Further Withaphysalin Derivatives from Acnistus arborescens

Two new epimeric chlorinated withaphysalins, rel‐(4β,5β,6α,18S,22R)‐ and rel‐(4β,5β,6α,18R,22R)‐6‐chloro‐18,20‐epoxy‐18‐ethoxy‐4,5‐dihydroxy‐1‐oxowitha‐2,24‐diene‐26,22‐lactone ( 1 and 2 resp.), together with the new rel‐(4β,5β,6α,18R,22R)‐6‐chloro‐18,20‐epoxy‐4,5‐dihydroxy‐18‐methoxy‐1‐oxowitha‐2,24‐diene‐26,22‐lactone ( 3 ) and rel‐(3β,4β,5β,6β,18R,22R)‐5,6:18,20‐diepoxy‐3,18‐diethoxy‐4‐hydroxy‐1‐oxowith‐24‐ene‐26,22‐lactone ( 4 ) were isolated from the leaves of Acnistus arborescens and named withaphysalins T–W, respectively. The final structures and the complete ¹H‐ and ¹³C‐NMR assignments of the three chlorowithaphysalins 1 – 3 were performed by means of HR‐ESI‐MS and 1D‐ and 2D‐NMR experiments, including COSY, HSQC, and HMBC, beside comparison with spectral data of analogous compounds from the literature. The structure of 4 was also confirmed by means of a single‐crystal X‐ray diffraction analysis.     

Efficient Cluster-Based Catalysts for Asymmetric Hydrogenation of α-Unsaturated Carboxylic Acids

The new clusters [H(4) Ru(4) (CO)(10) (μ-1,2-P-P)], [H(4) Ru(4) (CO)(10) (1,1-P-P)] and [H(4) Ru(4) (CO)(11) (P-P)] (P-P=chiral diphosphine of the ferrocene-based Josiphos or Walphos ligand families) have been synthesised and characterised. The crystal and molecular structures of eleven clusters reveal that the coordination modes of the diphosphine in the [H(4) Ru(4) (CO)(10) (μ-1,2-P-P)] clusters are different for the Josiphos and the Walphos ligands. The Josiphos ligands bridge a metal-metal bond of the ruthenium tetrahedron in the "conventional" manner, that is, with both phosphine moieties coordinated in equatorial positions relative to a triangular face of the tetrahedron, whereas the phosphine moieties of the Walphos ligands coordinate in one axial and one equatorial position. The differences in the ligand size and the coordination mode between the two types of ligands appear to be reflected in a relative propensity for isomerisation; in solution, the [H(4) Ru(4) (CO)(10) (1,1-Walphos)] clusters isomerise to the corresponding [H(4) Ru(4) (CO)(10) (μ-1,2-Walphos)] clusters, whereas the Josiphos-containing clusters show no tendency to isomerisation in solution. The clusters have been tested as catalysts for asymmetric hydrogenation of four prochiral α-unsaturated carboxylic acids and the prochiral methyl ester (E)-methyl 2-methylbut-2-enoate. High conversion rates (>94?%) and selectivities of product formation were observed for almost all catalysts/catalyst precursors. The observed enantioselectivities were low or nonexistent for the Josiphos-containing clusters and catalyst (cluster) recovery was low, suggesting that cluster fragmentation takes place. On the other hand, excellent conversion rates (99-100?%), product selectivities (99-100?% in most cases) and good enantioselectivities, reaching 90?% enantiomeric excess (ee) in certain cases, were observed for the Walphos-containing clusters, and the clusters could be recovered in good yield after completed catalysis. Results from high-pressure NMR and IR studies, catalyst poisoning tests and comparison of catalytic properties of two [H(4) Ru(4) (CO)(10) (μ-1,2-P-P)] clusters (P-P=Walphos ligands) with the analogous mononuclear catalysts [Ru(P-P)(carboxylato)(2) ] suggest that these clusters may be the active catalytic species, or direct precursors of an active catalytic cluster species.     

Ruthenium- and osmium-arene-based paullones bearing a TEMPO free-radical unit as potential anticancer drugs

A modified paullone ligand bearing a TEMPO free-radical unit (HL) and its ruthenium(ii) and osmium(ii)-arene complexes [M(p-cymene)(HL)Cl]Cl·nH(2)O (M = Ru, Os) exhibit high antiproliferative activity in human cancer cell lines.     

Limitations of high-intensity soft X-ray laser fields for the characterisation of water chemistry: Coulomb explosion of the octamer water cluster

In this work, the Coulomb explosion of the octamer water cluster has been studied employing a theoretical approach. Instead of the usual methodology that makes use of classical molecular dynamics, time-dependent density functional theory has been applied to tackle the problem. This method explicitly accounts for the laser field and thus does not impose any constraint on the interaction between the laser pulse and the cluster. We focus on the effects of energetic changes in the system under high-intensity soft X-ray laser pulses. The motions of the ions and their velocities during this process show significant differences for the three applied laser intensities (10(14), 10(15) and 10(16) W cm(-2)). Very strong soft X-ray free electron laser (FEL) pulses must be short to allow for investigations of ultra-fast wet chemistry, according to the principle of collect and destroy.     

