Design, synthesis, and biological evaluation of beta-ketosulfonamide adenylation inhibitors as potential antitubercular agents

[reaction: see text] The antitubercular nucleoside antibiotics 1 and 2 were recently described that inhibit the adenylate-forming enzyme MbtA and disrupt biosynthesis of the virulence-conferring siderophore known as mycobactin in Mycobacterium tuberculosis. Herein, we report efforts to refine this inhibitor scaffold by replacing the labile acylsulfamate linkage (highlighted) with the more chemically robust beta-ketosulfonamide linkage of 3 and 4.     

Modelling and simulation of injecting acrylic bone cement into osteoporotic vertebral bones within percutaneous vertebroplasty

Percutaneous vertebroplasty is a common clinical procedure to treat vertebral compression fractures and osteoporotic vertebral bodies. However, this operation technique is accompanied by different complications due to lack of knowledge about the complicated behaviour of bone cement within the human body. To contribute to a better understanding of the processes that take place inside the body during a vertebroplasty, a detailed model of the thermomechanical behaviour of acrylic bone cement has been developed. All important effects are covered, that influence the behaviour of acrylic bone cement during the injection in a human vertebral body. Implemented in the opensource CFD-code OpenFOAM^®, first results show that this comprehensive simulation of the minimal invasive injection is capable to accurately predict the cement distribution and temperature field of acrylic bone cement inside the vertebral body. (© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Tail dependence between order statistics

In this work, we introduce the s,k-extremal coefficients for studying the tail dependence between the s-th lower and k-th upper order statistics of a normalized random vector. If its margins have tail dependence then so do their order statistics, with the strength of bivariate tail dependence decreasing as two order statistics become farther apart. Some general properties are derived for these dependence measures which can be expressed via copulas of random vectors. Its relations with other extremal dependence measures used in the literature are discussed, such as multivariate tail dependence coefficients, the coefficient η of tail dependence, coefficients based on tail dependence functions, the extremal coefficient ?, the multivariate extremal index and an extremal coefficient for min-stable distributions. Several examples are presented to illustrate the results, including multivariate exponential and multivariate Gumbel distributions widely used in applications.     

Structural changes in metallothionein isoforms revealed by capillary electrophoresis and Brdicka reaction

Metallothionein (MT) as a potential cancer marker is at the center of interest and its properties, functions and behavior under various conditions is intensively studied. In the present study, two major mammalian MT isoforms (MT‐1 and MT‐2) were separated using capillary electrophoresis (CE) coupled with UV detector in order to describe their basic behavior. Under the optimized conditions, the separation of both isoforms was enabled as well as estimation of detection limits as subunits and units of ng per μL for MT‐2 and MT‐1, respectively. Further, the effects of thermal treatment and the presence of denaturing agent such as urea on MT‐1 and MT‐2 isoforms were studied by CE‐UV. Thermal treatment caused an increase in the signals of both isoforms. A new parameter called precipitation rate has been defined based on this finding. This parameter can be expressed as a slope of the linear regression of the time dependency curve recalculated on the MT concentration. The thermal precipitation rate for MT‐1 and MT‐2 was determined as 1.1 and 0.9 ng of MT/min, respectively. The chemical precipitation rate calculated from the linear regression for both isoforms provided the same value of 0.25 ng of MT/min. The results were confirmed by manual spectrometric measurements and by differential pulse voltammetry Brdicka reaction. Based on these results, a model of MT behavior under the conditions studied was suggested.     

Infrared (810 nm) low-level laser therapy in experimental model of strain-induced skeletal muscle injury in rats: effects on functional outcomes

Muscle strains are among the most prevalent causes for athletes' absence from sport activities. Low-level laser therapy (LLLT) has recently emerged as a potential contender to nonsteroidal anti-inflammatory drugs in muscle strain treatment. In this work we investigated effects of LLLT and diclofenac on functional outcomes in the acute stage after muscle strain injury in rats. Muscle strain was induced by overloading the tibialis anterior muscle of rats during anesthesia. The injured groups received either no treatment, or a single treatment with diclofenac 30 min prior to injury, or LLLT (810 nm, 100 mW) with doses of 1, 3, 6 or 9 J, at 1 h after injury. Functional outcome measures included a walking index and assessment of electrically induced muscle performance. All treatments (except 9 J LLLT) significantly improved the walking index 12 h postinjury compared with the untreated group. The 3 J group also showed a significantly better walking index than the drug group. All treatments significantly improved muscle performance at 6 and 12 h. LLLT dose of 3 J was as effective as the pharmacological agent in improving functional outcomes in the early phase after a muscle strain injury in rats.     

