Chemoenzymatic synthesis of chiral 2,2 '-bipyridine ligands and their N-oxide derivatives: applications in the asymmetric aminolysis of epoxides and asymmetric allylation of aldehydes

A series of enantiopure 2,2'-bipyridines have been synthesised from the corresponding cis-dihydrodiol metabolites of 2-chloroquinolines. Several of the resulting hydroxylated 2,2'-bipyridines were found to be useful chiral ligands for the asymmetric aminolysis of meso-epoxides leading to the formation of enantioenriched amino alcohols (-> 84%ee). N-oxide and N,N'-dioxide derivatives of these 2,2'-bipyridines, including separable atropisomers, have been synthesised and used as enantioselective organocatalysts in the asymmetric allylation of aldehydes to give allylic alcohols (-> 86%ee).

Nebular and auroral emission lines of [Cl III] in the optical spectra of planetary nebulae

Electron impact excitation rates in Cl III, recently determined with the R-matrix code, are used to calculate electron temperature (T-e) and density (N-e) emission line ratios involving both the nebular (5517.7, 5537.9 Angstrom) and auroral (8433.9, 8480.9, 8500.0 Angstrom) transitions. A comparison of these results with observational data for a sample of planetary nebulae, obtained with the Hamilton Echelle Spectrograph on the 3-m Shane Telescope, reveals that the R-1 = /(5518 Angstrom)/I(5538 Angstrom) intensity ratio provides estimates of N-e in excellent agreement with the values derived from other line ratios in the echelle spectra. This agreement indicates that R-1 is a reliable density diagnostic for planetary nebulae, and it also provides observational support for the accuracy of the atomic data adopted in the line ratio calculations. However the [Cl III] 8433.9 Angstrom line is found to be frequently blended with a weak telluric emission feature, although in those instances when the [Cl III] intensity may be reliably measured, it provides accurate determinations of T-e when ratioed against the sum of the 5518 and 5538 Angstrom line fluxes. Similarly, the 8500.0 Angstrom line, previously believed to be free of contamination by the Earth's atmosphere, is also shown to be generally blended with a weak telluric emission feature. The [CI III] transition at 8480.9 Angstrom is found to be blended with the He I 8480.7 Angstrom line, except in planetary nebulae that show a relatively weak He I spectrum, where it also provides reliable estimates of T-e when ratioed against the nebular lines. Finally, the diagnostic potential of the near-UV [Cl III] lines at 3344 and 3354 Angstrom is briefly discussed.

Nebular and Auroral Emission Lines of [Ar IV] in the Optical Spectra of Planetary Nebulae

Recent R-matrix calculations of electron impact excitation rates in Ar IV are used to calculate the emission-line ratio: ratio diagrams (R₁, R₂), (R_1, R₃), and (R_1, R₄), where K₁ = I(4711 Å)/I(4740 Å), R₂ = I(7238 Å)/I(4711 + 4740 Å), R₃ = I(7263 Å)/I(4711 + 4740 Å), and R₄ = I(7171 Å)/I(4711 + 4740 Å), for a range of electron temperatures (T_e = 5000-20,000 K) and electron densities (N_e = 10-10⁶ cm^-3) appropriate to gaseous nebulae. These diagrams should, in principle, allow the simultaneous determination of T_e and N_e from measurements of the [Ar IV] lines in a spectrum. Plasma parameters deduced for a sample of planetary nebulae from (R_1, R₃) and (R_1, R₄), using observational date obtained with the Hamilton echelle spectrograph on the 3 m Shane Telescope at the Lick Observatory, are found to show excellent internal consistency and to be in generally good agreement with the values of T_e and N_e estimated from other line ratios in the echelle spectra. These results provide observational support for the accuracy of the theoretical ratios and, hence, the atomic data adopted in their derivation. In addition, they imply that the 7171 Å line is not as seriously affected by telluric absorption as previously thought. However, the observed values of R₂ are mostly larger than the theoretical high-temperature and density limit, which is due to blending of the Ar IV 7237.54 Å line with the strong C II transition at 7236 Å. 

Effect of pioglitazone on endothelial function in impaired glucose tolerance

Aim: Flow-mediated dilation (FMD) is a surrogate marker of endothelial function, which has been proposed as a barometer of vascular health. Impaired microvascular response to reactive hyperaemia is thought to be the mechanism behind reduced shear stress and subsequently impaired FMD, which has been associated with cardiovascular events. This study aims to assess the effect of pioglitazone on the vasculature of patients with impaired glucose tolerance (IGT).

Materials and Methods: Forty IGT patients with no cardiovascular disease were compared with 24 healthy age- and sex-matched controls. Endothelial function was assessed using FMD of the brachial artery. Adiponectin (ADN) levels were measured and insulin sensitivity was calculated using homeostasis model assessment of insulin resistance (HOMA-IR). A randomised double-blind placebo-controlled trial of the IGT subjects was then performed, with subjects receiving either pioglitazone 30 mg od or matched placebo for 12 weeks before the measurements were repeated.

Results: The IGT subjects had a significantly impaired FMD compared with the controls (p < 0.001). Diastolic shear stress (DSS) was also significantly reduced in IGT (p = 0.04). High molecular weight (HMW) ADN was significantly lower in the IGT group than in controls (p = 0.03). On analysis of the IGT group after 12 weeks treatment, FMD was significantly increased in the pioglitazone group compared with placebo (p = 0.03) as was endothelium-independent dilation (EID) (p = 0.03). A significant increase in total ADN (p < 0.001), HMW ADN (p < 0.001) and HMW/total ratio (p = 0.001) occurred in the pioglitazone group compared with placebo.

Conclusions: Pioglitazone improved endothelial function in IGT. Treatment with pioglitazone may reduce the risk of cardiovascular disease in this patient group.

Novel in vitro assays for the characterization of EMT in tumourigenesis

Background Two novel assays quantifying Epithelial to Mesenchymal Transition (EMT) were compared to traditional motility and migration assays. TGF-ß1 treatment of AY-27 rat bladder cancer cells acted as a model of EMT in tumourigenesis. Methods AY-27 rat bladder cancer cells incubated with 3ng/ml TGF-ß1 or control media for 24 or 48h were assessed using novel and traditional assays. The Spindle Index, a novel measure of spindle phenotype, was derived from the ratio of maximum length to maximum width of cells. The area covered by cells which migrated from a fixed coverslip towards supplemented agarose was measured in a novel chemoattractant assay. Motility, migration and immunoreactivity for E-cadherin, Vimentin and cytokeratin were assessed. Results TGF-ß1 treated cells had increased “spindle” phenotype together with decreased E-cadherin, decreased Cytokeratin-18 and increased Vimentin immunoreactivity. After 48h, the mean Spindle Index of TGF-ß1 treated cells was significantly higher than Mock (p=0.02 Bonferroni test) and there were significant differences in migration across treatment groups measured using the novel chemoattractant assay (p = 0.02, Chi-Square). TGF-ß1 significantly increased matrigel invasion. Conclusion The Spindle Index and the novel chemoattractant assay are valuable adjunctive assays for objective characterization of EMT changes during tumourigenesis.