Systems-based design of bi-ligand inhibitors of oxidoreductases: filling the chemical proteomic toolbox

Genomics-driven growth in the number of enzymes of unknown function has created a need for better strategies to characterize them. Since enzyme inhibitors have traditionally served this purpose, we present here an efficient systems-based inhibitor design strategy, enabled by bioinformatic and NMR structural developments. First, we parse the oxidoreductase gene family into structural subfamilies termed pharmacofamilies, which share pharmacophore features in their cofactor binding sites. Then we identify a ligand for this site and use NMR-based binding site mapping (NMR SOLVE) to determine where to extend a combinatorial library, such that diversity elements are directed into the adjacent substrate site. The cofactor mimic is reused in the library in a manner that parallels the reuse of cofactor domains in the oxidoreductase gene family. A library designed in this manner yielded specific inhibitors for multiple oxidoreductases.     

测定核黄素的化学发光新方法

研究了核黄素的化学发光性质，建立了一种测定核黄素的化学发光新方法，并应用于实际样品中核黄素的测定，与文献相比，本方法无需避光，而且分析体系和样品处理简单；干扰小，牛血清白蛋白、抗坏血酸、天冬氨酸等８种生物有机物质和 Ｃｕ（Ⅱ）、Ｚｎ（Ⅱ）、Ｆｅ（Ⅲ）等１５种常见金属离子的允许量较大；核黄素溶液浓度在０． １０～５０ ｍｇ／Ｌ范围内，与化学发光强度成正比，方法线性范围宽；测定１．０ｍｇ／Ｌ核黄素溶液１２次，求得相对标准偏差为２．９％，方法精密度高；方法的检测限为０．０７５ ｍｇ／Ｌ，灵敏度高。     

CH自由基与O2反应的从头算研究

采用量子化学从头算法（UMP2／6－31G**水平），从理论上研究了CH＋O2反应的两个主要通道.根据计算所得的反应诸途径（连接反应物Cn＋）及两个通道的最终产物）讨论了复杂的反应机理．发现反应过程涉及O2的第一激发态1△g，且沿反应途径有势能面相交，反应途径中包括多个中间体及过渡态．     

蔥与菲的激发等离子体质谱的分析和比较

蒽和菲是一对同分异构体,由于它们的结构都很稳定,所以在常规的电子轰击质谱中,它们的分子离子峰都很突出,两者的谱图没有明显的差异,不能成为一种鉴别手段.我们最近在自制的仪器上,记录了以近红外激光作用于这两个稠环芳香烃所产生的正负离子质谱,两者的谱图具有明显的不同,其中包含了较为丰富的结构信息,显示了这一研究手段的结构分析能力。     

Synthesis and structure of intramolecularly hydrogen bonded dendrons

[reaction: see text] A convenient synthesis of monodendrons whose conformation is restricted through the intervention of intramolecular hydrogen bonding and repulsive electrostatic interactions is described. X-ray crystal structure analysis of the second generation dendron shows the presence of a propeller-type secondary structure and indicates that the dendrons have assembled into a symmetrically interdigitated dimer in the solid state. 1H NMR and IR spectral data are in agreement with the presence of intramolecular hydrogen bonding between the amides and the pyridine N throughout the dendron structure in solution.     

四个酰基硫脲衍生物及其配合物的合成与表征

本文报道了四个Ｎ－酰基硫脲衍生物及其Ｃｕ＾２＋，Ｎｉ＾２＋，Ｃｄ＾２＋，Ｓｎ＾４＋配合物的合成。用质谱、红外光谱、紫外光谱对它们进行了结构、性质表征。配体与金属离子配位主要是通过硫原子进行，配合物都是非离子型的。     

A facile solid-phase synthesis of substituted 2(5H)-furanones from polymer-supported alpha-selenocarboxylic acids

The synthesis of polystyrene-supported alpha-selenoacetic acid, alpha-selenopropionic acid, and alpha-selenophenylacetic acid is described. The reaction of the dilithio derivatives of polymer-supported alpha-selenocarboxylic acids with racemic epoxides or optically active styrene oxide afforded polystyrene-supported gamma-substituted alpha-selenobutyrolactones. The alpha-alkylation reaction of gamma-substituted polystyrene-supported alpha-selenobutyrolactones provided another route for the synthesis of polystyrene-supported alpha,gamma-disubstituted alpha-selenobutyrolactones. Subsequent oxidation-elimination with an excess of 30% hydrogen peroxide at room temperature afforded substituted (3- and 5-mono-; 3,4- and 3,5-di) 2(5H)-furanones in high yields and good purities.     

Synthesis of 1,3,4-oxadiazol-2-ones with aliphatic groups at N-3

A series of 3-substituted-5-methoxy-1,3,4-oxadiazol-2-ones were prepared from aldehydes, ketones, phenylacetic acids, and 1,2- and 1,3-diketones. Conditions for the formation of these oxadiazolones from the precursor N-carbamoyl chlorides depended on the structure, and varied from spontaneous ring closure to those requiring bases. Variation in the N-3 substituents sometimes produced mixtures of isomers which were separated and identified. These molecules were prepared in order to study the effect of the N-3 substituent variation on the biological properties of oxadiazolones.     

锆助剂对低温液相合成甲醇用铜铬硅催化剂性能的影响

考察了含锆的铜铬硅催化剂低温液相合成甲醇性能，并进行了BET、TPR-H2、TPD-H2、TPD-CO、XRD和XPS表征。结果表明，锆作为结构助剂及电子助剂对催化剂在低温液相合成甲醇反应中具有显著的促进作用，反应活性可提高32.25 ％。锆助剂能有效提高催化剂的比表面积，促进催化剂中铜铬组分的分散及表面富集。ZrO2加入在催化剂表面产生的Cu+与催化活性的改善密切相关，Zr4+、Cr3+、Cu+可形成复合中心，为价态的稳定性提供微环境，在H2活化及C O键的断裂等反应步骤中起重要作用。     

Studies on the properties of ionic liquid EMIInCl4

This paper reports that an ionic liquid (IL) has been prepared by directly mixing InCl₃ and 1-methyl-3-ethylimidazolium chloride (EMIC) with molar ratio 1/1 under dry argon atmosphere. The densities, and surface tension of the pure IL were determined at temperature range of 293.15 to 343.15 ± 0.1 K. The volumetric properties and the properties of surface for ionic liquid based on group III were discussed by Glasser's theory and Yang's interstice model.