Group 6 heteroatom- and non-heteroatom-stabilized carbene complexes. beta,beta'- and alpha,beta,beta'-annulation reactions of cyclic enamines

Cyclization reactions of group 6 Fischer carbene complexes with cyclopentanone and cyclohexanone enamines are described. Enamine 3a undergoes thermal alpha,beta,beta'-annulation with alkenylcarbene complexes 1 and 2 (THF, 60 degrees C), affording semibullvalenes 5. The metalate intermediates 6, resulting from beta,beta'-annulation of the enamines 3a and 4a, were quantitatively formed by running the reaction in hexane at room temperature. Acid-promoted demetalation of 6 afforded endo-2-bicyclo[3.2.1]octen-8-ones 7 and endo/exo-2-bicyclo[3.3.1]nonen-9-ones 8 (endo/exo = 5:1). Using (S)-methoxymethylpyrrolidine-derived enamines 3b and 4b,c allowed highly enantioenriched cycloadducts endo-(+)-7 as well as endo-(-)-8 and exo-(-)-8 to be accessed. The non-heteroatom-stabilized carbene complex 10 was formed from complex 6 by Me(3)SiOTf-promoted elimination of the methoxy group, characterized by (13)C NMR, and transformed into the organic compounds 7, 7-d, and 11 as well as into bicyclo[3.2.1]octan-2,8-diones 14 and cycloheptanones 15. On the basis of this sequence, enantioenriched cycloheptanones (+)-15 were efficiently prepared in one pot from carbene complexes 2 and enamine 3b (51-55% yield, 91-96% ee). Extension of this work to simple Fischer carbene complexes 16 allowed an appropriate way to generate the nonstabilized pentacarbonyl[(phenyl(alkyl)carbene]tungsten complex 17 to be designed, for which the thermal and chemical behavior leading to compounds 18-21 is described.     

Composition of the black crusts from the Saint Denis Basilica, France, as revealed by gas chromatography-mass spectrometry

The organic fraction of black crusts from Saint Denis Basilica, France, is composed of a complex mixture of aliphatic and aromatic compounds. These compounds were studied by two different analytical approaches: tetramethyl ammonium hydroxide (TMAH) thermochemolysis in combination with gas chromatography-mass spectrometry (GC-MS), and solvent extraction, fractionation by silica column, and identification of the fraction components by GC-MS. The first approach, feasible at the microscale level, is able to supply fairly general information on a wide range of compounds. Using the second approach, we were able to separate the complex mixture of compounds into four fractions, enabling a better identification of the extractable compounds. These compounds belong to different classes: aliphatic hydrocarbons (nalkanes, n-alkenes), aliphatic and aromatic carboxylic acids (n-fatty acids, alpha,omega-dicarboxylic acids, and benzenecarboxylic acids), polycyclic aromatic hydrocarbons (PAH), and molecular biomarkers (isoprenoid hydrocarbons, diterpenoids, and triterpenoids). With each approach, similar classes of compounds were identified, although TMAH thermochemolysis failed to identify compounds present at low concentrations in black crusts. The two proposed methodological approaches are complementary, particularly in the study of polar fractions.     

Hydration free energies and entropies for water in protein interiors

Free energy calculations for the transfer of a water molecule from the pure liquid to an interior cavity site in a protein are presented. Two different protein cavities, in bovine pancreatic trypsin inhibitor (BPTI) and in the I76A mutant of barnase, represent very different environments for the water molecule: one which is polar, forming four water-protein hydrogen bonds, and one which is more hydrophobic, forming only one water-protein hydrogen bond. The calculations give very different free energies for the different cavities, with only the polar BPTI cavity predicted to be hydrated. The corresponding entropies for the transfer to the interior cavities are calculated as well and show that the transfer to the polar cavity is significantly entropically unfavorable while the transfer to the nonpolar cavity is entropically favorable. For both proteins an analysis of the fluctuations in the positions of the protein atoms shows that the addition of a water molecule makes the protein more flexible. This increased flexibility appears to be due to an increased length and weakened strength of protein-protein hydrogen bonds near the cavity.     

