具三重识别功能的大环多胺的合成及分子识别的研究

3-hydroxyl-1, 5, 8-triaazacyclicamine (1) and 3, 13-dihydroxy1-1, 5, 8, 11, 15, 18-hexaazacyclicamine (2) were prepared in moderate yields. The crystal structure of 2 was determined by X-ray analysis. The NMR methods (including 1H NMR, variable temperature method and the 2D COSY technique) were employed to study the conformation of (2) in aqueous solution. Ni (Ⅱ),Ca(Ⅱ), Co(Ⅱ), Cu(Ⅱ)complexes of (1) and (2) could catalyze cleavage supercoiled pBR322 DNA (3) to the nicked and the linear form at near neutral conditions and 37℃. Little cleavage was found under comparable conditions by the metal ions or receptor alone. The efficiency of DNA cleavage with added metal decreases in the order Cu(Ⅱ)≈Co(Ⅱ)>Ni(Ⅱ)≈Ca(Ⅱ)for receptor (1); whlie the efficiency of DNA cleavage with added metal decreases in the order Ni(Ⅱ)≈Cu(Ⅱ)>Co(Ⅱ)≈Ca(Ⅱ) for receptor (2). Two receptors and their metal complexes exhibited promising antitumor activity in vitro, especially against the BEL-7402 cell lines. After stained with Hoechst 33258, BEL-7402 cells treated with complexes showed nuclear condensation and fragmentation. Simultaneously the dispersion of nucleus and appearance of apoptotic body were observed. BEL-7402 cells treated with complexes were collected and examined by a Becton Dickinson FACSort after DNA staining with propidium iodide (PI). Induction of tumor cell apoptosis was observed.

以三氮杂环壬烷、四氮杂环十二烷、单羟基四氮杂环十三烷和二羟基六氮杂环廿烷为起始的结构“板块”，构筑成桥连型、套索型和园筒型大环多胺及其金属络合物；经化学修饰引入具π堆叠作用的结构单元，使之成为具有三重识别功能的特定结构的接受体分子。试图模拟磷酸腺苷酶，实施对三磷酸腺苷的催化水解和合成；为探索新的酶模型提供重要依据。