A preliminary 3D model for cytochrome P450 2D6 constructed by homology model building

Summary A homology model building study of cytochrome P450 2D6 has been carried out based on the crystal structure of cytochrome P450 101. The primary sequences of P450 101 and P450 2D6 were aligned by making use of an automated alignment procedure. This alignment was adjusted manually by matching -helices (C, D, G, I, J, K and L) and -sheets (3/4) of P450 101 that are proposed to be conserved in membrane-bound P450s (Ouzounis and Melvin [Eur. J. Biochem., 198 (1991) 307]) to the corresponding regions in the primary amino acid sequence of P450 2D6. Furthermore, -helices B, B and F were found to be conserved in P450 2D6. No significant homology between the remaining regions of P450 101 and P450 2D6 could be found and these regions were therefore deleted. A 3D model of P450 2D6 was constructed by copying the coordinates of the residues from the crystal structure of P450 101 to the corresponding residues in P450 2D6. The regions without a significant homology with P450 101 were not incorporated into the model. After energy-minimization of the resulting 3D model of P450 2D6, possible active site residues were identified by fitting the substrates debrisoquine and dextrometorphan into the proposed active site. Both substrates could be positioned into a planar pocket near the heme region formed by residues Val³⁷⁰, Pro³⁷¹, Leu³⁷², Trp³¹⁶, and part of the oxygen binding site of P450 2D6. Furthermore, the carboxylate group of either Asp¹⁰⁰ or Asp³⁰¹ was identified as a possible candidate for the proposed interaction with basic nitrogen atom(s) of the substrates. These findings are in accordance with a recently published predictive model for substrates of P450 2D6 [Koymans et al., Chem. Res. Toxicol., 5 (1992) 211].     

Quantitative aspects of analyzing small molecules – monitoring singly or doubly charged ions? A case study of ximelagatran

Precision, reproducibility and lower limit of quantitation (LLOQ) are important characteristics of a quantitative method. We have investigated these properties for Ximelagatran (Xi), which has a high tendency to form doubly charged ions in electrospray ionization (ESI), by studying the percentage of doubly charged species formed when varying the formic acid (FA) concentration, analyte concentration, amount of organic modifier and flow rate. It was found that the percentage of [Xi + 2H]²⁺ can be controlled to be more than 90% or less than 10% by varying the amount of FA present, and that the change between these values is dramatic. Furthermore, the percentage of [Xi + 2H]²⁺ formed decreases with increased analyte concentration and increased flow rate. No apparent relationship with the amount of organic modifier was found. The results have the implication that, by carefully controlling the selected parameters, the LLOQ, precision and reproducibility can be improved. We have compared the fragmentation of the singly and doubly charged species and concluded that the [Xi + 2H]²⁺ ion is more inclined to undergo fragmentation than [Xi + H]⁺. As a consequence, unusual instrumental settings had to be used for the experiments. The fragmentation patterns are to a great extent similar, but the doubly charged species is more inclined to generate low‐mass product ions. Copyright © 2010 John Wiley & Sons, Ltd.     

Analogous circuits for plastic foams

Presented here are simple analogous circuits derived from Biot theory which allow predictions of the acoustical properties of low flow resistance and very high flow resistance foams.For different foams with low resistance absorption coefficients measured in a Kundt tube have been compared with the predicted ones.For foams with very high flow resistance only the frequency of the first normal incidence absorption peak for a large panel backed with a rigid layer has been measured. Kundt tube measurements being inaccurate because of sample frame vibrations which appear with this kind of foam, the experiment was done in an anechoic room by studying the stationary waves close to the foam.For the two kinds of foams studied, comparison between experimental results and predictions show that simple analogous circuits may supply useful estimations of the trend of absorption.     

Spatial extent of random laser modes

We have experimentally studied the distribution of the spatial extent of modes and the crossover from essentially single-mode to distinctly multimode behavior inside a porous gallium phosphide random laser. This system serves as a paragon for random lasers due to its exemplary high index contrast. In the multimode regime, we observed mode competition. We have measured the distribution of spectral mode spacings in our emission spectra and found level repulsion that is well described by the Gaussian orthogonal ensemble of random-matrix theory.     

