Pyridinethiones. XI. Diastereoselective aldol condensations with 2(1H)-pyridones, 2(1H)-pyridinethiones,and the crystal structure of 3-(1-hydroxy-2-methyl-3-oxo-3-(4-chlorophenyl)propyl-1-isoprpyl-2(1H)-pyridinethione

Aldol condensation of 3-formyl-2(1H)-pyridinethiones and the corresponding pyridones with ketones such as acetophenones in aqueous base yields 3-hydroxy-1-propanones in high yields. Reaction with propiophenone showed this reaction to be highly diastereoselective as only the erythro-isomer is formed at room temperature. This assignment was based on an X-ray crystallographic investigation of the compound given in the title. Aldol condensations of a number of related 3-acetyl-2(1H)-pyridinethiones with benzaldehyde yielded the corresponding trans-vinyl ketones.     

Complexation between low-molecular-weight cationic ligands and negatively charged polymers as studied by capillary electrophoresis frontal analysis

The potential of using capillary electrophoresis frontal analysis for the study of low-molecular-weight ligand-polyelectrolyte interactions was assessed. The interaction of the ligands 1-propylpyridinium bromide, 2-propylisochinolinium bromide, and paraquat with the polymer dextran sulfate was investigated as a function of polymer concentration and ionic strength of the buffer solution. Linear binding isotherms were obtained and association constants were determined. The complex formation was independent of the dextran sulfate concentration at low ionic strength. Ligand-polyelectrolyte interactions were strongly dependent on the ionic strength. The interaction of the divalent cation paraquat with the dextran sulfate was much stronger than the interactions of the monovalent cationic ligands with the polyelectrolyte. The binding data obtained were in accord with results obtained by equilibrium dialysis. Capillary electrophoresis frontal analysis has the potential to become a valuable tool for characterization of ligand-polyelectrolyte interactions in drug design as well as in other areas.     

A <Emphasis Type="Italic">k</Emphasis>-nearest neighbor classification of hERG K<Superscript>+</Superscript> channel blockers

A series of 172 molecular structures that block the hERG K⁺ channel were used to develop a classification model where, initially, eight types of PaDEL fingerprints were used for k-nearest neighbor model development. A consensus model constructed using Extended-CDK, PubChem and Substructure count fingerprint-based models was found to be a robust predictor of hERG activity. This consensus model demonstrated sensitivity and specificity values of 0.78 and 0.61 for the internal dataset compounds and 0.63 and 0.54 for the external (PubChem) dataset compounds, respectively. This model has identified the highest number of true positives (i.e. 140) from the PubChem dataset so far, as compared to other published models, and can potentially serve as a basis for the prediction of hERG active compounds. Validating this model against FDA-withdrawn substances indicated that it may even be useful for differentiating between mechanisms underlying QT prolongation.     

Generalized balanced power diagrams for 3D representations of polycrystals

Characterizing the grain structure of polycrystalline material is an important task in material science. The present paper introduces the concept of generalized balanced power diagrams as a concise alternative to voxelated mappings. Here, each grain is represented by (measured approximations of) its centre of mass position, its volume and, if available, and by its second-order moments (in the non-equiaxed case). Such parameters may be obtained from 3D X-ray diffraction. As the exact global optimum of our model results from the solution of a suitable linear programme it can be computed quite efficiently. Based on verified real-world measurements, we show that from the few parameters per grain (3, respectively, 6 in 2D and 4, respectively, 10 in 3D) we obtain excellent representations of both equiaxed and non-equiaxed structures. Hence our approach seems to capture the physical principles governing the forming of such polycrystals in the underlying process quite well.     

A Numerical Study of Characteristic Slow-Transient Behavior of a Compressible 2D Gas-Liquid Two-Fluid Model

The purpose of this paper is to gain some insight into the characteristic behavior of a general compressible two-fluid gas-liquid model in 2D by using numerical computations. Main focus is on mass transport phenomena. Relatively few numerical results in higher dimensions can be found in the literature for this two-fluid model, in particular, for cases where mass transport dynamics are essential. We focus on natural extensions to 2D of known 1D benchmark test cases, like water faucet and gas-liquid separation, previously employed by many researchers for the purpose of testing various numerical schemes. For the numerical investigations, the WIMF discretization method introduced in [SIAM J. Sci. Comput. 26 (2005), 1449] is applied, in combination with a standard dimensional splitting approach. Highly complicated flow patterns are observed reflecting the balance between acceleration forces, gravity, interfacial forces, and pressure gradients. An essential ingredient in these results is the appearance of single-phase regions in combination with mixture regions (dispersed flow). Solutions are calculated and shown from early times until a steady state is reached. Grid refinement studies are included to demonstrate that the obtained solutions are not grid-sensitive.