Intrinsic and Intramolecular Lipophilicity Effects in O-Glucuronides

In this study, we compared the lipophilicity of O-glucuronides and their aglycones. Distribution coefficients (log D) and P values of neutral species (log P) were determined by centrifugal partition chromatography (CPC) in octanol/buffer systems. Two-phase potentiometry was also used to measure the log P value of some lipophilic solutes. The experimentally determined global influence of glucuronidation on lipophilicity, obtained as the difference (decrement) log P_{(glucuronide)} ? log P_(aglycone), was found to be ?1.30 ± 0.16 (n = 4) for glucuronides of alcohols (methyl, menthyl, neomenthyl, and chloramphenicol O-glucuronide). The mean decrement was ?2.06 ± 0.31 (n = 9) for glucuronides of phenols (phenyl, p-nitrophenyl, 1-naphthyl, 6-bromo-2-naphthyl, 4-methylumbelliferyl, 3-coumarinyl, phenolphthalein, 4′-benzophenonyl O-glucuronide, and diflunisal phenolic glucuronide). For the acylglucuronide of diflunisal and its rearrangement isomers, the mean decrement was ?1.80 ± 0.08 (n = 4; range ?1.7 to ?1.9). Differences in through-bond proximity effects as parametrized in the CLOGP algorithm seem to account for much of this difference. Conformational factors may also play a role, although it appears modest and unassessable for the glucuronides investigated here. The results imply that in vivo glucuronidation should have a stronger influence on the excretion of phenols than on that of alcohols.     

Discharges in the JET tokamak where the safety factor profile is identified as the critical factor for triggering internal transport barriers

Joint European Torus discharges which demonstrate the critical role the safety factor profile, q, can play in the formation of internal transport barriers (ITB) are examined. In these discharges, the target parameters, including the E x B flows, were kept virtually the same, except for the q profile. In a discharge with a nonmonotonic q, an ITB was triggered whereas a discharge with monotone q made no such transition. Thus, there is strong evidence that the q profile was the critical factor for the triggering of an ITB. Possible interpretations of this finding are discussed.     

Observation of zero current density in the core of jet discharges with lower hybrid heating and current drive

Simultaneous current ramping and application of lower hybrid heating and current drive (LHCD) have produced a region with zero current density within measurement errors in the core ( r/a< or =0.2) of JET tokamak optimized shear discharges. The reduction of core current density is consistent with a simple physical explanation and numerical simulations of radial current diffusion including the effects of LHCD. However, the core current density is clamped at zero, indicating the existence of a physical mechanism which prevents it from becoming negative.     

Thermoregulatoren, Thermostaten und Druckregulatoren

Ohne Zusammenfassung     

Method for quantification of morphine and its 3- and 6- glucuronides, codeine, codeine glucuronide and 6-monoacetylmorphine in human blood by liquid chromatography-electrospray mass spectrometry for routine analysis in forensic toxicology.

Simultaneous determination of opiates and their glucuronides in body fluids has a great practical interest in the forensic assessment of heroin intoxication. A selective and sensitive method for quantification of morphine and its 3- and 6-glucuronides, codeine, codeine glucuronide and 6-monoacetylmorphine (6-MAM) based on liquid chromatography-electrospray ionisation mass spectrometry is described. The drugs were analysed in human autopsy whole blood after solid-phase extraction on a C8 cartridge. The separation was performed on an ODS column in acetonitrile (analysis time 15 min). For the quantitative analysis, deuterated analogues of each compound were used as internal standards. Selected-ion monitoring was applied where the molecular ion was chosen for quantification. The limits of quantification were 0.5 ng/ml for morphine and 6-MAM and 1 ng/ml for the 6-glucuronide of morphine, codeine-6-glucuronide and codeine and 5 ng/ml for the 3-glucuronide of morphine.     