Modeling the geometric, electronic, and redox properties of iron(III)-containing amphiphiles with asymmetric [NN'O] headgroups

Two iron(III)-containing amphiphiles 1 and 2 have been synthesized with the [NN'O] ligands HL(tBu-ODA) (2-((octadecyl(pyridin-2-ylmethyl)amino)methyl)-4,6-di-tert-butylphenol) and HL(I-ODA) (2-((octadecyl(pyridin-2-ylmethyl)amino)methyl)-4,6-diiodophenol), respectively. Compound 1 is monometallic, whereas EXAFS data suggest that 2 is a mixture of mono- and bimetallic species. The archetypical [Fe(III)(L(NN'O))(2)](+) complexes 3-9 have been isolated and characterized in order to understand the geometric, electronic, and redox properties of the amphiphiles. Preference for a monometallic or bimetallic nuclearity is dependent on (i) the nature of the solvent used for synthesis and (ii) the type of the substituent in the phenol moiety. In methanol, the tert-butyl-, methoxy-, and chloro-substituted 3, 4, and 5 are monometallic species, whereas the bromo- and iodo-substituted 6 and 7 form bimetallic complexes taking advantage of stabilizing methoxo bridges generated by solvent deprotonation. In dichloromethane, the bromo- and iodo-substituted 8 and 9 are monometallic species; however, these species favor meridional coordination in opposition to the facial coordination observed for the tert-butyl- and methoxy-substituted compounds. Molecular structures for species 5, 7, 8, and 9 have been solved by X-ray diffraction. Furthermore, the electronic spectrum of the amphiphile 1 was expected to be similar to those of facial/cis archetypes with similar substituents, but close resemblance was observed with the profile for those meridional/cis species, suggesting a similar coordination mode. This trend is discussed based on DFT calculations, where preference for the meridional/cis coordination mode appears related to the presence of tertiary amine nitrogen on the ligand, as when a long alkyl chain is attached to the [NN'O] headgroup.     

R?se's Methode der Milchfettbestimmung

Ohne Zusammenfassung     

Comparison of defect recovery in proton irradiated,deformed and ion implanted nickel as observed by PAC of111In

Plastically deformed and p⁺ irradiated Ni have been studied using perturbed gamma ray angular correlations of¹¹¹In. Isochronal annealing results in the temperature range 200 ≤T ≤ 700 K, and a comparison to earlier ion-implantation studies, lead to partial picture of defect migration and recovery in Ni.     

Formation of ultrasharp vertically aligned Cu-Si nanocones by a DC plasma process

We report an effective method for the production of ultrasharp vertically oriented silicon nanocones with tip radii as small as 5 nm. These silicon nanostructures were shaped by a high-temperature acetylene and ammonia dc plasma reactive ion etch (RIE) process. Thin-film copper deposited onto Si substrates forms a copper silicide (Cu3Si) during plasma processing, which subsequently acts as a seed material masking the single-crystal cones while the exposed silicon areas are reactive ion etched. In this process, the cone angle is sharpened continually as the structure becomes taller. Furthermore, by lithographically defining the seed material as well as employing an etch barrier material such as titanium, the cone location and substrate topography can be controlled effectively.     

Guest-host colloid crystals: experimental study and simulations

Disorder in colloid crystals was induced by doping them with a different number of large or small guest particles, which had a different deviation in size from the host colloids. The change in optical properties of the guest-host colloid crystals was assessed by using optical transmission spectroscopy while the variation in crystal structure was examined using scanning electron microscopy (SEM). The disruption in the crystalline lattices depended on the relative deviation in sizes of the guest and host particles and the concentration of the guest colloids. In parallel with experiments, the packing of spheres in guest-host crystals was modeled with a simulated annealing algorithm. A good correlation was found between the changes in crystal structure observed by SEM imaging and the simulated sphere packing. The experimental and simulated changes in the transmission spectra of guest-host colloid crystals were in good agreement.