Toluene Dioxygenase Catalysed synthesis and reactions of cis-diol metabolites derived from 2 and 3-methoxy phenols

Using toluene dioxygenase as biocatalyst, enantiopure cisdihydrodiol and cis-tetrahydrodiol metabolites, isolated as their ketone tautomers, were obtained from meta and ortho methoxyphenols. Although these isomeric phenol substrates are structurally similar, the major bioproducts from each of these biotransformations were found at different oxidation levels. The relatively stable cyclohexenone cis-diol metabolite from meta methoxyphenol was isolated, while the corresponding metabolite from ortho methoxyphenol was rapidly bioreduced to a cyclohexanone cis-diol. The chemistry of the 3-methoxycyclohexenone cis-diol product was investigated and elimination, aromatization, hydrogenation, regioselective O-exchange, Stork−Danheiser transposition and O-methylation reactions were observed. An offshoot of this technology provided a two-step chemoenzymatic synthesis, from meta methoxyphenol, of a recently reported chiral fungal metabolite; this synthesis also established the previously unassigned absolute configuration.

Facile synthesis of methyl 2-amino-3-(2-methyl-3-quinolyl)propanoate

Methyl 4-acetyl-5-(2-nitrophenyl)pyrrolidine-2-carboxylate 5, readily available in one step by a 1,3-dipolar cycloaddition, undergoes reduction, cyclisation and fragmentation to the corresponding quinoline when treated with hydrogen and palladium.

Preparation of Dess-Martin periodinane - The role of the morphology of 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide precursor

1-Hydroxy-1,2-benziodoxol-3(1H)-one I-oxide prepared by oxidation of o-iodobenzoic acid with potassium bromate forms either a microcrystalline powder, a macrocrystalline material, or a mixture of both forms. This difference in physical form is the source of the difficulty in reproducibly converting 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide to the corresponding I-triacetoxy derivative. A simple method is given for conversion of crystalline 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide to the more reactive powder form, The microcrystalline powder and macrocrystalline material are characterised by X-ray diffraction.

An investigation of the thermal stability and sulphur tolerance of Ag/Y-Al2O3 catalysts for the SCR of NOx with hydrocarbons and hydrogen

The sulphur tolerance and thermal stability of a 2 wt% Ag/gamma-Al2O3 catalyst was investigated for the H-2-promoted SCR of NO, with octane and toluene. The aged catalyst was characterised by XRD and EXAFS analysis. It was found that the effect of ageing was a function of the gas mix and temperature of ageing. At high temperatures (800 degrees C) the catalyst deactivated regardless of the reaction mix. EXAFS analysis showed that this was associated with the Ag particles on the surface of the catalyst becoming more ordered. At 600 and 700 degrees C, the deactivating effect of ageing was much less pronounced for the catalyst in the H-2-promoted octane-SCR reaction and ageing at 600 degrees C resulted in an enhancement in activity for the reaction in the absence of H-2. For the toluene + H-2-SCR reaction the catalyst deactivated at each ageing temperature. The effect of addition of low levels of sulphur (1 ppm SO2) to the feed was very much dependent on the reaction temperature. There was little deactivation of the catalyst at low temperatures ( 500 degrees C). The results can be explained by the activity of the catalyst for the oxidation Of SO2 to SO3 and the relative stability of silver and aluminium sulphates. The catalyst could be almost fully regenerated by a combination of heating and the presence of hydrogen in the regeneration mix. The catalyst could not be regenerated in the absence of hydrogen. (c) 2006 Published by Elsevier B.V.

Anomalous fluorinations of 3-aryl-2-hydroxypropanoic esters by diethylaminosulfur trifluoride (DAST).

Anomalous fluorinations of 3-aryl-2-hydroxypropanoic esters by diethylaminosulfur trifluoride (DAST). Haigh, David; Jefcott, Lee J.; Magee, Katherkine; McNab, Hamish. Dep. Med. chem., SmithKline Beecham Pharmaceuticals, Epsom, UK. Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1996), (24), 2895-2900. Publisher: Royal Society of Chemistry, CODEN: JCPRB4 ISSN: 0300-922X. Journal written in English. CAN 126:143928 AN 1997:56534 CAPLUS (Copyright (C) 2009 ACS on SciFinder (R)) Abstract Treatment of 3-aryl-2-hydroxypropanoic esters with diethylaminosulfur trifluoride (DAST) gives considerable amts. of rearranged 2-aryl-3-fluoropropanoic esters, together with the expected products. The extent of rearrangement is dependent on solvent and on the substitution pattern of the aryl ring; the mechanism of rearrangement probably involves anchimeric assistance by the aryl group in the SN1 component of the reaction pathway. Reaction of the isomeric 3-hydroxy-2-phenylpropanoic ester shows much less rearrangement under similar conditions, and an elimination product is also obtained.

