Identification of urinary metabolites of imperatorin with a single run on an LC/Triple TOF system based on multiple mass defect filter data acquisition and multiple data mining techniques

The detection of drug metabolites, especially for minor metabolites, continues to be a challenge because of the complexity of biological samples. Imperatorin (IMP) is an active natural furocoumarin component originating from many traditional Chinese herbal medicines and is expected to be pursued as a new vasorelaxant agent. In the present study, a generic and efficient approach was developed for the in vivo screening and identification of IMP metabolites using liquid chromatography-Triple TOF mass spectrometry. In this approach, a novel on-line data acquisition method mutiple mass defect filter (MMDF) combined with dynamic background subtraction was developed to trace all probable urinary metabolites of IMP. Comparing with the traditionally intensity-dependent data acquisition method, MMDF method could give the information of low-level metabolites masked by background noise and endogenous components. Thus, the minor metabolites in complex biological matrices could be detected. Then, the sensitive and specific multiple data-mining techniques extracted ion chromatography, mass defect filter, product ion filter, and neutral loss filter were used for the discovery of IMP metabolites. Based on the proposed strategy, 44 phase I and 7 phase II metabolites were identified in rat urine after oral administration of IMP. The results indicated that oxidization was the main metabolic pathway and that different oxidized substituent positions had a significant influence on the fragmentation of the metabolites. Two types of characteristic ions at m/z 203 and 219 can be observed in the MS/MS spectra. This is the first study of IMP metabolism in vivo. The interpretation of the MS/MS spectra of these metabolites and the proposed metabolite pathway provide essential data for further pharmacological studies of other linear-type furocoumarins.     

One-Pot Synthesis of Cefpirome Sulfate from GCLE

Abstract

Cefpirome was synthesized in 37.7% overall yield from 3-chloromethyl-7-phenylacetylamino cephalosporanic acid p-methoxybenzyl ester (GCLE) by sequential substitution of C-3 chloride with iodide and 2,3-cyclopentenopyridine, followed by a one-pot procedure including deprotection of carboxyl group, hydrolysis of 7-phenylacetamido, and reaction with 2-mercaptobenzothiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetate (MAEM). The reaction conditions were as follows: obtained from GCLE at low temperature (?5 to 0 °C) and absence of light, 3-iodomethyl-7-phenylacetylamino cephalosporanic acid p-methoxybenzyl ester (GILE) without purification was reacted directly with 2,3-cyclopentenopyridine, in which the molar ratio of GCLE, NaI, and 2,3-cyclopentenopyridine was 1:2:4, and the molar ratio of the resulting compound p-methoxybenzyl 7-phenylacetylamido-3-(2,3-cyclopenteno-1-pyridinio)methyl-3-cephem-4-carboxylate iodide and MAEM was 1:1.1. The structure of the intermediate and the target compound obtained were determined by nuclear magnetic resonance spectra and mass spectroscopy.     

A new intraparticle mass transfer rate model for cyclic adsorption and desorption in a slab, cylinder or sphere

A new intraparticle mass transfer rate model for cyclic adsorption and desorption in a slab, cylinder or sphere is proposed on the basis of the asymptotic behaviors of the adsorption rate for short and long cycle periods. Through comparison with the exact solution and the linear driving force (LDF) model, the new model is shown to provide a very good approximation for the instantaneous amount adsorbed as well as the adsorption rate for dimensionless half-cycle period τ _c =0.001～1 and is much better than the LDF model.     

新一代运载火箭时序仿真系统信号完整性分析

新一代运载火箭时序仿真系统具有数字电路速度快、集成度高的特点,系统要求发出多路高精度时序、时串信号以满足新一代运载火箭地面测试设备的检查与校准需求,因此信号完整性问题在系统设计中不容忽视。针对仿真系统的典型模块(USB 3.0 Super-speed差分线、FPGA外设数据走线、时钟走线)进行建模分析仿真得出PCB硬件电路设计参数,给出时序仿真系统设计信号完整性问题的抑制和解决方法,优化了板级信号质量,改善系统可靠性、工作连续性和输出精度,可有效提高新一代运载火箭测试效率和测试可靠性。     

Phosphine-mediated synthesis of trifluoromethyl substituted pyrroles using TFAA as the CF3 source

A phosphine-mediated synthesis of trifluoromethyl substituted pyrrole derivatives was achieved. The method described here is very fast, operationally simple, and easily amenable to scale-up, and commercially available trifluoroacetic anhydride (TFAA) is used as the only trifluoromethyl source. A wide range of products were obtained with good yields under mild condition using this method.     

Transformations of iodine species inside elliptical channels of AlPO4‐11 crystals at low temperature: a Raman study

Raman spectra of iodine species confined in one‐dimensional elliptical channels of AlPO₄‐11 (AEL) crystals have been studied from room temperature down to −196 °C. As temperature decreases, thermal fluctuations of individual iodine molecules confined in AEL channels are slowed down and they prefer to rotate to channel axis direction, which increases the population of iodine molecules along channel axis (i.e., lying molecules and chains). Such temperature‐driven orientation transformation of iodine molecules is found to be reversible upon heating up to room temperature. The experimental observations are in good agreement with our theoretical simulations by molecular dynamics on low density iodine‐filled AEL crystals. We thus provide a new way to modulate the orientation of iodine molecules in nanochannels, which may have implications in low‐temperature‐sensitive nanoscale devices. Copyright © 2015 John Wiley & Sons, Ltd.     

Characterization and properties of plywood bioadhesive derived from cottonseed protein and sawdust cellulose

Cellulose - The development of plant adhesive with good bonding strength, water resistance and thermal stability remains challenging to replace formaldehyde-based adhesive resins that usually...     

Advances in nucleic acid architectures for electrochemical sensing

Nucleic acid–based electrochemical sensors are ideally suited to the detection of molecular targets for which enzymatic detection or direct electrochemical oxidation – reduction reactions are not possible. Moreover, the versatility of nucleic acids in their ability to bind a great variety of target types, from small molecules to single-entity mesoscopic targets, makes them attractive receptors for the development of electrochemical biosensors. In this brief opinion piece, we discuss field advances from the past two years. We hope the works highlighted here will inspire the community to pursue creative designs enabling the detection of larger and more complex targets with a specific focus on analytical validation and translation into preclinical or clinical applications.     

Phase‐Junction Electrocatalysts towards Enhanced Hydrogen Evolution Reaction in Alkaline Media

To ensure sustainable hydrogen production by water electrolysis, robust, earth‐abundant, and high‐efficient electrocatalysts are required. Constructing a hybrid system could lead to further improvement in electrocatalytic activity. Interface engineering in composite catalysts is thus critical to determine the performance, and the phase‐junction interface should improve the catalytic activity. Here, we show that nickel diphosphide phase junction (c‐NiP₂/m‐NiP₂) is an effective electrocatalyst for hydrogen production in alkaline media. The overpotential (at 10 mA cm^?2) for NiP₂‐650 (c/m) in alkaline media could be significantly reduced by 26 % and 96 % compared with c‐NiP₂ and m‐NiP₂, respectively. The enhancement of catalytic activity should be attributed to the strong water dissociation ability and the rearrangement of electrons around the phase junction, which markedly improved the Volmer step and benefited the reduction process of adsorbed protons.