Mechanistic investigation of vinylic carbon-fluorine bond activation of perfluorinated cycloalkenes using Cp*2ZrH2 and Cp*2ZrHF

Cp*₂ZrH₂ (1) (Cp*: pentamethylcyclopentadienyl) reacts with cyclic perfluorinated olefins to give Cp*₂ZrHF (2) and hydrodefluorinated products under very mild conditions. Initial C-F bond activation occurs selectively at the vinylic positions of the cycloolefin to exchange fluorine for hydrogen. Several mechanisms are discussed for this H/F exchange: (a) olefin insertion/β-fluoride elimination, (b) olefin insertion/α-fluoride elimination, and (c) hydride/fluoride σ-bond metathesis. Following H/F σ-bond metathesis exchange of both vinylic C-F bonds of perfluorocyclobutene, 1 then reacts with allylic C-F bonds by insertion/β-fluoride elimination. A similar sequence is observed with perfluorocyclopentene. Cp*₂ZrHF reacts selectively with vinylic C-F bonds of perfluorocyclobutene to give 3,3,4,4-tetrafluorocyclobutene and Cp*₂ZrF₂ without further hydrodefluorination occurring. In the presence of excess 1 and H₂, perfluorocyclobutene and perfluorocyclopentene are reduced to cyclobutane and cyclopentane in 46% and 16% yield, respectively. DFT calculations exclude the pathway by way of the olefin insertion/α-fluoride elimination and suggest that the pathway by way of hydride/fluoride σ-bond metathesis is preferred.     

Surface modification of TiO2 nanoparticles with AHAPS aminosilane: distinction between physisorption and chemisorption

This paper addresses the surface modification of TiO₂ nanoparticles with n-(6-aminohexyl)aminopropyltrimethoxysilane (AHAPS) using various initial aminosilane concentrations. The main objective of this article is to show experimentally the importance of the physisorption during the grafting process. The distinction between chemisorbed and physisorbed aminosilane molecules on TiO₂ is thoroughly analyzed. The surface of bare and modified TiO₂ particles has been characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) to gain a better understanding of the adsorption mechanism of AHAPS on TiO₂. Quantitative information on surface energy of TiO₂, in terms of adsorption energy sites and heterogeneity, has been investigated by quasi-equilibrium low-pressure adsorption technique using nitrogen and argon as probe molecules. The FTIR and XPS data are combined to estimate and discuss the chemisorbed and physisorbed contribution. The results demonstrate that both physisorption and chemisorption occurs but they display a different behavior. The physisorbed amounts are much higher than the chemisorbed amounts. This shows that the main part of the adsorbed layer is composed of physisorbed molecules. The physisorbed uptake depends highly on the AHAPS concentration while the chemisorbed amount remains constant. Quasi-equilibrium Ar derivative adsorption isotherms reveal that the AHAPS molecules are mostly located on the {101} and {001} faces of titania and that the two faces display the same reactivity toward AHAPS sorption. Nitrogen adsorption experiments show that the sorption takes place on the three polar surface sites of high energy. The molecules are chemisorbed onto the site displaying the highest energy while they are physisorbed on the two lower energy sites.     

Multi-exponential analysis of magnitude MR images using a quantitative multispectral edge-preserving filter

A solution for discrete multi-exponential analysis of T(2) relaxation decay curves obtained in current multi-echo imaging protocol conditions is described. We propose a preprocessing step to improve the signal-to-noise ratio and thus lower the signal-to-noise ratio threshold from which a high percentage of true multi-exponential detection is detected. It consists of a multispectral nonlinear edge-preserving filter that takes into account the signal-dependent Rician distribution of noise affecting magnitude MR images. Discrete multi-exponential decomposition, which requires no a priori knowledge, is performed by a non-linear least-squares procedure initialized with estimates obtained from a total least-squares linear prediction algorithm. This approach was validated and optimized experimentally on simulated data sets of normal human brains.     

