A dinuclear monofunctional platinum(II) complex with an aromatic linker shows low reactivity towards glutathione but high DNA binding ability and antitumor activity.

Multinuclear Pt(II) complexes represent a novel class of antitumor agents. In this work, a dinuclear monofunctional Pt(II) complex {[cis-Pt(NH(3))(2)Cl](2)(4,4'-methylenedianiline)}(NO(3))(2) (1) was synthesized and characterized by (1)H NMR, electrospray mass spectrometry, and elemental analysis. The 2D [(1)H,(15)N] heteronuclear single quantum coherence NMR spectra of (15)N-labeled 1 revealed that the cationic core of this water-soluble complex hardly hydrolyzes in aqueous solution and reacts very slowly with glutathione. Hydrolysis appears not to be an essential step for the formation of Pt-guanosine-5'-monophosphate (5'-GMP) or Pt-DNA adducts because the complex can react readily with 5'-GMP and partially transform B-DNA into its Z form. Such properties are desired to achieve the goal of enhancing cytotoxicity and lowering side effects of Pt(II) complexes. In fact, complex 1 is highly cytotoxic against the murine leukemia (P-388) and the human non-small-cell lung cancer (A-549) cell lines, and it is more cytotoxic than cisplatin at most concentrations tested.