A new two-dimensional approach to quantitative prediction for collision cross-section of more than 110 singly protonated peptides by a novel moecular electronegativity-interaction vector through quantitative structure-spectrometry relationship studies

Based on two-dimensional topological characters, a novel method called molecular electronegativity-interaction vector (MEIV) is proposed to parameterize molecular structures. Applying MEIV into quantitative structure-spectrometry relationship studies on ion mobility spectrometry collision cross-sections of 113 singly protonated peptides, three models were strictly obtained, with correlative coefficient r and leave-one-out cross-validation q of 0.983, 0.979, 0.981, 0.979 and 0.980, 0.978, respectively. Thus, the MEIV is confirmed to be potent to structural characterizations and property predictions for organic and biologic molecules. Translated from Chinese Journal of Analytical Chemistry, 2006, 34(6) (in Chinese)     

Investigating direct current potentials that affect native protein conformation during trapped ion mobility spectrometry–mass spectrometry

Trapped ion mobility spectrometry–time-of-flight mass spectrometry (TIMS-TOFMS) has emerged as a tool to study protein conformational states. In TIMS, gas-phase ions are guided across the IM stages by applying direct current (DC) potentials (D1–6), which, however, might induce changes in protein structures through collisional activation. To define conditions for native protein analysis, we evaluated the influence of these DC potentials using the metalloenzyme bovine carbonic anhydrase (BCA) as primary test compound. The variation of DC potentials did not change BCA-ion charge and heme content but affected (relative) charge-state intensities and adduct retention. Constructed extracted-ion mobilograms and corresponding collisional cross-section (CCS) profiles gave useful insights in (alterations of) protein conformational state. For BCA, the D3 and D6 potential (which are applied between the deflection transfer and funnel 1 [F1] and the accumulation exit and the start of the ramp, respectively) had most profound effects, showing multimodal CCS distributions at higher potentials indicating gradual unfolding. The other DC potentials only marginally altered the CCS profiles of BCA. To allow for more general conclusions, five additional proteins of diverse molecular weight and conformational stability were analyzed, and for the main protein charge states, CCS profiles were constructed. Principal component analysis (PCA) of the obtained data showed that D1 and D3 exhibit the highest degree of correlation with the ratio of folded and unfolded protein (F/U) as extracted from the mobilograms obtained per set D potential. The correlation of D6 with F/U and protein charge were similar, and D2, D4, and D5 showed an inverse correlation with F/U but were correlated with protein charge. Although DC boundary values for induced conformational changes appeared protein dependent, a set of DC values could be determined, which assured native analysis of most proteins.     

脂肪醇的生物毒性与结构参数的相关性研究

应用量子化学从头算HF/3-21G方法得到了14种脂肪醇分子的优势构象,利用HF/3-21G法和分子图形学技术获得其电子结构、几何结构参数和连接性指数,并将这些参数与脂肪醇对番茄和红蜘蛛的毒性相关联.结果表明,脂肪醇对番茄的生物毒性与一阶分子连接性指数1X和羟基电荷QOH之间存在良好的二元线性相关性,而脂肪醇对红蜘蛛的生物毒性与一阶分子连接性指数1X和分子最高已占轨道能EH之间存在良好的二元线性相关性,成功地建立脂肪醇对番茄和红蜘蛛毒性的构效关系式.     

离子淌度谱及其近年进展

近年来离子淌度谱（ＩＭＳ）在样品引入技术，信号采集和数据处理、离子源等方面都有了显著的进展，其中以ＩＭＳ作为色谱检测器（ＩＭＤ）进行的研究尤为重要，而ＩＭＳ与Ｊ民喷雾郭子化（ＥＳＩ）技术的联用扩大其在非挥发性化合物和生物物质检测方面的应用评论还综述了近年来ＩＭＳ应用于环保、化学化工、违禁药物检测、爆炸物检测以及半导体表面挥发物分析等方面的最新研究成果。     

Characterizing ion mobility and collision cross section of fatty acids using electrospray ion mobility mass spectrometry

