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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

离子选择电极的开发和应用一直是研究的热点。由于有许多药物的分子中含有氨基，因此本研究特别关注有机铵离子选择性膜电极的开发。首先，我们使用合适的溶剂介质和亲脂性离子交换剂四硼酸钠[3,5-二（2-甲氧基六氟-2-丙基）苯基]硼酸钠构建了生物胺敏感膜电极。研究发现，P=S基团的硫代磷酸酯等溶剂介质对组胺等有机铵离子的反应普遍增强，而对Na^+、K^+等无机阳离子的反应则明显抑制，说明有机铵离子NH_3^+基团与P=S基团中负极化的硫原子之间的氢键会增强组胺等有机铵离子的反应。我们使用含有P=S基团的化合物之一——硫代虫硫磷构建的组胺电极来测定肥大细胞中组胺的释放。测定的组胺浓度与已建立的荧光法测定的浓度一致。其次，我们以四硼酸钠[3,5-二（2-甲氧基六氟-2-丙基）苯基]硼酸钠作为离子交换剂，2-苄基硝基苯基醚作为溶剂介质，构建了三乙基铵敏感膜电极，并将其用于测定细胞膜上的pH差异。该方法是基于监测pH梯度诱导的三乙胺的原位吸收。在脂质体实验中，根据脂质体膜上的pH值差异，定量诱导三乙胺进入脂质体。本方法成功地测定了大肠杆菌细胞的跨膜pH差异和光诱导形成的盐杆菌囊泡的pH差异。我们在这里只描述了两个结果。其他结果可以通过本报告后面的参考文献看到。少