Quantum mechanics/molecular mechanics studies of triosephosphate isomerase-catalyzed reactions: effect of geometry and tunneling on proton-transfer rate constants

The role of tunneling for two proton-transfer steps in the reactions catalyzed by triosephosphate isomerase (TIM) has been studied. One step is the rate-limiting proton transfer from Calpha in the substrate to Glu 165, and the other is an intrasubstrate proton transfer proposed for the isomerization of the enediolate intermediate. The latter, which is not important in the wild-type enzyme but is a useful model system because of its simplicity, has also been examined in the gas phase and in solution. Variational transition-state theory with semiclassical ground-state tunneling was used for the calculation with potential energy surface determined by an AM1 method specifically parametrized for the TIM system. The effect of tunneling on the reaction rate was found to be less than a factor of 10 at room temperature; the tunneling becomes more important at lower temperature, as expected. The imaginary frequency (barrier) mode and modes that have large contributions to the reaction path curvature are localized on the atoms in the active site, within 4 A of the substrate. This suggests that only a small number of atoms that are close to the substrate and their motions (e.g., donor-acceptor vibration) directly determine the magnitude of tunneling. Atoms that are farther away influence the effect of tunneling indirectly by modulating the energetics of the proton transfer. For the intramolecular proton transfer, tunneling was found to be most important in the gas phase, to be similar in the enzyme, and to be the smallest in water. The major reason for this trend is that the barrier frequency is substantially lower in solution than in the gas phase and enzyme; the broader solution barrier is caused by the strong electrostatic interaction between the highly charged solute and the polar solvent molecules. Analysis of isotope effects showed that the conventional Arrenhius parameters are more useful as experimental criteria for determining the magnitude of tunneling than the widely used Swain-Schaad exponent (SSE). For the primary SSE, although values larger than the transition-state theory limit (3.3) occur when tunneling is included, there is no clear relationship between the calculated magnitudes of tunneling and the SSE. Also, the temperature dependence of the primary SSE is rather complex; the value of SSE tends to decrease as the temperature is lowered (i.e., when tunneling becomes more significant). For the secondary SSE, the results suggest that it is more relevant for evaluating the "coupled motion" between the secondary hydrogen and the reaction coordinate than the magnitude of tunneling. Although tunneling makes a significant contribution to the rate of proton transfer, it appears not to be a major aspect of the catalysis by TIM at room temperature; i.e., the tunneling factor of 10 is "small" relative to the overall rate acceleration by 10(9). For the intramolecular proton transfer, the tunneling in the enzyme is larger by a factor of 5 than in solution.     

Influence of drying procedure on the mesoporosity and surface fractal dimensions of silica xerogels prepared with different agitation methods

Silica xerogels were prepared by thermal drying wet gels in an electric oven (70 degrees C) after certain duration of ambient drying, and the relevant effect is investigated on the mesopore structures and surface fractal dimensions of the resultant xerogels. The silica gels were derived from a hydrochloric acid-catalyzed TEOS (tetraethylorthaosilicate) system, and both magnetic stirring and ultrasonic vibration were adopted during sol preparation. The percentage mesoporosity and surface fractal dimensions are evaluated using image analysis methods, based on FE-SEM (field emission gun-scanning electron microscopy) images. The results show that the mesoporosity of the resultant xerogels decreases with the duration of ambient drying for samples prepared using magnetic stirring and low-intensity ultrasonic vibration, while samples subjected to high-intensity ultrasound show a somewhat reverse trend. Samples prepared with magnetic stirring have almost constant surface fractal dimensions (nearly 3), irrespective of the ambient drying before thermal drying. The surface fractal dimensions of samples prepared using ultrasound increase with the duration of ambient drying.     

The Synthesis of Some New N‐[1‐(2,5‐Dichlorophenyl)‐5‐Methyl‐1,2,3‐Triazol‐4‐yl]‐Carbamic Acid Ester Derivatives

The synthesis of some new N‐[1‐(2,5‐dichlorophenyl)‐5‐methyl‐1,2,3‐triazol‐4‐yl]‐carbamic acid ester derivatives are reported in this paper. The yielded products 6a‐l were confirmed by Elemental analyses, NMR, MS, and IR spectra.     

Identification and determination of effective components in Euphrasia regelii by capillary zone electrophoresis

A capillary zone electrophoresis (CZE) method has been developed for simultaneous determination of eukovoside, cinnamic acid and ferulic acid in Euphrasia regelii for the first time. The electrophoresis buffer was 20 mmol/L sodium borate containing 10% (v/v) methanol (pH 8.50). The effects of concentration of borate and electrolyte pH on electrophoretic behavior and separation were studied. Regression equations revealed linear relationships (correlation coefficients 0.9995-0.9998) between the peak area of each analyte and the concentration. The levels of analytes in the different parts of Euphrasia regelii were easily determined with recoveries ranging from 95.5 to 104.2%.     

Theoretical insights into the mechanism of acetylcholinesterase-catalyzed acylation of acetylcholine

Acylation of acetylcholine (ACh) catalyzed by acetylcholinesterase (AChE) has been studied using high-level theoretical calculations on a model system that mimics the reaction center of the enzyme, and compared with uncatalyzed acylation reaction. The geometries of all the intermediates and transition states, activation energies, and solvent effects have been calculated. The calculations predict simultaneous formation of two short-strong hydrogen bonds (SSHB) in the rate-determining transition state structures [the first SSHB involves the hydrogen atom of Ser-200 (H(s)) and another involves the hydrogen atom of His-440 (H(h))]. In the intermediate states, the H-bond corresponding to H(h) involves SSHB, whereas the one corresponding to H(s) does not.     

基于双尺度渐近分析的有限元算法

1．引言正如文山所说，由于复合材料和周期结构的材料系数ail（x）在局部区域内间断且跳跃性很大，加上区域内含有周期性洞穴或裂缝，且周期长度很小．一般而言，直接采用有限元方法进行数值模拟，其计算量大得惊人，甚至难以实现．文山针对这种特征，提出了一种可计算的双尺度渐近分析模式，本文在此基础上给出了相应的有限元算法，它包括：1．周期解在一个基本构造上的有限元计算；2．边界层的有限元计算．同时，给出了相应的误差分析．2．周期解的有限元计算首先考虑下列形式的边值问题；其中把，代E尸（on叫，iii（0关于E—（EI，ZZ…     

镝掺杂LaPO4拉曼光谱变化规律的探讨

采用水热法和后续热处理合成出单斜相LaPO4以及LaPO4:Dy3+,通过XRD对样品进行物相分析,结果表明:所得样品为LaPO4,且XRD图谱及拉曼光谱中峰位的偏移表明Dy的存在,即Dy被掺杂到LaPO4基质中。通过研究用Dy对LaPO4进行不同量掺杂后其拉曼光谱的变化规律,进而找出用Dy对LaPO4进行不同量掺杂后其内部结构的变化规律。结果显示,用Dy对LaPO4进行不同量掺杂后,随着掺杂比例的增大,晶格畸变程度先上升后下降,且在镧镝物质的量比例为1∶0.06时对基体晶格结构影响最大。