This study investigated the ion mobility (IM) and the collision cross section (CCS) of fatty acids (FAs) using electrospray IM MS. The IM analysis of 18 FA ions showed intriguing differences among the saturated FAs, monounsaturated FAs, multi‐unsaturated FAs, and cis‐isomer/trans‐isomer with respect to the aliphatic tail chains. The length of aliphatic tail chain present in the ion structures had a strong influence on the differentiation of drift, while the number of double bond showed a weaker influence. The tiny drift differences between cis‐isomer and trans‐isomer were also observed. In the CCS measurements, two internal standards were involved in the mobility calibration and accuracy estimation. It insured our empirical CCS values were of high experimental precision (±0.35% or better) and accuracy (±0.25% or better). Moreover, the mass‐to‐charge ratio (m/z) – mobility plots obtained by ion mobility spectrometry with mass spectrometry analysis of FAs – was used to investigate the structural relationship between the molecules. Each series of FAs sharing a similar structure was aligned in the linear plot. Finally, the developed procedure was applied to the determination of FAs in rat adipose tissues, and it allowed the presence of 13 FAs to be confirmed with their exact masses and CCS values. These studies reveal the direct relationship between the behaviors in IM and the molecular structures and thus may provide further validations to the FA identification process. Copyright © 2015 John Wiley & Sons, Ltd.     

分子电性作用矢量法定量预测单质子化肽段离子迁移谱碰撞截面

基于分子二维图形特征得到了一种新的结构参数化方法:分子电性作用矢量(MEIV)。将其应用于113个单质子化肽段样本集的结构表征及离子迁移谱碰撞截面模拟和预测当中,通过严格检验所得到3个回归模型的复相关系数Rcum及交叉验证Q分别为:0.984、0.981、0.980和0.979、0.979、0.978。结果表明MEIV对有机分子结构及其性质具有良好的表达和预测能力。     

Ultra-fast screening of free fatty acids in human plasma using ion mobility mass spectrometry

Free fatty acids are involved in many metabolic regulations in the human body. In this work, an ultra-fast screening method was developed for the analysis of free fatty acids using trapped ion mobility spectrometry coupled with mass spectrometry. Thirty-three free fatty acids possessing different unsaturation degrees and different carbon chain lengths were baseline separated and characterized within milliseconds. Saturated, monounsaturated, and polyunsaturated free fatty acids showed different linearities between collision cross-section values and m/z. The establishment of correlations between structures and collision cross-section values provided additional qualitative information and made it possible to determine free fatty acids which were out of the standards pool but possessed the confirmed linearity. The gas-phase separation made the quantitative analysis reliable and repeatable at a much lower time cost than chromatographic methods. The sensitivity was comparable to and even better than the reported results. The method was validated and applied to profiling free fatty acids in human plasma. Saturated free fatty acids abundance in the fasting state was found to be lower than that in the postprandial state, while unsaturated species abundance was found higher. The method was fast and robust with minimum sample pretreatment, so it was promising in the high-throughput screening of free fatty acids.     

A Strategy for Identification and Structural Characterization of Compounds from Plantago asiatica L. by Liquid Chromatography-Mass Spectrometry Combined with Ion Mobility Spectrometry

Plantago asiatica L. (PAL) as a medicinal and edible plant is rich in chemical compounds, which makes the systematic and comprehensive characterization of its components challenging. In this study, an integrated strategy based on three-dimensional separation including AB-8 macroporous resin column chromatography, ultra-high performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF MS), and ultra-high performance liquid chromatography-mass spectrometry with ion-mobility spectrometry (UHPLC-IM-MS) was established and used to separate and identify the structures of compounds from PAL. The extracts of PAL were firstly separated into three parts by AB-8 macroporous resin and further separated and identified by UHPLC-Q-TOF MS and UHPLC-IM-MS, respectively. Additionally, UHPLC-IM-MS was used to identify isomers and coeluting compounds, so that the product ions appearing at the same retention time (RT)can clearly distinguish where the parent ion belongs by their different drift times. UNIFI software was used for data processing and structure identification. A total of 86 compounds, including triterpenes, iridoids, phenylethanoid glycosides, guanidine derivatives, organic acids, and fatty acids, were identified by using MS information and fragment ion information provided by UHPLC-Q-TOF MS and UHPLC-IM-MS. In particular, a pair of isoforms of plantagoside from PAL were detected and identified by UHPLC-IM-MS combined with the theoretical calculation method for the first time. In conclusion, the AB-8 macroporous resin column chromatography can separate the main compounds of PAL and enrich the trace compounds. Combining UHPLC-IM-MS and UHPLC-Q-TOF MS can obtain not only more fragments but also their unique drift times and RT, which is more conducive to the identification of complex systems, especially isomers. This proposed strategy can provide an effective method to separate and identify chemical components, and distinguish isomers in the complex system of traditional Chinese medicine (TCM).     

