Mechanism of the decrease in catalytic activity of human cytochrome P450 2C9 polymorphic variants investigated by computational analysis

Cytochrome P450 (CYP) is deeply involved in the metabolism of chemicals including pharmaceuticals. Therefore, polymorphisms of this enzyme have been widely studied to avoid unfavorable side effects of drugs in chemotherapy. In this work, we performed computational analysis of the mechanism of the decrease in enzymatic activity for three typical polymorphisms in CYP 2C9 species: *2, *3, and *5. Based on the equilibrated structure obtained by molecular dynamics simulation, the volume of the binding pocket and the fluctuation of amino residues responsible for substrate holding were compared between the wild type and the three variants. Further docking simulation was carried out to evaluate the appropriateness of the binding pocket to accommodate substrate chemicals. Every polymorphic variant was suggested to be inferior to the wild type in enzymatic ability from the structural viewpoint. F‐G helices were obviously displaced outward in CYP2C9*2. Expansion of the binding pocket, especially the space near F′ helix, was remarkable in CYP2C9*3. Disappearance of the hydrogen bond between K helix and β4 loop was observed in CYP2C9*5. The reduction of catalytic activity of those variants can be explained from the deformation of the binding pocket and the consequent change in binding mode of substrate chemicals. The computational approach is effective for predicting the enzymatic activity of polymorphic variants of CYP. This prediction will be helpful for advanced drug design because calculations forecast unexpected change in drug efficacy for individuals. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010     

Diagonal composite order in a two-channel Kondo lattice

A novel type of symmetry breaking is reported for the two-channel Kondo lattice where conduction electrons have spin and orbital (channel) degrees of freedom. Using the continuous-time quantum Monte?Carlo and the dynamical mean-field theory, a spontaneous breaking of the orbital symmetry is observed. The tiny breakdown of orbital occupation number, however, vanishes if the conduction electrons have the particle-hole symmetry. The proper order parameter instead is identified as a composite quantity representing the orbital-selective Kondo effect. The single-particle spectrum of the selected orbital shows insulating property, while the other orbital behaves as a Fermi liquid. This composite order is the first example of odd-frequency order other than off-diagonal order (superconductivity), and is a candidate of hidden order in f-electron systems.     

Incommensurate magnetism in FeAs strips: neutron scattering from CaFe(4)As(3)

Magnetism in the orthorhombic metal CaFe(4)As(3) was examined through neutron diffraction for powder and single crystalline samples. Incommensurate [q(m) ≈ (0.37-0.39) × b*] and predominantly longitudinally (|| b) modulated order develops through a 2nd order phase transition at TN = 89.63(6) K with a 3D Heisenberg-like critical exponent β = 0.365(6). A 1st order transition at T2 = 25.6(9) K is associated with the development of a transverse component, locking q(m) to 0.375(2)b*, and increasing the moments from 2.1(1) to 2.2(3) μ B for Fe2+ and from 1.3(3) to 2.4(4) μB for Fe+. The ab initio Fermi surface is consistent with a nesting instability in cross-linked FeAs strips.     

Near-surface structural study of transition metal oxides to understand their electronic properties

The atomic arrangement in a solid contains a great amount of information, and observation of its structure is essential for understanding the electronic and magnetic properties of transition metal oxides at a microscopic level. Increasing interest in the surfaces and interfaces of oxide systems, which is partly driven by the anticipation of device applications, enhances the importance of structural studies of the near-surface region. We review various types of structural studies with x-ray scattering on the near-surface region of metal oxides-from thick films to surfaces-in order to clarify the structural effects on their electronic properties.     

Light focusing by slot Fabry-Perot photonic crystal nanoresonator on scanning tip

We numerically investigate the propagation of light through the photonic crystal (PhC) waveguide on low refraction index material for near-field light focusing at the visible wavelength (635 nm) by incorporating a center air slot and Fabry-Perot resonator on the scanning tip. Perturbations by water and substrate refraction index changes of the PhC are analyzed by the finite-difference time-domain method to show minimal impact on light confinement and throughput. Such a total dielectric probe tip design has great potential to complement the current widely used metal-coated optical-fiber-based light confinement probe.     

