The kinetics of substitution reactions of mixed platinum(II)-bis(nucleoside) complexes in aqueous solution in the presence of thiourea; X-ray crystalstructure determination of cis-[Pt(NH3)(2)(adenosine-N7)(2)](ClO4)(2)center dot 3.5 H2O

In aqueous solution, bis(nucleoside) complexes formed by the reaction of ci s-[Pt(NH3)(2)(H2O)(2)](2+) with an excess of either adenosine (ado) or a mi xture of adenosine and guanosine (guo) undergo a slow N7 --> N1 linkage iso merisation in the adenine moiety. The isomerisation probably involves the b reaking and reformation of Pt-nucieoside bonds, thus favouring the more sta ble N1 binding mode of the adenine base. Dynamic processes due to the prese nce of adenosine in the platinum coordination sphere are slow on the NMR ti me scale. The N7 binding mode of Pt-II in cis-[Pt(NH3)(2)(ado-N-7)(2)]-(ClO 4)(2). 3.5H(2)O was confirmed by X-ray crystal structure analysis. In both of the crystallographically independent cations, the Pt-II coordination sph ere is almost ideally square planar, with typical Pt-N bond lengths and ang les. The most significant difference between the two cations lies in the su gar conformation of the coordinated nucleosides. In one cation, both have a n anti (-ap) conformation, whilst in the other cation one has an anti (-ap) conformation and the other a syn (Ssc) conformation stabilised by a relati vely strong H-bond. Substitution of the nucleosides by thiourea follows an associative mechanism with only a negligible contribution by the solvent pa th. For symmetric complexes, the order of lability of different binding mod es is ado-N1 < guo-N7 < ado-N7 for substitution of the first nucleoside, wh ereas for the second nucleoside it is guo-N7 < ado-N1 < ado-N7. For asymmet ric complexes, the concomitant cleavage of different Pt-II-nucleoside bonds can be explained by two parallel reaction pathways. The change in the (PtI )-I-I coordination sphere affects the lability of the coordination nucleosi des in a different manner. The ado-N1 binding mode renders all binding mode s less labile, whereas the ado-N7 mode has the opposite effect, and the guo -N7 mode increases the lability of the ado-N1 mode but decreases that of th e ado-N7 mode. The mixed-ligand complex with (ado-N7)(guo-N7) mode is far m ore susceptible to attack by thiourea than the symmetric (guo-N7)2 species. These two species can be considered as models for the two most abundant Ci splatin-DNA adducts.