A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain‐Permeable OGA Inhibitors

Pyrrolidine‐based iminocyclitols are a promising class of glycosidase inhibitors. Reported herein is a convenient epimerization strategy that provides direct access to a range of stereoisomeric iminocyclitol inhibitors of O‐GlcNAcase (OGA), the enzyme responsible for catalyzing removal of O‐GlcNAc from nucleocytoplasmic proteins. Structural details regarding the binding of these inhibitors to a bacterial homologue of OGA reveal the basis for potency. These compounds are orally available and permeate into rodent brain to increase O‐GlcNAc, and should prove useful tools for studying the role of OGA in health and disease.     

Optimized water‐based ATRP of an anionic monomer: Comprehension and properties characterization

The effect of pH and the ligand nature over the atom transfer radical polymerization (ATRP) of the anionic monomer sodium 2‐acrylamido‐2‐methylpropanesulfonate (AMPSNa) was investigated in aqueous medium by using ω‐halogenated poly(ethylene oxide) and CuBr, as macroinitiator and catalyst, respectively. The stability of both catalytic complexes and macroinitiator was investigated in function of pH, that is, fixed between 7.5 and 12. UV‐VIS spectroscopy confirmed a good catalytic complex stability in the studied conditions. Hydrolysis of the macroinitiator ester group at pH higher than 7.5 was detected by ¹H NMR and GPC, yielding ill‐defined polymer samples when ATRP is performed in alkaline conditions. 2,2′‐Bipyridyl (Bpy), 1,1,4,7,10,10‐hexamethyltriethylenetetramine (HMTETA), and tris(2‐methylaminoethyl)amine (Me₆‐TREN)‐based complexes were compared at the optimal pH (pH 7.5). When polymerization was carried out in the presence of CuBr · 2Me₆‐TREN complex block copolymers with narrow molecular weight distribution (1.1 ≤ M _W/M _n ≤ 1.3), and good agreement between theoretical and experimental molar masses was obtained. Moreover, increasing the PAMPSNa polymerization degrees (n) did not affect the control over the polymerization. Preliminary characterization of the diblock copolymers behavior in aqueous medium revealed a strong polyelectrolyte effect independently of n. Interestingly, occurrence of interactions between the PEO and PAMPSNa‐blocks was also evidenced by differential scanning calorimetry and thermogravimetric analyses. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1108–1119, 2009     

Simulation Study for the Clan of Ancestors in a Perfect Simulation Scheme of a Continuous One-Dimensional Loss Network

Perfect simulation of a one-dimensional loss network on ℝ with length distribution π and cable capacity C is performed using the clan of ancestors method. Previous works estimated the region of convergence of this scheme using a domination by a branching process. In this work, we show that the domination by the branching process is far from sharp and that there is room for improvement. Moreover, we derive an empirical relation concerning the critical value using simulation studies on the number of rectangles present in the clan of ancestors.      

Synthesis, characterisation and complex forming ability towards ferric ions of oligo(ether-amide)s of Jeffamines ED and chelidamic acid

New chelating oligo(ether-amide)s (CA-PE)s containing chelidamic acid residues in the main chain were prepared by reacting chelidamic acid with Jeffamines ED^® in the presence of N,N^′-dicyclohexylcarbodiimide and 4-dimethylaminopyridine. A mixture of products having one or two polyether sequences with chelidamate end-groups was obtained. It was found spectrophotometrically that CA-PE polymers formed a complex with Fe³⁺ at pH 3-6 having a maximum absorbance in the 472-495 nm range. Fe³⁺ ion complexes of CA-PE were water soluble, except Fe³⁺-CA-PE₆₀₀. The stoichiometric ratio between chelidamic acid residues of oligo(ether-amide)s CA-PE and Fe³⁺ ions was found to be 2 at pH 5 by the method of shift of equilibrium. A hydroxypyridine structure of the chelidamic acid residues in the complex was suggested.     

Polymerization of ε-caprolactone initiated by stable salts. Initiation mechanism

The mechanism of initiation of ε-caprolactone polymerization by stable salts has been investigated. Gel permeation chromatography and ¹H-NMR spectroscopy were used for determining the compositions of the reaction mixtures and of the polymers. It was established that the initiation proceeds by addition of the initiator to the monomer.     

Group Divisible Covering Designs with Block Size 4: A Type of Covering Array with Row Limit

A k‐GDCD, group divisible covering design, of type is a triple , where V is a set of gu elements, is a partition of V into u sets of size g, called groups, and is a collection of k‐subsets of V, called blocks, such that every pair of elements in V is either contained in a unique group or there is at least one block containing it, but not both. This family of combinatorial objects is equivalent to a special case of the graph covering problem and a generalization of covering arrays, which we call CARLs. In this paper, we show that there exists an integer such that for any positive integers g and , there exists a 4‐GDCD of type which in the worst case exceeds the Schönheim lower bound by δ blocks, except maybe when (1) and , or (2) , , and or . To show this, we develop constructions of 4‐GDCDs, which depend on two types of ingredients: essential, which are used multiple times, and auxiliary, which are used only once in the construction. If the essential ingredients meet the lower bound, the products of the construction differ from the lower bound by as many blocks as the optimal size of the auxiliary ingredient differs from the lower bound.     

Electrospun Hybrid Nanofibers Based on Chitosan or N‐Carboxyethylchitosan and Silver Nanoparticles

Hybrid nanofibers from chitosan or N‐carboxyethylchitosan (CECh) and silver nanoparticles (AgNPs) were prepared by electrospinning using HCOOH as a solvent. AgNPs were synthesized in situ in the spinning solution. HCOOH slowed down the cross‐linking of the polysaccharides with GA enabling the reactive electrospinning in the presence of poly(ethylene oxide) (PEO). EDX analyses showed that AgNPs are uniformly dispersed in the nanofibers. Since AgNPs hampered the cross‐linking of chitosan and CECh with GA in the hybrid fibers, the imparting of water insolubility to the fibers was achieved at a second stage using GA vapors. The surface of chitosan/PEO/AgNPs nanofibers was enriched in chitosan and 15 wt.‐% of the incorporated AgNPs were on the fiber surface as evidenced by XPS.

     

Ab initio study of S dynamics on iron surfaces

Density functional theory was employed to examine the interactions of atomic sulfur with the Fe(1 0 0) and Fe(1 1 0) surfaces. Vibrational frequency calculations were performed to determine the nature of stationary points at the high symmetry atop, bridge and hollow adsorption sites and to indicate the direction the adsorbate would move across the surface. The values were also used in the determination of the rate constant for hopping of S from one energy minimum site to another. Ab initio molecular dynamics (MD) simulations were then performed to monitor the mobility of the S atom on the (1 0 0) surface at different temperatures up to the melting point of Fe (1808 K) and were compared to our previously obtained ab initio MD results for S/Fe(1 1 0) [N. Todorova, M.J.S. Spencer, I. Yarovsky, Australian Institute of Physics 16th Biennial Congress, 2005, Canberra, Australia, ISBN 0-9598064-8-2].