Struktur und Komplexbildung kleiner 1,3-dithiol-anellierter Thiakronenverbindungen

Structure and Complex Formation of Small 1,3-Dithiol Anellated Thia Crown Compounds The molecular structures of two 1,3-dithiol anellated nine membered thia crown compounds have been determined by X-ray diffraction. Their complex formation behaviour towards Ag^I and Hg^II is studied and discussed using solvent extraction experiments and molecular modeling calculations.     

Atmospheric aging of poly[methyl(phenyl)silanediyl] monitored by FTIR spectroscopy

Poly[methyl(phenyl)silanediyl] films were irradiated in ATLAS Weather-O-Meter Ci 3000+ for ca 3 h. Changes in the region of siloxane, carbonyl, hydroxyl, and C-H (aromatic) bands were monitored by FTIR. Main attention was paid to changes in siloxane formation, which could be reduced in the presence of phenolic UV absorber 1 and oxalanilide 3 .     

Structure‐Based Design of Nonpeptidic Thrombin Inhibitors: Exploring the D‐Pocket and the Oxyanion Hole

Structure‐activity relationships for new members of a class of nonpeptidic, low‐molecular‐weight inhibitors of thrombin, a key serine protease in the blood coagulation cascade, are described. These compounds, which originate from X‐ray‐structure‐based design, feature a conformationally rigid, bi‐ or tricyclic core from which side chains diverge into the four major binding pockets (distal D, proximal P, recognition or specificity S1, and oxyanion hole O) at the thrombin active site (Fig. 1). Phenylamidinium is the side chain of choice for the S1 pocket, while the most active inhibitors orient an i‐Pr group into the P‐pocket (Table 1). The key step in the synthesis of the inhibitors is the construction of the central bi‐ or tricyclic scaffold by 1,3‐dipolar cycloaddition of an in situ prepared azomethine ylide and an N‐substituted maleimide (Schemes 1–3, and 8–10). One series of compounds was designed to explore the binding features of the large hydrophobic D pocket. This pocket provides space for lipophilic residues as bulky as benzhydryl groups. A new strategy was developed, allowing introduction of these sterically demanding substituents very late in the synthesis (Schemes 5 and 6). Benzhydryl derivative (±)‐ 2 was found to be the most selective member (K_i (trypsin)/K_i (thrombin)=1200) of this class of nonpeptidic thrombin inhibitors, while the ‘dipiperonyl' analog (±)‐ 3 (K_i=9 nM , 7.60‐fold selectivity) displays the highest potency of all compounds prepared so far (Table 1). A second series of inhibitors features side chains designed to orient into the oxyanion hole and to undergo H‐bonding with the backbone NH groups lining the catalytic site of the enzyme. Unfortunately, neither activity nor selectivity could be substantially improved by introduction of these substituents (Table 2). Presumably, the high degree of pre‐organization and the rigidity of the tightly bound scaffolds prevents the new substituents from assuming a position that would allow favorable interactions in the oxyanion hole. However, the oxyanion hole and the S1′ pocket next to it were found to be capable of accommodating quite large groups, which leaves much room for further exploration.     

Light-Induced Change of Charge Carrier Mobility in Semiconducting Polymers

Summary: Light-driven devices based on reversible change of carrier mobility in semiconducting polymers were investigated. The mobility was altered using a photochromic spiropyran capable of a reversible change of permanent dipole moment and ionization potential. While the latter attribute may result in formation of chemical traps and is more important for matrices with similar ionization potential such as PVK, the former phenomenon results in formation of polar traps and is more pronounced in the case of lower-band-gap materials.     

Biochemometry-Based Discovery of Phenylpropanoids from Azadirachta indica Fruits as Inhibitors of In Vitro Osteoclast Formation

(1) Background: Inhibition of osteoclast differentiation is the key approach in treating osteoporosis. However, using state-of-the-art treatments such as bisphosphonates and estrogen-based therapy is usually accompanied by many side effects. As opposed to this, the use of natural products as an osteoporotic remedy delivers promising outcomes with minimal side effects. (2) Methods: In the present study, we implemented a biochemometric workflow comprising (i) chemometric approaches using NMR and mass spectrometry and (ii) cell biological approaches using an osteoclast cytochemical marker (TRAP). The workflow serves as a screening tool to pursue potential in vitro osteoclast inhibitors. (3) Results: The workflow allowed for the selective isolation of two phenylpropanoids (coniferyl alcohol and sinapyl alcohol) from the fruits of neem tree (Azadirachta indica). These two isolated phenylpropanoids showed a very promising dose-dependent inhibition of osteoclast differentiation with negligible effects in terms of cell viability. (4) Conclusion: The presented workflow is an effective tool in the discovery of potential candidates for osteoclast inhibition from complex extracts. The used biochemometric approach saves time, effort and costs while delivering precise hints to selectively isolate bioactive constituents.     

