EPR Identification of Zr(III) Complexes Formed upon Interaction of (2-PhInd)2ZrCl2 and rac-Me2Si(1-Ind)2ZrCl2 with MAO and MMAO

Reactions of 1 and 2 with MAO and MMAO were monitored by EPR. It was found that MMAO is a stronger reducing agent than MAO. 1 is more prone to reduction than 2 . The reduction of Zr^IV to Zr^III seems to be the essential pathway of some zirconocene catalysts' deactivation. Zr^III species with the following proposed structures can be identified in the 1 /MMAO system: (2-PhInd)₂Zr^III(ⁱBu), (2-PhInd)₂Zr^III(µ-Cl)₂AlⁱBu₂, (2-PhInd)₂Zr^III(µ-Cl)(ⁱBu)AlⁱBu₂, and [(2-PhInd)₂Zr^III]⁺[Me-MAO]⁻. The degree of reduction of Zr^IV species determined by EPR in the catalytic system 2 /MMAO can be masked by the formation of diamagnetic Zr^III/Zr^III dimers. Addition of monomers to the 2 /MAO system promotes reduction ot the zirconium species.

     

Activation of rac‐Me2Si(ind)2ZrCl2 by Methylalumoxane Modified by Aluminum Alkyls: An EPR Spin‐Probe, 1H NMR,and Polymerization Study

Summary: Solutions containing mixtures of methylalumoxane (MAO) and ⁱBu₃Al give rise to ¹H NMR signals indicative of the presence of the mixed alkyl aluminum dimers ⁱBu₂Al(µ‐Me)₂AlⁱBu₂ and of mixed clusters of the type (AlMe_{(1 + 2x ? y)}ⁱBu_yO_{(1 ? x)})_n. These mixed clusters, as well as related species present in solutions containing either MAO–Et₃Al or commercially available modified MAO (MMAO), appear to have stronger Lewis acidic sites and greater hydrodynamic radii than comparable clusters present in solutions of MAO alone, as judged from EPR signals observed in these solutions upon addition of TEMPO. When (SBI)ZrCl₂ (SBI = rac‐Me₂Si(ind)₂) is reacted with one of these mixed activator reagents, the mixed heterobinuclear cation [(SBI)Zr(µ‐Me)₂AlMeⁱBu]⁺ appears to be formed, together with its methyl counterpart [(SBI)Zr(µ‐Me)₂AlMe₂]⁺, which is normally predominant in the (SBI)ZrCl₂/MAO system at [Al]_MAO/[Zr] ratios above 100. In the presence of ⁱBu₃Al, the formation of heterobinuclear cations is suppressed in favor of ion pairs containing the cation [(SBI)ZrMe]⁺ in contact with a (MAO–TIBA)‐derived counter anion. The greater reactivity of these contact‐ion pairs, as compared to the normally prevalent AlMe₃ adducts, as well as an increased Lewis acidity of MMAO, and the ensuing decreased coordination ability of the [Me‐(MAO–TIBA)]^? counter ion as compared to [Me‐MAO]^?, are likely to contribute to the positive effects of TIBA additions on the co‐catalytic activity of MAO.

     

基于 C/S与B/S混合模式的重症肌无力管理系统的设计与研制

重症肌无力临床医生在就诊过程中收集了大量的临床资料,但是面对庞大而又杂乱的临床资料,人工对其进行管理、查询、统计分析等显然不可取,费时费力且更不用说从中“挖掘”出有用的信息以辅助诊断;此外,对于病人服药情况、疗效的随访等也难于开展,更不用说在医院各科室内部、Internet上共享临床资料。基于此,本文开发了以C/S和B/S混合模式的重症肌无力信息系统,以期为临床和科研做出一定的贡献。     

EPR analysis of the effects of accelerated carbon ion and fast neutron irradiations on table sugar

Table sugar samples were irradiated with accelerated carbon ions and fast neutrons. Electron paramagnetic resonance (EPR) analysis performed after the irradiation revealed a complex spectrum similar to that observed after γ-ray irradiations. The total concentration of the paramagnetic centers induced by accelerated carbon ions and neutrons was proportional to the absorbed dose. Good stability of the produced free radicals was observed for a typical period of sugar storage. Sugar was more sensitive to accelerated carbon ions than to neutrons. The results show that table sugar can be a useful material for dosimetry in the case of a radiation accident.     

Carbon blacks as EPR sensors for localized measurements of tissue oxygenation.

