Synthesis of Highly Substituted γ‐Butyrolactones by a Gold‐Catalyzed Cascade Reaction of Benzyl Esters

Easily accessible benzylic esters of 3‐butynoic acids in a gold‐catalyzed cyclization/rearrangement cascade reaction provided 3‐propargyl γ‐butyrolactones with the alkene and the carbonyl group not being conjugated. Crossover experiments showed that the formation of the new C?C bond is an intermolecular process. Initially propargylic–benzylic esters were used, but alkyl‐substituted benzylic esters worked equally well. In the case of the propargylic–benzylic products, a simple treatment of the products with aluminum oxide initiated a twofold tautomerization to the allenyl‐substituted γ‐butyrolactones with conjugation of the carbonyl group, the olefin, and the allene. The synthetic sequence can be conducted stepwise or as a one‐pot cascade reaction with similar yields. Even in the presence of the gold catalyst the new allene remains intact.     

Lipase‐Supported Metal–Organic Framework Bioreactor Catalyzes Warfarin Synthesis

A green and sustainable strategy synthesizes clinical medicine warfarin anticoagulant by using lipase‐supported metal–organic framework (MOF) bioreactors (see scheme). These findings may be beneficial for future studies in the industrial production of chemical, pharmaceutical, and agrochemical precursors.     

Azasugar inhibitors as pharmacological chaperones for Krabbe disease

Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe a new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease.     

Dielectric properties of a hydrated sulfonated poly(styrene-ethylene/butylenes-styrene) triblock copolymer

The present study showed that sulfonated poly(styrene-ethylene/butylenes-styrene) (S-SEBS) triblock copolymer ionomers can be made to exhibit dielectric constants on the order of a hundreds thousand. Although they are too lossy at this point to use as dielectric materials in capacitors or as electrostrictive Maxwell effect transducer materials because of their high hydrogen ion conductivity, the results of these initial dielectric studies as a function of ion content were used to try to understand the effects of a polar plasticizer, water, on dielectric properties of the acid form of this ionomer. This was done before moving on to more tightly bound ions (rather than the hydrogen ions of the sulfonic acid groups used here) and to other polar, less mobile plasticizers (which also interact strongly with the ionic dipoles). The discovery of such high dielectric constants suggested the possibility that low dielectric loss versions of this type of polymer, as well as other members of the class known as ionomers, might find future applications as extremely high dielectric constant materials in capacitors or transducers. Experimental results for films with degrees of sulfonation on the order of 10% or more showed dielectric constants on the order of ?′ ∼ 100,000 but dielectric loss tangents near D = tan δ ∼ 0.3, when the materials were exposed to high humidity conditions. Experiments to determine the effects of water content on the material's dielectric response showed that water can easily move into and out of the films studied and that this transport behavior is strongly correlated to the relative humidity of the environment and to the degree of sulfonation. Water content, in this case, was thus the primary consideration when attempting to understand the observed high dielectric constants in films with degree of sulfonation greater than 5.5%. However, vacuum-dried films were, also, examined and observed to exhibit a dielectric constant on the order of 2 until the degree of sulfonation was greater than 11%. Above this value, the dielectric constant increased by approximately 100% to a value on the order of 4.     

Extensions of Modules over Schur Algebras, Symmetric Groups and Hecke Algebras

We study the relation between the cohomology of general linear and symmetric groups and their respective quantizations, using Schur algebras and standard homological techniques to build appropriate spectral sequences. As our methods fit inside a much more general context within the theory of finite-dimensional algebras, we develop our results first in that general setting, and then specialize to the above situations. From this we obtain new proofs of several known results in modular representation theory of symmetric groups. Moreover, we reduce certain questions about computing extensions for symmetric groups and Hecke algebras to questions about extensions for general linear groups and their quantizations.     

An Application of Branch and Cut to Open Pit Mine Scheduling

The economic viability of the modern day mine is highly dependent upon careful planning and management. Declining trends in average ore grades, increasing mining costs and environmental considerations will ensure that this situation will remain in the foreseeable future. The operation and management of a large open pit mine having a life of several years is an enormous and complex task. Though a number of optimization techniques have been successfully applied to resolve some important problems, the problem of determining an optimal production schedule over the life of the deposit is still very much unresolved. In this paper we will critically examine the techniques that are being used in the mining industry for production scheduling indicating their limitations. In addition, we present a mixed integer linear programming model for the scheduling problems along with a Branch and Cut solution strategy. Computational results for practical sized problems are discussed.     

Variational conditions with smooth constraints: structure and analysis

 This is an expository paper about the analysis of variational conditions over sets defined in finite-dimensional spaces by fairly smooth functions satisfying a constraint qualification. The primary focus is on results that can provide quantitative and computable sensitivity information for particular instances of the problems under study, and our objective is to give a personal view of the state of current knowledge in this area and of gaps in that knowledge that require future work. The writing style is informal, in keeping with the objective of focusing the reader's attention on the basic concepts and the relationships between them, rather than on details of the particular results themselves. Received: December 1, 2002 / Accepted: April 25, 2003 Published online: May 28, 2003 Key words. variational condition – variational inequality – complementarity – sensitivity – stability – nondegeneracy Mathematics Subject Classification (2000): Primary: 90C31. Secondary: 47J20, 49J40, 49J53, 90C33     

Free Groups from Fields

In the nineteenth century, field theory brilliantly resolveda number of questions that had taxed mathematicians for centuries;for example, ‘The circle cannot be squared’ by straightedge and compass, and solving polynomial equations by radicalsis not always possible. These successes have continued to beheld up as superb examples of the power of mathematical thought,and are demonstrated at an undergraduate level. The purposeof this article is to provide another such natural example whichleads to a concrete realisation of the free group on 2 generators.     

Time-resolved synchrotron X-ray study of crystalline phase transition in poly(aryl ether ketone ketone) containing alternated terephthalic/isophthalic moieties

Unique crystallization and melting behavior in poly(aryl ether ketone ketone) containing alternated terephthalic and isophthalic moieties were studied by time-resolved synchrotron x-ray methods. Recently, this material has been shown to exhibit three polymorphs (forms I, II, and III). In this work, we further investigated their distinctive thermal properties and found that form I is the dominating and the most thermally stable phase while form II is favored by fast nucleation conditions and is the least stable phase. On the other hand, form III represents a minor intermediate phase that usually coexists with form I and can be transferred from form II and to form I. Structural and morphological changes in form I have been followed by simultaneous wide-angle x-ray diffraction (WAXD)/small-angle x-ray scattering (SAXS) measurements during cold- or melt-crystallization and subsequent melting. In all cases, a larger dimensional change was found in the crystallographic a-axis than the b-axis during heating and cooling. This may be due to the greater lateral stress variation with respect to temperature along the a direction of the primary lamellae which is induced by either the formation of secondary lamellae or the preferential chain-folding direction in poly(aryl ether ketone ketone)s. During the phase transitions of form II ← III in the cold-crystallized specimen and form III ← I in the melt-crystallized samples, lamellar variables (long period, lamellar thickness, and invariant) obtained from SAXS remain almost constant. This indicates that the density distribution in the long spacing is independent of the melting in form II or III. For melt-crystallization, the corresponding changes in unit-cell dimensions and lamellar morphology during the annealing-induced low endotherm are most consistent with the argument that these changes are due to the melting of thin lamellar population. © 1995 John Wiley & Sons, Inc.