Bacterial dioxygenase- and monooxygenase-catalysed sulfoxidation of benzo[b]thiophenes

Asymmetric heteroatom oxidation of benzo[b]thiophenes to yield the corresponding sulfoxides was catalysed by toluene dioxygenase (TDO), naphthalene dioxygenase (NDO) and styrene monooxygenase (SMO) enzymes present in P. putida mutant and E. coli recombinant whole cells. TDO-catalysed oxidation yielded the relatively unstable benzo[b] thiophene sulfoxide; its dimerization, followed by dehydrogenation, resulted in the isolation of stable tetracyclic sulfoxides as minor products with cis-dihydrodiols being the dominant metabolites. SMO mainly catalysed the formation of enantioenriched benzo[b] thiophene sulfoxide and 2-methyl benzo[b] thiophene sulfoxides which racemized at ambient temperature. The barriers to pyramidal sulfur inversion of 2- and 3-methyl benzo[b] thiophene sulfoxide metabolites, obtained using TDO and NDO as biocatalysts, were found to be ca.: 25-27 kcal mol(-1). The absolute configurations of the benzo[b] thiophene sulfoxides were determined by ECD spectroscopy, X-ray crystallography and stereochemical correlation. A site-directed mutant E. coli strain containing an engineered form of NDO, was found to change the regioselectivity toward preferential oxidation of the thiophene ring rather than the benzene ring.

Steam reforming of ethanol over Co3O4–Fe2O3 mixed oxides

Co3O4, Fe2O3 and a mixture of the two oxides Co–Fe (molar ratio of Co3O4/Fe2O3 = 0.67 and atomic ratio of Co/Fe = 1) were prepared by the calcination of cobalt oxalate and/or iron oxalate salts at 500 °C for 2 h in static air using water as a solvent/dispersing agent. The catalysts were studied in the steam reforming of ethanol to investigate the effect of the partial substitution of Co3O4 with Fe2O3 on the catalytic behaviour. The reforming activity over Fe2O3, while initially high, underwent fast deactivation. In comparison, over the Co–Fe catalyst both the H2 yield and stability were higher than that found over the pure Co3O4 or Fe2O3 catalysts. DRIFTS-MS studies under the reaction feed highlighted that the Co–Fe catalyst had increased amounts of adsorbed OH/water; similar to Fe2O3. Increasing the amount of reactive species (water/OH species) adsorbed on the Co–Fe catalyst surface is proposed to facilitate the steam reforming reaction rather than decomposition reactions reducing by-product formation and providing a higher H2 yield.

Ordering the cytochrome c-initiated caspase cascade:hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner

Exit of cytochrome c from mitochondria into the cytosol has been implicated as an important step in apoptosis. In the cytosol, cytochrome c binds to the CED-4 homologue, Apaf-1, thereby triggering Apaf-1-mediated activation of caspase-9. Caspase-9 is thought to propagate the death signal by triggering other caspase activation events, the details of which remain obscure. Here, we report that six additional caspases (caspases-2, -3, -6, -7, -8, and -10) are processed in cell-free extracts in response to cytochrome c, and that three others (caspases-1, -4, and -5) failed to be activated under the same conditions. In vitro association assays confirmed that caspase-9 selectively bound to Apaf-1, whereas caspases-1, -2, -3, -6, -7, -8, and -10 did not. Depletion of caspase-9 from cell extracts abrogated cytochrome c-inducible activation of caspases-2, -3, -6, -7, -8, and -10, suggesting that caspase-9 is required for all of these downstream caspase activation events. Immunodepletion of caspases-3, -6, and -7 from cell extracts enabled us to order the sequence of caspase activation events downstream of caspase-9 and reveal the presence of a branched caspase cascade. Caspase-3 is required for the activation of four other caspases (-2, -6, -8, and -10) in this pathway and also participates in a feedback amplification loop involving caspase-9.

