Oxidation of organic molecules in homogeneous aqueous solution catalyzed by hybrid biocatalysts (based on the Trojan Horse strategy)

New anionic metalloporphyrin–estradiol conjugates have been synthesized and fully characterized, and have been further associated to a monoclonal anti-estradiol antibody 7A3, to generate new artificial metalloenzymes following the so-called ‘Trojan Horse’ strategy. The spectroscopic characteristics and dissociation constants of these complexes were similar to those obtained for the artificial metalloproteins obtained by association of cationic metalloporphyrin–estradiol conjugates to 7A3. This demonstrates that the nature of the porphyrin substituents, anionic or cationic, had little influence on the association with the antibody that is mainly driven by the tight association of the estradiol anchor with the binding pocket of the antibody.These new biocatalysts appeared to have an interesting catalytic activity in oxidation reactions. The iron(III)–anionic-porphyrin–estradiol-antibody complexes were found able to catalyze the chemoselective and slightly enantioselective (ee = 10%) sulfoxidation of sulfides by H₂O₂. The Mn(III)–porphyrin–estradiol-antibody complexes were found to catalyze the oxidation of styrene by KHSO₅, the Mn(III)–cationic-porphyrin–estradiol-antibody complexes even showing the highest yields so far reported for the oxidation of styrene catalyzed by artificial metalloproteins. However, a lack of chemoselectivity and enantioselectivity was observed, which was probably due to a weak interaction of the metalloporphyrin cofactor with the binding pocket of antibody 7A3, as suggested by the similar UV–visible characteristics and catalytic activities obtained with both anionic and cationic porphyrins.     

Cyclic C-amino phosphorus ylides as a source of bidentate heteroditopic ligands (phosphine/aminocarbene) for transition metals

In contrast with most of their congeners, acyclic and cyclic C-amino phosphorus ylides behave as genuine carbene and phosphine transfer agents for transition metal centers. They allow the facile synthesis of a variety of metal complexes that feature heteroditopic ligands, such as 1,6-(phosphine)(aminocarbene) systems with a biphenyl backbone.     

Detecting the chemoselective ligation of peptides to silicon with the use of cobalt-carbonyl labels

While fluorescent-based methods are generally used to detect the immobilization and the interactions of biomolecules to solid supports, recent studies have shown their limitations in the case of silicon surfaces. As an alternative, we investigated the synthesis of peptides labeled with a metal transition complex and their subsequent immobilization to the silicon surfaces. The feasibility of using such probes has been explored by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). By starting with hydrogen-terminated or oxidized silicon surfaces, we functionalized those surfaces with semicarbazide groups and showed the site-specific linkage of glyoxylyl peptides labeled with a Co2(CO)6 moiety.     

Multivalent RGD synthetic peptides as potent alphaVbeta3 integrin ligands

We study herein the multivalency effect of a cluster of alphaVbeta3-ligands held on a cyclodecapeptide template. An array of RAFT(c[-RGDfK-])n derivatives containing from one to sixteen clustered RGD motifs were synthesized and comparatively assayed in vitro on alphaVbeta3-expressing cells. Efficient inhibition of the alphaVbeta3-specific 23C6 monoclonal antibody fixation was observed with ligands displaying three and four copies of the cyclo[-RGDfK-] peptide.     

Similarity of salt influences on the pH of buffers, polyelectrolytes, and proteins

Changes in pH induced by the addition of electrolytes to buffers, polyelectrolytes (a polycarboxy polymethylene and a polyethyleneimine), and proteins (casein, whey, and lysozyme) solutions are explored systematically. The two buffer systems are triethanolamine/triethanolammonium chloride and citric acid/sodium citrate. These are chosen because of the similarity of their acid-base equilibria with those of amino acids predominant in most proteins, that is, amino acids that include carboxylate or ammonium groups in their structures. The pH of triethanolamine and of citrate buffers respectively increases and decreases when salt is added. At low electrolyte concentrations (<0.15 mol/kg), the phenomenon is well accounted for by standard electrostatic theories. pH values at higher salt concentrations are not reliable when measured with a commercial glass electrode without cross-checking by a standard hydrogen electrode. The changes of the pH values of polyelectrolyte and protein solutions with added salts turn out to be remarkably similar to the salt induced pH changes in the buffer solutions. It is even possible to qualitatively predict these changes in protein solutions simply from the primary protein structure. At least in the systems considered here, the specific ion effects on pH seem to correlate with the bulk activity coefficients of the added electrolytes, at least at moderate salt concentrations.     

A one-pot synthesis of a 243-allyl dendrimer under ambient conditions

[reaction: see text] Hydrosilylation of a nonaallyl dendritic core using HSi(Me)(2)Cl followed by reaction with a phenolate dendronic brick bearing three allyl groups, followed by repetition of this sequence of reactions twice, allows a one-pot synthesis of a 243-allyl dendrimer under ambient conditions.     