Unique description of chemical structures based on hierarchically ordered extended connectivities (HOC procedures). III. Topological,chemical, and stereochemical coding of molecular structure

A topological code is devised on the basis of the unique topological representation of the molecule described in the preceding two parts of this series.¹ By adding to the topological code additional chemical information on atoms and/or bonds, as well as stereochemical information, a chemical and respectively stereochemical code (SHOC) are also constructed. The advantages of the new linear codes are that they are convention-free codes, preserving the symmetry of molecular graph, and easily implemented either manually or by means of computer programs. By concentrating all topological, chemical, and stereochemical information, our code (SHOC) is more compact and more general than the codes based on several separate lists.     

Mapping and sequencing of cardiolipins from Geobacillus stearothermophilus NRS 2004/3a by positive and negative ion nanoESI-QTOF-MS and MS/MS

In the course of systematic studies on surface layer (S-layer) glycoproteins of bacilli, the chloroform/methanol extract from whole cells of Geobacillus stearothermophilus NRS 2004/3a has been submitted to MS analysis. Glucosylated cardiolipins were found as minor components of the total lipid and phospholipid mixture by de novo identification. After purification of the crude extract using a combined column chromatography/2D TLC protocol, structural investigations of components in the lipid fraction by high resolution ESI-QTOF MS analysis provided evidence about homologous molecules attributable to the cardiolipin species containing a glycosylated backbone, and about a diversity of ester-linked fatty acid substituents. In comparative studies by positive and negative ion nanoESI-QTOF-CID-MS, maps of cardiolipin molecular ions were obtained, followed by MS/MS of the most abundant species, to provide structural details of D-glucopyranosylcardiolipin and the fatty acid substituent patterns. Experiments of the parent ion scan type revealed the presence of fatty acid moieties as isobaric combinations, represented in single molecular ion species.     

Predicting Thermodynamic Properties of Alkanes with L and B

Two new molecular topological indices of alkane:the logarithmic topological index (L) and the topological index (B) of carbon atomic ordinal, are defined as:L=∑[lg(δ_i+l)(δ_j)]^-1, B=[∑(S_j · S_j)^1/2]^1/2 respectively.     

Network pharmacology analysis of Chaihu Lizhong Tang treating non-alcoholic fatty liver disease

BackgroundIn this study, the network pharmacological methods were used to predict the target of active components of Chaihu Lizhong Tang (CHLZT) in the treatment of non-alcoholic fatty liver disease (NAFLD).MethodThe active components of "CHLZT", their targets, and NAFLD related targets were screened by multiple databases, and the potential targets of "CHLZT" in the treatment of NAFLD were predicted. The active component-target network of "CHLZT" was constructed by Cytoscape software. The potential target of "CHLZT" for the treatment of NAFLD constructed protein-protein interaction (PPI) network in the Search Tool for the Retrieval of Interacting Genes Database (STRING). The hub genes of “CHLZT” in the treatment of NAFLD were screened by network topological parameters, and the results were verified by molecular docking. "ClusterProfiler" in R was used for Gene Ontology (GO) analysis and KEGG pathway enrichment analysis.ResultsOB ≥ 30 % and DL ≥ 0.18 were selected as the screening criteria of active components. A total of 83 active components and 456 targets were selected. Based on the evaluation of topological parameters of degree network, five hub genes for interaction with "CHLZT" therapy for NAFLD were screened, that is, AKT1, ALB, IL6, EGFR, and CASP3. The results of molecular docking showed that the active components in "CHLZT" had a good binding ability with the key targets. The enrichment analysis results showed that the treatment of NAFLD with "CHLZT" mainly involved in cofactor binding, protease binding, AGE-RAGE signaling pathway in diabetic complications, and IL-17 signaling pathway, which mediated the potential mechanism of "CHLZT" intervention in NAFLD.ConclusionThe molecular mechanism of "CHLZT" in the treatment of NAFLD indicated the synergistic features of multi-component, multi-target, and multi-pathway of traditional Chinese medicine, which provided an important scientific basis for further elucidating the mechanism of "CHLZT" in the treatment of NAFLD.     