A simple and low-cost method for the preparation of self-supported TiO2-WO3 ceramic heterojunction wafers

Robust, bilayer heterojunction photodiodes of TiO₂-WO₃ were prepared successfully by a simple, low-cost powder pressing technique followed by heat-treatment. Exclusive photoirradiation of the TiO₂ side of the photodiode resulted in a rapid colour change (dark blue) on the WO₃ surface as a result of reduction of W⁶⁺ to W⁵⁺ (confirmed by X-ray photoelectron spectroscopy). This colour was long lived and shown to be stable in a dry environment in air for several hours. A similar photoirradiation experiment in the presence of a mask showed that charge transfer across the heterojunction occurred approximately normal to the TiO₂ surface, with little smearing out of the mask image. As a result of the highly efficient vectorial charge separation, the photodiodes showed a tremendous increase in photocatalytic activity for the degradation of stearic acid, compared to wafers of the respective individual materials when tested separately.

The reaction path of CO and Fe2O3 in a chemical-looping combustion system

The reaction mechanism of CO and Fe₂O₃ in a chemical-looping combustion (CLC) was studied based on density functional theory (DFT) at B3LYP level in this paper. The structures of all reactants, intermediate, transition structures and products of this reaction had been optimized and characterized. The reaction path was validated by means of the intrinsic reaction coordinate (IRC) approach. The result showed that the reaction was divided into two steps, the adsorbed CO molecule on Fe ₂O₃ surface formed a medium state with one broken Fe-O bond in step1, and in step2, O atom broken here oxidized a subsequent CO molecule in the fuel reactor. Thus, Fe₂O₃ molecule transport O from air to oxide CO continually in the CLC process. The activation energy and rate coefficients of the two steps were also obtained.

The optimized geometric structure of the (0001) surface of α-Fe 2O3

A tridimensional model of α-Fe₂O₃ and models of (0001) and (1102) surfaces on it were built. Then the structural optimization of the (0001) surface was presented which explored the influence of the system scale and the terminal surface configuration. Four different models including two different system scale structures (MODEL□ and MODEL□) and two different terminal structures (MODEL□ and MODEL□) were analyzed in this paper. It was concluded that the boundary effect was more important in a smaller system in the structure optimization. And the Fe-terminated was more stable than the O-terminated structure which was agreed with the experiences, this structural model can be used in further work including the monatomic adsorption/desorption and the chemical reactions on this surface.

Density functional study of the C atom adsorption on the α-Fe 2O3 (001) surface

The adsorption of C atoms on the α-Fe₂O₃ (001) surface was studied based on density function theory (DFT), in which the exchange-correlation potential was chosen as the PBE (Perdew, Burke and Ernzerhof) generalized gradient approximation (GGA) with a plane wave basis set. Upon the optimization on different adsorption sites with coverage of 1/20 and 1/5 ML, it was found that the adsorption of C atoms on the α-Fe ₂O₃ (001) surface was chemical adsorption. The coverage can affect the adsorption behavior greatly. Under low coverage, the most stable adsorption geometry lied on the bridged site with the adsorption energy of about 3.22 eV; however, under high coverage, it located at the top site with the energy change of 8.79 eV. Strong chemical reaction has occurred between the C and O atoms at this site. The density of states and population analysis showed that the s, p orbitals of C and p orbital of O give the most contribution to the adsorption bonding. During the adsorption process, O atom shares the electrons with C, and C can only affect the outermost and subsurface layers of α-Fe₂O₃; the third layer can not be affected obviously. Copyright © 2008 Chinese Journal of Structural Chemistry.

Tiotropium Respimat® in cystic fibrosis: Phase 3 and Pooled phase 2/3 randomized trials

Background: Tiotropium Respimat® improved lung function in a phase 2 trial in patients with cystic fibrosis (CF). We investigated its efficacy and safety in a phase 3 trial, including a pre-specified pooled analysis of the phase 2 and 3 trials. 

Methods: 12-week, randomized, double-blind, placebo-controlled trial of tiotropium Respimat® 5. μg once daily in patients with CF (N = 463). 

Results: Co-primary efficacy endpoints showed no statistical difference between tiotropium and placebo: percent-predicted forced expiratory volume in 1s (FEV₁) area under the curve from 0-4h (AUC_0-4h) (95% CI): 1.64% (0.27,3.55; p=0.092); percent-predicted trough FEV₁ (95% CI) 1.40% (0.50,3.30; p=0.15). Adverse events were similar between groups. Pooled phase 2/3 trial results showed a treatment difference in favor of tiotropium: percent-predicted FEV₁ AUC_0-4h (95% CI): 2.62% (1.34,3.90). 

Conclusion: Tiotropium was well tolerated in patients with CF; lung function improvements compared with placebo were not statistically significant in the phase 3 trial. Clinical trials: These studies are registered with clinical trial identifier numbers NCT00737100 and NCT01179347NCT00737100NCT01179347. These studies are also registered with the EudraCT number: 2008-001156-43 and 2010-019802-17.