X-ray absorption spectroscopy of Mn/Co/TiO2 Fischer-Tropsch catalysts: relationships between preparation method, molecular structure, and catalyst performance

The effects of the addition of manganese to a series of TiO(2)-supported cobalt Fischer-Tropsch (FT) catalysts prepared by different methods were studied by a combination of X-ray diffraction (XRD), temperature-programmed reduction (TPR), transmission electron microscopy (TEM), and in situ X-ray absorption fine structure (XAFS) spectroscopy at the Co and Mn K-edges. After calcination, the catalysts were generally composed of large Co(3)O(4) clusters in the range 15-35 nm and a MnO(2)-type phase, which existed either dispersed on the TiO(2) surface or covering the Co(3)O(4) particles. Manganese was also found to coexist with the Co(3)O(4) in the form of Co(3-x)Mn(x)O(4) solutions, as revealed by XRD and XAFS. Characterization of the catalysts after H(2) reduction at 350 degrees C by XAFS and TEM showed mostly the formation of very small Co(0) particles (around 2-6 nm), indicating that the cobalt phase tends to redisperse during the reduction process from Co(3)O(4) to Co(0). The presence of manganese was found to hamper the cobalt reducibility, with this effect being more severe when Co(3-x)Mn(x)O(4) solutions were initially present in the catalyst precursors. Moreover, the presence of manganese generally led to the formation of larger cobalt agglomerates ( approximately 8-15 nm) upon reduction, probably as a consequence of the decrease in cobalt reducibility. The XAFS results revealed that all reduced catalysts contained manganese entirely in a Mn(2+) state, and two well-distinguished compounds could be identified: (1) a highly dispersed Ti(2)MnO(4)-type phase located at the TiO(2) surface and (2) a less dispersed MnO phase being in the proximity of the cobalt particles. Furthermore, the MnO was also found to exist partially mixed with a CoO phase in the form of rock-salt Mn(1-x)Co(x)O-type solid solutions. The existence of the later solutions was further confirmed by scanning transmission electron microscopy with electron energy loss spectroscopy (STEM-EELS) for a Mn-rich sample. Finally, the cobalt active site composition in the catalysts after reduction at 300 and 350 degrees C was linked to the catalytic performances obtained under reaction conditions of 220 degrees C, 1 bar, and H(2)/CO = 2. The catalysts with larger Co(0) particles ( approximately >5 nm) and lower Co reduction extents displayed a higher intrinsic hydrogenation activity and a longer catalyst lifetime. Interestingly, the MnO and Mn(1-x)Co(x)O species effectively promoted these larger Co(0) particles by increasing the C(5+) selectivity and decreasing the CH(4) production, while they did not significantly influence the selectivity of the catalysts containing very small Co(0) particles.     

Assessing the scaffold diversity of screening libraries

Medicinal chemists have traditionally realized assessments of chemical diversity and subsequent compound acquisition, although a recent study suggests that experts are usually inconsistent in reviewing large data sets. To analyze the scaffold diversity of commercially available screening collections, we have developed a general workflow aimed at (1) identifying druglike compounds, (2) clustering them by maximum common substructures (scaffolds), (3) measuring the scaffold diversity encoded by each screening collection independently of its size, and finally (4) merging all common substructures in a nonredundant scaffold library that can easily be browsed by structural and topological queries. Starting from 2.4 million compounds out of 12 commercial sources, four categories of libraries could be identified: large- and medium-sized combinatorial libraries (low scaffold diversity), diverse libraries (medium diversity, medium size), and highly diverse libraries (high diversity, low size). The chemical space covered by the scaffold library can be searched to prioritize scaffold-focused libraries.     

Single-Directional Properties of Quasi-Monotone Operators

A large supply of quasi-monotone multivalued mappings with values in a weak* fragmentable dual Banach space is shown to be generically single-directional. This is of some interest in analysis of quasi-convex functions. The paper extends/strengthens some results of a recent paper by Aussel and Eberhard (Math Program 30, 2012).     

Visible-light photolysis of [FeCp(η6-toluene)][PF6] as a clean,convenient and general route to iron-vinylidene and iron-acetylide complexes

Visible-light photolysis of the cheap starting material [FeCp(η⁶-toluene)][PF₆] (Cpη⁵-C₅H₅) using a simple 100-W globe in the presence of diphenyldiphosphinoethane (dppe) and terminal alkynes cleanly yields the vinylidene complexes [FeCp(dppe)(CCHR)][PF₆] and, upon further deprotonation, the iron-alkynyl complexes; the reaction is extended to ferrocenylacetylene to yield a bimetallic complex.