A fully automated nanoelectrospray tandem mass spectrometric method for analysis of Caco-2 samples

Caco-2 cells offer a means to rapidly screen permeability of drug candidates, allowing pharmaceutical companies to eliminate candidates unable to cross the intestinal barrier early in the discovery process. This screening process is typically performed by conventional liquid chromatography/tandem mass spectrometry (LC/MS/MS), which can require time-consuming method development. An alternative to LC/MS/MS, automated nanoelectrospray tandem mass spectrometry (nanoESI-MS/MS), is introduced. This novel approach requires an off-line ZipTip desalting step followed by automated nanoESI-MS/MS, using the NanoMate 100 and ESI Chip. In addition to reduced method development time, automated nanoESI-MS/MS also offers no carry-over between samples, low sample consumption, and ease-of-use as compared with conventional pulled-capillary nanoelectrospray. Furthermore, the infusion system described has the potential to be high-throughput. A comparison of Caco-2 samples analyzed both by LC/MS/MS and by automated nanoESI-MS/MS is presented. The permeability and recovery data of the two compounds analyzed in this study obtained from conventional LC/MS/MS and by automated nanoESI-MS/MS were in excellent agreement.     

Sequential C–O decarboxylative vinylation/C–H arylation of cyclic oxalates via a nickel-catalyzed multicomponent radical cascade

A selective, sequential C–O decarboxylative vinylation/C–H arylation of cyclic alcohol derivatives enabled by visible-light photoredox/nickel dual catalysis is described. This protocol utilizes a multicomponent radical cascade process, i.e. decarboxylative vinylation/1,5-HAT/aryl cross-coupling, to achieve efficient, site-selective dual-functionalization of saturated cyclic hydrocarbons in one single operation. This synergistic protocol provides straightforward access to sp³-enriched scaffolds and an alternative retrosynthetic disconnection to diversely functionalized saturated ring systems from the simple starting materials.

A selective, sequential C–O decarboxylative vinylation/C–H arylation of cyclic alcohol derivatives enabled by visible-light photoredox/nickel dual catalysis has been described.     

模拟混凝土孔溶液中钢筋钝化膜生长动力学及孔蚀过程的研究

用恒电位电流衰减法及激光扫描光电化学显微技术研究了在于ＰＨ＝１２．５及１３．８的模拟混凝土孔溶液中钢筋钝化化膜的生长动力学及相应的破坏过程，实验结果表明，钢筋钝化膜的生长过程存在两个主要阶段，各阶段膜厚均与生长时间存在正比对数关系，但当ｔ＜３０秒和ｔ＞３０秒时，膜的生长表出出不同的动力学特征，在钝化发生点蚀前，钝化膜的微区光电流一定的预兆，腐蚀抑制剂ＮａＮＯ２影响膜的生长过程及膜厚，能提高钢筋的抗     

Oxidation of methionine residues in aqueous solutions: free methionine and methionine in granulocyte colony-stimulating factor

The free energy barriers and a mechanism of the oxidation of the amino acid methionine in water and in granulocyte colony-stimulating factor (G-CSF) are analyzed via combined quantum mechanical and molecular mechanical (QM/MM) methods, constrained molecular dynamics, and committor probability calculations. The computed free energy barrier of free methionine amino acid is very close to the measured value (14.7 +/- 1.2 versus 15.5 +/- 0.02 kcal/mol). The reaction coordinate was found to be the difference between the O-O bond of H2O2 and the S-O bond, where the S is the sulfur atom of the methionine residue. It was confirmed by computing the committor probability distribution and the distribution of constrained forces that this coordinate is not coupled to the activation of other degrees of freedom. The computed free energies of the oxidation of methionine residues in G-CSF indicate that the protein environment has insignificant effects on the reaction barriers of oxidation. This result further validates our proposal that the access of solvent to methionine sites, as measured by the two-shell water coordination number, governs the kinetics of the oxidation reaction of methionine groups in a protein molecule. We also found that the number of hydrogen bonds between the distal oxygen of H2O2 and the water molecules near the methionine increases along the reaction coordinate as oxidation progresses, indicating that the charge separation developed during the oxidation by H2O2 is stabilized by specific interactions with water molecules, such as hydrogen bonding.     

Studies of synergism for lowering dynamic interfacial tension in sodium alpha-(n-alkyl) naphthalene sulfonate/alkali/acidic oil systems

Alkylnaphthalene sulfonates with high purity were selected as model components to research synergism for lowering interfacial tension (IFT) in surfactant/alkali/acidic oil systems. The dynamic IFTs between alkylnaphthalene sulfonates with different alkyl chain length and n-decane, oleic acid model oil, or Shengli crude oil were measured. The results showed that the alkylnaphthalene sulfonates with different alkyl chain lengths had different synergism with different acidic components and their ionized acids under the same conditions. The synergism for lowering dynamic IFT in alkylnaphthalene sulfonate/alkali/acidic oil systems was controlled by alkylnaphthalene sulfonate concentration, alkyl chain length, alkali concentration, alkali type, and oleic acid concentration: optimal physicochemical conditions were necessary to the best synergism. This indicates that the synergism among added surfactant acidic components in crude oil and their ionized acids is controlled by the ratio of their interfacial concentrations.     

