A comparison of MOP-phosphonite ligands and their applications in Rh(i)- and Pd(ii)-catalysed asymmetric transformations.

Six chiral MOP-phosphonites have been synthesised and compared via experimental and computational methods in an effort to quantify their differing structural and electronic profiles. They were found to be electron-poor ligands in comparison to their arylphosphine analogues and have a larger trans influence in square planar Pt(ii) complexes. Four [Rh(LP)(η2:η2-cod)Cl] complexes were synthesised and characterised by NMR, HRMS and X-ray crystallography. Two [Rh(LP)2]BF4 complexes were prepared where one ligand acts as a chelating P,C-π-donor; detailed NMR studies demonstrated a hemilabile η6-coordination mode, which in one case was confirmed by X-ray crystallography. Rh(i) complexes were used as catalysts in asymmetric hydrogenation and hydroformylation reactions and in the addition of phenyl boronic acid to an isatin. Pd(ii) complexes were successfully employed in asymmetric Suzuki-Miyaura cross-coupling reactions yielding binaphthyl products. Two [Pd(LP)2Cl2] complexes were synthesised and characterised by X-ray crystallography, both adopting cis orientations, with one of the complexes crystallising as two pseudo-polymorphs.

The design of second generation MOP-phosphonites: efficient chiral hydrosilylation of functionalised styrenes.

A series of enantiopure MOP-phosphonite ligands, with tailored steric profiles, have been synthesised and are proven to be very successful in high-yielding, regio- and enantioselective catalytic hydrosilylation reactions of substituted styrenes, affording important chiral secondary alcohols.

Electronic interfacing with living cells.

The direct interfacing of living cells with inorganic electronic materials, components or systems has led to the development of two broad categories of devices that can (1) transduce biochemical signals generated by biological components into electrical signals and (2) transduce electronically generated signals into biochemical signals. The first category of devices permits the monitoring of living cells, the second, enables control of cellular processes. This review will survey this exciting area with emphasis on the fundamental issues and obstacles faced by researchers. Devices and applications that use both prokaryotic (microbial) and eukaryotic (mammalian) cells will be covered. Individual devices described include microbial biofuel cells that produce electricity, bioelectrical reactors that enable electronic control of cellular metabolism, living cell biosensors for the detection of chemicals and devices that permit monitoring and control of mammalian physiology.

Attributing effects of aqueous C60 nano-aggregates to tetrahydrofuran decomposition products in larval zebrafish by assessment of gene expression.

BACKGROUND: C(60) is a highly insoluble nanoparticle that can form colloidal suspended aggregates in water, which may lead to environmental exposure in aquatic organisms. Previous research has indicated toxicity from C(60) aggregate; however, effects could be because of tetrahydrofuran (THF) vehicle used to prepare aggregates. OBJECTIVE: Our goal was to investigate changes in survival and gene expression in larval zebrafish Danio rerio after exposure to aggregates of C(60) prepared by two methods: a) stirring and sonication of C(60) in water (C(60)-water); and b) suspension of C(60) in THF followed by rotovaping, resuspension in water, and sparging with nitrogen gas (THF-C(60)). RESULTS: Survival of larval zebrafish was reduced in THF-C(60) and THF-water but not in C(60)-water. The greatest differences in gene expression were observed in fish exposed to THF-C(60) and most (182) of these genes were similarly expressed in fish exposed to THF-water. Significant up-regulation (3- to 7-fold) of genes involved in controlling oxidative damage was observed after exposure to THF-C(60) and THF-water. Analyses of THF-C(60) and THF-water by gas chromatography-mass spectrometry did not detect THF but found THF oxidation products gamma-butyrolactone and tetrahydro-2-furanol. Toxicity of gamma-butyrolactone (72-hr lethal concentration predicted to kill 50% was 47 ppm) indicated effects in THF treatments can result from gamma-butyrolactone toxicity. CONCLUSION: This research is the first to link toxic effects directly to a THF degradation product (gamma-butyrolactone) rather than to C(60) and may explain toxicity attributed to C(60) in other investigations. The present work was first presented at the meeting "Overcoming Obstacles to Effective Research Design in Nanotoxicology" held 24-26 April 2006 in Cambridge, Massachusetts, USA.

In vitro immune toxicity of depleted uranium: effects on murine macrophages, CD4+ T cells, and gene expression profiles.

