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Development of drug electrodes with high sensitivity and selectivity

高灵敏度、高选择性药物电极的研制

基本信息

批准号：
10672019
负责人：
KATSU Takashi
金额：
$ 2.24万
依托单位：
OKAYAMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

The development and application of ion-selective electrodes continue to be an area of focus. In this study, special attention was paid to develop organic ammonium ion-selective membrane electrodes, because there are many drugs having the amino group in their molecules. First, we constructed biogenic amine-sensitive membrane electrode using the combinations of appropriate solvent mediators and a lipophilic ion-exchanger, sodium tetrakis [3,5-bis (2-methoxyhexafluoro-2-propyl) phenyl] borate. It was found solvent mediators, such as thiophosphate esters with a P=S group, generally strengthened response to organic ammonium ions including histamine, and markedly suppressed responses to inorganic cations, such as Na^+ and K^+, suggesting that hydrogen bonding between the NH_3^+ group of organic ammonium ions and the negatively polarized sulfur atom in the P=S group would enhance such responses. We applied the histamine electrode constructed using prothiofos, one of the compounds containing a … More P=S group, to determine histamine release from mast cells. The histamine concentrations determined agreed well with those determined by an established fluorimetric assay.Second, we constructed a triethylammonium-sensitive membrane electrode using sodium tetrakis [3,5-bis (2-methoxyhexafluoro-2-propyl) phenyl] borate as an ion-exchanger and benzyl 2-nitrophenyl ether as a solvent mediator and applied it for the determination of the pH difference across a cell membrane. The method is based on monitoring of the pH gradient-induced uptake of triethylammonium in situ. In experiments using liposomes, the uptake of triethylammonium into liposomes was quantitatively induced according to the pH difference across the liposomal membrane. The transmembrane pH difference in Escherichia coli cells and the light-induced formation of the pH difference across the envelop vesicles of Halobacterium halobium were successfully determined by the present method.We described here only two results. Other results can be seen through references described in the back of this report. Less

离子选择性电极的开发和应用仍然是一个焦点领域。由于许多药物分子中含有氨基，因此本研究特别关注有机铵离子选择性膜电极的研制。首先，我们使用适当的溶剂介体和亲脂性离子交换剂四[3，5-二（2-甲氧基六氟-2-丙基）苯基]硼酸钠的组合构建了生物胺敏感膜电极。结果表明，溶剂介质如含P=S基团的硫代磷酸酯一般能增强对有机铵离子（包括组胺）的反应，而对无机阳离子（如Na^+和K^+）的反应则有明显的抑制作用，这表明有机铵离子的NH_3^+基团与P=S基团中负极性的硫原子之间的氢键作用能增强这种反应。我们应用了由丙硫磷（prothiofos）构建的组胺电极，丙硫磷是一种含有 ...更多信息 P=S组，测定肥大细胞释放组胺的量。其次，我们以四[3，5-双（2-甲氧基六氟-2-丙基）苯基]硼酸钠为离子交换剂，苄基2-硝基苯基醚为溶剂介质，构建了三乙胺敏感膜电极，并将其用于测定细胞膜上的pH值。该方法是基于监测的pH梯度诱导的摄取三乙铵原位。在使用脂质体的实验中，根据脂质体膜上的pH差定量诱导三乙基铵摄入脂质体。用本方法成功地测定了大肠杆菌（Escherichia coli）细胞跨膜pH差和盐生盐杆菌（Halobacterium halobium）光诱导的跨膜pH差。其他结果可参见本报告后面所述的参考文献。少