Desorption electrospray ionization mass spectrometry: direct toxicological screening and analysis of illicit Ecstasy tablets

Desorption electrospray ionization mass spectrometry (DESI-MS) was used as a simple and rapid way to analyze drug tablets and powders without sample preparation. Experiments were performed with a home-made DESI source coupled to a triple-quadrupole linear-ion trap (QqQ(LIT)) mass spectrometer. Twenty-one commercial drugs as well as some illicit Ecstasy tablets and powders were analyzed. MS spectra almost exclusively showed the protonated or deprotonated ion of the drug after directing the pneumatically assisted electrospray onto the tablet's surface. With some tablets, inhomogeneity of the surface resulted in different spectra depending on the spot analyzed, thus showing that DESI could be used for imaging. Directly triggered MS/MS spectra were used for confirmatory analysis, with analysis times often below 10 s per tablet. For illicit Ecstasy tablets, DESI-MS, GC/MS and LC/MS analyses provided similar qualitative results for the main analytes. With MS/MS spectra library comparison or exact mass measurements, this technique could become very powerful for the rapid analysis of unknown tablets and shows the great potential of desorption techniques as an alternative to solution-based analysis.     

Replacement of Water Molecules in a Phosphate Binding Site by Furanoside‐Appended lin‐Benzoguanine Ligands of tRNA‐Guanine Transglycosylase (TGT)

The enzyme tRNA‐guanine transglycosylase has been identified as a drug target for the foodborne illness shigellosis. A key challenge in structure‐based design for this enzyme is the filling of the polar ribose‐34 pocket. Herein, we describe a novel series of ligands consisting of furanoside‐appended lin‐benzoguanines. They were designed to replace a conserved water cluster and differ by the functional groups at C(2) and C(3) of the furanosyl moiety being either OH or OMe. The unfavorable desolvation of Asp102 and Asp280, which are located close to the ribose‐34 pocket, had a significant impact on binding affinity. While the enzyme has tRNA as its natural substrate, X‐ray co‐crystal structures revealed that the furanosyl moieties of the ligands are not accommodated in the tRNA ribose‐34 site, but at the location of the adjacent phosphate group. A remarkable similarity of the position of the oxygen atoms in these two structures suggests furanosides as a potential phosphate isoster.     

Optimisation of pressurised liquid extraction by experimental design for quantification of pesticides and alkyl phenols in sludge,suspended materials and atmospheric fallout by liquid chromatography–tandem mass spectrometry

The study proposes an analytical method to quantify 10 alkylphenols and 12 pesticides at ultra-trace levels by liquid chromatography in reverse mode coupled to positive electrospray ionisation–tandem mass spectrometry. The extraction procedure from environmental solids was optimised by pressurised liquid extraction using acetonitrile:isopropanol (1:1, v/v). The influence of several extraction experimental factors, temperature, pressure, duration and number of cycles, related to the PLE was investigated by an original and efficient chemometric approach. The optimised extraction method (80 °C, 40 bar, 10 min, 1 cycle) exhibited recoveries between 67 and 127% with RSD mostly under 13%. The whole method was applied to real samples: sludge, suspended materials, atmospheric fallouts and roof deposit. Pollutant levels were between 1 μg kg⁻¹ and 5.9 mg kg⁻¹.     

Electron transport in a mesoscopic superconducting / ferromagnetic hybrid conductor

We present electrical transport experiments performed on submicron hybrid devices made of a ferromagnetic conductor (Co) and a superconducting (Al) electrode. The sample was patterned in order to separate the contributions of the Co conductor and of the Co-Al interface. We observed a strong influence of the Al electrode superconductivity on the resistance of the Co conductor. This effect is large only when the interface is highly transparent. We characterized the dependence of the observed resistance decrease on temperature, bias current and magnetic field. As the differential resistance of the ferromagnet exhibits a non-trivial asymmetry, we claim that the magnetic domain structure plays an important role in the electron transport properties of superconducting / ferromagnetic conductors. Received 9 July 2002 / Received in final form 22 October 2002 Published online 27 January 2003 RID="a" ID="a"e-mail: herve.courtois@grenoble.cnrs.fr RID="b" ID="b"associated to Université Joseph Fourier