Catalytic amination of lactic acid using Ru-zeolites.

In this work we investigate the synthesis of alanine from lactic acid, a biobased platform chemical, using ammonia as a nitrogen source and Ru/zeolite catalysts. We report a high alanine selectivity when using Ru/BEA of 80-93%. Reaction side products were identified as ethanol, propionic acid or propanamide and the reaction mechanism was investigated. We further optimised reaction conditions resulting in turn over numbers five times higher than previously reported and could reduce Ru leaching by 30-40%. However, leaching and catalyst stability remains a concern. Furthermore, we critically analyse the benefits of Ru/zeolites versus their stability under the basic, high temperature reaction conditions.

Polymeric Microspheres/Cells/Extracellular Matrix Constructs Produced by Auto-Assembly for Bone Modular Tissue Engineering.

Modular tissue engineering (MTE) is a novel "bottom-up" approach to create engineered biological tissues from microscale repeating units. Our aim was to obtain microtissue constructs, based on polymer microspheres (MSs) populated with cells, which can be further assembled into larger tissue blocks and used in bone MTE. Poly(L-lactide-co-glycolide) MS of 165 ± 47 µm in diameter were produced by oil-in-water emulsification and treated with 0.1 M NaOH. To improve cell adhesion, MSs were coated with poly-L-lysine (PLL) or human recombinant collagen type I (COL). The presence of oxygenated functionalities and PLL/COL coating on MS was confirmed by X-ray photoelectron spectroscopy (XPS). To assess the influence of medium composition on adhesion, proliferation, and osteogenic differentiation, preosteoblast MC3T3-E1 cells were cultured on MS in minimal essential medium (MEM) and osteogenic differentiation medium (OSG). Moreover, to assess the potential osteoblast-osteoclast cross-talk phenomenon and the influence of signaling molecules released by osteoclasts on osteoblast cell culture, a medium obtained from osteoclast culture (OSC) was also used. To impel the cells to adhere and grow on the MS, anti-adhesive cell culture plates were utilized. The results show that MS coated with PLL and COL significantly favor the adhesion and growth of MC3T3-E1 cells on days 1 and 7, respectively, in all experimental conditions tested. On day 7, three-dimensional MS/cell/extracellular matrix constructs were created owing to auto-assembly. The cells grown in such constructs exhibited high activity of early osteogenic differentiation marker, namely, alkaline phosphatase. Superior cell growth on PLL- and COL-coated MS on day 14 was observed in the OSG medium. Interestingly, deposition of extracellular matrix and its mineralization was particularly enhanced on COL-coated MS in OSG medium on day 14. In our study, we developed a method of spontaneous formation of organoid-like MS-based cell/ECM constructs with a few millimeters in size. Such constructs may be regarded as building blocks in bone MTE.

CO2 Hydrogenation to Methanol with Ga- and Zn-Doped Mesoporous Cu/SiO2 Catalysts Prepared by the Aerosol-Assisted Sol-Gel Process*.

The preparation of copper-based heterogeneous catalysts dedicated to the hydrogenation of CO2 to methanol typically relies on multi-step procedures carried out in batch. These steps are precisely tailored to introduce the active phase (Cu) and the promoters (e. g., zinc, gallium) onto a preformed support to maximize catalyst performance. However, each process step can be associated with the formation of waste and with the consumption of energy, thereby negatively impacting the environmental performance of the overall catalyst preparation procedure. Here, a direct and continuous production process is proposed for the synthesis of efficient catalysts for the CO2 -to-methanol reaction. Gallium- and zinc-promoted mesoporous Cu-SiO2 catalysts were prepared in one step by the aerosol-assisted sol-gel process. The catalysts consisted of spherical microparticles and featured high specific surface area and pore volume, with interconnected pores of about 6 nm. A strong promoting effect of Ga and Zn was highlighted, boosting the selectivity for methanol at the expense of CO. Upon calcination, it was shown that Cu species (initially trapped in the silica matrix) underwent a migration towards the catalyst surface and a progressive sintering. After optimization, the catalysts obtained via such direct, continuous, simple, and scalable route could compete with the best catalysts reported in the literature and obtained via multi-step approaches.

Reversible Protein Adsorption on Mixed PEO/PAA Polymer Brushes: Role of Ionic Strength and PEO Content.

