A new efficient route to chiral 1,3-disubstituted ferrocenes: application to the syntheses of (R(p))- and (S(p))-17alpha-[(3'-formylferrocenyl)ethynyl]estradiol

Starting from (2S,4S)-2-ferrocenyl-4-(methoxymethyl)-1,3-dioxane (4), use of the stereogenic ortho-directing menthyl para-tolyl sulfoxide group, which occupies the 2' position in the ferrocenyl ring and redirects subsequent lithiation to the 3' position, allowed the synthesis of optically pure (S(p))-1-formyl-3-iodoferrocene (8), that was characterized by single-crystal X-ray diffraction. Combination of this method with a protection-deprotection strategy, using trimethylsilyl as a temporary blocking group, yielded (R(p))-1-formyl-3-iodoferrocene (13). Separate Sonogashira coupling of each of the enantiomeric iodoformylferrocenes 8 and 13 with 17alpha-ethynyl-estradiol produced (R(p))-17alpha-[(3'-formylferrocenyl)ethynyl]estradiol (14) and (S(p))-17alpha-[(3'-formylferrocenyl)ethynyl]estradiol (15), respectively.     

Hepatic lipid composition analysis using 3.0-T MR spectroscopy in a steatotic rat model

Purpose

To investigate the feasibility of in vivo assessment of hepatic lipid composition using 3.0-T proton magnetic resonance spectroscopy (¹H-MRS) in a steatotic rat model and compare it to histopathological and biochemical assessment.

Materials and Methods

Hepatic steatosis was induced by feeding rats with a methionine/choline-deficient (MCD) diet for 1, 2, 3, 5 or 7 weeks (n=5 per group). At the end of the diet period, ¹H-MRS of the liver was performed, and rats were sacrificed for histopathological and biochemical assessment of the liver. Spectra were acquired in a single voxel (1.2 cc) using a point-resolved spectroscopic sequence with TE/TR=35/2000 ms and 64 signal acquisitions. From the MR spectra, peak area ratios were calculated to estimate hepatic lipid composition.

Results

During MCD diet periods, hepatic steatosis significantly increased on histopathology (P<.001). The ¹H-MRS measurements of total hepatic fat content [1.3/(1.3+4.65) ppm] correlated strongly with histological macrovesicular hepatic steatosis (r=0.93, P<.001) and with the biochemical total hepatic fatty acids (r=0.94, P<.001). Total unsaturated fatty acids [TUFA, 5.4/(1.3+4.65) ppm] estimated with ¹H-MRS strongly correlated with the biochemical unsaturated fatty acids (r=0.90, P<.001). Polyunsaturated fatty acids [PUFA, 2.8/(1.3+4.65) ppm] estimated with ¹H-MRS strongly correlated with biochemical PUFA (r=0.91, P<.001). The proportion of total unsaturated fatty acids relative to the amount of total fatty acids (rTUFA, 5.4/1.3ppm) measured with ¹H-MRS strongly correlated with the biochemical amount of unsaturated relative to total hepatic fatty acids (r=0.81, P<.001). The proportion of PUFA relative to the amount of total fatty acids (rPUFA, 2.8/1.3 ppm) measured with ¹H-MRS correlated with the biochemical amount of PUFA relative to total fatty acids (r=0.59, P=0.005,) and with the biochemical amount of omega-6 PUFA relative to total fatty acids (r=0.73, P<.001).PUFA at ¹H-MRS correlated with the histopathologically assessed degree of lobular inflammation in the liver (r=0.57, P=.001).

Conclusion

3.0T ¹H-MRS is able to measure poly- and unsaturated hepatic fatty acids and this strongly correlates with biochemical assessment. This study provides evidence that 3.0-T ¹H-MRS is a noninvasive technique to assess hepatic lipid composition.     

