Determination of arsenic species in Solanum Lyratum Thunb using capillary electrophoresis with inductively coupled plasma mass spectrometry

A simple and highly efficient interface to couple capillary electrophoresis with inductively coupled plasma mass spectrometry by a microflow polyfluoroalkoxy nebulizer and a quadruple ion deflector was developed in this study. By using this interface, six arsenic species, including arsenite, arsenate, monomethylarsonic acid, dimethylarsinic acid, arsenobetaine, and arsenocholine, were baseline‐separated and determined in a single run within 11 min under the optimized separation conditions. The instrumental detection limit was in the range of 0.02–0.06 ng/mL for the six arsenic compounds. Repeatability expressed as the relative standard deviation (n = 5) of both migration time and peak area were better than 2.5 and 4.3% for six arsenic compounds. The proposed method, combined with a closed‐vessel microwave‐assisted extraction procedure, was successfully applied for the determination of arsenic species in the Solanum Lyratum Thunb samples from Anhui province in China with the relative standard deviations (n = 5) ≤4%, method detection limits of 0.2–0.6 ng As/g and a recovery of 98–104%. The experimental results showed that arsenobetaine was the main speciation of arsenic in the Solanum Lyratum Thunb samples from different provinces in China, with a concentration of 0.42–1.30 μg/g.     

基于支持向量机、支持向量回归和分子对接的CYP450 1A2抑制剂的发现研究

支持向量机,支持向量回归和分子对接的计算方法已广泛应用于化合物的药理活性计算。为了提高计算的准确性和可靠性,拟以细胞色素P450酶1A2为研究载体,运用建立的联合SVM-SVR-Docking计算模型预测潜在的CYP1A2抑制剂。其中,建立的最优SVM定性模型训练集,内部测试集和外部测试集的准确率分别为99.432%,97.727%和91.667%。最优SVR定量模型训练集和测试集的R和MSE分别为0.763,0.013和0.753,0.056。实验表明两个模型具有较高的准确性和可靠性。通过对SVM和SVR模型结果的比较分析,发现连接性指数、分子构成描述符和官能团数目等分子描述符可能与CYP1A2抑制剂的辨识和活性预测密切相关。随后利用分子对接技术分析化合物与CYP1A2的结合构象及相互作用的稳定性。形成氢键相互作用的关键氨基酸包括THR124,ASP320;形成疏水相互作用的关键氨基酸包括ALA317和GLY316。所获得模型可用于天然产物化学成分中CYP1A2潜在抑制剂的活性计算及其介导的药物-药物相互作用预测提供理论指导,也为合理联合用药提供一定参考。共获得20个对CYP1A2具有潜在抑制活性的化合物。部分结果与文献结果相互印证,进一步说明了模型的准确性和联合计算策略的可靠性.     

Externally applied stress sign and film elastic properties effects on brittle film fracture

Rectangular stainless steel samples with TiN film deposited on the front lateral surface were loaded in three-point bending to the maximum normal strain of 6%. Scanning electron microscopy showed that vertical cracks appeared in the tension zone when the tensile strain exceeded 1.5%, while horizontal cracks appeared in the compression zone when the compressive strain exceeded –2.9%. Film cracks in the compressive zone originate from the tensile stress imposed by the plastically deformed substrate due to the Poisson’s expansion. Taking plastic deformation and Poisson’s expansion of the substrate in compression into account, theoretical analysis of normal stress distribution along the cracked film segment in compression is presented. Substrate strain and film elastic properties affect film cracking in the compressive zone. At larger compressive strain, some transverse cracks along with buckling cause the film spallation. The presented method is useful for studying brittle film fracture with variable strain levels in a single sample.     

光学元件亚表层裂纹成核临界条件研究

基于压痕实验和连续刚度测量法得到了熔石英材料硬度和弹性模量随压入深度的变化曲线, 系统分析了材料由延性到脆性转变的过程, 确定了熔石英晶体在静态/准静态印压和动态刻划时产生裂纹的临界载荷和临界深度。渐变载荷刻划实验结果表明, 划痕过程诱发的裂纹对法向载荷有很强的依赖性, 载荷较小时材料去除方式为延性域去除。随着法向载荷的增加, 首先产生垂直于试件表面的中位裂纹和平行于试件表面方向扩展的侧向裂纹, 而在试件表面上并没有产生明显的特征。载荷进一步增加后, 侧向裂纹扩展并形成了明亮区域, 最终诱发了沿垂直于或近似垂直于压头运动方向扩展的径向裂纹, 实现了材料的脆性去除。     

Rational design based on bioactive conformation analysis of pyrimidinylbenzoates as acetohydroxyacid synthase inhibitors by integrating molecular docking, CoMFA, CoMSIA, and DFT calculations

