Chemical mapping of ceramide distribution in sphingomyelin-rich domains in monolayers

The incorporation of ceramide in phase-separated monolayers of ternary lipid mixtures has been studied by a combination of atomic force microscopy (AFM), fluorescence, and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Replacement of a fraction of the sphingomyelin by ceramide in DOPC/SM/cholesterol monolayers leads to changes in the SM-cholesterol-rich liquid-ordered domains. AFM shows the formation of heterogeneous domains with small raised islands that are assigned to a ceramide-rich gel phase. ToF-SIMS provides conclusive evidence for the localization of SM and ceramide in ordered domains and shows that ceramide is heterogeneously distributed in small islands throughout the domains. The results indicate the utility of combining AFM and ToF-SIMS for understanding compositions of phase-separated membranes.     

Concise routes to pyrazolo[1,5-a]pyridin-3-yl pyridazin-3-ones

Cycloaddition of pyridine N-imine with 6-alkyl-4-oxohex-5-ynoates followed by condensation with hydrazine provides concise access to pharmacologically active 6-(pyrazolo[1,5-a]pyridin-3-yl)pyridazinones. For the first time alkynyl heterocycles are also shown to be effective dipolarophiles for pyridine N-imine, and analogous compounds can be accessed directly in modest yields through the reaction of 6-(alkyn-1-yl)pyridazin-3-one derivatives.     

A formal enantioselective acetate Mannich reaction: the nitro functional group as a traceless agent for activation and enantiocontrol in the synthesis of beta-amino acids

A two-step procedure involving the enantioselective addition of alpha-nitro esters to imines, followed by reductive denitration, provides a convenient new enantioselective synthesis of beta-amino acids. Specifically, beta-phenyl alanine derivatives with up to 98% ee are formed in good yield (64-88%) over two steps. The utility of the approach is demonstrated through the first enantioselective synthesis of the key beta-amino acid of (+)-chaenorhine.     

Covalent inhibitors of human monoacylglycerol lipase: ligand-assisted characterization of the catalytic site by mass spectrometry and mutational analysis

The active site of recombinant hexa-histidine-tagged human monoacylglycerol lipase (hMGL) is characterized by mass spectrometry using the inhibitors 5-((biphenyl-4-yl)methyl)-N,N-dimethyl-2H-tetrazole-2-carboxamide (AM6701), and N-arachidonylmaleimide (NAM) as probes. Carbamylation of Ser(129) by AM6701 in the putative hMGL catalytic triad demonstrates this residue's essential role in catalysis. Partial NAM alkylation of hMGL cysteine residues 215 and/or 249 was sufficient to achieve approximately 80% enzyme inhibition. Although Cys(215) and/or Cys(249) mutations to alanine(s) did not affect hMGL hydrolytic activity as compared with nonmutated hMGL, the C215A displayed heightened NAM sensitivity, whereas the C249A evidenced reduced NAM sensitivity. These data conclusively demonstrate a sulfhydryl-based mechanism for NAM inhibition of hMGL in which Cys(249) is of paramount importance. Identification of amino acids critical to the catalytic activity and pharmacological modulation of hMGL informs the design of selective MGL inhibitors as potential drugs.     

Characterizing the frequency of orders received by a stockist

John E. Boylan Applied Social Sciences and Humanities, Buckinghamshire Chilterns University College, Buckinghamshire HP11 2JZ, UK F. R. Johnston Kerridge Computer Company, Charnham Park, Hungerford RG17 0YU, UK Email: estelle.shale{at}warwick.ac.uk Received on 26 January 2007. Accepted on 19 November 2007. It is regularly asserted that the frequency of orders receivedby a stockist can be represented as a Poisson process, but verylittle corroborative evidence has been published. This paperpresents some results supporting the assumption. An adaptationto the standard testing methodology is presented which overcomesthe complications arising from the necessity of sampling fromtime series data. The new approach is applied to a large rangeof stock-keeping units. Except for the extreme tail of the distribution,which is of little interest for most inventory applications,it is found that the frequency of orders is well representedby a Poisson process.     

