thanks to online GPC analyses. Furthermore, the continuous-flow microprocess has been upgraded by a new process unit aiming at inline polymer recovery in the form of nanoparticles suspension. This micromixer-assisted nanoprecipitation unit enabled to obtain size-controlled particles (average size around 100 nm) by tuning operating conditions. Micromixing also impacted the size of the nanoparticles as supported by hydrodynamics numerical simulations within the microstructure. Drug-loaded nanoparticles were then formulated at high polymer solution flow rate and led to diffusion-controlled drug delivery systems. Finally, the synthesis of pH-sensitive polymers has been adapted from the work conducted on the previous chemical system in order to consider targeted drug delivery. Macromolecular characteristics, such as molecular weight and architecture (linear vs. branched), impacted drug loading and release, operating at two different pH values

Synthèse d architectures macromoléculaires branchées selon un procédé continu microfluidique,vers des applications biomédicales

Des architectures macromoléculaires branchées ont été synthétisées dans le but de développer des matériaux vecteurs de principes actifs. Dans un premier temps, une étude mécanistique a été réalisée en réacteur fermé afin de mieux comprendre la formation de ces architectures selon une technique de polymérisation contrôlée/ vivante . L'efficacité de branchement présentait des limites, ce qui fut à l'origine du développement d'un microprocédé continu. Ce procédé microfluidique a permis d'accroître significativement la densité de l'architecture macromoléculaire. De plus, des bibliothèques de polymères, aux caractéristiques modulables, ont été générées et analysées grâce à une chromatographie d'exclusion stérique en ligne. Ce microprocédé, complété par un dispositif de nanoprécipitation du polymère synthétisé, a permis d'obtenir en continu une suspension colloïdale de nanoparticules d'environ 100 nm. La taille des nanoparticules pouvait être ajustée par les paramètres opératoires, notamment grâce à l'utilisation d'un micromélangeur, au sein duquel une étude de simulation numérique de l'hydrodynamique a aussi été réalisée. Ce procédé de nanoprécipitation, réalisé à haut débit, a ensuite été transposé à l'encapsulation d'un principe actif, les nanoparticules formulées constituant un système de délivrance de principe actif à diffusion contrôlée. Enfin, la synthèse de polymères sensibles au pH a été adaptée du précédent travail afin de développer des systèmes de délivrance localisée. Les caractéristiques macromoléculaires, telles que la masse molaire et l'architecture, ont montré un effet sur les propriétés de piégeage et libération d'un principe actif.Branched macromolecular architectures have been synthesized for the development of drug delivery systems. A mechanistic study has first been performed in batch reactors in order to understand the formation of branched polymers, conducted through a controlled polymerization technique, adapted from ATRP. Branching efficiency limitations led to the development of a continuous-flow microprocess, which enabled the production of denser branched architectures. In addition, polymer libraries have been conveniently generated and characterized, thanks to online GPC analyses. Furthermore, the continuous-flow microprocess has been upgraded by a new process unit aiming at inline polymer recovery in the form of nanoparticles suspension. This micromixer-assisted nanoprecipitation unit enabled to obtain size-controlled particles (average size around 100 nm) by tuning operating conditions. Micromixing also impacted the size of the nanoparticles as supported by hydrodynamics numerical simulations within the microstructure. Drug-loaded nanoparticles were then formulated at high polymer solution flow rate and led to diffusion-controlled drug delivery systems. Finally, the synthesis of pH-sensitive polymers has been adapted from the work conducted on the previous chemical system in order to consider targeted drug delivery. Macromolecular characteristics, such as molecular weight and architecture (linear vs. branched), impacted drug loading and release, operating at two different pH values

Synthèse d architectures macromoléculaires branchées selon un procédé continu microfluidique,vers des applications biomédicales

Des architectures macromoléculaires branchées ont été synthétisées dans le but de développer des matériaux vecteurs de principes actifs. Dans un premier temps, une étude mécanistique a été réalisée en réacteur fermé afin de mieux comprendre la formation dBranched macromolecular architectures have been synthesized for the development of drug delivery systems. A mechanistic study has first been performed in batch reactors in order to understand the formation of branched polymers, conducted through a contro

Synthèse d architectures macromoléculaires branchées selon un procédé continu microfluidique (vers des applications biomédicales)