Effect of Thermal Treatment on the Textural Properties of CeO2 Powders Synthesized in Near‐ and Supercritical Alcohols

CeO₂ nanocrystals (NCs) have attracted increasing interest over the past few years, in particular for their use in catalytic reactions. Syntheses mediated by near‐ and supercritical alcohols have proven to be innovative ways to obtain CeO₂ NCs with controlled crystallite sizes (from 3 to 8 nm depending on the alcohol) and surface functionalities, with alcohol moieties. When submitted to a thermal treatment at 500 °C, required to desorb/degrade surface organic species, these powders displayed different behaviors depending on the alcohol used during the synthesis. Cerium oxide powders synthesized in sc‐MeOH, sc‐EtOH and sc‐iPrOH undergo sintering during treatment at 500 °C, with a decrease of their specific surface area. Conversely, those synthesized in sc‐BuOH, nc‐PentOH and nc‐HexOH keep their initial crystallite sizes and morphology, but show a great enhancement of their specific surface area (up to 200 m² g^?1), which is unprecedented after such a thermal treatment.     

Exploring the substrate specificity of OxyB, a phenol coupling P450 enzyme involved in vancomycin biosynthesis

OxyB is a cytochrome P450 enzyme that catalyzes the first oxidative phenol coupling reaction during vancomycin biosynthesis. The preferred substrate is a linear peptide linked as a C-terminal thioester to a peptide carrier protein (PCP) domain of the glycopeptide antibiotic non-ribosomal peptide synthetase. Previous studies have shown that OxyB can efficiently oxidize a model hexapeptide-PCP conjugate (R-Leu(1)-R-Tyr(2)-S-Asn(3)-R-Hpg(4)-R-Hpg(5)-S-Tyr(6)-S-PCP) (Hpg = 4-hydroxyphenylglycine) into a macrocyclic product by phenolic coupling of the aromatic rings in residues-4 and -6. In this work, the substrate specificity of OxyB has been explored using a series of N-terminally truncated peptides related in sequence to this model hexapeptide-PCP conjugate. Deletion of one or three residues from the N-terminus afforded a penta- (Ac-Tyr-Asn-Hpg-Hpg-Tyr-S-PCP) and a tri- (Ac-Hpg-Hpg-Tyr-S-PCP) peptide that were also efficiently transformed into the corresponding macrocyclic cross-linked product by OxyB. The tripeptide, representing the core of the macrocycle in vancomycin created by OxyB, is thus sufficient, as a thioester with the PCP domain, for phenol coupling to occur. The related tetrapeptide-PCP thioester was not cyclized by OxyB, neither was a related model hexapeptide containing tryptophan in place of tyrosine-6, nor were tripeptides (related to the natural product K-13) with the sequence Ac-Tyr-Tyr-Tyr-S-PCP cross-linked by OxyB.     

Validation of the M-C/H-C bond enthalpy relationship through application of density functional theory

Density functional theory has been used to calculate H-C and M-C bond dissociation enthalpies in order to evaluate the feasibility of correlating relative M-C bond enthalpies Delta H(M-C)rel with H-C bond enthalpies Delta H(H-C) via computational methods. This approach has been tested against two experimental correlations: a study of (a) Rh(H)(R)(Tp')(CNCH2CMe3) [R = hydrocarbyl, Tp' = HB(3,5-dimethylpyrazolyl)3] (Wick, D. D.; Jones, W. D. Organometallics 1999, 18, 495) and (b) Ti(R)(silox)2(NHSit-Bu3) (silox = OSit-Bu3) (Bennett, J. L.; Wolczanski, P. T. J. Am. Chem. Soc. 1997, 119, 10696). We show that the observation that M-C bond enthalpies increase more rapidly with different substituents than H-C bond enthalpies is reproduced by theory. Quantitative slopes of the correlation lines are reproduced within 4% of the experimental values with a B3PW91 functional and with very similar correlation coefficients. Absolute bond enthalpies are reproduced within 6% for H-C bonds, and relative bond enthalpies for M-C bonds are reproduced within 30 kJ mol(-1) for Rh-C bonds and within 19 kJ mol(-1) for Ti-C bonds. Values are also calculated with the BP86 functional.     

Measurements of the Protective Effect of Topically Applied Sunscreens using in vitro Three-dimensional Dermal and Skin Equivalents

