REACTIONS OF PLATINUM(II) ANTICANCER DRUGS - KINETICS OF ACID-HYDROLYSIS OF IAMMINE(CYCLOBUTANE-1,1-DICARBOXYLATO)PLATINUM(II) CARBOPLATIN

The kinetics of acid hydrolysis of ''carboplatin'' ammine(cyclobutane- 1,1-dicarboxylato)platinum(II)] has been studied over a range of acidi ties at constant ionic strength (I = 1.0 mol dm(-3)) and various tempe ratures. 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 ste p (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 t he 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 ter ms of the kinetic results obtained. (C) 1998 Elsevier Science Ltd. All rights reserved.