Quantification of asenapine and three metabolites in human plasma using liquid chromatography-tandem mass spectrometry with automated solid-phase extraction: application to a phase I clinical trial with asenapine in healthy male subjects

The development and validation of methods for determining concentrations of the antipsychotic drug asenapine (ASE) and three of its metabolites [N-desmethylasenapine (DMA), asenapine-N(+) -glucuronide (ASG) and 11-O-sulfate-asenapine (OSA)] in human plasma using LC-MS/MS with automated solid-phase extraction is described. The three assessment methods in human plasma were found to be acceptable for quantification in the ranges 0.0250-20.0 ng/mL (ASE), 0.0500-20.0 ng/mL (DMA and OSA) and 0.250-50.0 ng/mL (ASG).     

New Cu-based catalysts supported on TiO2 films for Ullmann S(N)Ar-type C-O coupling reactions

New routes for the preparation of highly active TiO(2)-supported Cu and CuZn catalysts have been developed for C-O coupling reactions. Slurries of a titania precursor were dip-coated onto glass beads to obtain either structured mesoporous or non-porous titania thin films. The Cu and CuZn nanoparticles, synthesized using a reduction by solvent method, were deposited onto calcined films to obtain a Cu loading of 2 wt%. The catalysts were characterized by inductively coupled plasma (ICP) spectroscopy, temperature-programmed oxidation/reduction (TPO/TPR) techniques, (63)Cu nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction (XRD), scanning and transmission electron microscopy (S/TEM-EDX) and X-ray photo-electron spectroscopy (XPS). The activity and stability of the catalysts obtained have been studied in the C-O Ullmann coupling of 4-chloropyridine and potassium phenolate. The titania-supported nanoparticles retained catalyst activity for up to 12 h. However, catalyst deactivation was observed for longer operation times due to oxidation of the Cu nanoparticles. The oxidation rate could be significantly reduced over the CuZn/TiO(2) catalytic films due to the presence of Zn. The 4-phenoxypyridine yield was 64% on the Cu/nonporous TiO(2) at 120 °C. The highest product yield of 84% was obtained on the Cu/mesoporous TiO(2) at 140 °C, corresponding to an initial reaction rate of 104 mmol g(cat) (-1) s(-1). The activation energy on the Cu/mesoporous TiO(2) catalyst was found to be (144±5) kJ mol(-1), which is close to the value obtained for the reaction over unsupported CuZn nanoparticles (123±3 kJ mol(-1)) and almost twice the value observed over the catalysts deposited onto the non-porous TiO(2) support (75±2 kJ mol(-1)).     

Correction to: Evaluation of gross-α, gross-β, U,Th and K values in groundwater and related health hazards: a case study,Arıklı mineralization area and its surroundings,Ayvacık, Çanakkale,Turkey

Journal of Radioanalytical and Nuclear Chemistry -     

List of participants

List of participants     

Sol–gel routes for microporous zirconia and titania membranes

Zirconia and titania nanoparticle sols were prepared, using either ligand-based precursor stabilization or acid stabilization routes. These sols were used to prepare microporous coatings on γ-alumina substrates. The acetylacetonate-based particles have very small hydrodynamic diameters (1–2 nm), which lead to sol intrusion into the supports. As a result no appropriate membrane layer was formed. A microemulsion-based zirconia sol leads to a membrane that was selective in pervaporation dehydration of a water/n-butanol mixture. An optimized membrane showed stable separation performance for 120 days with a high selectivity toward water. Permporometry and gas permeation results on a titania membrane based on an acid-stabilized sol not only show microporosity, but also a significant contribution from defect flow.     

How medical quality is improved: clinical management of patients with acute cardiac ischaemia

The clinical management of patients with acute ischaemic syndromes continues to evolve. It is therefore useful to review the most common categories of such patients, with specific emphasis on the contribution of some well-known laboratory assessments. Key questions on diagnosis, prognosis and medical quality are discussed.Presented at the 9th Conference on Quality in the Spotlight, 18–19 March 2004, Antwerp, Belgium