Rhenium ethoxy- and hydroxycarbene complexes with thiophene substituents

Reaction of mono- and dilithiated thiophene (a), bithiophene (b) and 2,5-dibromothiophene (c) with [Re(2)(CO)(10)] afforded, after subsequent alkylation with triethyloxonium tetrafluoroborate, tetra- and binuclear Fischer carbene complexes, [Re(2)(CO)(9){C(OEt){C(4)H(2)S}(n)X}], n = 1, X = H (1a); n = 2, X = H (1b); n = 1, X = Br (1c); n = 1, X = C(OEt)Re(2)(CO)(9), (2a); n = 2, X = C(OEt)Re(2)(CO)(9) (2b), as major products. The dirhenium acylate intermediates from this reaction not only gave the expected novel ethoxycarbene complexes with alkylation but after rhenium-rhenium bond breaking afforded a number of minor products. The (1)H NMR spectrum of the crude reaction mixture revealed the formation of four metal hydride complexes and aldehydes. Protonation with HBF(4) instead of alkylation with Et(3)OBF(4) significantly increased the yields of the hydride complexes, which enabled the positive identification of three of these complexes. In addition to the known compounds [Re(CO)(5)H] and [Re(3)(CO)(14)H] (3), a unique complex displaying a hydroxycarbene fragment connected to an acyl fragment via an O-H···O hydrogen bond and a Re···H···Re bond linking the two Re centers, [(μ-H){Re(CO)(4)C(OH){C(4)H(2)S}(n)H}{Re(CO)(4)C(O){C(4)H(2)S}(n)H}], n = 1 (4a) or n = 2 (4b), were isolated. The formation of thiophene aldehydes, H{C(O)}(m){C(4)H(2)S}(n)C(O)H (m = 0 or 1 and n = 1 or 2), were observed and the novel monocarbene complexes with terminal aldehyde groups, [Re(2)(CO)(9){C(OEt){C(4)H(2)S}(n)C(O)H}], n = 1 (5a) and n = 2 (5b) could be isolated. A higher yield of 5b was obtained after stirring crystals of 2b in wet THF. The crystal structures of 1a, 2a, 4a and 5b are reported.     

Total synthesis of (+)-grandifloracin by iron complexation of a microbial arene oxidation product

(+)-Grandifloracin was synthesized from sodium benzoate by means of a dearomatizing dihydroxylation that proceeds with unusual regioselectivity. Iron diene complexes formed from the arene oxidation product permit the use of otherwise inaccessible transformations. The synthetic material was shown to be antipodal to the natural product, thus determining the absolute configuration of grandifloracin for the first time.     

Facile ring-opening of azabicyclic [3.1.0]- and [4.1.0]aminocyclopropanes to afford 3-piperidinone and 3-azepinone

Azabicyclic [3.1.0] and [4.1.0] Kulinkovich products underwent a facile reduction/fragmentation to afford a variety of 3-piperidinones and 3-azepinones, respectively, in the presence of catalytic palladium on carbon and formic acid in an atmosphere of hydrogen.     

DEKOIS: demanding evaluation kits for objective in silico screening--a versatile tool for benchmarking docking programs and scoring functions

For widely applied in silico screening techniques success depends on the rational selection of an appropriate method. We herein present a fast, versatile, and robust method to construct demanding evaluation kits for objective in silico screening (DEKOIS). This automated process enables creating tailor-made decoy sets for any given sets of bioactives. It facilitates a target-dependent validation of docking algorithms and scoring functions helping to save time and resources. We have developed metrics for assessing and improving decoy set quality and employ them to investigate how decoy embedding affects docking. We demonstrate that screening performance is target-dependent and can be impaired by latent actives in the decoy set (LADS) or enhanced by poor decoy embedding. The presented method allows extending and complementing the collection of publicly available high quality decoy sets toward new target space. All present and future DEKOIS data sets will be made accessible at www.dekois.com.     

Upper Bound on the Packing Density of Regular Tetrahedra and Octahedra

Aristotle contended that (regular) tetrahedra tile space, an opinion that remained widespread until it was observed that non-overlapping tetrahedra cannot subtend a solid angle of 4π around a point if this point lies on a tetrahedron edge. From this 15th century argument, we can deduce that tetrahedra do not tile space but, more than 500 years later, we are unaware of any known non-trivial upper bound to the packing density of tetrahedra. In this article, we calculate such a bound. To this end, we show the existence, in any packing of regular tetrahedra, of a set of disjoint spheres centered on tetrahedron edges, so that each sphere is not fully covered by the packing. The bound on the amount of space that is not covered in each sphere is obtained in a recursive way by building on the solid angle argument. The argument can be readily modified to apply to other polyhedra. The resulting lower bound on the fraction of empty space in a packing of regular tetrahedra is 2.6…×10⁻²⁵ and reaches 1.4…×10⁻¹² for regular octahedra.     

