新型离子液体基质用于MALDI-MS高效离子化寡糖/糖肽

本研究发展了四种基于三羟基苯乙酮(THAP)的新型离子液体基质, 即2',3',4'-THAP/二甲基苯胺(DMA)、2',4',6'-THAP/DMA、2',3',4'-THAP/吡啶(Py)及2',4',6'-THAP/Py, 用于提高寡糖/糖肽在MALDI-TOF MS中的离子化效率. 与传统的固体基质2,5-二羟基苯甲酸(DHB)和2',4',6'-三羟基苯乙酮(2',4',6'-THAP)相比, 新型离子液体体系分析不同类型的寡糖链, 均可获得更高的检测灵敏度. 可使葡聚糖(dextran 1000)和环状寡聚糖β-环糊精在MALDI质谱中的信噪比提高10倍以上, RNase B的复杂寡糖链也实现了高灵敏度的检测. 在糖肽分析中, 2',3',4'-THAP/DMA离子液体高灵敏度地检测到辣根过氧化酶的7条糖肽, 而2',3',4'-THAP作为基质时却无法检测到任何信号.     

New Lignans from the Aerial Parts of Rudbeckia laciniata

Three new furofuran lignans, (+)‐4,4′‐O‐diangeloylpinoresinol ( 1 ), (+)‐4,4′‐O‐diangeloylmedioresinol ( 2 ), and (+)‐4,4′‐O‐diangeloylsyringaresinol ( 3 ), together with the known compound (+)‐syringaresinol, were isolated from the MeOH extract of Rudbeckia laciniata. The structure elucidation of these compounds were based on 1D‐ and 2D‐NMR, and HR‐ESI‐MS data. The additional structural evidence was obtained from alkaline hydrolysis of the compounds.     

TargetATPsite: A template‐free method for ATP‐binding sites prediction with residue evolution image sparse representation and classifier ensemble

Understanding the interactions between proteins and ligands is critical for protein function annotations and drug discovery. We report a new sequence‐based template‐free predictor (TargetATPsite) to identify the Adenosine‐5′‐triphosphate (ATP) binding sites with machine‐learning approaches. Two steps are implemented in TargetATPsite: binding residues and pockets predictions, respectively. To predict the binding residues, a novel image sparse representation technique is proposed to encode residue evolution information treated as the input features. An ensemble classifier constructed based on support vector machines (SVM) from multiple random under‐samplings is used as the prediction model, which is effective for dealing with imbalance phenomenon between the positive and negative training samples. Compared with the existing ATP‐specific sequence‐based predictors, TargetATPsite is featured by the second step of possessing the capability of further identifying the binding pockets from the predicted binding residues through a spatial clustering algorithm. Experimental results on three benchmark datasets demonstrate the efficacy of TargetATPsite. © 2013 Wiley Periodicals, Inc.     

Sensitive Determination of 2‐Methoxyestradiol in Pharmaceutical Preparations and Biological Fluids by KMnO4‐Na2SO3 Chemiluminescence System

A simple and novel flow‐injection chemiluminescence (FI‐CL) method was established for the determination of 2‐Methoxyestradiol (2‐ME) in pharmaceutical preparations and biological fluids. The method was based on the significant enhancement of the CL from the KMnO₄‐Na₂SO₃ reaction by 2‐ME in acidic medium. Under optimized conditions, the CL intensity was correlated linearly with concentration of 2‐ME in the range of 5.0 × 10^?8‐5.0 × 10^?6 M (r = 0.9995). The detection limit (3σ) of 2‐ME was 7.5 × 10^?9 M and the relative standard deviation was 0.8% at 5.0 × 10^?7 M 2‐ME (n = 8). The proposed method was successfully applied for the flow‐injection CL determination of 2‐ME in pharmaceutical preparations and biological fluids with the recoveries from 92.4 to 106.8%. The possible CL reaction mechanism was also discussed briefly.     

Determination of docetaxel in rat plasma and its application in the comparative pharmacokinetics of Taxotere and SID530, a novel docetaxel formulation with hydroxypropyl‐β‐cyclodextrin

In this study, a sensitive, simple and reliable method for the quantification of docetaxel in rat plasma was developed and validated using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). The plasma samples were prepared by protein precipitation, and paclitaxel was used as an internal standard (IS). Chromatographic separation was achieved using a Gemini C₁₈ column (2.0 × 150 mm, 5 µm) with a mobile phase consisting of 0.1% formic acid–acetonitrile (30:70, v/v). The precursor–product ion pairs used for multiple reaction monitoring were m/z 808.5 → 527.5 (docetaxel) and m/z 854.2 → 286.5 (IS, paclitaxel). A calibration curve for docetaxel was constructed over the range 1–1000 ng/mL. The developed method was specific, precise and accurate, and no matrix effect was observed. The validated method was applied in a comparative pharmacokinetic study in which two docetaxel formulations, SID530, a new parenteral formulation of docetaxel with hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD), and Taxotere, were administered to rats at a dose of 5 mg/kg. For SID530 and Taxotere, the mean C₀ values were 1494 and 1818 ng/mL, respectively, and the AUC_last values were 837 and 755 h ng/mL, respectively. These two formulations did not show any statistical differences with regard to the pharmacokinetic parameters, thus establishing that the SID530 and Taxotere products are pharmacokinetically comparable in male rats. Copyright © 2012 John Wiley & Sons, Ltd.     