Synthesis of nanoporous graphite-derived carbon-silica composites by a mechanochemical intercalation approach

A mechanochemical intercalation approach which applies a simple mechanical milling to induce intercalation reaction was applied to introduce controlled amount of tetraethoxylsilane (TEOS) into surfactant-preexpanded graphite oxide, and the relationships between the intercalation structure, the porosities of the calcined products, and the Si addition were examined. It was found that a small added amount of TEOS produced a more expanded ordered layer structure with the interlayer distance and silicon content increasing with the amount of TEOS added, although a large amount of added TEOS easily induces layer delamination, resulting in a less ordered structure. The silica structure in the composite is changed from a disordered structure having enhanced bond strain to a condensed silica network when the amount of TEOS added increases. The porosities of the final calcined samples increase with the increase of silicon content but then decrease slightly after reaching a maximum where silicon content starts to become constant, indicating that both silicon content and the composition state of silica particles and carbon layers play important roles in porosity formation.     

Purification,Characterization and Mechanistic Study of β-Glucosidase from Flavobacterium meningosepticum (ATCC 13253)

A β-glucosidase (EC 3.2.1.21) from Flavobacterium meningosepticum has been purified and characterized. Purity was enhanced at least 530-fold from crude cell extract with 16.6% yield. The estimated molecular mass of the purified enzyme is 150 kDa by gel filtration and 78 kDa by SDS-PAGE. This dimeric enzyme has a pI = 9.0 and an optimal activity at pH 5.0 and temperature of 50 °C. Divalent metal ions (Hg²⁺, Cu²⁺, Ca²⁺, Mg²⁺) and EDTA have negligible effect on the enzyme activity. The enzyme exhibited a high specificity on the glycon portion of aryl-β-D -glycosides. NMR spectroscopy revealed the enzyme catalyzed hydrolysis of p-nitrophenyl-β-D -glucopyranoside with the retention of anomeric configuration, indicating that a double displacement mechanism was involved. A preliminary study of the Bronsted relationship showed a concave-downward plot, which is consistent with the two-step mechanism.     

Ti基IrO2＋Ta2O5阳极在H2SO4溶液中的电解时效行为

研究了450 ℃制备所得Ti/70％IrO2 30％Ta2O5（摩尔分数）高寿命阳极在H2SO4溶液电解过程中电极的物理、化学及电化学性能的时效行为.结果发现，整个电解过程可分为“活化”、“稳定”及“失效”三个阶段.在“活化”及“稳定”区内主要发生电极表面活性氧化物的溶解，涂层中IrO2金红石相的（110）、（101）晶面择优取向随电解时间延长而减弱，而（002）晶面择优增强.但是在“失效区”内，各晶面的择优程度却不随电解时间的变化而变化，这表明在“失效区”内氧化物的损失机制发生了变化.电化学阻抗谱测试表明，电极的析氧电化学反应电阻随电解时间的延长发生缓慢而连续的上升，而整个电极的物理阻抗在“失效区”内却发生突升现象.X射线衍射分析（XRD）表明，随电解时间的延长TiO2金红石相的衍射强度增大，达“失效区”时衍射强度发生突升.根据实验现象特别是“失效区”内阳极的时效行为提出高寿命Ti基氧化物涂层阳极的失效机制.     

Pyrimido[5,4-b]quinolines. II. Reactions at the heterocyclic ring-carbon and nitrogen atoms

10-Chloro-7,8-dimethylpyrimido[5,4-b]quinolin-2,4(1H,3H)dione (I) was unreactive toward ammonia but it reacted with 2 molecules of n-butylamine, presumably via Dimroth-type ring-opening and closure, to give the N₃-butyl, N₁₀-butylamino derivative (IV). In similar reactions of 10-chloro-2,4-dimethoxy-7,8-dimethylpyrimido[5,4-b]quinoline (II) only the 4-meth-oxyl was displaced by either ammonia or n-butylamine. Alkyllithium reagents also displaced the 4-methoxyl as well as added to the 3,4 double bond of II to yield the corresponding gem-dialkyl substituted (C₄) derivatives; the C₁₀ chlorine remained unreactive. 2,4-Dimethoxy-7,8-di-methylpyrimido[5,4-b]quinoline-10-one (III) could be alkylated only in the form of the thallium salt. Treatment of the benzyl derivative of III with methylmagnesium bromide led only to the displacement of the 4-methoxyl by a methyl group.