芪参益气滴丸治疗心血管疾病的计算药理学研究

利用计算药理学方法研究了中药芪参益气滴丸中含1729个化合物在化学空间分布,结果表明大部分化合物具有较好的类药性质．利用分子对接方法研究了1729个与26个心血管疾病相关的公认靶标的相互作用及它们在靶空间的分布,阐明了芪参益气滴丸抗血管疾病的可能作用机理及活性分子．     

An integrated approach of high-performance liquid chromatography–mass spectrometry-based chemical profiling,network pharmacology,and molecular docking to reveal the potential mechanisms of Qishen Gubiao granules for treating coronavirus disease 2019

Qishen Gubiao granules, a traditional Chinese medicine preparation composed of nine herbs, have been widely used to prevent and treat coronavirus disease 2019 with good clinical efficacy. In the present study, an integrated strategy based on chemical profiling followed by network pharmacology and molecular docking was employed, to explore the active components and potential molecular mechanisms of Qishen Gubiao granules in the therapy of coronavirus disease 2019. Using the ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technique, a total of 186 ingredients corresponding to eight structure types in Qishen Gubiao preparation were identified or structurally annotated with the elucidation of the fragmentation pathways in the typical compounds. The network pharmacology analysis screened 28 key compounds including quercetin, apigenin, scutellarein, luteolin and naringenin acting on 31 key targets, which possibly modulated signal pathways associated with immune and inflammatory responses in the treatment of coronavirus disease 2019. The molecular docking results observed that the top 5 core compounds had a high affinity for angiotensin-converting enzyme 2 and 3-chymotrypsin-like protease. This study proposed a reliable and feasible approach for elucidating the multi-components, multi-targets, and multi-pathways intervention mechanism of Qishen Gubiao granules against coronavirus disease 2019, providing a scientific basis for its further quality evaluation and clinical application.     

Chemical Variations among Shengmaisan-Based TCM Patent Drugs by Ultra-High Performance Liquid Chromatography Coupled with Hybrid Quadrupole Orbitrap Mass Spectrometry

Shengmaisan (SMS) is a famous traditional Chinese medicine (TCM) formula to treat coronary heart diseases. It has been developed into several TCM patent drugs to meet the demands of different patients. In this study, a research strategy was proposed to reveal the chemical variations among four SMS-based patent drugs, including Shengmai Oral Solution (Shengmaiyin, SMY), Shengmai Capsule (Shengmai Jiaonang, SMJN), Yiqi Fumai Injection (YQFMI), and Yiqi Fumai Capsule (Yiqi Fumai Jiaonang, YQJN). Firstly, 227 compounds were tentatively identified using an Orbitrap-MS in the full scan/dd-MS² mode. Secondly, untargeted metabolomics analysis suggested that ginsenosides, steroidal saponins, and lignans were the main types of differential compounds for the four patent drugs. Finally, the contents of 25 compounds were simultaneously determined in 30 batches of samples in the parallel reaction monitoring (PRM) mode. Partial least squares discriminant analysis (PLS-DA) revealed the contents of ginsenosides Re, Rg1, Rb1, Ro, and Rg3, and schisandrin showed the highest intergroup variations. These compounds were chemical markers to differentiate the SMS-based patent drugs.     

Simultaneous determination of eight bioactive components of Qishen Yiqi dripping pills in rat plasma using UFLC–MS/MS and its application to a pharmacokinetic study

In this study, a rapid and reliable ultra‐fast liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous determination of eight active ingredients, including astragaloside IV, ononin, tanshinol, protocatechualdehyde, protocatechuic acid, salvianolic acid D, rosmarinic acid and ginsenoside Rg₁, in rat plasma. The plasma samples were pretreated by protein precipitation with acetonitrile. Chromatographic separation was performed on a Waters Acquity UPLC® BEH C₁₈ column (1.7 μm particles, 2.1 × 100 mm). The mobile phase consisted of 0.1% aqueous formic acid (A)–acetonitrile with 0.1% formic acid (B) at a flow rate of 0.4 mL/min. Quantification was performed on a triple quadruple tandem mass spectrometry with electrospray ionization by multiple reaction monitoring both in the negative and in the positive ion mode. The lower limit of quantification of tanshinol was 2.0 ng/mL and the others were 5.0 ng/mL. The extraction recoveries, matrix effects, intra‐ and inter‐day precision and accuracy of eight tested components were all within acceptable limits. The validated method was successfully applied to the pharmacokinetic study of the eight active constituents after intragastric administration of three doses (1.0, 3.0, 6.0 g/kg body weight) of Qishen Yiqi Dripping Pills to rats.     

A novel frequency distribution selection method for efficient plate layout of a diverse combinatorial library.

