The influence of pressure on the capillary flow of poly(methyl methacrylate)

Summary Pressure effects in the capillary flow of a single sample of poly(methyl methacrylate),M _v = 1.33 · 10⁵, were evaluated. The length/diameter ratios of the different capillaries used varied from 4 to 100. The tests were made with an Instron rheometer in the range 160–250 °C. The pressure-viscosity model, derived from the free volume-WLF equation, was used to pressure correct the capillary data. The corrected data agreed well with data obtained at atmospheric pressure using aWeissenberg rheogoniometer. A derived expression to calculate an increase in the flow activation energy with increasing stress predicts the observed increase in activation energy.

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Zusammenfassung Druckeffekte bei der Kapillarströmung einer einzelnen Polymethylmethacrylat-ProbeM _v = 1,33 · 10⁵ werden abgeschätzt. Die Längen/Durchmesserverhältnisse der verschiedenen verwendeten Kapillaren variierten zwischen 4 und 100. Im Temperaturbereich zwischen 160 und 250 °C wurden die Versuche mit einem Instron-Rheometer durchgeführt. Das Druck-Viskositätsmodell, das aus der WLF-Gleichung abgeleitet war, wurde zur Druckkorrektur der Kapillardaten verwendet. Die korrigierten Werte zeigten eine gute Übereinstimmung mit den Werten, die bei Atmosphärendruck mit Hilfe einesWeissenberg-Rheogoniometers gewonnen worden waren. Ein abgeleiteter Ausdruck zur Berechnung des Anstiegs der Strömungs-Aktivierungsenergie mit steigender Spannung sagt den beobachteten Anstieg in der Aktivierungsenergie voraus.

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On leave from Montecatini Edison, Milan (Italy).     

Calculation of a conductive-laminar thermo-convection regime of a Newtonian fluid in a rectangular cavity with isothermal vertical boundaries

A method of calculating a free-convection flow of a viscous incompressible medium in a rectangular cavity is proposed. The lateral boundaries of the cavity have the same constant temperature, the top and bottomboundaries are thermally insulated, and the half-width to height ratio is much smaller than unity. A decomposition of the flow domain into zones with ascending and descending flows made it possible to formulate and solve analytically a coupled parabolic system of linear equations based on the classic Oberbeck-Boussinesq assumptions.     

NMR-assisted computational studies of peptidomimetic inhibitors bound in the hydrophobic pocket of HIV-1 glycoprotein 41

Due to the inherently flexible nature of a protein–protein interaction surface, it is difficult both to inhibit the association with a small molecule, and to predict how it might bind to the surface. In this study, we have examined small molecules that mediate the interaction between a WWI motif on the C-helix of HIV-1 glycoprotein-41 (gp41) and a deep hydrophobic pocket contained in the interior N-helical trimer. Association between these two components of gp41 leads to virus–cell and cell–cell fusion, which could be abrogated in the presence of an inhibitor that binds tightly in the pocket. We have studied a comprehensive combinatorial library of α-helical peptidomimetics, and found that compounds with strongly hydrophobic side chains had the highest affinity. Computational docking studies produced multiple possible binding modes due to the flexibility of both the binding site and the peptidomimetic compounds. We applied a transferred paramagnetic relaxation enhancement experiment to two selected members of the library, and showed that addition of a few experimental constraints enabled definitive identification of unique binding poses. Computational docking results were extremely sensitive to side chain conformations, and slight variations could preclude observation of the experimentally validated poses. Different receptor structures were required for docking simulations to sample the correct pose for the two compounds. The study demonstrated the sensitivity of predicted poses to receptor structure and indicated the importance of experimental verification when docking to a malleable protein–protein interaction surface.     

Characterization of viscous fingering in a radial Hele-Shaw cell by image analysis

Methods based on image analysis and mathematical morphology are proposed to study fingering patterns obtained in a radial Hele-Shaw cell. They have been used to study miscible displacement patterns obtained under various conditions of initial viscosity, viscosity ratio and injection rate. Their application domain can be extended to other type of fingering patterns as well as diffusion-limited aggregates. Received: 28 October 1997/Accepted: 16 April 1998     

