Kinetic and Structural Studies on the Intermediates Formed in the Reactions of 5'-Adenosine Monophosphate and 5'-Guanosine Monophosphate with cis-Dichlorodiammineplatinum( 11) Using H and 195Pt Magnetic Resonance Spectroscopy

The kinetics of the reactions of 5'-AMP and 5'-GMP with excess cis-[Pt(NH,),CI,] in the presence of KCI at pH* 6.5 have been investigated by 'H NMR and analyzed by nonlinear numerical integration and optimization techniques. The species formed have been further characterized by 195Pt NMR. The reaction with 5'-AMP involves a branching pathway: 5'-AMP reacts with ~ i s [ P t ( N H ~ ) ~ c l , ] to form either species IA or IIA; species IA and IIA then react with cis-[Pt(NH3),CI,] to form species IIIA, the final product of the reaction. Species IA, IIA, and IIIA arise from Pt binding in a monodentate mode to N7, N1, and both N1 and N7 of the adenine ring, respectively. The reaction with 5'-GMP proceeds as follows: 5'-GMP reacts with ~ i s [ P t ( N H ~ ) ~ c l ~ ] to form species IG and IIG either simultaneously or in sequence (the latter being unlikely on structural grounds); species IG and IIG are in equilibrium which is rapid in terms of the overall reaction, such that the ratio of the concentrations of species IG to that of species IIG is constant throughout the entire course of the reaction, but slow on the 'H NMR scale as two distinct signals are seen in the 'H NMR spectrum, separated by only 10 Hz at the spectrometer frequency of 270 MHz. The final step of the reaction involves the conversion of species IG and IIG into species IIIG. From the kinetic data, one cannot discern whether species IIIG is formed directly from species IG and indirectly from species IIG via species IG. or vice versa. We propose that species IG and IIG are rotamers with Pt binding in a monodentate mode at N7 of the guanine ring, rotation occurring about the Pt-N7 bond, and that species IIIG is a chelate in which the Pt atom forms a bridge between N7 and the 6-keto group.