Influence of DNA on the rate of ligand substitution in platinum(II) terpyridine complexes

The kinetics of substitution of pyridine or 2-methylpyridine, by iodide or thiourea, in the complexes [Pt(4'-R'terpy)(2-Rpy)](BF4)(2) (R' = o-tolyl or H; R = H or CH3) has been studied, at 25 degrees C, pH 7, and various ioni c strength values, in the presence of and without calf thymus DNA. The reac tions occur in one observable step, and plots of k(obsd) against nucleophil e concentration give straight lines with zero intercepts. DNA inhibits all the reactions studied without altering the rate law; the second-order rate constants k(2) decrease systematically on increasing DNA concentration and are larger at higher ionic strength values. Partitioning of the ionic react ants in solution on electrostatic grounds can account for this kinetic effe ct in the reaction with iodide. Iodide is kept off the double helix proximi ty while the dicationic complexes concentrate on it. The inhibiting effect observed for the uncharged reagent thiourea can be related to the specific binding mode of the complexes to DNA. The complexes studied are effective i ntercalators to double helix, and this type of interaction, which prevents attack of thiourea at platinum, decreases their actual concentration in sol ution. The inhibiting effect is larger for [Pt(terpy)(py)](2+) that is a be tter intercalator. Likewise, the decrease in the rate of substitution of 2- Rpy, at a given [DNA] on decreasing ionic strength, is due to the influence of ionic strength on the complex-DNA interactions.