Departamento de Química Inorgànica, Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain.
Bioinorg Chem Appl. 2007;2007:98732. doi: 10.1155/2007/98732.
Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and (1)H, (13)C, and (195)Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae Pd(9AA)(mu-Cl) . 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh(3) or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl(2)(DMSO(2)]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula Pd(9AA)(mu-Cl) has significant antiproliferative activity, although it is less active than cisplatin.
合成了四个新的金属配合物{ M = Pd(II) 或 Pt(II)}，其中包含配体 9-氨基吖啶（9AA）。通过 FT-IR 和（1）H、（13）C 和（195）Pt NMR 光谱对化合物进行了表征。通过 X 射线衍射确定了[Pd（9AA）（mu-Cl）]（2）·2DMF 的钯配合物的晶体结构。两个 9-吖啶分子以亚胺形式通过亚胺氮原子和氨基吖啶的 C（1）原子以双齿配位方式对称地与金属离子结合，形成新的五元环。通过与膦或吡啶反应，Cl 桥断裂，形成通式为[Pd（9AA）Cl（L）]（其中 L = PPh（3）或 py）的化合物。通过 9-氨基吖啶与配合物[PtCl（2）（DMSO）（2）]的直接反应，也得到了铂的单核配合物[Pt（9AA）Cl（DMSO）]。通过圆二色性和电泳迁移率评估了化合物修饰 DNA 二级和三级结构的能力。钯和铂化合物均能有效修饰 DNA 的二级和三级结构。原子力显微镜图像显示，化合物可能通过插入 DNA 分子的碱基对，对质粒 pBR322 DNA 的形态进行了明显的修饰。最后，测试了钯配合物对三种不同人肿瘤细胞系的抗增殖活性。结果表明，通式为[Pd（9AA）（mu-Cl）]（2）的钯配合物具有显著的抗增殖活性，尽管其活性低于顺铂。