Abstract— For preventing or minimizing acute and chronic skin damage caused by UV radiation, the use of sunscreens is probably the most important measure. To screen the protective efficacy of new sunscreen molecules or formulations against UV rays, we evaluated as in vitro testing methods the use of two three-dimensional models, a dermal equivalent (DE) and a skin equivalent (SE). The DE is composed of a porous collagen-glycosaminoglycans-chitosan matrix populated by normal human fibroblasts. The SE is comprised of a fully differentiated epidermis realized by seeding keratinocytes onto the DE. In this study, we demonstrated that the DE and SE models react to the deleterious effects of UVA and UVB. Then, we extended our research to the evaluation of their usefulness for photoprotection trials. Sunscreen agents (Euso-lex 8020 and 6300) and commercially available sunscreens (chemical and physical filter formulations) that protect the skin against either UVA or UVB were evaluated. The tested products were applied (n = 6) topically (10 μL) and incubated for 30 min prior to irradiation over a range of UVA (0-50 J/cm²) or UVB (0-5 J/cm²). The photoprotection provided by the tested sunscreen molecules and formulations was evaluated by measurement of residual cellular viability 24 h postirradiation using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide (MTT) test and assessment of the inflammation response by interleukin-la release assay. When sunscreens were applied prior to UV exposure, a higher residual cellular viability versus control was obtained, demonstrating the photoprotective effects of the tested products. These in vitro models could be used for screening tests to evaluate the protective effects of sunscreen molecules and formulations, especially for UVA trials because there is a lack of consensus for an in vivo method.     

Synthesis of the perovskite ceramic Li3xLa2/3–xTiO3 by a chemical solution route using a triblock copolymer surfactant

The synthesis of the perovskite Li_3xLa_2/3–x□_1/3–2xTiO₃ by a chemical solution route, using a triblock copolymer surfactant, PEO_n–PPO_m–PEO_n, is described. This titanate is a non-hygroscopic fast lithium conductor and therefore is a good candidate for electrochemical applications. It is generally prepared by a conventional solid-state reaction (SSR) method. However this synthesis method does not allow the preparation of nanopowders or the formation of thin films. For these special purposes, synthesis by a chemical solution route, with the formation of a polymeric precursor during synthesis, has been investigated. By using the above-mentioned non-ionic surfactant, the preparation of nanopowders of complex oxides can be done. Furthermore, this way of synthesis leads to the formation of an intermediate polymeric precursor which can be easily spread on substrates to obtain films. We show that the formation of a pure phase of the perovskite Li_3xLa_2/3–x□_1/3–2xTiO₃ is highly dependent on the synthesis conditions, namely the presence of water in the solvent, the EO/metal ratio, the Li⁺ content in the precursor and the calcination temperature. The influence of these parameters on the microstructure of the oxide is studied by X-ray diffraction, scanning electron microscopy and granulometry. A powder of Li_3xLa_2/3–x□_1/3–2xTiO₃ (x = 0.10), with an average particles size of 200 nm, has been obtained. The ionic conductivity of this oxide is the same as the one obtained with oxide prepared by SSR (a bulk conductivity of 1.4 × 10⁻³ S/cm at 37 °C). The ceramic obtained from this powder after sintering at 1,150 °C shows a good pH response. This material can then be used as a sensitive membrane in a potentiometric pH sensor. The presence of hydrophobic PPO groups in the polymer precursor allowed preparing films of Li_3xLa_2/3–x□_1/3–2xTiO₃ with a good adherence on Pt substrate. This kind of synthesis is then very promising to prepare micro pH sensors.     

Semi-synthesis of unusual chondroitin sulfate polysaccharides containing GlcA(3-O-sulfate) or GlcA(2,3-di-O-sulfate) units

The extraction from natural sources of Chondroitin sulfate (CS), a polysaccharide used for management of osteoarthritis, leads to very complex mixtures. The synthesis of CS by chemical modification of other polysaccharides has seldom been reported due to the intrinsic complexity that arises from fine chemical modifications of the polysaccharide structure. In view of the growing interest in expanding the application of CS to pharmacological fields other than osteoarthritis treatment, we launched a program to find new sources of known or even unprecedented CS polysaccharides. As part of this program, we report herein on an investigation of the use of a cyclic orthoester group to selectively protect the 4,6-diol of N-acetyl-galactosamine residues in chondroitin (obtained from a microbial source), thereby facilitating its transformation into CSs. In particular, three CS polysaccharides were obtained and demonstrated to possess rare or hitherto unprecedented sulfation patterns by 2D NMR spectroscopy characterization. Two of them contained disaccharide subunits characterized by glucuronic acid residues selectively sulfated at position 3 (GlcA(3S)), the biological functions of which are known but have yet to be fully investigated. This first semi-synthetic access to GlcA(3S)-containing CS could greatly expedite such studies, since it can easily furnish considerable amounts of these polysaccharides, which are usually isolated with difficulty and in very low quantity from natural sources.