Platinum(II)-adenosine phosphothiorate complexes: kinetics of formation and phosphorus-31 NMR characterization...

Reactions of chloro(diethylenetriamine)platinum(II) chloride with adenosine 5'-O-thiomonophosphate, adenosine 5'-O-(2-thiodiphosphate), and adenosine 5'-O-(3-thiotriphosphate) yielded exclusively (phosphothiorato)platinum(II) complexes. Phosphorus-31 NMR data for the coordinated phosphothiorate phosphorus atom exhibited about 15-20 ppm upfield chemical shift compared to chemical shifts for free nucleotides. Uncoordinated phosphate groups exhibited insignificant changes in the chemical shift upon complexation. Likewise, proton NMR data indicate no significant changes in chemical shift for the purine or ribose protons. Reactions between phosphothiorates and the platinum complex predominately take place through a second-order process, first order with respect to each of the reactants indicating that the aquated pathway contributes insignificantly toward complexation. The second-order rate constants, 1.9 +/- 0.1 M-1 s-1 for the AMP-S, 2.4 +/- 0.2 M-1 s-1 for the ADP-beta-S, and 2.7 +/- 0.2 M-1 s-1 for the ATP-gamma-S reactions were evaluated at pH 6.5 and at 25 degrees C. These rate data were compared with those reactions of adenosine 5'-monophosphate (AMP) and guanosine 5'-monophosphate (GMP) with the same platinum(II) complex. These reactions proceed through the direct interaction between the starting platinum complex and nucleotides as well as through the reaction between the aquaplatinum complex and nucleotides. The rate constant for the aquation process was evaluated to be (2.0 +/- 0.1) x 10(-4) s-1 for both AMP and GMP reactions.(ABSTRACT TRUNCATED AT 250 WORDS)