A deterministic method (frequency distribution method) for selecting compounds from a partitioned virtual combinatorial library for efficient synthesis is presented here. The method is based on reagent frequency analysis and can be applied to any library of molecules distributed in any given partitioned chemical space (cluster, cell-based, etc.). Compound selection by reagent frequency distribution can produce a unique, diverse set of molecules that adequately represents the library while requiring the least amount of compounds to be synthesized and minimizing the number of different reagents that must be used. This method also provides a practical solution to the configuration of plate layout. Because the method essentially identifies "expensive" regions in the chemical space to synthesize for a desired diversity or similarity coverage, decisions concerning the necessity to synthesize these compounds can be addressed. Minimum compound generation and efficient plate layout results in savings both in time of synthesis and cost of materials. This method always results in a discrete solution, which can be used for any given library size as well as any combination of reagents and is also readily adaptable to robotic automation.     

Synthesis and mass spectrometric study of α,ω-bis(heptamethylcyclotetrasiloxanyloxy)oligodimethylsilanes

α,ω-Bis(heptamethylcyclotetrasiloxanyloxy)oligodimethylsilanes were synthesized by the reaction of dichlorodimethylsilane and 1,3-dichlorohexamethyltrisilane with hydroxyheptamethylcyclotetrasiloxane. The peculiarities of fragmentation of the compounds obtained by electron impact mass spectrometry are discussed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1729–1733, September, 1999.     

补中益气汤对肝硬化患者机体微量元素的影响

为探讨补中益气汤对肝硬化患者机体微量元素水平的影响,采用全自动生化分析仪检测了30例服用补中益气汤肝硬化患者及30例肝硬化对照组患者血清中镁、铁、铜、锌的水平。结果表明,服用补中益气汤患者血清镁、铁、锌水平均显著高于对照组患者(P0.05),服用补中益气汤患者血清铜水平均显著低于对照组患者(P0.05)。提示了补中益气汤能显著提高肝硬化患者机体微量元素水平,对改善患者肝脏功能具有一定的作用。     

3D QSAR investigation of the blood-brain barrier penetration of chemical compounds

In the present study, we investigated structure-permeability relationships for the blood-brain barrier (BBB) of 16 imipramine and phenothiazine derivatives. The compounds belong to structurally related chemical classes of catamphiphiles, representatives of which have previously been investigated for membrane activity and ability to overcome multidrug resistance (MDR) in tumour cells. These studies show that phenothiazines and structurally related drugs (imipramines, thioxanthenes, acridines) interact with membrane phospholipids, and additionally inhibit the MDR transport P-glycoprotein. This study aimed to identify common 3D structural characteristics of these compounds related to their mechanism of transport across the BBB. For this purpose Genetic Algorithm Similarity Programme (GASP), Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA) were applied. The results demonstrate the importance of the spatial distribution of molecular hydrophobicity for the BBB penetration of the investigated compounds. It suggests that the compounds should follow a specific profile of two hydrophobic and one hydrophilic centres in a particular space configuration, for optimal BBB penetration.     

Nature and centers of localization of extraframework particles in Y zeolite dealuminated by silicon tetrachloride

X-ray diffraction, XPS, and NMR have been used to investigate the nature and centers of localization of nonframework particles in Y zeolite dealuminated by silicon tetrachloride. It has been established that the reaction products formed upon dealumination consist mainly of aluminum compounds that migrate from the volume of the zeolite to the surface and are also partially localized in internal supercages and small cages (sodalite cells). Water washing removes the particles localized in the supercages but does not affect the particles localized in sodalite cells. It has been shown that, by plotting maps of electron density on the basis of x-ray powder diffraction patterns, the sites of localization of extraframework particles can be determined. The results are consistent with those obtained by other methods, and the maps of electron density give a graphic picture of changes in internal structure of the Y zeolite.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1729–1734, August, 1989.The authors wish to express their appreciation to V. M. Mastikhin for assistance in taking the²⁷Al and²⁹Si NMR spectra.     

Sonochemical immobilization of silver nanoparticles on porous polypropylene

Silver nanoparticles were immobilized on the surface of polypropylene (PP) porous beads by an ultrasound‐assisted reduction method. The structure and properties of the silver–PP composite were characterized with XRD, TEM, HRSEM, EDX, XPS, and Raman spectroscopy. Water‐soluble polymers such as PEG, PVA, and PVP were used as stabilizing agents for preventing the agglomeration of the silver nanoparticles. With PVP, a homogeneous distribution of silver nanocrystals, 50 nm in size, on the PP surface was achieved. The mechanism proposed for the silver anchoring to the inert polymer accounts for a localized melting of the PP. The beads of the silver PP composite demonstrated good stability and high antibacterial activity. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1719–1729, 2008     

Effect of solvent and electrospray mass spectrometer parameters on the charge state distribution of peptides--a case study using liquid chromatography/mass spectrometry method development for beta-endorphin assay

