树形高分子包裹多金属氧酸簇杂化物的合成和超分子结构的研究

Dendrimers have unique molecular weight, regular chemical structure and specific molecular shape and thus can assemble into specific supramolecular structures. Some dendrimers with excellent biocompatibility and bioactivity have been developed. Polyoxometalates (POMs) are a class of anion clusters with unique structure and composed by bridging early-transition metal atoms with oxygen ligands. They have good transport and storage capacities of electrons and protons, special oxidation-reduction potential and strong Br?nsted acidity. Their anti-tumor and -HIV performances are also very attractive. However, strong cytotoxicity hampered their applications as a class of inorganic drugs in biology and medicine. In this proposal we suggest to covalently link biocompatible dendrons with organic modified POMs to form a POM-containing dendritic molecule or molecular aggregates. Given continuously growing dendritic features, the dendrons or dendrimer may package POM clusters. In this way the cytotoxicity of POM clusters can be greatly reduced and their drug functions can be optimized. Our purpose is to develop a new class of organic-inorganic hybrid drugs. If peripheral groups of dendrons or dendrimers used can be tailored using some selected targeting motifs, the modified POMs will be endowed with targeted functionalities. In this way their biological and drug functions can be further maximized. In order to achieve this goal, it is necessary to develop synthetic methods of such hybrid molecules, study their physical properties and assembled supramolecular structures.

树形高分子具有确定的分子量、规整的化学结构以及特定分子形状，能够组装成的特定超分子结构，也能呈现良好的生物相容和生物活性。多金属氧酸簇（POM）是由过渡金属原子通过氧配位桥连而成的一类具有确定结构的阴离子簇合物，具有良好的电子和质子的传输、储存能力，特殊的氧化还原电位和较强的质子酸性，呈现诱人的抗肿瘤和抗HIV的药物功能。但是，强的细胞毒性妨碍了作为一类无机药物在生物和医药领域里的应用。我们提出将树枝片高分子与经过有机改性的POM通过共价键相连接，形成含有POM的树枝高分子或者多分子聚集体，利用不断支化形成的树枝状分子包裹POM，从而降低细胞毒性，优化POM的药物功能，发展一类新型的有机－无机杂化药物。若将树枝片的外围基团进行有目的的修饰，可以赋予改性POM靶向功能，最大化生物和药物功能。为了实现这个目标，就要发展这类杂化分子的合成方法，研究物理性质和组装形成的超分子结构。

我们设计并合成了以多金属氧酸簇（Polyoxometalates, POM）和倍半硅氧烷簇（Polyhedral Oligomeric SilSesquioxanes，POSS)为构筑单元，一个有机分子为连接链的一系列杂化分子POM-nPOSS（n = 1 到4）。当有机连接链是线性的，POM-1POSS为哑铃形杂化分子。当有机连接链是刚性树枝状的分子，POM-nPOSS（n = 2 到4）为扇形杂化分子。当有机连接链是柔性树枝状的分子，POM-nPOSS（n = 2 到4）为锥形杂化分子。我们实施了这些杂化分子在水表面和在溶液中的自组装，然后，研究了超分子结构。我们发现如下结果：在水表面哑铃形POM-1POSS很快地形成具有不同有序结构的膜。在极性有机溶剂和水的混合溶剂中，POM-1POSS自组装成六边形的晶体，高分辨电子显微镜揭示POM簇构筑成的双层膜中的精细结构。在低极性的溶液中扇形的POM-4POSS自组装成具有罕见的蜂巢晶格的膜。在极性有机溶剂和水的混合溶剂中,锥形的POM-3POSS自组装成紧密堆积的六棱POM柱结构。这些研究清楚地阐明了分子形状与自组装的超分子结构之间的关联性。这些研究结果清楚地表明，构筑基元的三维分子几何形状是精确控制其自组装纳米结构的一个关键因素。