热解吸反压低温等离子体电离源质谱检测食品中的邻苯二甲酸酯EI北大核心CSCD

基于低温等离子体设计并实现了一套热解吸反压低温等离子体电离(TD-iLTPI)装置。TD-iLTPI装置由热解吸模块和电离源模块集成在一个π型四通管上组成,进样探针取得样品后插入热解吸模块使其气化,之后随载气进入电离区域被电离。iLTPI内部的针电极接交流电,外部的环形电极接地,电极连接方式与LTP相反。该文对热解吸反压低温等离子体电离源进行了参数的优化,并与三重四极杆质谱联用检测了12种代表性的邻苯二甲酸酯,同时考察了TD-iLTPI-MS的分析性能,并对含有邻苯二甲酸酯的实际样品进行了检测。结果表明,邻苯二甲酸丁苄酯(BBP)的标准曲线具有良好的线性相关系数(R;=0.9958),加标回收率为89.7%~116.8%,相对标准偏差为4.5%~8.2%,对邻苯二甲酸酯的检出限也远低于其他敞开式离子源。对白酒、果汁、面包、奶酪和黄油中的邻苯二甲酸酯进行了快速筛查,并定量检测了果汁中的邻苯二甲酸丁苄酯。     

基于内聚力模型的快速荷载下CFRP-混凝土界面剪切剥离模拟

鉴于纤维增强复合材料(Fiber Reinforced Polymer, FRP)已在混凝土结构加固中普遍应用, 能有效提高结构的承载和变形能力. 为揭示动载作用下FRP-混凝土界面的剥离机理, 本文基于ABAQUS平台, 采用内聚力模型模拟CFRP-混凝土界面层, 实现了快速荷载下CFRP-混凝土界面剥离的高效模拟. 结果表明: CFRP表面应变在加载过程中由加载端向自由端方向传递, 随着加载速率的提高, 界面承载能力也随之提高; 界面峰值剪应力也存在显著的应变率效应; 模拟结果与试验结果基本吻合, 说明了新方法的有效性.     

Similar,or dissimilar,that is the question. How different are methods for comparison of compounds similarity?

Comparison of compounds similarity is one of the main strategies of virtual screening protocols. Both similarity and dissimilarity concepts are of great importance during the search for new active compounds. Similarity is important due to the assumption that underlies the process of searching for new drug candidates: structurally similar compounds should induce similar biological response. On the other hand, we are also interested in dissimilarity, as we usually aim to find structurally novel ligands. In the study, we compared several approaches of evaluating compound similarity. Various representations and metrics were applied and we indicated the rate of variation of the results that can occur when shifting from one strategy to another. We compared both general similarity of datasets using different approaches, as well as examined the changes in the set of nearest neighbors when changing one compound representation into another, and the influence of representation/metric settings on the clustering outcome. We hope that the study will be of great help during the preparation of virtual screening experiments, stressing the need for careful selection of the way, the compound similarity is assessed. The differences in the results that can be obtained via the application of particular strategy can significantly influence the outcome of comparison studies; therefore, its settings should be carefully selected beforerunning the comparison.     

Synthesis,characterization, and biological screening of metal complexes of novel sulfonamide derivatives: Experimental and theoretical analysis of sulfonamide crystal

