微量元素与嘌呤类PMOFs的构筑及药物控缓释性能

Metal Organic Frameworks(MOFs) have generated intense interest owing to their potential application in gas storage,separation,ion exchange, nonlinear optics,catalysis and chemical sensing.However,another avenue now being explored is the use of MOFs for biomedical applications such as drug delivery,drug release, and biomedical imaging.The purines are ideal ligands for constructing bio-MOFs because (a) it is rigid and has mutiple possible metal binding modes,(b)it is endogenous purine nucleobased with anti-cancer, anti-metabolizable properties. Meanwhile, trace elements play an essential role in the life. We chose purines as biomolecular ligands, and trace elements as metal ions, to construct bulk porous MOFs in which low and/or non toxic carboxylate acid can be introduced.The drug load and release properties of anticancer drugs will be examined for as-synthesised bulk porous MOFs.In addition,the relationship will be summarized between structure, size and properties as drug delivery and release,thus providing the theoretical basis for designing novel drug carrier.

近年来金属有机骨架(MOFs)因其在气体存储、选择性分离、非线性光学材料、催化、化学传感、离子交换等方面的潜在应用而备受人们关注，而将MOFs应用于药物传递和释放方面是新兴发展起来的一个分支。刚性嘌呤类配体含多个配位N原子，配位方式灵活，而且它是核酸的组成部分，是抗癌药物中抗代谢药的主体，是构筑生物相容性MOFs的理想选择。而人体必需的微量元素在抗病、防癌等方面都起着不可忽视的作用。本项目选用人体微量元素与嘌呤类配体构筑多孔MOFs块材，并研究所合成的多孔MOFs对抗癌药物的负载及释放性能。并总结MOFs结构、粒度大小与其载药性能的关系，为设计、寻找新型抗癌药物载体提供理论基础。

近年来MOFs应用于药物传递和释放是新兴发展起来的一个分支。以药物分子为配体，并辅以低毒芳香羧酸与人体必需微量元素可构筑配合物，避免了控缓释过程中药物本身的毒性和降解问题。原计划的嘌呤类单独为配体的合成实验中遇到困难，得到的几乎是寡聚体。而在(嘌呤+辅助芳香羧酸)混合配体构筑MOFs时，仅得到羧酸配位的化合物。中期选取含羧基的喹诺酮药物替代嘌呤，开展了环丙沙星(Hcf)和萘啶酮酸(Hnd)，并辅以低毒羧酸的配合物工作。项目后期，开展了二膦酸的合成及配合物的构筑。.(1) 以5-(4-苯羧基)-尼古丁酸(H2cpna)为配体得到仅含H2cpna的四例化合物Ni(cpna)(H2O)2, M2(cpna)2(H2O)3•0.5H2O•DMF [M=Ni and Co] and Ni3(Hcpna)2 -(cpna)2(H2O)4•2H2O。四例化合物中cpna2-均充当3-连接子，分别于共边二聚体,共顶点二聚体,线性三聚体连接形成2D (3,6)-kgd层；3D (3,6)-anh (flu-3, P6222)拓扑结构；(3,8)-tfz-d拓扑网络。.(2) 以H2cpna为配体与钴盐得到三例不同网络拓扑的真正超分子异构体[Co(cpna)(H2O)2] (5a, 5b and 5c)。5a与5b、5c的不同在于金属中心和配体的配位模式均不同。而5b和5c的异构主要由于配体的中苯环和吡啶环的夹角不同。.(3)以Hcf, Hnd成功构筑四例化合物：[Fe(cf)2]•2H2O (6), [Cu(cf)2(H2O)]•SO4•6H2O (7), [Cu(cf)(Ac)]•H2O (8), [Cu(cf)2(H2O)]•(H2pta)•H2O (9)，[Cu(nd))]•H2O (10) 。化合物6、7、9是单核化合物，化合物8为1D链状化合物。.(4)依据文献顺利合成唑来膦酸，并应用于合成膦酸杂化材料。目前得到三例化合物Zn(H3zol)2∙4H2O (11), [Zn(H3L)2∙H2O]∙2H2O (12), Zn2(zol)(H2O) (13)。