New electron paramagnetic resonance (EPR) oximetry probes were identified in the class of carbon black materials. These compounds exhibit very high oxygen sensitivity and favorable EPR characteristics for biological applications. At low pO(2), the linewidth is particularly sensitive to changes in oxygen tension (sensitivity of 750 mG/mmHg). The application of the probes for oximetry was demonstrated in vivo: the pO(2) was measured in muscle in which the blood flow was temporarily restricted as well as in tumor-bearing mice during a carbogen breathing challenge. The responsiveness to pO(2) was stable in muscle for at least 3 months. No toxicity was observed using these materials in cellular experiments and in histological studies performed 2, 7, and 28 days after implantation. In view of their EPR characteristics (high sensitivity) as well as the well-characterized production procedure that make them available on a large scale, these probes can be considered as very promising tools for future developments in EPR oximetry.     

eNOS T-786C polymorphism affects atorvastatin-induced changes in erythrocyte membrane fluidity

Purpose  Statins have pleiotropic effects, including endothelial nitric oxide synthase (eNOS) upregulation and increased nitric oxide formation, which can be modulated by a genetic polymorphism in the promoter region of the eNOS gene (T-786C). Here, we report our investigation of whether this polymorphism modulates the effects of atorvastatin on the fluidity of erythrocyte membranes. Methods  We genotyped 200 healthy subjects (males, 18–60 years of age) and then randomly selected 15 of these with the TT genotype and 15 with the CC genotype to receive placebo or atorvastatin (10 mg/day oral administration) for 14 days. Cell membrane fluidity was evaluated by electron paramagnetic resonance (EPR) and spin-labeling method. The EPR spectra were registered on a VARIAN-E4 spectrometer. Thiobarbituric acid-reactive species (TBA-RS) and plasma membrane cholesterol were determined in the erythrocytes. Results  Atorvastatin reduced membrane fluidity in CC subjects (P < 0.05) but not in those with the TT genotype (P > 0.05). While no significant differences were found in plasma membrane cholesterol concentrations, higher TBA-RS concentrations were found in the CC subjects than in the TT subjects (P < 0.05). Conclusions  These findings suggest that a short treatment with atorvastatin is disadvantageous to subjects with the CC genotype for the T-786C polymorphism compared to those with TT genotype, at least in terms of the hemorheological properties of erythrocytes.     

用于制作于EPR氧生物传感器的功能性有机材料的调查研究

纳米生物技术将纳米技术和生物技术相集成,是现代生物工程的重要组成部分.近年来,基于自然界原型的纳米生物材料、分子马达、芯片技术、纳米生物探针等纳米生物技术取得了迅速发展.本课题组参加Received date:Apr.3,2005了欧盟第六框架计划中的(NACBO)项目,它是建立在以前的研究基础之上,集中了各成员国在该研究领域的领先技术及顶尖专业技术人员,如纳米材料的自组装技术、纳米生物技术、多功能纳米生物材料研究的基础知识,纳米材料的包覆手段与材料、生物体与非生物体之间的界面研究等等.欧盟第六框架计划旨在集中各合作方在各领域的专家和先进技术,加入此框架的成员国的研究项目所取得的成果在各成员国之间具有通用性,可以相互使用,互通有无,使资源得到几乎完全应用.本课题组作为中国在纳米生物学领域唯一的参与者,具备得天独厚的研究条件,在对整个合作研究做出自己应尽的义务同时,还将利用其他成员国的研究成果,进一步开展研究,利国利民.本课题组主要在有机功能性材料的研究方面承担责任.EPR(Electronic Paramagnetic Resonance)氧生物医学传感器是一类具有在线检测能力的传感器,它是利用生物体组织的不同氧分压(或氧含量)来实施对异常组织、肿瘤组织的检测.近年来,EPR在生物体系中氧含量的测定中表现出独特性,提供了全时在线氧含量的测定,而且顺磁氧生物医学传感器因其使用成本较低,受到世界各国的关注.生命科学是EPR应用的一个较大的领域,几乎所涉及的生物体系都曾直接或间接的作过EPR测量,其中也包括生物医学和药物学方面的工作.目前使用的测氧材料多是无机材料,可供选择的种类有限.有机化合物的分子设计为这一领域提供了一个可供发展的极大空间--可以有目的的在所选母体化合物上引入所需的官能团,使之具有EPR信号,且具有氧敏性.将这些可选择的已在实际中应用的有机化合物作为母体,可以使材料的毒性降至最底限度;而且相对于无机材料的选择,有机化合物的合成具有很大的人为性与灵活性,也就是说,一旦得到合适的官能团,就可以有目的的合成众多的材料以供筛选.考虑到材料的应用方向,选择了一些在生物医学方面已经应用的有机功能性材料,如菁染料、卟啉及它们的相关化合物作为研究对象,开发其在生物医学领域的新应用.笔者在现有实验的基础上,利用自由基理论和单线态氧理论,设计并合成对氧敏感的顺磁新材料.进而完成对顺磁性新材料的表面处理及成膜研究,得到可应用的纳米EPR氧生物医学传感器.     