This study reports the synthesis of sulfonamide-derived Schiff bases as ligands L ¹ and L ² as well as their transition metal complexes [VO(IV), Fe(II), Co(II), Ni(II), Cu(II), and Zn(II)]. The Schiff bases (4-{E-[(2-hydroxy-3-methoxyphenyl)methylidene]amino}benzene-1-sulfonamide ( L ¹ ) and 4-{[(2-hydroxy-3-methoxyphenyl)methylidene]amino}-N-(5-methyl-1,2-oxazol-3-yl)benzene-1-sulfonamide ( L ² ) were synthesized by the condensation reaction of 4-aminobenzene-1-sulfonamide and 4-amino-N-(3-methyl-2,3-dihydro-1,2-oxazol-5-yl)benzene-1-sulfonamide with 2-hydroxy-3-methoxybenzaldehyde in an equimolar ratio. Sulfonamide core ligands behaved as bidentate ligands and coordinated with transition metals via nitrogen of azomethine and the oxygen of the hydroxyl group. Ligand L ¹ was recovered in its crystalline form and was analyzed by single-crystal X-ray diffraction technique which held monoclinic crystal system with space group (P2₁/c). The structures of the ligands L ¹ and L ² and their transition metal complexes were established by their physical (melting point, color, yields, solubility, magnetic susceptibility, and conductance measurements), spectral (UV–visible [UV–Vis], Fourier transform infrared spectroscopy, ¹H NMR, ¹³C NMR, and mass analysis), and analytical (CHN analysis) techniques. Furthermore, computational analysis (vibrational bands, frontier molecular orbitals (FMOs), and natural bonding orbitals [NBOs]) were performed for ligands through density functional theory utilizing B3LYP/6-311+G(d,p) level and UV–Vis analysis was carried out by time-dependent density functional theory. Theoretical spectroscopic data were in line with the experimental spectroscopic data. NBO analysis confirmed the extraordinary stability of the ligands in their conjugative interactions. Global reactivity parameters computed from the FMO energies indicated the ligands were bioactive by nature. These procedures ensured the charge transfer phenomenon for the ligands and reasonable relevance was established with experimental results. The synthesized compounds were screened for antimicrobial activities against bacterial (Streptococcus aureus, Bacillus subtilis, Eshcheria coli, and Klebsiella pneomoniae) species and fungal (Aspergillus niger and Aspergillus flavous) strains. A further assay was designed for screening of their antioxidant activities (2,2-diphenyl-1-picrylhydrazine radical scavenging activity, total phenolic contents, and total iron reducing power) and enzyme inhibition properties (amylase, protease, acetylcholinesterase, and butyrylcholinesterase). The substantial results of these activities proved the ligands and their transition metal complexes to be bioactive in their nature.     

Computational Design of Novel Allosteric Inhibitors for Plasmodium falciparum DegP

The serine protease, DegP exhibits proteolytic and chaperone activities, essential for cellular protein quality control and normal cell development in eukaryotes. The P. falciparum DegP is essential for the parasite survival and required to combat the oscillating thermal stress conditions during the infection, protein quality checks and protein homeostasis in the extra-cytoplasmic compartments, thereby establishing it as a potential target for drug development against malaria. Previous studies have shown that diisopropyl fluorophosphate (DFP) and the peptide SPMFKGV inhibit E. coli DegP protease activity. To identify novel potential inhibitors specific to PfDegP allosteric and the catalytic binding sites, we performed a high throughput in silico screening using Malaria Box, Pathogen Box, Maybridge library, ChEMBL library and the library of FDA approved compounds. The screening helped identify five best binders that showed high affinity to PfDegP allosteric (T0873, T2823, T2801, {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, CD00811) and the catalytic binding site (T0078L, T1524, T2328, BTB11534 and 552691). Further, molecular dynamics simulation analysis revealed {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, BTB11534 as the best hits forming a stable complex. WaterMap and electrostatic complementarity were used to evaluate the novel bio-isosteric chemotypes of {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, that led to the identification of 231 chemotypes that exhibited better binding affinity. Further analysis of the top 5 chemotypes, based on better binding affinity, revealed that the addition of electron donors like nitrogen and sulphur to the side chains of butanoate group are more favoured than the backbone of butanoate group. In a nutshell, the present study helps identify novel, potent and Plasmodium specific inhibitors, using high throughput in silico screening and bio-isosteric replacement, which may be experimentally validated.     

