Structure-and-mechanism-based design and discovery of therapeutics for cocaine overdose and addiction

(-)-Cocaine is a widely abused drug and there is currently no available anti-cocaine therapeutic. Promising agents, such as anti-cocaine catalytic antibodies and high-activity mutants of human butyrylcholinesterase (BChE), for therapeutic treatment of cocaine overdose have been developed through structure-and-mechanism-based design and discovery. In particular, a unique computational design strategy based on the modeling and simulation of the rate-determining transition state has been developed and used to design and discover desirable high-activity mutants of BChE. One of the discovered high-activity mutants of BChE has a approximately 456-fold improved catalytic efficiency against (-)-cocaine. The encouraging outcome of the structure-and-mechanism-based design and discovery effort demonstrates that the unique computational design approach based on transition state modeling and simulation is promising for rational enzyme redesign and drug discovery. The general approach of the structure-and-mechanism-based design and discovery may be used to design high-activity mutants of any enzyme or catalytic antibody.     

Theoretical investigation of novel silsesquioxane-supported Phillips-type catalyst by density functional theory (DFT) method

In spite of great commercial importance of the Phillips CrO_x/SiO₂ catalyst and long term research efforts, the precise physicochemical nature of active sites and polymerization mechanisms still remains unclear. The difficulties in a clear mechanistic understanding of this catalyst mainly come from the complexity of the surface chemistry of the amorphous silica gel support. In this work, novel silsesquioxane-supported Phillips Cr catalysts are utilized as realistic models of the industrial catalyst for theoretical investigation using the density functional theory (DFT) method in order to elucidate the effects of surface chemistry of silica gel in terms of supporting of chromium compounds and fluorination of the silica surface on the catalytic properties of the Phillips catalyst. Both qualitative and quantitative aspects with respect to various electronic properties and thermodynamic characteristics of the model catalysts were achieved. The future prospects of a state-of-the-art catalyst design and mechanistic approaches for the heterogeneous SiO₂-supported Phillips catalyst has been demonstrated. The text was submitted by the authors in English.     

Solvent effects on infrared spectra of methyl 4-hydroxybenzoate in pure organic solvents and in ethanol/CCl4 binary solvents

Infrared spectroscopy studies of methyl 4-hydroxybenzoate (MHB) in 17 different organic solvents and in ethanol/CCl4 binary solvent were undertaken to investigate the solvent-solute interactions. The frequencies of carbonyl stretching vibration nu(C=O) of MHB in single solvents were correlated with the solvent acceptor number (AN) and the linear solvation energy relationships (LSER). The assignments of the two bands of nu(C=O) of MHB in alcohols and the single one of that in non-alcoholic solvents were discussed. The shifts of nu(C=O) of MHB in ethanol/CCl4 binary solvents showed that several kinds of solute-solvent hydrogen bonding interactions coexisted in the mixture solvents, with a change in the mole fraction of ethanol in the binary solvents.     

Synthesis and Characterization of Ordered Mesoporous Silica Spheres Using Anionic and Nonionic Mixed Surfactants for Their Potential Application in LC

Ordered mesoporous silicas (OMSs) with spherical morphology were synthesized by using mixed surfactants of anionic sodium dodecyl sulfate and nonionic block copolymer EO₂₀PO₇₀EO₂₀ (P123) as template through an acid-catalyzed silica sol?Cgel process. A variety of characterizations demonstrated that the silica products exhibited well-formed spherical morphology, ordered mesostructure, narrow pore size distribution and large surface area (~700 m² g^?1). It was found that the synthesized OMSs had high adsorption capacity by using oxymatrine as model solute. The column packed with the silica spheres exhibited low back pressure and baseline separation of aromatic compounds such as benzene and nitrobenzene could be achieved. These results demonstrated the synthesized OMSs as a potential stationary phase for liquid chromatography.     

Self-assembled biotinylated disulfide derivative monolayer on gold electrode for immobilizing enzymes

Based on self-assembled biotinylated disulfide derivative monolayer on gold electrode, the sensors immobilized monolayer or multilayer membranes composed of avidin and biotinlabeled glucose oxidase (B.GOD) or of avidin-B.GOD complex (ABC) and B.COD were prepared. The present technique may be useful for controlling the enzyme content of the sensors in molecular level by repeating the deposition of enzyme layers. The sensors have the characteristics of shorter response time, higher sensitivity. The linear range is from 6.0 x 10(-6) - 5.0 x 10(-3) M. The sensor can be used for more than 1 month and can be reactivated. The sensor was used to determine glucose in human blood serum, and the results are satisfactory.     

Synthesis and characterization of chitosan-graft-polycaprolactone copolymers

The graft copolymers of chitosan with polycaprolactone (PCL) were prepared through a protection-graft-deprotection route using phthaloylchitosan as intermediate. PCL macromonomers terminated with isocyanate groups reacted with hydroxyl groups of phthaloyl-protected chitosan regioselectively, and then phthaloyl groups were deprotected to give the free amino groups. The graft reaction was carried out in homogeneous system and yielded copolymers with high grafting content due to solubilization. FTIR, NMR and XRD were detected to characterize the resultant chitosan-graft-PCL copolymers.     

Multimetallic synergic sedation of a labile sodium atrane: synthesis and characterization of a tetranuclear sodium atrane cation complex

A series of sodium and aluminum atrane complexes of Na(3)L(THF)(5) (1), [AlLMe][Na(4)L(THF)(6)] (2), AlL(THF) (3), AlNaLMe(THF)(2) (4), and AlNaLOBn(THF)(2) (5), wherein L = tris(2-oxy-4,6-di-tert-butyl-benzyl)amine, were synthesized and characterized by NMR, X-ray crystallography, and elemental analysis. The trinuclear sodium atrane complex of Na(3)L(THF)(5) (1) is labile at room temperature; however, the tetranuclear sodium atrane cation in complex 2 can be stabilized by a multimetallic synergetic effect due to a firm interaction ring of -[Na-O-benzene](3)-. Complex 2 is also the first example of a sodatrane and alumatrane ion-paired complex in which both the cationic and anionic moieties contain an atrane ligand.     

用θ-2θ型衍射仪测定溶液结构的新方法

叙述了用θ－２θ型Ｘ射线衍射仪精确测定电解质溶液结构的新实验技术。设计制作了具有恒温功能的超厚液体样品池，并建立了样品池窗口强度的校正方法。优化了液体Ｘ射线衍射数据和结构参数精细化的计算机程序，获得了非常令人满意的实验结果。由θ－２θ型Ｘ射线衍射仪精确测定的径向分布函数与θ－θ型衍射仪自由散射比较，表明ＤＲＦ分辨率有所提高。