Gliadin as a measure of gluten in foods containing wheat, rye, and barley-enzyme immunoassay method based on a specific monoclonal antibody to the potentially celiac toxic amino acid prolamin sequences: collaborative study

The Working Group on Prolamin Analysis and Toxicity (WGPAT) organized a collaborative study to confirm whether the two R5 antibody-based ELISA test kits are able to detect gliadin in the lower mg/kg (ppm) level. Twenty laboratories investigated 12 blind-coded samples, spiked and naturally contaminated, to show the possibility of determining traces of gliadin in heat-treated or nonheat-treated foods by ELISA. It was shown that very small amounts of gliadin (below 100 ppm) could be detected by ELISA with a reproducibility RSD(R) (37%) and a repeatability RSD, (27%) common for ELISA under these conditions. The recovery of gliadin from the spiked samples was between 84 and 109%, based on the results of all laboratories, including those with poor performance. No false positives were found by the method (P < or =0.05), but one negative sample was contaminated during the bakery process. It is recommended that the method be accepted by AOAC as Official First Action.     

Comparison of protein expression profiles between monolayer and spheroid cell culture of HT-29 cells revealed fragmentation of CK18 in three-dimensional cell culture

The use of three-dimensional cell culture models, so-called multicellular tumor spheroids, is a special approach in experimental cancer research, because spheroids are similar to in vivo tumors in structural as well as functional sense. Cells grown in spheroids exhibit alterations of cell cycle regulation, induction of apoptosis and differentiation and can acquire multidrug resistance. In this study we investigated the protein expression in human colorectal cancer cells grown in monolayer and in spheroid cultures using proteomics. Evaluation by computer-assisted image analysis revealed overexpression of three cytokeratin 18 fragments that were generated in vivo. Cytokeratin 18 has previously been described as a target for caspase-mediated cleavage during apoptosis and our results indicate that apoptosis may take place in spheroids. Other proteins upregulated in spheroids include calreticulin precursor, a rho GDP dissociation inhibitor variant, several cytokeratins and peroxiredoxin 4. Some of these proteins have already been linked to chemoresistance and apoptotic phenomena.     

A gas chromatography/combustion/isotope ratio mass spectrometry system for high-precision delta13C measurements of atmospheric methane extracted from ice core samples

Past atmospheric composition can be reconstructed by the analysis of air enclosures in polar ice cores which archive ancient air in decadal to centennial resolution. Due to the different carbon isotopic signatures of different methane sources high-precision measurements of delta13CH4 in ice cores provide clues about the global methane cycle in the past. We developed a highly automated (continuous-flow) gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) technique for ice core samples of approximately 200 g. The methane is melt-extracted using a purge-and-trap method, then separated from the main air constituents, combusted and measured as CO2 by a conventional isotope ratio mass spectrometer. One CO2 working standard, one CH4 and two air reference gases are used to identify potential sources of isotope fractionation within the entire sample preparation process and to enhance the stability, reproducibility and accuracy of the measurement. After correction for gravitational fractionation, pre-industrial air samples from Greenland ice (1831 +/- 40 years) show a delta13C(VPDB) of -49.54 +/- 0.13 per thousand and Antarctic samples (1530 +/- 25 years) show a delta13C(VPDB) of -48.00 +/- 0.12 per thousand in good agreement with published data.     

Amino acids: aspects of impurity profiling by means of CE

Quality control of active pharmaceutical ingredients (API) is commonly performed by means of HPLC. However, CE offers a suitable alternative, especially for the analysis of easily chargeable substances, i.e., amino acids. The article reviews, on the one hand, CE methods developed for impurity profiling of synthesized amino acid analogs. However, nowadays, production of amino acids/peptides is dominated by fermentation. Therefore, on the other hand, CE methods for the analysis of amino acids and small peptides are reported. The results of CE analysis of glutathione samples according to the monograph in the European Pharmacopoeia (Ph. Eur.) 5.7 and amino acid samples after derivatization with 9-fluorenylmethyl chloroformate (FMOC) and 3-(4-carboxybenzoyl)quinoline-2-carboxaldehyde (CBQCA) may pave the way for impurity profiling of fermentatively produced API by means of CE.