title: The role of bridging ligands in determining DNA-binding ability and cross-linking patterns of dinuclear platinum(II) antitumour complexes.
abstract: The DNA binding ability and binding mode of platinum complexes are crucial factors that govern their cytotoxic activity. In this work, circular dichroism spectroscopy, gel electrophoresis and MALDI-TOF MS spectrometry combined with enzymatic degradation have been used to elucidate the role of bridging ligands in DNA-binding ability and cross-linking patterns of two dinuclear antitumour active platinum(II) complexes, {[cis-Pt(NH(3))(2)Cl](2)L1}(NO(3))(2) (1, L1= 4,4'-methylenedianiline) and {[cis-Pt(NH(3))(2)Cl](2)L2}(NO(3))(2) (2, L2 = alpha,alpha'-diamino-p-xylene). Although both complexes have two cis-diammine-Pt(II) moieties (1,1/c,c), complex 1 exhibits much higher DNA-binding ability than complex 2. The former readily forms both 1,3- and 1,4-intrastrand cross-links with DNA oligonucleotides, while the latter preferentially forms 1,4- rather than 1,3-intrastrand cross-links. Cytotoxicity studies against a human non-small-cell lung cancer cell line (A549) demonstrate that complex 1 has higher activity than 2. These results show that the linker properties play a critical role in controlling the DNA-binding and cross-linking abilities and in modulating the cytotoxicity of dinuclear platinum complexes.
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhu
authors.forename: Miaoxin
authors.initials: M
authors.lastname: Lin
authors.forename: Damin
authors.initials: D
authors.lastname: Fan
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Wu
authors.forename: Yuncong
authors.initials: Y
authors.lastname: Chen
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Zijian
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D001483:Base Sequence; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000633:toxicity; D010984:Platinum / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D008024:Ligands; D009944:Organoplatinum Compounds; D010984:Platinum; D004247:DNA