Comparison of the mode of action of a dinuclear platinum complex containing a pyridine derivative with its monomeric analog

The DNA binding and interstrand cross-linking properties of the dinuclear p latinum: complex [{cis-Pt(NH3)(2)Cl}(2)bpsu](NO3)(2) (bpsu is 4,4'-dipyridy l sulfide) (II) and the mononuclear complex [cis-Pt(NH3)(2)Cl(4-methylpyrid ine)]NO3 (I) were compared with those of [{cis-Pt(NH3)(2)Cl}(2)H2N(CH2)(4)N H2](NO3)(2) (III) in order to understand the mode of action of complexes I and II. Both compound I and compound II caused significantly different chan ges of conformation in poly(dG-dC).poly(dG-dC) than compound III did. Studi es of DNA binding, interstrand cross-linking and fluorescence assay suggest that compound I monofunctionally binds to DNA and compound II bifunctional ly binds to DNA, that the dinuclear platinum complex II more efficiently in teracts with DNA compared to its monomeric analog, and that platinum I and II complexes both interact with DNA in a non-intercalative mode. All the re sults indicate that the mode of action of the dinuclear complex II is diffe rent from that of the mononuclear complex I. (C) 1998 Elsevier Science Irel and Ltd. All rights reserved.