| Project/Area Number |
16590027
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Okayama University |
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Principal Investigator |
KATSU Takashi Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (40112156)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUSHIMA Tohru Kumamoto University, Graduate School of Medical and Pharmaceutical Sciences, Professor, 大学院医学薬学研究部, 教授 (00264060)
MASUDA Kazufumi Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Assistant, 大学院医歯薬学総合研究科, 助手 (00243486)
KOMAGOE Keiko Okayama University, Faculty of Pharmaceutical Sciences, TedhnicaI Employees, 薬学部, 技官 (50437563)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Ion-selective electrode / Molecular recognition chemistry / Organic ammonium ion / Membrane potential / Membrane permeability / Calcein / Liposome / Non-steroidal anti-inflammatory drug / 有機リン化合物 / メキシレチン定量 / リポソーム / 膜透過性変化 / ポルフィリン / トリス(2-エチルヘキシル)ホスフィンオキシド / セロトニン定量 / 胃粘膜障害作用 / 分子レセプター / カリックス[6]アレーン誘導体 / メラシクロファン誘導体 |
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| Research Abstract |
The development and application of ion-selective electrodes continue to be an area of focus. In this study, we developed organic ammonium ion-selective electrodes by modifying the upper rim of calix[6]arene.hexaacetic acid hexaethyl ester with various alkyl substituents. We found that the substitution of bulkier alkyl groups enabled a more effective discrimination of simple aliphatic ammonium ions such as methylammonium and ethylammonium. In particular, an electrode based on p.1,1,3,3-tetramethylbutylcalix[6]arene-hexaacetic acid hexaethyl ester showed the highest response to methylammonium among various organic ammonium ions and inorganic cations. We further developed serotonin and mexiletine electrodes using the electrostatic interaction between the NH3+ group of these amines and the negatively polarized oxygen atoms in the phosphoryl (P=O) groups of phosphorus compounds. Among a series of the phosphorus compounds containing P=0 groups, tris(2-ethylhexyl)phosphine oxide and S, S, S-tris(2-ethylhexyl) phospho otrithioate proved to be effective for constructing serotonin and mexiletine electrodes, respectively.
As for the application of ion-selective electrodes, we used K+ and tetraphenylphosphonium electrodes simultaneously in order to evaluate the ability of antimicrobial peptides to form channels (or more generally to increase permeability) and to abolish membrane potential in bacterial cytoplasmic membranes in situ. Furthermore, the changes induced by biologically active substances in the permeability to K+ and calcein of liposomes were measured simultaneously in order to rapidly screen the sizes of pores formed in a membrane, using different sized markers. We also applied K+ electrode to analyze gastric mucosal cell damage mediated by non-steroidal anti-inflammatory drugs.
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