基于结构虚拟筛选发现蛋白质精氨酸甲基转移酶5抑制剂

蛋白质精氨酸甲基转移酶5(PRMT5)是蛋白质甲基转移酶家族(PRMTs)的重要一员,其主要生理功能是催化精氨酸单对称二甲基化。PRMT5的上调发生在不同类型的肿瘤中,并与不良预后密切相关,已被视为肿瘤治疗中的潜在靶点。近年来,已有多种PRMT5抑制剂进入临床试验,但目前尚未有药物获批上市。本研究基于Glide对接的虚拟筛选和生物活性实验,发现化合物8018-1271对PRMT5酶的抑制活性IC₅₀值为13.56±0.86μmol/L,并通过分子动力学揭示其与PRMT5蛋白结构域的相互作用模式。本研究所得化合物8018-1271可作为进一步改造的先导化合物,为新型PRMT5抑制剂的发现提供参考。     

The use of proton transfer reaction mass spectrometry for high throughput screening of terpene synthases

In this work, we introduce the application of proton transfer reaction mass spectrometry (PTR-MS) for the selection of improved terpene synthase mutants. In comparison with gas chromatography mass spectrometry (GC-MS)-based methods, PTR-MS could offer advantages by reduction of sample preparation steps and analysis time. The method we propose here allows for minimal sample preparation and analysis time and provides a promising platform for the high throughput screening (HTS) of large enzyme mutant libraries. To investigate the feasibility of a PTR-MS-based screening method, we employed a small library of Callitropsis nootkatensis valencene synthase (CnVS) mutants. Bacterial cultures expressing enzyme mutants were subjected to different growth formats, and headspace terpenes concentrations measured by PTR-Qi-ToF-MS were compared with GC-MS, to rank the activity of the enzyme mutants. For all cultivation formats, including 96 deep well plates, PTR-Qi-ToF-MS resulted in the same ranking of the enzyme variants, compared with the canonical format using 100 mL flasks and GC-MS analysis. This study provides a first basis for the application of rapid PTR-Qi-ToF-MS detection, in combination with multi-well formats, in HTS screening methods for the selection of highly productive terpene synthases.     

Functional Peptides from One-bead One-compound High-throughput Screening Technique

Combinatorial chemistry provides a cost-effective method for the rapid discovery of new functional peptides. One-bead one-compound(OBOC) high-throughput screening technique offers a lot of structurally diverse peptides to be rapidly synthesized and screened for binding to a target of interest. The OBOC peptide library screening involves three main steps: library construction, positive beads separation, and peptide sequencing. This review mainly summarizes some special technique tips during functional peptide screening and potential future directions of the OBOC high-throughput screening technique.     

An integrated strategy for the geographical origin traceability of Goji berries by antioxidants characteristic fingerprint based online ultra-performance liquid chromatography-2,2-diphenyl-1-picrylhydrazyl- photodiode array detector-mass spectrometry combined with multivariate statistics analysis

Goji berries are now becoming increasingly popular in the human diet due to their potential health benefits. Unscrupulous traders deliberately mislabel with certain origins to gain illegal profits, which seriously affected the consumers’ benefits. In this study, an online ultra-performance liquid chromatography-2,2-diphenyl-1 -picrylhydrazyl-photodiode array detector-electrospray ionization-quadrupole time of flight mass was developed for rapid screening and identification of the antioxidants from Goji berry; then, the antioxidants characteristic fingerprint was established and explored in the origins discrimination of Goji berries from China combined with multivariate statistics analysis. As a result, twenty-eight compounds were screened from Goji berry extract, 19 of which were identified by accurate molecular and ultraviolet information according to references. Principal components analysis and partial least squares discrimination analysis achieved the accurate classification from the four regions, eight compounds were selected as origin-related antioxidant markers with variable importance in projection >1 and one-way analysis of variance (P<0.05), including rutin, rutin di-hexose, P-coumaric acid tri-hexose, dicaffeoylquinic acid isomer, Quercetin-rhamno-di-hexoside, peak14, peak16, and peak27. This study provides a feasible strategy for the geographical origins discrimination of Goji berries based on antioxidant ingredients difference and will be helpful for improving the quality control level of Goji berries.