Reactions of Pd(dien)Cl+ with thione-containing nucleosides, nucleotides and oligonucleotides: increase of both enthalpy and entropy of activation in the DNA-environment

Reactions of chloro(diethylenetriamine)palladium(II) with 4-thio-2′-deoxyuridine, 4-thiouridine-5′-monophosphate, d(T8s4UT8), 6-thio-2′-deoxyinosine, 6-mercapto-purine riboside-5′-monophosphate and d(T8s6IT8) have been investigated using diode-array and conventional stopped-flow spectroscopy in acidic aqueous solution as a function of excess concentration of Pd(II) and temperature. The observed rate constants and activation parameters indicated a reaction mechanism where the labile chloro ligand is directly replaced by the thione unit in the coordination sphere of the Pd(II) complex. Incorporation of both thionucleosides into single-stranded oligonucleotides was found to increase the rate of adduct formation by a factor of ca. 2–3, compared to reactions of the corresponding mononucleotides. Compared to the monomer reactions, adduct formation in DNA-environment results in an increase of both the ΔH≠- and ΔS≠-values. The observed DNA-promoted reactivity is thus a consequence of the reduced contribution to the activation energy from the ΔS≠-term.