Edge-to-face CH/pi aromatic interaction and molecular self-recognition in epi-cinchona-based bifunctional thiourea organocatalysis

The impact of cooperativity between intermolecular interactions is demonstrated by the molecular self-recognition properties of highly enantioselective epi-cinchona bifunctional thiourea organocatalysts. Low-temperature NMR experiments in inert solvents have revealed two sets of nonequivalent resonances in equal population for thiourea-modified members of the epi-quinine and epi-quinidine families. In solution, the predominance of an asymmetric (C1) dimeric self-assembly with noteworthy structural motifs became evident: simultaneous intra- and intermolecular thiourea hydrogen bonding and a CH/pi interaction were observed. Both the stereochemical and the diverse conformational features of the system favor the observed quinoline T-shaped aromatic pi-pi stacking interaction. The structure findings are supported by quantitative proton-proton distance data that were available from NOE buildup curves. The 3D structure of the dimeric assembly has been modeled in agreement with the H-H distance restraints. Owing to the geometrical preference associated with the dimerization process, the self-assembled bifunctional system is interpreted as a charge-transfer complex with the potential for catalyst self-activation.     

Impact of ligand protonation on virtual screening against beta-secretase (BACE1)

Structure-based virtual screens were carried out against beta-secretase (BACE1) to investigate the impact of ligand protonation on screening efficacy. A comparative evaluation of the performance and its dependence on ligand protonation states docking by Surflex, eHiTS, GOLD, and FlexX-Pharm was performed. Virtual screening performed by FlexX-Pharm (EF(1%)=69) and Surflex (EF(1%)=58) provided the best efficiency. Screening protocols by FlexX-Pharm and GOLD were affected by ligand protonation, while performance of Surflex did not depend on ligand protonation.     

Adsorption of sodium alkyl sulfate homologues at the air/solution interface

Experimental results are presented on the adsorption of sodium alkyl sulfate homologues (nC = 8-14) at the air/solution interface. The adsorption isotherms calculated from equilibrium surface-tension vs concentration data and the critical micelle concentration change regularly with the length of the alkyl chain; the odd/even effect was not observed. The isotherms were analyzed using a model-independent approach. The analysis indicates that the total driving force of adsorption reaches a plateau value and becomes constant in the function of the adsorbed amount in the case of each homologue. With the use of different electrostatic models, it was demonstrated that this behavior is consistent with a saturation-type hydrophobic driving-force contribution, which can be interpreted by the development of a liquidlike alkane environment in the adsorbed layer above a "critical" adsorbed amount.     

A receptor-binding-based bioassay to determine the potency of a plasmid biopharmaceutical encoding VEGF-C

Over the last decade biological assays (bioassays) have gained much importance for quality control in biopharmaceutical development and manufacturing. Here we describe the development and validation of a bioassay to determine the biological activity (potency) of the plasmid biopharmaceutical pVGI.1 which encodes the VEGF-C (VEGF-2) protein. This assay was developed to test drug substance and drug product for release and stability testing for phase I and II clinical trials. The main focus was on fast assay development and easy handling of the assay, combined with valid results representing the specific therapeutic mechanism. The method includes the expression of the VEGF-C protein in mammalian cells and its binding to the cell surface receptor VEGFR-3. The binding activity of VEGF-C to its immobilized receptor is quantified in a colorimetric assay. IC₅₀ values of VEGF-C expressed after transfection with sample plasmid and an in-house standard plasmid are determined. The ratio of the IC₅₀ value of the test article to that of the reference standard reflects the potency of the sample. The potency assay meets the criteria generally requested by authorities for precision, linearity, accuracy, and range. Therefore the assay can be used in pharmaceutical quality control and is a suitable basis for development of related bioassays.     

Molecular constants of aluminum monohalides: caveats for computations of simple inorganic molecules

Quantum chemical calculations have become an everyday tool in chemistry. There are commercial program packages and downloadable basis sets for most needs. However, many chemists rarely go beyond the routine use of these programs, rarely, if ever, checking the original references for basis sets. In this letter, we point out some of the pitfalls of such an approach. Structural parameters of the aluminum-monohalides, AlF, AlCl, AlBr, and AlI, have been calculated using the Gaussian 03 program package and different basis set combinations.     

Smart nanocomposite polymer gels

The combination of polymers with nanomaterials displays novel and often enhanced properties compared to the traditional materials. They can open up possibilities for new technological applications. The magnetic polymer gel represents a new type of composites consisting of small magnetic particles, usually from the nanometer range to the micron range, dispersed in a highly elastic polymeric gel matrix. Combination of magnetic and elastic properties leads to a number of striking phenomena that are exhibited in response to impressed magnetic fields. Giant deformational effects, high elasticity, anisotropic properties, temporary reinforcement and quick response to magnetic field open new opportunities for using such materials for various applications.     

The specific grain-boundary electrical resistivity of Ni

The purpose of the present study was to provide a reliable value for the specific grain-boundary resistivity ρ_SGBR of Ni metal. New results are presented on the room-temperature electrical resistivity of nanocrystalline (nc) Ni metal samples produced by electrodeposition with various grain sizes. These resistivity data were compared with previous reports on nc-Ni and all results were analysed according to the procedure of Andrews [Phys. Lett. 19, 558 (1965)] who found that the resistivity increment due to grain boundaries is proportional to the grain-boundary surface area per unit volume which is, on the other hand, inversely proportional to the grain size. It is pointed out that the grain size directly accessible by transmission electron microscopy imaging is the relevant parameter for the evaluation of ρ_SGBR whereas the crystallite size deduced from X-ray diffraction line broadening leads to an underestimation of ρ_SGBR because coherency-breaking intragrain defects not contributing significantly to the resistivity also cause a line broadening. From the evaluation of the nc-Ni resistivity data at room temperature, we find that 4.45·10^?16?Ω·m²?ρ_SGBR(Ni)??16?Ω·m² and our upper bound agrees exactly with the most recent calculated value in the literature.     

Conductance distribution at criticality: one‐dimensional Anderson model with random long‐range hopping

We study numerically the conductance distribution function w(T) for the one‐dimensional Anderson model with random long‐range hopping described by the Power‐law Banded Random Matrix model at criticality. We concentrate on the case of two single‐channel leads attached to the system. We observe a smooth transition from localized to delocalized behavior in the conductance distribution by increasing b, the effective bandwidth of the model. Also, for b < 1 we show that w(ln T/T_typ) is scale invariant, where T_typ = exp 〈 ln T 〉 is the typical value of T. Moreover, we find that for T < T_typ, w(ln T/T_typ) shows a universal behavior proportional to (T/T_typ)^‐1/2.     

XAS and XMCD studies of amorphous FeCo-based ribbons

This paper reports x-ray absorption spectroscopy (XAS) and x-ray magnetic circular dichroism (XMCD) studies at Fe L_3,2 and Co L_3,2-edges to investigate the electronic structure of (Fe_100 ? xCo_x)₇₈Si₉Nb₃B₉Cu₁ (0 < x < 95) alloys. The influence of controlled Co addition on electronic structural and magnetic properties of (Fe_100 ? xCo_x)₇₈Si₉Nb₃B₉Cu₁ (x = 0, 20, 40, and 60) alloys has been investigated and it has been observed that Co exists as Co²⁺/Co³⁺, while Fe exists as a mixture of Fe⁰ (metallic) and Fe²⁺. The XMCD studies confirm these results and reveal that Co-ions are responsible for the room temperature ferromagnetism (RTFM) in the system, while at Fe L_3,2-edge it shows a diamagnetic behavior.