Reactions of platinum(II) anticancer drugs. Kinetics of acid hydrolysis of cis-diammine(cyclobutane-1,1-dicarboxylato)platinum(II) "Carboplatin"

The kinetics of acid hydrolysis of "carboplatin" [cis-diammine(cyclobutane-1,1-dicarboxylato)platinum(II)] has been studied over a range of acidities at constant ionic strength (I = 1.0 mol dm(-3)) and various temperatures. Loss of the substituted malonato ligand occurs in a biphasic reaction involving a ring opening step and a slower step in which loss of the monodentate malonato ligand occurs. At low acidities the first step k(obs) (1) is approximately ten times faster than the second step (k(obs) (2)). At higher acidities this ratio falls to ca four fold. Plots of k(obs) (1) vs [H+] are linear with a positive intercept and the plots can be adequately described by the relationship k(obs) (1) = k(0)+k(1)[H+] with k(0) = 6 x 10(-5) s(-1) and k(1) = 3.3 x 10(-4) s(-1) at 25 degrees C and I = 1.0 mol dm(-3). The rate constant k(obs) (2) = k(2)[H+] with k(2) = 1.1 x 10(-4) s(-1) at 25 degrees C and I = 1.0 mol dm-3. The antitumour activity of carboplatin is discussed in terms of the kinetic results obtained. (C) 1998 Elsevier Science Ltd. All rights reserved