Hydrolysis of cis- and trans-diammineplatinum(II) complexes: Hydration, equilibrium, and kinetics properties

We have used a combination of ultrasound and density techniques to measure the hydration parameters, apparent molar volume, and apparent molar adiabatic compressibility, of the antitumor drug cis-dichlorodiammineplatinum(II), cis-[Pt(NH₃)₂Cl₂], and its inactive isomer trans-dichlorodiammineplatinum(II), trans-[Pt(NH₃)₂Cl₂], in 10 mM NaNO₃, pH 5.6 at 37°C. The data have been interpreted in terms of the overall hydration of each isomer, the actual hydration contribution to the adiabatic compressibility, ΔK_h, ranges from -56.4 × 10^-4 to -20.3 × 10^-4 cm³-mol^-1-bar^-1, and the volume contribution, ΔV_h, ranges from -16.3 to -6.4 cm³-mol^-1. The negative signs of these hydration contributions indicate that the volume and compressibility of the water immobilized by the platinum complexes is smaller than the volume and compressibility of bulk water. The ΔV_h and ΔK_h parameters for all platinum complexes investigated are linearly dependent on the relative amount of hydrolyzed chlorides. The values of each parameter become more negative with increasing hydrolysis, and show that the degree of hydration increases. The similar dependence of the amount of hydrolyzed chloride ligands reveals similar hydration properties for these two complexes. Thus, the symmetry of the complexes, which is of crucial importance for anticancer activity, has no influence on their hydration properties. Under our experimental conditions, the equilibrium constants for the hydrolysis of cis-[Pt(NH₃)₂Cl₂] are K₁ = 2.52 mM and K₂ = 0.04 mM. The equilibrium constant for the first step of hydrolysis of trans-[Pt(NH₃)₂Cl₂] is 0.03 mM, while the second chloride ligand cannot be substituted by water, even in the irreversible reaction with AgNO₃. Furthermore, continuous measurements of the ultrasonic velocity during hydrolysis permits the accurate evaluation of the pseudo-first-order rate constant k₁ for the hydrolysis of the first chloride ligand of cis-[Pt(NH₃)₂Cl₂], which is 16±1 × 10^-5 s^-1.