Beta-endorphin was used as a model peptide to study the effect of solvent and electrospray mass spectrometer parameters in the optimisation of an assay method for multiply charged compounds using liquid chromatography/mass spectrometry (LC/MS). Unlike with singly charged compounds, the charge state distribution has a significant impact in the method development of multiply charged compounds such as peptides. Using a 50% acetonitrile/water solvent mixture, we found that the ion spray voltage had no influence on the charge state distribution. However, increasing declustering potential led to deprotonation of the higher charge states of the peptide thus causing a shift to lower charge states. The mechanism leading to the deprotonation was examined. It was concluded that the deprotonation is due to endoergic proton transfer from the peptide to solvent molecules clustered to the peptide that occurs in the declustering region. The extent of deprotonation increases with increasing proton affinity of the molecules of the non-aqueous solvent component used. Thus, if desired, deprotonation can be avoided by selecting a low proton affinity solvent such as methanol. The focusing potential was also found to have a great influence on the charge state distribution observed. The results of this study enabled us to select the optimum ion to be used in single ion/reaction monitoring mode. They also provided the most favourable parameter values to be used in the method to obtain the best sensitivity for the ion of choice. The results demonstrate the importance of considering the charge state distribution in the optimisation of electrospray LC/MS methods for multiply charged compounds.     

碱活化多孔碳用于分离甲苯及活化/吸附机理

采用生物质木质素磺酸钠(SLS)为碳源, 先与硬模板NaCl混合预碳化, 再加入活化剂NaOH在氮气保护下升温至850 ℃碳化, 得到SLS基碱活化的多孔碳吸附剂(SPCN). 将SPCN用于吸附液体石蜡中芳香烃甲苯, 对比研究了不同活化剂加入量对SPCN结构、 性质及吸附效果的影响. 结果表明, SPCN表面具有丰富的官能团和发达的微/介孔结构, 活化剂加入量对比表面积的影响为先增大后减小, 碱/碳质量比为1∶1时比表面积达到最大值(710.4 m ²/g); 吸附量与比表面积呈正相关, 样品SPCN-1的最大吸附量为2875.17 mg/g, 远高于商业吸附剂, 经5次吸附-解吸循环后仍保持92.5%的吸附效率. 探究了活化机理, NaOH、 碳质和气体发生氧化还原反应释放气体留下孔隙, 经充分酸洗、 水洗后得到永久孔道. 最后, 结合扫描电子显微镜(SEM)、 透射电子显微镜(TEM)、 拉曼光谱(Raman)、 X射线衍射(XRD)、 傅里叶变换红外光谱(FTIR)和比表面积分析等结果证明了吸附机理主要是孔隙填充效应、 范德华力、 π-π相互作用及电子供/受体作用的共同作用. 首次报道了SPCN应用的新方向并探究了活化与吸附机理, 制备方法简易、 经济, 产品循环稳定性好、 无污染, 有望用于工业化生产.     

SYNTHESIS AND CRYSTAL STRUCTURE OF Eu[（CH3O）2PO2]3

<正> The title complex has been synthesized and characterized by elementary analysis,FT-IR and Raman spectra. The crystal and molecular structure was determined by X-ray diffraction analysis. The crystal of this complex C6H18O12P3Eu(Mr = 527. 08) is monoclinic with space group P21/c and cell parameters a= 10. 418(2) ,b= 16. 596(6) ,c =10. 766(2) A ,β=111. 67(2)°,V=1729. 8(8) A3 and Z=4. Dimethyl phosphate an-ions coordinate with europium ions through double O-P-O bridges to form a special network of rings-linking-rings. The local coordination geometry of Eu is a slightly distorted octahedron.     

HPLC-NMR for tissue-specific analysis of phenylphenalenone-related compounds in Xiphidium caeruleum (Haemodoraceae)

HPLC-(1)H NMR has been used to study the tissue-specific distribution of phenylphenalenones, polyphenolic natural products of Xiphidium caeruleum, a neotropical member of the Haemodoraceae plant family. The present results provide insight into the occurrence of phenylphenalenone-related compounds in root segments of whole plants and different in vitro culture lines of the same species.     

A canonical averaging in the second-order quantized Hamilton dynamics

Quantized Hamilton dynamics (QHD) is a simple and elegant extension of classical Hamilton dynamics that accurately includes zero-point energy, tunneling, dephasing, and other quantum effects. Formulated as a hierarchy of approximations to exact quantum dynamics in the Heisenberg formulation, QHD has been used to study evolution of observables subject to a single initial condition. In present, we develop a practical solution for generating canonical ensembles in the second-order QHD for position and momentum operators, which can be mapped onto classical phase space in doubled dimensionality and which in certain limits is equivalent to thawed Gaussian. We define a thermal distribution in the space of the QHD-2 variables and show that the standard beta=1/kT relationship becomes beta'=2/kT in the high temperature limit due to an overcounting of states in the extended phase space, and a more complicated function at low temperatures. The QHD thermal distribution is used to compute total energy, kinetic energy, heat capacity, and other canonical averages for a series of quartic potentials, showing good agreement with the quantum results.