Proteins at interfaces are a key for many applications in the biomedical field, in biotechnologies, in biocatalysis, in food industry, etc. The development of surface layers that allow to control and manipulate proteins is thus highly desired. In previous works, we have shown that mixed polymer brushes combining the protein-repellent properties of poly(ethylene oxide) (PEO) and the stimuli-responsive adsorption behavior of poly(acrylic acid) (PAA) could be synthesized and used to achieve switchable protein adsorption. With the present work, we bring more insight into the rational design of such smart thin films by unravelling the role of PEO on the adsorption/desorption of proteins. The PEO content of the mixed PEO/PAA brushes was regulated, on the one hand, by using PEO with different molar masses and, on the other hand, by varying the ratio of PEO and PAA in the solutions used to synthesize the brushes. The influence of ionic strength on the protein adsorption behavior was also further examined. The behavior of three proteins-human serum albumin, lysozyme, and human fibrinogen, which have very different size, shape, and isoelectric point-was investigated. X-ray photoelectron spectroscopy, quartz crystal microbalance, atomic force microscopy, and streaming potential measurements were used to characterize the mixed polymer brushes and, in particular, to estimate the fraction of each polymer within the brushes. Protein adsorption and desorption conditions were selected based on previous studies. While brushes with a lower PEO content allowed the higher protein adsorption to occur, fully reversible adsorption could only be achieved when the PEO surface density was at least 25 PEO units per nm2. Taken together, the results increase the ability to finely tune protein adsorption, especially with temporal control. This opens up possibilities of applications in biosensor design, separation technologies, nanotransport, etc.

Proteins dominate in the surface layers formed on materials exposed to extracellular polymeric substances from bacterial cultures.

The chemical compositions of the surface conditioning layers formed by different types of solutions (from isolated EPS to whole culture media), involving different bacterial strains relevant for biocorrosion were compared, as they may influence the initial step in biofilm formation. Different substrata (polystyrene, glass, steel) were conditioned and analyzed by X-ray photoelectron spectroscopy. Peak decomposition and assignment were validated by correlations between independent spectral data and the ubiquitous presence of organic contaminants on inorganic substrata was taken into account. Proteins or peptides were found to be a major constituent of all conditioning layers and polysaccharides were not present in appreciable concentrations; the proportion of nitrogen which may be due to DNA was lower than 15%. There was no significant difference between the compositions of the adlayers formed from different conditioning solutions, except for the adlayers produced with tightly bound EPS extracted from D. alaskensis.

Minimal amounts of dipalmitoylphosphatidylcholine improve aerosol performance of spray-dried temocillin powders for inhalation.

Administration of antibiotics by inhalation can greatly improve drug targeting to the site of respiratory infections. In addition, dry powder inhalers are particularly convenient for the patients. The purposes of this study were to demonstrate the interest of pulmonary temocillin delivery to reach high temocillin concentrations locally in the lungs as well as to prepare a spray-dried temocillin powder for inhalation using a minimal amount of generally recognized as safe excipients. Intratracheal instillation of a temocillin solution allowed to reach higher and more sustained drug concentrations in the lungs than intravenous injection in mice, although a 10-fold lower temocillin dose was delivered intratracheally than systemically. A spray-dried powder of pure temocillin presented a fine particle fraction of 9% of the dose loaded in the inhaler. However, the incorporation of 0.5% to 20% of dipalmitoylphosphatidylcholine (DPPC) in the powder increased the fine particle fraction 4- to 5-fold. X-ray photoelectron spectroscopy and X-ray diffraction revealed that DPPC concentrated at the particle surface with its aliphatic chains laterally packed. The minimal amount of DPPC needed to improve the aerosol performance of temocillin supports the use of this excipient in the formulation of cohesive antibiotic powders for inhalation.

Polythiolactone-based redox-responsive layers for the reversible release of functional molecules.

The development of thin macromolecular layers with incorporated disulfide bonds that can be disrupted and formed again under redox stimulation is of general interest for drug release applications, because such layers can provide rapid and reversible responses to specific biological systems and signals. However, the preparation of such layers from polythiols remains difficult, because of the fast oxidation of thiol groups in ambient conditions. Here we propose water-soluble thiolactone-containing copolymers as stable precursors containing protected thiol groups, allowing us to produce on demand polythiol layers on gold substrates in the presence of amine derivatives. Electrochemical, water contact angle, X-ray photoelectron spectroscopy, and X-ray reflectometry measurements evidence the formation of uniform copolymer layers containing both anchored and free thiol groups. The number of free thiols increases with the content of thiolactone units in the copolymers. In a second step, a thiolated dye, used as a model drug, was successfully grafted on the free thiol groups through disulfide bonds using mild oxidizing conditions, as proved by fluorescence and quartz crystal microbalance measurements. Finally, the reversible release/regrafting of the dye under redox stimulation is demonstrated.

Controlling the dispersion of supported polyoxometalate heterogeneous catalysts: impact of hybridization and the role of hydrophilicity-hydrophobicity balance and supramolecularity.

