Translational energy release and stereochemistry of steroids. VIII-The mechanism of the elimination of water from metastable ions in epimeric 3-hydroxy steroids of the 5α-series

The mechanism of water elimination from metastable molecular, [M ? CH₃˙]⁺ and [M ? ring D]⁺˙ ions of epimeric 3-hydroxy steroids of the 5α-series has been elucidated. Deuterium labelling, the measurement of the translational energy released during the loss of water, and collision-induced decomposition mass-analysed kinetic energy spectrometry were the techniques used. It was found that the mechanisms of water loss from metastable M⁺˙ and [M ? ring D]⁺˙ ions is different from that from [M ? CH₃˙]⁺ ions.     

A new thermoelectric material: CsBi4Te6

The highly anisotropic material CsBi(4)Te(6) was prepared by the reaction of Cs/Bi(2)Te(3) around 600 degrees C. The compound crystallizes in the monoclinic space group C2/m with a = 51.9205(8) A, b = 4.4025(1) A, c = 14.5118(3) A, beta = 101.480(1) degrees, V = 3250.75(11) A(3), and Z = 8. The final R values are R(1) = 0.0585 and wR(2) = 0.1127 for all data. The compound has a 2-D structure composed of NaCl-type [Bi(4)Te(6)] anionic layers and Cs(+) ions residing between the layers. The [Bi(4)Te(6)] layers are interconnected by Bi-Bi bonds at a distance of 3.2383(10) A. This material is a narrow gap semiconductor. Optimization studies on the thermoelectric properties with a variety of doping agents show that the electrical properties of CsBi(4)Te(6) can be tuned to yield an optimized thermoelectric material which is promising for low-temperature applications. SbI(3) doping resulted in p-type behavior and a maximum power factor of 51.5 microW/cm.K(2) at 184 K and the corresponding ZT of 0.82 at 225 K. The highest power factor of 59.8 microW/cm.K(2) at 151 K was obtained from 0.06% Sb-doped material. We report here the synthesis, physicochemical properties, doping characteristics, charge-transport properties, and thermal conductivity. Also presented are studies on n-type CsBi(4)Te(6) and comparisons to those of p-type.     

On the existence of SH3, SeH3, and TeH3: Discrepancies between all-electron and pseudopotential calculations

Ab initio calculations using both pseudopotential and double and triple-ζ all-electron basis sets, with and without electron correlation (MP2, QCISD), have been performed on the λ⁴-sulfanyl (SH₃), λ⁴-selanyl (SeH₃), and λ⁴-tellanyl (TeH₃) radicals. All-electron basis sets of double-ζ quality predict that SH₃ and SeH₃ correspond to transition states on their respective potential energy surfaces. In contrast, the pseudopotentials of Hay and Wadt predict that SH₃ and SeH₃ correspond to local minima at the QCISD level of theory while the pseudopotentials of Christiansen and Stevens predict transition states. By comparison, TeH₃ proved to be a local minimum at all levels of theory. Interestingly, when a very large (triple-ζ) all-electron basis set was used, SH₃ proved to be a transition state; however, in this instance the potential energy surface was found to be much flatter than in the case for which a double-ζ basis set was used, suggesting that further improvements in the basis set may lead to a local minimum. Further improvements in the all-electron selenium basis also led to a local minimum for SeH₃ at the QCISD level of theory. © 1995 by John Wiley & Sons, Inc.     

