Development and validation of a rapid method for the detection of latrunculol A in plasma

Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than latrunculin A against both murine and human colon tumor cell lines in vitro. Currently, there are no reports regarding the bioavailability of latrunculol A in vivo. This study was undertaken as a prelude to pharmacokinetic assessments and it is the first work where bioavailability of latrunculol A was studied. In the present work, a simple plasma preparation and a rapid HPLC method have been developed. Mouse plasma containing latrunculol A was first treated by acetonitrile and then centrifuged at 14,000 rpm at 4 °C for 25 min. The supernatant was injected in an HPLC system comprising a Waters Symmetry NH₂ column, a mobile phase of acetonitrile/water (95/5, v/v), a flow rate of 1.0 mL/min, at 220 nm. The method was validated by parameters including a good linear correlation, a limit of quantification of 9 ng/mL, and a good precision with a coefficient variation of 1.65, 1.86, and 1.26% for 20, 400, and 800 ng/mL, respectively. With this simple method, excellent separation and sensitivity of latrunculol A are achieved, thus allowing a rapid analysis of the plasma samples for absorption, distribution, and metabolism studies.     

Total synthesis and biological evaluation of +-kalkitoxin, a cytotoxic metabolite of the cyanobacterium Lyngbya majuscula

+-Kalkitoxin, a metabolite of the marine cyanobacterium Lyngbya majuscula, was synthesized from (R)-2-methylbutyric acid, (R)-cysteine, and (3S, 4S, 6S)-3,4,6-trimethyl-8-(methylamino)octanoic acid. A key step in the synthesis was installation of the anti,anti methyl stereotriad by means of a tandem asymmetric conjugate addition of an organocopper species to an alpha,beta-unsaturated N-acyl oxazolidin-2-one followed in situ by alpha-methylation of the resultant enolate. The thiazoline portion of kalkitoxin was assembled by titanium tetrachloride catalyzed cyclization of a vinyl substituted amido thiol.     

Discriminating varieties

In this paper we determine those locally finite varieties that generate decidable discriminator varieties when augmented by a ternary discriminator term.Dedicated to Bjarni Jonsson on the occasion of his 70th birthdayPresented by G. McNulty.The first author gratefully acknowledges the support of NSERC.     

用纵横波声时比法测螺栓轴力精度研究

用纵横波测量螺栓轴力的技术已取得较大发展,本文介绍了纵横波比值法原理,通过理论推导,获得比值法计算的简易公式。建立试验平台,用现场用螺栓进行标定和测量,得出比值法在工程实践状态下的测量误差为10%以内,基本能满足工程应用的要求。此外,针对试验结果,本文还初步探讨了误差出现的原因以及提高精度的方法。本文介绍的比值法,无需精确测量标定螺栓长度和纵横波声速,现场应用更加简洁,具有较大的工程应用价值。     

The unexpected isolation of CTP-431, a novel thiopyrone from the sponge Cacospongia mycofijiensis

A reinvestigation of a Fijian collection of Cacospongia mycofijiensis has yielded the known mycothiazole and a novel heterocyclic, CTP-431 (1). Its structure including absolute configuration as 8R,9R,10S,13S was established using NMR data, calculated DFT (13)C chemical shifts and results from X-ray crystallography. It is possible that the tricyclic skeleton of CTP-431 (1) is biosynthetically related to the macrolide latrunculin A, however the thiopyrone moiety of 1 has no previous precedent in natural products chemistry.     

A Dual Read-out Molecularly Imprinted Composite Membrane Sensor Based on Zinc Porphyrin for the Detection of Dimethyl Methylphosphonate

Molecularly imprinted membrane-zinc porphyrin-mathacrylate(MIM-Zn-MAA), a dual read-out sensor based on a molecularly imprinted membrane, was developed to recognize and detect dimethyl methylphosphonate (DMMP) as an intermediate molecule of organophosphorus pesticides. The membranes were prepared via thermal polymerization of two functional monomers(zinc porphyrin and mathacrylate) on the surface of a glass slide functionalized with ethylene glycol dimethacrylate and azobisisobutyronitrile. The morphology of the as-synthesized MIM-Zn-MAA was determined with scanning electronic microscopy. The composite membranes exhibited macrovoid morphologies, which were affected by the functional monomers. These membranes were selectively adsorbed onto the template molecule and displayed higher adsorbing capacity toward DMMP compared with their structural analogs. Changes in the fluorescent spectra were qualitatively and quantitatively monitored via fluorescence photometry. Difference maps were also obtained using colorimetry before and after the reaction between MIM-Zn-MAA and DMMP at various concentrations. The maps showed a wide linear range varying from 0.1 μmol/L to 10 mmol/L with a low detection limit of 0.1 μmol/L. These preliminary results demonstrate that the as-fabricated dual read-out sensor displays good sensitivity and selectivity toward DMMP, indicating its considerable potential in DMMP detection in practical applications.     

基于液体阵列味觉仿生传感器鉴别白酒香型的新方法

通过模拟哺乳动物的味觉系统, 建立了交叉响应的液体阵列传感器, 为鉴别白酒香型提供了新方法. 选用7种染料和1种卟啉化合物作为传感单元, 构建液体阵列传感器, 集合8个传感单元的光谱响应信号构成分析物的指纹图谱, 达到识别的目的. 使用96孔板酶标仪采集响应数据, 结合主成分分析(PCA)、分层聚类分析(HCA)和判别分析(LDA)等模式识别方法进行数据处理, 对9种具有代表性的不同香型白酒样品进行了鉴别分析. PCA结果表明, 该方法对于白酒的检测主要基于酒体微量成分, 其中酸类物质对识别的贡献最大(贡献率达54.3%), 芳香类物质贡献率为18.6%; 同时, 仅用63.4%的数据信息量即可对白酒香型进行区分. HCA结果表明, 平行样均正确归类, 各白酒之间的相似程度在聚类图上得到体现. LDA结果表明, 该阵列对于9种白酒样品香型识别的准确率达到100%.     

Fluorescence and Thermostability of Nanometer Porphyrin Trimer

IntroductionPorphyrin possesses some unique properties.Incomparison with the porphyrin monomer,porphyrin oli-gomers are much attracting owing to their much betterproperties in some aspects,such as light harvest,ener-gy transformation and electron transiti…