Synthesis and Application of Ion Recognition Compounds with High Sensitivities for Medical Science

本研究的目的是开发基于杯芳烃的新型荧光离子探针测量细胞内钠离子和钾离子浓度的方法。杯芳烃是由酚醛缩合而成的一类新型离子结合化合物。与冠醚和冠醚等聚醚离子载体相比，杯芳烃具有很高的亲油性。因此，杯芳烃可以很容易地被结合到生物膜中。为了将杯芳烃用作离子探针，有必要研究它们在生物膜中的电离发光性质。我们用平面膜系统研究了对叔丁基杯[4，6或8]芳烃酯类化合物的电致发光性质。通过研究，我们发现杯[4]芳烃酯具有钠离子探针的能力，具有很高的Na~+/K~+选择性。此外，我们还发现，由杯[4]芳烃酯衍生物衍生的荧光钠探针具有很高的Na~+/K~+选择性：合成的钠探针的Na~+/K~+选择性约为40。对于杯[6]芳烃酯，我们还发现了钾离子探针的用途。然而，对于杯[8]芳烃酯，我们不能在磷脂双层膜上表现出离子激发活性。通过本研究，我们得出结论：杯[4]芳烃和杯[6]芳烃的酯类衍生物具有作为钠和钾荧光探针用于生物膜的潜力。这些杯芳烃在生物系统中的应用正在进行中。

Purpose of our study is to develop the method for measurements of sodium and potassium ion concentrations in cells using new fluorescent ion probes based on calixarenes. Calixarenes are known as new class of ion-binding compounds prepared from the phenol-aldehyde condensation. In comparison with polyether ionophores such as crown ethres and cryptands, the lipophilicities of calixarenes are very high. Thus it is expected that the calixarenes can be easily incorporated into biological membanes. In order to use calixarens as ion probes, it is nessesarry to investigate their ionophoric properties in biological membranes. We investigated the ionophoric propeties of ester derivatives of p-tert-butylcalix[4,6, or8]arenes using a planarbilayr membrane system. Through this investigation, we found that the calix[4]arene ester has a ability of a sodiumion probe with a high Na^+/K^+ selectivity. Further, we found that a fluorescentsodium probe derived from the calix[4]arene ester derivative exhibits a high Na^+/K selectivity : the value of the Na^+/K^+ selectivity of the synthesized sodium probe was found to be ca. 40.For the calix[6]arene ester, we also found the utility of the potassium ion probe. However, for the calix[8]arene ester, we could not the ionophoric activity in phospholipd bilayr membranes. From this study, we conclude that ester derivatives of the calix[4]arene and calix[6]arene have potentials for use as sodium and potassium fluorescent probe in biological membranes. Applications of these calixarenes in biologicalsystems are in progress.