This paper reports a mechanistic investigation of the aquation and anation reactions of substituted ethylenediamine platinum(II) complexes, which were shown to have very different in vivo antitumor activities. The general formula of the complexes is rac-[Pt(R-en)XY](n+) (X, Y = H2O. Cl-; n = 0, 1, 2), where the substituted ethylenediamine (R-en) is(1R,2R,4S)-exo-2-(aminomethyl)-2-amino-7-oxabicyclo[2.2.1]heptane (R(1)-en), (1R,2S,4S)-endo-2-(aminomethyl)-2-amino-7-oxabicyclo[2.2.1]heptane (R(2)-en), or (1S,2S,4S)-exo-2-(aminomethyl)-2-amino-7- bicyclo[2,2,1]heptane (R(3)-en). The two ligands X and Y are shown to be kinetically equivalent for X = Y within the accuracy of N-15, Pt-195, O-17 NMR, although the diamine is asymmetric. Using UV-vis spectrophotometry, it was possible to determine the rate constants (k(1), k(-1), k(2), k(-2)) for the following two successive aquation/anation reactions : [Pt(R-en)Cl-2] + H-2) reversible arrow [Pt(R-en)(H2O)Cl](+) + Cl- (k(1)/k(-1)) K-1 = k(1)/k(-1) [Pt(R-en)(H2O)Cl](+) + H2O reversible arrow [Pt(R-en)(H2O)(2)](2+) + Cl- (k(2)/k(-2)) K-2 = k(2)/k(-2) The first aquation/anation rate constants for the complex rac-[Pt(R(3)-en)Cl-2] have been found to be independent of pH in the range 2.2-5.8 and identical to those relative to R(1)-en and R(2)-en at pH = 2.2 within experimental error. The first and second aquation/anation rate constants obtained for rac-[Pt(R(1)-en)Cl-2] can be compared with those of the literature for [Pt(en)Cl-2 (in parentheses) : 10(5)k(1)(298)/s(-1) = 3.2 +/- 0.2 (3.4 +/- 0.4); 10(2)k(-1)(298)/ M(-1) s(-1) = 4.4 +/- 0.2 (1.54 +/- 0.03); 10(5)k(2)(298)/s(-1) = 7.8 +/- 1.0 (4.4 +/- 0.6); k(-2)(298)/M(-1) s(-1) = 0.67 +/- 0.01 (0.31 +/- 0.04). The kinetic studies as a function of temperature for rac-[Pt(R(1)-en)CW gave the activation and thermodynamic enthalpies and entropies. The high-pressure studies allowed the determination of the complete volume profile (values given in cm(3) mol(-1)) : Delta V-1(double dagger) = -9.4 +/- 0.7; Delta V-double dagger (-1) = -4.0 +/- 0.4; Delta V-1(o) = -5.3 +/- 1.1; Delta V-double dagger (2) = -6.6 +/- 1.7; Delta V-double dagger (-2) = -4.4 +/- 0.5; Delta V-2(o) = -2.2 +/- 2.0. The volume profile obtained for the aquation of rac-[Pt(R1-en)Cl-2] clearly precludes any dissociative mechanism that could have been correlated to a nucleophilic assistance of the 2-substituted norbornyl group. A common mechanism of aquation for [Pt(R-en)Cl-2] complexes involving a pentacoordinate intermediate is proposed. Thus, the rate constants for the aquation of [Pt(R-en)Cl-2] complexes, which is an essential step in the reaction with important biological nucleophiles like DNA cannot be used to establish a structure-activity relationship.