The role of bridging ligands in determining DNA-binding ability and cross-linking patterns of dinuclear platinum(II) antitumour complexes

Jianhui Zhu, Miaoxin Lin, Damin Fan, Ziyi Wu, Yuncong Chen, Junfeng Zhang, Yi Lu, Zijian Guo

Research output: Contribution to journalArticlepeer-review

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(NH3)2Cl] 2L1}(NO3)2 (1, L1= 4,4′- methylenedianiline) and {[cis-Pt(NH3)2Cl] 2L2}(NO3)2 (2, L2 = α,α′- 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.

Original languageEnglish (US)
Pages (from-to)10889-10895
Number of pages7
JournalDalton Transactions
Issue number48
DOIs
StatePublished - Dec 14 2009

ASJC Scopus subject areas

  • Inorganic Chemistry

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