An efficient synthesis of 5-aminoimidazol-2-ones via cyclization reactions of 2-aminoacetonitriles and isocyanates

The scope of a cyclization reaction between amino-acetonitriles and isocyanates was investigated. The study revealed that this reaction tolerates various functional groups leading to highly functionalized 5-amino-imidazole-2-ones, which are useful intermediates for purine synthesis.     

Thermal stability of shear-induced precursor structures in isotactic polypropylene by rheo-X-ray techniques with couette flow geometry

Combined in situ rheo-SAXS (small-angle X-ray scattering) and -WAXD (wide-angle X-ray diffraction) studies using couette flow geometry were carried out to probe thermal stabilty of shear-induced oriented precursor structure in isotactic polypropylene (iPP) at around its normal melting point (162 °C). Although SAXS results corroborated the emerging consensus about the formation of “long-living” metastable mesomorphic precursor structures in sheared iPP melts, these are the first quantitative measures of the limiting temperature at which no oriented structures survive. At the applied shear, rate = 60 s⁻¹ and duration t_s = 5 s, the oriented iPP structures survived a temperature of 185 °C for 1 h after shear, while no stable structures were detected at and above 195 °C. Following Keller's concepts of chain orientation in flow, it is proposed that the chains with highly oriented high molecular weight fraction are primarily responsible for their stability at high temperatures. Furthermore, the effects of flow condition, specifically the shear temperature, on the distributions of oriented and unoriented crystals were determined from rheo-WAXD results. As expected, at a constant flow intensity (i.e., rate = 30 s⁻¹ and duration, t_s = 5 s), the oriented crystal fraction decreased with the increase in temperature above 155 °C, below which the oriented fraction decreased with the decrease in temperature. As a result, a crystallinty “phase” diagram, i.e., temperature versus crystal fraction ratio, exhibited a peculiar “hourglass” shape, similar to that found in many two-phase polymer–polymer blends. This can be explained by the competition between the oriented and unoriented crystals in the available crystallizable species. Below the shear temperature (155 °C), the unoriented crystals crystallized so rapidly that they overwhelmed the crystallization of the oriented crystals, thus depleting a major portion of the crystallizable species and increasing their contribution in the final total crystalline phase. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 3553–3570, 2006     

Inner multipliers of de Branges's spaces

For a given functionb in the unit ball ofH and an arbitraryH functionm, the question of whenm is a multiplier of the de Branges space (that is, when is invariant under multiplication bym) is examined. Some necessary and sufficient conditions thatm be a multiplier of are found and it is shown that there are no nonconstant inner multipliers of whenb is a nonconstant extreme point of the unit ball ofH . A new proof is given of the known fact that is invariant under multiplication byz whenb is not an extreme point of the unit ball ofH . Finally, we give a new proof of the known fact that an inner functionm is a multiplier of forb(z)=(1+z)/2 if and only ifm belongs to the range of .Some of the work in this paper originally appeared in the author's doctoral disseratation written at the University of California at Berkeley under the supervision of Donald Sarason.     

On the Role of Mixed Strategies in Elementary Decision Analysis and Related Decision-Support-System Treatments

We first demonstrate that mixed strategies are relevant in decision analysis for a maximin decision-maker quite apart from any game-theory considerations. This rectifies the apparent misconception that results from MS/OR textbooks which discuss mixed strategies only in the game-theory setting. Next we show an example of an implementable mixed strategy, by which we mean a mixed decision strategy which does not require randomization for its implementation. This application is to portfolio construction.     

