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

Reactions of chloro(diethylenetriamine)palladium(II) with 4-thio-2'-deoxyur idine, 4-thiouridine-5'-monophosphate, d((T8UT8)-U-s4), 6-thio-2'-deoxyinos ine, 6-mercapto-purine riboside-5'-monophosphate and d((T8IT8)-I-s6) have b een investigated using diode-array and conventional stopped-flow spectrosco py in acidic aqueous solution as a function of excess concentration of Pd(I I) and temperature. The observed rate constants and activation parameters i ndicated a reaction mechanism where the labile chloro ligand is directly re placed by the thione unit in the coordination sphere of the Pd(II) complex. Incorporation of both thionucleosides into single-stranded oligonucleotide s 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 t he monomer reactions, adduct formation in DNA-environment results in an inc rease of both the Delta H-not equal- and Delta S-not equal-values. The obse rved DNA-promoted reactivity is thus a consequence of the reduced contribut ion to the activation energy from the Delta S-not equal-term. (C) 2000 Else vier Science S.A. All rights reserved.