Kinetics and mechanism of the reduction of (ImH)[trans-RuCl4(dmso)(Im)] by ascorbic acid in acidic aqueous solution

A systematic study of the reduction of (ImH)[trans-RuCl4(dmso)(Im)] (NAMI-A; dmso is dimethyl sulfoxide, Im is imidazole), a promising antimetastasing agent entering phase II clinical trial, by L-ascorbic acid is reported. The rapid reduction of trans-[(RuCl4)-Cl-III(dmso)(Im)](-) results in formation of trans-[(RuCl4)-Cl-II(dmso)(Im)](2-) in acidic medium (pH = 5.0) and is followed by successive dissociation of the chloride ligands, which cannot be suppressed even in the presence of a large excess of chloride ions. The reduction of NAMI-A strongly depends on pH and is accelerated on increasing the pH. Over the small pH range 4.9-5.1, the reaction is quite pH-independent and the influence of temperature and pressure on the reaction could be studied. On the basis of the reported activation parameters and other experimental data, it is suggested that the redox process follows an outer-sphere electron transfer mechanism. A small contribution from a parallel reaction ascribed to inner-sphere reduction of aqua derivatives of NAMI-A, was found to be favored by lower concentrations of the NAMI-A complex and higher temperature. In the absence of an excess of chloride ions, the reduction process is catalyzed by the Ru(II) products being formed. The reduction of NAMI-A is also catalyzed by Cu(II) ions and the apparent catalytic rate constant was found to be 1.5 x 10(6) M-2 s(-1) stop at 25 degrees C.