Comparison of the reactivity of oxaliplatin, Pt(diaminocyclohexane)Cl-2 and Pt(diaminocyclohexane(1))(OH2)(2)(2+) with guanosine and L-methionine

The initial rates of reactivity of oxaliplatin, its metabolites Pt(dach)Cl- 2 and Pt(dach)(OH2)(2)(2+) with guanosine and L-met in water, NaCl and phos phate were compared. Versus guanosine, the most reactive molecule was Pt(da ch)(OH2)(2)(2+) about 40 fold that of oxaliplatin, the least reactive was P t(dach)Cl-2. Versus L-met, Pt(dach)(OH2)(2)(2+), was also the most reactive species but only about 2 fold more reactive than Pt(dach)Cl-2 and oxalipla tin. Pt(dach)(OH2)(2)(2+) was approximately 3 fold less reactive versus met hionine than guanosine whereas oxaliplatin and Pt(dach)Cl-2 were about seve n fold more reactive versus methionine than guanosine. Thus, the three plat inum compounds oxaliplatin, Pt(dach)Cl-2 and Pt(dach)(OH2)(2)(2+) react wit h L-met but only the Pt(dach)(OH2)(2)(2+) has a high reactivity with guanos ine. Oxaliplatin, which is stable in water, has to be transformed in the pr esence of chloride in chloro-derivatives which are aquated to become active particularly versus guanosine. These data demonstrate that oxaliplatin has similarities with cisplatin in terms of chloride versus water coordination and in terms of dependence on chloride concentration for transformations. (C) 2001 Elsevier Science B.V. All rights reserved.