Cisplatin carbonato complexes. Implications for uptake, antitumor properties, and toxicity

Cisplatin is a potent cytotoxic agent used for the treatment of ovarian and testicular cancer and other malignancies.1 The cyto-toxicity of cisplatin is thought to be related to its ability to modify cellular DNA.2 In plasma, where the chloride concentration is 105 mM, cisplatin is believed to partially solvate to its aquated forms.3 Since aquated complexes can react with components present in blood and the cytosol, they may be important for the antitumor effects, resistance, and toxicity associated with cisplatin.4 Earlier, we used HSQC NMR and low concentrations of 15N-labeled cisplatin, cis-Pt(15NH3)2Cl2 (1, Figure 1), to identify the platinum species in culture media (RPMI + 10 % fetal bovine serum) in the presence and absence of Jurkat cells.5 We interpreted the NMR measurements as showing that 1 hydrolyzes to the monoaquo complex, 2, which is in equilibrium with the monohy-droxo species, 3, as is known to occur in aqueous solution.3 W