Des architectures macromoléculaires branchées ont été synthétisées dans le but de développer des matériaux vecteurs de principes actifs. Dans un premier temps, une étude mécanistique a été réalisée en réacteur fermé afin de mieux comprendre la formation de ces architectures selon une technique de polymérisation contrôlée/ vivante . L efficacité de branchement présentait des limites, ce qui fut à l origine du développement d un microprocédé continu. Ce procédé microfluidique a permis d accroître significativement la densité de l architecture macromoléculaire. De plus, des bibliothèques de polymères, aux caractéristiques modulables, ont été générées et analysées grâce à une chromatographie d exclusion stérique en ligne. Ce microprocédé, complété par un dispositif de nanoprécipitation du polymère synthétisé, a permis d obtenir en continu une suspension colloïdale de nanoparticules d environ 100 nm. La taille des nanoparticules pouvait être ajustée par les paramètres opératoires, notamment grâce à l utilisation d un micromélangeur, au sein duquel une étude de simulation numérique de l hydrodynamique a aussi été réalisée. Ce procédé de nanoprécipitation, réalisé à haut débit, a ensuite été transposé à l encapsulation d un principe actif, les nanoparticules formulées constituant un système de délivrance de principe actif à diffusion contrôlée. Enfin, la synthèse de polymères sensibles au pH a été adaptée du précédent travail afin de développer des systèmes de délivrance localisée. Les caractéristiques macromoléculaires, telles que la masse molaire et l architecture, ont montré un effet sur les propriétés de piégeage et libération d un principe actif.Branched macromolecular architectures have been synthesized for the development of drug delivery systems. A mechanistic study has first been performed in batch reactors in order to understand the formation of branched polymers, conducted through a controlled polymerization technique, adapted from ATRP. Branching efficiency limitations led to the development of a continuous-flow microprocess, which enabled the production of denser branched architectures. In addition, polymer libraries have been conveniently generated and characterized, thanks to online GPC analyses. Furthermore, the continuous-flow microprocess has been upgraded by a new process unit aiming at inline polymer recovery in the form of nanoparticles suspension. This micromixer-assisted nanoprecipitation unit enabled to obtain size-controlled particles (average size around 100 nm) by tuning operating conditions. Micromixing also impacted the size of the nanoparticles as supported by hydrodynamics numerical simulations within the microstructure. Drug-loaded nanoparticles were then formulated at high polymer solution flow rate and led to diffusion-controlled drug delivery systems. Finally, the synthesis of pH-sensitive polymers has been adapted from the work conducted on the previous chemical system in order to consider targeted drug delivery. Macromolecular characteristics, such as molecular weight and architecture (linear vs. branched), impacted drug loading and release, operating at two different pH values.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Rôle du quorum-sensing et prévalence des bactériophages chez la bactérie phytostimulatrice Azospirillum

Le but de ce travail était d identifier les fonctions régulées par quorum-sensing (QS) chez la bactérie phytostimulatrice Azospirillum. Les effets phytobénéfiques in vitro des souches B518 et TVV3 (isolées du riz) ne sont pas altérées par l inactivation des molécules signal impliquées dans le QS. La combinaison d une approche ciblée et d une approche globale par protéomique montre que le QS régule des fonctions liées à l adaptation à la plante, notamment à la colonisation racinaire chez B518. Chez TVV3, aucune fonction régulée par QS n a pu être identifiée mais les gènes impliqués dans le QS sont localisés dans un environnement atypique, constitué de gènes prophagiques. La mise en évidence d un prophage chez TVV3 a conduit à la caractérisation de phages tempérés chez dix autres souches et au séquençage du premier génome d un bactériophage isolé d Azospirillum. Ce travail montre que la régulation de type QS est souche spécifique et révèle la prévalence des phages chez AzospirillumThe aim of this work was to identify quorum-sensing (QS) regulated functions in the phytobeneficial bacterium Azospirillum. Inactivation of signal molecules involved in QS has no deleterious effect on the in vitro phytostimulatory properties of strains B518 and TVV3 (isolated from rice). By combining a targeted approach and a global proteomic approach, QS was shown to regulate functions linked to adaptation to the plant, notably to root colonization, in strain B518. In strain TVV3, no QS-regulated function was identified but QS genes were localized in an atypical environment containing genes of prophage origin. The isolation of phage particles in strain TVV3 led to the characterization of temperate phages in ten other strains and to the sequencing of the first bacteriophage genome isolated from an Azospirillum strain. This work indicates that QS regulation is strain-specific and reveals bacteriophage prevalence in AzospirillumLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Micromixer-assisted polymerization processes

