Piezoelectric properties and phase transition temperatures of the solid solution of (1 − x)(Bi0.5Na0.5)TiO3–xSrTiO3

The phase diagram of (1 ? x)(Bi_0.5Na_0.5)TiO₃–xSrTiO₃ was completed and investigations on polarization and strain in this system were carried out. (1 ? x)(Bi_0.5Na_0.5)TiO₃–xSrTiO₃-ceramics were prepared by conventional mixed oxide processing. The depolarization temperature (T_d), the temperature of the rhombohedral–tetragonal phase transition (T_r–t) and the Curie temperature (T_m) were determined by measuring the temperature dependence of the relative permittivity. All solid solutions of (1 ? x)(Bi_0.5Na_0.5)TiO₃–xSrTiO₃ show relaxor behavior (A-site relaxor). From XRD-measurements a broad maximum of the lattice parameter can be observed around x = 0.5 but no structural evidence for a morphotropic phase boundary was found. SEM-analysis revealed a decrease of the grain size for increasing SrTiO₃-content. At room temperature a maximum of strain of about 0.29% was found at x = 0.25 which coincides with a transition from a ferroelectric to an antiferroelectric phase. The temperature dependence of the displacement indicates an additional contribution from a structural transition (rhombohedral–tetragonal), which would be of certain relevance for the existence of a morphotropic phase boundary.     

Chemical experiments with superheavy elements

Unnoticed by many chemists, the Periodic Table of the Elements has been extended significantly in the last couple of years and the 7th period has very recently been completed with eka-Rn (element 118) currently being the heaviest element whose synthesis has been reported. These 'superheavy' elements (also called transactinides with atomic number > or = 104 (Rf)) have been artificially synthesized in fusion reactions at accelerators in minute quantities of a few single atoms. In addition, all isotopes of the transactinide elements are radioactive and decay with rather short half-lives. Nevertheless, it has been possible in some cases to investigate experimentally chemical properties of transactinide elements and even synthesize simple compounds. The experimental investigation of superheavy elements is especially intriguing, since theoretical calculations predict significant deviations from periodic trends due to the influence of strong relativistic effects. In this contribution first experiments with hassium (Hs, atomic number 108), copernicium (Cn, atomic number 112) and element 114 (eka-Pb) are reviewed.     

Comparison of Structure‐ and Ligand‐Based Virtual Screening Protocols Considering Hit List Complementarity and Enrichment Factors

Structure‐ and ligand‐based virtual‐screening methods (docking, 2D‐ and 3D‐similarity searching) were analysed for their effectiveness in virtual screening against four different targets: angiotensin‐converting enzyme (ACE), cyclooxygenase 2 (COX‐2), thrombin and human immunodeficiency virus 1 (HIV‐1) protease. The relative performance of the tools was compared by examining their ability to recognise known active compounds from a set of actives and nonactives. Furthermore, we investigated whether the application of different virtual‐screening methods in parallel provides complementary or redundant hit lists. Docking was performed with GOLD, Glide, FlexX and Surflex. The obtained docking poses were rescored by using nine different scoring functions in addition to the scoring functions implemented as objective functions in the docking algorithms. Ligand‐based virtual screening was done with ROCS (3D‐similarity searching), Feature Trees and Scitegic Functional Fingerprints (2D‐similarity searching). The results show that structure‐ and ligand‐based virtual‐screening methods provide comparable enrichments in detecting active compounds. Interestingly, the hit lists that are obtained from different virtual‐screening methods are generally highly complementary. These results suggest that a parallel application of different structure‐ and ligand‐based virtual‐screening methods increases the chance of identifying more (and more diverse) active compounds from a virtual‐screening campaign.     

Prospective Validation of a Comprehensive In silico hERG Model and its Applications to Commercial Compound and Drug Databases

