Identification of terfenadine as an inhibitor of human CD81-receptor HCV-E2 interaction: synthesis and structure optimization

Terfenadine (4-[4-(hydroxydiphenylmethyl)-1-piperidyl]-1-(4-tert-butylphenyl)-butan-1-ol) was identified in a biological screening to be a moderate inhibitor (27% inhibition) of the CD81-LEL-HCV-E2 interaction. To increase the observed biological activity, 63 terfenadine derivates were synthesized via microwave assisted nucleophilic substitution. The prepared compounds were tested for their inhibitory potency by means ofa fluorescence labeled antibody assay using HUH7.5 cells. Distinct structure-activity relationships could be derived. Optimization was successful, leading to 3g, identified as the most potent compound (69 % inhibition). Experiments with viral particles revealed that there might be additional HCV infection reducing mechanisms.     

Two-phase damage modeling of concrete affected by alkali–silica reaction under variable temperature and humidity conditions

In the present work the concrete affected by alkali–silica reaction (ASR) is represented as a two-phase material made of a solid skeleton and a wet expanding gel, which exerts a pressure capable of severely damaging the concrete surrounding the reactive sites. Both the effects of temperature and humidity conditions on the kinetic of the chemical reaction and on the final value of the consequent expansion are included in the proposed model. The mechanical degradation induced by the ASR is described by a phenomenological isotropic damage model. The constitutive model, implemented in a finite element code, is used for the analyses of structures made of reactive concrete in the presence of temperature and moisture gradients. Firstly the temperature and humidity fields are obtained through uncoupled heat and moisture transport analyses and then the chemo-mechanical analysis is performed starting from the values of temperature and humidity preliminary calculated.     

New polymer matrix system for phosphorescent organic light‐emitting diodes and the role of the small molecular co‐host

A new matrix system for phosphorescent organic light‐emitting diodes (OLEDs) based on an electron transporting component attached to an inert polymer backbone, an electronically neutral co‐host, and a phosphorescent dye that serves as both emitter and hole conductor are presented. The inert co‐host is used either as small molecules or covalently connected to the same chain as the electron‐transporting host. The use of a small molecular inert co‐host in the active layer is shown to be highly advantageous in comparison to a purely polymeric matrix bearing the same functionalities. Analysis of the dye phosphorescence decay in pure polymer, small molecular co‐host film, and their blend lets to conclude that dye molecules distribute mostly in the small molecular co‐host phase, where the co‐host prevents agglomeration and self‐quenching of the phosphorescence as well as energy transfer to the electron transporting units. In addition, the co‐host accumulates at the anode interface where it acts as electron blocking layer and improves hole injection. This favorable phase separation between polymeric and small molecular components results in devices with efficiencies of about 47 cd/A at a luminance of 1000 cd/m². Investigation of OLED degradation demonstrates the presence of two time regimes: one fast component that leads to a strong decrease at short times followed by a slower decrease at longer times. Unlike the long time degradation, the efficiency loss that occurs at short times is reversible and can be recovered by annealing of the device at 180 °C. We also show that the long‐time degradation must be related to a change of the optical and electrical bulk properties. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Potentiometrie

Ohne Zusammenfassung     

Pressure effects in the isoelectronic REFe0.85Ir0.15AsO system

The effect of chemical and hydrostatic pressure has been studied systematically in a selected system belonging to the 1111 family of iron pnictide high-temperature superconductors. The results show a surprising similarity between the trend of critical temperature vs hydrostatic pressure for isoelectronic samples with different rare earths (RE) on the RE site and samples of the SmFeAsO(1-x)F(x) series with different doping levels. These results open new questions about the underlying mechanism for superconductivity in iron pnictides.     

The allosteric properties of hemoglobin: insights from natural and site directed mutants

After over a century of extensive research, hemoglobin has become the prototype of allosteric and cooperative proteins. Its molecular structure, known in great detail, has allowed the design of hundreds of site directed mutations, aimed at interfering with its function, and thus at testing our hypotheses on the molecular mechanisms of allostery. The wealth of information thus obtained is difficult to read except for specialists, not only because it makes use of many different technical approaches, but also because of its intrinsically patchy nature. Moreover, several researchers have tried to assign specific roles to segments of the polypeptide chains, rather than to single residues, and have tested their hypotheses by multiple point mutations or by complete replacement with the homologous segment from a different hemoglobin to produce chimeric macromolecules. This approach is in great need of a revision since putative functionally relevant segments partially overlap. This review briefly describes the structure and function of hemoglobin, and analyzes the effect of point mutations, multiple mutations and segment replacement, with special attention to possible biotechnological applications, ranging from pharmacology (Hb solutions as resuscitating fluids and sources of the protein found in hemoglobinopathies for biochemical studies) to bioreactors. Occasional reference is made to site directed mutants of myoglobin, whenever this helps clarifying perplexing results obtained on hemoglobin.