The ICP-MS approach to environmental studies

The certification of marine materials for trace metals is a process which challenges every technique involved, especially if a technique is as recent as inductively coupled plasma mass spectrometry (ICP-MS), Developmental work was required for several materials (natural waters, biological materials, marine sediments). It is reviewed here, in an attempt to show how one can take full advantage of ICP-MS. This includes a review of the digestion procedures developed for the multielement analysis of biological materials and marine sediments in order to minimize spectroscopic interferences. The multielement analysis of natural waters is also reviewed, in particular that of saline waters which requires a separation of the analytes from the alkali and alkaline earths elements and a preconcentration of the analytes on a column of silicaimmobilized 8-hydroxyquinoline. The potential of performing this separation/preconcentration procedure on-line is showed using both published and original results. Finally, the application of ICP-MS to speciation is illustrated by the determination of methylmercury in biological materials after extraction, and by the determination of arsenic species by high performance liquid chromatography coupled to ICP-MS.Presented in part at the 1989 European Winter Conference on Plasma Spectrochemistry, Reutte, AustriaThe work described was carried out while the author was a Research Associate at the Analytical Chemistry Section, Chemistry Division, National Research Council of Canada, Ottawa, K1A OR9, Canada     

Kinetic and structural characterization of human manganese superoxide dismutase containing 3-fluorotyrosines

Incorporation of 3-fluorotyrosine and site-specific mutagenesis have been used with stopped-flow spectrophotometry and pulse radiolysis to investigate the catalytic properties of human manganese superoxide dismutase (MnSOD). All of the nine tyrosine residues in each of the four subunits of the homotetramer of human MnSOD were replaced with 3-fluorotyrosine. Previous studies showed that the crystal structures of the unfluorinated and fluorinated human MnSOD are nearly superimposable with the root-mean-square deviation for 198 -carbon atoms at 0.3 Å. However, the catalytic activity k_cat/K_m of the fluorinated MnSOD at 30 μM⁻¹ s⁻¹ was less than unfluorinated wild type at 800 μM⁻¹ s⁻¹. Comparison of the values of k_cat/K_m for fluorinated and unfluorinated wild-type andY34F MnSOD showed that this decrease for the fluorinated enzyme was in significant part due to 3-fluorotyrosine residues distant (>7 Å) from the active-site metal, not to 3-fluorotyrosine at position 34 close (5 Å) to the metal. Although many rate constants for the catalysis are decreased by this fluorination, the rate of dissociation of the product-inhibited complex appears unchanged by the presence of fluorinated tyrosines. These results suggest that Tyr34 is not a proton donor in the release of the product-inhibited complex, which involves protonation of a peroxo complex of the metal with release of hydrogen peroxide.     

Phase separation of p53 precedes aggregation and is affected by oncogenic mutations and ligands

Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF). The mechanism of the formation of the aggregates in the nucleus remains uncertain. The present study demonstrated that the DNA-binding domain of p53 (p53C) underwent phase separation (PS) on the pathway to aggregation under various conditions. p53C phase separated in the presence of the crowding agent polyethylene glycol (PEG). Similarly, mutant p53C (M237I and R249S) underwent PS; however, the process evolved to a solid-like phase transition faster than that in the case of wild-type p53C. The data obtained by microscopy of live cells indicated that transfection of mutant full-length p53 into the cells tended to result in PS and phase transition (PT) in the nuclear compartments, which are likely the cause of the GoF effects. Fluorescence recovery after photobleaching (FRAP) experiments revealed liquid characteristics of the condensates in the nucleus. Mutant p53 tended to undergo gel- and solid-like phase transitions in the nucleus and in nuclear bodies demonstrated by slow and incomplete recovery of fluorescence after photobleaching. Polyanions, such as heparin and RNA, were able to modulate PS and PT in vitro. Heparin apparently stabilized the condensates in a gel-like state, and RNA apparently induced a solid-like state of the protein even in the absence of PEG. Conditions that destabilize p53C into a molten globule conformation also produced liquid droplets in the absence of crowding. The disordered transactivation domain (TAD) modulated both phase separation and amyloid aggregation. In summary, our data provide mechanistic insight into the formation of p53 condensates and conditions that may result in the formation of aggregated structures, such as mutant amyloid oligomers, in cancer. The pathway of mutant p53 from liquid droplets to gel-like and solid-like (amyloid) species may be a suitable target for anticancer therapy.

Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF).     

pH dependent self-assembly of dimetallic lanthanide complexes

pH dependent self-association has been observed in a series of DO3A-derived lanthanide complexes bearing a carboxylate group that can act as a bridging ligand at high pH, switching on the luminescence from the lanthanide.