Rapid screening and confirmation of drugs and toxic compounds in biological specimens using liquid chromatography/ion trap tandem mass spectrometry and automated library search

Recent advances in liquid chromatography/tandem mass spectrometry (LC/MS/MS) technology have provided an opportunity for the development of more specific approaches to achieve the ‘screen’ and ‘confirmation’ goals in a single analytical step. For this purpose, this study adapts the electrospray ionization ion trap LC/MS/MS instrumentation (LC/ESI‐MS/MS) for the screening and confirmation of over 800 drugs and toxic compounds in biological specimens. Liquid‐liquid and solid‐phase extraction protocols were coupled to LC/ESI‐MS/MS using a 1.8‐µm particle size analytical column operated at 50°C. Gradient elution of the analytes was conducted using a solvent system composed of methanol and water containing 0.1% formic acid. Positive‐ion ESI‐MS/MS spectra and retention times for each of the 800 drugs and toxic compounds were first established using 1–10 µg/mL standard solutions. This spectra and retention time information was then transferred to the library and searched by the identification algorithm for the confirmation of compounds found in test specimens – based on retention time matches and scores of fit, reverse fit, and purity resulting from the searching process. The established method was found highly effective when applied to the analyses of postmortem specimens (blood, urine, and hair) and external proficiency test samples provided by the College of American Pathology (CAP). The development of this approach has significantly improved the efficiency of our routine laboratory operation that was based on a two‐step (immunoassay and GC/MS) approach in the past. Copyright © 2009 John Wiley & Sons, Ltd.     

A New ent-Kaurane Diterpenoid from Isodon enanderianus

Isodon enanderianus (Hand. -Mazz.) H. W. Li, has been used in folk medicine as anti-inflammatory and detoxified agent1. The Isodon genus is known to be rich in ent-kaurane diterpenoids, a series of new ent-kaurane diterpenoids have been isolated from the dried leaves of I. enanderianus2-4. In order to find more biologically active substances, we have carefully investigated the chemical constituents of I. enanderianus collected in Shiping county of Yunnan province, and as a result, enanderi…     

若干经济数学模型的研究与应用

本文论述了近些年我们在投入产出模型、广告最优随机控制模型、最佳营销管理模型以及时间序列—马尔可夫链组合预测模型等方面所做的研究工作，同时也论及国内外在上述几方面的研究状况．     

不同含水量尾砂的光谱特征与遥感模型

我国尾矿库数量众多,分布广泛,在低含水量条件下,风力作用引起的尾砂扬尘会对周边环境造成污染。而尾矿库表面积大,含水量变化快,传统的含水量监测方法效率低、安全性差、成本高,难以实现尾矿库含水量的大面积、实时、快速的监测。目前,基于光谱特征的遥感模型虽可以较为准确地预测土壤含水量,但矿区尾砂与常规土壤在成分上存在差异性,使得土壤含水量的光谱预测遥感模型可能无法适用于尾矿库含水量的预测。为此,选择辽宁省风水沟尾矿库作为研究区,采集尾砂配置成不同含水量的样品,测试其可见光-近红外光谱,分析不同含水量样品的光谱特征以及含水量与光谱特征之间的关系,建立针对尾砂的含水量遥感预测模型,并应用于辽宁省风水沟尾矿库表面含水量的预测。结果表明：（1）含水量对尾砂的光谱特征有显著影响,二者存在高度的相关性,光谱反射率随含水量增加而下降,且波长越长,含水量对光谱的影响越显著;（2）构建了基于尾砂光谱特征的含水量遥感预测模型,选择Landsat8-OLI传感器的B6和B7波段,定义了比值指数（RTI）、归一化差异指数（NDTI）和差值指数（DTI）3种尾砂光谱指数,并将这3种指数作为输入自变量,使用随机森林方法进行训练以及含水量的建模预测,并与B7波段建立的对数反射率预测模型进行比较。结果表明,光谱指数+随机森林的预测模型效果优于基于B7波段建立的对数反射率模型。（3）使用光谱指数+随机森林的预测模型,通过Landsat8-OLI数据对实地尾矿库提取了含水量的空间分布图,结果表明模型预测的含水量与实测结果之间的决定系数R2达0.798,均方根误差RMSE为0.077,相对分析误差RPD为1.970,平均相对精度ARE为20.1%,在现有技术条件下,达到了较好的预测效果。该研究为变质型铁矿尾矿库含水量的预测提供一种大面积、实时、快速的实用方法。     

Rare earth‐doped calcium‐based magnetic catalysts for transesterification of glycerol to glycerol carbonate

Several rare earth‐doped, calcium‐based magnetic catalysts were prepared for the synthesis of glycerol carbonate. The basicity and basic strength analysis of the catalysts showed that the doping of rare earth improved the basicity of the catalysts, and the doping of lanthanum maximized it. In addition, with the doping of lanthanum, the particle size of the catalyst became smaller to promote the organic reactants near the active sites of catalysts, thereby effectively improving the performance. NiFe₂O₄@[CaO‐La₂O₃] shows better catalytic performance with 99.0% yield of glycerol carbonate compared to the other catalysts. The NiFe₂O₄@(CaO‐La₂O₃) could be reused in six cycles without significant loss in activity.     

