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 adiabat ic compressibility, of the antitumor drug cis-dichlorodiammineplatinum(II), cis[Pt(NH3)(2)Cl-2], and its inactive isomer trans-dichlorodiammineplatinu m(II), trans[Pt(NH3)(2)Cl-2], in 10 mM NaNO3, pH 5.6 at 37 degrees C. The d ata have been interpreted in terms of the overall hydration of each isomer, the actual hydration contribution to the adiabatic compressibility, Delta K-h, ranges from -56.4 x 10(-4) to -20.3 x 10(-4) cm(3)-mol(-1)-bar(-1), an d the volume contribution, Delta V-h, ranges from - 16.3 to -6.4 cm(3)-mol( -1). The negative signs of these hydration contributions indicate that the volume and compressibility of the water immobilized by the platinum complex es is smaller than the volume and compressibility of bulk water The Delta V -h and Delta K-h parameters for all platinum complexes investigated are lin early 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 amou nt of hydrolyzed chloride ligands reveals similar hydration properties for these two complexes. Thus, the symmetry of the complexes, which is of cruci al importance for anticancer activity, has no influence on their hydration properties. Under our experimental conditions, the equilibrium constants fo r the hydrolysis of cis-[Pt(NH3)(2)Cl-2] are K-1 = 2.52 mM and K-2 = 0.04 m M. The equilibrium constant for the first step of hydrolysis of trans-[Pt(N H3)(2)Cl-2] is 0.03 mM, while the second chloride ligand cannot be substitu ted by water, even in the irreversible reaction with AgNO3. Furthermore, co ntinuous measurements of the ultrasonic velocity during hydrolysis permits the accurate evaluation of the pseudo-first-order rate constant k(1) for th e hydrolysis of the first chloride ligand of cis[Pt(NH3)(2)Cl-2], which is 16+/-1x10(-5) s(-1).