In vitro biotransformation of (R)- and (S)-thalidomide: application of circular dichroism spectroscopy to the stereochemical characterization of the hydroxylated metabolites

Circular dichroism (CD) spectroscopy was successfully used for the stereochemical characterization of the hydroxylated metabolites formed during the in vitro biotransformation of (R)- and (S)-thalidomide. Incubation extracts of the individual enantiomers were analyzed by HPLC on an achiral stationary phase combined with CD detection. The CD data of the almost enantiopure eluates of the metabolites were compared with the CD spectra quantum chemically calculated for the respective structures. The results allowed us a reliable determination of the absolute stereostructure for all of the metabolites. The chiral center of thalidomide is unaffected by the stereoselective biotransformation process. (3'R,5'R)-trans-5'-hydroxythalidomide is the main metabolite of (R)-thalidomide, which epimerizes spontaneously to give the more stable (3'S,5'R)-cis isomer. On the contrary, (S)-thalidomide is preferentially metabolized by hydroxylation in the phthalimide moiety, resulting in the formation of (S)-5-hydroxythalidomide.     

Two-color photorefractive effect in Mg-doped lithium niobate

The two-color photorefractive response of near stoichiometric lithium niobate (SLN) doped with Mg above a critical threshold has been investigated. Striking differences as compared with non Mg-doped material were observed: The intermediate level in the two-color writing process has approximately a two orders of magnitude longer lifetime in SLN:Mg than in nominally undoped SLN, the grating is written in a shallower level but can be fixed via a simple thermal process and complementary electron-hole gratings are formed. It is proposed that the Fe impurity level moves from below the small-polaron level in nonMgO-doped material to above it, resulting in the increased lifetime of the small polaron. These changes are associated with a shift of the Fe from a Li site to a Nb site. The two-color sensitivity is higher than in the absence of MgO but the dynamic range is much lower.     

On the efficient implementation of conditional critical regions and the construction of monitors

Summary A method is presented that allows the efficient implementation of conditional critical regions combined with scheduling of the waiting processes. It is based on the knowledge of static and invariant relations that exist among the conditional critical regions of a process system. Mathematical methods are applied in order to show the nature of these relations, and to determine them for practical applications.By collecting the conditional critical regions in a program module, a monitor is obtained. Its rather abstract user level allows clear and well structured programming style. It also shows some advantages in comparison to other monitor proposals on the implementation level.Work done mainly at the Fakultät für Informatik, Universität Karlsruhe, Karlsruhe, and also at the Department of Computer Science, University of Toronto, Toronto.     

Flip the tip: an automated,high quality,cost-effective patch clamp screen

The race for creating an automated patch clamp has begun. Here, we present a novel technology to produce true gigaseals and whole cell preparations at a high rate. Suspended cells are flushed toward the tip of glass micropipettes. Seal, whole-cell break-in, and pipette/liquid handling are fully automated. Extremely stable seals and access resistance guarantee high recording quality. Data obtained from different cell types sealed inside pipettes show long-term stability, voltage clamp and seal quality, as well as block by compounds in the pM range. A flexible array of independent electrode positions minimizes consumables consumption at maximal throughput. Pulled micropipettes guarantee a proven gigaseal substrate with ultra clean and smooth surface at low cost.