纳米钼配合物的仿生合成与抗癌抗肿瘤研究

项目名称： 纳米钼配合物的仿生合成与抗癌抗肿瘤研究

项目编号： No.20871085

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 化学工业

项目作者： 鲁晓明

作者单位： 首都师范大学

项目金额： 32万元

中文摘要： 选择含多齿配位原子的平面芳香环配体如多酚、萘酚、蒽环以及邻菲咯啉等有机物与钼配位，仿生合成了具有钼氧转移酶活性端结构的钼仿生配合物；选择具备易挥发的、易形成氢键的、系列有机小分子作为晶体晶格中质子化的抗衡阳离子或填充分子，使主体配合物在晶格中以一维、二维、以及三维点阵排列等构成宏观晶体。利用研磨，超声分离等，将宏观晶体解体为纳米尺度。对宏观晶体以及纳米体系进行谱学和电化学表征。对比单晶衍射、TEM以及SEM结果，研究了芳环配体、配合物的结构、晶体的结构基元以及结构基元间的作用，作为质子化的抗衡阳离子或填充小有机分子其几何构型、挥发性、形成氢键的能力，以及反应温度和反应物浓度对最终纳米形貌的形成的影响。对所得到的目标配合物进行了体外白血病、胃癌、肝癌、鼻咽癌、肺癌和结肠腺癌、乳腺癌以及子宫癌等癌症的细胞筛选工作，测定了IC50；进行了体内小白鼠肝癌H22、肺癌Lewis以及乳腺癌的药效和毒性ID50的研究，申请和获批了相关中国专利。用液相核磁共振、裂解DNA以及WT方法，揭示了钼配合物主要以DNA为靶点的抗癌抗肿瘤机理，并通过理论计算证实了该类配合物抗癌抗肿瘤活性的决定因素。

中文关键词： 钼配合物；纳米；结构基元；抗癌药效；IC50

英文摘要： The series single crystals consisted in molybedum biomimetic complexes with aromatic ligands such as phenol with different aromatic rings and heterocyclic compounds, small organic diamine which are volatile and easy to form hydrogen bonds have been synthesizes, their nano-structure including one-, two- and three- dimensional structure have been prepared using grounding and untra-sonicaion technical, and characterized by X-crystal diffraction, TEM and SEM, spectrum and electrochemical analysis. Comparing the results from X-crystal diffraction, TEM and SEM, the affections of the aromatic ligands with different rings and numbers, the molybdenum complexes with different structures, the motifs of the crystals and the interactions among the motifs, the volatilities of the diamines and their abilities to form hydrogen bonds, the temperature of reaction, and the concentration of the reactors, to the morphologies of the nano-structures have been studied. The inhibition to cancer cell lines and IC50 such as A-549, Bel-7402, HCT-8, BCG-832, HL, KB in vitra, and the inhibition and ID50 to liver cancer H22, lung cancer lewis, and breast cancer in viva have been tested, and their mechanism of the anticancer activities have been researched by liquid NMR of the complex with ATP in H2O, DNA cleaver, the WT method, and quantum computation.

英文关键词： molybedenum complex;nano-; motifs; anti-cancer; IC50