Chemoenzymatic synthesis of the enantiomerically pure 1,2,3,4-tetrahydroquinoline moiety of the antithrombotic (21R)- and (21S)-argatroban

The synthetic antithrombotic argatroban is a dipeptide between the nonproteogenic (2R,4R)-4-methyl-2-piperidine carboxylic acid and l-arginine, in turn bonded to a 3-methyltetrahydroquinoline sulfonyl group; the drug is usually prepared and administered as a mixture of C-21-diastereoisomers. By means of a biocatalytic transformation enantiomerically pure (R)- and (S)-synthons, suitable for the synthesis of separate (21R)- and (21S)- argatroban, were obtained.     

Diastereoselective synthesis of an argatroban intermediate,ethyl (2R,4R)-4-methylpipecolate,by means of a Mandyphos/rhodium complex-catalyzed hydrogenation

The synthetic antithrombotic argatroban is a dipeptide between the nonproteogenic (2R,4R)-4-methyl-2-piperidine carboxylic acid and l-arginine, in turn bonded to a methyltetrahydroquinoline sulfonyl group. An extensive screening of transition metal-based complexes with different ligands was performed in order to identify the best catalyst for the diastereoselective hydrogenation of a suitable 4,5-dehydropiperidine precursor aimed toward a synthesis of the (2R,4R)-4-methyl piperidine moiety.     

On EXAFS Debye‐Waller factor and recent advances

The effects of structural and vibrational disorder on the EXAFS signals are parameterized in terms of the Debye Waller (DW) factor. Here the vibrational contribution is addressed, which for most systems can be singled out by studying the temperature dependence of the EXAFS DW factor, which corresponds to a good accuracy to the parallel mean square relative displacement (MSRD) around the inter‐atomic equilibrium distance. By comparing the first‐shell EXAFS thermal expansion with the crystallographic thermal expansion one can evaluate the perpendicular MSRD. The results of recent measurements on copper and on several tetrahedral semiconductors are here critically compared and some properties of the MSRDs are discussed, such as the dependence of correlation, force constants and vibrational anisotropy on crystal structure and bond ionicity as well as the relative merits of the correlated Debye and Einstein models. The anharmonic contribution to the parallel MSRD of CdTe has been evaluated and a quasi‐harmonic analysis has been attempted, leading to an estimation of the bond Grüneisen parameter.     

Local thermal expansion in a cuprite structure: the case of Ag(2)O

The local thermal behavior of the Ag(2)O framework structure has been studied by extended x-ray absorption fine structure. The average Ag-O nearest-neighbor distance expands upon heating, while the Ag-Ag next-nearest-neighbor distance contracts. An original implementation of the cumulant analysis shows that the Ag-O expansion is a joint effect of potential anharmonicity and geometrical deformation of the Ag(4)O basic tetrahedral units. Accordingly, the negative thermal expansion of the lattice parameter in Ag(2)O cannot be explained uniquely in terms of rigid unit modes.     

Time-of-flight resolved transmission-grating diffraction of molecular beams

Diffraction of molecular beams of CH₃F, CHF₃, and metastable He^* and Ne^* from a 100-nm-period micro-fabricated transmission grating has been observed. Due to the finite velocity spread and the corresponding temporal coherence of the molecular beams, diffraction peaks of only the first few orders are resolved in total-intensity measurements, while higher order peaks are increasingly broadened and smeared-out. Combining time-of-flight (TOF) measurements with angular scans has allowed to observe TOF-resolved diffraction data which yield full resolution of all detected diffraction peaks. Here, this method has been applied to investigate atom/molecule-surface interactions. In general, it can be used to observe resolved diffraction patterns of a wide range of atomic and molecular beams whose broad velocity distributions prevent peak-resolution in conventional total-intensity measurements.Received: 3 September 2003, Published online: 21 October 2003PACS: 39.20. + q Atom interferometry techniques - 03.75.Be Atom and neutron optics - 07.77.Gx Atomic and molecular beam sources and detectors - 34.50.Dy Interactions of atoms and molecules with surfaces; photon and electron emission; neutralization of ionsW. Schöllkopf: Present address: Fritz-Haber-Institut der Max-Planck-Gesellschaft, Abteilung Molekülphysik, Faradayweg 4-6, 14195 Berlin, Germany.R.E. Grisenti: Present address: Johann Wolfgang Goethe-Universität, Institut für Kernphysik, August-Euler-Str. 6, 60486 Frankfurt, Germany.     

