Structures of semi crystalline high‐molecular weight polyethylene and their changes with temperature were studied by analysis of Raman spectra. Decomposition of spectra into contributions of an orthorhombic crystalline phase, a meltlike phase, and two kinds of transition regions yields the respective mass fractions. The results of temperature dependent measurements is indicative of a largely reversible surface melting process, the transition regions being located at the crystal surfaces. As‐polymerized samples show a large fraction of the intermediate phase. Annealing leads to a reduction of this phase. © 1993 John Wiley & Sons, Inc.

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The order-to-disorder transition in a nearly symmetric diblock copolymer of polystyrene/poly(cis-1,4)isoprene (M, = 15 700) was reproducibly observed in heating and cooling runs using small-angle scattering and rheological measurements. Small-angle X-ray scattering characterizes the ordered structure as consisting of stacks of about 20 lamellae. The transition temperature is T m T = 362 K and about 30 K below the spinodal temperature T, which is extrapolated from the high-temperature phase. Measurements of the dynamic shear modulus reveal a drastic change of the spectrum of relaxation times at T M S T . The transition is shown to be discontinuous and accompanied by strong concentration fluctuations in accordance with theoretical expectations.

Transmissible spongiform encephalopathies (TSEs) or prion diseases are a family of invariably fatal neurodegenerative disorders, and there are no effective therapeutics currently available. In this paper, we report on the design, synthesis, and screening of a series of pyridine dicarbonitriles as potential novel prion disease therapeutics. A virtual reaction-based library of 1050 compounds was constructed. Docking and evaluation using GOLD scores assisted the initial selection of compounds for synthesis. The selection was augmented with further compounds to increase structural diversity. A total of 45 compounds were synthesized via a one-pot three-component coupling reaction. The mechanism of the three-component coupling reaction was investigated, and it was discovered that chemical oxidation is required for the last step, forming the pyridine ring (aromatization). A total of 19 compounds were identified as binders to one or more forms of prion protein by in vitro screening using surface plasmon resonance (SPR). A selection of compounds were investigated for activity in cells, resulting in the discovery of a new inhibitor of PrP(Sc) formation.

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Transmissible spongiform encephalopathies (TSEs) are a family of invariably fatal neurodegenerative disorders for which no effective therapeutics are currently available. In this paper, we report on the synthesis and screening of a small library of 2,4-diphenylthiazol-5-ylamine and 2,4-diphenyloxazol-5-ylamine derivatives as potential novel prion disease therapeutics. Various synthetic strategies were investigated, including a novel phosgene-mediated cyclization of 2-N-benzoylphenylglycinonitrile, and a total of 45 compounds were synthesized. Library members were tested for both binding to prion protein (PrPC) using the surface plasmon resonance technique and for inhibition of PrPSc formation in persistently infected SMB cells. Of the compounds prepared, 15 were found to bind to human PrPC and six showed inhibition of PrPSc formation, displaying EC50s between 1.5 and 20 microM.

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