A structural model for the time-dependent recovery of mineral suspensions

A thixotropic recovery model has been developed that is based on consideration of the microstructural interactions that occur between particles within a suspension particle network. The model is based on Smoluchowski coagulation rate theory, utilizing second order kinetics to describe the thixotropic recovery behavior. The model is applied to Na-montmorillonite-based coal tailings suspensions and is also shown to be applicable to brown coal and bauxite residue suspensions. The model describes all the recovery data well, especially at intermediate to large recovery times. The recovery of the montmorillonite suspensions at short times was faster than predicted, indicating the existence of additional factors in early-time structure development. The discrepancy may have also been due to the highly anisotropic nature of the clay platelets. The recovery rate constant, K _r , increases with increasing solids concentration (for constant surface chemical conditions) as would be expected from the basis of the model. Received: 22 September 2000 Accepted: 16 March 2001     

Evaluation of chlorofusin, its seven chromophore diastereomers, and key analogues

Chlorofusin, its seven chromophore diastereomers, and key analogues were comparatively examined for inhibition of MDM2-p53 binding revealing that the chromophore, but not simple replacements, contributes significantly to the natural products properties, and that this contribution is independent of its relative and absolute stereochemistry.     

A simple, high-resolution method for establishing DNA binding affinity and sequence selectivity.

Full details of the development of a simple, nondestructive, and high-throughput method for establishing DNA binding affinity and sequence selectivity are described. The method is based on the loss of fluorescence derived from the displacement of ethidium bromide or thiazole orange from the DNA of interest or, in selected instances, the change in intrinsic fluorescence of a DNA binding agent itself and is applicable for assessing relative or absolute DNA binding affinities. Enlisting a library of hairpin deoxyoligonucleotides containing all five base pair (512 hairpins) or four base pair (136 hairpins) sequences displayed in a 96-well format, a compound's rank order binding to all possible sequences is generated, resulting in a high-resolution definition of its sequence selectivity using this fluorescent intercalator displacement (FID) assay. As such, the technique complements the use of footprinting or affinity cleavage for the establishment of DNA binding selectivity and provides the information at a higher resolution. The merged bar graphs generated by this rank order binding provide a qualitative way to compare, or profile, DNA binding affinity and selectivity. The 96-well format assay (512 hairpins) can be conducted at a minimal cost (presently ca. $100 for hairpin deoxyoligonucleotides/assay with ethiduim bromide or less with thiazole orange), with a rapid readout using a fluorescent plate reader (15 min), and is adaptable to automation (Tecan Genesis Workstation 100 robotic system). Its use in generating a profile of DNA binding selectivity for several agents including distamycin A, netropsin, DAPI, Hoechst 33258, and berenil is described. Techniques for establishing binding constants from quantitative titrations are compared, and recommendations are made for use of a Scatchard or curve fitting analysis of the titration binding curves as a reliable means to quantitate the binding affinity.     

Energetic preferences for alpha,beta versus beta,gamma unsaturation

Density functional theory has been applied at the B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) level to examine the energetics of alpha,beta- versus beta,gamma-unsaturation for some common organic functional groups. Specifically, the relative stabilities of allyl-X (H2C=CHCH2X) and 1-propenyl-X (H3CCH=CHX) isomers have been computed for X = methyl, vinyl, phenyl, formyl, acetyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl, sulfamoyl, and methoxysulfonyl, and the results are compared to available experimental data. The intrinsic preference of 3 kcal/mol for the 1-propenyl isomer when X = CH3 is exceeded by 2-4 kcal/mol for first-row conjugating groups, but it is not met for the sulfur-containing groups. In particular, alpha,beta-unsaturation is favored by less than 1 kcal/mol for the sulfone and sulfonamide analogues, while it is preferred by 8 kcal/mol for the vinyl-substituted case. Detailed structural results and torsional energy profiles are also reported.     

Streptonigrin and lavendamycin partial structures. Preparation of 7-amino-2-(2′-pyridyl)quinoline-5,8-quinone-6′-carboxylic acid: A probe for the minimum,potent pharmacophore of the naturally occurring antitumor-antibiotics

The preparation of 7-amino-2-(2′-pyridyl)quinoline-5,8-quinone-6′-carboxylic acid (4) constituting a potential minimum, potent pharmacophore of streptonigrin (1) and lavendamycin (2) , two structurally-related naturally-occurring antitumor-antibiotic, is detailed. In contrast to observations associated with streptonigrin and lavendamycin in which the C-6′ acid potentiates the antitumor, antimicrobial, and cytotoxic activity of the naturally-occurring, substituted 7-aminoquinoline-5,8-quinone AB ring systems, the C-6′ carboxylic acid of 4 diminishes the observed antimicrobial and cytotoxic properties of 7-amino-2-(2′-pyridyl)quinoline-5,8-quinone.