Reorientational dynamics and solid-phase transformation of ammonium dicyanamide into dicyandiamide: a (2)H solid-state NMR study

The reorientational dynamics of ammonium dicyanamide ND4[N(C[triple bond]N)2] and the kinetics as well as the mechanism of the solid-state isomerization reaction from ammonium dicyanamide into dicyandiamide (N[triple bond]C-N==C(NH2)2) was studied by means of 2H and 14N solid-state NMR spectroscopy in a temperature range between 38 and 390 K. Whereas in previous investigations the mechanism of the solid-state transformation was investigated by means of vibrational and magic angle spinning solid-state NMR spectroscopy as well as neutron diffraction, we here present a comprehensive 2H study of the ammonium ion dynamics prior to and during the course of the reaction, thereby highlighting possible cross correlations between dynamics and reactivity involving the ammonium ion. The ND4+ group was found to undergo thermally activated random jumps in a tetrahedral potential, which is increasingly distorted with increasing temperature, giving rise to an asymmetrically compressed or elongated tetrahedron with deviations from the tetrahedral angle of up to 6 degrees . The correlation time follows an Arrhenius law with an activation energy of Ea = 25.8(2) kJ mol(-1) and an attempt frequency of tau0(-1) = 440(80) THz. The spin-lattice relaxation times were fitted according to a simple Bloembergen-Purcell-Pound type model with a T1 minimum of 4 ms at 230 K. Temperature-dependent librational amplitudes were extracted by line-shape simulations between 38 and 390 K and contrasted with those obtained by neutron diffraction, their values ranging between 5 and 28 degrees . The onset and progress of the solid-phase transformation were followed in situ at temperatures above 372 K and could be classified as a strongly temperature-dependent, heterogeneous two-step reaction proceeding with rapid evolution of ammonia and comparatively slow subsequent reintegration into the solid. On the microscopic level, this correlates with a rapid proton transfer -- possibly triggered by a coupling between the ammonium ion dynamics and phonon modes on the terahertz time scale -- and an essentially decoupled nucleophilic attack of ammonia at the nitrile carbon, giving rise to significantly differing time constants for the two processes.     

Total synthesis and mechanism of action of the antibiotic armeniaspirol A

Emerging antimicrobial resistance urges the discovery of antibiotics with unexplored, resistance-breaking mechanisms. Armeniaspirols represent a novel class of antibiotics with a unique spiro[4.4]non-8-ene scaffold and potent activities against Gram-positive pathogens. We report a concise total synthesis of (±) armeniaspirol A in six steps with a yield of 20.3% that includes the formation of the spirocycle through a copper-catalyzed radical cross-coupling reaction. In mechanistic biological experiments, armeniaspirol A exerted potent membrane depolarization, accounting for the pH-dependent antibiotic activity. Armeniaspirol A also disrupted the membrane potential and decreased oxygen consumption in mitochondria. In planar lipid bilayers and in unilamellar vesicles, armeniaspirol A transported protons across membranes in a protein-independent manner, demonstrating that armeniaspirol A acted as a protonophore. We provide evidence that this mechanism might account for the antibiotic activity of multiple chloropyrrole-containing natural products isolated from various origins that share a 4-acylphenol moiety coupled to chloropyrrole as a joint pharmacophore. We additionally describe an efflux-mediated mechanism of resistance against armeniaspirols.

The antibiotic armeniaspirol A depolarized bacterial and mammalian cell membranes through a protonophore activity, that accounts for its potent antibiotic effects. A total synthesis of (±) armeniaspirol A was achieved in six steps.     

