DETERMINATION OF THE ACID DISSOCIATION-CONSTANT FOR CIS-DIAMMINEAQUACHLOROPLATINUM(II) ION - A HYDROLYSIS PRODUCT OF CISPLATIN

The biological activity of the anticancer drug cisplatin is supposed to be mediated by its reactive hydrolysis product cis-diammineaquachloroplatinum(II) ion (monoaqua). The monohydrated complex (monoaqua and its deprotonated form monohydroxy) was isolated from an equilibrium mixture of cisplatin in distilled water using a strong cationic exchanger. The structure of the monoaqua complex was established by Cf-252 time-of-flight mass spectrometry. The acid dissociation constant was determined at 37 degrees C by studying the influence of pH on the reaction between the monoaqua complex and chloride ion (0.1 M). The concentration of monohydrated compound was determined by liquid chromatography with post-column derivatization using sodium diethyldithiocarbamate as a reagent. The pK(a) was determined to 6.56 +/- 0.01 (SEM). Thus, at physiological pH, the monoaqua complex is present mostly in its less reactive monohydroxy form.