Substitution reactions of platinum(II)-nucleobase complexes by associativemechanism involving pseudorotation of the five-coordinate intermediate

Substitution reactions of N7-platinated guanosine and adenosine complexes { [Pt(dien)(Guo-N7)](2+) (1), [Pt(dien)-(Ado-N7)](2+) (2), dien = diethylenet riamine} by thiourea (tu) and I- have been studied in aqueous solution in t he pH range 1.4-8.3 at different temperatures. Reactions of both complexes with I- follow the usual associative two-path mechanism throughout the pH r ange studied, as do reactions with thiourea under neutral conditions (pH 6. 5). With both nucleophiles (Y), the observed rate constant linearly increas es with increasing [Y] up to 1000-fold excess of Y. Plots of k(1,obs) VS [Y ] were employed to calculate the rate parameters k(s) for the solvent path and ky for the nucleophile-dependent path by the equation k(1,obs) = k(s) k(Y)[Y] at different temperatures. The following activation parameters wer e obtained at 298.2 K for the reaction of thiourea with 1, Delta H double d agger = (72 +/- 1) kJ mol(-1) and Delta S double dagger = (-79 +/- 4) J K-1 mol(-1), and with 2, Delta H double dagger = (72.8 +/- 0.3) kJ mol(-1) and Delta S double dagger = (-86 +/- 1) J K-1 mol(-1). The corresponding data for I- with 1 are Delta H double dagger = (83 +/- 3) kJ mol(-1) and Delta S double dagger = (-49 +/- 8) J K-1 mol(-1), and with 2, Delta H double dagg er = (78 +/- 3) kJ mol(-1) and Delta S double dagger = (-67 +/- 10) J K-1 m ol(-1). Activation parameters for the solvent path are Delta H double dagge r = (85 +/- 1) kJ mol(-1) and Delta S double dagger = (-105 +/- 2) J K-1 mo l(-1) for 1, and Delta H double dagger = (87 +/- 7)kJ mol(-1) and Delta S d ouble dagger = (-98 +/- 22) J K-1 mol(-1) for 2, on the basis of the data f ound for reactions with thiourea. Rate parameters for the formation and sol volytic decomposition gave log K values of 7.5 +/- 0.1 and 6.1 +/- 0.2 for the equilibrium constants of 1 and 2, respectively, in aqueous 0.1 M NaClO4 solution at 298.2 K. Ring opening of the tridentate dien group in acidic s olution provides a competing route for the overall substitution by thiourea . All experimental data found are consistent with an associative mechanism involving pseudorotation of the five-coordinate intermediate formed by the attack of thiourea, including activation parameters (298.2 K) Delta H doubl e dagger = (69.2 +/- 0.3) kJ mol(-1) and Delta S double dagger = (-81 +/- 1 ) J K-1 mol(-1) for 1, and Delta H double dagger = (70.9 +/- 0.7) kJ mol(-1 ) and Delta S double dagger = (-79 +/- 2) J K-1 mol(-1) for 2. According to kinetic analysis, about 60% of I and 70% of 2 yield free nucleoside via th e ring-opening step, whereas the remainder give free nucleoside by direct r eplacement with thiourea. The ratio of these routes is practically independ ent of thiourea concentration and temperature. The H-1, C-13, and Pt-195 NM R spectroscopic data for the isolated ring-opened species 3(1) and 3(2) (fr om 1 and 2, respectively) are consistent with a four-coordinate species [Pt (dienH)(L-N7)(tu)](3+), in which the dien group acts a bidentate ligand and one of the dien amino groups is trapped by protonation. Although both 3(1) and 3(2) are stable in cold acidic solution, they decompose predominantly back to the starting material when the pH of the solution is increased. Acc ording to HPLC analysis, the former gives I and guanosine in a 12:1 ratio, and the latter yields 2 and adenosine in a 10:1 ratio. The ability of the dien-NH2 group to displace coordinated thiourea from Pt( II) contradicts the trans effect S > N and exemplifies the nucleophilic pow er of the NH2 group of a partially chelated amine.