Pyrimidinylthiobenzoates constitute an important kind of herbicides targeting acetohydroxyacid synthase (AHAS, EC 2.2.1.6), which catalyze the first common step in branched-chain amino acid biosynthesis. Due to the symmetry of 4,6-dimethoxypyrimidyl, there are two kinds of conformation of pyrimidinylthiobenzoates: one's phenyl is left-extending (named conformation-L); the other's phenyl is right-extending (named conformation-R). On the basis of the assumption that 3D quantitative structure-activity relationship (QSAR) models derived from the bioactive conformation should give the best result, a strategy of density-functional-theory-based 3D-QSAR was proposed to identify the bioactive conformation of pyrimidinylthiobenzoates by integrating the techniques of molecular docking, comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and density functional theory calculation. The combination of three criteria of q2, r2, and r2pred obtained from CoMFA and CoMSIA analyses clearly indicated that conformation-R rather than conformation-L might be the bioactive conformation for pyrimidinylthiobenzoates. A further comparison between the two binding modes indicated that pyrimidinylthiobenzoates and sulfonylureas have very similar binding sites, such as Trp586, Arg380, and Pro192. However, Lys251 formed H bonds with sulfonylureas rather than pyrimidinylthiobenzoates. In addition, the orientation of phenyl groups of the two classes of compounds in the binding pocket were revealed to be opposite, which explained why the mutation of Pro192 displayed different sensitivity to sulfonylureas and pyrimidinylthiobenzoates. On the basis of the understanding of interactions between pyrimidinyl-thiobenzoates and AHAS, we designed and synthesized six 8-(4,6-dimethoxypyrimidin-2-yloxy)-4-methylphthalazin-1-one derivatives according to the 3D-QSAR models. The excellent correlation between the tested Ki values against wild-type A. thaliana acetohydroxyacid synthase and the predicted IC50 values demonstrated the high reliability of the established 3D-QSAR models. To our knowledge, this is the first report highlighting the binding mode of herbicidal pyrimidinylthiobenzoates, which consisted of the reported results of herbicide resistance.     

Simultaneous characterization of isoflavonoids and astragalosides in two Astragalus species by high-performance liquid chromatography coupled with atmospheric pressure chemical ionization tandem mass spectrometry

A method was developed for the simultaneous identification of astragalosides (AGs) and isoflavonoids (IFs) in the roots of Astragalus membranaceus and Astragalus mongholicus by HPLC coupled with atmospheric pressure chemical ionization MS/MS (HPLC-APCI-MS/MS). Diagnostic fragment ions of AGs and different group of IFs were obtained with one AG and eight IF standards analyzed by CID-MS, which were adopted as characteristic MS/MS fingerprints for further identification of these compounds in the two Astragalus species by using HPLC-APCI-MS/MS. A total of 20 IFs and 10 AGs were identified or tentatively identified. Among them, six IFs were detected in A. membranaceus for the first time and five IFs were firstly identified in A. mongholicus. The results indicate that HPLC-APCI-MS/MS is a powerful tool for the simultaneous characterization of IFs and AGs in complex matrix.     

High-resolution intermolecular zero-quantum coherence spectroscopy under inhomogeneous fields with effective solvent suppression

Intermolecular zero-quantum coherences (iZQCs) are not susceptible to magnetic field inhomogeneities significantly larger than the dipolar correlation distance and can be used to obtain 1D high-resolution spectra in an inhomogeneous field. However, with the iZQC methods proposed previously, residual conventional single-quantum coherences (SQCs) originating mainly from solvent resonance result in strong t(1) ridge noises. A modified HOMOGENIZED with an intermolecular double-quantum filter (iDQF), named iDQF-HOMOGENIZED, is presented in this work to suppress the residual conventional SQC signals as well as solvent iZQC signals. The solvent-suppression efficiency of the iDQF-HOMOGENIZED is analyzed and a thorough comparison of the new sequence with several relevant pulse sequences is made. Dramatic resolution enhancement and solvent suppression in the measurements of a piece of grape sarcocarp suggest potential applications of the method in in vivo spectroscopy.     

First-principles calculation of pKa for cocaine, nicotine, neurotransmitters, and anilines in aqueous solution

The absolute pKa values of 24 representative amine compounds, including cocaine, nicotine, 10 neurotransmitters, and 12 anilines, in aqueous solution were calculated by performing first-principles electronic structure calculations that account for the solvent effects using four different solvation models, i.e., the surface and volume polarization for electrostatic interaction (SVPE) model, the standard polarizable continuum model (PCM), the integral equation formalism for the polarizable continuum model (IEFPCM), and the conductor-like screening solvation model (COSMO). Within the examined computational methods, the calculations using the SVPE model lead to the absolute pKa values with the smallest root-mean-square-deviation (rmsd) value (1.18). When the SVPE model was replaced by the PCM, IEFPCM, and COSMO, the rmsd value of the calculated absolute pKa values became 3.21, 2.72, and 3.08, respectively. All types of calculated pKa values linearly correlate with the experimental pKa values very well. With the empirical corrections using the linear correlation relationships, the theoretical pKa values are much closer to the corresponding experimental data and the rmsd values become 0.51-0.83. The smallest rmsd value (0.51) is also associated with the SVPE model. All of the results suggest that the first-principles electronic structure calculations using the SVPE model are a reliable approach to the pKa prediction for the amine compounds.     

Al掺杂α-Fe2O3材料的制备、表征和气敏特性

采用均相沉淀法制备了纯α-Fe2O3(300 ℃煅烧)和Al掺杂α-Fe2O3(300和400 ℃煅烧), 使用SEM, XRD, ICP和红外光谱等手段进行表征, 并利用气敏仪测试无水乙醇和90＃汽油在不同条件下对材料的响应性能. 结果表明, 微量Al掺杂不改变α-Fe2O3材料的物相, 但会阻碍晶粒生长, 使颗粒变小及Fe2O3晶格间隙中的铁原子数目增多, 材料的导电率增大, 从而显著提高材料的气敏性能. Al掺杂α-Fe2O3对乙醇的响应性能优于对汽油的响应性能, 在乙醇气氛中, 材料对湿度仍然不敏感. 经400 ℃煅烧的Al掺杂α-Fe2O3稳定性较好, 可作为检测乙醇气体的半导体气敏材料.