Depleted uranium (DU) is a by-product of the uranium enrichment process and shares chemical properties with natural and enriched uranium. To investigate the toxic effects of environmental DU exposure on the immune system, we examined the influences of DU (in the form of uranyl nitrate) on viability and immune function as well as cytokine gene expression in murine peritoneal macrophages and splenic CD4+ T cells. Macrophages and CD4+ T cells were exposed to various concentrations of DU, and cell death via apoptosis and necrosis was analyzed using annexin-V/propidium iodide assay. DU cytotoxicity in both cell types was concentration dependent, with macrophage apoptosis and necrosis occurring within 24 hr at 100 microM DU exposure, whereas CD4+ T cells underwent cell death at 500 microM DU exposure. Noncytotoxic concentrations for macrophages and CD4+ T cells were determined as 50 and 100 microM, respectively. Lymphoproliferation analysis indicated that macrophage accessory cell function was altered with 200 microM DU after exposure times as short as 2 hr. Microarray and real-time reverse-transcriptase polymerase chain reaction analyses revealed that DU alters gene expression patterns in both cell types. The most differentially expressed genes were related to signal transduction, such as c-jun, NF- kappa Bp65, neurotrophic factors (e.g., Mdk), chemokine and chemokine receptors (e.g., TECK/CCL25), and interleukins such as IL-10 and IL-5, indicating a possible involvement of DU in cancer development, autoimmune diseases, and T helper 2 polarization of T cells. The results are a first step in identifying molecular targets for the toxicity of DU and the elucidation of the molecular mechanisms for the immune modulation ability of DU.

Evaluation of a plasmid-based 16S-23S rDNA intergenic spacer region array for analysis of microbial diversity in industrial wastewater.

A plasmid-based 16S-23S rDNA intergenic spacer region (ISR) array was developed and optimized for analysis of microbial diversity within complex environmental samples. Plasmid probes with 16S-23S rDNA ISR inserts (800-1500 bp) from industrial wastewater treatment plant (WWTP) microorganisms were arrayed onto glass slides. Hybridization of fluorescently labeled target sequences from two clones from the ISR WWTP library to arrayed probes showed that there was a good linear relationship between hybridization intensity and ISR similarity (r(2)=0.82). Hybridization was highly specific (average background from arrayed probes with less than 80% similarity in ISR sequence was less than 7%). Strong fluorescence intensity corresponded to near-perfect match clones (99% or greater similarity in ISR sequence). A majority of probes (79%) showed no background hybridization. However, weak background (less than 50% for arrayed probes with 90% and 95% similarity in the 16S rRNA genes) was observed from closely related microorganisms. Background fluorescence from the negative control (plasmid vector with no insert) was similar to water and dimethyl sulfoxide (DMSO)-negative controls. Hybridization using fluorescently labeled ISR sequences from a mixed community sample produced strong fluorescent signals with no background from negative controls. A Cy5-labeled reference standard, part of the vector and present in every spotted probe, was used to normalize hybridization values. These results indicate that arrayed plasmid containing ISR probe insert sequences provides specificity and sensitivity for microbial community analysis in a high-throughput array format.

Fingerprinting of prokaryotic 16S rRNA genes using oligodeoxyribonucleotide microarrays and virtual hybridization.

An oligonucleotide microarray hybridization system to differentiate microbial species was designed and tested. Seven microbial species were studied, including one Bacillus and six Pseudomonas strains. DNA sequences near the 5' end of 16S rRNA genes were aligned and two contiguous regions of high variability, flanked by highly conserved sequences, were found. The conserved sequences were used to design PCR primers which efficiently amplified these polymorphic regions from all seven species. The amplicon sequences were used to design 88 9mer hybridization probes which were arrayed onto glass slides. Single-stranded, fluorescence-tagged PCR products were hybridized to the microarrays at 15 degrees C. The experimental results were compared with the DeltaG(0) values for all matched and mismatched duplexes possible between the synthetic probes and the 16S target sequences of the seven test species, calculated using a 'virtual hybridization' software program. Although the observed hybridization patterns differed significantly from patterns predicted solely on the basis of perfect sequence matches, a unique hybridization fingerprint was obtained for each of the species, including closely related Pseudomonas species, and there was a reasonable correlation between the intensity of observed hybridization signals and the calculated DeltaG(0) values. The results suggest that both perfect and mismatched pairings can contribute to microbial identification by hybridization fingerprinting.