The hybridization of polyoxometalates (POMs) through an organic-inorganic association offers several processing advantages in the design of heterogeneous catalysts. A clear understanding of the organization of these hybrid materials on solid surfaces is necessary to optimise their properties. Herein, we report for the first time the organization of Keggin phosphotungstic [PW12O40](3-) and Wells-Dawson (WD) phosphomolybdic [P2Mo18O62](6-) anions deposited on mica (hydrophilic), and highly oriented pyrolytic graphite (HOPG) (hydrophobic) surfaces. Next, the supramolecular organization of the organic-inorganic hybrid materials formed from the association of POM anions and dimethyldioctadecylammonium bromide (DODA) is investigated as a function of the hydrophilic or hydrophobic nature of the surfaces. The height of the Keggin-POM anions, measured with tapping mode (TM-AFM) is always in good agreement with the molecular dimension of symmetric Keggin-POM anions (ca. 1 nm). However, the asymmetric WD-POM anions form monolayer assemblies on the surfaces with the orientation of their long molecular axis (ca. 1.6 nm) depending on the hydrophilic or hydrophobic properties of the substrate. Namely, the long axis is parallel on mica, and perpendicular on HOPG. When hybridized with DODA, the organization of the hybrid material is dictated by the interaction of the alkyl side chains of DODA with the substrate surface. On HOPG, the DODA-POM hybrid forms small domains of epitaxially arranged straight nanorod structures with their orientation parallel to each other. Conversely, randomly distributed nanospheres are formed when the hybrid material is deposited on freshly cleaved mica. Finally, a UV-ozone treatment of the hybrid material allows one to obtain highly dispersed isolated POM entities on both hydrophilic and hydrophobic surfaces. The hybridization strategy to prevent the clustering of POMs on various supports would enable to develop highly dispersed POM-based heterogeneous catalysts with enhanced functionalities.

In vitro lipolysis and intestinal transport of ß-arteether-loaded lipid-based drug delivery systems.

PURPOSE: We aimed to assess the fate of ß-arteether lipid-based drug delivery systems (AE-LBDDS) in terms of resistance to lipolysis and permeation across intestinal cells. METHODS: AE-LBDDS contained Tween 80 or Cremophor EL as surfactants, ethanol, Maisine 35-1 and vegetable oil. The solubilization behavior of AE was investigated during dynamic in vitro lipolysis. The permeation of AE-LBDDS was evaluated using Caco-2, HT29-MTX and M cell monolayers. RESULTS: A higher level of AE precipitation was observed for formulations containing Cremophor EL (~30%) compared to formulations containing Tween 80 (~10%) after lipolysis. However, rapid re-dissolution of the precipitated AE from LBDDS containing Cremophor EL in the intestinal biorelevant media was observed. The transport of AE loaded in LBDDS was enhanced in comparison to that of free drug due to the increased AE solubility. The apparent permeability of all AE-LBDDS across Caco-2 cell monolayers was approximately 3.10(-6) cm/s. A decrease in the permeability was observed at 4°C. M cells did not influence the transport of AE-LBDDS, and mucus decreased AE permeability when formulated with Tween 80. Furthermore, AE is not a P-glycoprotein substrate. CONCLUSION: LBDDS that are partly resistant to in vitro lipolysis significantly increased the transport of AE across intestinal cell monolayers.

Tuning the acid/metal balance of carbon nanofiber-supported nickel catalysts for hydrolytic hydrogenation of cellulose.

Carbon nanofibers (CNFs) are a class of graphitic support materials with considerable potential for catalytic conversion of biomass. Earlier, we demonstrated the hydrolytic hydrogenation of cellulose over reshaped nickel particles attached at the tip of CNFs. The aim of this follow-up study was to find a relationship between the acid/metal balance of the Ni/CNFs and their performance in the catalytic conversion of cellulose. After oxidation and incipient wetness impregnation with Ni, the Ni/CNFs were characterized by various analytical methods. To prepare a selective Ni/CNF catalyst, the influences of the nature of oxidation agent, Ni activation, and Ni loading were investigated. Under the applied reaction conditions, the best result, that is, 76 % yield in hexitols with 69 % sorbitol selectivity at 93 % conversion of cellulose, was obtained on a 7.5 wt % Ni/CNF catalyst prepared by chemical vapor deposition of CH(4) on a Ni/γ-Al(2)O(3) catalyst, followed by oxidation in HNO(3) (twice for 1 h at 383 K), incipient wetness impregnation, and reduction at 773 K under H(2). This preparation method leads to a properly balanced Ni/CNF catalyst in terms of Ni dispersion and hydrogenation capacity on the one hand, and the number of acidic surface-oxygen groups responsible for the acid-catalyzed hydrolysis on the other.

Formation of ZSM-22 zeolite catalytic particles by fusion of elementary nanorods.

An ZSM-22 aluminosilicate zeolite was synthesized using the hydrothermal gel method at 150 degrees C. Products obtained after different synthesis times were characterized using various techniques and catalytic testing. Massive formation of ZSM-22 nanocrystals occurs after only a short synthesis time, appearing as isolated rods with a cross section of 12+/-4 nm. Nanorods have aluminum enriched at their external surface. Later in the crystallization process nanorods align and fuse sideways, whereby the external surface is systematically converted into an internal micropore surface. The formation of aluminum bearing micropores by the joining of nanorod surfaces is responsible for the enhanced catalytic activity. For this, the zeolite synthesis of nanoscale crystallites is ineffective for enhancing catalytic activity.