X‐Treme beamline at SLS: X‐ray magnetic circular and linear dichroism at high field and low temperature

X‐Treme is a soft X‐ray beamline recently built in the Swiss Light Source at the Paul Scherrer Institut in collaboration with École Polytechnique Fédérale de Lausanne. The beamline is dedicated to polarization‐dependent X‐ray absorption spectroscopy at high magnetic fields and low temperature. The source is an elliptically polarizing undulator. The end‐station has a superconducting 7 T–2 T vector magnet, with sample temperature down to 2 K and is equipped with an in situ sample preparation system for surface science. The beamline commissioning measurements, which show a resolving power of 8000 and a maximum flux at the sample of 4.7 × 10¹² photons s^?1, are presented. Scientific examples showing X‐ray magnetic circular and X‐ray magnetic linear dichroism measurements are also presented.     

Spectrophotometric determination of osmium (VIII) with promazine hydrochloride

Promazine hydrochloride is proposed as a new reagent for the spectrophotometric determination of osmium (VIII). The reagent forms orange oxidation product with osmium tetroxide at room temperature in acidic media. The effects of acid concentration, time, temperature, and foreign ions are reported. Beer's law is obeyed in the osmium concentration range 1–10 μg/ml.     

Crystalline complexes,coordination polymers and aggregation modes of tetra(4-pyridyl)porphyrin

Aggregation patterns of tetra(4-pyridyl)porphyrin and of its zinc(II) complex in seven new solid materials have been investigated by X-ray diffraction. The metalloporphyrin compound forms two types of coordination polymers through ligation of the porphyrin periphery on one molecule to the metal center of an adjacent porphyrin. These include one-dimensional chains with a zigzag conformation, as well as three-dimensional, extensively interlinked, polymeric structures. The non-metallated compound reveals a characteristic layered arrangement and interporphyrin stacking of the type which is commonly observed in the structures of tetraphenylporphyrin derivatives. In the absence of a metal center, the basic functionality of the pyridyl substituents is utilized for effective H-bond directed coordination and co-crystallization with solvent/guest components. The stoichiometry of the porphyrin solvation, and the consequent interporphyrin organization in the solid phase, are quite sensitive to the nature of the coordinating solvent.Author for correspondence. Supplementary Data relating to this article are deposited with the British Library as supplementary publication No. SUP 82174 (37 pages).     

Structural patterns in clathrates and crystalline complexes of zinc-tetra(4-chlorophenyl)porphyrin and zinc-tetra(4-fluorophenyl)porphyrin

Twelve new crystalline materials based on zinc-tetra(4-chlorophenyl)porphyrin (8 compounds) and zinc-tetra(4-fluorophenyl)prophyrin (4 compounds) building blocks have been prepared and characterized by X-ray diffraction analysis. Several different modes of guest solvent incorporation into the porphyrin lattice, including enclathration (of solvents of low polarity) and complex formation (with strong Lewis bases), and of intermolecular organization have been detected. Unique interporphyrin architectures, affected by directional Cl...Cl interactions, characterize most of the known solid structures of the chlorosubstituted materials. A small number of the latter, as well as the fluorosubstituted derivatives, exhibit interporphyrin arrangements of the type which are commonly observed in the clathrates of unsubstituted tetraphenylmetalloporphyrins. The pore structure of these compounds is affected to a large extent by the nature of the incorporated solvate and, consequently, the degree of coordination of the metal center. In crystals of four-coordinate porphyrins the solvent guest components are usually incorporated into channel-type cavities formed between columns and layers of densely stacked hosts. In five-coordinate and six-coordinate materials the guest sites coincide with the axial coordination sites of the porphyrin metal atoms. The latter structures reveal a tight fit between adjacent layers of the complexed entities, the axial ligands of one layer being incorporated into localized interporphyrin cavities of another layer. Dipolar forces play also an important role in the interporphyrin organization.Supplementary Data relating to this article have been deposited with the British Library as supplementary publication No. SUP 82183 (97 pages).