Stereochemistry of the Inhibition of δ-Chymotrypsin with Optically Active Bicyclic Organophosphates: 31P-NMR studies

The inhibition of δ-chymotrypsin with optically active, axially and equatorially substituted trans-3-(2,4-dini-trophenoxy)-2,4-dioxa-3λ⁵-phospbubicyclo[4.4.0]decan-3-ones ( = hexahydro-4H-1,3,2-benzodioxaphosphorin 3-oxides) was investigated. Their inhibitory power was determined by kinetic measurements, and the stereochemical course of the reaction of stoichiometric amounts of the enzyme and inhibitor was monitored with ³¹P-NMR spectroscopy at pH 7.8. The irreversible inhibitors show significant enantioselectivity (the (S_p)-enantiomer reacting faster) and yield diastereoisomeric, covalently phosphorylated derivatives of δ-chymotrypsin. ³¹P-NMR Spectroscopic studies of the inhibition by the axially substituted inhibitor revealed for the racemic (±) -2a first a resonance at –4.4 ppm and later, while inhibition proceeded, a second one at –4.5 ppm. The reaction with optically active (+) -2a showed only one signal at –4.4 ppm and its enantiomer (–) -2a only one signal at –4.5 ppm. Using the equatorially substituted racemic epimer (±) -2b , we observed the main resonance at –5.3 ppm and two minor ones at –4.4 and –4.5 ppm. The optically active compound (+) -2b showed two peaks at –4.5 and –5.3 ppm, whereas its antipode (–) -2b revealed two signals at –4.4 and –5.3 ppm. Comparing the ³¹P chemical shifts of the corresponding covalent phosphoserine derivatives 4a (-5.7 ppm, axial) and 4b (-4.5 ppm, equatorial) shows the inhibition with the axial compounds 2a to proceed via neat inversion of the configuration at the P-atom, whereas the equatorial epimers 2b with a higher conformational flexibility seem to follow a different stereochemical pathway which results in both inversion and retention.     

N-methyl-N-trimethylsilyltrifluoroacetamide-promoted synthesis and mass spectrometric characterization of deuterated ephedrines

Synthesis and mass spectrometric characterization of drugs or metabolites labeled by stable isotopes has been of great interest in fields of clinical, forensic and doping control analysis. Deuterated ephedrine and p-hydroxypseudoephedrine were prepared from corresponding amines by a novel procedure utilizing N- methyl-N-trimethylsilyltrifluoroacetamide and deuterated iodomethane. The mechanism of methylation was studied by mass spectrometry using phenylethylamine as a model compound, and a rearrangement based on an intermediate six-membered ring structure with a trimethylsilyl-enol-ether is proposed giving rise to a leaving group of trimethyliodosilane and the desired monomethylated product. Deuterated analogues to frequently quantitated ephedrines were readily synthesized with purities >90%, and mass spectra recorded under different ionization and dissociation conditions presented distinct fragmentation processes including eliminations of water and methylamine as well as the generation of a benzyl cation.     

Synthesis, modeling, and anti-tubulin activity of a D-seco paclitaxel analogue

[reaction: see text] We have previously described a model of paclitaxel-microtubule binding that led to the prediction that analogues of paclitaxel lacking any D ring could stabilize microtubules as well as paclitaxel if the substituent present at C4 did not have unfavorable steric interactions with the binding pocket. We report the synthesis of a 4-methyl paclitaxel analogue, compound 1, which bears this prediction out. Compound 1 is as potent as paclitaxel at microtubule stabilization in vitro; however, it has only about one-four-hundredth the cytotoxicity of paclitaxel.     

Optimal control methods applied on the ionization processes of alkali dimers

We present two novel optimization methods by employing shaped fs-laser pulses in a closed feedback loop. The first describes control pulse cleaning where extraneous features were removed by applying genetic pressure on certain pulse components. The second reports parametric optimization with intuitive parameters such as subpulse distances, chirps, phase differences, and spectral peak patterns. These methods were conducted on the ionization process of alkali dimers produced in a molecular beam and improved the performances of the optimized pulses compared with short pulses at the same pulse energy. Moreover, we attempt to analyze the obtained pulse shapes regarding the underlying optimized processes. Further investigations concerning isotope selective fragmentation and optimal control of excitation processes of ultracold rubidium dimers in a magneto-optical trap (MOT) are also shown.     

1,6- and 2,6-di-t-butyl-cyclopent [f] azulenide; double bond localization in a planar 14 π-perimeter

The stable diatropic 1,6- and 2,6-di-t-butyl-cyclo-pent[f]azulenides $\text{9a}$ and $\text{b}$ are prepared and shown to be dominated by polymethide conjugation rather than by 14π-perimeter conjugation.     

Preparation and characterization of hollow spheres of rutile

Hollow spherical particles of rutile were obtained by coating colloidal polystyrene beads with a titanium oxide hydrate layer and subsequently calcining at elevated temperatures under an oxygen atmosphere. In order to investigate the optimum conditions for the preparation of these hollow beads the maximum temperature and heating rate were systematically varied. The dimensions of the voids and the shell thickness of the hollow beads can be tailored by the size of the polystyrene beads and the thickness of the inorganic layer, respectively.     

Anisotropy of the low temperature resistivity of hexagonal single crystalline spin glass systems

The impurity contribution to the resistivity in zero field (T) of dilute hexagonal single crystals of ZnMn, CdMn and MgMn has been studied in the mK range on samples cut parallel () and perpendicular () to thec-axis, using a SQUID technique for the measurements. Typical spin glass behavior is found in (T) as well as (T) for all alloys, with Kondo like logarithmic increases at higher temperatures and maxima atT _m at lower temperatures, indicating the influence of impurity interactions. The differences in the corresponding isotropic resistivity _poly(T) between the three systems can qualitatively be understood within the framework of a theoretical model by Larsen, describing (T) as a function of universal quantitiesT/T _K and _RKKY/T _K , where _RKKY is the RKKY-interaction strength andT _K the Kondo temperature. With respect to the two lattice directions studied, the behavior of (T and (T is anisotropic in the Kondo regime as well as in the range where ordering becomes important. While the anisotropy in the Kondo slope can be understood by an anisotropic unitarity limit, the understanding of the anisotropy in region where impurity interactions are important remains problematic.Dedicated to Prof. Dr. S. Methfessel on the occasion of his 60th birthday     

Über die Alkalienbestimmung in Mineralien mit Hilfe des Interferometers

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