KINETICS AND MECHANISM OF THE COMPLEXATION OF TRANS-DIAMMINEDIAQUAPLATINUM(II) WITH THE 6-OXOPURINE NUCLEOSIDES INOSINE AND 1-METHYLINOSINEIN AQUEOUS-SOLUTION AS A FUNCTION OF THE PH

Kinetics of complexation of trans-[Pt(NH3)(2)(H2O)(2)](2+) with the mo del nucleobases inosine and 1-methylinosine has been studied in aqueou s solution at 298.2 K in the pH range 2.8-9.6 (I = 0.1 M) by using HPL C as an analytical tool. The complexation of aquated trans-Pt-II(NH3)( 2) with the nucleobases employed can be quantitatively explained by re placement of the aqua ligand with the nucleobase, while the hydroxo gr oup bound to Pt(LI) is inert to substitution reaction relative to the coordinated water molecule. The stepwise acidity constants of trans-[P t(NH3)(2)(H2O)(2)](2+) Obtained from kinetic measurements were in exce llent agreement with those found potentiometrically (pK(a1) = 4.48 +/- 0.02, pK(a2) = 7.20 +/- 0.05). The reactivity of the Pt(II) dication is 7-8 times higher than that of the monocation despite the moderate t rans effect OH- > H2O. In excess of the nucleobase, stepwise formation of 1:1 and 1:2 complexes is observed. 1-Methylinosine forms only N7-b ound species, as does inosine when pH < 5.5. Although deprotonation of inosine NIH offers an additional binding site for Pt(II), the ability of the N7 site to accommodate Pt(II) is increased by the loss of the N1H proton, as well. Consequently, the N7 binding mode predominates in the formation of 1:1 complexes throughout the pH range studied. In th e case of 1-methylinosine the second complexation step is mechanistica lly straightforward. With inosine, instead, proton transfer formally f rom N1H to the deprotonated OH group bound to Pt(II) gives substitutio n labile aqua ligand, the reactivity of which is comparable to that of the dicationic species. Even at high pH the N7 site is preferred over the N1 site also in 1:2 complexes. At pH 9.5, the inosine N1/N7 bindi ng ratio is about 0.6 in 1:1 complexes, whereas the approximate percen tage of different 1:2 complexes formed is as follows (Pt(II) binding s ites in parentheses): (N7,N7) 44%, (N1,N7) 44%, and (N1,N1) 12%. In tr ans-[Pt(NH3)(2)(InoH-N7)(H2O)](2+) the inosine NTH proton is acidified by 1.7 log units, whereas in trans-[Pt(OH)(NH3)(2)(InoH-N7)](+) the i nfluence of the Pt(II) unit on the N1H acidity is 1.4 log units.