Kinetic aspects of interactions between DNA and platinum complexes

Kinetic studies on reactions between oligonucleotides and platinum complexe s related to the antitumor drug cisplatin are described. These studies were motivated by the sequence-selectivity observed for the reaction between ci splatin and DNA. Comparison of oligonucleotide platination rate constants m easured for the three complexes cis-[PtCl(NH3)(2)(H2O)](+), cis-[Pt(NH3)(2) (H2O)(2)](2+), and [Pt(NH3)(3)(H2O)](2+) suggests that the hydrogen bond do nating capacity of the platinum ligands enhances the platination rate. The binding preferences of cis-[Pt(NH3)(2)(H2O)(2)](2+) and cis-[PtCl(NH3)(2)(H 2O)](+) indicate that the latter species is unlikely to be the major specie s interacting with DNA in vivo. This conjecture is corroborated by reactivi ty and availability considerations. We also address the sequence-dependence observed for the hydrolysis of chloro-monoadducts and for the conversion o f aqua-monoadducts to diadducts, and discuss possible mechanisms. (C) 1999 Elsevier Science S.A. All rights reserved.