新型间苯二甲酸类纳米孔MOFs材料的合成：取代基效应及药物控释模拟

Controlled delivery of drugs has the significant technical application in clinical drug use due to a better control of the drug plasmatic levels, increasing the efficiency and decreasing the toxicity. In this project, aiming to controllable synthesis of higher drug control-release materials, flexible nanoporous metal-organic frameworks will be designed and constructed by adjusting rigid spacer, concentration-temperature parameters, synthesis techniques, variable molecular backbone by "short axis - long axis" assembly of 5-R-isophthalates and V-shaped bridging nanoscale bipyridine-like molecules. The target nanoporous MOFs will be characterized by X-ray single crystal diffraction and some physico-chemical analyses. Their control-release properties of ibuprofen under physiological conditions and topological structures will be investigated in detail. Furthermore, bridging model between control-release properties and topological structures will be established to explore structure-activity relationship of nanoporous MOFs. In conclusion, this work provides undoubtedly a better choice to construct rationally nanoporous MOFs, in favor of the discovery of bioactive control- delivery materials with high therapeutic activity.

利用药物控释技术给药具有药效长、血药浓度稳定、毒副作用小等特点。纳米孔MOFs材料因其空腔大、溶解度小、结构可控和筛选方便可作为高效率的药物控释材料。本项目拟从构筑非穿插具有纳米孔结构的MOFs入手，选用短链结构的间苯二甲酸衍生物和V型半刚性纳米尺寸的联吡啶有机物协同作用利用"短轴-长轴"模式定向合成纳米孔MOFs，并从合成工艺和方法、取代基调控方面探明纳米孔MOFs材料的合成机理，并进行拓扑学分析。通过对MOFs进行布洛芬药物小分子的控释模拟，建立控释性能和微观结构的模型连接，找出其成键规律和构效关系，为从理性合成和筛选结构可控、合成方便、有实际应用价值和安全性的药物控释材料提供预测指导。

金属有机骨架材料（MOFs）具有低密度、大孔道、均匀的孔径分布以及不饱和金属配位点等特点，在气体储存、分离、催化和药物缓释等方面有广阔的前景。本研究开展了具有多孔性能的MOFs材料的定向合成研究，系统选用间苯二甲酸衍生物，从位阻基团、浓度-温度因素、辅助基元、pH值、溶剂诱导等方面控制合成了一系列多孔MOFs材料，并对其进行了结构表征和性能测试，对于有稳定孔径的MOFs进行了一些孔道性能的测试以及拓扑学分析，探索得到了性能和拓扑结构关联的一些模型参数，为合成多孔MOFs材料提供了新的思路，丰富了多孔MOFs的种类，为研究多孔MOFs的构效关系提供了一定的理论依据。