Dioxygenase-catalysed Oxidation of Disubstituted Benzene Substrates: Benzylic Monohydroxylation versus Aryl cis-Dihydroxylation and the Meta Effect

Biotransformations of a series of ortho-, meta- and para-substituted ethylbenzene and propylbenzene substrates have been carried out, using Pseudomonas putida UV4, a source of toluene dioxygenase (TDO). The ortho- and para-substituted alkylbenzene substrates yielded, exclusively, the corresponding enantiopure cis-dihydrodiols of the same absolute configuration. However, the meta isomers, generally, gave benzylic alcohol bioproducts, in addition to the cis-dihydrodiols (the meta effect). The benzylic alcohols were of identical (R) absolute configuration but enantiomeric excess values were variable. The similar (2R) absolute configurations of the cis-dihydrodiols are consistent with both the ethyl and propyl groups having dominant stereodirecting effects over the other substituents. The model used earlier, to predict the regio- and stereo-chemistry of cis-dihydrodiol bioproducts derived from substituted benzene substrates has been refined, to take account of non-symmetric subsituents like ethyl or propyl groups. The formation of benzylic hydroxylation products, from meta-substituted benzene substrates, without further cis-dihydroxylation to yield triols provides a further example of the meta effect during toluene dioxygenase-catalysed oxidations.

Association of Functional Heme Oxygenase-1 Gene Promoter Polymorphism with Renal Transplantation Outcomes

Heme oxygenase-1 (HO-1) is a cytoprotective molecule and increased expression in experimental transplant models correlates with reduced graft injury. A functional dinucleotide repeat (GT)n polymorphism, within the HO-1 promoter, regulates gene expression; a short number of repeats (S-allele

Rational design of a dual-mode optical and chemical prodrug

Purpose. The purpose of this study is to demonstrate the rational design and behaviour of the first dual mode optical and chemical prodrug, exemplified by an acetyl salicylic acid-based system. Methods. A cyclic 1,4-benzodioxinone prodrug was synthesised by reaction of 3,5-dimethoxybenzoin and acetyl salicoyl chloride with pyridine. After purification by column chromatography and recrystallization, characterization was achieved using infrared and NMR spectroscopies, mass spectrometry, elemental analysis and single crystal X-ray diffraction. Light-triggered drug liberation was characterised via UV-visible spectroscopy following low-power 365 nm irradiation for controlled times. Chemical drug liberation was characterised via UV-visible spectroscopy in pH 5.5 solution. Results. The synthetic method yielded pure prodrug, with full supporting characterisation. Light-triggered drug liberation proceeded at a rate of 8.30 10j2 sj1, while chemical, hydrolytic liberation proceeded independently at 1.89 10j3 sj1. The photochemical and hydrolytic reactions were both quantitative. Conclusions. This study demonstrates the first rational dual-mode optical and chemical prodrug, using acetyl salicylic acid as a model, acting as a paradigm for future dual-mode systems. Photochemical drug liberation proceeds 44 times faster than chemical liberation, suggesting potential use in drug-eluting medical devices where an additional burst of drug is required at the onset of infection.

A method for carbon stable isotope analysis of methyl halides and chlorofluorocarbons at pptv concentrations

A pre-concentration system has been validated for use with a gas chromatography/mass spectrometry/isotope ratio mass spectrometer (GC/MS/IRMS) to determine ambient air 13C/12C ratios for methyl halides (MeCl and MeBr) and chlorofluorocarbons (CFCs). The isotopic composition of specific compounds can provide useful information on their atmospheric budgets and biogeochemistry that cannot be ascertained from abundance measurements alone. Although pre-concentration systems have been previously used with a GC/MS/IRMS for atmospheric trace gas analysis, this is the first study also to report system validation tests. Validation results indicate that the pre-concentration system and subsequent separation technologies do not significantly alter the stable isotopic ratios of the target methyl halides, CFC-12 (CCl2F2) and CFC-113 (C2Cl3F3). Significant, but consistent, isotopic shifts of -27.5 to -25.6 do occur within the system for CFC-11 (CCl3F), although the shift is correctible. The method presented has the capacity to separate these target halocarbons from more than 50 other compounds in ambient air samples. Separation allows for the determination of stable carbon isotope ratios of five of these six target trace atmospheric constituents within ambient air for large volume samples (10 L). Representative urban air analyses from Belfast City are also presented which give carbon isotope results similar to published values for 13C/12C analysis of MeCl (-39.1) and CFC-113 (-28.1). However, this is the first paper reporting stable carbon isotope signatures for CFC-11 (-29.4) and CFC-12 (-37.0).

Theory of the near K-edge structure in electron energy loss spectroscopy

Arguments are given that lead to a formalism for calculating near K-edge structure in electron energy loss spectroscopy (EELS). This is essentially a one electron picture, while many body effects may be introduced at different levels, such as the local density approximation to density functional theory or the GW approximation to the electron self-energy. Calculations are made within the all electron LMTO scheme in crystals with complex atomic and electronic structures, and these are compared with experiment. (c) 2004 Elsevier B.V. All rights reserved.

Material effects on stress-induced defect generation in trenched silicon-on-insulator structures

We have investigated the influence of the material properties of the silicon device layer on the generation of defects, and in particular slip dislocations, in trenched and refilled fusion-bonded silicon-on-insulator structures. A strong dependence of the ease of slip generation on the type of dopant species was observed, with the samples falling into three basic categories; heavily boron-doped silicon showed ready slip generation, arsenic and antimony-doped material was fairly resistant to slip, while silicon moderately or lightly doped with phosphorous or boron gave intermediate behavior. The observed behavior appears to be controlled by differences in the dislocation generation mechanism rather than by dislocation mobility. The introduction of an implanted buried layer at the bonding interface was found to result in an increase in slip generation in the silicon, again with a variation according to the dopant species. Here, the greatest slip occurred for both boron and antimony-implanted samples. The weakening of the implanted material may be related to the presence of a band of precipitates observed in the silicon near the bonding interface. (C) 2001 The Electrochemical Society.