Carbene triel bonds between TrR3 (Tr = B,Al) and N-heterocyclic carbenes

The carbene triel bond is predicted and characterized by theoretical calculations. The C lone pair of N-heterocyclic carbenes (NHCs) is allowed to interact with the central triel atom of TrR₃ (Tr = B and Al; R = H, F, Cl, and Br). The ensuing bond is very strong, with an interaction energy of nearly 90 kcal/mol. Replacement of the C lone pair by that of either N or Si weakens the binding. The bond is strengthened by electron-withdrawing substituents on the triel atom, and the reverse occurs with substitution on the NHC. However, these effects do not strictly follow the typical pattern of F > Cl > Br. The TrR₃ molecule suffers a good deal of geometric deformation, requiring on the order of 30 kcal/mol, in forming the complex. The R(C···Tr) bond is quite short, for example, 1.6 Å for Tr = B, and shows other indications of at least a partially covalent bond, such as a high electron density at the bond critical point and a good deal of intermolecular charge transfer.     

Synthesis and Antitumor Effect of Sophoridine Derivatives Bearing an Acyclic Aryloxy Phosphoramidate Mustard Functionality

To elevate the potency of sophoridine, phosphoramidate mustard motif was incorporated to D‐ring opened sophoridine scaffold. A series of acyclic aryloxy phosphoramidate mustard functionalized sophoridine derivatives were synthesized and screened for cytostatic activity in a range of different tumor cell lines (S180, H22, K562, MCF‐7, SMMC‐7721, and LoVo). All these compounds were shown to be more sensitive to S180 and H22 cells with IC₅₀ values ranging from 2.10 to 7.21 μM. In addition, all targeted derivatives distinctly are more cytotoxic to cancer cells than normal cell L929. Compounds 8b , 8c , 8d , and 8e displayed moderate tumor suppression without apparent organ toxicity in vivo against mice bearing H22 liver tumors. Their potential binding modes with DNA topoisomerase I complex have also been investigated.     

Revisiting the structural and electronic properties of neutral,mono- and di-anionic titanium-doped silicon clusters TiSin0/−/2− (n = 6-16)

The systematic structures search for neutral and Zintl anionic Ti-doped silicon clusters TiSi_n^0/−/2− (n = 6-16) have been carried out using the ABCluster global search technique combined with a double-hybrid density functional method. Based on the predicted energies, adiabatic electron affinities, vertical detachment energies and the consistency between simulated and experimental photoelectron spectroscopy, the true global minimum structures are confirmed. The results show that structural growth pattern of neutral TiSi_n clusters is from linked structures (n = 10-12) to encapsulated configurations (n = 13-16). In contrast, the evolution pattern of Zintl anionic TiSi_n^−/2− clusters begins with the pentagonal bipyramid structure (n = 6). As the Si atoms increase, these Si atoms attach to the surface adjacent to Ti atom, and gradually surround Ti atom. Eventually, the encapsulated structure is formed when n = 12. Moreover, two extra electrons not only perfect the structure of TiSi₁₂ but also improve its chemical and thermodynamic stability.     

Rhodium(III)-catalyzed direct C-7 sulfonamidation and amination of indolines with arylsulfonamides and trifluoroacetamide

A rhodium-catalyzed direct C–H sulfonamidation and amidation of C-7 position of indolines by simple and commercially available arylsulfonamides and trifluoroacetamide has been developed, affording a series of N-arylsulfonamides and N-aryltrifluoroacetamides in moderate to excellent yields, respectively. Notably, this catalytic system is highly convenient on mmol scale.     

Nitrogen‐rich Salts based on 3‐Dinitromethyl‐[1,2,4]triazine: Synthesis,Characterization, and Performance

1,1‐Diamino‐2,2‐dinitroethylene (FOX‐7), one of the most well‐known energetic materials, has attracted broad attention around the world. To extend the chemistry of FOX‐7, we present here a series of energetic salts based on 3‐dinitromethyl‐[1,2,4]triazine, which is prepared from FOX‐7. All these salts were fully characterized using ¹H NMR, ¹³C NMR, IR, and elemental analysis. In addition, the potassium salt ( 2 ), ammonium salt ( 5 ), and guanidinium salt ( 7 ) were further confirmed by single‐crystal X‐ray diffraction. Extensive hydrogen bonds were observed in these salts. The salts exhibit moderate densities varying from 1.63 to 1.76 g · cm^–3. All the compounds possess good thermal stability with decomposition temperatures from 118 to 267 °C. The detonation performance for salts were calculated by using EXPLO 5, their detonation velocities are in the range from 6807 to 8614 m · s^–1 and detonation pressures fall between 18.8 to 31.6 GPa. All the salts exhibit very low mechanical sensitivity, which indicates their potential application as insensitive energetic materials.