Synthesis and characterisation of biocompatible organic-inorganic core-shell nanocomposite particles based on ureasils.

Organic-inorganic core-shell nanocomposites have attracted increasing attention for applications in imaging, controlled release, biomedical scaffolds and self-healing materials. While tunable properties can readily be achieved through the selection of complementary building blocks, synergistic enhancement requires management of the core-shell interface. In this work, we report a one-pot method to fabricate hybrid core-shell nanocomposite particles (CSNPs) based on ureasils. The native structure of ureasils, which are poly(oxyalkylene)/siloxane hybrids, affords formation of an organic polymer core via nanoprecipitation, while the terminal siloxane groups act as a template for nucleation and growth of the silica shell via the Stöber process. Through optimisation of the reaction conditions, we demonstrate the reproducible synthesis of ureasil CSNPs, with a hydrodynamic diameter of ∼150 nm and polydispersity 50 days. Selective functionalisation, either through the physical entrapment of polarity-sensitive fluorescent probes (coumarin 153, pyrene) or covalent-grafting to the silica shell (fluorescein isothiocyanate) is also demonstrated and provides insight into the internal environment of the particles. Moreover, preliminary studies using a live/dead cell assay indicate that ureasil CSNPs do not display cytotoxicity. Given the simple fabrication method and the structural tunability and biocompatability of the ureasils, this approach presents an efficient route to multifunctional core-shell nanocomposite particles whose properties may be tailored for a targeted application

Insertion of fluorescent manganese compounds - models of catalase - into mesoporous nanoparticles of silica, resol-silica and carbon-silica

[eng] ROS (Reactive Oxygen Species), such as H2O2, HO● and O2-●, are naturally produced by the metabolism of living beings. However, they can appear in large quantities in the case of certain diseases (Alzheimer's, Parkinson's, sclerosis, cancer). Overproduction of ROS leads to higher cell mortality. Some microorganisms have an Mn-based enzyme capable of catalyzing the disproportionation reaction of H2O2 into O2 and H2O. Several molecules have been synthesized to reproduce this process, however very few of them are active in aqueous environment. Recently, polynuclear synthetic Mn species have been introduced into mesoporous silica to protect them from the environment. Thus, these complexes of Mn are stable and even see their catalytic activity increase. In order to persevere in this way, this thesis presents new compounds of formula [Mn(bpy)(AntCO2)2]n and [{Mn(bpy)(AntCO2)}2(µ-AntCO2)2(µ-OH2)] for MnII (chain and dinuclear respectively) and [Mn4O2(AntCO2)6(bpy)2(ClO4)2] for MnIII (tetranuclear) based on this concept. These compounds have two types of ligands, 2,2'-bipyridine, commonly found for similar compounds and 9-anthracene carboxylate, a fluorescent ligand added for theragnostic purposes. The resolution of the crystal structure of the MnII dinuclear compound shows a compression along the axis on the direction of the monodentate anthracene carboxylate. Moreover, by hydrolysis the one- dimensional system can be converted to the dinuclear compound. In the synthesis of the Mn(III) compound some oxidation of the anthracene is observed and two organic compounds are obtained, an anthraquinone and an ester formed by reaction between the quinone and the carboxylate. The manganese compounds were inserted into silica nanoparticles (NPs), resol (a polyphenol resin) -silica and carbon-silica hybrids in order to allow their vectorization and to study the compatibility of hybrid NPs with this type of system. This work explores the magnetic properties of the complexes and the luminescent properties of the coordination compounds and materials. The Mn(II) compounds show weak antiferromagnetic interaction, and the best way to differentiate these compounds is by EPR spectroscopy: the chain shows a unique band at g~2 while for the dinculear compound the spectrum is more complex, with several features at low fields. Magnetic properties of the Mn(III) compound confirms that it is a tetranuclear with butterfly type geometry with stronger antiferromagnetic interaction between the central ions than between central-terminal ions. The study of the porosity of the materials and the quantification of the presence of manganese inside the materials shows a good incorporation rate of the compounds. However it seems that the compounds are not present homogenously inside the support and that they are broken into smaller units. This is confirmed with the study of the magnetic properties of the hybrid [Mn]@NPs materials. In addition, fluoresecence measurement show that both the support and the compounds are luminescent but that both emission are strongly quenched when the compounds are inside the nanoparticles. The study of the optic properties of the materials show that a large amount of the compounds is released when the loaded silica and carbon-silica nanoparticles are redispersed in ethanol. However, resol-silica nanoparticles seem a lot more efficient to retain the complexes inside and apparently do not need further functionalization to achieve this goal. Finally, some preliminary test of disproportionation of H2O2 catalyzed by the manganese systems show low to moderate activity of Mn compounds in acetonitrile and paves the way for optimizing hybrid systems in aqueous media

