Structural characterization of a pentacene monolayer on an amorphous SiO2 substrate with grazing incidence x-ray diffraction

Grazing incidence X-ray diffraction reveals that a pentacene monolayer, grown on an amorphous SiO2 substrate that is commonly used as a dielectric layer in organic thin film transistors (OTFTs), is crystalline. A preliminary energy-minimized model of the monolayer, based on the GIXD data, reveals that the pentacene molecules adopt a herringbone arrangement with their long axes tilted slightly from the substrate normal. Although this arrangement resembles the general packing features of the (001) layer in single crystals of bulk pentacene, the monolayer lattice parameters and crystal structure differ from those of the bulk. Because carrier transport in pentacene OTFTs is presumed to occur in the semiconductor layers near the dielectric interface, the discovery of a crystalline monolayer structure on amorphous SiO2 has important implications for transport in OTFTs.     

Structural basis for the highly selective inhibition of MMP-13

Inhibitors for matrix metalloproteinases (MMPs) are under investigation for the treatment of cancer, arthritis, and cardiovascular disease. Here, we report a class of highly selective MMP-13 inhibitors (pyrimidine dicarboxamides) that exhibit no detectable activity against other MMPs. The high-resolution X-ray structures of three molecules of this series bound to MMP-13 reveal a novel binding mode characterized by the absence of interactions between the inhibitors and the catalytic zinc. The inhibitors bind in the S1' pocket and extend into an additional S1' side pocket, which is unique to MMP-13. We analyze the determinants for selectivity and describe the rational design of improved compounds with low nanomolar affinity.     

Aging effect on the mechanical properties of hybrid gels

Sol-gel derived unsupported films and thin rods have been obtained from co-hydrolysis of triethoxysilane and methyldiethoxysilane. The materials are flexible, dense and transparent. Films and rods have been aged for different periods of time in air at room temperature. The elastic modulus has been measured by means of tensile or flexural tests. Measurements showed an increase of elastic modulus with aging time and showed different values for films and rods. The observed evolution of mechanical properties has been related to a corresponding structural modification as highlighted mainly by MAS-NMR studies. Analyses pointed out the crucial role of condensation processes and showed that the stiffness increase arises from the formation of relatively few bonds which link and constrain pre-existing mobile network regions.     

Relative quantification of erythropoietin receptor-dependent phosphoproteins using in-gel 18O-labeling and tandem mass spectrometry

On examining different proteomics approaches for the investigation of structure-function relationships of erythropoietin (EPO) receptor signaling, it was found that two-dimensional gel electrophoresis/mass spectrometry procedures are clearly limited in their ability to detect low-expressed signaling proteins. Instead it was found that a strategy involving anti-phosphotyrosine immunoprecipitation, one-dimensional gel electrophoresis (1DE), and capillary liquid chromatography/tandem mass spectrometry (LC/MS/MS) provides the sensitivity required for identification of signaling proteins. In the present work the immunoprecipitation/1DE/LC/MS approach was combined with an in-gel 18O-labeling technique to analyze EPO receptor-dependent proteins. Identification and relative quantification of more than 180 EPO receptor-dependent proteins were achieved directly based on the in-gel 18O-labeling approach.     

A formal total synthesis of (-)-FR901483, using a tandem cationic aza-Cope rearrangement/Mannich cyclization approach

A formal total synthesis of the immunosuppressant FR901483 has been accomplished. The key step in the synthesis utilizes a tandem cationic aza-Cope rearrangement/Mannich cyclization reaction for accessing the unprecedented bridging tricyclic azaspirane substructure of this compound. The tandem reaction proceeds through a bridgehead iminium ion, a functionality that has rarely been explored in the context of natural product syntheses. Improved stereoselectivity was observed in an aldol reaction when using a Boc-protected amino aldehyde and zinc chloride as an additive. A stereoselective epimerization of the aldehyde-containing stereocenter was achieved with l-phenylalanine upon completion of the Mannich cyclization. Finally, this synthesis is the only one to date that controls the stereochemistry of the oxygen-bearing stereocenters. All other synthetic routes required late stage adjustments to at least one of these stereocenters.     

Standard pH values for potassium hydrogenphthalate reference buffer solutions in 10, 30 and 50% (w/w) 1,4-dioxane/water mixed solvents at temperatures from 288.15 to 318.15 K

Standard pH(S) values for 0.05 mol kg^?1 potassium hydrogenphthalate (KHpH) reference buffer solutions in 10, 30 and 50% (w/w) 1,4-dioxane/water solvent mixtures within the temperature range 288.15–318.15 K are determined from e.m.f. measurements of the cell without transference Pt|H₂|KHPh + KCl|AgCl|Ag|Pt. The consistency of the results is analysed by a recently described method of multilinear regression of the quantity p(a_Hγ_Cl) as a function of both solution composition and temperature. The standard pH(S) determined can be reproduced to within ±0.01 by the equation pH(S) - 4.004 + 3.309w + 0.408z + 1.037w³ - 14.95zw² + 27.1zw³, where w is the weight fraction of dioxane in the solvent mixture,z = (T –θ)/θ, and θ - 298.15 K. Values of the first ionization constant of phthalic acid (H₂Ph; benzene-1,2-dicarboxylic acid) in the above solvent mixtures are also determined from e.m.f. measurements of the cell without transference Pt|H₂|H₂Ph + KHPh + KCl|AgCl|Ag|Pt.     

Temperature dependence of the resolution of diastereomeric isoprenoids in capillary GC. Experiments with 50 μm, 100 μm,and 250 μm i.d. Columns

The resolution of the diastereoisomers of norpristane, pristane, and phytane was studied as a function of the column internal diameter and/or the residence time of the compounds in the column. Increasing the residence time in the column by operating the column at a lower temperature program rate enhances the resolution more than reducing the internal diameter of the column. Practical experience with ultra narrow bore columns is also presented.     

CCR5 antagonists: 3-(pyrrolidin-1-yl)propionic acid analogues with potent anti-HIV activity

[reaction: see text] A novel approach to alpha,alpha-disubstituted-beta-amino acids (beta(2,2)-amino acids) was employed in the synthesis of a series of 3-(pyrrolidin-1-yl)propionic acids possessing high affinity for the CCR5 receptor and potent anti-HIV activity. The rat pharmacokinetics for these new analogues featured higher bioavailabilities and lower rates of clearance as compared to cyclopentane 1.