Effect of cation doping on ionic and electronic properties for lanthanum silicate-based solid electrolytes

Electronic as well as ionic conducting properties for oxyapatite-type solid electrolytes based on lanthanum silicate, La_9.333 + xSi₆O_26 + 1.5x (LSO) were investigated in the oxygen-excess region (x > ca. 0.3). We have found that the oxygen excess-type LSO (OE-LSO), namely La₁₀Si₆O₂₇ on weighted basis, exhibited high conductivity, and substitution of the Si-site of LSO with some dopants (Mⁿ⁺) had a positive effect toward the conducting property. Furthermore, it was also found that addition of a very small amount of iron ions into the M-doped OE-LSO, La₁₀(Si_6-yMⁿ⁺_y)O_27-(2-0.5n)y, improved its conductivity. On the other hand, replacement of the La-site with various ions for La₁₀(Si_6-yMⁿ⁺_y)O_27-(2-0.5n)y did little to improve conductivity. The electronic transport numbers for Al-doped OE-LSO with Fe-addition, (1-α){La₁₀(Si_5.8Al_0.2)O_26.9}-α(FeO_γ), evaluated with the Hebb-Wagner polarization method were very low: i.e., 1.1 × 10^− 3 and 2.9 × 10^− 3 under P(O₂) = 1.1 × 10⁴ Pa at 1073 K for α = 0.00 and 0.005, respectively. Conductivity for each sample was unchanged under humidified atmosphere at 1073 K sustained for over 50 h, revealing that both compositions were chemically stable. It was concluded that 0.995{La₁₀(Si_5.8Al_0.2)O_26.9}-0.005(FeO_γ) is suitable for the fuel cell electrolytes because of its high and almost pure ionic conductivity, and its good chemical stability under humidified as well as reducing conditions.     

Compounds having thiourea moiety as derivatization reagents in liquid chromatography/electrospray ionization–tandem mass spectrometry (LC/ESI‐MS/MS): synthesis of derivatization reagents for carboxylic acids

The derivatization reagents for carboxylic acids, N‐(Pyridin‐3‐yl)hydrazinecarbothioamide, N‐[4‐(dimethylamino)phenyl]hydrazinecarbothioamide, 1‐(2‐aminoethyl)‐3‐(pyridin‐3‐yl)thiourea, 1‐(2‐aminoethyl)‐3‐[4‐(dimethylamino)phenyl]thiourea and 4‐(2‐aminoethyl)‐N‐phenylpiperazine‐1‐carbothioamide were synthesized. These reagents reacted with carboxylic acids at 60°C for 45 min in the presence of the condensation reagents. The generated derivatives were favorably separated on the reversed‐phase column and sensitively detected by electrospray ionization tandem mass spectrometry. These reagents enhanced the electrospray ionization response of the analyte and generated a particular product ion efficiently by collision‐induced dissociation, and thus they were suitable for MS/MS detection. Copyright © 2010 John Wiley & Sons, Ltd.     

Marked fatgraph complexes and surface automorphisms

Combinatorial aspects of the Torelli–Johnson–Morita theory of surface automorphisms are extended to certain subgroups of the mapping class groups. These subgroups are defined relative to a specified homomorphism from the fundamental group of the surface onto an arbitrary group K. For K abelian, there is a combinatorial theory akin to the classical case, for example, providing an explicit cocycle representing the first Johnson homomophism with target Λ ³ K. Furthermore, the Earle class with coefficients in K is represented by an explicit cocyle.     

A large hydrothermal reservoir beneath Taal Volcano (Philippines) revealed by magnetotelluric observations and its implications to the volcanic activity

Taal Volcano is one of the most active volcanoes in the Philippines. The magnetotelluric 3D forward analyses indicate the existence of a large high resistivity anomaly (∼100 Ω·m) with a volume of at least 3 km × 3 km × 3 km, which is capped by a conductive layer (∼10 Ω·m), beneath the Main Crater. This high resistivity anomaly is hypothesized to be a large hydrothermal reservoir, consisting of the aggregate of interconnected cracks in rigid and dense host rocks, which are filled with hydrothermal fluids coming from a magma batch below the reservoir. The hydrothermal fluids are considered partly in gas phase and liquid phase. The presence of such a large hydrothermal reservoir and the stagnant magma below may have influences on the volcano’s activity. Two possibilities are presented. First, the 30 January 1911 explosion event was a magmatic hydrothermal eruption rather than a base-surge associated with a phreato-magmatic eruption. Second, the earlier proposed four eruption series may be better interpreted by two cycles, each consisting of series of summit and flank eruptions.     

General Information to Obtain Spherical Particles with Ordered Mesoporous Structures

Conditions for the synthesis of aluminum organophosphonate (AOP) and aluminophosphate (AlPO) spheres containing periodic mesopores were optimized and demonstrated to be general morphological controls for the surfactant‐assisted synthesis of mesoporous materials. High‐quality AOP and AlPO spheres with uniform mesopores were obtained at low and high temperatures, respectively. The aerosol‐assisted synthesis of materials with uniform mesopores was categorized by using the difference in relative density of soluble AOP and AlPO oligomers that interact with ethylene oxide (EO) units in EO_nPO_mEO_n triblock copolymer (PO=propylene oxide). Then, ordered mesoporous structures are constructed with the adequate amount of species in resultant frameworks, and the number of interactive points in soluble species determines the resultant density of the frameworks after self‐assembly. Consequently, temperature‐dependent synthesis, which allows controlled infiltration of soluble species to match the density of resultant frameworks, is required for the formation of ordered mesoporous structures under morphological control.