Insertion de composés fluorescents du manganèse - modèles de la catalase – à l'intérieur de nanoparticules mésoporeuses de silice, résol-silice et carbone-silice

ROS (Reactive Oxygen Species), such as H2O2, HO● and O2-●, are naturally produced by themetabolism of living beings. However, they can appear in large quantities in the case of certaindiseases (Alzheimer's, Parkinson's, sclerosis, cancer). Overproduction of ROS leads to highercell mortality.Some microorganisms have an Mn-based enzyme capable of catalyzing the disproportionationreaction of H2O2 into O2 and H2O. Several molecules have been synthesized to reproduce thisprocess, however very few of them are active in aqueous environment. Recently, synthetic Mn species have been introduced into mesoporous silica to protect themfrom the environment. Thus, these complexes of Mn are stable and even see their catalyticactivity increase. In order to persevere in this way, this thesis presents new compounds ofMnII (dinuclear and chain) and MnIII (tetranuclear) based on this concept. They havefluorescent ligands (9-anthracene carboxylate), added for theragnostic purposes. Thesecompounds were inserted into silica nanoparticles (Nps), resol (a polyphenol resin) -silica andcarbon-silica hybrids in order to allow their vectorization and to study the compatibility ofhybrid NPs with this type of system.This work explores the magnetic properties of the complexes, the luminescent properties of thecompounds and materials and shows the good insertion of the compounds into the hybrid NPs,not requiring, in contrast to pure silica NPs, additional functionalization for the retention of thecomplexes. It also highlights the activity of Mn compounds in acetonitrile and paves the wayfor optimizing hybrid systems in aqueous media.Les ROS (Reactive Oxygen Species), tels H2O2, HO● et O2-●, sont produites naturellementpar le métabolisme des êtres vivants. Cependant, elles peuvent apparaître en trop grandesquantités dans le cas de certaines maladies (Alzheimer, Parkinson, scléroses, cancers). Lasurproduction de ROS conduit à une mortalité des cellules plus élevée.Certains micro-oragnismes possèdent une enzyme à base de Mn capable de catalyser laréaction de dismutation du H2O2 en O2 et H2O. Plusieurs molécules ont été synthétisées pourreproduire ce procédé, cependant très peu d'entre elle sont actives en environnement aqueux.Récemment, des espèces synthétiques du Mn ont été introduites dans des silicesvoient même leur activité catalytique augmenter. Afin de perséverer dans cette voie, cettethèse présente de nouveaux composés de MnII (dinucléaire et chaîne) et MnIII(tetranucléaire) basés sur ce concept. Ils sont dotés de ligands fluorescents, ajoutés pour desfin théragnostiques. Ces composés ont été insérés dans des nanoparticules (NPs) de silice ethybrides carbone-silice afin, de permettre leur vectorisation et d'étudier la compatibilité desNPs hybrides avec ce type de système.Le travail fourni explore les propriétés magnétiques des complexes, les propriétésluminescentes des composés et matériaux et montre la bonne insertion des composés dans lesNPs hybrides, ne nécessitant pas, contrairement aux NPs de silice pure, de fonctionnalisationsupplémentaire pour la rétention des complexes. Il met aussi en évidence l'activité descomposés du Mn dans l'acétonitrile et ouvre des pistes pour une optimisation des systèmeshybrides en milieu aqueux.Le travail fourni explore les propriétés magnétiques des complexes, les propriétésluminescentes des composés et matériaux et montre la bonne insertion des composés dans lesNPs hybrides, ne nécessitant pas, contrairement aux NPs de silice pure, de fonctionnalisationsupplémentaire pour la rétention des complexes. Il met aussi en évidence l'activité descomposés du Mn dans l'acétonitrile et ouvre des pistes pour une optimisation des systèmeshybrides en milieu aqueux

