Identification and Structure–Activity Relationship Studies of Small‐Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1

The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small‐molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure‐ and ligand‐based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds. Our in silico studies coupled with in vitro testing were successful in identifying novel Spindlin1 inhibitors. Several 4‐aminoquinazoline and quinazolinethione derivatives were among the active hit compounds, which indicated that these scaffolds represent promising lead structures for the development of Spindlin1 inhibitors. Subsequent lead optimization studies were hence carried out, and numerous derivatives of both lead scaffolds were synthesized. This resulted in the discovery of novel inhibitors of Spindlin1 and helped explore the structure–activity relationships of these inhibitor series.     

4‐Biphenylalanine‐ and 3‐Phenyltyrosine‐Derived Hydroxamic Acids as Inhibitors of the JumonjiC‐Domain‐Containing Histone Demethylase KDM4A

Overexpression of the histone lysine demethylase KDM4A, which regulates H3K9 and H3K36 methylation states, has been related to the pathology of several human cancers. We found that a previously reported hydroxamate‐based histone deacetylase (HDAC) inhibitor (SW55) was also able to weakly inhibit this demethylase with an IC₅₀ value of 25.4 μm . Herein we report the synthesis and biochemical evaluations, with two orthogonal in vitro assays, of a series of derivatives of this lead structure. With extensive chemical modifications on the lead structure, also by exploiting the versatility of the radical arylation with aryldiazonium salts, we were able to increase the potency of the derivatives against KDM4A to the low‐micromolar range and, more importantly, to obtain demethylase selectivity with respect to HDACs. Cell‐permeable derivatives clearly showed a demethylase‐inhibition‐dependent antiproliferative effect against HL‐60 human promyelocytic leukemia cells.     

Gallium gradients in Cu(In,Ga)Se2 thin‐film solar cells

The gallium gradient in Cu(In,Ga)Se₂ (CIGS) layers, which forms during the two industrially relevant deposition routes, the sequential and co‐evaporation processes, plays a key role in the device performance of CIGS thin‐film modules. In this contribution, we present a comprehensive study on the formation, nature, and consequences of gallium gradients in CIGS solar cells. The formation of gallium gradients is analyzed in real time during a rapid selenization process by in situ X‐ray measurements. In addition, the gallium grading of a CIGS layer grown with an in‐line co‐evaporation process is analyzed by means of depth profiling with mass spectrometry. This gallium gradient of a real solar cell served as input data for device simulations. Depth‐dependent occurrence of lateral inhomogeneities on the µm scale in CIGS deposited by the co‐evaporation process was investigated by highly spatially resolved luminescence measurements on etched CIGS samples, which revealed a dependence of the optical bandgap, the quasi‐Fermi level splitting, transition levels, and the vertical gallium gradient. Transmission electron microscopy analyses of CIGS cross‐sections point to a difference in gallium content in the near surface region of neighboring grains. Migration barriers for a copper‐vacancy‐mediated indium and gallium diffusion in CuInSe₂ and CuGaSe₂ were calculated using density functional theory. The migration barrier for the In_Cu antisite in CuGaSe₂ is significantly lower compared with the Ga_Cu antisite in CuInSe₂, which is in accordance with the experimentally observed Ga gradients in CIGS layers grown by co‐evaporation and selenization processes. Copyright © 2014 John Wiley & Sons, Ltd.     

Time‐resolved investigation of Cu(In,Ga)Se2 growth and Ga gradient formation during fast selenisation of metallic precursors

Ga segregation at the backside of Cu(In,Ga)Se₂ solar cell absorbers is a commonly observed phenomenon for a large variety of sequential fabrication processes. Here, we investigate the correlation between Se incorporation, phase formation and Ga segregation during fast selenisation of Cu–In–Ga precursor films in elemental selenium vapour. Se incorporation and phase formation are analysed by real‐time synchrotron‐based X‐ray diffraction and fluorescence analysis. Correlations between phase formation and depth distributions are gained by interrupting the process at several points and by subsequent ex situ cross‐sectional electron microscopy and Raman spectroscopy. The presented results reveal that the main share of Se incorporation takes place within a few seconds during formation of In–Se at the top part of the film, accompanied by outdiffusion of In out of a ternary Cu–In–Ga phase. Surprisingly, CuInSe₂ starts to form at the surface on top of the In–Se layer, leading to an intermediate double graded Cu depth distribution. The remaining Ga‐rich metal phase at the back is finally selenised by indiffusion of Se. On the basis of a proposed growth model, we discuss possible strategies and limitations for the avoidance of Ga segregation during fast selenisation of metallic precursors. Solar cells made from samples selenised with a total annealing time of 6.5 min reached conversion efficiencies of up to 14.2 % (total area, without anti‐reflective coating). The evolution of the Cu(In,Ga)Se₂ diffraction signals reveals that the minimum process time for high‐quality Cu(In,Ga)Se₂ absorbers is limited by cation ordering rather than Se incorporation. Copyright © 2014 John Wiley & Sons, Ltd.     