Linear Elastic Wave Propagation in Unsaturated,Unconsolidated Soils

By means of a macroscopic linear model for a poroelastic medium with three deformable components the acoustic behavior of four unconsolidated soil types, filled by water and air, is studied. Necessary material parameters are mainly gathered from the German standard DIN 4220. It provides some useful parameters, as for example, van Genuchten parameters, for thirty-one different soil types including sands, silts and clays. There appear four body waves: three longitudinal waves and one shear wave. The slowest compressional wave does only exist if at least two pore fluids appear and is driven by the capillary pressure between the pore fluids. The wave analysis yields the dependence of velocities and attenuations of these waves on the saturation and on the frequency. This is compared to the so far most frequently studied case of partially saturated sandstones. (© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Polychromatic Colorings of Plane Graphs

We show that the vertices of any plane graph in which every face is incident to at least g vertices can be colored by ⌊(3g−5)/4⌋ colors so that every color appears in every face. This is nearly tight, as there are plane graphs where all faces are incident to at least g vertices and that admit no vertex coloring of this type with more than ⌊(3g+1)/4⌋ colors. We further show that the problem of determining whether a plane graph admits a vertex coloring by k colors in which all colors appear in every face is in ℘ for k=2 and is -complete for k=3,4. We refine this result for polychromatic 3-colorings restricted to 2-connected graphs which have face sizes from a prescribed (possibly infinite) set of integers. Thereby we find an almost complete characterization of these sets of integers (face sizes) for which the corresponding decision problem is in ℘, and for the others it is -complete. Research of N. Alon was supported in part by the Israel Science Foundation, by a USA–Israeli BSF grant, and by the Hermann Minkowski Minerva Center for Geometry at Tel Aviv University. Research of R. Berke was supported in part by JSPS Global COE program “Computationism as a Foundation for the Sciences.” Research of K. Buchin and M. Buchin was supported by the Netherlands’ Organisation for Scientific Research (NWO) under BRICKS/FOCUS project no. 642.065.503. Research of P. Csorba was supported by DIAMANT, an NWO mathematics cluster. Research of B. Speckmann was supported by the Netherlands’ Organisation for Scientific Research (NWO) under project no. 639.022.707.     

Dealing with label switching in mixture models under genuine multimodality

The fitting of finite mixture models is an ill-defined estimation problem, as completely different parameterizations can induce similar mixture distributions. This leads to multiple modes in the likelihood, which is a problem for frequentist maximum likelihood estimation, and complicates statistical inference of Markov chain Monte Carlo draws in Bayesian estimation. For the analysis of the posterior density of these draws, a suitable separation into different modes is desirable. In addition, a unique labelling of the component specific estimates is necessary to solve the label switching problem. This paper presents and compares two approaches to achieve these goals: relabelling under multimodality and constrained clustering. The algorithmic details are discussed, and their application is demonstrated on artificial and real-world data.     

VLES Modeling of Flow Over Walls with Variably-shaped Roughness by Reference to Complementary DNS

Turbulent flow over variably-shaped rough walls, characterized by either a regular or a random arrangement of axisymmetric roughness elements in an open channel flow configuration, is investigated computationally within a VLES (Very Large Eddy Simulation) framework by utilizing a volumetric forcing-based roughness model. The prime objective of the present work is to assess the roughness model’s capability to predict mean velocities and turbulent intensities in conjunction with this recently formulated hybrid LES/RANS (Reynolds-Averaged Navier-Stokes) model. The friction velocity-based Reynolds number is in the range Re_τ =?460 ? 500. A non-dimensional drag function accounting for the shape of the roughness elements is introduced and evaluated based on the results of complementary direct numerical simulations (DNS). The dynamics of the residual motion of the presently adopted VLES methodology is described by an appropriately modified elliptic-relaxation-based ζ ? f (\(\zeta =\overline {v^{2}}/k\)) RANS model.     

Ruthenium Lewis Acid‐Catalyzed Asymmetric Diels–Alder Reactions: Reverse‐Face Selectivity for α,β‐Unsaturated Aldehydes and Ketones