Design, synthesis, and evaluation of a mechanism-based inhibitor for gelatinase A

[structure: see text] Matrix metalloproteinases (MMPs), of which 26 are known, have been implicated in a number of pathological conditions, including tumor metastasis. We have previously described the first mechanism-based inhibitor for MMPs (J. Am. Chem. Soc. 2000, 122, 6799-6800), which in chemistry mediated by the active site zinc ion selectively and covalently inhibits MMP-2, -3, and -9. Computational analyses indicated that this selectivity in inhibition of MMPs could be improved by design of new variants of the inhibitor class. We report herein the syntheses of methyl 2-(4-{4-[(2-thiiranylpropyl)sulfonyl]phenoxy}phenyl)acetate (3) and 2-(4-{4-[(2-thiiranylpropyl)sulfonyl]phenoxy}phenyl)acetic acid (4), and show that compound 3 serves as a mechanism-based inhibitor exclusively for MMP-2. This molecule should prove useful in delineating the functions of MMP-2 in biological systems.     

How a single photon can mediate entanglement between two others

We describe a novel quantum information protocol, which probabilistically entangles two distant photons that have never interacted. Different from the entanglement swapping protocol, which requires two pairs of maximally entangled photons as the input states, as well as a Bell-state measurement (BSM), the present scheme only requires three photons: two to be entangled and another to mediate the correlation, and no BSM, in a process that we call “entanglement mediation”. Furthermore, in analyzing the paths of the photons in our arrangement, we conclude that one of them, the mediator, exchanges information with the two others simultaneously, which seems to be a new quantum-mechanical feature.     

A space–time hybridizable discontinuous Galerkin method for incompressible flows on deforming domains

We present the first space–time hybridizable discontinuous Galerkin (HDG) finite element method for the incompressible Navier–Stokes and Oseen equations. Major advantages of a space–time formulation are its excellent capabilities of dealing with moving and deforming domains and grids and its ability to achieve higher-order accurate approximations in both time and space by simply increasing the order of polynomial approximation in the space–time elements. Our formulation is related to the HDG formulation for incompressible flows introduced recently in, e.g., [N.C. Nguyen, J. Peraire, B. Cockburn, A hybridizable discontinuous Galerkin method for Stokes flow, Comput. Methods Appl. Mech. Eng. 199 (2010) 582–597]. However, ours is inspired in typical DG formulations for compressible flows which allow for a more straightforward implementation. Another difference is the use of polynomials of fixed total degree with space–time hexahedral and quadrilateral elements, instead of simplicial elements. We present numerical experiments in order to assess the quality of the performance of the methods on deforming domains and to experimentally investigate the behavior of the convergence rates of each component of the solution with respect to the polynomial degree of the approximations in both space and time.     

The structural development of linear canonical transforms

Physics of Atomic Nuclei - We consider that the simultaneous development of the theory of linear canonical integral transforms among two quite distinct scientific communities, provides an...     

A Bis(p-tert-butyloctahomotetraoxacalix[8]arene) Capsule with [(UO2)2(OH)2] Links and a Disordered [Rb4(H2O)4] Inner Core

p-tert-Butyloctahomotetraoxacalix[8]arene (LH⁸) reacts with uranyl nitrate hexahydrate in the presence of rubidium hydroxide to give a mixed complex that can be viewed as a tetrauranate dimer [(UO²)⁴(LH⁴)²(OH)⁴] containing four disordered rubidium ions and water molecules. Two uranyl ions are complexed in an “external” fashion by each macrocycle, each of them bound to two phenoxide groups and one ether group, as well as to two bridging hydroxide ions. The latter ensure the formation of a dimeric capsule that contains the disordered set of alkali metal ions. Apart from water molecules, the Rb⁺ ions are bound to the uranyl oxo groups directed towards the inner cavity, and to phenol and ether oxygen atoms from the macrocycle. The resulting octanuclear complex presents an unprecedented geometry evidencing the assembling potential of uranyl ions.

p-tert-Butyloctahomotetraoxacalix[8]arene (LH₈) reacts with uranyl nitrate hexahydrate in the presence of rubidium hydroxide to give a mixed complex that can be viewed as a tetrauranate dimer [(UO₂)₄(LH₄)₂(OH)₄] containing four disordered rubidium ions and water molecules. Two uranyl ions are complexed in an “external” fashion by each macrocycle, each of them bound to two phenoxide groups and one ether group, as well as to two bridging hydroxide ions. The latter ensure the formation of a dimeric capsule that contains the disordered set of alkali metal ions. Apart from water molecules, the Rb^+| ions are bound to the uranyl oxo groups directed towards the inner cavity, and to phenol and ether oxygen atoms from the macrocycle. The resulting octanuclear complex presents an unprecedented geometry evidencing the assembling potential of uranyl ions.