Chemikalienfreie Bekämpfung von Holzschädlingen durch dielektrische Erwärmung mit Radiowellen und Mikrowellen

Thermal pest control requires long treatment times due to the low thermal conductivity of wood and may lead to the formation of cracks. Here, the thermal treatment with radio waves as well as microwaves has been studied. The direct dielectric heating has the advantage of a good homogeneity. The obtained temperature profiles for radio waves were more homogeneous compared to microwaves. Detailed studies showed that elimination of pests was not related to the application of the electromagnetic field itself, but due to the temperature increase.     

Shear‐induced shish‐kebab structures in isotactic polypropylene using acicular precipitated calcium carbonate as whisker

It has been reported in the technical literature that whiskers of rodlike single crystals can be used in order to generate shish‐kebab structures or other different lamellae morphologies during isothermal or dynamic crystallization of sheared or presheared polymer melts. The expected advantage of the changed crystalline structure is a reinforcing effect of the composite. A lot of papers reported about the application of inorganic and organic whiskers such as cellulose and chitin whiskers. This study reports on an attempt to use acicular PCC as appropriate whisker for improving mechanical properties of polypropylene. In this article special attention is given to demonstrate the effect of flow induced crystallization under varying shear conditions in order to improve the mechanical properties. The effects were demonstrated using rheology, thermal analysis, tensile testing, and transmission electron microscopy. POLYM. ENG. SCI., 54:2057–2063, 2014. © 2013 Society of Plastics Engineers     

Photokatalytische Bildung von Wasserstoff aus Thiolen in Gegenwart von Vitamin B12-Modellverbindungen mit Azid als photochemischem Opferliganden

Photocatalytic Hydrogen Formation from Thioles in the Presence of Vitamin-B₁₂ Model Complexes with Azide as Photochemical Sacrificial Ligand The photolysis of [N₃Co(chelat)B] complexes ( 1–3 ) (chelat = dimethylglyoxime, dmg; N,N′-o-phynylenebis(salicylidenimine), salphen; N,N′-ethylene-bis(salicylidenimine), salen; B = pyridine) leads by homolytic cleavage of the Co–N₃ bond to both coordinatively unsaturated cobalt(II) chelates [Co(chelat)B] and N₃ ligand radicals that undergo fast decay to dinitrogen. The photolysis of the cobalt (III) complexes 1–3 in the presence of thiophenole and other thioles proceeds catalytically and yields the corresponding disulphides and dihydrogen. The mechanism of this photocatalytic generation of dihydrogen is due to the catalytic activity of the coordinatively unsaturated cobalt(II) species formed photochemically. A photocatalytic cycle is proposed describing the generation of hydrogen. Possible photochemical and thermal steps of that cycle are discussed.     

Starch-Derived Products for Detergents

Recent developments in the formulation of detergents have been driven by a strong consumer demand for natural and biodegradable products. Detergent manufacturers responded to this demand with corresponding products and advertising slogans such as “fully biodegradable”, “natural” or even “double natural” to oust their competitors. In a detergent formulation, starch- derived products can in principle be used for the following purposes: as the hydrophilic head group in surfactants, as the starting material for (poly)carboxylate co-builders and as the backbone of bleaching activators. Non-ionic classical surfactants can be replaced by alkylpolyglucosides (APGs), a class of products completely based on renewable resources such as glucose and fatty alcohols derived from natural fatty acids. Sodium tripolyphosphate (STPP), the product responsible for the eutrophication of surface waters, can be substituted by a combination of an inorganic zeolite and highly oxidised starch (dicarboxylic starch) or by citrate. Acetylated polyols derived from hydrogenated carbohydrates such as sorbitol can take over the function of the petrochemically-based tetraacetyl ethylene diamine (TAED) used as activator to allow perborate bleaching at lower washing temperatures.