Mixing in polymerization processes is an extremely important issue as uneven mixing inevitably leads to the synthesis of polymer with undesired characteristics. Ontheotherhand, microeaction technology has enabled the development of extremely efficient micromixers which, within typical few milli seconds, allow mixing fluids at the microscale level. Recent developments in polymerization reaction engineering include the use of such micromixers to mix either initial reactants or reactive viscous solutions in multistep processes. Thus, polymerswithimprovedcontrolovertheirmolecular weights and molecular weight distributions, chemical compositions and architectures can be synthesized. Micromixers can also be used to open new operating windows in which controlled polymerization can be performed faster or underless stringent reaction conditions

Capnocytophaga canimorsus. interaction with the innate immune system

We show that Capnocytophaga canimorsus strain 5 (Cc5) is even more resistant to phagocytosis and killing by murine macrophages (J774.1) and human polymorphonuclear neutrophils (PMNs) than Yersinia enterocolitica, which is known as a model bacterium for resistance against phagocytosis due to its type 3 secretion system (Grosdent et al., 2002). We observed that Cc5 even becomes completely resistant to phagocytosis at high multiplicity of infection (moi of 50). In addition, we demonstrate that the Cc5 transposon mutant Y1C12, identified during a serum sensitivity screen, has an increased sensitivity to phagocytosis and killing by either murine macrophages or human PMNs even in the unopsonized state. This indicated that not an increased susceptibility for antibody binding or complement deposition led to an increased phagocytosis of the mutant, but that rather the outer surface was more readily recognized by the phagocytes. Furthermore, we demonstrate that Cc5 induces the formation of neutrophil extracellular traps upon infection of human PMNs in vitro and that Cc5 is trapped and killed within neutrophil extracellular traps, indicating sensitivity of Cc5 towards antimicrobial peptides present in PMN granules. Analysis of serum resistance in Cc5 revealed that serum resistance is probably linked to its lipopolysaccharide, which prevents deposition of the membrane attack complex on the bacterial surface. Moreover, we have observed that upon growth in the presence of cells, Cc5 releases or modifies factor(s) in the medium, which interfere with the killing ability of macrophages. Investigating the underlying mechanism, we could show that Cc5 does not affect phagosome maturation, but blocks the oxidative burst. This capacity was shown to depend on the release of the zinc metallopeptidase pitrilysin by Cc5. First analyses on the prevalence of the hypothetical virulence factors serum resistance and interference with the oxidative burst indicated that C. canimorsus strains might display strain variability. While 59% of the strains (50% of case strains, 61% of dog isolates) were able to block the killing ability of macrophages, 60% of the strains were highly serum resistant (100% of case strains, 54% of dog isolates). However, serum resistance could not be directly linked to a specific polysaccharide structure in C. canimorsus. November 2009, Salome Casutt-Meye

Mechanistic study of Atom Transfer Radical Polymerization in the Presence of an Inimer: Toward Highly Branched Controlled Macromolecular Architectures through One-Pot Reaction

Highly branched polymethacrylates have recently offered new perspectives in lithographic performance and drug delivery. The control of branching remains yet challenging and requires fundamental investigation to consider new applications. Therefore, an advanced study of the formation mechanism of branched polymers synthesized by self-condensing vinyl copolymerization (SCVCP) of a methacrylic AB* inimer, 2-(2-bromoisobutyryloxy)ethyl methacrylate (BIEM), with methyl methacrylate (MMA) via atom transfer radical polymerization (ATRP) has been performed. Evidence of branched structures was obtained with a conventional GPC apparatus equipped with a multiangle light scattering detector and detailed (1)H NMR analyses. A three-step reaction scheme is suggested according to the dependence of molecular weight with conversion. Controlled radical polymerization mainly occurs until moderate conversions, with the participation of inimer as chain initiator. Then the polymerization of small macromolecules, through consumption of polymerizable moiety, dramatically increases the molecular weight of polymer. Finally, a loss of control partially due to thermal decomposition of residual comonomers occurs at high conversion. This mechanistic methodology will allow, with adequate reaction process, the one-step preparation of controlled branched macromolecular architectures leading to functional materials