Ionization dynamics of helium dimers in fast collisions with He++

By employing the cold target recoil ion momentum spectroscopy technique, we have investigated the (He+, He+) breakup of a helium dimer (He2) caused by transfer ionization and double capture in collisions with alpha particles (E = 150 keV/u). Surprisingly, the results show a two-step process as well as a one-step process followed by electron exchange. In addition, interatomic Coulombic decay [L.?S. Cederbaum, J. Zobeley, and F. Tarantelli, Phys. Rev. Lett. 79, 4778 (1997).] is observed in an ion collision for the first time.     

Accuracy evaluation in temperature‐dependent EXAFS measurements of CdTe

The evaluation of uncertainty in temperature‐dependent EXAFS measurements is discussed, considering the specific case of a recent experiment performed on CdTe. EXAFS at both Cd and Te K‐edges was measured at different times and at different beamlines in a temperature range from 5 to 300 K. Attention is focused on the nearest‐neighbours parameters: bond thermal expansion, parallel and perpendicular mean‐square relative displacements and the third cumulant. Different causes of uncertainty, a comparison of experimental results with theoretical models, the difference between EXAFS and crystallographic thermal expansions and the meaning of the third cumulant are discussed.     

Oscillations in the expansion of solid 4He into vacuum

The particle flux through a micron-sized orifice into vacuum from a source chamber filled with solid 4He exhibits a striking sequence of periodic bursts. The period increases (decreases) with pressure (temperature), vanishing at the melting point for temperatures above the upper lambda point at 1.76 K. The oscillations are attributed to a periodic collapse of the solid induced by the accumulation of excess vacancies injected at the orifice and the period provides information on vacancy diffusivity. Dramatic deviations from this behavior below 1.76 K suggest important modifications in the flow properties of solid 4He induced by the excess vacancies.     

Suppression of nitric oxide production in mouse macrophages by soybean flavonoids accumulated in response to nitroprusside and fungal elicitation

Background

The anti-inflammatory properties of some flavonoids have been attributed to their ability to inhibit the production of NO by activated macrophages. Soybean cotyledons accumulate certain flavonoids following elicitation with an extract of the fungal pathogen Diaporthe phaseolorum f. sp. meridionalis (Dpm). Sodium nitroprusside (SNP), a nitric oxide donor, can substitute for Dpm in inducing flavonoid production. In this study, we investigated the effect of flavonoid-containing diffusates obtained from Dpm- and SNP-elicited soybean cotyledons on NO production by lipopolysaccharide (LPS)- and LPS plus interferon-γ (IFNγ)-activated murine macrophages.

Results

Significant inhibition of NO production, measured as nitrite formation, was observed when macrophages were activated in the presence of soybean diffusates from Dpm- or SNP-elicited cotyledons. This inhibition was dependent on the duration of exposure to the elicitor. Daidzein, genistein, luteolin and apigenin, the main flavonoids present in diffusates of elicited cotyledons, suppressed the NO production by LPS + IFNγ activated macrophages in a concentration-dependent manner, with IC₅₀ values of 81.4 μM, 34.5 μM, 38.6 μM and 10.4 μM respectively. For macrophages activated with LPS alone, the IC₅₀ values were 40.0 μM, 16.6 μM, 10.4 μM and 2.8 μM, respectively. Western blot analysis showed that iNOS expression was not affected by daidzein, was reduced by genistein, and was abolished by apigenin, luteolin and Dpm- and SNP-soybean diffusates at concentrations that significantly inhibited NO production by activated macrophages.

Conclusions

These results suggest that the suppressive effect of flavonoids on iNOS expression could account for the potent inhibitory effect of Dpm- and SNP-diffusates on NO production by activated macrophages. Since the physiological concentration of flavonoids in plants is normally low, the treatment of soybean tissues with SNP may provide a simple method for substantially increasing the concentration of metabolites that are beneficial for the treatment of chronic inflammatory diseases associated with NO production.

     

Emissive chromium(III) complexes with substituted arylethynyl ligands

Arylethynylchromium(III) complexes of the form trans-[Cr(cyclam)(CCC(6)H(4)R)(2)]OTf (where cyclam = 1,4,8,11-tetraazacyclotetradecane, R = H, CH(3), or CF(3) in the para position, and OTf = trifluoromethanesulfonate) have been prepared and characterized by IR spectroscopy and X-ray diffraction. The complexes are emissive with excited-state lifetimes in a deoxygenated fluid solution between 200 and 300 micros.