Defect‐band photoluminescence imaging on multi‐crystalline silicon wafers

Defect‐band emission photoluminescence (PL) imaging with an indium‐gallium‐arsenide (InGaAs) camera was applied to multi‐crystalline silicon (mc‐Si) wafers, which were taken from different heights of different Si bricks. Neighboring wafers were picked at six different processing steps, from as‐cut to post‐metallization. By using different cut‐off filters, we were able to separate the band‐to‐band emission images from the defect‐band emission images. On the defect‐band emission images, the bright regions that originate from extend‐ ed defects were extracted from the PL images. The area fraction percentage of these regions at various processing stages shows a correlation with the final cell electrical parameters. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Theoretical studies of Pt-Ti nanoparticles for potential use as PEMFC electrocatalysts

A theoretical investigation is presented of alloying platinum with titanium to form binary Pt-Ti nanoalloys as an alternative to the expensive pure platinum catalysts commonly used for Proton Exchange Membrane Fuel Cell cathode electrocatalysts. Density Functional Theory calculations are performed to investigate compositional effects on structural properties as well as Oxygen Reduction Reaction kinetics and poisoning effects. High symmetry A(32)-B(6) clusters are studied to investigate structural properties. From these structures binding energies of hydroxyl and carbon monoxide are studied on a range of sites on the surface of the clusters. Promising results are obtained suggesting that the bimetallic Pt-Ti nanoalloys may exhibit enhanced properties compared to pure platinum catalysts.     

Diastereoselective synthesis of aliphatic α,α-difluoro-β3-amino esters via a sonocatalyzed Reformatsky reaction

(R)-2-Phenylglycine ethyl ester was found to be a cheap and effective auxiliary for the preparation of aliphatic α,α-difluoro-β(3)-amino esters via a Reformatsky reaction performed under sonication conditions. The products were obtained in good to high yield and ≥96:4 dr, thus providing a new stereoselective route to this under-represented class of compounds. A facile one-pot removal of the phenylglycine moiety and concomitant Boc protection subsequently afforded the corresponding Boc-protected β(3)-amino esters in excellent yield.     

Probing the dynamic nature of DNA multilayer films using förster resonance energy transfer

DNA films are of interest for use in a number of areas, including sensing, diagnostics, and as drug/gene delivery carriers. The specific base pairing of DNA materials can be used to manipulate their architecture and degradability. The programmable nature of these materials leads to complex and unexpected structures that can be formed from solution assembly. Herein, we investigate the structure of DNA multilayer films using F?rster resonance energy transfer (FRET). The DNA films are assembled on silica particles by depositing alternating layers of homopolymeric diblocks (polyA(15)G(15) and polyT(15)C(15)) with fluorophore (polyA(15)G(15)-TAMRA) and quencher (polyT(15)C(15)-BHQ2) layers incorporated at predesigned locations throughout the films. Our results show that DNA films are dynamic structures that undergo rearrangement. This occurs when the multilayer films are perturbed during new layer formation through hybridization but can also take place spontaneously when left over time. These films are anticipated to be useful in drug delivery applications and sensing applications.     

Bismuth-doped tin clusters: experimental and theoretical studies of neutral Zintl analogues

The electron count of gas-phase clusters is increased gradually by element substitution in order to mimic the total number of electrons of known stable closo-clusters. A combination of elements from the fourth and fifth group of the periodic table such as Sn and Bi is well-suited for this approach. Hence, these small Sn-Bi clusters are investigated by employing the electric field deflection method. For clusters in the series Sn(M-N)Bi(N) (M = 5-13, N = 1-2), the beam profiles obtained in cryogenic experiments are dominated by beam broadening, indicating the presence of a permanent electric dipole moment that is sensitive to the (rigid) cluster structure. An intensive search for the global minimum structure employing a density functional theory/genetic algorithm method is performed. Dielectric properties for the identified low-energy isomers are computed. The structural and dielectric properties are used in beam profile simulations in order to discuss the experimental data. Comparison of theoretical and experimental results enables identification of the growing pattern of these small bimetallic clusters. For multiply doped clusters, it is concluded that the dopant atoms do not form direct Bi-Bi bonds, but more interestingly, a rearrangement of the cluster skeleton becomes apparent. The structural motifs are different from pure tin clusters but rather are rationalized using the corresponding structures of tin anions or are based on the Wade-Mingos concept. Further evidence for this idea is deduced from nuclear independent chemical shift calculations, which show nearly identical behavior for negatively charged pure and neutral bimetallic clusters. All of these findings are consistent with the idea of neutral Zintl analogues in the gas phase.