Temperature dependence of thermal diffusion for aqueous solutions of monosaccharides, oligosaccharides, and polysaccharides

We studied the thermal diffusion behavior for binary aqueous solutions of glucose, maltotriose, maltohexaose, pullulan, and dextran by means of thermal diffusion forced Rayleigh scattering (TDFRS). The investigated saccharides with molar masses between 0.180 and 440 kg mol(-1) were studied in the temperature range between 15 and 55 °C. The thermal diffusion coefficient D(T) and the Soret coefficient S(T) of all solutions increase with increasing temperature. For maltohexaose and the polymers the thermal diffusion coefficient changes sign from negative to positive with increasing temperature, whereas glucose and maltotriose show only positive values in the entire investigated temperature range. While we were able to find a master curve to describe the temperature dependence of D(T), we were not able to find a similar expression for S(T). This comprehensive study allows for the first time the determination of the interaction parameters for the polymer and the solvent within the theoretical framework suggested by Würger [Phys. Rev. Lett., 2009, 102, 078302].     

Polyominoes Determined by Permutations: Enumeration via Bijections

A permutominide is a set of cells in the plane satisfying special connectivity constraints and uniquely defined by a pair of permutations. It naturally generalizes the concept of permutomino, recently investigated by several authors and from different points of view [1, 2, 4, 6, 7]. In this paper, using bijective methods, we determine the enumeration of various classes of convex permutominides, including, parallelogram, directed convex, convex, and row convex permutominides. As a corollary we have a bijective proof for the number of convex permutominoes, which was still an open problem.     

Population genetics in compressible flows

We study competition between two biological species advected by a compressible velocity field. Individuals are treated as discrete Lagrangian particles that reproduce or die in a density-dependent fashion. In the absence of a velocity field and fitness advantage, number fluctuations lead to a coarsening dynamics typical of the stochastic Fisher equation. We investigate three examples of compressible advecting fields: a shell model of turbulence, a sinusoidal velocity field and a linear velocity sink. In all cases, advection leads to a striking drop in the fixation time, as well as a large reduction in the global carrying capacity. We find localization on convergence zones, and very rapid extinction compared to well-mixed populations. For a linear velocity sink, one finds a bimodal distribution of fixation times. The long-lived states in this case are demixed configurations with a single interface, whose location depends on the fitness advantage.     

Extensive Adiabatic Invariants for Nonlinear Chains

We look for extensive adiabatic invariants in nonlinear chains in the thermodynamic limit. Considering the quadratic part of the Klein-Gordon Hamiltonian, by a linear change of variables we transform it into a sum of two parts in involution. At variance with the usual method of introducing normal modes, our constructive procedure allows us to exploit the complete resonance, while keeping the extensive nature of the system. Next we construct a nonlinear approximation of an extensive adiabatic invariant for a perturbation of the discrete nonlinear Schrödinger model. The fluctuations of this quantity are controlled via Gibbs measure estimates independent of the system size, for a large set of initial data at low specific energy. Finally, by numerical calculations we show that our adiabatic invariant is well conserved for times much longer than predicted by our first order theory, with fluctuation much smaller than expected according to standard statistical estimates.     

Spectroscopic measurement of the refractive index of ion-implanted diamond

We present the results of variable-angle spectroscopic ellipsometry and transmittance measurements to determine the variation of the complex refractive index of ion-implanted single-crystal diamond. An increase is found in both real and imaginary parts at increasing damage densities. The index depth variation is determined in the whole wavelength range between 250 and 1690 nm. The dependence from the vacancy density is evaluated, highlighting a deviation from linearity in the high-damage-density regime. A considerable increase (up to 5%) in the real part of the index is observed, attributed to an increase in polarizability, thus offering new microfabrication possibilities for waveguides and other photonic structures in diamond.     

Combination of a two-step fluorescence assay and a two-step anti-Factor Xa assay for detection of heparin falsifications and protein in heparins

There are several methods for sensitive detection of oversulfated chondroitin sulfate (OSCS) in heparin. Although contamination with OSCS is unlikely to be repeated, use of other compounds to counterfeit heparin must be considered. We have previously developed a two-step fluorescence microplate assay (two-step FI assay) for detection of OSCS. First, the heparin sample is incubated with heparinase I, then its increasing effect on the fluorescence intensity (FI) of the sensor molecule Polymer-H is measured (PolyH assay). The high sensitivity of the assay is shown to be based on heparinase I inhibition by OSCS. The objective of this study was to evaluate another assay option — indirect quantification of OSCS after heparinase I incubation by means of the anti-Factor Xa (aXa) activity of the remaining undegraded heparin (two-step aXa assay). We also examined, whether other heparin mimetics (HepM), direct Factor Xa inhibitors (DXI), and protein impurities are detectable by use of these assays. Heparin was spiked with different amounts of HepM including OSCS, pentosan polysulfate, dextran sulfate, curdlan sulfate, the natural contaminant dermatan sulfate, the DXI rivaroxaban, and BSA as a protein. These samples were compared with pure heparin in the two-step FI assay, the two-step aXa assay, and in the PolyH assay and the aXa assay without heparinase I incubation. Both two-step assays sensitively measured contamination with all the HepM (LOD ≤ 0.5%, LOQ ≤ 0.7%). The two-step aXa assay also detected rivaroxaban (LOD 0.3%, LOQ 0.4%), whereas the two-step FI assay was shown to be suited to determination of protein impurities (LOD 0.11%, LOQ 0.13%). Use of two different heparinase I inactivation procedures enabled clear differentiation between protein, HepM, and both contaminants. Finally, with the aXa assay the heparin potency can be determined in the same assay run, whereas the FI increase in the PolyH assay was shown to be useful for identification. In conclusion, both the two-step FI assay and the two-step aXa assay are sensitive, rapid, and simple tests for the detection of counterfeit heparin. Comprehensive information about heparin quality can be obtained by their combined use and the parallel measurement of non-incubated heparin samples.