title: Determination of the acid dissociation constant for cis-diammineaquachloroplatinum(II) ion. A hydrolysis product of cisplatin.
abstract: 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 252Cf 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 pKa was determined to 6.56 +/- 0.01 (SEM). Thus, at physiological pH, the monoaqua complex is present mostly in its less reactive monohydroxy form.
authors.affiliation: Karolinska Pharmacy, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Andersson
authors.forename: H
authors.initials: H
authors.lastname: Hedenmalm
authors.forename: B
authors.initials: B
authors.lastname: Elfsson
authors.forename: H
authors.initials: H
authors.lastname: Ehrsson
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002945:Cisplatin / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin