Synthesis of macrocyclic hosts having multiple cyclophanes for fluorescent detecting of drug release

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K05761
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional solid state chemistry
• Research Institution: Fukuoka University
• Principal Investigator: Hayashida Osamu 福岡大学, 理学部, 教授 (20231532)
• Co-Investigator(Kenkyū-buntansha): 草野 修平 国立研究開発法人理化学研究所, 環境資源科学研究センター, 研究員 (80759291)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: ホストゲスト化学 / 分子認識 / ゲスト放出 / 薬物送達 / ジスルフィド

Outline of Final Research Achievements

Cysteine-linked cyclophane dimer having two rhodamine moieties (2) was synthesized as a reduction-responsive host. Owing to self-quenching property of the two rhodamine moieties, cyclophane dimer 2 showed weak fluorescence intensity relative to that of the rhodamine B moiety itself. The cleavage of disulfide bond of 2 was performed by a treatment with reducing agents such as dithiothreitol, to give the corresponding monomeric cyclophanes having a rhodamine moiety. Such reductive degradation of 2 was detected by the increase on fluorescence intensity. As a host, cyclophane dimer 2 was found to show a stronger guest-binding affinity than the monomeric cyclophanes due to concentration effects of the macrocycles. In addition, reduction-responsive release of entrapped guest molecules by 2 was also monitored by fluorescence spectroscopy.

Free Research Field

ホストゲスト化学

Academic Significance and Societal Importance of the Research Achievements

本研では“薬剤(ゲスト)を放出する”と同時に“光り出す”などの機能をもった多環状ホストを開発することに成功した。還元剤などの外部刺激に応じてゲストを放出し、ホストの蛍光強度が約3倍に上昇することがわかった。これらの結果は、分子認識化学の分野においてホスト分子の更なる機能化のための貴重な分子設計指針を与えるともに、薬剤運搬システムの開発に繋がるものと期待できる。