三梯级和四梯级圆筒和Mbius分子的拓扑特性研究

Walba等以其卓越的工作,合成了三-THYME(C_(42)H_(72)O_(18))和四-THYME(C_(56)H_(96)O_(24))圆筒及其Mbius扭曲环带分子,被誉为拓扑学进入有机化学领域的奇迹,成为迄今为止拓扑立体化学研究的重要内容,但从拓扑学的观点探索分子图拓扑结构特性尚缺乏深入研究,本文作者考虑到一般性,曾将扭曲数T为偶数(0,2,4)的定义为Hckel型,扭曲数     

Reversible Photoswitching of Isolated Ionic Hemiindigos with Visible Light

Indigoid chromophores have emerged as versatile molecular photoswitches, offering efficient reversible photoisomerization upon exposure to visible light. Here we report synthesis of a new class of permanently charged hemiindigos (HIs) and characterization of photochemical properties in gas phase and solution. Gas-phase studies, which involve exposing mobility-selected ions in a tandem ion mobility mass spectrometer to tunable wavelength laser radiation, demonstrate that the isolated HI ions are photochromic and can be reversibly photoswitched between Z and E isomers. The Z and E isomers have distinct photoisomerization response spectra with maxima separated by 40–80 nm, consistent with theoretical predictions for their absorption spectra. Solvation of the HI molecules in acetonitrile displaces the absorption bands to lower energy. Together, gas-phase action spectroscopy and solution NMR and UV/Vis absorption spectroscopy represent a powerful approach for studying the intrinsic photochemical properties of HI molecular switches.     

脂肪酸多聚甘油酯分子结构与性能相关性研究

采用量子化学MM+和AM1方法计算聚甘油和脂肪酸多聚甘油酯的分子结构参数,然后用逐步线性回归方法建立脂肪酸多聚甘油酯HLB值的定量结构性质(QSPR)模型,所得的预测模型中包含四个参数(单位质量分子所含氧原子数Xo、生成热ΔfHm、电子能Ee和水合能Eh),预测值及外部检验的复相关系数(R2)和标准偏差(SD)分别为0.9553、0.73722和0.9678、6.34426。结果表明,量子化学方法计算简单,对脂肪酸多聚甘油酯结构的表征能力较强,所建QSPR模型具有能较好的预测能力和较强的稳健性,并在一定程度上阐明了脂肪酸多聚甘油酯分子结构与性能之间的关系。     

QSPR study on GC relative retention time of organic pesticides on different chromatographic columns

In the present study, Lu index and distance-based atom type topological index (DAI) previously developed in our team, were introduced and combined with molecular electronegativity chi ep to characterize quantitative structure-property relationship of GC relative retention time (RRT) for several types of structurally diverse organic pesticides on the four kinds of chromatographic columns. Using multiple linear regression technique, four several-variable models are obtained with the estimations correlation coefficient (R(2)) being between 0.9655 and 0.9285, and the correlation coefficient (R(2)cv) in the leave-one-out cross-validation procedure are between 0.9560 and 0.9143, respectively. The results in this study indicate that the three topological indices Lu index, DAI, and molecular electronegativity chi ep can predict the gas chromatographic RRT of organic pesticides with diverse hetero-atoms.     

Am指数的扩展与手性化合物的构效关系研究

构效关系研究中的分子拓扑指数(Am)通常仅代表一个化合物的拓扑特征,所以预测手性化合物活性的能力较差.我们对Am指数进行了扩展,得到eAm指数,并将其应用于手性分子的结构-活性相关研究.结果表明,由手性拓扑指数得到的QSAR模型比传统的拓扑指数有更好的统计和预测手性化合物活性的能力.