Reactivity of 9-anthracenecarboxylate in the presence of Mn(II) and Mn(III) ions: Biomimetic aerobic oxidative decarboxylation catalysed by a manganese(III) 2,2′-bipyridine complex

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Research data supporting "Synthesis and Characterisation of Biocompatible Organic- Inorganic Core-Shell Nanocomposite Particles based on Ureasils"

The folder “figure 3” contains dynamic light scattering data for CSNP’s made using method B showing the evolution of the hydrodynamic diameter, polydispersity and PDI as a function of time. The data points are an average of three values obtained for the samples. The folder “figure 4” contains tapping-mode AFM images of the CSNPs. (1,3) and (2,4) represent the same scale. (1,2) are height contrast images, whereas (3,4) are phase contrast images. The folder “figure 5” contains dynamic light scattering data for CSNPs made using method C (TEOS addition rate 60 µL/60mins and 10mM NH4OH solution) showing hydrodynamic diameter and polydispersity. The folder “figure 6” contains emission spectra for (a) Py@CSNPs and Py in water and ethanol (2.5x10-5 mol L-1) with (ex = 335nm), (c) C154 and C153@CSNPs after dialysis with (ex = 420 nm), (d) FITC@CSNPs before and after dialysis (ex = 465 nm). Also included is (b) I3/I1 ratio for Py@CSNPs over time and normalized intensity of the emission maximum of the excimer emission. The folder “figure 7” contains fluorescence microscopy images of a live/dead cell assay of HEK293 cells exposed to ureasil CSNPS for concentrations 0.001-1 mg/ml for 24 h. The folder “figure S2” contains dynamic light scattering data for CSNPs made using method A. Samples were prepared on different days. A correlogram and size distribution are given. The folder “figure S3” contains data showing the change in hydrodynamic diameter and polydispersity, recorder for CSNP’s mad using method A, with respect to time. Measurements were made using dynamic light scattering. The folder “figure S5” contains dynamic light scattering data showing the change in nanoparticle size and polydispersity for CSNPs prepared using method C. Samples differ by base concentration and TEOS addition rate. The folder “figure S6” contains I3/I1 fluorescence intensity ratios for pyrene in water/ethanol mixtures at different volume percentage of water (dye conc. = 2.5 × 10-5 mol L-1). λex = 335 nm. The folder “figure S7” contains normalized absorption, emission (λex = 420 nm) and excitation (λem = 550 nm) spectra of C153 in water and upon incorporation into CSNPs. (dye conc. = 3.6 × 10-5 mol L-1). The folder “figure S8” contains dynamic light scattering data showing the change in nanoparticle size and polydispersity for APTES and FTIC doped CSNPs. The folder “figure S9” contains time-resolved fluorescence data for FNa and FITC@CSNPs before and after dialysis. Also given are data fits with weighted residuals and instrument response functions

Strawberry marginal chlorosis (SMC): A disease of various bacterial and viral etiologies in France

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Incorporation of Manganese Complexes within HybridResol-Silica and Carbon-Silica Nanoparticles

The incorporation of a luminescent probe into a nano-vector is one of the approaches used to design chemosensors and nanocargos for drug delivery and theranostics. The location of the nanovector can be followed using fluorescence spectroscopy together with the change of environment that affects the fluorescence properties. The ligand 9-anthracene carboxylate is proposed in this study as a luminescent probe to locate two types of manganese complexes inside three series of porous nanoparticles of different composition: resol-silica, carbon-silica and pure silica. The manganese complexes are a tetranuclear MnIII cluster [MnIII 4 (µ-O)2 (µ-AntCO2 )6 (bpy)2 (ClO4 )2 ] with a butterfly core, and a MnII dinuclear complex [{MnII(bpy)(AntCO2 )}2 (µ-AntCO2 )2 (µ-OH2 )]. The magnetic measurements indicate that both complexes are present as dinuclear entities when incorporated inside the particles. Both the Mn complexes and the nanoparticles are luminescent. However, when the metal complexes are introduced into the nanoparticles, the luminescent properties of both are altered. The study of the fluorescence of the nanoparticles' suspensions and of the supernatants shows that MnII compounds seem to be more retained inside the particles than MnIII compounds. The resol-silica nanoparticles with MnII complexes inside is the material that presents the lowest complex leaching in ethanol