Interspecies in vitro metabolism of the phosphodiesterase-4 (PDE4) inhibitor L-454,560

L-454,560 is a potent phosphodiesterase 4 (PDE4) inhibitor which was identified as a development candidate for the treatment of asthma and chronic obstructive pulmonary disease (COPD). As part of the discovery of this compound, interspecies in vitro metabolism data was generated using liver microsomes and hepatocytes in order to understand the metabolic fate of the compound. In microsomes, metabolism of the 3-methyl-1,2,4-oxadiazole ring was the predominant pathway observed, including ring cleavage. In rat hepatocytes, hydroxylation of the methyl group on the oxadiazole ring and double-bond isomerization were the most abundant metabolites observed. No major species differences were found in terms of microsomal metabolite profiles. The use of LC with UV and MS detection is highlighted, as well as information from tandem mass spectrometry and NMR.     

The stability of fcc (1 1 1) metal surfaces

The results of a theoretical study on the stability of fcc (1 1 1) metal surfaces to certain commensurate-incommensurate reconstructive phase transformations is presented. Specifically, we have performed computer simulation studies of the 22×√3 surface reconstruction of Au(1 1 1). This reconstruction involves a uniaxial contraction of the top monolayer corresponding to a surface strain of about 4.3% and has been observed to be the stable structure for the clean surface at low temperatures. The driving force for the reconstruction has been associated with the quantity (f−γ), where f is the surface stress and γ is the surface free energy, while the opposing force is due to the disregistry with the underlying lattice. A continuum model yields a stability criterion that depends on the knowledge of a small number of physical quantities: f, γ, the equilibrium nearest-neighbor spacing r₁ and the shear modulus G. We have performed molecular dynamics simulations as a general stability analysis of these types of reconstructions. The results are in excellent agreement with the continuum model. The simulations using embedded-atom method potentials also accurately reproduce many observed features of the reconstruction on Au(1 1 1).     

Ueber den Gerbstoff des Holzes der Edelkastanie (Castanea vesca)

Ohne Zusammenfassung     

Molecular derivation of the hydrodynamic equations for a binary fluid

In this paper, the hydrodynamic equations and the associated transport coefficients are derived for a simple binary fluid from molecular considerations. This is a generalization of the methods of Felderhof and Oppenheim and of Selwyn to multicomponent systems. A linear response formalism is used to describe the relaxation of the binary system from an initial nonequilibrium state. Explicit molecular expressions are given for the transport coefficients in terms of time correlation functions of generalized current densities. These densities have the useful property of not containing a conserved part. The correlation functions are then related to a set of phenomenological coefficients in the theory of nonequilibrium thermodynamics. This explicit identification enables one to relate the correlation functions to experimentally measured transport coefficients.Supported by the National Science Foundation.     

Electrocapillarity behavior of Au111 in SO4(2-) and F-

We present the first set of results measuring the change in interfacial free energy and surface stress for Au(111) electrodes in an electrolyte containing a nonspecifically adsorbing anion and compare this behavior to that in an electrolyte containing an anion known to undergo specific adsorption. Generally, we find that the surface stress is more sensitive to changes in electrode potential and adsorption then the interfacial free energy. The results obtained in fluoride electrolytes are compared to the predictions of a thermodynamic analysis.     

Perovskite-like La1−xKxMnO3 and related compounds: Solid state chemistry and the catalysis of the reduction of NO by CO and H2

The new compounds La_1?xM_xMnO₃ (0.05 ? x ? 0.4 for M = K; x = 0.2 for M = Na, Rb) have been prepared. La_1?xK_xMnO₃ (0.05 ? x ? 0.4), LaMnO_3.01, LaMnO_3.15, La_0.8Na_0.2MnO₃, and La_0.8Rb_0.2MnO₃ have been used as catalysts in the reduction of NO. La_0.8K_0.2MnO₃ has also been used in the catalytic decomposition of NO. The activity of these catalysts is related to the presence of a Mn³⁺/Mn⁴⁺ mixed valence and to the relative ease of forming oxygen vacancies in the solid. The presence of cation vacancies in LaMnO_3.15 and the substitution of La³⁺ by alkali ions in LaMnO₃ increases the catalytic activity. The reduction of NO involves both molecular and dissociative adsorption of NO.