Hapten-induced changes in pig anti-dansyl antibodies revealed by EPR spectra of spin-labelled antibodies

Pig anti-Dns antibodies were labelled by 2, 2, 6, 6- tetramethyl-N1-oxylpiperidine-4-amino (N-dichlorotriazine) (label SL I) or by 4-amino-2,2,6,6-tetramethyl-piperidine-N1-oxyl (label SL II). SL I presumably reacted with Fab parts, whereas SL II was attached to the carbohydrate moiety of the Fc part of the antibody molecule. The new method of intramolecular mobility estimation based on viscosity-dependent correlation times of the N-O group of spin-labelled proteins was used, making it possible to separate the correlation times of the spin-label relative to the protein carrier (tauR) and of the labelled protein itself (tauM). The altered shape of the EPR spectrum observed upon binding of epsilon-Dns-lysine indicates that the relative fluctuations of the liganded antibody domains within the Fab part are reduced. The character of temperature dependence of the correlation times of the labelled antibody changed upon hapten binding as well, suggesting an altered interaction between antibody subunits. Evidence of hapten-induced changes of both tauR and tauM was obtained at 1 degrees C and 5 degree C using the label SL II bound to the Fc part. The character of the changes can be interpreted in terms of mobilization of the domains and of altered interaction between labelled carbohydrate and the protein moiety. At 5 degree C the addition of 3% of D2O to the antibody labelled by SL II brought about a substantial effect qualitatively similar to that induced by the hapten.     

High‐Temperature Propagation and Termination Kinetics of Styrene to High Conversion Investigated by Electron Paramagnetic Resonance Spectroscopy

Summary: The free radical bulk polymerization of styrene at 120 °C has been investigated over almost the entire conversion range using electron paramagnetic resonance spectroscopy, Fourier‐transform near‐infrared spectroscopy and gel permeation chromatography. The free radical concentration went through a sharp maximum that coincided with the peak in the rate of polymerization during the gel effect, and shifted to higher conversion with increasing initiator concentration. The termination rate coefficient (k_t), decoupled from the initiator efficiency (f) by use of the instantaneous degree of polymerization, remained close to constant up to as high as approximately 80% conversion, at which a dramatic decrease occurred. Both the propagation rate coefficient (k_p) and f fell orders of magnitude near 80% conversion in spite of the temperature being above the glass transition temperature of the system. The value of k_p increased with the initiator concentration at a given conversion in the highest (diffusion‐controlled) conversion range.

Termination rate coefficient (k_t) versus conversion for bulk free radical polymerization of St initiated by TBP at 120 °C. [TBP] = 0.15 (○), 0.10 (?) and 0.05 M ().     

Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin

NK911 is a novel supramolecular nanocarrier designed for the enhanced delivery of doxorubicin (DXR) and is one of the successful polymer micelle systems to exhibit an efficient accumulation in solid tumours in mice. The purpose of this study was to define the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of NK911 and to evaluate its pharmacokinetic profile in man. NK911 was given intravenously to patients with solid tumours every 3 weeks using an infusion pump at a rate of 10 mg DXR equivalent min(-1). The starting dose was 6 mg DXR equivalent m(-2), and the dose was escalated according to the accelerated titration method. A total of 23 patients participated in this study. Neutropenia was the predominant haematological toxicity, and grade 3 or 4 neutropenia was observed at doses of 50 and 67 mg m(-2). Common nonhaematological toxicities were mild alopecia, stomatitis, and anorexia. In the dose identification part of the study, DLTs were observed at a dose of 67 mg m(-2) (grade 4 neutropenia lasting more than 5 days). Thus, this dosage level was determined to be the MTD. Infusion-related reactions were not observed in any cases. The C(5 min) and area under the concentration curve parameters of NK911 exhibited dose-dependent characteristics. Among the 23 patients, a partial response was obtained in one patient with metastatic pancreatic cancer. NK911 was well tolerated and produced only moderate nausea and vomiting at myelosuppressive dosages. The recommended phase II dose was determined to be 50 mg m(-2) every 3 weeks.