Reductive Catenation of Phosphine Antimony Complexes

Reactions of triarylphosphines with fluoroantimony(III) triflates give phosphine antimony(III) complexes, which undergo spontaneous reductive elimination of fluorophosphonium cations. The resulting phosphine antimony(I) complexes catenate to give the first examples of cationic antimony bicyclic compounds, [(R₃P)₄Sb₆]⁴⁺, featuring a bicyclo[3.1.0]hexastibine framework stabilized by four phosphine ligands. The unprecedented 14‐electron redox process illustrates the generality of the reductive catenation method.     

Disruption of Wnt planar cell polarity signaling by aberrant accumulation of the MetAP-2 substrate Rab37

Identification of methionine aminopeptidase-2 (MetAP-2) as the molecular target of the antiangiogenic compound TNP-470 has sparked interest in N-terminal Met excision's (NME) role in endothelial cell biology. In this regard, we recently demonstrated that MetAP-2 inhibition suppresses Wnt planar cell polarity (PCP) signaling and that endothelial cells depend on this pathway for normal function. Despite this advance, the substrate(s) whose activity is altered upon MetAP-2 inhibition, resulting in loss of Wnt PCP signaling, is not known. Here we identify the small G protein Rab37 as a MetAP-2-specific substrate that accumulates in the presence of TNP-470. A functional role for aberrant Rab37 accumulation in TNP-470's mode of action is demonstrated using a Rab37 point mutant that is resistant to NME, because expression of this mutant phenocopies the effects of MetAP-2 inhibition on Wnt PCP signaling-dependent processes.     

Study of OSEM with different subsets in grating-based X-ray differential phase-contrast imaging

Impressive developments in X-ray imaging are associated with X-ray phase contrast computed tomography based on grating interferometry, a technique that provides increased contrast compared with conventional absorption-based imaging. A new "single-step" method capable of separating phase information from other contributions has been recently proposed. This approach not only simplifies data-acquisition procedures, but, compared with the existing phase step approach, significantly reduces the dose delivered to a sample. However, the image reconstruction procedure is more demanding than for traditional methods and new algorithms have to be developed to take advantage of the "single-step" method. In the work discussed in this paper, a fast iterative image reconstruction method named OSEM (ordered subsets expectation maximization) was applied to experimental data to evaluate its performance and range of applicability. The OSEM algorithm with different subsets was also characterized by comparison of reconstruction image quality and convergence speed. Computer simulations and experimental results confirm the reliability of this new algorithm for phase-contrast computed tomography applications. Compared with the traditional filtered back projection algorithm, in particular in the presence of a noisy acquisition, it furnishes better images at a higher spatial resolution and with lower noise. We emphasize that the method is highly compatible with future X-ray phase contrast imaging clinical applications.     

Copper redox cycling in the prion protein depends critically on binding mode

The prion protein (PrP) takes up 4-6 equiv of copper in its extended N-terminal domain, composed of the octarepeat (OR) segment (human sequence residues 60-91) and two mononuclear binding sites (at His96 and His111; also referred to as the non-OR region). The OR segment responds to specific copper concentrations by transitioning from a multi-His mode at low copper levels to a single-His, amide nitrogen mode at high levels (Chattopadhyay et al. J. Am. Chem. Soc. 2005, 127, 12647-12656). The specific function of PrP in healthy tissue is unclear, but numerous reports link copper uptake to a neuroprotective role that regulates cellular stress (Stevens, et al. PLoS Pathog.2009, 5 (4), e1000390). A current working hypothesis is that the high occupancy binding mode quenches copper's inherent redox cycling, thus, protecting against the production of reactive oxygen species from unregulated Fenton type reactions. Here, we directly test this hypothesis by performing detailed pH-dependent electrochemical measurements on both low and high occupancy copper binding modes. In contrast to the current belief, we find that the low occupancy mode completely quenches redox cycling, but high occupancy leads to the gentle production of hydrogen peroxide through a catalytic reduction of oxygen facilitated by the complex. These electrochemical findings are supported by independent kinetic measurements that probe for ascorbate usage and also peroxide production. Hydrogen peroxide production is also observed from a segment corresponding to the non-OR region. Collectively, these results overturn the current working hypothesis and suggest, instead, that the redox cycling of copper bound to PrP in the high occupancy mode is not quenched, but is regulated. The observed production of hydrogen peroxide suggests a mechanism that could explain PrP's putative role in cellular signaling.     