Evolution equations in Riemannian geometry

A fundamental question in Riemannian geometry is to find canonical metrics on a given smooth manifold. In the 1980s, R.S. Hamilton proposed an approach to this question based on parabolic partial differential equations. The goal is to start from a given initial metric and deform it to a canonical metric by means of an evolution equation. There are various natural evolution equations for Riemannian metrics, including the Ricci flow and the conformal Yamabe flow. In this survey, we discuss the global behavior of the solutions to these equations. In particular, we describe how these techniques can be used to prove the Differentiable Sphere Theorem.     

Determination of open boundary conditions for computational fluid dynamics (CFD) from interior observations

An optimization approach for the determination of open boundary conditions for Computational Fluid Dynamics is introduced, whereas the error between the solution σ and interior observations ω is minimized. The numerical weather prediction (NWP) model ALADIN–Austria provides data of wind speed and wind direction at virtual weather stations within the area of interest. Also, data from real weather stations and other sources can be incorporated into the model, respectively. In this work, the optimization method is applied to the constant density Navier–Stokes Equations. Thereby, for stabilizing the ill-posed pseudo inverse problem several regularization methods are reviewed. Further, numerical studies are carried out to identify the supreme regularization method for the presented application. Finally, the algorithm is applied to the micro- and meso-scale flow over the Grimming mountain, Austria. The results are compared with real weather station data and show suitable correlation with the measurements.     

Single atom hot-spots at Au-Pd nanoalloys for electrocatalytic H2O2 production

A novel strategy to direct the oxygen reduction reaction to preferentially produce H(2)O(2) is formulated and evaluated. The approach combines the inertness of Au nanoparticles toward oxidation, with the improved O(2) sticking probability of isolated transition metal "guest" atoms embedded in the Au "host". DFT modeling was employed to screen for the best alloy candidates. Modeling indicates that isolated alloying atoms of Pd, Pt, or Rh placed within the Au surface should enhance the H(2)O(2) production relative to pure Au. Consequently, Au(1-x)Pd(x) nanoalloys with variable Pd content supported on Vulcan XC-72 were prepared to investigate the predicted selectivity toward H(2)O(2) production for Au alloyed with Pd. It is demonstrated that increasing the Pd concentration to 8% leads to an increase of the electrocatalytic H(2)O(2) production selectivity up to nearly 95%, when the nanoparticles are placed in an environment compatible with that of a proton exchange membrane. Further increase of Pd content leads to a drop in H(2)O(2) selectivity, to below 10% for x = 0.5. It is proposed that the enhancement in H(2)O(2) selectivity is caused by the presence of individual surface Pd atoms surrounded by gold, whereas surface ensembles of contiguous Pd atoms support H(2)O formation. The results are discussed in the context of exergonic electrocatalytic H(2)O(2) synthesis in Polymer Electrolyte Fuel Cells for the simultaneous cogeneration of chemicals and electricity, the latter a credit to production costs.     

Dissection of complex molecular recognition interfaces

The synthesis of a family of zinc porphyrins and pyridine ligands equipped with peripheral H-bonding functionality has provided access to a wide range of closely related supramolecular complexes featuring between zero and four intramolecular H-bonds. An automated UV/vis titration system was used to characterize 120 different complexes, and these data were used to construct a large of number of different chemical double mutant cycles to quantify the intramolecular H-bonding interactions. The results probe the quantitative structure-activity relationship that governs cooperativity in the assembly of complex molecular recognition interfaces. Specifically, variations in the chemical structures of the complexes have allowed us to change the supramolecular architecture, conformational flexibility, geometric complementarity, the number and nature of the H-bond interactions, and the overall stability of the complex. The free energy contributions from individual H-bonds are additive, and there is remarkably little variation with architecture in the effective molarity for the formation of intramolecular interactions. Intramolecular H-bonds are not observed in complexes where they are geometrically impossible, but there are no cases where excellent geometric complementarity leads to very high affinities. Similarly, changes in conformational flexibility seem to have limited impact on the values of effective molarity (EM). The major variation that was found for all of the 48 intramolecular interactions that were examined using double mutant cycles is that the values of EM for intramolecular carboxylate ester-phenol H-bonds (200 mM) are an order of magnitude larger than those found for phosphonate diester-phenol H-bonds (30 mM). The corresponding intermolecular phosphonate diester-phenol H-bonds are 2 orders of magnitude more stable than carboxylate ester-phenol H-bonds, and the large differences in EM may be due to some kind of compensation effect, where the stronger H-bond is harder to make, because it imposes tighter constraints on the geometry of the complex.