基于羧酸修饰的含硫吡啶金属化合物的合成及活性研究

项目名称： 基于羧酸修饰的含硫吡啶金属化合物的合成及活性研究

项目编号： No.21201025

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 无机化学

项目作者： 唐晓艳

作者单位： 常熟理工学院

项目金额： 23万元

中文摘要： DNA的二级特殊结构G-四链体存在于人体基因组的一些重要位置，是很好的肿瘤药物作用靶点。研究作用于G-四链体的小分子金属配合物，寻找具有较高抗肿瘤活性和高效选择性的金属配合物将有助于开发新型金属抗肿瘤药物。本项目设计合成一系列羧酸修饰的含硫吡啶配体，并将这些配体与具有抗肿瘤活性的贵金属离子和其他过渡金属离子反应合成金属配合物。综合利用化学和生物学的方法研究金属配合物的结构-性质-生物活性之间的关系，通过紫外可见吸收光谱法、荧光光谱法、圆二色谱法、核磁、X-射线单晶衍射等手段研究金属配合物诱导产生G-四链体的能力、与G-四链体的作用、结合模式以及对G-四链体结构的稳定能力。考察配体上取代基的位置、体积大小、电子效应等对金属配合物的结构和性质的影响，探索此类金属配合物作为抗肿瘤药物的可能性。

中文关键词： 金属配合物；合成；结构；活性；性质

英文摘要： G-quadruplex DNA dose exist in most important positions of human genes, which is a good target for antitumor drugs. It is helpful to develop new metal antitumor agents by studying metal complexes acting on G-quadruplex DNA with high and specific antitumor activity. In this project, a series of carboxyl sulfur-containing pyridine ligands were design and the reactions of these ligands with metal ions with anticancer activity will be investigated. The relationship of structure-properties-bioactivity of these metal complexes will be carried out via the comprehensive application of biological and chemical methods. The ability of these ligands and their metal complexes to induce the formation of G-quadruplex, the interaction and the binding mode between these metal complexes and G-quadruplex, and the stability of the G-quadruplex will be studied via UV-visible absorption spectroscopy, fluorescence spectroscopy, circular dichroism et al. NMR spectroscopy and X-ray spectroscopy can also be used to obtain detailed structural information on the interactions occurring between these metal complexes and G-quadruplex. The influence of the position of substituents, the stereo effect, electronic effect on the structure and properties of these metal complexes will be analyzed, and the possibility of such metal complexes as the p

英文关键词： metal coordination compounds；synthesis；structure；activity；properties