An approach to computer-aided inhibitor design: Application to cathepsin L

Summary We have developed an approach to search for molecules that can be used as lead compounds in designing an inhibitor for a given proteolytic enzyme when the 3D structure of a homologous protein is known. This approach is based on taking the cast of the binding pocket of the protease and comparing its dimensions with that of the dimensions of small molecules. Herein the 3D structure of papain is used to model cathepsin L using the comparative modeling technique. The cast of the binding pocket is computed using the crystal structure of papain because the structures of papain and the model of cathepsin L are found to be similar at the binding site. The dimensions of the cast of the binding site of papain are used to screen for molecules from the Cambridge Structural Database (CSD) of small molecules. Twenty molecules out of the 80 000 small molecules in the CSD are found to have dimensions that are accommodated by the papain binding pocket. Visual comparison of the shapes of the cast and the 20 screened molecules resulted in identifying brevotoxin b, a toxin isolated from the red tide dinoflagellate Ptycho brevis (previously classified as Gymonodium breve), as the structure that best fits the binding pocket of papain. We tested the proteolytic activity of papain and cathepsin L in the presence of brevotoxin b and found inhibition of papain and cathepsin L with K_is of 25 M and 0.6 M, respectively. We also compare our method with a more elaborate method in the literature, by presenting our results on the computer search for inhibitors of the HIV-1 protease.     

Theoretical study on the isomerization behavior between alpha,beta-unsaturated acyl radicals and alpha-ketenyl radicals

[reaction: see text] Ab initio calculations using 6-311G**, cc-pVDZ, aug-cc-pVDZ, and a (valence) double-zeta pseudopotential (DZP) basis set, with (QCISD, CCSD(T)) and without (UHF) the inclusion of electron correlation, and density functional methods (BHandHLYP, B3LYP) predict that alpha,beta-unsaturated acyl radicals and alpha-ketenyl radicals exist as isomers. At the CCSD(T)/cc-pVDZ//BHandHLY/cc-pVDZ level of theory, energy barriers of 15.1 and 17.7-21.7 kJ mol(-)(1) are calculated for the isomerization of s-trans-propenoyl and s-trans-crotonoyl radical to ketenylmethyl and 1-ketenylethyl radical, respectively. Similar results are obtained for the reactions of s-trans isomers involving silyl, germyl, and stannyl groups with energy barriers (DeltaE++) of 12.2-12.4, 13.1-13.9, and 12.9-18.2 kJ mol(-)(1) at the CCSD(T)/DZP//BHandHLYP/DZP calculation, respectively. These results suggest that alpha,beta-unsaturated acyl radicals and alpha-ketenyl radicals are not canonical forms but are isomeric species that can rapidly interconvert.     

Nanoscale organization of the pathogen receptor DC-SIGN mapped by single-molecule high-resolution fluorescence microscopy.

DC-SIGN, a C-type lectin exclusively expressed on dendritic cells (DCs), plays an important role in pathogen recognition by binding with high affinity to a large variety of microorganisms. Recent experimental evidence points to a direct relation between the function of DC-SIGN as a viral receptor and its spatial arrangement on the plasma membrane. We have investigated the nanoscale organization of fluorescently labeled DC-SIGN on intact isolated DCs by means of near-field scanning optical microscopy (NSOM) combined with single-molecule detection. Fluorescence spots of different intensity and size have been directly visualized by optical means with a spatial resolution of less than 100 nm. Intensity- and size-distribution histograms of the DC-SIGN fluorescent spots confirm that approximately 80 % of the receptors are organized in nanosized domains randomly distributed on the cell membrane. Intensity-size correlation analysis revealed remarkable heterogeneity in the molecular packing density of the domains. Furthermore, we have mapped the intermolecular organization within a dense cluster by means of sequential NSOM imaging combined with discrete single-molecule photobleaching. In this way we have determined the spatial coordinates of 13 different individual dyes, with a localization accuracy of 6 nm. Our experimental observations are all consistent with an arrangement of DC-SIGN designed to maximize its chances of binding to a wide range of microorganisms. Our data also illustrate the potential of NSOM as an ultrasensitive, high-resolution technique to probe nanometer-scale organization of molecules on the cell membrane.     

An Inexpensive Laser Raman Spectrometer Based on CCD Detection

We describe an inexpensive modular Raman spectrometer system that can be assembled from commercial components for under $5000. Three typical applications are presented: a demonstration of a vibrational isotope effect, a Raman polarization experiment, and a resonance Raman experiment. This spectrometer system should make it easier to include the important topic of Raman spectroscopy in the undergraduate physical and analytical chemistry laboratory curricula.