KINETICS AND MECHANISM OF THE COMPLEXATION OF TRANS-DIAMINEDICHLOROPLATINUM(II) WITH THE PURINE NUCLEOSIDE INOSINE IN AQUEOUS-SOLUTION

Kinetics of the complexation of trans-[PtCl2(NH3)(2)] (1), and its hyd rolysis products trans-[PtCl(NH3)2(H2O)(2)](2+) (2) and trans-[Pt(NH3) 2(H2O)(2)](2+) (3), With the purine nucleoside inosine (L) has been st udied by HPLC in aqueous solution at 318.2 K (pH = 2.8-3.4, I = 0.1 M) . The relative ability of 1-3 to bind inosine is about 1:200:10 as giv en by the second-order rate constants k(3) = (6.5 +/- 0.4) x 10(-3) M( -1) s(-1) (1), k(4) and k(5) = (6.6 +/- 0.6) x 10(-2) M(-1) s(-1) (3). An excess of ligand gives stepwise formation of the 1:2 complex. When [L] < 0.02 M, hydrolysis of the first chloro ligand (k(1) = (1.05 +/- 0.03) x 10(-3) s(-1)) is the rate-limiting step in the binding of ino sine to 1 as well as to the 1:1 complex (4), in which the fourth ligan d is Cl- (b = (9.4 +/- 0.7) x 10(-5) s(-1)). In higher ligand concentr ation direct substitution of Cl- becomes significant both in 1 and 4; the second-order rate constant for the latter is k(7) = (8 +/- 1) x 10 (-4) M(-1) s(-1). Under acidic conditions aquation of 2 is very slow ( k(2) = (4 +/- 2) x 10(-6) s(-1)) and strongly reversible. In basic sol ution (pH > 11), instead, hydrolysis of 2 is irreversible (k(2,OH) = ( 2 +/- 0.2) x 10(-5) s(-1)). Competition of inosine and Cl- for 2 and 3 was employed to study the Cl- anation of aquated Pt(II) species. The second-order rate constants are k(-1) 2 2.2 +/- 0.4 M(-1) s(-1) for 2 and k(-2) = 0.20 +/- 0.02 M(-1) s(-1) for 3. Thus, the equilibrium con stants for the stepwise hydrolysis of 1 are K-1 =;(4.8 +/- 1.2) x 10(- 4) M and K-2 = (1.8 +/- 0.8) X 10(-5) M(-1) The rate constant for the chloride anation of the 1:1 complex (5) bearing H2O as the fourth liga nd is k(-6) = 0.62 +/- 0.12 M(-1) s(-1), which gives the equilibrium c onstant K-6 = (1.5 +/- 0.5) x 10(-4) M for the reaction between 4 and 5. The second-order rate constant for the conversion of 5 into the 1:2 complex (6) is k(8) = 0.35 +/- 0.03 M(-1) s(-1). Comparison of the ki netic data obtained to those of the cis isomer reveals econsiderable d ifferences in the hydrolysis reactions and in the formation of monofun ctional adducts. In particular, the properties of the diaqua species d iffer markedly. By contrast, the second complexation step appears to b e kinetically similar in both configurations.