KINETICS FOR PH-DEPENDENT COMPLEXATION OF AQUATED CIS-DIAMMINEPLATINUM(II) WITH INOSINE AND 1-METHYLINOSINE

Kinetics of the complex formation between aquated cw-PtII(NH3)2and inosine or 1-methylinosine has been studied by HPLC in aqueous solution over a pH range of 4.1–8.6 at 298.2 K. The complexation of aquated cii-PtII(NH3)2can be completely explained by substitution of the aqua ligand(s) with incoming nucleosides. Deprotonation of one of the aqua ligands results in a 10-fold decrease in the displacement rate of the remaining one. In ligand excess, a subsequent formation of 1:1 and 1:2 complexes takes place. I-Methylinosine forms only N7-bound complexes, which is also the predominant binding mode of neutral inosine. Deprotonation of inosine N1H makes this site available for Pt(II) and also facilitates N7 coordination. With anionic inosine, the intrinsic formation rates of the Nl- and N7-bound 1:1 complexes appear to be equal. Nevertheless, the N7 binding mode predominates in the first complexation step throughout the pH range studied. With 1-methylinosine, the binding of the second nucleoside depends only on deprotonation of the remaining aqua ligand in the 1:1 complex. By contrast, introduction of the second ligand to the N7-bound inosine 1:1 complex is facilitated by deprotonation of N1H with concomitant attachment of the proton to the deprotonated OH group in the Pt(II) moiety. This gives a substitutionally labile aqua ligand, the reactivity of which is about one-third of that for the dication. In the N7-bound inosine 1:1 complexes, the N1H proton is acidified by 1.8 or 1.2 log units when the fourth ligand is a water molecule or a hydroxide ion. Intrinsically, anionic inosine exhibits almost an equal tendency to bind through the N1 and N7 sites to the differently charged N7-bound 1:1 complexes. © 1990, American Chemical Society. All rights reserved.