Comparison of structure and reactivity of phosphine-amido and hemilabile phosphine-amine chelates of rhodium

A series of mono- and binuclear rhodium(I) complexes bearing ortho-phosphinoanilido and ortho-phosphinoaniline ligands has been synthesized. Reactions of the protic monophosphinoanilines, Ph(2)PAr or PhPAr(2) (Ar = o-C(6)H(4)NHMe), with 0.5 equiv of [Rh(μ-OMe)(COD)](2) result in the formation of the neutral amido complexes, [Rh(COD)(P,N-Ph(2)PAr(-))] or [Rh(COD)(P,N-PhP(Ar(-))Ar)] (Ar(-) = o-C(6)H(4)NMe(-)), respectively, through stoichiometrically controlled deprotonation of an amine by the internal methoxide ion. Similarly, the binuclear complex, [Rh(2)(COD)(2)(μ-P,N,P',N'-mapm(2-))] (mapm(2-) = Ar(Ar(-))PCH(2)P(Ar(-))Ar), can be prepared by reaction of the protic diphosphinoaniline, mapm (Ar(2)PCH(2)PAr(2)), with 1 equiv of [Rh(μ-OMe)(COD)](2). An analogous series of hemilabile phosphine-amine compounds can be generated by reactions of monophosphinoanilines, Ph(2)PAr' or PhPAr'(2) (Ar' = o-C(6)H(4)NMe(2)), with 1 equiv of [Rh(NBD)(2)][BF(4)] to generate [Rh(NBD)(P,N-Ph(2)PAr')][BF(4)] or [Rh(NBD)(P,N-PhPAr'(2))][BF(4)], respectively, or by reactions of diphosphinoanilines, mapm or dmapm (Ar'(2)PCH(2)PAr'(2)), with 2 equiv of the rhodium precursor to generate [Rh(2)(NBD)(2)(μ-P,N,P',N'-mapm)][BF(4)](2) or [Rh(2)(NBD)(2)(μ-P,N,P',N'-dmapm)][BF(4)](2), respectively. Displacement of the diolefin from [Rh(COD)(P,N-Ph(2)PAr(-))] by 1,2-bis(diphenylphosphino)ethane (dppe) yields [Rh(P,P'-dppe)(P,N-Ph(2)PAr(-))] which, while unreactive to H(2), reacts readily and irreversibly with oxygen to form the peroxo complex, [RhO(2)(P,P'-dppe)(P,N-Ph(2)PAr(-))], and with iodomethane to yield [RhI(CH(3))(P,P'-dppe)(P,N-Ph(2)PAr(-))]. Hemilabile phosphine-amine compounds can also be prepared by reactions of [Rh(P,P'-dppe)(P,N-Ph(2)PAr(-))] with Me(3)OBF(4) or HBF(4)·Et(2)O, resulting in (thermodynamic) additions at nitrogen to form [Rh(P,P'-dppe)(P,N-Ph(2)PAr')][BF(4)] or [Rh(P,P'-dppe)(P,N-Ph(2)PAr)][BF(4)], respectively. The nonlabile phosphine-amido and hemilabile phosphine-amine complexes were tested as catalysts for the silylation of styrene. The amido species do not require the use of solvents in reaction media, can be easily removed from product mixtures by protonation, and appear to be more active than their hemilabile, cationic congeners. Reactions catalyzed by either amido or amine complexes favor dehydrogenative silylation in the presence of excess olefin, showing modest selectivities for a single vinylsilane product. The binuclear complexes, which were prepared in an effort to explore possible catalytic enhancements of reactivity due to metal-metal cooperativity, are in fact somewhat less active than mononuclear species, discounting this possibility.     

Ferromagnetic spin-delocalized electron donors for multifunctional materials: π-conjugated benzotriazinyl radicals

We have developed new synthetic methodology for benzotriazinyl radicals that exhibit spin delocalization, low oxidation potentials, and ferromagnetic interactions in the solid state via π-π interactions, making them promising candidates for multifunctional magnetic materials.     

Thermodynamic and dielectric properties of polar lattices

Monte Carlo results are presented for the free energy and dielectric constant of systems of permanent dipoles disposed on the sites of simple cubic and face-centred cubic lattices as functions of the parameter ? = μ²ρ/kT. Alternative schemes are considered for taking account of the long-range character of the dipolar interaction, based on an Ewald-type sum or a reaction-field approximation; use of such a procedure is essential if the system is to have the correct dielectric properties. Different methods of calculating the dielectric constant are also compared. It is shown that the two methods of treating the long-range contribution to the energy lead to similar results for the dielectric constant, but use of the Ewald method apparently introduces a small but systematic error. The results on both free energy and dielectric constant are discussed in the light of predictions of a number of analytical approaches. In the case of the simple cubic lattice the general trend in the computed dielectric constant as a function of ? is in closer accord with the solution of the mean spherical approximation than with a simple Padé approximant to the Clausius-Mossotti function.     

A cryogenic underground observatory for rare events: CUORE, an update

CUORE is a proposed tightly packed array of 1000 TeO₂ bolometers, each being a cube 5 cm on a side with a mass of 750 g. The array consists of 25 vertical towers, arranged in a square of 5 towers by 5 towers, each containing ten layers of four crystals. The design of the detector is optimized for ultralow-background searches for neutrinoless double beta decay of ¹³⁰Te (33.8% abundance), cold dark matter, solar axions, and rare nuclear decays. A preliminary experiment involving 20 crystals of various sizes (MIBETA) has been completed, and a single CUORE tower is being constructed as a smaller scale experiment called CUORICINO. The expected performance and sensitivity, based on Monte Carlo simulations and extrapolations of present results, are reported.