Ligand‐based in silico hERG models were generated for 2 644 compounds using linear discriminant analysis (LDA) and support vector machines (SVM). As a result, the dataset used for the model generation is the largest publicly available (see Supporting Information). Extended connectivity fingerprints (ECFPs) and functional class fingerprints (FCFPs) were used to describe chemical space. All models showed area under curve (AUC) values ranging from 0.89 to 0.94 in a fivefold cross‐validation, indicating high model consistency. Models correctly predicted 80 % of an additional, external test set; Y‐scrambling was also performed to rule out chance correlation. Additionally models based on patch clamp data and radioligand binding data were generated separately to analyze their predictive ability when compared to combined models. To experimentally validate the models, 50 of the predicted hERG blockers from the Chembridge database and ten of the predicted non‐hERG blockers from an in‐house compound library were selected for biological evaluation. Out of those 50 predicted hERG blockers, tested at a concentration of 10 μM , 18 compounds showed more than 50 % displacement of [³H]astemizole binding to cell membranes expressing the hERG channel. K_i values of four of the selected binders were determined to be in the micromolar and high nanomolar range (K_i (VH 01 )=2.0 μM , K_i (VH 06 )=0.15 μM , K_i (VH 19 )=1.1 μM and K_i (VH 47 )=18 μM ). Of these four compounds, VH 01 and VH 47 showed also a second, even higher affinity binding site with K_i values of 7.4 nM and 36 nM , respectively. In the case of non‐hERG blockers, all ten compounds tested were found to be inactive, showing less than 50 % displacement of [³H]astemizole binding at 10 μM . These experimentally validated models were then used to virtually screen commercial compound databases to evaluate whether they contain hERG blockers. 109 784 (23 %) of Chembridge, 133 175 (38 %) of Chemdiv, 111 737 (31 %) of Asinex and 11 116 (18 %) of the Maybridge database were predicted to be hERG blockers by at least two of the models, a prediction which could, for example, be used as a pre‐filtering tool for compounds with potential hERG liabilities.     

Fluorous Iminoalditols: A New Family of Glycosidase Inhibitors and Pharmacological Chaperones

A collection of new reversible glycosidase inhibitors of the iminoalditol type featuring N‐substituents containing perfluorinated regions has been prepared for evaluation of physicochemical, biochemical and diagnostic properties. The vast variety of feasible oligofluoro moieties allows for modular approaches to customised structures according to the intended applications, which are influenced by the fluorine content as well as the distance of the fluorous moiety from the ring nitrogen. The first examples, in particular in the D ‐galacto series, exhibited excellent inhibitory activities. A preliminary screen with two human cell lines showed that, at subinhibitory concentrations, they are powerful pharmacological chaperones enhancing the activities of the catalytically handicapped lysosomal D ‐galactosidase mutants associated with GM1 gangliosidosis and Morquio B disease.     

Deposition welding of hot forging dies using nanoparticle reinforced weld metal

In the application field of forging, the form-giving tool components are subject to process-related severe environmental conditions, such as high mechanical loads acting simultaneously with high tribological and thermal charges. Due to high machine hour rates as well as increasing environmental requirements in terms of energy consumption, wear protection methods and suitable repair measures for forging tools become more and more important. Laser deposition welding represents an established process for the repair of complex shaped surfaces. A new approach is the addition of nano-sized ceramic particles to improve the mechanical properties. The main idea is to reduce the grain size of the cladded layers by adding nano-sized nuclei. A fine grained microstructure will improve strength as well as ductility and fatigue resistance. Furthermore small hard particles can improve the wear resistance without affecting the friction of the surface. After the cladding process the surface has to be finished usually by turning, milling and grinding operations. Within the presented paper the potential of nanoparticle-reinforced deposition welding with regard to increasing the wear resistance of forging dies will be examined. First, the process of nanoparticle-reinforced deposition welding will be presented. Afterwards it will be shown that yttrium oxide, titanium carbide and tungsten carbide nanoparticles in an AISI H10 matrix material will influence the friction coefficient between forging tool and material as well as the wear properties.     

Effect of Inclusion Size and Distribution on the Corrosion Behavior of Medical-Device Grade Nitinol Tubing

Nonmetallic inclusions in Nitinol, such as carbides (TiC) and intermetallic oxides (Ti₄Ni₂O _x ), are known to be triggers for fatigue failure of Nitinol medical devices. These mechanically brittle inclusions are introduced during the melting process. As a result of hot and cold working in the production of Nitinol tubing inclusions are fractionalized due to the mechanical deformation imposed. While the role of inclusions regarding Nitinol fatigue performance has been studied extensively in the past, their effect on Nitinol corrosion behavior was investigated in only a limited number of studies. The focus of the present work was to understand the effect of inclusion size and distribution on the corrosion behavior of medical-device grade Nitinol tubing made from three different ingot sources during different manufacturing stages: (i) for the initial stage (hollow: round bar with centric hole), (ii) after hot drawing, and (iii) after the final drawing step (final tubing dimensions: outer diameter 0.3 mm, wall thickness 0.1 mm). For one ingot source, two different material qualities were investigated. Potentiodynamic polarization tests were performed for electropolished samples of the above-mentioned stages. Results indicate that inclusion size rather than inclusion quantity affects the susceptibility of electropolished Nitinol to pitting corrosion.