Determination of PF‐04620110, a novel inhibitor of diacylglycerol acyltransferase‐1, in rat plasma using liquid chromatography–tandem mass spectrometry and its application in pharmacokinetic studies

In this study, we developed a method for the determination of PF‐04620110 (2‐{(1r,4r)‐4‐[4‐(4‐amino‐5‐oxo‐7,8‐dihydropyrimido[5,4‐f][1,4]oxazepin‐6(5H)‐yl)phenyl]cyclohexyl}acetic acid), a novel diacylglycerol acyltransferase 1 (DGAT‐1) inhibitor, in rat plasma and validated it using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Rat plasma samples were processed following a protein precipitation method by using acetonitrile and were then injected into an LC‐MS/MS system for quantification. PF‐04620110 and imipramine (internal standard) were separated using a Hypersil Gold C₁₈ column, with a mixture of acetonitrile and 10 mm ammonium formate (90:10, v/v) as the mobile phase. The ion transitions monitored in positive‐ion mode [M + H]⁺ of multiple‐reaction monitoring were m/z 397.0 → 260.2 for PF‐04620110 and m/z 280.8 → 86.0 for imipramine. The detector response was specific and linear for PF‐04620110 at concentrations within the range 0.05–50 µg/mL and the signal‐to‐noise ratios for the samples were ≥10. The intra‐ and inter‐day precision and accuracy of the method matched the acceptance criteria for assay validation. PF‐04620110 was stable under various processing and/or handling conditions. PF‐04620110 concentrations in the rat plasma samples could be measured up to 24 h after intravenous or oral administration of PF‐04620110, suggesting that the assay is useful for pharmacokinetic studies in rats. Copyright © 2013 John Wiley & Sons, Ltd.     

Cleaved Iron Oxide Nanoparticles as T2 Contrast Agents for Magnetic Resonance Imaging

Iron oxide nanoparticles as contrast agents are reported to effectively improve magnetic resonance imaging of tissues and cells. In this work, cleaved iron oxide nanoparticles (CIONPs) were generated from hydrophobic FeO nanoparticles (HIONPs) by coating their surfaces with PEG‐phospholipids, oxidizing them under water, and slowly removing the residual FeO phase in phthalate buffer. The synthesized CIONPs showed good r₂ values of up to 258 s^?1 mM ^?1. Thus, the CIONPs can be employed as vectors for drug delivery due to their unique structure with an empty inner space, which enables their use in a wide range of applications.     

Solvatochromic Behavior of Chiral Mesoporous Metal–Organic Frameworks and Their Applications for Sensing Small Molecules and Separating Cationic Dyes

Two anionic metal–organic frameworks (MOFs) with 1D mesoporous tubes ( 1 ) and chiral mesoporous cages ( 2 ) have been rationally constructed by means of a predesigned size‐extended hexatopic ligand, namely, 5,5′,5′′‐(1,3,5‐triazine‐2,4,6‐triyl)tris‐ (azanediyl)triisophthalate (TATAT). Charge neutrality is achieved by protonated dimethylamine cations. Notably, the two MOFs can be used to separate large molecules based on ionic selectivity rather than the size‐exclusion effect so far reported in the literature. Owing to the imino triazine backbone and carboxyl groups of the hexatopic ligand, which provide important host–guest interactions, rare solvatochromic phenomena of 1 and 2 are observed on incorporating acetone and ethanol guests. Furthermore, guest‐dependent luminescence properties of compound 2 were investigated, and the results show that luminescence intensity is significantly enhanced in toluene and benzene, while quenching effects are observed in acetone and ethanol. Thus, compound 2 may be a potential material for luminescent probes.     

Significant change in water contact angle of electrospray‐synthesized SiO2 films depending on their surface morphology

Amorphous SiO₂ films were deposited by means of an electrospray technique. The relation between the water contact angle (WCA) of the deposited SiO₂ films and the surface morphology is investigated. The feeding rate of the electrospray process greatly affects the morphology of the synthesized SiO₂ films. There is also a significant change in the WCA on the surface of the films: the rougher the surface, the greater the WCA. A model based on the Cassie–Baxter formulation is used to explain the change observed in the WCA on the SiO₂ films. Copyright © 2012 John Wiley & Sons, Ltd.