Acrolein, methacrolein, methyl vinyl ketone, ethyl vinyl ketone, 3‐methyl‐3‐en‐2‐one, and divinyl ketone were coordinated to a cationic cyclopentadienyl ruthenium(II) Lewis acid incorporating the electron‐poor bidentate BIPHOP–F ligand. Analysis by NOESY and ROESY NMR techniques allowed the determination of conformations of enals and enones present in solution in CD₂Cl₂. The results were compared to solid‐state structures and to the facial selectivities of catalytic asymmetric Diels–Alder reactions with cyclopentadiene. X‐Ray structures of four Ru‐enal and Ru‐enone complexes show the α,β‐unsaturated C=O compounds to adopt an anti‐s‐trans conformation. In solution, enals assume both anti‐s‐trans and anti‐s‐cis conformations. An additional conformation, syn‐s‐trans, is present in enone complexes. Enantioface selectivity in the cycloaddition reactions differs for enals and enones. Reaction products indicate enals to react exclusively in the anti‐s‐trans conformation, whereas with enones, the major product results from the syn‐s‐trans conformation. The alkene in s‐cis conformations, while present in solution, is shielded and cannot undergo cycloaddition. A syn‐s‐trans conformation is found in the solid state of the bulky 6,6‐dimethyl cyclohexanone‐Ru(II) complex. The X‐ray structure of divinyl ketone is unique in that the Ru(II) center binds the enone via a η² bond to one of the alkene moieties. In solution, coordination to Ru–C=O oxygen is adopted. A comparison of facial preference is also made to the corresponding indenyl Lewis acids.     

A Continuous-Wave Electron Paramagnetic Resonance Study of Carbon Dioxide Adsorption on the Metal–Organic Frame-Work MIL-53

Continuous-wave electron paramagnetic resonance spectroscopy is applied to explore the adsorption of carbon dioxide (CO₂) over the metal organic framework (MOF) MIL-53. Therefore, paramagnetic Cr³⁺ ions, which replace a small amount of the bulk Al³⁺ ions in MIL-53(Al/Cr), are used as magnetically active probes. CO₂ was adsorbed on samples of MIL-53(Al/Cr) at equilibrium pressures between 0 and 2.5 bar. The transformation from the large pore phase to the narrow pore phase of MIL-53 was observed by electron paramagnetic resonance spectroscopy at small CO₂ pressures between 0.2 and 0.4 bar, which is in accordance with adsorption results reported in literature. By analyzing the electron paramagnetic resonance signal intensities of the corresponding Cr³⁺ probes, the ratio between the amount of the narrow pore phase and the large pore phase before and after this phase transformation was quantified. A small fraction of the large pore phase remains even after this phase transition. CO₂ adsorption at 77  K indicates the occurrence of the transformation of this MOF from a narrow pore phase to a large pore phase triggered by the adsorbed CO₂. Similar observations were already made using powder X-ray diffraction or infrared spectroscopy. But in contrast to these methods electron paramagnetic resonance spectroscopy on Cr³⁺ seems to be very sensitive not only to large differences between crystallographic conformations like large pores and narrow pores but also to different amounts and configurations of CO₂ molecules trapped in the same structural phase of MIL-53, taking advantage of the high sensitivity of the fine structure interaction of Cr³⁺.     

Applicability of tandem mass spectrometry to the automated comparative sequencing of long-chain oligonucleotides

An algorithm for the comparative sequencing (COMPAS) of oligonucleotides is shown to be suitable for the sequence verification of nucleic acids ranging in length from a few to 80 nucleotides. The algorithm is based on the matching of a fragment ion spectrum generated by collision-induced dissociation to m/z values predicted from a known reference sequence employing established fragmentation pathways. Prior to mass spectrometric investigation, the oligonucleotides were on-line purified by ion-pair reversed-phase high-performance liquid chromatography using monolithic separation columns. This study evaluated the potential and the limits of COMPAS regarding the length and the charge state of oligonucleotides, the selected collision energy, and the analyzed amount of sample using a quadrupole ion trap mass spectrometer. The results revealed that oligonucleotides could be very reliably re-sequenced up to 60-mers, although the algorithm was successfully used to even verify sequences up to 80-mers. The relative collision energy was typically in the range between 13 and 20%, which allowed in most cases a verification of the reference sequence in a window of at least three consecutive collision energies. To select a proper charge state for fragmentation, a compromise had to be found between high signal intensity and low charge state. Furthermore, by reducing the eluent flow rate during elution of the oligonucleotide, the sequence of a 50-mer was successfully verified from the analysis of 295 fmol of the raw product. COMPAS was proven to be reproducible and was applied to the genotyping of the polymorphic, Y-chromosomal locus M9 contained in a 62-base pair polymerase chain reaction product.